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Chen X, Zhang W, Pan Y, Ran J, Liu X, Yu X, He Q. Preparation, identification, and molecular mechanism of novel DPP-IV inhibitory peptides from pumpkin seed: In silico screening and experimental validation. Food Chem 2025; 486:144530. [PMID: 40339413 DOI: 10.1016/j.foodchem.2025.144530] [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: 01/30/2025] [Revised: 04/22/2025] [Accepted: 04/24/2025] [Indexed: 05/10/2025]
Abstract
The rising prevalence of Type 2 diabetes mellitus (T2DM) and the limitations of synthetic DPP-IV inhibitors emphasize the need for natural alternatives with fewer side effects. This study explored pumpkin seed protein (PSP) as a source of potential DPP-IV inhibitory peptides. Through in silico screening and experimental validation, seven novel peptides were identified, with LPGFF, LPGF, and MPLPA exhibiting potent inhibitory activities (IC50: 449.68-478.88 μM). Molecular docking and dynamics simulations revealed stable binding to DPP-IV's active site, interacting with key residues (Tyr547, Ser630, Tyr662, Arg125, Glu205). Kinetic analysis indicated competitive inhibition. In vivo studies in C57BL/6 J mice demonstrated significant hypoglycemic effects, reducing blood glucose AUC by 14.98-18.65 % at 100 mg/kg. The peptides also exhibited stability under varying temperatures, pH, and gastrointestinal conditions. These findings position PSP as a promising source of DPP-IV inhibitors and highlight the potential of in silico screening for bioactive peptide discovery in T2DM management.
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Affiliation(s)
- Xiya Chen
- Engineering Research Center of Active Substance and Biotechnology, Ministry of Education, College of Life Science, Chongqing Normal University, Chongqing 401331, China
| | - Wenhao Zhang
- Engineering Research Center of Active Substance and Biotechnology, Ministry of Education, College of Life Science, Chongqing Normal University, Chongqing 401331, China
| | - Yuexin Pan
- Engineering Research Center of Active Substance and Biotechnology, Ministry of Education, College of Life Science, Chongqing Normal University, Chongqing 401331, China
| | - Jia Ran
- Engineering Research Center of Active Substance and Biotechnology, Ministry of Education, College of Life Science, Chongqing Normal University, Chongqing 401331, China
| | - Xia Liu
- Engineering Research Center of Active Substance and Biotechnology, Ministry of Education, College of Life Science, Chongqing Normal University, Chongqing 401331, China
| | - Xiaodong Yu
- Engineering Research Center of Active Substance and Biotechnology, Ministry of Education, College of Life Science, Chongqing Normal University, Chongqing 401331, China.
| | - Qiyi He
- Engineering Research Center of Active Substance and Biotechnology, Ministry of Education, College of Life Science, Chongqing Normal University, Chongqing 401331, China.
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Thal SC, Shityakov S, Salvador E, Förster CY. Heart Rate Variability, Microvascular Dysfunction, and Inflammation: Exploring the Potential of taVNS in Managing Heart Failure in Type 2 Diabetes Mellitus. Biomolecules 2025; 15:499. [PMID: 40305215 PMCID: PMC12024555 DOI: 10.3390/biom15040499] [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: 02/10/2025] [Revised: 03/19/2025] [Accepted: 03/27/2025] [Indexed: 05/02/2025] Open
Abstract
Patients with type 2 diabetes mellitus (T2DM) predominantly experience mortality due to cardiovascular diseases (CVD), particularly in low- and middle-income nations. Among these, heart failure (HF) is the most severe cardiovascular complication in terms of prognosis and management. Despite advancements in individualized glycemic control and cardiovascular risk management, including the development of novel glucose- and lipid-lowering agents, the prevalence of HF in T2DM patients remains persistently high. This indicates that factors beyond hyperglycemia significantly contribute to the heightened risk of HF associated with T2DM. This review examines critical factors influencing CVD risk in T2DM, particularly the roles of reduced heart rate variability (HRV), a marker of autonomic dysfunction, and chronic inflammation, both of which play pivotal roles in HF pathogenesis. Recent evidence highlights the potential of vagus nerve activation to modulate these risk factors, underscoring its capacity to reduce T2DM-related cardiovascular complications. Specifically, we discuss the therapeutic promise of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive intervention to enhance vagal tone, decrease systemic inflammation, and improve cardiovascular outcomes in T2DM. By addressing the interplay among HRV, microvascular disease, and inflammation, this review provides a comprehensive perspective on the potential utility of taVNS in managing HF in T2DM.
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Affiliation(s)
- Serge C. Thal
- Department of Anesthesiology, Helios University Hospital, Witten/Herdecke University, 42283 Wuppertal, Germany;
| | - Sergey Shityakov
- Laboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO University, 197101 Saint-Petersburg, Russia;
| | - Ellaine Salvador
- Section Experimental Neurosurgery, Department of Neurosurgery, University Hospital Würzburg, 97080 Würzburg, Germany;
| | - Carola Y. Förster
- Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Section Cerebrovascular Sciences and Neuromodulation, University Hospital Würzburg, 97080 Würzburg, Germany
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Malaba J, Kosiyo P, Guyah B. Haemoglobin types and variant interference with HbA1c and its association with uncontrolled HbA1c in type 2 diabetes mellitus. BMC Res Notes 2024; 17:342. [PMID: 39574185 PMCID: PMC11583738 DOI: 10.1186/s13104-024-06982-7] [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: 03/29/2024] [Accepted: 10/19/2024] [Indexed: 11/24/2024] Open
Abstract
Diabetes mellitus is among the leading global health concerns, causing over 1.5 million deaths alongside other significant comorbidities and complications. Conventional diagnosis involves estimating fasting, random blood glucose levels and glucose tolerance test. For monitoring purposes, long-term glycaemic control has been achieved through the measurement of glycated haemoglobin (HbA1c) which is considered reliable and preferred tool. However, its estimation could be affected by haemoglobin types like HbA0, HbA2, and HbF concentrations whose magnitude remains unclear as well as other haematological parameters. As such, the current study determined the association between HbA1c and haemoglobin types and determined correlation between haemoglobin types and haematological parameters among patients with type 2 diabetes mellitus (T2DM) compared to healthy non-diabetic participants. In this cross-sectional study, participants [n = 144 (72 per group), ages 23-80 years] were recruited and the desired parameter measured. HbA1c and other Haemoglobin variants were measured using ion-exchange high-performance liquid chromatography (HPLC) by the Bio-Rad D-10 machine (Bio-Rad Laboratories, Inc). Haematological parameters were measured using the Celtac G MEK-i machine (Nihon Kohden Europe). SPSS version 27 (IBM Corporation, Chicago, Illinois, United States) was used for the analysis. Chi-square (χ2) analysis, Mann-Whitney U test, Binary logistic regression and Pearson correlation were used to determine the differences between proportions, compare laboratory characteristics, associations and correlations respectively. With non-diabetics as the reference group, HbA1c was associated with increased HbA0 [OR = 1.509, 95% CI = 1.020-1.099, p = 0.003] and increased HbA2 [OR = 3.893, 95% CI = 2.161-7.014, p = 0.001]. However, there was no significant association between HbA1c and HbF [OR = 2.062, 95% CI = 0.873-4.875, p = 0.099]. Further, haematocrit (HCT) had a negative correlation with HbAO and a positive correlation with HbAS in participants with controlled diabetes. Mean cell volume (MCV) and mean cell haemoglobin (MCH) had a negative correlation with HbF. MCHC (mean cell haemoglobin concentration) had a negative correlation with HbA2 in participant with uncontrolled diabetes. The study concluded that levels of various haemoglobin types should be considered while monitoring glycaemic control through HbA1c. Additionally, MCHC should be considered in individuals with high concentration of HbA2 among T2DM patients while interpretating results for HbA1c.
