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Krajewski A, Perussolo J, Ercal P, Gkranias N, Donos N. The Effect of Non-Surgical Periodontal Therapy on Subgingival Microbiota: A Systematic Review and Meta-Analysis. J Periodontal Res 2025. [PMID: 40347039 DOI: 10.1111/jre.13409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 04/02/2025] [Accepted: 04/04/2025] [Indexed: 05/12/2025]
Abstract
AIM The objective of this systematic review and meta-analysis was to evaluate the influence of non-surgical periodontal therapy (NSPT) on subgingival microbiota in systemically healthy patients with periodontitis. METHODS A systematic literature search was conducted in Medline, Embase, LILACS, and the Cochrane Library, supplemented by a manual search for studies investigating the effect of NSPT on subgingival microbiota in systemically healthy patients. RESULTS In this review, 115 studies were included, of which 41 used checkerboard DNA-DNA hybridisation technology, 30 real-time quantitative PCR, 36 bacterial culture, and 8 16S ribosomal ribonucleic acid (rRNA) gene sequencing technology. Meta-analyses showed a significant decrease in mean counts of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Treponema denticola (T. denticola), Porphyromonas gingivalis (P. gingivalis), Tannerella forsythia (T. forsythia), Eubacterium nodatum (E. nodatum), Prevotella intermedia (P. intermedia), and Campylobacter rectus (C. rectus) after NSPT. Supportive periodontal care provided a further decrease in mean counts of P. gingivalis and T. denticola at 6 months after NSPT. Qualitative analysis of 16S rRNA gene sequencing studies indicated significant effects of NSPT on the relative abundance of selected disease-and health-associated species and genera, whereas findings on changes in alpha and beta diversity in the subgingival microbiome were heterogeneous. CONCLUSION This systematic review showed that NSPT leads to significant reduction of mean abundance of disease-associated microbial species. However, 16S rRNA gene sequencing studies reported heterogeneous findings, which may be associated with methodological aspects. To deepen the understanding of the effect of NSPT on subgingival microbiota, further studies, powered for microbiome changes and with clustered analysis of site-specific samples, are needed.
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Affiliation(s)
- Anna Krajewski
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Jeniffer Perussolo
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Pinar Ercal
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Nikolaos Gkranias
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Nikos Donos
- Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
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Elbarbary NS, Khattab DA, Sultan BM, Rahman Ismail EA. Periodontal disease in adolescents with type 1 diabetes mellitus: A cross link between continuous glucose monitoring-derived metrics, caspase-3 levels, diabetic nephropathy and subclinical atherosclerosis. Diabetes Res Clin Pract 2025; 224:112234. [PMID: 40339704 DOI: 10.1016/j.diabres.2025.112234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 04/16/2025] [Accepted: 05/03/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND Periodontitis can lead to the development of atherosclerotic heart disease. AIM To assess the relation between periodontal disease and continuous glucose monitoring (CGM)-derived metrics, caspase-3 and carotid intima media thickness (CIMT) in adolescents with type 1 diabetes mellitus (T1DM). METHODS This cross-sectional study included 115 participants with T1DM (15.91 ± 2.14 years). CIMT, CGM-derived metrics, periodontal probing depths (PPD) and amount of loss clinical attachment (CAL) were assessed. Serum caspase-3 levels were measured in T1DM participants compared with 40 healthy controls. RESULTS Periodontitis was found in 69.6 % of T1DM group. Serum caspase-3 levels were significantly elevated in T1DM participants compared with controls (median 8.4 versus 1.2 ng/mL; p < 0.001. Participants with periodontitis had higher percentage of nephropathy with elevated CIMT, caspase-3 levels, glucose management indicator (GMI) (7.5 ± 0.58 versus 7.1 ± 0.51 %; p = 0.047), coefficient of variation (CV) (36.4 ± 5.6 versus 33.2 ± 5.9 %; p = 0.008) and glycemic risk index while time in range (TIR) was significantly lower (58.5 ± 14.1 versus 69.7 ± 11.5 %; p = 0.002) compared with those without periodontitis. Participants using advanced hybrid close loop system had lower caspase 3 levels and CIMT compared with those on multiple daily injections. There were positive correlations between caspase-3 and GMI (r = 0.587), CV (r = 0.434), CIMT (r = 0.425), PPD (r = 0.952) and CAL (r = 0.739) while caspase-3 was negatively correlated to TIR(r = -0.481; p < 0.001 for all). CONCLUSION Periodontitis is prevalent among adolescents with T1DM and is linked to glycemic variability and poor metabolic control while associated with diabetic nephropathy and subclinical atherosclerosis. Elevated caspase-3 highlights the involvement of apoptosis in periodontal disease and subclinical atherosclerosis in T1DM.
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Affiliation(s)
| | - Doaa Adel Khattab
- Oral Medicine, Periodontology and Diagnosis Department, Faculty of Dentistry, Ain Shams University, Cairo, Egypt
| | - Basma Mohamed Sultan
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Caetano GDDC, Martins ADS, Cardoso MVS, Paula WVDF, Saraiva JR, Borges NC, Schweitzer CM, Gaetti-Jardim Júnior E, Dutra IDS, Borsanelli AC. Epidemiological survey on the oral health of cattle slaughtered in Goiás, Brazil. Vet Rec 2025; 196:e5220. [PMID: 40040539 DOI: 10.1002/vetr.5220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/18/2024] [Accepted: 01/16/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND Good oral health is essential for the performance and welfare of cattle, as it directly affects their feed intake and feed efficiency. However, little is currently known about the epidemiology of dental disease in cattle. METHODS This study investigated the prevalence of lesions in the dental arcades of 1006 slaughtered cattle. The periodontal evaluation was performed by the same person, using a periodontal probe and flashlight as the heads passed down the slaughter line, and the results were recorded on an odontogram. RESULTS Of the 1006 slaughtered animals evaluated, 115 (11.4%) were male and 891 (88.6%) were female; 735 (73.1%) were beef cattle and 271 (26.9%) were dairy cattle. Gingival recession was more frequent in incisors, while periodontal pockets were observed mainly in incisors and molars. Dairy cattle showed a higher prevalence of gingival recession and periodontal pockets than beef cattle. In beef cattle, an association was observed between age and gingival recession, while in dairy cattle, age was linked to tooth wear. No significant differences were observed between males and females. LIMITATIONS As the examinations were carried out postmortem, it was not possible to evaluate the prevalence of gingivitis. CONCLUSION The findings of this study contribute to our understanding of the complex relationship between sex, breed type, age and oral health in cattle, highlighting the need for further research to clarify these associations and develop targeted management strategies to promote animal health and welfare.
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Affiliation(s)
| | - Andressa da Silva Martins
- Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, Universidade Federal de Goiás, Goiânia, Brazil
| | - Maria Vitória Soares Cardoso
- Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, Universidade Federal de Goiás, Goiânia, Brazil
| | - Warley Vieira de Freitas Paula
- Postgraduate Program in Animal Science, School of Veterinary Medicine and Animal Science, Universidade Federal de Goiás, Goiânia, Brazil
| | - Júlia Rebecca Saraiva
- Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, Universidade Federal de Goiás, Goiânia, Brazil
| | - Naida Cristina Borges
- Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, Universidade Federal de Goiás, Goiânia, Brazil
| | - Christiane Marie Schweitzer
- Department of Mathematics, Ilha Solteira School of Engineering, São Paulo State University (UNESP), Ilha Solteira, Brazil
| | | | - Iveraldo Dos Santos Dutra
- Department of Production and Animal Health, Araçatuba School of Veterinary Medicine, São Paulo State University (UNESP), Araçatuba, Brazil
| | - Ana Carolina Borsanelli
- Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, Universidade Federal de Goiás, Goiânia, Brazil
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Bao Y, Gu Q, Xu W, Sun Q, Ding B. Association between Life's Essential 8 score and periodontitis in patients with diabetes: Insights from the National Health and Nutrition Examination Survey 2009-2014. J Am Dent Assoc 2025; 156:374-381.e3. [PMID: 40192607 DOI: 10.1016/j.adaj.2025.02.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 02/17/2025] [Accepted: 02/22/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND The authors explored the relationship between Life's Essential 8 (LE8) scores and periodontitis among patients with diabetes in the United States. METHODS The authors used data from a large cohort in the United States. A weighted multivariable logistic regression model was used to analyze the association between LE8 score and the prevalence of periodontitis, adjusting for sociodemographic factors, health behaviors, and other relevant factors. Restricted cubic splines were applied to explore nonlinear relationships. RESULTS A total of 1,164 people participated in this study; 51.8% were male and 48.2% were female. In a multivariable logistic regression model, the LE8 score was inversely associated with periodontitis prevalence (odds ratio, 0.98; 95% CI, 0.97 to 0.99; P = .001), and this association was consistent across low, medium, and high LE8 score groups. Participants in the highest LE8 score group had 64% lower odds of periodontitis prevalence than those in the lowest group (odds ratio, 0.36; 95% CI, 0.13 to 0.99; P = .04). Restricted cubic spline regression analysis indicated no significant nonlinear association between LE8 score and periodontitis. CONCLUSIONS Elevated LE8 scores were significantly associated with lower prevalence odds of periodontitis in participants with diabetes. PRACTICAL IMPLICATIONS The study results indicated an association between cardiovascular health (assessed by the LE8 score) and periodontitis in patients with diabetes, suggesting that both cardiovascular health and periodontal status should be considered in the management of diabetes.
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La Rosa GRM, Pedullà E, Chapple I, Kowalski J, Walicka M, Piro S, Polosa R. A systematic review of oral health outcomes following smoking cessation in type 2 diabetes: Clinical and research implications. J Dent 2025; 156:105665. [PMID: 40058483 DOI: 10.1016/j.jdent.2025.105665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 03/02/2025] [Accepted: 03/06/2025] [Indexed: 03/16/2025] Open
Abstract
OBJECTIVE This systematic review analyzes the effects of smoking cessation on oral health outcomes in individuals with type 2 diabetes. DATA The review followed PRISMA guidelines, and the protocol was registered on PROSPERO (CRD42024604271). Risk of bias was assessed using the Joanna Briggs Institute's critical appraisal tools. SOURCES PubMed, Scopus, and Web of Science were searched on November 7, 2024, alongside references from highly cited journals and conference proceedings. No language or date restrictions were applied. STUDY SELECTION Inclusion criteria were human clinical studies (randomized controlled trials, cohort, case-control, or cross-sectional studies) involving patients with type 2 diabetes, stratified by smoking status (former, current, never smokers), assessing oral health outcomes (e.g., periodontal disease, caries). Studies without detailed smoking status data were excluded. RESULTS The search retrieved 549 studies, of which 4 (N = 926 participants) met the inclusion criteria. These studies examined smoking status in relation to periodontitis progression and response to periodontal therapy. Overall, the effects smoking cessation in improving periodontal outcomes in this population appears limited. However, methodological limitations were identified, and the studies may have been underpowered for the smoking status subgroup. CONCLUSION Evidence on the impact of smoking cessation on oral health in patients with type 2 diabetes remains inconclusive, as large prospective studies specifically designed for this purpose are lacking. While smoking cessation benefits oral health in the general population, its effects on oral outcomes in patients with diabetes remain unclear. Further research is needed to elucidate its impact on patients with type 2 diabetes. CLINICAL SIGNIFICANCE A multidisciplinary approach to managing diabetic patients is essential, where dentists not only address oral health but also support healthy behaviors, including smoking cessation, to improve overall diabetes-related complications.
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Affiliation(s)
| | - Eugenio Pedullà
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy
| | - Iain Chapple
- Periodontal Research Group, Institute of Clinical Sciences, College of Medical & Dental Sciences, The University of Birmingham, Birmingham, UK; Birmingham Community Healthcare NHS Foundation Trust, Birmingham, UK
| | - Jan Kowalski
- Department of Periodontology, Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Walicka
- Department of Human Epigenetics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland; Department of Internal Diseases, Endocrinology and Diabetology, National Medical Institute, Poland
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; Center of Excellence for the Acceleration of Harm Reduction (CoEHAR), University of Catania, Catania, Italy
| | - Riccardo Polosa
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; Center of Excellence for the Acceleration of Harm Reduction (CoEHAR), University of Catania, Catania, Italy
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Tsimpiris A, Tsolianos I, Grigoriadis A, Tsimtsiou Z, Goulis DG, Grigoriadis N. Association of Chronic Periodontitis with Hemorrhagic Stroke: A Systematic Review and Meta-Analysis. Eur J Dent 2025; 19:265-274. [PMID: 39657943 PMCID: PMC12020598 DOI: 10.1055/s-0044-1793844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2024] Open
Abstract
Periodontitis is a chronic, multifactorial inflammatory condition linked to dysbiotic plaque biofilms and characterized by the gradual destruction of the structures supporting the teeth owing to compromised immune system function. Hemorrhagic stroke, which primarily occurs within the brain tissue or in the subarachnoid space as a blood leak of ruptured vessels, is a sudden neurological impairment caused by vascular damage in the central nervous system, resulting in focal neurological deficits. Chronic periodontitis (CP) and hemorrhagic stroke may share common pathogenic features involving inflammation and immune system activation, prompting researchers to investigate their potential connection. The aim of the study is to systematically review the literature on the epidemiological association between CP and hemorrhagic stroke in adults. The study protocol adhered to the PRISMA 2020 guidelines, and the design followed the Cochrane methodology. A thorough literature search encompassing PubMed, Scopus, and Web of Science databases and a manual search and evaluation of gray literature was conducted. Meta-analysis was performed using Review Manager (RevMan) 5.4, with the effect size represented by the odds ratio (OR) and a 95% confidence interval (CI). Heterogeneity was assessed using the chi-squared and I 2 statistics. The selected articles, written in English without time constraints, focused on observational studies involving patients and controls and included disease diagnostic criteria. Duplicate entries were eliminated. The reliability of each study's results was evaluated using the Newcastle-Ottawa Scale and GRADE tools. Two reviewers conducted the assessments, and a third reviewer resolved any disagreements. The meta-analysis comprised four observational studies involving 1,882 individuals. It revealed that individuals diagnosed with hemorrhagic stroke were notably more likely to have concurrent CP (OR: 6.32; 95% CI: 1.35-29.49; p = 0.02) or severe CP (OR: 3.08; 95% CI: 1.56-6.06; p = 0.001) compared with healthy controls. A notable occurrence of CP was detected in patients with hemorrhagic stroke compared with controls. Health care professionals need to acknowledge the connection between the two conditions, as it allows them to provide optimal holistic care through a thorough approach to diagnosis and treatment.
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Affiliation(s)
| | - Ioannis Tsolianos
- Dental School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Andreas Grigoriadis
- Dental Sector, 424 General Military Training Hospital, Thessaloniki, Greece
- Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Zoi Tsimtsiou
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios G. Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Nikolaos Grigoriadis
- 2nd Department of Neurology, AHEPA Hospital, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Abraham D, Gupta A, Duraisamy AK, Mrinalini M. The influence of chronic periodontitis and type 2 diabetes mellitus on resistin levels of gingival crevicular fluid- a systematic review and meta-analysis. J Oral Biol Craniofac Res 2025; 15:612-623. [PMID: 40248519 PMCID: PMC12005886 DOI: 10.1016/j.jobcr.2025.03.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 03/30/2025] [Accepted: 03/31/2025] [Indexed: 04/19/2025] Open
Abstract
Aim Chronic periodontitis (CP), a prevalent inflammatory dental disease, has been linked to systemic conditions like Type 2 Diabetes Mellitus (T2DM). This systematic review and meta-analysis aimed to evaluate resistin levels in the Gingival Crevicular Fluid (GCF) of CP individuals with T2DM. The objective was to determine if resistin could be a potential biomarker for periodontal disease in T2DM individuals. Methods The review included data from seventeen clinical studies that investigated resistin levels in GCF of individuals diagnosed with CP and T2DM. Data were sourced from PubMed, Scopus, and EBSCOhost, selected for their extensive coverage of medical and dental research, ensuring thorough retrieval of relevant studies. From the initial seventeen studies, five complied with the strict inclusion criteria for meta-analysis. Results Using a comprehensive meta-analysis, the significance of GCF Resistin levels in individuals with CP and T2DM relative to the healthy groups was examined. In addition, a meta-analysis was carried out to look into the relationship between periodontal probing depth (PPD) and CP and T2DM. The results indicated that individuals with T2DM and CP had significantly higher GCF resistin levels than the other groups. Furthermore, the PPD in T2DM with CP was significantly greater than in the other groups. Conclusion The present review highlights the potential role of resistin as a biomarker to diagnose individuals with chronic periodontitis and T2DM. Clinical significance The significantly elevated levels of resistin suggest that resistin could serve as a potential biomarker for T2DM in individuals with CP. This could lead to improved methods of early diagnosis and treatment, which could enhance individual outcomes and quality of life. Prospero registration The registration number CRD42023467186.