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Affiliation(s)
- Joseph Malaba
- Department of Biomedical Science and Technology, School of Public Health Maseno University, Private Bag, Maseno, Kenya
| | - Paul Kosiyo
- Department of Medical Laboratory Sciences, School of Medicine, Maseno University, Private Bag, Maseno, Kenya.
| | - Bernard Guyah
- Department of Biomedical Science and Technology, School of Public Health Maseno University, Private Bag, Maseno, Kenya
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Wang Z, Guo Z, Luo Y, Ma L, Hu X, Chen F, Li D. A review of the traditional uses, pharmacology, and toxicology of areca nut. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 134:156005. [PMID: 39241389 DOI: 10.1016/j.phymed.2024.156005] [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: 03/22/2024] [Revised: 05/24/2024] [Accepted: 05/31/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND Areca nut, the fruit of A. catechu, is an important Chinese herbal medicine and is the first of China's "four southern medicines". The main chemical components are alkaloids, phenols, polysaccharides, amino acids, and terpenoids. The flowers, leaves, fruits and seeds of A. catechu contain high medicinal value. However, with the emergence of adverse reactions in people who chew areca nut, people have doubts about the safety of the use of areca nut. PURPOSE In view of the two sides of pharmacology and toxicology of areca nut, this study comprehensively reviewed the components of different parts of A. catechu, the mechanism of pharmacology and toxicology, and the relationship between dosage and pharmacology and toxicology, in order to provide a new reference for the safe application of areca nut. METHODS We used "Areca nut", "Betel nut", and known biologically active ingredients in areca nut, combined with "natural active ingredients", "pharmacological activity", and "toxicological effect" as keywords to search in PubMed, Web of Science, Science Direct and CNKI up to March 2024. RESULTS A large number of studies have shown that low-dose areca nut has pharmacological effects such as deworming, anti-inflammatory, improving gastrointestinal function, lowering blood lipids, preventing atherosclerosis, anti-depression properties. The important mechanism involved in these effects is to reduce the generation of ROS, inhibit the activation of NADPH oxidase, increase the activity of antioxidant enzymes, affect MAPK, AKT, TLR, NF-κB, Nrf-2, PI3 K, STAT3 signaling pathway, reduce COX-2, IL-1β m RNA, MCP-1 and ICAM-1 mRNA gene expression, reduce IL-6, IL-8, IGE levels, activate AMPK signaling pathway, change the ion level in cells, and increase Bax/Bcl-2 ratio. It interferes with the biochemical metabolic process of bacteria. Long-term consumption of areca nut in large quantities will cause some adverse reactions or related malignant diseases to the human body. CONCLUSION We reviewed the pharmacological and toxicological effects and related mechanisms of areca nut, revealed the relationship between dose and pharmacological and toxicological effects, and discussed how to reduce the toxicity of areca nut and improve the comprehensive utilization of areca nut. It provides a reference for the study of the relationship between areca nut and human health, as well as the safe and rational use and full development and utilization of areca nut.
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Affiliation(s)
- Zihan Wang
- College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Ziyuan Guo
- College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Yinghua Luo
- College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Lingjun Ma
- College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Xiaosong Hu
- College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China.
| | - Daotong Li
- College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China.
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Li X, Li Y, Lei C. Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Metabolism in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Int J Endocrinol 2024; 2024:1785321. [PMID: 39309475 PMCID: PMC11416174 DOI: 10.1155/2024/1785321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 08/09/2024] [Accepted: 08/22/2024] [Indexed: 09/25/2024] Open
Abstract
Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an intriguing class of antihyperglycemic drugs for type 2 diabetes mellitus (T2DM). Such drugs not only play a primary role in regulating blood glucose levels but also exhibit additional pleiotropic effects, including potential impacts on bone metabolism and fracture risk. However, the mechanism of such drugs is unclear. The purpose of this study was to evaluate the effect of GLP-1 RAs on bone metabolism in T2DM. Methods From database inception to May 1, 2023, the searches were conducted on multiple databases such as Web of Science, Embase, PubMed, CNKI, the Cochrane Library, Wanfang, and VIP. We systematically collected all randomized controlled trials of bone metabolism in patients with T2DM treated with GLP-1 RAs. The quality evaluation was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. Data extraction was analyzed using Review Manager 5.4 software, and funnel plots were drawn to evaluate publication bias. Results Twenty-six randomized controlled trials that met the inclusion criteria were included, involving a total of 2268 participants. In this study, compared to other antidiabetic drugs or placebo, GLP-1 RAs were found to significantly increase serum calcium (mean difference (MD) = 0.05, 95% confidence interval (CI) (0.01, 0.09), P = 0.002], bone alkaline phosphatase [standardized MD (SMD) = 0.76, 95% CI (0.29, 1.24), and P = 0.001), and osteocalcin (SMD = 2.04, 95% CI (0.99, 3.08), and P = 0.0001) in T2DM. Specifically, liraglutide increased procollagen type 1 N-terminal propeptide (SMD = 0.45, 95% CI (0.01, 0.89), and P = 0.04). GLP-1 RAs were also associated with a reduction in cross-linked C-terminal telopeptides of type I collagen (SMD = -0.36, 95% CI (-0.70, -0.03), and P = 0.03). In additionally, GLP-1 RAs increased lumbar spine bone mineral density (BMD) (SMD = 1.04, 95% CI (0.60, 1.48), and P < 0.00001) and femoral neck BMD (SMD = 1.29, 95% CI (0.36, 2.23), and P = 0.007). Conclusions GLP-1 RAs can not only improve BMD in the lumbar spine and femoral neck of patients with T2DM but also protect bone health by inhibiting bone resorption and promoting bone formation. Systematic Review Registration. PROSPERO, identifier CRD42023418166.
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Affiliation(s)
- Xin Li
- Department of NutritionGeneral Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Yang Li
- Department of Geriatrics and Special NeedsGeneral Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Chen Lei
- Department of Geriatrics and Special NeedsGeneral Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
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Neuhauser C, Schwarzinger B, Schwarzinger C, Feichtinger M, Stadlbauer V, Arnaut V, Drotarova I, Blank-Landeshammer B, Weghuber J. Insulin-Mimetic Activity of Herbal Extracts Identified with Large-Scale Total Internal Reflection Fluorescence Microscopy. Nutrients 2024; 16:2182. [PMID: 39064624 PMCID: PMC11280383 DOI: 10.3390/nu16142182] [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: 06/20/2024] [Revised: 07/01/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
Diabetes mellitus is a spreading global pandemic. Type 2 diabetes mellitus (T2DM) is the predominant form of diabetes, in which a reduction in blood glucose uptake is caused by impaired glucose transporter 4 (GLUT4) translocation to the plasma membrane in adipose and muscle cells. Antihyperglycemic drugs play a pivotal role in ameliorating diabetes symptoms but often are associated with side effects. Hence, novel antidiabetic compounds and nutraceutical candidates are urgently needed. Phytogenic therapy can support the prevention and amelioration of impaired glucose homeostasis. Using total internal reflection fluorescence microscopy (TIRFM), 772 plant extracts of an open-access plant extract library were screened for their GLUT4 translocation activation potential, resulting in 9% positive hits. Based on commercial interest and TIRFM assay-based GLUT4 translocation activation, some of these extracts were selected, and their blood glucose-reducing effects in ovo were investigated using a modified hen's egg test (Gluc-HET). To identify the active plant part, some of the available candidate plants were prepared in-house from blossoms, leaves, stems, or roots and tested. Acacia catechu (catechu), Pulmonaria officinalis (lungwort), Mentha spicata (spearmint), and Saponaria officinalis (common soapwort) revealed their potentials as antidiabetic nutraceuticals, with common soapwort containing GLUT4 translocation-activating saponarin.
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Affiliation(s)
- Cathrina Neuhauser
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Stelzhamerstraße 23, 4600 Wels, Austria; (C.N.); (B.S.); (M.F.); (V.S.); (V.A.); (I.D.)
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Technopark 1D, 3430 Tulln, Austria;
| | - Bettina Schwarzinger
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Stelzhamerstraße 23, 4600 Wels, Austria; (C.N.); (B.S.); (M.F.); (V.S.); (V.A.); (I.D.)
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Technopark 1D, 3430 Tulln, Austria;
| | - Clemens Schwarzinger
- Institute for Chemical Technology of Organic Materials, Johannes Kepler University, 4040 Linz, Austria;
| | - Michaela Feichtinger
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Stelzhamerstraße 23, 4600 Wels, Austria; (C.N.); (B.S.); (M.F.); (V.S.); (V.A.); (I.D.)
| | - Verena Stadlbauer
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Stelzhamerstraße 23, 4600 Wels, Austria; (C.N.); (B.S.); (M.F.); (V.S.); (V.A.); (I.D.)
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Technopark 1D, 3430 Tulln, Austria;
| | - Verena Arnaut
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Stelzhamerstraße 23, 4600 Wels, Austria; (C.N.); (B.S.); (M.F.); (V.S.); (V.A.); (I.D.)
| | - Ivana Drotarova
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Stelzhamerstraße 23, 4600 Wels, Austria; (C.N.); (B.S.); (M.F.); (V.S.); (V.A.); (I.D.)
| | - Bernhard Blank-Landeshammer
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Technopark 1D, 3430 Tulln, Austria;
| | - Julian Weghuber
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Stelzhamerstraße 23, 4600 Wels, Austria; (C.N.); (B.S.); (M.F.); (V.S.); (V.A.); (I.D.)