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Affiliation(s)
- Dax Abraham
- Department of Conservative Dentistry and Endodontics, Manav Rachna Dental College, School of Dental Sciences, Faridabad, Haryana, 121001, India
| | - Alpa Gupta
- Department of Conservative Dentistry and Endodontics, Manav Rachna Dental College, School of Dental Sciences, Faridabad, Haryana, 121001, India
| | - Arun Kumar Duraisamy
- Department of Conservative Dentistry and Endodontics, All India Institute of Medical Sciences- CAPFIMS Center, New Delhi, 110068, India
| | - Mrinalini Mrinalini
- Department of Conservative Dentistry and Endodontics, Manav Rachna Dental College, School of Dental Sciences, Faridabad, Haryana, 121001, India
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Kitamura T, Shimazaki Y, Hashimoto H, Ito M, Fukumori T, Inamoto Y, Okuno Y, Maruyama A. The impact of a workplace dental-health program on glycemic control in Japanese working adults: a cohort study. BMC Oral Health 2025; 25:670. [PMID: 40307804 PMCID: PMC12044998 DOI: 10.1186/s12903-025-06039-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 04/21/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND This study implemented a workplace dental-health program to encourage those at risk of diabetes to visit a dentist, and examined factors associated with changes in glycemic control. METHODS The participants included 342 people aged 40-64 years old with an A1c value of 5.6% or higher, and those with diabetes, prediabetes, or needing to exercise caution with regard to diabetes. Participants underwent a dental checkup at a dental clinic in 2018, after which their diabetes status was followed for 3 years. Multivariate multinomial logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the effect of each independent variable on the 3-year change in the A1c value (decrease, stable, or increase). RESULTS Having a greater number of teeth was associated with a significantly lower OR for an increased A1c value (decrease ≥ 0.3%) (OR, 0.88; 95% CI, 0.79-0.97). Visiting a dentist regularly was associated with a significantly higher OR for a decreased A1c value (increase ≥ 0.3%) (OR, 4.20; 95% CI, 1.45-12.2). CONCLUSION Among working adults, those who visited a dentist regularly had better A1c values, and those with a greater number of teeth were less likely to experience worsening of A1c values.
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Affiliation(s)
- Takumi Kitamura
- Department of Preventive Dentistry and Dental Public Health, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan
| | - Yoshihiro Shimazaki
- Department of Preventive Dentistry and Dental Public Health, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan.
| | - Hiroko Hashimoto
- Department of Preventive Dentistry and Dental Public Health, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan
| | - Manabu Ito
- Mie Dental Association, Tsu, 514-0003, Japan
| | | | | | - Yutaka Okuno
- Mie Prefectural Government, Tsu, 514-8570, Japan
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Kusu Y, Furuta M, Kageyama S, Yamashita Y, Takeshita T. Mediating factors associated with alcohol intake and periodontal condition. FRONTIERS IN ORAL HEALTH 2025; 6:1524772. [PMID: 40342576 PMCID: PMC12058805 DOI: 10.3389/froh.2025.1524772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 04/04/2025] [Indexed: 05/11/2025] Open
Abstract
Background Alcohol consumption has been reported to increase the risk of periodontal disease and various health abnormalities such as obesity, hyperglycemia, and liver abnormalities. While the link between these health abnormalities and periodontal disease has been established, their potential mediating role in the association between alcohol consumption and periodontal disease remains unclear. Therefore, this study aims to investigate the multiple mediating roles of obesity, hyperglycemia, and liver abnormalities in this association. Methods A cross-sectional study was conducted on 6,529 individuals aged 35-64 years who underwent workplace health check-ups in 2003 (mean age: 45.7 ± 8.7 years). The periodontal condition was evaluated using the mean pocket depth (PD), and participants were classified into no, light/moderate (alcohol consumption 0.1-29.9 g/day), and heavy (≥30 g/day) drinking groups. Causal mediation analysis was performed. Results Heavy drinking had a direct effect on the mean PD. Light/moderate drinking had a indirect effect on the mean PD through the body mass index (BMI), glucose level, alanine aminotransferase level (ALT), with proportion mediated of 25.1%, 8.9%, and 18.9%, respectively. The mediating role of glucose level was found in the association between heavy drinking and the mean PD with proportion mediated of 32.7%. Conclusion This study confirmed that alcohol consumption was associated with worse periodontal condition among Japanese adults who received workplace health check-ups. This association was partially contributed by several factors such as BMI, glucose level, and ALT.
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Affiliation(s)
- Yuto Kusu
- Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Michiko Furuta
- Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Shinya Kageyama
- Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Yoshihisa Yamashita
- Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
- Kyushu Dental University, Kitakyushu, Japan
| | - Toru Takeshita
- Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
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Bachtiar BM, Tahapary DL, Fath T, Theodorea CF, Haerani N, Soeroso Y, Shahab SN, Wildan A, Runtu FMJG, Tadjoedin FM, Ayuningtyas D, Amir L, Bachtiar EW. Saccharibacteria (TM7) in saliva and subgingival microbiome as a predictor for gingivitis in individuals with type2 diabetes evaluated by qPCR. FRONTIERS IN DENTAL MEDICINE 2025; 6:1550936. [PMID: 40331023 PMCID: PMC12053271 DOI: 10.3389/fdmed.2025.1550936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 03/17/2025] [Indexed: 05/08/2025] Open
Abstract
Oral samples are widely used for studying oral microbiome in health and diseases. In this study, saliva and subgingival biofilm (SGB) samples obtained from patients with type2 diabetes (T2DM), without periodontitis (G1 group), with gingivitis (G2 group), and periodontitis (G3 group), were used to compare the abundance of Saccharibacteria (TM7), its host's bacteria (Schaalia odontolytica), periodontopathogen (Represented by Fusobacterium nucleatum), and nitrate-reducing bacteria (represented by Rothia mucilaginosa). The gingival crevicular fluid were also used to analyze the transcription levels of interleukin-6 (IL-6) and C-reactive protein (CRP). Healthy individuals' oral samples served as a control, and the targeted bacteria and inflammatory indicators were detected and measured using real-time PCR. The results showed that in either sample, the abundance of TM7 and other targeted bacteria showed a similar profile. Notably, within participants with T2DM, the abundance of TM7 was similar in G1 and G2 groups, but significantly decreased in G3 group. With the exception of the SGB of the G3 group, the relationship between TM7 and its bacterial host was strongly positive across all evaluated samples. Furthermore, CRP had higher transcription levels than IL-6 across the entire group. Despite the fact that the G3 group showed an adverse relationship between TM7 and CRP, patients with T2DM generally showed a positive correlation between TM7 and IL-6/CRP, which was verified by a receiver operating curve.
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Affiliation(s)
- Boy M. Bachtiar
- Department of Oral Biology and Oral Science Research Center, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Dicky L. Tahapary
- Clinical Research Unit RSCM, Metabolic-Endocrine-Diabetes Division, Department Internal Medicine, Faculty of Medicine, Universitas Indonesia - Ciptomangunkusumo Hospital Metabolic Disorder, Cardiovascular, and Aging Research Cluster, Indonesian Medical Education and Research Institute, Jakarta, Indonesia
- Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
- Clinical Research Unit RSCM, Department Microbiology, Faculty of Medicine, Universitas Indonesia - Ciptomangunkusumo Hospital, Jakarta, Indonesia
| | - Turmidzi Fath
- Department of Oral Biology and Oral Science Research Center, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Citra F. Theodorea
- Department of Oral Biology and Oral Science Research Center, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Natalina Haerani
- Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Yuniarti Soeroso
- Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Selvi Nafisa Shahab
- Clinical Research Unit RSCM, Metabolic-Endocrine-Diabetes Division, Department Internal Medicine, Faculty of Medicine, Universitas Indonesia - Ciptomangunkusumo Hospital Metabolic Disorder, Cardiovascular, and Aging Research Cluster, Indonesian Medical Education and Research Institute, Jakarta, Indonesia
- Clinical Research Unit RSCM, Jakarta, Indonesia
| | - Ardy Wildan
- Metabolic-Endocrine-Diabetes Division, Department of Internal Medicine, FKUI-RSCM, Jakarta, Indonesia
| | | | - Fatimah Maria Tadjoedin
- Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Dewi Ayuningtyas
- Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Lisa Amir
- Department of Oral Biology and Oral Science Research Center, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Endang W. Bachtiar
- Department of Oral Biology and Oral Science Research Center, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
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11
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Bolchis V, Jumanca D, Dumitrescu R, Balean O, Toderas NA, Popescu S, Marcu A, Marian C, Galuscan A. Glycemic Control, Inflammatory Mediators, and Periodontal Health: A Cross-Sectional Study in Patients with Diabetes. J Clin Med 2025; 14:2847. [PMID: 40283677 PMCID: PMC12028111 DOI: 10.3390/jcm14082847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 04/15/2025] [Accepted: 04/20/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: The bidirectional relationship between diabetes mellitus (DM) and periodontal disease (PD) has garnered increasing attention due to shared inflammatory mechanisms and mutual disease exacerbation. In Romania, despite a high prevalence of diabetes and PD, integration of oral health into diabetes care remains limited. This study aimed to investigate the association between glycemic control, salivary inflammatory biomarkers (IL-1β, IL-6, MMP-8), and periodontal status in diabetic patients. Additionally, it evaluated patients' awareness of oral health risks and their communication with healthcare providers regarding periodontal care. Methods: A cross-sectional, observational study was conducted between May and December 2024, involving 79 adult patients with confirmed type 1 or type 2 DM. Periodontal examinations assessed probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP). Salivary samples were collected to quantify IL-1β, IL-6, and MMP-8. Participants also completed a structured questionnaire on oral symptoms, hygiene practices, and awareness of the diabetes-periodontitis link. Correlation and t-test analyses were used to explore associations between clinical, biochemical, and self-reported variables. Results: Most participants had advanced periodontitis (65.8% Stage IV; 72.2% Grade C). IL-1β and IL-6 were positively correlated (r = 0.34, p < 0.01), while MMP-8 correlated with PI (r = 0.28) and BOP (r = 0.26). Inflammatory markers showed weak correlation with HbA1c. Notably, patients with higher oral health knowledge reported worse clinical indices, suggesting increased symptom awareness rather than preventive effectiveness. Conclusions: This study reinforces the inflammatory link between DM and PD and highlights the need for integrated care models. Periodontal screening and education should be embedded within diabetes management, particularly in high-risk populations.
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Affiliation(s)
- Vanessa Bolchis
- Translational and Experimental Clinical Research Centre in Oral Health, Department of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, 300040 Timisoara, Romania; (V.B.); (D.J.); (A.G.)
| | - Daniela Jumanca
- Translational and Experimental Clinical Research Centre in Oral Health, Department of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, 300040 Timisoara, Romania; (V.B.); (D.J.); (A.G.)
| | - Ramona Dumitrescu
- Translational and Experimental Clinical Research Centre in Oral Health, Department of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, 300040 Timisoara, Romania; (V.B.); (D.J.); (A.G.)
- Clinic of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No 2, 300041 Timisoara, Romania
| | - Octavia Balean
- Translational and Experimental Clinical Research Centre in Oral Health, Department of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, 300040 Timisoara, Romania; (V.B.); (D.J.); (A.G.)
- Clinic of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No 2, 300041 Timisoara, Romania
| | - Nicoleta A. Toderas
- Specialization in Clinical Psychology and Psychotherapy, Department of Psychology, Faculty of Sociology and Psychology, West University of Timișoara, 300223 Timisoara, Romania;
| | - Simona Popescu
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania
| | - Anca Marcu
- Department of Biochemistry and Pharmacology, “Victor Babes” University of Medicine and Pharmacy, PtaEfimie Murgu Nr. 2, 300041 Timisoara, Romania; (A.M.); (C.M.)
| | - Catalin Marian
- Department of Biochemistry and Pharmacology, “Victor Babes” University of Medicine and Pharmacy, PtaEfimie Murgu Nr. 2, 300041 Timisoara, Romania; (A.M.); (C.M.)
| | - Atena Galuscan
- Translational and Experimental Clinical Research Centre in Oral Health, Department of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, 300040 Timisoara, Romania; (V.B.); (D.J.); (A.G.)
- Clinic of Preventive, Community Dentistry and Oral Health, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No 2, 300041 Timisoara, Romania
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12
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Wang L, Liu T, Zhang W, Liu H, Qi Y, Li M. BMAL1-downregulation drives PANoptosis and the osteogenic differentiation impairment of PDLSCs by ERK/AP-1 signaling pathway. J Periodontol 2025. [PMID: 40259757 DOI: 10.1002/jper.24-0497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 11/24/2024] [Accepted: 12/21/2024] [Indexed: 04/23/2025]
Abstract
BACKGROUND One strategy to delay bone loss in periodontitis involves maintaining the osteogenic differentiation function of periodontal ligament stem cells (PDLSCs). The core circadian gene BMAL1 influences the fate of mesenchymal stem cells and is essential for regulating pyroptosis, apoptosis, and necroptosis. PANoptosis, a novel form of programmed cell death, simultaneously activates all 3 pathways. This study focuses on the role of BMAL1, the process of PANoptosis, and the osteogenic impairment of PDLSCs. METHODS A mouse periodontitis model was established to evaluate the expression of BMAL1 and osteogenic factors. We stimulated PDLSCs with lipopolysaccharide (LPS) and used a Western blot to detect PANoptosis-related factors. Osteogenic factors in PDLSCs were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, alkaline phosphatase, and alizarin red staining. The expression of ERK pathway proteins was examined by immunofluorescence and Western blot to investigate how BMAL1 regulates PANoptosis under inflammatory conditions. RESULTS Treatment with LPS leads to the downregulation of BMAL1 expression, which subsequently induces RIPK1-PANoptosome-mediated PANoptosis in PDLSCs, impairing their osteogenic differentiation function. Inhibition of the RIPK1-PANoptosome with Nec-1S improved the expression of osteogenic differentiation-related genes and proteins. Overexpression of BMAL1 using the synthetic ligand SR1078 alleviated these detrimental effects. Inhibition of the ERK pathway with U0126 reduced the expression of its downstream target AP-1, effectively reversing the impact of BMAL1 on PANoptosis. CONCLUSIONS The downregulation of BMAL1 triggers PANoptosis in PDLSCs, leading to impaired osteogenic function under inflammatory conditions. This study provides new insights into the pathogenesis of periodontitis and suggests novel targets for its prevention and treatment. PLAIN LANGUAGE SUMMARY Periodontitis is a chronic inflammatory condition of the oral cavity marked by the destruction of periodontal attachment and resorption of alveolar bone. One strategy to delay alveolar bone loss in periodontitis involves maintaining the osteogenic differentiation function of periodontal ligament stem cells (PDLSCs). The circadian rhythm influences the fate of mesenchymal stem cells, with the core circadian gene BMAL1 playing a crucial role in regulating pyroptosis, apoptosis, and necroptosis. PANoptosis is a novel form of programmed cell death, encompassing pyroptosis, apoptosis, and necroptosis, which may play a role in regulating the osteogenic activity of PDLSCs. Our study aims to detect the role of PANoptosis of PDLSCs in periodontitis and elucidate the underlying relationship between BMAL1 and PANoptosis. We found that treatment with lipopolysaccharide leads to the downregulation of BMAL1 expression, which subsequently induces RIPK1-PANoptosome-mediated PANoptosis in PDLSCs, impairing their osteogenic differentiation function. Notably, inhibition of the RIPK1-PANoptosome improved the expression of osteogenic differentiation-related genes and proteins. Mechanistic exploration revealed that BMAL1 downregulation induces PANoptosis in PDLSCs through the ERK/AP-1 signaling pathway. This study highlights the potential therapeutic targets for mitigating bone loss in periodontitis.
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Affiliation(s)
- Luxu Wang
- School of Stomatology, Jinzhou Medical University, Jinzhou, China
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
- Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Ting Liu
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
- Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Weidong Zhang
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
- Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Hongrui Liu
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
- Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yuping Qi
- Department of Oral Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Minqi Li
- School of Stomatology, Jinzhou Medical University, Jinzhou, China
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
- Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
- School of Clinical Medicine, Jining Medical University, Jining, China
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13
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Sachelarie L, Stefanescu CL, Murineanu RM, Grigorian M, Zaharia A, Scrobota I, Hurjui LL. Role of Salivary Biomarkers IL-1β and MMP-8 in Early Detection and Staging of Periodontal Disease. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:760. [PMID: 40283051 PMCID: PMC12028559 DOI: 10.3390/medicina61040760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 04/06/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025]
Abstract
Background: Periodontal disease is a chronic inflammatory condition affecting the supporting tissues of the teeth. Early diagnosis is crucial for preventing severe complications. This study investigates and compares the utility of two salivary biomarkers, interleukin-1 beta (IL-1β) and matrix metalloproteinase-8 (MMP-8), in the early detection and staging of periodontal disease. Methods: This study included 189 patients, all of whom were evaluated both clinically and biologically. Each participant provided unstimulated saliva samples, which were analyzed using ELISA methods to quantify IL-1β and MMP-8 levels. Clinical periodontal data, including probing depth (3.9 ± 0.6 mm), clinical attachment loss (3.4 ± 0.6 mm), and Plaque Index (2.35 ± 0.55), were collected for all subjects. Biomarker concentrations were then correlated with these clinical parameters and with disease severity, classified according to the 2018 EFP/AAP criteria. Results: IL-1β levels (210 ± 95 pg/mL) were strongly associated with early gingival inflammation, while MMP-8 levels (185 ± 140 ng/mL) correlated with periodontal tissue destruction (p < 0.01). MMP-8 showed a higher sensitivity for diagnosing advanced stages (p = 0.002), whereas IL-1β was more effective in detecting early inflammatory changes (p = 0.01). Logistic regression identified MMP-8 as a significant predictor of advanced disease (coefficient 0.85, p < 0.001) and IL-1β as an indicator of early inflammation (coefficient 0.25, p = 0.02). Conclusions: Both biomarkers are valuable tools for the diagnosis and staging of periodontal disease. MMP-8 is relevant for identifying advanced cases, while IL-1β supports early detection. Their combined use may enhance diagnostic accuracy and guide personalized periodontal care.