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Technopark 1D, 3430 Tulln, Austria;
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Fröhlich H, Bossmeyer A, Kazmi S, Goode KM, Agewall S, Atar D, Grundtvig M, Frey N, Cleland JGF, Frankenstein L, Clark AL, Täger T. Glycaemic control and insulin therapy are significant confounders of the obesity paradox in patients with heart failure and diabetes mellitus. Clin Res Cardiol 2024; 113:822-830. [PMID: 37608126 PMCID: PMC11108876 DOI: 10.1007/s00392-023-02268-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 09/13/2022] [Indexed: 08/24/2023]
Abstract
BACKGROUND A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown. METHODS We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated. RESULTS We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%. CONCLUSION In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker.
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Affiliation(s)
- Hanna Fröhlich
- Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Anna Bossmeyer
- Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Syed Kazmi
- Hull University Teaching Hospitals NHS Trust, Hull, UK
| | - Kevin M Goode
- Hull University Teaching Hospitals NHS Trust, Hull, UK
| | - Stefan Agewall
- Department of Cardiology, and Institute of Clinical Medicine, Oslo University Hospital Ulleval, University of Oslo, Oslo, Norway
| | - Dan Atar
- Department of Cardiology, and Institute of Clinical Medicine, Oslo University Hospital Ulleval, University of Oslo, Oslo, Norway
| | - Morten Grundtvig
- Medical Department, Innlandet Hospital Trust Division Lillehammer, Lillehammer, Norway
| | - Norbert Frey
- Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - John G F Cleland
- National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK
- Robertson Centre for Biostatistics and Clinical Trials, Glasgow, UK
| | - Lutz Frankenstein
- Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
| | | | - Tobias Täger
- Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
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Chen S, Ling Y, Zhou F, Qiao X, Reinhardt JD. Trajectories of cognitive function among people aged 45 years and older living with diabetes in China: Results from a nationally representative longitudinal study (2011~2018). PLoS One 2024; 19:e0299316. [PMID: 38787866 PMCID: PMC11125531 DOI: 10.1371/journal.pone.0299316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 02/08/2024] [Indexed: 05/26/2024] Open
Abstract
OBJECTIVES Diabetes is associated with decline of cognitive function. Exploring different trajectories of cognitive function occurring in people with diabetes is important to improved prognosis. This study aimed to investigate differential patterns of trajectories of cognitive function and baseline determinants of trajectory group membership utilizing data from middle-aged and older Chinese adults with diabetes. METHODS Participants of the Chinese Health And Retirement Longitudinal Study (CHARLS) aged 45 years and above received biennial assessments between 2011 and 2018. The primary outcome was overall cognitive function score operationalized as sum of mental intactness and episodic memory scores derived from the Telephone Interview of Cognitive Status (TICS). A weighted growth mixture model was used to estimate cognitive function trajectories of CHARLS participants with diabetes, and baseline factors associated with trajectory group membership were investigated with weighted multinomial logistic regression. RESULTS Data from 1,463 participants with diabetes aged 45 years and above were analyzed, a three-group trajectory model showed the best fit for overall cognitive scores: low baseline, linear declining (22.1%); moderate baseline, linear declining (37.5%) and high-stable (40.3%). Older participants, females, participants with low education, with nighttime sleep <6 h, without daytime napping habits, and with depressive symptoms were at a higher risk of unfavorable cognitive function trajectories. CONCLUSIONS We identified heterogeneous trajectories of cognitive function among middle-aged and older people living with diabetes in China. Socially vulnerable groups including females, rural residents, and those with low education were at a higher risk for unfavorable trajectories. In health programs aimed at preventing and mitigating cognitive decline in individuals with diabetes more attention should be given to vulnerable groups. Reduced nighttime sleep, lack of daytime napping, and depressive symptoms appear to be modifiable risk factors.
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Affiliation(s)
- Shi Chen
- Institute for Disaster Management and Reconstruction of Sichuan University and Hong Kong Polytechnic University, Sichuan University, Chengdu, China
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Yuewei Ling
- Department of Management Science and Engineering, Stanford University, Stanford, CA, United States of America
| | - Faquan Zhou
- Department of Vascular Surgery, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Xu Qiao
- Institute for Disaster Management and Reconstruction of Sichuan University and Hong Kong Polytechnic University, Sichuan University, Chengdu, China
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Jan D. Reinhardt
- Institute for Disaster Management and Reconstruction of Sichuan University and Hong Kong Polytechnic University, Sichuan University, Chengdu, China
- Department of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland
- Rehabilitation Medicine Centre, Jiangsu Province Hospital/Nanjing Medical University First Affiliated Hospital, Nanjing, China
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Lee H, Kang EY, Lee J, Kim Y, Kang S, Kim H, Kim HK, Gang G, Lee SG, Lei C, Go GW. A combined extract containing Schisandra chinensis (SCE) reduced hepatic triglyceride accumulation in rats fed a high-sucrose diet. Food Sci Biotechnol 2024; 33:1449-1457. [PMID: 38585559 PMCID: PMC10992756 DOI: 10.1007/s10068-023-01464-1] [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: 07/03/2023] [Revised: 09/28/2023] [Accepted: 10/10/2023] [Indexed: 04/09/2024] Open
Abstract
Excessive hepatic lipid accumulation is closely linked to inflammation, insulin resistance, and metabolic syndromes. We hypothesized that a combined extract containing Schisandra chinensis (SCE) could alleviate hepatic lipid accumulation. Male Sprague-Dawley rats fed a high-sucrose diet (HSD) were randomly assigned to three groups (n = 6): normal diet (ND), HSD (60% kcal from sucrose), and HSD + SCE (HSD with 2.44% SCE). Liquid chromatography-tandem mass spectrometry revealed that SCE contains chlorogenic acid (5.514 ± 0.009 mg/g) and schisandrin (0.179 ± 0.002 mg/g) as bioactive components. SCE did not alter the body weight, fat mass, lean mass, or glucose levels. Strikingly, SCE effectively reduced the plasma triglyceride (TG) and hepatic TG levels compared to the HSD group. Adiposity reduction is due to decreased activity of hepatic de novo lipogenic enzymes. These results indicated that SCE has nutraceutical potential for the prevention and treatment of hepatic steatosis. Supplementary Information The online version contains supplementary material available at 10.1007/s10068-023-01464-1.
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Affiliation(s)
- Haneul Lee
- Department of Food and Nutrition, Hanyang University, Seoul, 04763 Republic of Korea
| | - Eun Young Kang
- Department of Food and Nutrition, Hanyang University, Seoul, 04763 Republic of Korea
| | - Joowon Lee
- Department of Food Science and Nutrition, Pukyong National University, Busan, 48513 Republic of Korea
| | - Yejin Kim
- Department of Food and Nutrition, Hanyang University, Seoul, 04763 Republic of Korea
| | - Sumin Kang
- Department of Food and Nutrition, Hanyang University, Seoul, 04763 Republic of Korea
| | - Hayoon Kim
- Department of Food and Nutrition, Hanyang University, Seoul, 04763 Republic of Korea
| | - Hyun Kyung Kim
- Department of Food and Nutrition, Hanyang University, Seoul, 04763 Republic of Korea
| | - Gyoungok Gang
- Department of Food Science and Nutrition, Pukyong National University, Busan, 48513 Republic of Korea
| | - Sang-gil Lee
- Department of Food Science and Nutrition, Pukyong National University, Busan, 48513 Republic of Korea
| | - Cao Lei
- Department of Food Science and Biotechnology, College of BioNano Technology, Gachon University, Seongnam, Republic of Korea
| | - Gwang-woong Go
- Department of Food and Nutrition, Hanyang University, Seoul, 04763 Republic of Korea
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10
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Ray A, Atal S, Sharma S, Sampath A. Comparison of Glycated Hemoglobin (HbA1c) Values Estimated by High-Performance Liquid Chromatography and Spectrophotometry: A Pilot Study. Cureus 2024; 16:e56964. [PMID: 38665712 PMCID: PMC11044070 DOI: 10.7759/cureus.56964] [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] [Accepted: 03/25/2024] [Indexed: 04/28/2024] Open
Abstract
Background Invasive blood sample collection followed by high-performance liquid chromatography (HPLC) based analysis is the gold standard for estimating glycated hemoglobin level or HbA1c currently. Spectrophotometry could be an alternative that holds the potential to be translated into a portable, non-invasive device for glycated hemoglobin level estimation. This study compares HbA1c values obtained from HPLC and spectrophotometry. Methods Venous blood samples were collected from both diabetic and non-diabetic participants in a cross-sectional study. The samples were subjected to both HPLC and spectrophotometry-based estimation of HbA1c%. The results obtained were compared, and the relationship between the two estimations were assessed. Results About 15 diabetic and non-diabetic individuals participated in the study and 28 samples were included in the final analysis. The Pearson's correlation coefficient was 0.65 (95% CI, 0.37-0.82), indicating that there was a strong positive association. This was further supported by the findings from linear regression analysis with a p-value of <0.001. Conclusions The positive correlation between the HPLC and spectrophotometric values supports the hypothesis that spectrophotometry could be an alternative to conventional HPLC for the measurement of HbA1c. This needs to be further validated through larger, well-powered studies.
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Affiliation(s)
- Avik Ray
- Epidemiology and Public Health, Harvard T.H. Chan School of Public Health, Boston, USA
| | - Shubham Atal
- Pharmacology, All India Institute of Medical Sciences, Bhopal, Bhopal, IND
| | - Swati Sharma
- Pharmacology and Therapeutics, Cactus Communications, Mumbai, IND
| | - Ananyan Sampath
- Medicine, All India Institute of Medical Sciences, Bhopal, Bhopal, IND
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11
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Feng X, Cai Y, Xin R. Optimizing diabetes classification with a machine learning-based framework. BMC Bioinformatics 2023; 24:428. [PMID: 37957549 PMCID: PMC10644638 DOI: 10.1186/s12859-023-05467-x] [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: 04/27/2023] [Accepted: 09/04/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Diabetes is a metabolic disorder usually caused by insufficient secretion of insulin from the pancreas or insensitivity of cells to insulin, resulting in long-term elevated blood sugar levels in patients. Patients usually present with frequent urination, thirst, and hunger. If left untreated, it can lead to various complications that can affect essential organs and even endanger life. Therefore, developing an intelligent diagnosis framework for diabetes is necessary. RESULT This paper proposes a machine learning-based diabetes classification framework machine learning optimized GAN. The framework encompasses several methodological approaches to address the diverse challenges encountered during the analysis. These approaches encompass the implementation of the mean and median joint filling method for handling missing values, the application of the cap method for outlier processing, and the utilization of SMOTEENN to mitigate sample imbalance. Additionally, the framework incorporates the employment of the proposed Diabetes Classification Model based on Generative Adversarial Network and employs logistic regression for detailed feature analysis. The effectiveness of the framework is evaluated using both the PIMA dataset and the diabetes dataset obtained from the GEO database. The experimental findings showcase our model achieved exceptional results, including a binary classification accuracy of 96.27%, tertiary classification accuracy of 99.31%, precision and f1 score of 0.9698, recall of 0.9698, and an AUC of 0.9702. CONCLUSION The experimental results show that the framework proposed in this paper can accurately classify diabetes and provide new ideas for intelligent diagnosis of diabetes.
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Affiliation(s)
- Xin Feng
- School of Science, Jilin Institute of Chemical Technology, Jilin, 130000, People's Republic of China
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, 130012, People's Republic of China
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130012, People's Republic of China
| | - Yihuai Cai
- School of Science, Jilin Institute of Chemical Technology, Jilin, 130000, People's Republic of China.
| | - Ruihao Xin
- College of Information and Control Engineering, Jilin Institute of Chemical Technology, Jilin, 130000, People's Republic of China.
- College of Computer Science and Technology, and Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun, 130012, People's Republic of China.
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12
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Marin-Garaundo E, Torre-Beteta RL, Munive-Degregori A, Alvitez J, Barja-Ore J, Mayta-Tovalino F. Use of Artificial Pancreas in the Management of Diabetes Mellitus: A Bibliometric Study. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2023; 11:332-338. [PMID: 37970460 PMCID: PMC10634467 DOI: 10.4103/sjmms.sjmms_12_23] [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: 01/08/2023] [Revised: 05/06/2023] [Accepted: 08/09/2023] [Indexed: 11/17/2023]
Abstract
Objectives To describe the trends and characteristics of the worldwide scientific production on the use of artificial pancreas (AP) in the management of diabetes mellitus (DM). Materials and Methods Scientific papers published between 2017 and 2022 were retrieved from the Scopus database using relevant keywords. Only original articles, reviews, and short surveys were included. The metadata were exported to the SciVal software for retrieving quantitative data and the main characteristics such as journals, authors, institutions, journal metrics by quartiles, subcategories, and collaborative networks were extracted. Results A total of 642 articles were included after applying the inclusion/exclusion criteria: original articles, 489; reviews, 151; and short surveys, 2. The most common type of collaboration was at the national level (38.3%; citations per publication: 22.3; field-weighted citation index [FWCI]: 2.2) followed by international collaboration (29.4%; citations per publication: 19.6; FWCI: 1.94). More than 70% of articles in each year were published in journals listed in Q1. Two journals, Diabetes Technology and Therapeutics and Journal of Diabetes Science and Technology, accounted for about 22% of all publications. Six of the top 10 universities were from the United States, with The University of Virginia having the most publications (n = 54; 59 authors; citations per publication: 38.4; FWCI: 3.73). Conclusions The findings of this study highlight that most research on this topic is published in high-quality journals and has a good citation impact. Notably, most research has been conducted in developed countries, thereby indicating the need for research efforts in this field from developing countries.
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Affiliation(s)
- Eileen Marin-Garaundo
- Academic Department, Faculty of Health Sciences, School of Human Medicine, Universidad Cientifica Del Sur, Peru
| | - Rosario La Torre-Beteta
- Academic Department, Faculty of Health Sciences, School of Human Medicine, Universidad Cientifica Del Sur, Peru
| | | | - Juan Alvitez
- Postgraduate Department, Universidad Nacional Federico Villarreal, Lima, Peru
| | - John Barja-Ore
- Academic Department, Universidad Privada Del Norte, Lima, Peru
| | - Frank Mayta-Tovalino
- Academic Department, Faculty of Health Sciences, School of Human Medicine, Universidad Cientifica Del Sur, Peru
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Ling J, Yang YH. Effect of sitagliptin combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in early diabetic nephropathy. World J Diabetes 2023; 14:1412-1421. [PMID: 37771333 PMCID: PMC10523236 DOI: 10.4239/wjd.v14.i9.1412] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 07/27/2023] [Accepted: 08/07/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Early diabetic nephropathy (DN) is a complication of diabetes mellitus. It mainly affects kidney microvessels and glomerular function, and its timely and effective treatment is critical for early DN. However, the effects of treatments comprising simple Western medicine are not optimal. With the promotion and implementation of integrated Chinese and western medicine treatments, remarkable results have been achieved for many diseases. To this end, we explored the clinical efficacy of integrated traditional Chinese and western medicines for the treatment of early DN. AIM To investigate the effect of sitagliptin tablets combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in patients with early DN. METHODS Through a retrospective analysis, 123 patients with early DN were admitted to the endocrinology clinic of the Changzhou NO. 7 People's Hospital from January 2021 to October 2022 and were selected as study subjects. After rigorous screening, 100 patients with early DN were enrolled. The control group (CG, n = 50) and the observation group (OG, n = 50) were divided according to the treatment method. The CG were treated with sitagliptin, and the OG were treated with sitagliptin plus the Yiqi yangyin huoxue decoction. Both groups were treated for 3 mo. For both groups, the baseline data and clinical efficacy were compared, and changes in blood glucose levels, lipid levels, renal function, and hematological indicators before (T0) and after (T1) treatment were assessed. RESULTS The total effective rate for the OG was 94.00% and that of the CG was 80.00% (P < 0.05). After treatment (T1), the levels of fasting blood glucose, 2 h postprandial glucose, total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol in OG patients were obviously lower than those in the CG (P < 0.05), and cystatin C, homocysteine, urinary microalbumin, and blood creatinine values in OG patients were also obviously lower than those in the CG (P < 0.05); erythrocyte deposition, plasma viscosity, whole blood high shear viscosity, and whole blood low shear viscosity were markedly lower in OG patients than in the CG (P < 0.05). CONCLUSION Sitagliptin combined with Yiqi yangyin huoxue decoction has a remarkable effect when used to treat patients with early DN. Further, it is helpful in improving hemorheological indices and controlling disease progression.