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Affiliation(s)
- Liliana Sachelarie
- Department of Preclinical Discipline, Faculty of Dental Medicine, Apollonia University, 700511 Iasi, Romania
| | - Corina Laura Stefanescu
- Faculty of Medicine and Pharmacy, University Ovidius, 900527 Constanta, Romania; (R.M.M.); (M.G.); (A.Z.)
| | - Rodica Maria Murineanu
- Faculty of Medicine and Pharmacy, University Ovidius, 900527 Constanta, Romania; (R.M.M.); (M.G.); (A.Z.)
| | - Mircea Grigorian
- Faculty of Medicine and Pharmacy, University Ovidius, 900527 Constanta, Romania; (R.M.M.); (M.G.); (A.Z.)
| | - Agripina Zaharia
- Faculty of Medicine and Pharmacy, University Ovidius, 900527 Constanta, Romania; (R.M.M.); (M.G.); (A.Z.)
| | - Ioana Scrobota
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 10 1st December Street, 410073 Oradea, Romania;
| | - Loredana Liliana Hurjui
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, University Street 16, 700115 Iasi, Romania;
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14
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Zhuang J, Ren Y, Chen M, Yue M, Yuan C, Duan R. Efficacy of localized sustained-release drugs in periodontitis and comorbid diabetes: A systematic review and meta-analysis. iScience 2025; 28:112182. [PMID: 40201124 PMCID: PMC11978340 DOI: 10.1016/j.isci.2025.112182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 01/19/2025] [Accepted: 03/04/2025] [Indexed: 04/10/2025] Open
Abstract
Our meta-analysis aimed to evaluate the efficacy of localized sustained-release drugs in periodontitis and comorbid diabetes. PubMed, Cochrane Library, Embase, and Web of Science were comprehensively searched until 4 December 2024, and 10 randomized controlled trials (RCTs) were included. The results indicated that, compared to the control group, localized sustained-release drugs significantly reduced probing depth (PD) (SMD = -0.77, 95% confidence interval [CI] (-1.37, -0.16)) but did not reduce clinical attachment loss (CAL) (SMD = -0.18, 95% CI (-0.60, 0.23)), sites with glycated hemoglobin (HbA1c) (SMD = 0.03, 95% CI (-0.38, 0.43)), plaque index (SMD = -0.37, 95% CI (-0.80, 0.06)), sites with bleeding on probing (BOP) (SMD = -0.26, 95% CI (-0.68, 0.16)), and gingival index (SMD = 0.07, 95% CI (-0.30, 0.44)). Subgroup analysis by different drugs elicited that, compared to the control treatment, chlorhexidine was effective in reducing BOP% (SMD = -0.55, 95% CI (-0.90, -0.19)). Our meta-analysis finds that the efficacy of localized sustained-release drugs in periodontitis and comorbid diabetes is limited.
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Affiliation(s)
- Jingru Zhuang
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
| | - Ying Ren
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
| | - Minmin Chen
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
| | - Minghui Yue
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
| | - Changyong Yuan
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- The Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
| | - Rongquan Duan
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Sichuan Vista Medical Devices Co., Ltd., Luzhou, Sichuan 646000, China
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15
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Adamowicz K, Lima Ribeiro AS, Golda A, Wadowska M, Potempa J, Schmaderer C, Anders HJ, Koziel J, Lech M. Bidirectional Interaction Between Chronic Kidney Disease and Porphyromonas gingivalis Infection Drives Inflammation and Immune Dysfunction. J Immunol Res 2025; 2025:8355738. [PMID: 40276114 PMCID: PMC12021489 DOI: 10.1155/jimr/8355738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 12/22/2024] [Accepted: 02/04/2025] [Indexed: 04/26/2025] Open
Abstract
Introduction: Chronic kidney disease (CKD) is characterized by a decline in renal function, increased mortality, and significant impairments in the immune system and function of immune cells. These alterations are often derived by uremic toxins, which, in turn, modify the immune system's response to infections. Our research investigates the progression of Porphyromonas gingivalis (P. gingivalis) infection during CKD and its subsequent impact on kidney failure. Methods: We utilized two infectious models, a chamber model representing short-term local inflammation and alveolar bone loss that mimic chronic infection of periodontium, both in conjunction with a CKD model. Additionally, our in vitro studies employed primary macrophages, osteoclasts, and lymphocytes to characterize the immune responses to P. gingivalis and pathogen-associated molecular patterns (PAMPs) in the presence of uremic toxins. Results and Conclusion: Our findings demonstrate that uremic toxins, such as indoxyl sulfate (IS), alter responses of macrophages and lymphocytes to P. gingivalis. In vivo, CKD significantly enhanced P. gingivalis survival and infection-induced alveolar bone loss. The increased distribution of pathogen within peripheral tissues was associated with altered inflammatory responses, indicating that CKD promotes infection. Moreover, P. gingivalis-infected mice exhibited a marked increase in renal inflammation, suggesting that the relationship between uremia and infection is bidirectional, with infection exacerbating kidney dysfunction. Furthermore, we observed that infected CKD mice exhibit decreased serum immunoglobulin G (IgG) levels compared to infected mice without CKD, implying that uremia is associated with immune dysfunction characterized by immunodepression and impaired B lymphocyte function.
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Affiliation(s)
- Karina Adamowicz
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland
| | - Andrea Sofia Lima Ribeiro
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
- TUM University Hospital, Technical University Munich (TUM), Munich, Germany
| | - Anna Golda
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland
| | - Marta Wadowska
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland
| | - Jan Potempa
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland
- Department of Oral Immunity and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA
| | | | - Hans-Joachim Anders
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Joanna Koziel
- Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland
| | - Maciej Lech
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
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16
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Puzhankara L, Janakiram C, Gutjahr G, Bijukumar SC, Vasthare R, Kedlaya MN, Shetty S, Pai AR, Rao S, Srinivasan S, Fenol A. Risk correlates of cardiovascular diseases, diabetes, and periodontal diseases: a cross-sectional study in India. BMC Oral Health 2025; 25:576. [PMID: 40234889 PMCID: PMC12001716 DOI: 10.1186/s12903-025-05742-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 03/03/2025] [Indexed: 04/17/2025] Open
Abstract
BACKGROUND Quantifying shared risk factors among periodontal disease (PD), cardiovascular disease (CVD), type 2 diabetes (DM2) can bolster Common Risk Factor Approach (CRFA), enabling integration of PD prevention into non-communicable disease (NCD) prevention strategies. The objective of the study is to assess extent of overlap of shared risk factors between CVD, DM2, PD. MATERIALS AND METHODS This is an analytical cross-sectional study conducted at a tertiary care medical and dental teaching hospital in South India, from July 2022 to April 2024. Study included 600 participants (ages 18-75) divided into three groups: Group A: DM2, CVD, or both and PD; Group B: DM2 or CVD; and Group C: PD alone. Various demographic, metabolic, habit related, dietary and periodontal disease severity related risk factors were evaluated in the study. RESULTS Among 600 participants, 55.5% were male, 58.8% were under 50 years. Statistically significant odds ratios (ORs) for shared risk factors between Group A and Group B were observed for age > 50 (0.58), sedentary lifestyle (0.43), fat intake > 41 g/d (1.87), HbA1C ≥ 6.5% (0.56), FBS > 126 mg/dL (2.35) and family history of NCDs (9.8). For Group A versus Group C, statistically significant ORs were seen for age > 50 (0.55), HbA1c 5.7%-6.4% (0.34), triglycerides > 150 mg/dL (0.04), education (0.52), alcohol use (1.53) and poor oral hygiene (3.01). Severity of periodontal disease assessed using PSR, HbA1c, triglycerides, fat intake, age, education, obesity were identified as vital shared risk factors. CONCLUSION AND RELEVANCE: Age, education, obesity, PSR, HbA1c, triglycerides emerged as significant shared risk factors. Integrating these factors into surveillance tools may enhance NCD and PD risk identification, supporting CRFA-based healthcare approach. TRIAL REGISTRATION CTRI/ 2022/06/043279 registered on 15th of June 2022.
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Affiliation(s)
- Lakshmi Puzhankara
- Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | | | - Georg Gutjahr
- Department of Health Science Research, Amrita Institute of Medical Sciences and Research Center, Kochi, Kerala, India
| | | | - Ramprasad Vasthare
- Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Madhurya N Kedlaya
- Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Sahana Shetty
- Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Aparna Ramakrishna Pai
- Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | | | - Sowmya Srinivasan
- Department of Periodontics, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Angel Fenol
- Department of Periodontics, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
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17
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Luo R, Liang Z, Chen H, Bao D, Lin X. Potential diagnostic markers and therapeutic targets for DM2 and periodontitis based on bioinformatics analysis. PLoS One 2025; 20:e0320061. [PMID: 40173189 PMCID: PMC11964240 DOI: 10.1371/journal.pone.0320061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 02/11/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND Diabetes Mellitus type 2 (DM2) is thought to have a bidirectional relationship with Periodontitis (PD). However, the complex molecular interactions between DM2 and PD remain unclear. This study aimed to explore the shared genes and common signatures of DM2 and PD via bioinformatic analysis. METHODS Firstly, using bioinformatic methods to investigate common genes. The series matrix files of GSE6751 for DM and GSE15932 for PD were downloaded from the Gene Expression Omnibus (GEO) database. The data was normalized using the R package, and the limma package was utilized to identify the Differentially Expressed Genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs were performed using the "clusterProfiler" package in the R software. The protein-protein network was constructed to analyze the potential relationship among the proteins. CytoHubba, a plugin for the Cytoscape software, was used to identify the hub genes. The validation datasets selected for DM2 and PD were GSE10334 and GSE7014, respectively. Receiver Operating Characteristic (ROC) curve analysis was performed to obtain the area under the ROC curve. Lipopolysaccharide (LPS) + high glucose-induced DM-related PD was simulated to verify the three hub genes through quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot (WB). RESULTS In total, 44 common DEGs were identified. ITGAM, H2BC21, S100A9 was identified as he hub genes of DM2 and PD, with all of them were up-regulated. In addition, the area under the curve of all three hub genes was more than 0.65. In-vitro experiments revealed that the relative expression of S100A9 was increased after the treatment with LPS + high glucose. Besides, TLR4 and p-NF-κB levels were also improved in model group. CONCLUSION S100A9 was identified as the hub gene of DM2 and PD. S100A9 could trigger TLR4 signaling way to promote disease development, which can be the potential targets for diagnosis and treatment.
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Affiliation(s)
- Rong Luo
- Department of Pharmacy, Taizhou First People’s Hospital, Taizhou, China
| | - Zhenye Liang
- Department of Pharmacy, Taizhou First People’s Hospital, Taizhou, China
| | - Huijun Chen
- Department of Pharmacy, Taizhou First People’s Hospital, Taizhou, China
| | - Dandan Bao
- Department of Pharmacy, Taizhou First People’s Hospital, Taizhou, China
| | - Xinlu Lin
- Department of Pharmacy, Taizhou First People’s Hospital, Taizhou, China
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18
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Anil S, Joseph B, Pereira MA, Arya S, Syamala S, Sweety VK, Jayasinghe R. Diabetic Retinopathy and Periodontitis: Implications from a Systematic Review and Meta-Analysis. Int Dent J 2025; 75:453-463. [PMID: 39592324 PMCID: PMC11976626 DOI: 10.1016/j.identj.2024.10.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/28/2024] [Accepted: 10/27/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Diabetes mellitus, a chronic metabolic disorder affecting millions worldwide, is associated with microvascular complications, including diabetic retinopathy (DR) and periodontitis. Understanding their interrelationship is crucial for comprehensive patient care. OBJECTIVE This systematic review and meta-analysis aim to investigate the association between DR and periodontitis in patients with Type 1 and Type 2 diabetes. METHODOLOGY Using the PECO framework, we searched PubMed/MEDLINE, Scopus, EMBASE, Google Scholar, and Web of Science databases (Inception to April 2023) for studies on the association between DR and periodontitis. Ten studies (n = 1828 participants), including observational and cross-sectional studies, met the inclusion criteria. We conducted qualitative synthesis, risk of bias analysis using the ROBINS-E tool, Grading of Recommendations, Assessment, Development, and Evaluations assessment (GRADE), and random-effects meta-analysis. RESULTS Eight studies found a significant association between severe periodontitis (pocket depth ≥5 mm) and DR, while two found no association. Meta-analysis of 843 participants showed diabetics with periodontitis had 4.48 times higher odds (95% confidence interval: 1.67-12.07, P = .003) of developing retinopathy compared to diabetics without periodontitis. High heterogeneity was observed (I2 = 86%). Subgroup analysis by diabetes type showed no significant difference. The overall GRADE level of evidence was very low. CONCLUSION While most included studies suggest an association between severe periodontitis and increased DR risk, the overall certainty of evidence is low. These findings highlight the potential importance of periodontal health in diabetic patients. High-quality longitudinal studies with adequate control of confounders are required to determine if periodontitis contributes to the progression of DR or if the conditions are merely coincidentally related.
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Affiliation(s)
- Sukumaran Anil
- Oral Health Institute, Hamad Medical Corporation, Doha, Qatar; College of Dental Medicine, Qatar University, Doha, Qatar.
| | - Betsy Joseph
- Department of Periodontology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Pushpagiri Institute of Medical Sciences and Research Centre, Medicity, Thiruvalla, Kerala, India
| | - Merlyn Anjali Pereira
- Department of Ophthalmology, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Saket Arya
- Department of Ophthalmology, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | | | - Vishnupriya K Sweety
- Pushpagiri Institute of Medical Sciences and Research Centre, Medicity, Thiruvalla, Kerala, India
| | - Ruwan Jayasinghe
- Department of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka
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Yang J. Unveiling the multifaceted roles of long non-coding RNA CTBP1-DT in human diseases: Special attention to its microprotein-encoding potential. Pathol Res Pract 2025; 268:155870. [PMID: 40020329 DOI: 10.1016/j.prp.2025.155870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/30/2025] [Accepted: 02/25/2025] [Indexed: 03/03/2025]
Abstract
C-terminal binding protein 1 divergent transcript (CTBP1-DT) is a novel long non-coding RNA (lncRNA) located on human chromosome 4p16.3. Numerous studies have shown that CTBP1-DT plays a critical regulatory role in various human malignancies and non-malignant diseases. In several cancers, the expression of CTBP1-DT is upregulated, closely associated with the risk of 12 types of cancer, and strongly correlated with the clinical pathological features and poor prognosis of 10 of these cancers. Mechanistically, CTBP1-DT is stimulated by the transcription factors ETV5 and Sp1, or methylated by YTHDC1. By competitively inhibiting 12 microRNAs, it activates 3 signaling pathways that influence malignant behaviors of tumor cells, including proliferation, apoptosis, cell cycle arrest, migration, invasion, immune evasion, and chemoresistance. Importantly, it also encodes the microprotein DNA damage up-regulated protein (DDUP), which mediates cisplatin resistance through sustained response to DNA damage signals. Furthermore, CTBP1-DT has been implicated in the progression of non-malignant diseases such as diabetes and related conditions, cardiovascular diseases, and osteoarthritis. This review summarizes the latest research on the RNA and protein functions of CTBP1-DT in human diseases, outlines various molecular regulatory networks centered around CTBP1-DT, and discusses the opportunities and challenges of its clinical applications.
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Affiliation(s)
- Jingjie Yang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
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20
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Adachi N, Sugimoto K, Suzuki H, Shinada K. Influence of oral health status on absenteeism and presenteeism as indices of work productivity loss. J Dent Sci 2025; 20:794-801. [PMID: 40224118 PMCID: PMC11993063 DOI: 10.1016/j.jds.2024.09.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 09/27/2024] [Indexed: 04/15/2025] Open
Abstract
Background/Purpose Work productivity reduction due to oral health problems has not been well investigated. This study aimed to examine the impact of oral health status, including periodontitis, dental caries, and oral health-related quality of life (QOL), on absenteeism and presenteeism. Materials and methods This cross-sectional study included 559 workers of a Japanese industrial company. Data on dental health and general health checkups were obtained from workers' health records, and the workers responded to questionnaires on work productivity loss due to oral health problems, job stress, and oral health-related QOL. The odds ratio (OR) and 95% confidence interval (CI) for presenteeism and absenteeism were calculated using multiple logistic regression analyses of oral health status and oral health-related QOL adjusting with sex, age, educational background, occupation, job stress, current smoking, and hypertension. Results Of the 559 participants, 6.6% and 8.9% reported absenteeism and presenteeism, respectively, due to oral health problems. Multiple logistic regression analyses identified the number of decayed teeth (OR = 1.12, 95%CI = 1.02-1.24) as a significantly associated factor with presenteeism, and additionally low oral health-related QOL with both absenteeism (OR = 2.48, 95%CI = 1.20-5.11) and presenteeism (OR = 5.00, 95%CI = 2.46-10.19). Conclusion The number of decayed teeth and low oral health-related QOL were significantly associated with presenteeism and/or absenteeism. This highlights oral health problem as a potential factor for productivity loss.
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Affiliation(s)
- Naoko Adachi
- Department of Preventive Oral Health Care Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kumiko Sugimoto
- Department of Preventive Oral Health Care Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Oral Health Care Education, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hitomi Suzuki
- Department of Oral Health Care Education, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kayoko Shinada
- Department of Preventive Oral Health Care Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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Liu RL, Ou YP, Zhang Q, Yang YF. Mendelian Randomization Reveals No Causal Association Between Periodontitis and Infective Endocarditis. Int Dent J 2025; 75:832-839. [PMID: 39097439 PMCID: PMC11976596 DOI: 10.1016/j.identj.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/15/2024] [Accepted: 07/17/2024] [Indexed: 08/05/2024] Open
Abstract
OBJECTIVES Clarifying the uncertain causal relationship between periodontitis and infective endocarditis using Mendelian randomization analysis, given their historically perceived association and clinical significance. METHODS Genetic variation data for acute periodontitis, chronic periodontitis, aggressive periodontitis, and infective endocarditis were obtained from published GWAS in individuals of European ancestry. Instrumental variables significantly associated with periodontitis were selected and univariable Mendelian randomization was conducted to infer the causal association between periodontitis and infective endocarditis. Multivariable Mendelian randomization was also performed to adjust for potential confounders including smoking, drinking, diabetes, and education. RESULTS Our analysis found no evidence of a causal association between periodontitis and infective endocarditis, with odds ratios (ORs) of 0.992 (95% CI: 0.879-1.120), 0.947 (95% CI: 0.738-1.214), and 1.056 (95% CI: 0.916-1.217) for acute periodontitis, chronic periodontitis, aggressive periodontitis, respectively. The robustness of our findings was confirmed by heterogeneity tests, pleiotropy tests, leave-one-out analyses, and MR-PRESSO. In the multivariable MR analysis, adjusting for smoking, drinking, diabetes, and education, the overall patterns between genetic liability to periodontitis and infective endocarditis remained consistent (all P > .05). CONCLUSION Our findings indicate that there is no genetic causal association between periodontitis and infective endocarditis.
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Affiliation(s)
- Rui-Lin Liu
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China
| | - Yu-Ping Ou
- Department of Ultrasound, Chen Zhou No. 1 People's Hospital, ChenZhou, China
| | - Qian Zhang
- Department of Stomatology, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China
| | - Yi-Feng Yang
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.
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Li C, Du L, Xiao Y, Fan L, Li Q, Cao CY. Multi-active phlorotannins boost antimicrobial peptide LL-37 to promote periodontal tissue regeneration in diabetic periodontitis. Mater Today Bio 2025; 31:101535. [PMID: 39990735 PMCID: PMC11847560 DOI: 10.1016/j.mtbio.2025.101535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 12/23/2024] [Accepted: 01/30/2025] [Indexed: 02/25/2025] Open
Abstract
The bidirectional correlation between diabetes and periodontitis positions the latter as the most prevalent complication of the former. Rehabilitation of the periodontal tissues damaged by diabetic periodontitis presents a significant clinical challenge. The multifaceted nature of the pathogenesis of diabetic periodontitis necessitates a comprehensive approach in its treatment to mitigate its adverse effects. To address this, a temperature-sensitive hydrogel containing phlorotannins (PL) and antimicrobial peptide LL-37 was developed to shift the microenvironment of diabetic periodontitis from an exacerbated high-glycemic inflammatory state to a regenerative one. The addition of PL significantly enhanced the antimicrobial properties, stability, and safety of LL-37. Vitro experiments confirmed that PL/LL-37 had good biocompatibility and promoted osteogenic differentiation of bone. PL/LL-37 demonstrated antioxidant properties by scavenging DPPH free radicals and inhibiting NO production. Furthermore, PL/LL-37 effectively modulated macrophage polarization from a M1 phenotype to an M2 phenotype through NF-κB P-p65 inflammatory pathway, thereby reducing the release of pro-inflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Interestingly, it could downregulate the AGE-RAGE signaling pathway, exerting a protective effect against diabetes. In addition, PL/LL-37 could attenuate inflammation levels, inhibit osteoclast production, promote bone regeneration, inhibit apoptosis and decrease RAGE levels in a rat model of diabetic periodontitis. These combined features synergistically accelerate diabetic periodontal bone regeneration. Consequently, PL/LL-37 emerges as a promising candidate for clinical treatment of diabetic periodontitis.
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Affiliation(s)
- Cancan Li
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China
| | - Luowen Du
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China
| | - Yingying Xiao
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China
| | - Lei Fan
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China
| | - Quanli Li
- Institute of Oral Science, Department of Stomatology, Longgang Otorhinolaryngology Hospital of Shenzhen, Shenzhen, 518172, China
| | - Chris Ying Cao
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China
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Sólis‐Suarez DL, Cifuentes‐Mendiola SE, González‐Alva P, Rodríguez‐Hernández AP, Martínez‐Dávalos A, Llamosas‐Hernandez FE, Godínez‐Victoria M, García‐Hernández AL. Lipocalin-2 as a fundamental protein in type 2 diabetes and periodontitis in mice. J Periodontol 2025; 96:369-382. [PMID: 39189666 PMCID: PMC12062733 DOI: 10.1002/jper.24-0215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 08/07/2024] [Accepted: 08/07/2024] [Indexed: 08/28/2024]
Abstract
BACKGROUND Lipocalin-2 (LCN-2) is an osteokine that suppresses appetite, stimulates insulin secretion, regulates bone remodeling, and is induced by proinflammatory cytokines. The aim of this work was to investigate the participation of LCN-2 in periodontitis associated with type 2 diabetes (T2D) by evaluating alveolar bone loss, glycemic control, inflammation, and femur fragility. METHODS A murine model of periodontitis with T2D and elevated LCN-2 concentration was used. Functional LCN-2 inhibition was achieved using an anti-LCN-2 polyclonal antibody, and isotype immunoglobulin G was used as a control. The alveolar bone and femur were evaluated by micro-CT. Glucose metabolism was determined. Tumor necrosis factor (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in alveolar bone lysates were quantified using ELISA, and serum cytokines were quantified using flow cytometry. A three-point bending test was performed in the femur, and RANKL levels were measured in femur lysates using ELISA. RESULTS Functional inhibition of LCN-2 in T2D-periodontitis mice decreased alveolar bone loss in buccal and palatal surfaces and preserved the microarchitecture of the remaining bone, decreased TNF-α and RANKL in alveolar bone, reduced hyperglycemia, glucose intolerance, and insulin resistance, and increased insulin production through improving the functionality of pancreatic β cells. Furthermore, this inhibition increased serum free-glycerol levels, decreased serum interleukin (IL)-6, increased serum IL-4, and reduced femur fragility and RANKL expression in the femur. CONCLUSIONS LCN-2 participates in periodontitis associated with T2D. Inhibiting its function in mice with T2D and periodontitis improves pancreatic β-cell function, and glucose metabolism and decreases inflammatory cytokines and bone-RANKL levels, which results in the preservation of femoral and alveolar bone microarchitecture. PLAIN LANGUAGE SUMMARY In this study, we explored the role of a bone protein known as lipocalin-2 (LCN-2) in the connection between periodontitis and type 2 diabetes (T2D). Periodontitis is a destructive gum and alveolar bone disease. LCN-2 levels are increased in both T2D and periodontitis. Using a mouse model of T2D with periodontitis, we examined how blocking LCN-2 function affected various aspects of these two diseases. We found that this inhibition led to significant improvements. First, it reduced alveolar bone loss and preserved bone structure by decreasing local inflammation and bone resorption. Second, it improved glucose and lipid metabolism, leading to better blood-sugar control and decreased insulin resistance. Blocking the functions of LCN-2 also decreased systemic inflammation throughout the body and strengthened bone integrity. Overall, our results suggest that LCN-2 plays a crucial role in the periodontitis associated with T2D. By inhibiting LCN-2 function, we were able to improve pancreatic function, improve glucose metabolism, reduce inflammation, and enhance bone health. Targeting LCN-2 could be a promising strategy for the harmful effects of T2D and periodontitis.
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Affiliation(s)
- Diana Laura Sólis‐Suarez
- Laboratory of Dental Research, Section of Osteoimmunology and Oral Immunology, FES IztacalaNational Autonomous University of Mexico (UNAM)State of MexicoMexicoMexico
- Postgraduate Course in Dental SciencesNational Autonomous University of MexicoMexico CityMexico
| | - Saúl Ernesto Cifuentes‐Mendiola
- Laboratory of Dental Research, Section of Osteoimmunology and Oral Immunology, FES IztacalaNational Autonomous University of Mexico (UNAM)State of MexicoMexicoMexico
| | - Patricia González‐Alva
- Laboratory of Tissue Bioengineering, Faculty of DentistryNational Autonomous University of Mexico (UNAM)Mexico CityMexico
| | | | - Arnulfo Martínez‐Dávalos
- Endo‐periodontology DepartmentPhysics InstituteNational Autonomous University of Mexico (UNAM)Mexico CityMexico
| | | | - Marycarmen Godínez‐Victoria
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de MedicinaInstituto Politécnico NacionalMexico CityMexico
| | - Ana Lilia García‐Hernández
- Laboratory of Dental Research, Section of Osteoimmunology and Oral Immunology, FES IztacalaNational Autonomous University of Mexico (UNAM)State of MexicoMexicoMexico
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Pawlowska E, Szczepanska J, Derwich M, Sobczuk P, Düzgüneş N, Blasiak J. DNA Methylation in Periodontal Disease: A Focus on Folate, Folic Acid, Mitochondria, and Dietary Intervention. Int J Mol Sci 2025; 26:3225. [PMID: 40244046 PMCID: PMC11990040 DOI: 10.3390/ijms26073225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/19/2025] [Accepted: 03/30/2025] [Indexed: 04/18/2025] Open
Abstract
Although periodontal disease (PD) is reported to be associated with changes in various genes and proteins in both invading bacteria and the host, its molecular mechanism of pathogenesis remains unclear. Changes in immune and inflammatory genes play a significant role in PD pathogenesis. Some reports relate alterations in cellular epigenetic patterns to PD characteristics, while several high-throughput analyses indicate thousands of differentially methylated genes in both PD patients and controls. Furthermore, changes in DNA methylation patterns in inflammation-related genes have been linked to the efficacy of periodontal therapy, as demonstrated by findings related to the cytochrome C oxidase II gene. Distinct DNA methylation patterns in mesenchymal stem cells from PD patients and controls persisted despite the reversal of phenotypic PD. Methyl groups for DNA methylation are supplied by S-adenosylmethionine, which is synthesized with the involvement of folate, an essential nutrient known to play a role in maintaining mitochondrial homeostasis, reported to be compromised in PD. Folate may benefit PD through its antioxidant action against reactive oxygen and nitrogen species that are overproduced by dysfunctional mitochondria. As such, DNA methylation, dietary folate, and mitochondrial quality control may interact in PD pathogenesis. In this narrative/hypothesis review, we demonstrate how PD is associated with changes in mitochondrial homeostasis, which may, in turn, be improved by folate, potentially altering the epigenetic patterns of immune and inflammatory genes in both the nucleus and mitochondria. Therefore, a folate-based dietary intervention is recommended for PD prevention and as an adjunct therapy. At the same time, further research is needed on the involvement of epigenetic mechanisms in the beneficial effects of folate on PD studies.
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Affiliation(s)
- Elzbieta Pawlowska
- Department of Pediatric Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland; (E.P.); (J.S.); (M.D.)
| | - Joanna Szczepanska
- Emergency Medicine and Disaster Medicine Department, Medical University of Lodz, Pomorska 251, 92-209 Lodz, Poland;
| | - Marcin Derwich
- Department of Pediatric Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland; (E.P.); (J.S.); (M.D.)
| | - Piotr Sobczuk
- Emergency Medicine and Disaster Medicine Department, Medical University of Lodz, Pomorska 251, 92-209 Lodz, Poland;
- Department of Orthopaedics and Traumatology, Polish Mothers’ Memorial Hospital—Research Institute, Rzgowska 281, 93-338 Lodz, Poland
| | - Nejat Düzgüneş
- Department of Biomedical Sciences, University of the Pacific—San Francisco Campus, San Francisco, CA 94103, USA;
| | - Janusz Blasiak
- Faculty of Medicine, Collegium Medicum, The Mazovian University in Plock, 04-920 Plock, Poland
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Menezes CFS, Lage LM, Santos LGS, Nascimento GC, Magalhães M, Facundo A, Silva DA, Porto LC, Gomes MB, Faria MDS, Azulay RS, Rodrigues V. HLA Polymorphisms Linked to the Severity and Extent of Periodontitis in Patients with Type 1 Diabetes from a Brazilian Mixed Population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2025; 22:512. [PMID: 40283738 PMCID: PMC12026859 DOI: 10.3390/ijerph22040512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 03/25/2025] [Accepted: 03/26/2025] [Indexed: 04/29/2025]
Abstract
This study aimed to investigate the relationship between Class II human leukocyte antigen (HLA) alleles (DRB1, DQA1, and DQB1) and the severity and extent of periodontitis in patients with Type 1 diabetes (T1D). A cross-sectional study was conducted with 49 patients with T1D. Demographic data and diabetes history were collected. A clinical examination was performed to assess periodontal variables. The patients were categorized by the periodontitis severity and the extent of periodontitis. Peripheral blood samples were analyzed to identify the percentage of autosomal ancestry (Native American, European, and African) and the HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles. The DRB1*03 and DRB1*15 haplogroups were significantly associated with an increased risk of generalized periodontitis (OR = 19.8, 95% CI = 1.14-346, p = 0.003; OR = 41.2, 95% CI = 1.85-917, p < 0.001) and severe periodontitis (OR = 7.7, 95% CI = 1.68-35.5, p = 0.003; OR = 21.2, 95% CI = 0.97-461, p = 0.005). No associations were observed between the HLA-DQA1 and HLA-DQB1 alleles and periodontitis. These findings suggest that patients with T1D from a highly mixed Brazilian population carrying the DRB1*03 and DRB1*15 haplogroups are at higher risk for developing more severe and generalized forms of periodontitis.
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Affiliation(s)
- Carlos Felipe Sousa Menezes
- School of Dentistry, Federal University of Maranhão, São Luís 65085-580, MA, Brazil; (C.F.S.M.); (L.M.L.); (L.G.S.S.)
| | - Lucas Meneses Lage
- School of Dentistry, Federal University of Maranhão, São Luís 65085-580, MA, Brazil; (C.F.S.M.); (L.M.L.); (L.G.S.S.)
| | - Luís Gustavo Souza Santos
- School of Dentistry, Federal University of Maranhão, São Luís 65085-580, MA, Brazil; (C.F.S.M.); (L.M.L.); (L.G.S.S.)
| | - Gilvan Cortês Nascimento
- Research Group in Clinical Endocrinology and Molecular Metabolism, São Luís 65020-070, MA, Brazil; (G.C.N.); (M.M.); (A.F.); (M.d.S.F.); (R.S.A.)
- School of Medicine, Federal University of Maranhão, São Luís 65020-240, MA, Brazil
| | - Marcelo Magalhães
- Research Group in Clinical Endocrinology and Molecular Metabolism, São Luís 65020-070, MA, Brazil; (G.C.N.); (M.M.); (A.F.); (M.d.S.F.); (R.S.A.)
- Graduate Program in Adult Health, Federal University of Maranhão, São Luís 65085-580, MA, Brazil
| | - Alexandre Facundo
- Research Group in Clinical Endocrinology and Molecular Metabolism, São Luís 65020-070, MA, Brazil; (G.C.N.); (M.M.); (A.F.); (M.d.S.F.); (R.S.A.)
| | - Dayse Aparecida Silva
- DNA Diagnostic Laboratory, Rio de Janeiro State University, Rio de Janeiro 20550-900, RJ, Brazil; (D.A.S.); (L.C.P.)
| | - Luís Cristóvão Porto
- DNA Diagnostic Laboratory, Rio de Janeiro State University, Rio de Janeiro 20550-900, RJ, Brazil; (D.A.S.); (L.C.P.)
| | - Marília Brito Gomes
- Diabetes Unit, State University of Rio de Janeiro, Rio de Janeiro 20551-030, RJ, Brazil;
| | - Manuel dos Santos Faria
- Research Group in Clinical Endocrinology and Molecular Metabolism, São Luís 65020-070, MA, Brazil; (G.C.N.); (M.M.); (A.F.); (M.d.S.F.); (R.S.A.)