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Affiliation(s)
- Jun Ling
- Department of Pharmacy, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People’s Hospital, Changzhou 213000, Jiangsu Province, China
| | - Yan-Hua Yang
- Department of Pharmacy, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People’s Hospital, Changzhou 213000, Jiangsu Province, China
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14
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Mylavarapu M, Maheta D, Clarke S, Parmar K, Mohammed M, Vuyyuru CS. Diabetes Mellitus on YouTube: A Cross-Sectional Observational Study to Assess the Quality and Reliability of Videos. Cureus 2023; 15:e43704. [PMID: 37724237 PMCID: PMC10505448 DOI: 10.7759/cureus.43704] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2023] [Indexed: 09/20/2023] Open
Abstract
Introduction Diabetes mellitus (DM) encompasses a group of heterogeneous, chronic, and non-communicable diseases characterized by an increase in blood glucose levels. As it has become easily accessible for patients to know about their symptoms and treatment of diseases, it is of utmost importance that reliable information is conveyed on the internet. If not managed appropriately, it may result in the dissemination of false information, leading to risky practices and incorrect treatment, further resulting in detrimental consequences. Aim To assess the quality and reliability of information related to DM on YouTube. Methodology A cross-sectional observational study was conducted in April 2023, wherein top YouTube videos related to 'diabetes' were analyzed for baseline characteristics, type of uploader, as well as quality and reliability using Global Quality Score (GQS) and Reliability Score (DISCEN), respectively. Statistical analysis was performed using SPSS software. Results A total of 87 videos were evaluated in the study. Unfortunately, only 21% of those were uploaded by doctors. The median Video Power Index (VPI) for videos uploaded by other sources was the highest (184.7), and the lowest was for videos uploaded by hospitals (12.6), and this was statistically significant (p = 0.038). The median GQS was highest for videos uploaded by doctors (4) and lowest for videos uploaded by others (3.5). The reliability score was higher in videos uploaded by healthcare organizations (4), which was not significant (p > 0.05). Conclusions Videos uploaded by physicians and healthcare organizations contained reliable information with a high global quality score. Videos uploaded by sources other than doctors and healthcare professionals should consult physicians, as self-diagnosis or self-treatment can lead to potential harm to patients.
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Affiliation(s)
| | | | - Shereece Clarke
- Department of Obstetrics and Gynaecology, University of the West Indies, Montego Bay, JAM
| | - Kashish Parmar
- Department of Internal Medicine, GMERS Medical College, Valsad, Valsad, IND
| | - Majaazuddin Mohammed
- Department of Internal Medicine, Shadan Institute of Medical Sciences, Hyderabad, IND
| | - Chaitanya Sai Vuyyuru
- Department of Internal Medicine, St. Martinus University Faculty of Medicine, Willemstad, CUW
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15
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Iqbal S, Jayyab AA, Alrashdi AM, Reverté-Villarroya S. The Predictive Ability of C-Peptide in Distinguishing Type 1 Diabetes From Type 2 Diabetes: A Systematic Review and Meta-Analysis. Endocr Pract 2023; 29:379-387. [PMID: 36641115 DOI: 10.1016/j.eprac.2023.01.004] [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: 10/19/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/13/2023]
Abstract
OBJECTIVE This systematic review and meta-analysis aimed to investigate the predictive ability of plasma connecting peptide (C-peptide) levels in discriminating type 1 diabetes (T1D) from type 2 diabetes (T2D) and to inform evidence-based guidelines in diabetes classification. METHODS We conducted a holistic review and meta-analysis using PubMed, MEDLINE, EMBASE, and Scopus. The citations were screened from 1942 to 2021. The quality criteria and the preferred reporting items for systematic reviews and meta-analysis checklist were applied. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022355088). RESULTS A total of 23,658 abstracts were screened and 46 full texts reviewed. Of the 46 articles screened, 12 articles were included for the meta-analysis. Included studies varied by race, age, time, and proportion of individuals. The main outcome measure in all studies was C-peptide levels. A significant association was reported between C-peptide levels and the classification and diagnosis of diabetes. Furthermore, lower concentrations and the cutoff of <0.20 nmol/L for fasting or random plasma C-peptide was indicative of T1D. In addition, this meta-analysis revealed the predictive ability of C-peptide levels in discriminating T1D from T2D. Results were consistent using both fixed- and random-effect models. The I2 value (98.8%) affirmed the variability in effect estimates was due to heterogeneity rather than sampling error among all selected studies. CONCLUSION Plasma C-peptide levels are highly associated and predictive of the accurate classification and diagnosis of diabetes types. A plasma C-peptide cutoff of ≤0.20 mmol/L is indicative of T1D and of ≥0.30 mmol/L in the fasting or random state is indicative of T2D.
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Affiliation(s)
- Sajid Iqbal
- Nursing Department, Universitat Rovira Virgili, Campus Terres de l'Ebre, Avenue Remolins, Tarragona, Spain; Department of Health and Medical Science, Liwa College of Technology, Abu Dhabi, United Arab Emirates.
| | - Abdulrahim Abu Jayyab
- Department of Health and Medical Science, Liwa College of Technology, Abu Dhabi, United Arab Emirates
| | - Ayah Mohammad Alrashdi
- Department of Health and Medical Science, Liwa College of Technology, Abu Dhabi, United Arab Emirates
| | - Silvia Reverté-Villarroya
- Nursing Department, Universitat Rovira Virgili, Campus Terres de l'Ebre, Avenue Remolins, Tarragona, Spain; Hospital de Tortosa Verge de la Cinta, Catalan Institute of Health, Pere Virgili Institute, Carretera Esplanetes, Tarragona, Spain
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16
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Cleven L, Dziuba A, Krell-Roesch J, Schmidt SCE, Bös K, Jekauc D, Woll A. Longitudinal associations between physical activity and five risk factors of metabolic syndrome in middle-aged adults in Germany. Diabetol Metab Syndr 2023; 15:82. [PMID: 37098550 PMCID: PMC10131386 DOI: 10.1186/s13098-023-01062-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 04/14/2023] [Indexed: 04/27/2023] Open
Abstract
BACKGROUND We examined the longitudinal association between (change in) physical activity (PA) with new onset of five risk factors of metabolic syndrome among 657 middle-aged adults (mean age 44.1 (standard deviation (SD) 8.6) years) who were free of the respective outcome at baseline, in a longitudinal cohort study spanning over 29 years. METHODS Levels of habitual PA and sports-related PA were assessed by a self-reported questionnaire. Incident elevated waist circumference (WC), elevated triglycerides (TG), reduced high-density lipoprotein cholesterols (HDL), elevated blood pressure (BP), and elevated blood-glucose (BG) were assessed by physicians and by self-reported questionnaires. We calculated Cox proportional hazard ratio regressions and 95% confidence intervals. RESULTS Over time, participants developed (cases of incident risk factor; mean (SD) follow-up time) elevated WC (234 cases; 12.3 (8.2) years), elevated TG (292 cases; 11.1 (7.8) years), reduced HDL (139 cases; 12.4 (8.1) years), elevated BP (185 cases; 11.4 (7.5) years), or elevated BG (47 cases; 14.2 (8.5) years). For PA variables at baseline, risk reductions ranging between 37 and 42% for reduced HDL levels were detected. Furthermore, higher levels of PA (≥ 16.6 METh per week) were associated with a 49% elevated risk for incident elevated BP. Participants who increased PA levels over time, had risk reductions ranging between 38 and 57% for elevated WC, elevated TG and reduced HDL. Participants with stable high amounts of PA from baseline to follow-up had risk reductions ranging between 45 and 87% for incident reduced HDL and elevated BG. CONCLUSIONS PA at baseline, starting PA engagement, maintaining and increasing PA level over time are associated with favorable metabolic health outcomes.
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Affiliation(s)
- Laura Cleven
- Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131, Karlsruhe, Germany.
| | - Anna Dziuba
- Institute of Sport Sciences, Department of Sport Psychology, Goethe University Frankfurt, Ginnheimer Landstraße 39, 60487, Frankfurt, Germany
| | - Janina Krell-Roesch
- Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131, Karlsruhe, Germany
| | - Steffen C E Schmidt
- Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131, Karlsruhe, Germany
| | - Klaus Bös
- Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131, Karlsruhe, Germany
| | - Darko Jekauc
- Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131, Karlsruhe, Germany
| | - Alexander Woll
- Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131, Karlsruhe, Germany
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17
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Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus. Int J Mol Sci 2023; 24:ijms24054852. [PMID: 36902283 PMCID: PMC10003369 DOI: 10.3390/ijms24054852] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/06/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Nonunion and delayed union are common complications of diabetes mellitus that pose a serious health threat to people. There are many approaches that have been used to improve bone fracture healing. Recently, exosomes have been regarded as promising medical biomaterials for improving fracture healing. However, whether exosomes derived from adipose stem cells can promote bone fracture healing in diabetes mellitus remains unclear. In this study, adipose stem cells (ASCs) and exosomes derived from adipose stem cells (ASCs-exos) are isolated and identified. Additionally, we evaluate the in vitro and in vivo effects of ASCs-exos on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone repair and the regeneration in a rat model of nonunion via Western blotting, immunofluorescence assay, ALP staining, alizarin red staining, radiographic examination and histological analysis. Compared with controls, ASCs-exos promoted BMSC osteogenic differentiation. Additionally, the results of Western blotting, radiographic examination and histological analysis show that ASCs-exos improve the ability for fracture repair in the rat model of nonunion bone fracture healing. Moreover, our results further proved that ASCs-exos play a role in activating the Wnt3a/β-catenin signaling pathway, which facilitates the osteogenic differentiation of BMSCs. All these results show that ASCs-exos enhance the osteogenic potential of BMSCs by activating the Wnt/β-catenin signaling pathway, and also facilitate the ability for bone repair and regeneration in vivo, which provides a novel direction for fracture nonunion in diabetes mellitus treatment.