- Graduate Program in Adult Health, Federal University of Maranhão, São Luís 65085-580, MA, Brazil
| | - Rossana Sousa Azulay
- Research Group in Clinical Endocrinology and Molecular Metabolism, São Luís 65020-070, MA, Brazil; (G.C.N.); (M.M.); (A.F.); (M.d.S.F.); (R.S.A.)
- Graduate Program in Adult Health, Federal University of Maranhão, São Luís 65085-580, MA, Brazil
| | - Vandilson Rodrigues
- School of Dentistry, Federal University of Maranhão, São Luís 65085-580, MA, Brazil; (C.F.S.M.); (L.M.L.); (L.G.S.S.)
- Research Group in Clinical Endocrinology and Molecular Metabolism, São Luís 65020-070, MA, Brazil; (G.C.N.); (M.M.); (A.F.); (M.d.S.F.); (R.S.A.)
- Graduate Program in Adult Health, Federal University of Maranhão, São Luís 65085-580, MA, Brazil
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Kang TG, Kim NY, Lee SM, Chung KH. Atherogenic index of plasma and periodontitis in non-dyslipidemic adults: a nationwide study. Clin Oral Investig 2025; 29:208. [PMID: 40140104 DOI: 10.1007/s00784-025-06277-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025]
Abstract
BACKGROUND This study investigated the association between atherogenic index of plasma (AIP)-related indices and periodontal diseases in adults without dyslipidemia using healthcare big data from Korea National Health & Nutrition Examination Survey (KNHANES). METHODS This cross-sectional study analyzed data from 16,343 adults in the 2010-2018 KNHANES. Periodontal status was assessed using the Community Periodontal Index (CPI), while AIP-related indices, including AIP, triglycerides (TG), and high-density lipoprotein cholesterol (HDL), were evaluated. Statistical analyses included chi-square tests and t-tests for group comparisons, multivariate logistic regression to calculate odds ratios (ORs) for periodontitis risk, and receiver operating characteristic (ROC) curve analysis to assess diagnostic accuracy. RESULTS Higher AIP-related indices (excluding HDL) were associated with an increased risk of periodontitis, while lower HDL levels also correlated with higher disease prevalence. (p < 0.0001). The AIP adjusted with waist-to-height ratio (AIP*WHtR) exhibited the highest diagnostic accuracy among all indices analyzed, with the highest area under the ROC curve (AUC), whereas HDL showed the lowest predictive value. CONCLUSIONS AIP-related indices were significantly associated with periodontitis in adults without dyslipidemia, with higher AIP-related indices linked to an increased risk of periodontitis. Among these, AIP*WHtR exhibited the highest diagnostic accuracy. However, due to the cross-sectional study design, causality cannot be determined. Thus, longitudinal studies are required to validate the predictive value of AIP-related indices for periodontitis risk.
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Affiliation(s)
- Tae-Gu Kang
- Chonnam National University School of Dentistry, Gwangju, Republic of Korea
| | - Na-Yeong Kim
- Department of Preventive and Public Health Dentistry, Chonnam National University School of Dentistry, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Sang-Min Lee
- Chonnam National University School of Dentistry, Gwangju, Republic of Korea
| | - Ki-Ho Chung
- Chonnam National University School of Dentistry, Gwangju, Republic of Korea.
- Department of Preventive and Public Health Dentistry, Chonnam National University School of Dentistry, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.
- Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea.
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Lipták K, Lipták L, Haba KS, Bányai D, Veres DS, Rózsa NK, Hermann P, Végh D. Oral health practices and literacy in Hungarian diabetes patients: insights from a pilot-study using a WHO-adapted questionnaire. BMC Oral Health 2025; 25:431. [PMID: 40140841 PMCID: PMC11938766 DOI: 10.1186/s12903-025-05820-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 03/17/2025] [Indexed: 03/28/2025] Open
Abstract
INTRODUCTION This study aimed to compare the self-reported oral health status, knowledge, and habits of individuals living with diabetes mellitus and healthy controls. To achieve this, the modified version of the World Health Organization's Oral Health Questionnaire for Adults (ANNEX 7; Google Forms) was employed for data collection. METHODS The study included 99 diabetes patients (33 with type 1 and 66 with type 2 diabetes mellitus) and 102 non-diabetic controls. Logistic regression models, adjusted for demographic factors, were applied to examine associations between oral hygiene practices, dietary habits, and the number of natural teeth. RESULTS Individuals with diabetes exhibited a greater frequency of oral pathological conditions. Despite 74% of people with diabetes mellitus (PwDM) brushing their teeth twice daily, they had fewer natural teeth compared to the control group (20 or more teeth: DM: 54.5%, controls: 70.6%). In our study, there is no evidence that number of teeth is dependent on HbA1c levels, and we found that neither age nor gender influenced the change in HbA1c levels. Lower interdental cleaning habits and frequent fruit consumption were identified as significant risk factors for severe tooth loss. CONCLUSION AND CLINICAL RELEVANCE This study highlights significant oral health disparities in diabetes patients, particularly those with T2DM, who reported poorer oral health, more frequent denture use, and fewer natural teeth. These findings underscore the need for integrating oral health education, preventive care, and interdisciplinary collaboration into diabetes management to improve overall health outcomes.
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Affiliation(s)
- Klaudia Lipták
- Department of Prosthodontics, Semmelweis University, Szentkirályi u. 47, Budapest, 1088, Hungary
| | - Laura Lipták
- Department of Paediatric Dentistry and Orthodontics, Semmelweis University, Szentkirályi u. 47, Budapest, 1088, Hungary
| | - Kata Sára Haba
- Department of Prosthodontics, Semmelweis University, Szentkirályi u. 47, Budapest, 1088, Hungary
| | - Dorottya Bányai
- Department of Paediatric Dentistry and Orthodontics, Semmelweis University, Szentkirályi u. 47, Budapest, 1088, Hungary
| | - Dániel S Veres
- Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, Budapest, 1094, Hungary
| | - Noémi Katinka Rózsa
- Department of Paediatric Dentistry and Orthodontics, Semmelweis University, Szentkirályi u. 47, Budapest, 1088, Hungary
| | - Péter Hermann
- Department of Prosthodontics, Semmelweis University, Szentkirályi u. 47, Budapest, 1088, Hungary
| | - Dániel Végh
- Department of Prosthodontics, Semmelweis University, Szentkirályi u. 47, Budapest, 1088, Hungary.
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Alsharari T, Felemban MF, Khattak O, Algahtani FS, Alzahrani A. Periodontal Disease in Saudi Arabia: A Systematic Review of Prevalence and Associated Risk Factors. Diagnostics (Basel) 2025; 15:812. [PMID: 40218162 PMCID: PMC11988613 DOI: 10.3390/diagnostics15070812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 03/15/2025] [Accepted: 03/18/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: The oral health disorder periodontal disease is widespread around the world and has a public health dimension. This study aimed to perform a systematic review and an appraised analysis that looks at both the prevalence and diversity of risk factors associated with periodontal disease in Saudi Arabia. It places a particular focus on subgroup analyses and pooled prevalence estimates to identify certain populations that could be described as high risk. Methods: Several databases, including PubMed, Scopus, and Google Scholar, were used to conduct the present systematic review. The search was designed to identify relevant studies published from 1980 to 2023. Both quantitative and qualitative studies were included. Subgroup analyses and meta-analyses were performed using a random-effects model to calculate pooled prevalence rates. The studies were evaluated using three criteria that focused on bias. Finally, the authors created a narrative synthesis of the review findings for ease of understanding. Results: The pooled overall prevalence of periodontal disease was 46.2% (95% CI: 40.5-51.8), with high heterogeneity (I2 = 85%). Subgroup analyses identified obese adults as having the highest prevalence of this condition (71.3%), and individuals diagnosed with diabetes also displayed a significantly high prevalence (52.1%). Adolescents aged 15-19 years had an age-specific prevalence of 8.6%, which was significantly lower than that of the other age groups analyzed. Poor oral hygiene, tobacco use, diabetes, and obesity have been recognized as risk factors for periodontal disease. Conclusions: The substantial burden of periodontal disease in Saudi Arabia, especially among high-risk groups, such as obese and diabetic adults, cannot be overstated. Our public health initiatives need to focus on these high-risk individuals, who are likely to be both periodontally and systemically compromised, to provide lifestyle modification counseling and oral hygiene education for them, as well as to routinize their dental care in a way that minimizes the chances of becoming periodontally compromised.
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Affiliation(s)
- Thani Alsharari
- Department of Restorative Dental Science, Faculty of Dentistry, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Mohammed Fareed Felemban
- Department of Oral and Maxillofacial Surgery and Dagnostic Sciences, Faculty of Dentistry, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Osama Khattak
- Department of Restorative Dentistry, College of Dentistry, Jouf University, Sakaka 72311, Saudi Arabia
| | - Fahad Saeed Algahtani
- Department of Restorative Dental Science, Faculty of Dentistry, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Abdulrahman Alzahrani
- Department of Prosthodontics, Faculty of Dentistry, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
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Chen L, Zhao R, Zhang Y. Association between adjustable dietary factors and periodontitis: NHANES 2009-2014 and Mendelian randomization. J Transl Med 2025; 23:353. [PMID: 40114212 PMCID: PMC11927362 DOI: 10.1186/s12967-024-05972-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 12/13/2024] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Periodontitis is the major cause of tooth loss in adults and one of the most common non-communicable diseases. Clinically, periodontitis impairs oral health and associated with various systemic diseases. Maintaining a healthy diet is considered risk reduction of periodontitis. To explore the causal effect between dietary data and periodontitis by Mendelian randomization (MR) analyses. METHODS A total of 11,704 participants and 21 dietary variables from the NHANES were in random forest to rank the importance in predicting periodontitis. Data were from the genome wide association studies (GWASs) database to estimate causal relationships between diet data and periodontitis. Two-sample MR analyses were conducted by using the inverse-variance weighted (IVW) method. RESULTS The MR showed alcohol consumption and sugars intake increased the risk of chronic periodontitis with odds ratio (OR) 2.768 (95% CI: 1.03e + 00-7.42e + 00) and 2.123 (95% CI: 1.06e + 00-4.26e + 00) respectively. Vitamins and minerals, including folic acid and folate, magnesium, vitamin A, vitamin E, vitamin C, calcium, vitamin D and zinc, were not causally associated with chronic periodontitis. Alcohol consumption greater than 2.5 drinks per day and sugar intake more than 4.88 g increased the risk of periodontitis, with a calculated relative risk of 1.33 and 1.61, respectively. CONCLUSION It is suggested to drink alcohol less than 2.5 drinks/day and consume sugar less than 4.88 g/day to avoid alcohol and sugar consumption promoting the development of periodontitis. Establishing a dietary pattern conducive to periodontal health may be the focus of further clinical research.
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Affiliation(s)
- Li Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Rui Zhao
- Department of Anesthesiology, Laboratory of Mitochondria Metabolism, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
- Division of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.
| | - Yarong Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
- Department of Anesthesiology, Laboratory of Mitochondria Metabolism, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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Huang C, Song M, Wei X, Wang X, Dai H, Gou Z, Chenwu F, Jiang Y, Wan J, Guo Y, Yu X. Modelling analysis of dietary behaviors and oral health status to assess the impact on the mental well-being of elderly individuals: a cross-sectional survey study. Front Nutr 2025; 12:1486987. [PMID: 40177178 PMCID: PMC11961438 DOI: 10.3389/fnut.2025.1486987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 02/13/2025] [Indexed: 04/05/2025] Open
Abstract
Background and objective Global aging is becoming a pressing concern, with a heightened focus on the mental well-being of the elderly population. The mental health of the elderly is influenced by a plethora of factors such as physical health, social support, lifestyle, and psychological aspects. This study investigates the influence of oral health and eating behaviors on depression, anxiety, and dementia in elderly individuals aged 65 and older in China. The aim is to determine the effect sizes of these factors and establish a foundation for implementing tailored intervention strategies. Study design and methods The cross-sectional survey study employed data from the 2020 follow-up of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) released in April 2020. The study included a cohort of 3,188 eligible older adults. Seven aspects of oral health were assessed, encompassing the evaluation of the number of teeth, dental restorations, tooth brushing habits, occurrence of tooth pain, as well as cheek or jaw pain. Additionally, 17 items pertaining to eating behaviors were examined, covering dietary aspects such as staple foods, vegetables, fruits, tastes, and the use of cooking oils. The study assessed depression and sleep through 11 items, with higher scores reflecting a predisposition toward depression. A scoring threshold of over 27 identified individuals in the group prone to depression. Anxiety levels were assessed through seven items, where higher scores denoted a predisposition toward anxiety. Participants scoring above 0 were categorized into the anxiety-prone group. Cognitive function was assessed through seven items, with higher scores suggestive of a propensity toward dementia. Participants with scores exceeding 8 were categorized into the dementia-prone group. Rank-sum tests and chi-square tests were employed for the univariate analysis of variations in depression, anxiety, and dementia among elderly individuals with varying oral health and eating behaviors. Variables demonstrating statistical significance in the univariate analysis were further examined in logistic regression analysis. Results This study uncovered a correlation between the oral health and dietary behaviors of middle-aged and elderly individuals and their vulnerability to depression, anxiety, and dementia. Our findings showed that about 7.62% of middle-aged and elderly individuals in China were prone to depression. Meanwhile, around 49% of this population had inadequate teeth to chew and digest properly, and nearly 10% lacked dental restorations. Elderly individuals who had dental surgery had a 50% lower risk of depression compared to those who did not (OR = 0.58). Additionally, 36.7% of this group were prone to anxiety, and 7.53% were at risk of developing dementia. Elderly individuals who brushed their teeth at least twice a day and maintained oral hygiene were less likely to develop anxiety and dementia, with odds ratios of 0.72 and 0.78, respectively. This study conducted in China revealed that among individuals aged 65 and older, 22% reported experiencing tooth pain, while 11% reported experiencing cheek or jaw pain. Controlling tooth, cheek, or jaw pain significantly diminished the likelihood of anxiety in elderly population, with odds ratios of 0.79 and 0.69, respectively. The study also uncovered that consuming an adequate amount of fresh vegetables on a daily basis was highly advantageous in preserving the mental well-being of elderly individuals, and might reduce the risk of depression by 32.5%, anxiety by 50.3%, and dementia by 50%. Elderly individuals could potentially prevent anxiety and dementia by consuming an adequate amount of fruits daily. Conversely, a diet high in salt and spice was potentially associated with an increased risk of anxiety in this population. Furthermore, middle-aged elderly individuals (under 80) exhibited a potentially higher susceptibility to anxiety compared to older elderly individuals (aged 80 and above). Conclusion An immediate imperative exists to enhance oral health education, elevate oral hygiene standards, and guarantee prompt dental restoration among middle-aged and elderly populations in order to mitigate their susceptibility to depression, anxiety, and dementia. Safeguarding the mental health of elderly individuals necessitates the coordination of diverse disciplines, encompassing dentistry, nutrition, and public health expertise.
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Affiliation(s)
- Chan Huang
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Mingzhu Song
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Xiao Wei
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Xingyan Wang
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Honglin Dai
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Zhiqiong Gou
- Department of Respiratory and Thoracic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Feiyang Chenwu
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Yanqiu Jiang
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Jie Wan
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Yurun Guo
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
| | - Xiaoping Yu
- School of Preclinical Medicine & School of Nursing, Chengdu University, Chengdu, China
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Wu YK, Liu M, Zhou HL, He X, Wei J, Hua WH, Li HJ, Yuan QH, Xie YF. O-linked β-N-acetylglucosamine transferase regulates macrophage polarization in diabetic periodontitis: In vivo and in vitro study. World J Diabetes 2025; 16:95092. [PMID: 40093279 PMCID: PMC11885980 DOI: 10.4239/wjd.v16.i3.95092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 09/30/2024] [Accepted: 12/23/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND Periodontitis, when exacerbated by diabetes, is characterized by increased M1 macrophage polarization and decreased M2 polarization. O-linked β-N-acetylglucosamine (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), promotes inflammatory responses in diabetic periodontitis (DP). Additionally, p38 mitogen-activated protein kinase regulates macrophage polarization. However, the interplay between OGT, macrophage polarization, and p38 signaling in the progression of DP remains unexplored. AIM To investigate the effect of OGT on macrophage polarization in DP and its role in mediating O-GlcNAcylation of p38. METHODS For in vivo experiments, mice were divided into four groups: Control, DP model, model + short hairpin (sh) RNA-negative control, and model + sh-OGT. Diabetes was induced by streptozotocin, followed by ligation and lipopolysaccharide (LPS) administration to induce periodontitis. The impact of OGT was assessed by injecting sh-OGT lentivirus. Maxillary bone destruction was evaluated using micro-computed tomography analysis and tartrate-resistant acid phosphatase staining, while macrophage polarization was determined through quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry. For in vitro experiments, RAW264.7 cells were treated with LPS and high glucose (HG) (25 mmol/L D-glucose) to establish a cell model of DP. OGT was inhibited by OGT inhibitor (OSMI4) treatment and knocked down by sh-OGT transfection. M1/M2 polarization was analyzed using qPCR, immunofluorescence, and flow cytometry. Levels of O-GlcNAcylation were measured using immunoprecipitation and western blotting. RESULTS Our results demonstrated that M1 macrophage polarization led to maxillary bone loss in DP mice, associated with elevated O-GlcNAcylation and OGT levels. Knockdown of OGT promoted the shift from M1 to M2 macrophage polarization in both mouse periodontal tissues and LPS + HG-induced RAW264.7 cells. Furthermore, LPS + HG enhanced the O-GlcNAcylation of p38 in RAW264.7 cells. OGT interacted with p38 to promote its O-GlcNAcylation at residues A28, T241, and T347, as well as its phosphorylation at residue Y221. CONCLUSION Inhibition of OGT-mediated p38 O-GlcNAcylation deactivates the p38 pathway by suppressing its self-phosphorylation, thereby promoting M1 to M2 macrophage polarization and mitigating DP. These findings suggested that modulating macrophage polarization through regulation of O-GlcNAcylation may represent a novel therapeutic strategy for treating DP.
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Affiliation(s)
- Ye-Ke Wu
- Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
| | - Min Liu
- Department of Gynaecology, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
| | - Hong-Ling Zhou
- Center of Stomatology, West China Xiamen Hospital of Sichuan University, Xiamen 361021, Fujian Province, China
| | - Xiang He
- Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
| | - Jing Wei
- Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
| | - Wei-Han Hua
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hui-Jing Li
- Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
| | - Qiang-Hua Yuan
- Department of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
| | - Yun-Fei Xie
- Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan Province, China
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Aji NRAS, Sahni V, Penttala MT, Sakellari D, Grigoriadis A, Pätilä T, Pärnänen P, Neefs D, Pfützner A, Gupta S, Sorsa T, Räisänen IT. Oral Medicine and Oral Clinical Chemistry Game Changers for Future Plaque Control and Maintenance: PerioSafe ® aMMP-8 POCT, Lumoral ® 2× PDT- and Lingora ® Fermented Lingonberry Oral Rinse-Treatments. Dent J (Basel) 2025; 13:127. [PMID: 40136755 PMCID: PMC11940983 DOI: 10.3390/dj13030127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 02/06/2025] [Accepted: 03/10/2025] [Indexed: 03/27/2025] Open
Abstract
Background: Periodontitis is a global health crisis that affects almost half of the world's population and commonly goes unnoticed because of its asymptomatic and pain-free nature. For early and easy detection and treatment, safe and non-invasive chair-side oral fluid biomarker (aMMP-8) diagnostics and new anti-microbial, anti-inflammatory and anti-proteolytic treatment modalities have been developed, which this review aims to introduce. Methods: For convenient diagnosis and tackling of periodontitis, adoption of an oral fluid aMMP-8 chair-side point-of-care rapid diagnostic test (POCT) has been proposed, comparable to home pregnancy and COVID-19 antigen tests, to be conveniently used by healthcare professionals and by patients themselves. To improve treatment of detected periodontitis, Finnish scientists have also developed a potentially industry-altering, biofilm-modulating, anti-microbial, anti-inflammatory, and anti-proteolytic (i) dual-light-activated photodynamic-therapy (2×PDT) and (ii) fermented lingonberry juice (FLJ) oral rinse designed for home personalized medicine and professional use. These new oral medicine technologies are reviewed and some unpublished results are presented. Results: aMMP-8 is the superior biomarker for grade of periodontitis (progression rate) when compared to the total latent/proform MMP-8 (total-MMP-8) and microbial lipopolysaccharide (LPS/LAL) activity. Cut-off 20 ng/mL is the optimal cut-off for aMMP-8 POCT and does not make false positives. Antibacterial 2× PDT light and anti-microbial FLJ treatments can eliminate and reduce problem-causing bacteria and Candida-yeasts from the mouth. Conclusions: These new oral medicine technologies have shown promising results and could have the potential to revolutionize diagnosis, prevention, oral care, plaque control and maintenance. These new game-changer oral medicine technologies have launched a new clinical field in dentistry: oral clinical chemistry.
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Affiliation(s)
- Nur Rahman Ahmad Seno Aji
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
- Department of Periodontics, Faculty of Dentistry, Universitas Gadjah Mada, Jalan Denta No. 1 Sekip Utara, 10 Sleman, Yogyakarta 55281, Indonesia
| | - Vaibhav Sahni
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
- Research & Evidence (RF&E), New Delhi 110001, India
| | - Miika T. Penttala
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
| | - Dimitra Sakellari
- Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Andreas Grigoriadis
- Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- Dental Sector, 424 General Military Training Hospital, 56429 Thessaloniki, Greece
| | - Tommi Pätilä
- Department of Congenital Heart Surgery and Organ Transplantation, New Children’s Hospital, University of Helsinki, 00290 Helsinki, Finland
| | - Pirjo Pärnänen
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
| | - Dirk Neefs
- Department of Biomedical Surgical and Dental Sciences, Faculty of Medicine and Surgery, University of Milan, 20122 Milan, Italy
| | - Andreas Pfützner
- Department of Internal Medicine and Laboratory Medicine, University for Digital Technologies in Medicine and Dentistry, 9516 Wiltz, Luxembourg
| | - Shipra Gupta
- Oral Health Sciences Centre, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
| | - Timo Sorsa
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
- Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden
| | - Ismo T. Räisänen
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland
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Gu Y, Golub LM, Lee HM, Walker SG. Diabetes, periodontal disease, and novel therapeutic approaches- host modulation therapy. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2025; 6:1529086. [PMID: 40099283 PMCID: PMC11911344 DOI: 10.3389/fcdhc.2025.1529086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/10/2025] [Indexed: 03/19/2025]
Abstract
Diabetes mellitus is a much-studied disorder, characterized by hyperglycemia and numerous oral and medical complications. The latter includes (above all) decreased life-span - and these are widely discussed in the dental and medical literature. The oral complications include impaired wound healing; increased severity of periodontal disease and peri-implantitis; dry mouth (xerostomia); and dental caries. The relationship between diabetes and oral health is bi-directional: Optimal management of local oral disease can profoundly affect the systemic metabolic control of the diabetic patient, and strict management of the patient's hyperglycemia can reduce its impact on oral disease. The only host modulation therapy (HMT), approved by the U.S. Food and Drug Administration (FDA) to treat periodontal disease, is a novel NON-antimicrobial (low-dose) formulation of doxycycline (Periostat®; 20 mg b.i.d). A publication in Scientific Reports (2017), which supported the clinical rationale of efficacy and safety of low-dose doxycycline in diabetics, stated: "doxycycline not only ameliorated insulin resistance, fasting blood glucose, and insulin levels, and lipid profiles in the circulation and liver, but also improved islet morphology and increased glucose-stimulated insulin secretion." Additional developments include the biphenolic chemically-modified curcumins, as HMT for managing oral diseases. A lead compound, chemically-modified curcumin 2.24 (CMC2.24), has demonstrated safety and efficacy in vitro, in cell culture, and in vivo using mouse, rat, rabbit, and dog models of disease. In conclusion, novel host-modulation compounds have shown significant promise as adjuncts to traditional local therapy in the clinical management of periodontal and other oral diseases.
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Affiliation(s)
- Ying Gu
- Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY, United States
| | - Lorne M Golub
- Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, United States
| | - Hsi-Ming Lee
- Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, United States
| | - Stephen G Walker
- Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, United States
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Yang Q, Xiao J, Liu Y, Yang Z, Wang C, Sun J, Wang H, Liu H, Wang X, Ma L, Huang X, Cao Z. METTL3-mediated m6A modifications of NLRP3 accelerate alveolar bone resorption through enhancing macrophage pyroptosis. Cell Signal 2025; 127:111572. [PMID: 39708895 DOI: 10.1016/j.cellsig.2024.111572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 11/26/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024]
Abstract
Periodontitis (PD) is twice as prevalent in diabetics compared to nondiabetics, and diabetes-associated PD is characterized by increased inflammation and aggravated tissue damage. Pyroptosis has recently been implicated in diabetes-associated PD; however, the underlying mechanisms remain largely unknown, resulting in a lack of effective treatments. In this study, we investigated the role of methyltransferase-like 3 (METTL3) in macrophage pyroptosis and found that it inhibits the osteogenic differentiation of osteoblasts via pyroptotic macrophages in a diabetes-associated periodontitis mouse model. Further analysis and validation revealed that nod-like receptor family pyrin domain-containing 3 (NLRP3) is a target of METTL3, with its mRNA stability regulated through a binding of insulin-like growth factor 2 binding protein 3 (IGF2BP3)-dependent pathway. Additionally, local injection of adeno-associated virus 9 (AAV9) demonstrated that METTL3 deficiency in macrophages significantly ameliorates periodontal inflammation and alveolar bone loss in diabetes-associated PD mice. Collectively, our findings indicate that METTL3-mediated modulation of NLRP3 expression is a crucial factor in macrophage pyroptosis during diabetes-associated PD progression. This suggests that the METTL3/IGF2BP3/NLRP3 axis is a novel and promising target for the improvement of periodental inflammation and alveolar bone loss in diabetes-associated PD.
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Affiliation(s)
- Qiudong Yang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Junhong Xiao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Yuqi Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Zhengkun Yang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Chuan Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Jiahui Sun
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Huiyi Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Heyu Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Xiaoxuan Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Li Ma
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Xin Huang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
| | - Zhengguo Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
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Satoh Y, Ishihara K, Kubota T. Characterization of the anti-Porphyromonas gingivalis compound in bilberry (Vaccinium myrtillus L.) and comparison with its analogs. J Oral Biosci 2025; 67:100610. [PMID: 39746511 DOI: 10.1016/j.job.2024.100610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/29/2024] [Accepted: 12/31/2024] [Indexed: 01/04/2025]
Abstract
OBJECTIVES The bacterium Porphyromonas gingivalis is a major causative agent of periodontitis. In this study, the anti-P. gingivalis compound in bilberry (Vaccinium myrtillus L.) was identified and its activity was compared with that of its related analogs. METHODS An acetone-soluble bilberry fruit extract was purified using silica gel column chromatography, and the minimum inhibitory concentrations (MICs) of the purified fractions were determined against P. gingivalis. After purification, mass spectrometry, nuclear magnetic resonance, and optical rotation analyses were performed to identify the anti-P. gingivalis compounds. Furthermore, cell assays were performed to assess the anti-P. gingivalis activity and cytotoxicity of the identified compounds. The activity of these compounds was compared with that of their pentacyclic triterpene analogs. RESULTS The anti-P. gingivalis in bilberry extracts was identified as ursolic acid, a pentacyclic triterpene (PCT). The MIC of ursolic acid against P. gingivalis was between 6.25 and 12.5 μg/mL; it killed P. gingivalis within 4 h of treatment at these concentrations. However, it showed no cytotoxicity against gingival carcinoma Ca9-22 cells at the MIC. Ursane-type PCT, including ursolic acid and oleanane-type PCT, exhibited anti-P. gingivalis activity. CONCLUSIONS Ursolic acid found in bilberry fruit extract exhibits anti-P. gingivalis activity. Similar activity is observed in a class of PCTs with a common structure.
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Affiliation(s)
- Yutaroh Satoh
- Department of Natural Products Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama-city, Okayama, Japan; Department of Microbiology, Tokyo Dental College, 2-9-18 Kandamisaki-cho, Chiyoda-ku, Tokyo, Japan.
| | - Kazuyuki Ishihara
- Department of Microbiology, Tokyo Dental College, 2-9-18 Kandamisaki-cho, Chiyoda-ku, Tokyo, Japan
| | - Takaaki Kubota
- Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, kita-ku, Okayama, Japan
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Song D, He J, Cheng T, Jin L, Li S, Chen B, Li Y, Liao C. Cystathionine γ-lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia. J Periodontol 2025; 96:255-267. [PMID: 38937859 DOI: 10.1002/jper.23-0811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 05/19/2024] [Accepted: 05/20/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND Diabetes is one of the major inflammatory comorbidities of periodontitis via 2-way interactions. Cystathionine γ-lyase (CTH) is a pivotal endogenous enzyme synthesizing hydrogen sulfide (H2S), and CTH/H2S is crucially implicated in modulating inflammation in various diseases. This study aimed to explore the potential role of CTH in experimental periodontitis under a hyperglycemic condition. METHODS CTH-silenced and normal human periodontal ligament cells (hPDLCs) were cultured in a high glucose and Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) condition. The effects of CTH on hPDLCs were assessed by Cell Counting Kit 8 (CCK8), real-time quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The model of experimental periodontitis under hyperglycemia was established on both Cth-/- and wild-type (WT) mice, and the extent of periodontal destruction was assessed by micro-CT, histology, RNA-Seq, Western blot, tartrate-resistant acid phosphatase (TRAP) staining and immunostaining. RESULTS CTH mRNA expression increased in hPDLCs in response to increasing concentration of P.g-LPS stimulation in a high glucose medium. With reference to WT mice, Cth-/- mice with experimental periodontitis under hyperglycemia exhibited reduced bone loss, decreased leukocyte infiltration and hindered osteoclast formation, along with reduced expression of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in periodontal tissue. RNA-seq-enriched altered NF-κB pathway signaling in healthy murine gingiva with experimental periodontitis mice under hyperglycemia. Accordingly, phosphorylation of p65 (P-p65) was alleviated in CTH-silenced hPDLCs, leading to decreased expression of IL6 and TNF. CTH knockdown inhibited activation of nuclear factor kappa-B (NF-κB) pathway and decreased production of proinflammatory cytokines under high glucose and P.g-LPS treatment. CONCLUSION The present findings suggest the potential of CTH as a therapeutic target for tackling periodontitis in diabetic patients.
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Affiliation(s)
- Danni Song
- Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Orthodontics, Stomatological Hospital and Dental School, Tongji University, Shanghai, China
| | - Jiangfeng He
- Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Orthodontics, Stomatological Hospital and Dental School, Tongji University, Shanghai, China
| | - Tianfan Cheng
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Lijian Jin
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Sijin Li
- Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Orthodontics, Stomatological Hospital and Dental School, Tongji University, Shanghai, China
| | - Beibei Chen
- Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Orthodontics, Stomatological Hospital and Dental School, Tongji University, Shanghai, China
| | - Yongming Li
- Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Orthodontics, Stomatological Hospital and Dental School, Tongji University, Shanghai, China
| | - Chongshan Liao
- Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Orthodontics, Stomatological Hospital and Dental School, Tongji University, Shanghai, China
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Wang P, Sun F, Ling X. Effectiveness of photodynamic therapy as an adjunctive treatment for periodontitis: A systematic review and meta-analysis. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2025; 126:102036. [PMID: 39244026 DOI: 10.1016/j.jormas.2024.102036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 09/04/2024] [Indexed: 09/09/2024]
Abstract
OBJECTIVE Periodontitis is a prevalent inflammatory disease affecting the supporting structures of teeth. While scaling and root planing (SRP) remains the gold standard for treatment, adjunctive therapies are being explored to enhance outcomes. This systematic review and meta-analysis aimed to evaluate the effectiveness of photodynamic therapy (PDT) as an adjunct to SRP in the treatment of periodontitis. METHODS A comprehensive literature search was conducted in PubMed, Embase, Web of Science, CNKI, Wanfang, and Weipu databases. Randomized controlled trials (RCTs) comparing SRP alone to SRP with adjunctive PDT were included. The primary outcomes were changes in clinical attachment level (CAL) and probing depth (PD). Secondary outcomes included plaque index (PI). Random-effects models were used for meta-analysis, and heterogeneity was assessed using I² statistics. RESULTS Eighteen RCTs met the inclusion criteria. Meta-analysis revealed that adjunctive PDT significantly improved CAL (SMD: -0.16; 95% CI: -0.40, -0.07; P < 0.001; I² = 60.7%) and PD (SMD: -0.55; 95% CI: -0.97, -0.13; P < 0.001; I² = 76.2%) compared to SRP alone. PI also showed improvement with adjunctive PDT (SMD: -0.40; 95% CI: -0.67, -0.14; P = 0.072; I² = 43.0%). Egger's test indicated a borderline significant publication bias for CAL, while no significant publication bias for PD. CONCLUSION This meta-analysis provides evidence that PDT as an adjunct to SRP can significantly improve clinical outcomes in periodontitis treatment. However, the high heterogeneity observed suggests that optimal PDT protocols need further investigation. Future research should focus on standardizing PDT parameters and exploring its long-term effects.
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Affiliation(s)
- Peng Wang
- Department of Periodontology, Shaoxing Stomatological Hospital, Shaoxing City, 312000, PR China
| | - Fei Sun
- Department of Periodontology, Shaoxing Stomatological Hospital, Shaoxing City, 312000, PR China
| | - Xiaoxu Ling
- Department of Endodontics, Shaoxing Stomatological Hospital, Shaoxing City, 312000, PR China.