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18
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Wu Y, Wu X, Wang J, Chen S, Chen H, Liu J, Zeng T, Hu M, Liang Y, Sun K, Yang C, Yan L, Ren M. Fibroblast-Derived Extracellular Vesicle-Packaged Long Noncoding RNA Upregulated in Diabetic Skin Enhances Keratinocyte MMP-9 Expression and Delays Diabetic Wound Healing. J Transl Med 2023; 103:100019. [PMID: 36925202 DOI: 10.1016/j.labinv.2022.100019] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 09/29/2022] [Accepted: 10/09/2022] [Indexed: 01/11/2023] Open
Abstract
Accurate communication between fibroblasts and keratinocytes is crucial for diabetic wound healing. Extracellular vesicles are being explored as essential mediators of intercellular communication in the skin. However, the mechanisms underlying wound healing mediated by fibroblast-derived extracellular vesicles (Fib-EVs) remain unclear. The present study evaluated the role of long noncoding RNA upregulated in diabetic skin (lnc-URIDS) packed in Fib-EVs in the wound healing of streptozotocin-induced diabetes and the potential mechanisms of the effects. We demonstrated that high glucose induced the enrichment of lnc-URIDS in Fib-EVs, facilitated the transfer of lnc-URIDS to primary rat epidermal keratinocytes, and increased the expression of matrix metalloproteinase-9. Mechanistically, the binding of lnc-URIDS to YTH domain family protein-2 enhanced the degradation of YTH domain family protein-2 in the lysosomes, which increased the translational activity of the messenger RNA of matrix metalloproteinase-9 and ultimately induced the degradation of collagen for wound healing. The results provided an insight into the crosstalk and cooperation between fibroblasts and keratinocytes in collagen homeostasis in diabetic wounds and clarified the mechanism by which lnc-URIDS degrades collagen for diabetic wound healing.
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Affiliation(s)
- Yuxi Wu
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoying Wu
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Peking University Fifth School of Clinical Medicine, Beijing, China
| | - Jiahuan Wang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Sifan Chen
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hongxing Chen
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jing Liu
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tingting Zeng
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mengdie Hu
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ying Liang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Kan Sun
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chuan Yang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Li Yan
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Meng Ren
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
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Huber J, Smeikal M, Saely CH, Stingl H, Clodi M, Lechleitner M, Fasching P. [Geriatric aspects for the management of diabetes mellitus (Update 2023)]. Wien Klin Wochenschr 2023; 135:307-318. [PMID: 37101051 PMCID: PMC10133361 DOI: 10.1007/s00508-022-02124-w] [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] [Accepted: 11/09/2022] [Indexed: 04/28/2023]
Abstract
There is a high prevalence of diabetes mellitus in the elderly population of industrial countries. The present article provides recommendations for the screening, prevention and treatment of elderly diabetic patients according to current scientific evidence.
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Affiliation(s)
- Joakim Huber
- Abteilung für Innere Medizin mit Akutgeriatrie und Palliativmedizin, Franziskus Spital, Standort Landstraße, Landstraßer Hauptstraße 4a, 1030 Wien, Österreich
| | - Michael Smeikal
- Abteilung für Innere Medizin mit allgemeiner Geriatrie und Palliativmedizin, Haus der Barmherzigkeit, Wien, Österreich
| | - Christoph H. Saely
- Abteilung für Innere Medizin und Kardiologie/VIVIT-Institut, Landeskrankenhaus Feldkirch, Feldkirch, Österreich
| | - Harald Stingl
- Interne Abteilung, Landesklinikum Melk, Melk, Österreich
| | - Martin Clodi
- ICMR—Institute for Cardiovascular and Metabolic Research, Johannes Kepler Universität Linz (JKU Linz), 4040 Linz, Österreich
| | - Monika Lechleitner
- Interne Abteilung, Landeskrankenhaus Hochzirl – Natters, Hochzirl, Österreich
| | - Peter Fasching
- 5. Medizinische Abteilung mit Endokrinologie, Rheumatologie und Akutgeriatrie, Klinik Ottakring der Stadt Wien, Wien, Österreich
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20
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Xu Z, Zhao L, Yin L, Liu Y, Ren Y, Yang G, Wu J, Gu F, Sun X, Yang H, Peng T, Hu J, Wang X, Pang M, Dai Q, Zhang G. MRI-based machine learning model: A potential modality for predicting cognitive dysfunction in patients with type 2 diabetes mellitus. Front Bioeng Biotechnol 2022; 10:1082794. [PMID: 36483770 PMCID: PMC9725113 DOI: 10.3389/fbioe.2022.1082794] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 11/10/2022] [Indexed: 07/27/2023] Open
Abstract
Background: Type 2 diabetes mellitus (T2DM) is a crucial risk factor for cognitive impairment. Accurate assessment of patients' cognitive function and early intervention is helpful to improve patient's quality of life. At present, neuropsychiatric screening tests is often used to perform this task in clinical practice. However, it may have poor repeatability. Moreover, several studies revealed that machine learning (ML) models can effectively assess cognitive impairment in Alzheimer's disease (AD) patients. We investigated whether we could develop an MRI-based ML model to evaluate the cognitive state of patients with T2DM. Objective: To propose MRI-based ML models and assess their performance to predict cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM). Methods: Fluid Attenuated Inversion Recovery (FLAIR) of magnetic resonance images (MRI) were derived from 122 patients with T2DM. Cognitive function was assessed using the Chinese version of the Montréal Cognitive Assessment Scale-B (MoCA-B). Patients with T2DM were separated into the Dementia (DM) group (n = 40), MCI group (n = 52), and normal cognitive state (N) group (n = 30), according to the MoCA scores. Radiomics features were extracted from MR images with the Radcloud platform. The variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) were used for the feature selection. Based on the selected features, the ML models were constructed with three classifiers, k-NearestNeighbor (KNN), Support Vector Machine (SVM), and Logistic Regression (LR), and the validation method was used to improve the effectiveness of the model. The area under the receiver operating characteristic curve (ROC) determined the appearance of the classification. The optimal classifier was determined by the principle of maximizing the Youden index. Results: 1,409 features were extracted and reduced to 13 features as the optimal discriminators to build the radiomics model. In the validation set, ROC curves revealed that the LR classifier had the best predictive performance, with an area under the curve (AUC) of 0.831 in DM, 0.883 in MIC, and 0.904 in the N group, compared with the SVM and KNN classifiers. Conclusion: MRI-based ML models have the potential to predict cognitive dysfunction in patients with T2DM. Compared with the SVM and KNN, the LR algorithm showed the best performance.
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Affiliation(s)
- Zhigao Xu
- Department of Radiology, Radiology-Based AI Innovation Workroom, The Third People’s Hospital of Datong, Datong, China
| | - Lili Zhao
- Department of Radiology, Radiology-Based AI Innovation Workroom, The Third People’s Hospital of Datong, Datong, China
| | - Lei Yin
- Graduate School, Changzhi Medical College, Changzhi, China
| | - Yan Liu
- Department of Endocrinology, The Third People’s Hospital of Datong, Datong, China
| | - Ying Ren
- Department of Materials Science and Engineering, Henan University of Technology, Zhengzhou, China
| | - Guoqiang Yang
- College of Medical Imaging, Shanxi Medical University, Taiyuan, China
- Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jinlong Wu
- Department of Radiology, Radiology-Based AI Innovation Workroom, The Third People’s Hospital of Datong, Datong, China
| | - Feng Gu
- Department of Radiology, Radiology-Based AI Innovation Workroom, The Third People’s Hospital of Datong, Datong, China
| | - Xuesong Sun
- Medical Department, The Third People’s Hospital of Datong, Datong, China
| | - Hui Yang
- Department of Radiology, Radiology-Based AI Innovation Workroom, The Third People’s Hospital of Datong, Datong, China
| | - Taisong Peng
- Department of Radiology, The Second People’s Hospital of Datong, Datong, China
| | - Jinfeng Hu
- Department of Radiology, The Second People’s Hospital of Datong, Datong, China
| | - Xiaogeng Wang
- Department of Radiology, Affiliated Hospital of Datong University, Datong, China
| | - Minghao Pang
- Department of Radiology, The People’s Hospital of Yunzhou District, Datong, China
| | - Qiong Dai
- Huiying Medical Technology (Beijing) Co. Ltd, Beijing, China
| | - Guojiang Zhang
- Department of Cardiovasology, Department of Science and Education, The Third People’s Hospital of Datong, Datong, China
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21
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Cleven L, Krell-Roesch J, Schmidt SCE, Dziuba A, Bös K, Jekauc D, Woll A. Longitudinal association between physical activity and the risk of incident metabolic syndrome in middle-aged adults in Germany. Sci Rep 2022; 12:19424. [PMID: 36371479 PMCID: PMC9653435 DOI: 10.1038/s41598-022-24052-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 11/09/2022] [Indexed: 11/13/2022] Open
Abstract
We examined the longitudinal association between physical activity (PA) and the risk of incident metabolic syndrome (MetS) among middle-aged, community-dwelling adults, including 591 individuals (314 females; mean (SD) age, 43.8 (8.5) years) who were free of MetS at baseline. Habitual and sports-related PA was assessed by a self-reported questionnaire. MetS was defined based on HDL-cholesterols, triglycerides, glucose or HbA1c, blood pressure, and waist circumference. We calculated Cox proportional hazard ratios (HR) and 95% confidence intervals (CI) using regression analyses. Over a mean follow-up of 12.5 years, 205 participants developed incident MetS. Four different sports-related PA measures were associated with a decreased risk of incident MetS: (1) Engaging in ≥ 75 min/week (HR 0.71, 95% CI 0.53-0.94), (2) maintaining a continuously high amount from baseline to follow-up of ≥ 75 min/week (HR 0.66, 95% CI 0.46-0.94), (3) starting from < 150 min/week at baseline to ≥ 150 min/week at follow-up (HR 0.65, 95% CI 0.45-0.94), and (4) increasing from < 16.6 MET-hours/week at baseline to ≥ 16.6 MET-hours/week at follow-up (HR 0.47, 95% CI 0.31-0.71). Thus, maintaining, starting or increasing sports-related PA is associated with a lower risk of incident MetS.
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Affiliation(s)
- Laura Cleven
- grid.7892.40000 0001 0075 5874Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131 Karlsruhe, Germany
| | - Janina Krell-Roesch
- grid.7892.40000 0001 0075 5874Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131 Karlsruhe, Germany
| | - Steffen C. E. Schmidt
- grid.7892.40000 0001 0075 5874Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131 Karlsruhe, Germany
| | - Anna Dziuba
- grid.7892.40000 0001 0075 5874Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131 Karlsruhe, Germany ,grid.7839.50000 0004 1936 9721Institute of Sports Sciences, Goethe University Frankfurt, Ginnheimer Landstraße 39, 60487 Frankfurt, Germany
| | - Klaus Bös
- grid.7892.40000 0001 0075 5874Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131 Karlsruhe, Germany
| | - Darko Jekauc
- grid.7892.40000 0001 0075 5874Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131 Karlsruhe, Germany
| | - Alexander Woll
- grid.7892.40000 0001 0075 5874Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Engler-Bunte-Ring 15, 76131 Karlsruhe, Germany
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22
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Mehra N, Varmeziar A, Chen X, Kronick O, Fisher R, Kota V, Mitchell CS. Cross-Domain Text Mining to Predict Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia. Cancers (Basel) 2022; 14:4686. [PMID: 36230609 PMCID: PMC9563938 DOI: 10.3390/cancers14194686] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/04/2022] [Accepted: 09/23/2022] [Indexed: 12/02/2022] Open
Abstract
Tyrosine kinase inhibitors (TKIs) are prescribed for chronic myeloid leukemia (CML) and some other cancers. The objective was to predict and rank TKI-related adverse events (AEs), including under-reported or preclinical AEs, using novel text mining. First, k-means clustering of 2575 clinical CML TKI abstracts separated TKIs by significant (p < 0.05) AE type: gastrointestinal (bosutinib); edema (imatinib); pulmonary (dasatinib); diabetes (nilotinib); cardiovascular (ponatinib). Next, we propose a novel cross-domain text mining method utilizing a knowledge graph, link prediction, and hub node network analysis to predict new relationships. Cross-domain text mining of 30+ million articles via SemNet predicted and ranked known and novel TKI AEs. Three physiology-based tiers were formed using unsupervised rank aggregation feature importance. Tier 1 ranked in the top 1%: hematology (anemia, neutropenia, thrombocytopenia, hypocellular marrow); glucose (diabetes, insulin resistance, metabolic syndrome); iron (deficiency, overload, metabolism), cardiovascular (hypertension, heart failure, vascular dilation); thyroid (hypothyroidism, hyperthyroidism, parathyroid). Tier 2 ranked in the top 5%: inflammation (chronic inflammatory disorder, autoimmune, periodontitis); kidney (glomerulonephritis, glomerulopathy, toxic nephropathy). Tier 3 ranked in the top 10%: gastrointestinal (bowel regulation, hepatitis, pancreatitis); neuromuscular (autonomia, neuropathy, muscle pain); others (secondary cancers, vitamin deficiency, edema). Results suggest proactive TKI patient AE surveillance levels: regular surveillance for tier 1, infrequent surveillance for tier 2, and symptom-based surveillance for tier 3.
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Affiliation(s)
- Nidhi Mehra
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Armon Varmeziar
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Xinyu Chen
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Olivia Kronick
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Rachel Fisher
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Vamsi Kota
- Division of Hematology and Oncology, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA
| | - Cassie S. Mitchell
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
- Center for Machine Learning, Georgia Institute of Technology, Atlanta, GA 30332, USA
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23
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Gao H, Chen J, Zhao Z, Wang G. A combination of ultrasonic debridement and topical cortex phellodendri compound fluid in patients with diabetic foot ulcers. Medicine (Baltimore) 2022; 101:e29604. [PMID: 35960115 PMCID: PMC9371514 DOI: 10.1097/md.0000000000029604] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVE To evaluate the combination of ultrasonic debridement and cortex phellodendri compound fluid (CPCF) in patients with diabetic foot ulcers (DFU). PATIENTS AND METHODS Patients with DFU received the combination of ultrasonic debridement and CPCF in the experimental group and Kangfuxin liquid in the control group for 4 weeks. Patients total clinical efficiency, adverse events, ulcer areas, healing rate, and positive bacterial culture rate were compared. RESULTS The total clinical efficacy was 98% in the treatment group and 68% in the control group (P < .0001). Patients' adverse events did not show significant difference between 2 groups. Patients who received the combination of ultrasonic debridement and CPCF in the experimental group had smaller ulcer areas (2.88 ± 0.2408 vs 6.912 ± 0.4044), higher healing rate (96.25 ± 0.5263 vs 55 ± 0.8888), and lower positive bacterial culture rate (0 vs 20%) than patients received Kangfuxin liquid in the control group after 4 weeks of treatment. CONCLUSIONS In conclusion, patients with DFU receiving the combination of ultrasonic debridement and CPCF had better clinical efficacy, smaller ulcer areas, higher healing rate, and lower positive bacterial culture rate without increasing the adverse events compared to patients receiving Kangfuxin liquid.