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Xian X, Zhang Y, Fu G, Li Z, Chen J, Wang M, Zheng Q. Influencing Factors of Diabetic Patients of on Oral Health-Related Quality of Life: A Scoping Review. IRANIAN JOURNAL OF PUBLIC HEALTH 2025; 54:465-477. [PMID: 40330188 PMCID: PMC12051797 DOI: 10.18502/ijph.v54i3.18240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 12/10/2024] [Indexed: 05/08/2025]
Abstract
Background The oral health-related quality of life in diabetic patients is regarded as a significant factor for assessing their dental health. This study aimed to examine the current research state, frequently utilized research instruments, and factors impacting the oral health quality of life in individuals with diabetes. Methods Our review was conducted according to the PRISMA extended guidelines for scoping review. We conducted a literature review on the oral health and quality of life of diabetic patients using PubMed, Embase, and additional databases. This research proposal has been formally submitted to the Open Science Framework. Results Out of 3827 materials, merely 17 publications satisfied the review requirements for our study. The search period extended from the inception of the library until Feb 5, 2024. The research encompassed seven countries, including China, the United States, and Iran, utilizing the Oral Health Evaluation Index for the Elderly and the Oral Health Impact Scale as prevalent assessment instruments. The quality of life connected to oral health was predominantly low among diabetic patients, influenced by socio-demographic characteristics, oral health status, biochemical indicators, psychosocial elements, lifestyle choices, and oral-related factors. Conclusion The oral health-related quality of life among diabetic patients is typically diminished. Oral health care professionals must devise strategies to promptly identify, assess, and manage the factors influencing the oral health-related quality of life in diabetic patients, while incorporating necessary preventive measures and screenings to enhance oral disease prevention in routine evaluations.
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Affiliation(s)
- Xiaomin Xian
- Department of Geriatric Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yanping Zhang
- Department of Geriatric Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Guifen Fu
- Department of Nursing, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Ziqiang Li
- Department of Geriatric Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Jingfeng Chen
- Department of Geriatric Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Miao Wang
- Otolaryngology Head and Neck Department, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Qiuping Zheng
- Department of Geriatric Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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Feng Y, Xiao L, Fu LL, Gosau M, Vollkommer T, Speth U, Smeets R, Rutkowski R, Friedrich RE, Yan M. Global, Regional and National Burden of Edentulism and Periodontal Diseases from 1990 to 2021: Analysis of Risk Factors and Prediction of Trends in 2050. In Vivo 2025; 39:1148-1161. [PMID: 40011004 PMCID: PMC11884469 DOI: 10.21873/invivo.13919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/13/2025] [Accepted: 01/20/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND/AIM Periodontal diseases and edentulism remain a prevalent and disabling oral health condition worldwide, with significant regional disparities. This study systematically evaluated the burden of periodontal disease and edentulism at global, regional, and national levels from 1990 to 2021, using the Global Burden of Disease (GBD) 2021 framework. PATIENTS AND METHODS We analyzed trends in incidence, prevalence, and years lived with disability (YLD), exploring their associations with the socio-demographic index (SDI) and other risk factors. RESULTS The findings reveal considerable variations across SDI regions, with low and low-middle SDI regions experiencing the highest burden. In 2021, the global prevalence of periodontal diseases reached approximately 1.07 billion cases, and the age-standardized incidence and prevalence rates varied significantly by SDI levels. The burden of periodontal disease showed an increasing trend among middle-aged and elderly populations. While sex differences were present in both edentulism and periodontal diseases, they were relatively minor. ARIMA model projections indicate that the burden of edentulism will fluctuate by 2050, while the burden of periodontal diseases will remain stable. CONCLUSION This study underscores the need for targeted public health interventions, particularly in resource-limited regions, to improve access to oral healthcare and integrate preventive strategies into broader health initiatives.
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Affiliation(s)
- Yong Feng
- Department of Implantology, Guiyang Hospital of Stomatology, Guiyang, P.R. China
- ZBH-Center for Bioinformatics, Universität Hamburg, Hamburg, Germany
| | - Liyuan Xiao
- Department of Implantology, Guiyang Hospital of Stomatology, Guiyang, P.R. China;
| | - Ling-Ling Fu
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martin Gosau
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tobias Vollkommer
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ulrike Speth
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ralf Smeets
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Oral and Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Rico Rutkowski
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Reinhard E Friedrich
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ming Yan
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Oral and Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Zhu J, Xu W, Wu S, Song D. Vitamin B6 status, type 2 diabetes mellitus, and periodontitis: evidence from the NHANES database 2009-2010. BMC Oral Health 2025; 25:299. [PMID: 39994649 PMCID: PMC11852513 DOI: 10.1186/s12903-025-05597-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 02/03/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Periodontitis is a chronic inflammatory disease that seriously affects the quality of patients' life. Diabetes mellitus (DM) is the independent risk factor of periodontitis. The association between vitamin B6 with several inflammatory diseases have been reported in previous studies. However, the effect of vitamin B6 on the association of T2DM and periodontitis remains unclear. This study aimed to explore the effect of vitamin B6 [evaluated by serum pyridoxal 5'-phosphate (PLP)] on the association of T2DM and periodontitis in American population. METHODS Data of this cross-sectional study were extracted from the National Health and Nutrients Examination Survey (NHANES) 2009-2010. Serum PLP level was the indicator of vitamin B6 status in vivo and measured by enzymatic assay. Covariates included demographic information, physical examination, lifestyle characteristics, laboratory parameters and complications. The weighted univariate and multivariate logistics regression models were conducted to explore the association of PLP, T2DM and periodontitis, with the odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were further performed to explore these associations based on age, body mass index (BMI), cardiovascular disease (CVD) and dental decay. RESULTS Finally, 3,491 eligible adults with the information of periodontitis measurement, T2DM diagnosis and PLP detection were included. Among them, 1,999 (57.26%) had periodontitis. After adjusted confounders, we found adults with T2DM had high odds of periodontitis (OR = 1.45, 95%CI: 1.04-2.02); while no significant association between PLP and periodontitis was observed. Adults with low PLP level (< 67.20 nmol/L) and combined with T2DM had high odds of periodontitis (OR = 1.82, 95%CI: 1.29-2.55), no significant association was found between T2DM and periodontitis in adults with high PLP level (≥ 67.20 nmol/L). These results suggested that serum PLP levels may have the modulatory effect on the association of T2DM and periodontitis. This modulatory effect remains robust in subgroup analysis, especially in adults aged ≥ 60 years (OR = 4.54, 95%CI: 2.15-9.62), with obese (OR = 3.06, 95%CI: 1.31-7.18), without the history of CVD (OR = 2.25, 95%CI: 1.06-4.79) and without dental decay (OR = 2.93, 95%CI: 1.51-5.68) (all P < 0.05). CONCLUSION Our study suggested that adults with T2DM had the high odds of periodontitis, and serum PLP may plays a modulatory effect in this association. T2DM patients maintaining a higher intake of vitamin B6 may have potential benefits in reducing the periodontitis risk.
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Affiliation(s)
- Jiang Zhu
- Department of Stomatology, Affiliated Hospital of Nantong University, No.20 Xisi Road, Chongchuan District, Nantong, 226001, China
| | - Wushuang Xu
- Department of Stomatology, Affiliated Hospital of Nantong University, No.20 Xisi Road, Chongchuan District, Nantong, 226001, China
| | - Senbin Wu
- Department of Stomatology, Affiliated Hospital of Nantong University, No.20 Xisi Road, Chongchuan District, Nantong, 226001, China
| | - Donghui Song
- Department of Stomatology, Affiliated Hospital of Nantong University, No.20 Xisi Road, Chongchuan District, Nantong, 226001, China.
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Scrobota I, Iova GM, Marcu OA, Sachelarie L, Vlad S, Duncea IM, Blaga F. An Artificial Intelligence-Based Fuzzy Logic System for Periodontitis Risk Assessment in Patients with Type 2 Diabetes Mellitus. Bioengineering (Basel) 2025; 12:211. [PMID: 40150676 PMCID: PMC11939156 DOI: 10.3390/bioengineering12030211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Since periodontitis prevalence has increased globally and there is a bidirectional relationship between periodontitis and diabetes mellitus (DM), new methods of preventing and screening involving DM biomarkers could impact periodontitis management. We aimed to develop a fuzzy system to estimate the risk of periodontitis in patients with DM. METHODS Body mass index (BMI), glycemia (G), total cholesterol (C), and triglyceride (T) measurements were collected from 87 patients diagnosed with DM. Oral examinations were performed, and the number of the periodontal pockets (nrPPs) was determined. A fuzzy system was developed: BMI and G as inputs resulted in Periodontitis Risk 1 (PRisk1) output; C and T as inputs resulted in Periodontitis Risk 2 (PRisk2) output. From PRisk1 and PRisk2, the cumulative periodontitis risk (PCRisk) was assessed. Linguistic terms and linguistic grades (very small, small, medium, big, and very big) were assigned to the numerical variables by using 25 different membership functions. PCRisk and nrPP values were statistically processed. RESULTS In our developed fuzzy system, BMI, G, C, and T as input data resulted in periodontitis risk estimation. PCRisk was correlated with nrPP: when PCRisk increased by 1.881 units, nrPP increased by 1 unit. The fuzzy logic-based system effectively estimated periodontitis risk in type 2 diabetes patients, showing a significant correlation with the number of periodontal pockets. These findings highlight its potential for early diagnosis and improved interdisciplinary care.
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Affiliation(s)
- Ioana Scrobota
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 10 1st Decembrie Street, 410073 Oradea, Romania; (I.S.); (G.M.I.)
| | - Gilda Mihaela Iova
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 10 1st Decembrie Street, 410073 Oradea, Romania; (I.S.); (G.M.I.)
| | - Olivia Andreea Marcu
- Preclinics Department, Faculty of Medicine and Pharmacy, University of Oradea, 10 1st Decembrie Street, 410073 Oradea, Romania;
| | - Liliana Sachelarie
- Department of Preclinical Discipline, Faculty of Medicine, Apollonia University, 700511 Iasi, Romania
| | - Siviu Vlad
- Department of Surgical Specialties, Faculty of Medicine and Pharmacy, University of Oradea, 10 1st Decembrie Street, 410073 Oradea, Romania;
| | - Ioana Monica Duncea
- Prosthetic Dentistry and Dental Materials Department, Iuliu Hațieganu University of Medicine and Pharmacy, 32 Clinicilor Street, 400006 Cluj-Napoca, Romania;
| | - Florin Blaga
- Industrial Engineering Department, Faculty of Management and Technological Engineering, University of Oradea, 1 Universității Street, 410087 Oradea, Romania;
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Tian Z, Zhang J, Fan Y, Sun X, Wang D, Liu X, Lu G, Wang H. Diabetic peripheral neuropathy detection of type 2 diabetes using machine learning from TCM features: a cross-sectional study. BMC Med Inform Decis Mak 2025; 25:90. [PMID: 39966886 PMCID: PMC11837659 DOI: 10.1186/s12911-025-02932-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 02/11/2025] [Indexed: 02/20/2025] Open
Abstract
AIMS Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Early identification of individuals at high risk of DPN is essential for successful early intervention. Traditional Chinese medicine (TCM) tongue diagnosis, one of the four diagnostic methods, lacks specific algorithms for TCM symptoms and tongue features. This study aims to develop machine learning (ML) models based on TCM to predict the risk of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 4723 patients were included in the analysis (4430 with T2DM and 293 with DPN). TFDA-1 was used to obtain tongue images during a questionnaire survey. LASSO (least absolute shrinkage and selection operator) logistic regression model with fivefold cross-validation was used to select imaging features, which were then screened using best subset selection. The synthetic minority oversampling technique (SMOTE) algorithm was applied to address the class imbalance and eliminate possible bias. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model's performance. Four ML algorithms, namely logistic regression (LR), random forest (RF), support vector classifier (SVC), and light gradient boosting machine (LGBM), were used to build predictive models for DPN. The importance of covariates in DPN was ranked using classifiers with better performance. RESULTS The RF model performed the best, with an accuracy of 0.767, precision of 0.718, recall of 0.874, F-1 score of 0.789, and AUC of 0.77. With a value of 0.879, the LGBM model appeared to be the best regarding recall Age, sweating, dark red tongue, insomnia, and smoking were the five most significant RF features. Age, yellow coating, loose teeth, smoking, and insomnia were the five most significant features of the LGBM model. CONCLUSIONS This cross-sectional study demonstrates that the RF and LGBM models can screen for high-risk DPN in T2DM patients using TCM symptoms and tongue features. The identified key TCM-related features, such as age, tongue coating, and other symptoms, may be advantageous in developing preventative measures for T2DM patients.
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Affiliation(s)
- Zhikui Tian
- School of Rehabilitation Medicine, Qilu Medical University, Shandong, 255300, China
| | - JiZhong Zhang
- School of Rehabilitation Medicine, Qilu Medical University, Shandong, 255300, China
| | - Yadong Fan
- Medical College of Yangzhou University, YangZhou, 225000, China
| | - Xuan Sun
- College of Traditional Chinese Medicine, Binzhou Medical University, Shandong, China
| | - Dongjun Wang
- College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, 063000, China
| | - XiaoFei Liu
- School of Rehabilitation Medicine, Qilu Medical University, Shandong, 255300, China
| | - GuoHui Lu
- School of Rehabilitation Medicine, Qilu Medical University, Shandong, 255300, China.
| | - Hongwu Wang
- School of Health Sciences and Engineering, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
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Gao C, Iles MM, Bishop DT, Larvin H, Bunce D, Wu B, Luo H, Nibali L, Pavitt S, Wu J, Kang J. Genetic risk factors for periodontitis: a genome-wide association study using UK Biobank data. Clin Oral Investig 2025; 29:129. [PMID: 39951158 PMCID: PMC11828758 DOI: 10.1007/s00784-025-06205-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 02/03/2025] [Indexed: 02/17/2025]
Abstract
OBJECTIVES Periodontitis is linked with many health conditions, but its genetic basis is not yet understood. This genome-wide association study (GWAS) aimed to investigate the genetic variants associated with periodontitis. MATERIALS AND METHODS This study utilised UK Biobank participants of European descent. Individuals were categorised as "having periodontitis" if they self-reported having 'painful gums', 'bleeding gums' or 'loose teeth' (n = 68,482), or as "controls" for those without these symptoms (n = 307,342). We conducted GWAS of this binary periodontitis phenotype using logistic regression models with PLINK2.0 adjusting for age, sex and the first 15 principal components to account for population stratification. RESULTS There were 376,611 participants (mean baseline age = 57 ± 7.9 SD) included in the GWAS, and four significant loci were identified: rs775476621 on chromosome 11 (Odds Ratio, OR[T]: 3.08, p = 1.01 × 10- 8), rs751014048 on chromosome 11 (OR[G]: 3.07, p = 1.04 × 10- 8), rs149922301 on chromosome 4 near gene RP11-61G19.1 (OR[A]: 1.18, p = 2.71 × 10- 8) and rs368467810 on chromosome 6 near gene HIST1H3L (OR[TTTA]: 0.96, p = 3.88 × 10- 8). CONCLUSIONS Within the current limitations, such as self-reported phenotype and older age of the study population, four loci were detected for periodontitis that have not previously been linked with this condition. Further exploration of the function of these loci may contribute to improved understanding of periodontitis aetiology and subsequent drug development. CLINICAL RELEVANCE These findings offer new targets for future research to investigate the genetic impact on periodontitis and aid the future understanding of periodontitis pathology and the disease's progression.
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Affiliation(s)
- Chenyi Gao
- Wolfson Institute of Population Health, Queen Mary University of London, London, UK
- School of Dentistry, University of Leeds, Leeds, UK
| | - Mark M Iles
- Leeds Institute for Data Analytics, University of Leeds, Leeds, UK
- NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - David Timothy Bishop
- Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK
| | - Harriet Larvin
- Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - David Bunce
- School of Psychology, University of Leeds, Leeds, UK
| | - Bei Wu
- Rory Meyers College of Nursing, New York University, New York, US
| | - Huabin Luo
- Department of Public Health, East Carolina University, Greenville, US
| | - Luigi Nibali
- Periodontology Unit, Centre for Host Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College, London, UK
| | - Susan Pavitt
- School of Dentistry, University of Leeds, Leeds, UK
| | - Jianhua Wu
- Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - Jing Kang
- Oral Clinical Research Unit, Faculty of Dentistry Oral Craniofacial Sciences, King's College London, London, UK.
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Chen J. Development of a machine learning model related to explore the association between heavy metal exposure and alveolar bone loss among US adults utilizing SHAP: a study based on NHANES 2015-2018. BMC Public Health 2025; 25:455. [PMID: 39905341 PMCID: PMC11796195 DOI: 10.1186/s12889-025-21658-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/28/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Alveolar bone loss (ABL) is common in modern society. Heavy metal exposure is usually considered to be a risk factor for ABL. Some studies revealed a positive trend found between urinary heavy metals and periodontitis using multiple logistic regression and Bayesian kernel machine regression. Overfitting using kernel function, long calculation period, the definition of prior distribution and lack of rank of heavy metal will affect the performance of the statistical model. Optimal model on this topic still remains controversy. This study aimed: (1) to develop an algorithm for exploring the association between heavy metal exposure and ABL; (2) filter the actual causal variables and investigate how heavy metals were associated with ABL; and (3) identify the potential risk factors for ABL. METHODS Data were collected from National Health and Nutrition Examination Survey (NHANES) between 2015 and 2018 to develop a machine learning (ML) model. Feature selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression with 10-fold cross-validation. The selected data were balanced using the Synthetic Minority Oversampling Technique (SMOTE) and divided into a training set and testing set at a 3:1 ratio. Logistic Regression (LR), Support Vector Machines (SVM), Random Forest (RF), K-Nearest Neighbor (KNN), Decision Tree (DT), and XGboost were used to construct the ML model. Accuracy, Area Under the Receiver Operating Characteristic Curve (AUC), Precision, Recall, and F1 score were used to select the optimal model for further analysis. The contribution of the variables to the ML model was explained using the Shapley Additive Explanations (SHAP) method. RESULTS RF showed the best performance in exploring the association between heavy metal exposure and ABL, with an AUC (0.88), accuracy (0.78), precision (0.76), recall (0.83), and F1 score (0.79). Age was the most important factor in the ML model (mean| SHAP value| = 0.09), and Cd was the primary contributor. Sex had little effect on the ML model contribution. CONCLUSION In this study, RF showed superior performance compared with the other five algorithms. Among the 12 heavy metals, Cd was the most important factor in the ML model. The relationship of Co & Pb and ABL are weaker than that of Cd. Among all the independent variables, age was considered the most important factor for this model. As for PIR, low-income participants present association with ABL. Mexican American and Non-Hispanic White show low association with ABL compared to Non-Hispanic Black and other races. Gender feature demonstrates a weak association with ABL. In the future, more advanced algorithms should be developed to validate these results and related parameters can be tuned to improve the accuracy of the model. CLINICAL TRIAL NUMBER not applicable.
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Affiliation(s)
- Jiayi Chen
- Department of stomatology, Suzhou Wujiang District Hospital of Traditional Chinese Medicine, Dachun road 999, Wujiang District, Suzhou, 215221, PR China.
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Massarenti L, Nielsen CH, Danielsen AK, Jensen PØ, Enevold C, Damgaard C. Evaluation of circulating IgG antibodies against Porphyromonas gingivalis or its gingipains as serological markers of periodontitis and carriage of the bacterium. J Periodontol 2025; 96:119-128. [PMID: 38884611 PMCID: PMC11866731 DOI: 10.1002/jper.23-0766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 12/12/2023] [Accepted: 04/21/2024] [Indexed: 06/18/2024]
Abstract
BACKGROUND Increasing evidence indicates that periodontitis contributes to systemic low-grade inflammation. Porphyromonas gingivalis is strongly associated with periodontitis, and antibodies against the bacterium may be used as a serological proxy to account for periodontal status, when studying diseases associated with periodontitis. The aim of the present study is to identify an easily accessible and reliable serological biomarker for determination of periodontal status and oral carriage of the bacterium. METHODS Saliva and serum samples were collected from periodontally healthy controls (n = 27), and patients with periodontitis stage II (n = 12) or stages III or IV (n = 44). Serum levels of immunoglobulin G (IgG) antibodies against intact and fragmented P. gingivalis, recombinant gingipains (RgpA and RgpB), and the bacteria Escherichia coli and Capnocytophaga ochracea as controls were quantified with a multiplex bead-based assay. P. gingivalis was identified in saliva using quantitative polymerase chain reaction (qPCR). RESULTS Serum IgG antibodies against P. gingivalis whole bacteria were good indicators of periodontitis (area under the curve [AUC]: 0.75, 95% confidence interval [CI]: 0.64-0.85). The same was observed for levels of antibodies against P. gingivalis fragments (AUC: 0.78, 95% CI: 0.68-0.88). Likewise, levels of antibodies against P. gingivalis whole bacteria or P. gingivalis fragments were good indicators of oral carriage of P. gingivalis (AUC: 0.92, 95% CI: 0.86-0.98 and AUC: 0.96, 95% CI: 0.92-1, respectively). Conversely, antibodies against recombinant RgpA and RgpB were not good indicators of periodontitis or oral carriage of the bacterium. None of the antibody levels differed significantly between stage II and stage III or IV periodontitis. CONCLUSION Serum IgG antibody levels against heat-inactivated whole P. gingivalis proved to be the preferable biomarker for periodontitis and oral carriage of the bacterium.
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Affiliation(s)
- Laura Massarenti
- Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen University HospitalCopenhagenDenmark
| | - Claus Henrik Nielsen
- Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen University HospitalCopenhagenDenmark
| | - Anne Katrine Danielsen
- Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
| | - Peter Østrup Jensen
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen University HospitalCopenhagenDenmark
- Costerton Biofilm Center, Department of Immunology and MicrobiologyUniversity of Copenhagen Faculty of Health and Medical SciencesCopenhagenDenmark
- Department of Clinical MicrobiologyRigshospitaletCopenhagenDenmark
| | - Christian Enevold
- Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen University HospitalCopenhagenDenmark
| | - Christian Damgaard
- Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen University HospitalCopenhagenDenmark
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Dong S, Mei Y, Zhang Y, Bu W, Zhang Y, Sun C, Zou R, Niu L. A Novel Therapeutic Calcium Peroxide Loaded Injectable Bio-adhesive Hydrogel Against Periodontitis. Int Dent J 2025; 75:352-362. [PMID: 39127517 PMCID: PMC11806305 DOI: 10.1016/j.identj.2024.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/06/2024] [Accepted: 05/22/2024] [Indexed: 08/12/2024] Open
Abstract
OBJECTIVES Periodontitis is a prevalent oral disease that can significantly impact patients' life quality and systemic health. However, non-surgical subgingival scaling is largely compromised due to poor patient compliance, leading to a high recurrence rate of periodontitis. Therefore, this research aims to explore new approaches to enhance the effectiveness of existing local drug administration therapies. MATERIALS AND METHODS Gelatin-oxidized dextran hydrogel loaded with calcium peroxide and penicillin (CP-P hydrogel) was synthesized and characterized using Universal mechanical testing machine, Fourier transform infrared spectroscopy, swelling test, and dissolved oxygen meter. Furthermore, the cytotoxicity, osteogenic ability, antibacterial behavior, and alveolar bone regenerating capability of CP-P hydrogel were conducted both in vitro and in vivo. RESULTS The CP-P hydrogel demonstrated excellent mechanical properties, minimal swelling, and ideal biocompatibility. It created more favorable environments in the periodontal pocket by reversing anaerobic environment, eliminating drug-resistant bacteria and enhancing the therapeutic potency of drugs. By continuously releasing drugs in the periodontal pocket, the CP-P hydrogel effectively inhibited bacteria and reduce local inflammation response. In addition to bacteriostatic effects, the CP-P hydrogel also promoted the expression of osteogenic genes and enhanced osteogenic differentiation of PDLSCs in vitro. CONCLUSIONS CP-P hydrogel can be developed as a new therapeutic platform to enhance the effectiveness of local drug administration strategy against periodontitis.
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Affiliation(s)
- Shaojie Dong
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China; Department of Prosthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Yukun Mei
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China
| | - Yuwei Zhang
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China
| | - Wenqing Bu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China
| | - Yifei Zhang
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China
| | - Changjie Sun
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China
| | - Rui Zou
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China.
| | - Lin Niu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi'an, Shaanxi Province, China; Department of Prosthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
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Shirakura K, Nemoto TK, Nemoto YO, Nishimata H, Sawase M, Shimoyama Y, Nakasato-Suzuki M, Ito K, Tanoue N. Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini. Biol Chem 2025; 406:51-64. [PMID: 39918301 DOI: 10.1515/hsz-2024-0156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 01/21/2025] [Indexed: 03/06/2025]
Abstract
Dipeptide production mediated by dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11 plays a crucial role in growth of Porphyromonas gingivalis, a periodontopathic asaccharolytic bacterium. Given the particular P1-position specificity of DPPs, it has been speculated that DPP5 or DPP7 might be responsible for degrading refractory P1 amino acids, i.e., neutral (Thr, His, Gly, Ser, Gln) and hydrophilic (Asn) residues. The present results identified DPP7 as an entity that processes these residues, thus ensuring complete production of nutritional dipeptides in the bacterium. Activity enhancement by the P1' residue was observed in DPP7, as well as DPP4 and DPP5. Toward the refractory P1 residues, DPP7 uniquely hydrolyzed HX|LD-MCA (X = His, Gln, or Asn) and their hydrolysis was most significantly suppressed in dpp7 gene-disrupted cells. Additionally, hydrophobic P2 residue significantly enhanced DPP7 activity toward these substrates. The findings propose a comprehensive 20 P1 × 20 P2 amino acid matrix showing the coordination of four DPPs to achieve complete dipeptide production along with subsidiary peptidases. The present finding of a broad substrate specificity that DPP7 accounts for releasing 48 % (192/400) of N-terminal dipeptides could implicate its potential role in linking periodontopathic disease to related systemic disorders.
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Affiliation(s)
- Kana Shirakura
- Department of Pediatric Dentistry, Course of Medical and Dental Sciences, 200674 Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, 852-8588, Japan
| | - Takayuki K Nemoto
- Department of Pediatric Dentistry, Course of Medical and Dental Sciences, 200674 Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, 852-8588, Japan
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Yahaba-cho, 028-3694, Japan
| | - Yuko Ohara Nemoto
- Department of Pediatric Dentistry, Course of Medical and Dental Sciences, 200674 Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, 852-8588, Japan
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Yahaba-cho, 028-3694, Japan
| | - Haruka Nishimata
- Department of Pediatric Dentistry, Course of Medical and Dental Sciences, 200674 Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, 852-8588, Japan
| | - Momo Sawase
- Department of Pediatric Dentistry, Course of Medical and Dental Sciences, 200674 Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, 852-8588, Japan
| | - Yu Shimoyama
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Yahaba-cho, 028-3694, Japan
| | - Manami Nakasato-Suzuki
- Division of Periodontology, Department of Conservative Dentistry, Iwate Medical University School of Dentistry, Morioka, 020-8505, Japan
| | - Kiyoshi Ito
- Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, 573-0101, Japan
| | - Naomi Tanoue
- Department of Pediatric Dentistry, Course of Medical and Dental Sciences, 200674 Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, 852-8588, Japan
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Liu H, Sun C, Jiang Y, Gao R, Ying Q, Li X, Liu H, Guo J, Li M. Eldecalcitol alleviates diabetic periodontitis by regulating macrophage efferocytosis and polarization via SOCE machinery. Int Immunopharmacol 2025; 146:113894. [PMID: 39729922 DOI: 10.1016/j.intimp.2024.113894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/15/2024] [Accepted: 12/16/2024] [Indexed: 12/29/2024]
Abstract
Diabetes exacerbates the occurrence and severity of periodontitis, the pathogenesis of diabetic periodontitis (DPD) is influenced by the delayed resolution of inflammation. Eldecalcitol (ED-71) has shown promise in preventing bone loss in DPD. We herein aimed to investigate the role of ED-71 in the inflammatory regression phase of DPD and elucidate the underlying mechanisms. Type-2 diabetes was induced by streptozotocin injection in Wistar rats, and to explore the in vivo effect of ED-71 on macrophage efferocytosis, periodontitis was induced by ligation combined with lipopolysaccharide. Alveolar bone destruction was assessed using micro-computed tomography, hematoxylin-eosin, immunohistochemistry, and tartrate-resistant acid phosphatase staining. Immunofluorescence staining and flow cytometry detected neutrophils, apoptotic cells, and macrophage polarization in periodontal tissue. Additionally, flow cytometry, real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to examine macrophage efferocytosis and changes in store-operated calcium entry (SOCE). We found that rats with diabetes exhibited more severe alveolar bone destruction and increased neutrophil aggregates in periodontal tissue. Following the ED-71 administration, alveolar bone loss significantly decreased, and the immune microenvironment of periodontal tissue tended to suppress inflammation. Macrophages stimulated with high glucose experienced disruption of SOCE machinery, leading to the inhibition of efferocytosis in vitro. ED-71 demonstrated the ability to restore macrophage efferocytosis by correcting SOCE, and preventing sustained inflammatory damage to periodontal tissue. In conclusion, diabetes impairs macrophage efferocytosis and M2 polarization in periodontitis rats, resulting in the delayed resolution of inflammation. ED-71 could attenuate alveolar bone loss by mitigating macrophage via SOCE machinery in DPD.
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Affiliation(s)
- Hongrui Liu
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Changyun Sun
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Yujun Jiang
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Ruihan Gao
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Qiaohui Ying
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Xiaolin Li
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
| | - Hongrui Liu
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China; Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China
| | - Jie Guo
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China.
| | - Minqi Li
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China; School of Clinical Medicine, Jining Medical University, Jining, China; Institute of Oral Basic Research, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University.
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Penttala M, Sorsa T, Thomas JT, Grigoriadis A, Sakellari D, Gupta S, Pärnänen P, Pätilä T, Räisänen IT. Periodontitis Home Screening with Mouth Rinse Cut-Off 20 Ng/mL aMMP-8 Test and Mobile Application. Diagnostics (Basel) 2025; 15:296. [PMID: 39941225 PMCID: PMC11816464 DOI: 10.3390/diagnostics15030296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/22/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
Background: In this study, we describe a method by which a patient can independently assess their own periodontitis risk, for example, at home, with a mobile application. The aim of the study is to use active matrix metalloproteinase aMMP-8 mouth rinse cut-off 20 ng/mL point-of-care testing (POCT) and a polynomial function to reveal patients' statistical risk of periodontitis. Methods: The polynomial function presented in this study was modeled with multiple logistic regression and the function estimates the risk of periodontitis using a probability measure. To investigate variables associated with periodontitis, we used data from adult patients visiting dental clinics in Thessaloniki, Greece. Results: The research results revealed that with appropriate information it is possible to obtain sufficient accuracy about a patient's potential risk of periodontitis. The function for estimating risk of periodontitis is PERIORISK = (1 + e-(3.392×X1+0.002×X2+1.858×X3-9.151))-1, where X1 = aMMP-8 test result and tobacco smoking status, X2 = age × waist circumference and X3 = patient's individual and parental history of diabetes. Conclusions: The prediction of periodontitis risk using an aMMP-8 test and a polynomial function seems to be a useful, non-invasive, safe-to-use and cost-effective tool for all people. Overall, in the model created, mouth rinse cut-off 20 ng/mL aMMP-8 test result, age, waist circumference, tobacco smoking status and patient's individual and parental history of diabetes were found to be good factors explaining the risk of periodontitis.
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Affiliation(s)
- Miika Penttala
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; (T.S.); (J.T.T.); (P.P.); (I.T.R.)
| | - Timo Sorsa
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; (T.S.); (J.T.T.); (P.P.); (I.T.R.)
- Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Julie Toby Thomas
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; (T.S.); (J.T.T.); (P.P.); (I.T.R.)
| | - Andreas Grigoriadis
- Department of Preventive Dentistry, Periodontology and Implant Biology, Faculty of Health Sciences, Dental School, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.G.); (D.S.)
- Dental Sector, 424 General Military Training Hospital, 564 29 Thessaloniki, Greece
| | - Dimitra Sakellari
- Department of Preventive Dentistry, Periodontology and Implant Biology, Faculty of Health Sciences, Dental School, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.G.); (D.S.)
| | - Shipra Gupta
- Oral Health Sciences Centre, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India;
| | - Pirjo Pärnänen
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; (T.S.); (J.T.T.); (P.P.); (I.T.R.)
| | - Tommi Pätilä
- Department of Pediatric Surgery, New Children’s Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland;
| | - Ismo T. Räisänen
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; (T.S.); (J.T.T.); (P.P.); (I.T.R.)
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Li Y, Liu Y, Gou M. Peptide with Dual Roles in Immune and Metabolic Regulation: Liver-Expressed Antimicrobial Peptide-2 (LEAP-2). Molecules 2025; 30:429. [PMID: 39860298 PMCID: PMC11767564 DOI: 10.3390/molecules30020429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/10/2025] [Accepted: 01/16/2025] [Indexed: 01/30/2025] Open
Abstract
Liver-expressed antimicrobial peptide 2 (LEAP-2) was originally discovered as an antimicrobial peptide that plays a vital role in the host innate immune system of various vertebrates. Recent research discovered LEAP-2 as an endogenous antagonist and inverse agonist of the GHSR1a receptor. By acting as a competitive antagonist to ghrelin, LEAP-2 influences energy balance and metabolic processes via the ghrelin-GHSR1a signaling pathway. LEAP-2 alone or the LEAP-2/ghrelin molar ratio showed potential as therapeutic targets for obesity, diabetes, and metabolic disorders. This review explores the recent advances of LEAP-2 in immune modulation and energy regulation, highlighting its potential in treating the above diseases.
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Affiliation(s)
- Yitong Li
- College of Life Science, Liaoning Normal University, Dalian 116081, China;
- Lamprey Research Center, Liaoning Normal University, Dalian 116081, China
| | - Ying Liu
- Haixia Institute of Science and Technology, College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350007, China;
| | - Meng Gou
- College of Life Science, Liaoning Normal University, Dalian 116081, China;
- Lamprey Research Center, Liaoning Normal University, Dalian 116081, China
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