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Affiliation(s)
- Hang Gao
- Acupuncture Department, Master of Science, the Affiliated Hospital of Guizhou Medical University, Guizhou Province, China
| | - Jiali Chen
- Acupuncture Department, Master of Science, the Affiliated Hospital of Guizhou Medical University, Guizhou Province, China
| | - Ziying Zhao
- Acupuncture Department, Master of Science, the Affiliated Hospital of Guizhou Medical University, Guizhou Province, China
| | - Guangyi Wang
- Acupuncture Department, Master of Science, the Affiliated Hospital of Guizhou Medical University, Guizhou Province, China
- *Correspondence: Guangyi Wang, Acupuncture Department, The Affiliated Hospital of Guizhou Medical University, Guizhou Province 550004, China (e-mail: )
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24
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Shityakov S, Nagai M, Ergün S, Braunger BM, Förster CY. The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function. Biomolecules 2022; 12:biom12081113. [PMID: 36009007 PMCID: PMC9405668 DOI: 10.3390/biom12081113] [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: 06/28/2022] [Revised: 08/05/2022] [Accepted: 08/11/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus is a common disease affecting more than 537 million adults worldwide. The microvascular complications that occur during the course of the disease are widespread and affect a variety of organ systems in the body. Diabetic retinopathy is one of the most common long-term complications, which include, amongst others, endothelial dysfunction, and thus, alterations in the blood-retinal barrier (BRB). This particularly restrictive physiological barrier is important for maintaining the neuroretina as a privileged site in the body by controlling the inflow and outflow of fluid, nutrients, metabolic end products, ions, and proteins. In addition, people with diabetic retinopathy (DR) have been shown to be at increased risk for systemic vascular complications, including subclinical and clinical stroke, coronary heart disease, heart failure, and nephropathy. DR is, therefore, considered an independent predictor of heart failure. In the present review, the effects of diabetes on the retina, heart, and kidneys are described. In addition, a putative common microRNA signature in diabetic retinopathy, nephropathy, and heart failure is discussed, which may be used in the future as a biomarker to better monitor disease progression. Finally, the use of miRNA, targeted neurotrophin delivery, and nanoparticles as novel therapeutic strategies is highlighted.
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Affiliation(s)
- Sergey Shityakov
- Division of Chemoinformatics, Infochemistry Scientific Center, Lomonosova Street 9, 191002 Saint-Petersburg, Russia
| | - Michiaki Nagai
- Department of Cardiology, Hiroshima City Asa Hospital, 2-1-1 Kabeminami, Aaskita-ku, Hiroshima 731-0293, Japan
| | - Süleyman Ergün
- Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, 97070 Würzburg, Germany
| | - Barbara M. Braunger
- Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, 97070 Würzburg, Germany
- Correspondence: (B.M.B.); (C.Y.F.)
| | - Carola Y. Förster
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg University, 97080 Würzburg, Germany
- Correspondence: (B.M.B.); (C.Y.F.)
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25
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Khashayar P, Shirzad N, Zarbini A, Esteghamati A, Hemmatabadi M, Sharafi E. Diabetes-related distress and its association with the complications of diabetes in Iran. J Diabetes Metab Disord 2022; 21:1569-1575. [PMID: 35915591 PMCID: PMC9328774 DOI: 10.1007/s40200-022-01103-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 07/04/2022] [Indexed: 11/24/2022]
Abstract
Purpose Diabetes-related distress (DRD) has negative emotional effects on the patients’ quality of life. This is while the condition often goes undiagnosed despite it being common among diabetic patients. This study investigated the prevalence of DRD and its association with diabetes complications among a group of Iranian type 2 diabetic patients (T2DM). Methods This descriptive-analytical cross-sectional study was conducted on 186 T2DM patients referred to a diabetes clinic in a teaching hospital from the beginning of May 2019 to the end of April 2020. Two questionnaires on disease-related information and diabetes distress screening scale (DDS) were filled out for each patient. The latter was divided into four domains, emotional burden (EB), diabetes-related interpersonal distress (ID), physician-related distress (PD), and regimen-related distress (RD). In addition to the frequency of DRD and its association with age, sex, body mass index (BMI), hypertension, hemoglobin A1C, duration of disease, and type of medication regimen (oral, insulin, or mix) along with the history of cardiovascular disease (CVDs), retinopathy, nephropathy, and diabetic foot were assessed. Results DRD was reported in 47% of the patients. Being female, old age, hypertension, high hemoglobin A1C levels, nephropathy, and retinopathy were significantly associated with DRD (P-value = < 0.001, 0.013, 0.014, 0.007, 0.001, and 0.004, respectively). The history of the diabetic foot had a significant relationship with PD and ID (P-value = 0.007 and < 0.001, respectively). Multivariate regression showed gender and the existence of complications to have a direct effect on the development of DRD. Conclusion DRD prevalence is relatively high and requires screening to identify and treat high-risk patients. Further studies are needed to study diabetes, its complications and their relation with DRD to help reduce such conditions and improve the patient’s quality of life.
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Affiliation(s)
- Pouria Khashayar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Nooshin Shirzad
- Department of Endocrinology, Vali-Asr Hospital, Endocrinology and Metabolism Research Center (EMRC), Imam Khomeini Complex Hospital, Tehran University of Medical Sciences, P. O. Box, Tehran, 13145-784 Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Aghil Zarbini
- Cardiovascular Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Department of Endocrinology, Vali-Asr Hospital, Endocrinology and Metabolism Research Center (EMRC), Imam Khomeini Complex Hospital, Tehran University of Medical Sciences, P. O. Box, Tehran, 13145-784 Iran
| | - Mahboobeh Hemmatabadi
- Department of Endocrinology, Vali-Asr Hospital, Endocrinology and Metabolism Research Center (EMRC), Imam Khomeini Complex Hospital, Tehran University of Medical Sciences, P. O. Box, Tehran, 13145-784 Iran
| | - Elham Sharafi
- Department of Psychiatry, Psychosomatic Research Center, Tehran University of Medical Sciences, Tehran, Iran
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26
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R-spondin 3 Inhibits High Glucose-Induced Endothelial Activation Through Leucine-Rich G Protein-Coupled Receptor 4/Wnt/β-catenin Pathway. J Cardiovasc Pharmacol 2022; 80:70-81. [PMID: 35767713 DOI: 10.1097/fjc.0000000000001295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 04/22/2022] [Indexed: 11/26/2022]
Abstract
ABSTRACT High glucose-induced endothelial activation plays critical roles in the development of diabetic vascular complications. R-spondin 3 could inhibit inflammatory damage, and diabetic vascular inflammation is secondary to endothelial activation. In this article, we identify R-spondin 3 as a novel regulator of high glucose-induced endothelial activation. We found that the serum levels of R-spondin 3 were significantly reduced in type 2 diabetic patients and db/db mice. We observed that the increased expressions of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 (endothelial activation makers) in high glucose-stimulated human umbilical vein endothelial cell lines (HUVECs) could be inhibited by overexpressing R-spondin 3 or human R-spondin 3 recombinant protein. Subsequently, high glucose-induced adhesion and migration of human myeloid leukemia mononuclear cells (THP-1 cells) to HUVECs were markedly suppressed by the overexpression of R-spondin 3 in HUVECs. Moreover, the inhibitory effect of R-spondin 3 on the expressions of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 in high glucose-treated HUVECs could be blocked by knockdown of leucine-rich G protein-coupled receptor 4 (R-spondin 3 receptor) or the specific inhibitor of Wnt/β-catenin pathway. Taken together, R-spondin 3 could suppress high glucose-induced endothelial activation through leucine-rich G protein-coupled receptor 4/Wnt/β-catenin pathway.
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27
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Zhang M, Du H, Guan Y, Liu J, Wang S, Li H, Zhang W, Han H, Zhang M, Chen L. Study on the Effect of PDA-PLGA Scaffold Loaded With Islet Cells for Skeletal Muscle Transplantation in the Treatment of Diabetes. Front Bioeng Biotechnol 2022; 10:927348. [PMID: 35845408 PMCID: PMC9280155 DOI: 10.3389/fbioe.2022.927348] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/10/2022] [Indexed: 11/13/2022] Open
Abstract
At present, islet cells transplantation was limited by the way in which islet cells are implanted into the body, their ability to adapt to the microenvironment and the maintenance time for relieving diabetic symptoms. In order to solve this problem, we made PDA-PLGA scaffold loaded with islet cells and used it for skeletal muscle transplantation to investigate its therapeutic effect in the treatment of diabetes. The PLGA scaffold was prepared by the electrospinning method, and modified by polydopamine coating. A rat diabetic model was established to evaluate the efficacy of PDA-PLGA scaffold loaded with RINm5f islet cells through skeletal muscle transplantation. The results showed that the PDA-PLGA scaffold has good biosafety performance. At the same time, transplantation of the stent to the skeletal muscle site had little effect on the serum biochemical indicators of rats, which was conducive to angiogenesis. The PDA-PLGA scaffold had no effect on the secretory function of pancreatic islet cells. The PDA-PLGA scaffold carrying RINm5f cells was transplanted into the skeletal muscle of type I diabetic rats. 1 week after the transplantation of the PDA-PLGA cell scaffold complex, the blood glucose of the treatment group was significantly lower than that of the model group (p < 0.001) and lasted for approximately 3 weeks, which further indicated the skeletal muscle transplantation site was a new choice for islet cell transplantation in the future.
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Affiliation(s)
- Meishuang Zhang
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
| | - Hongwei Du
- Research Institution of Paediatrics, Department of Pediatric Endocrinology, The First Clinical Hospital Affiliated to Jilin University, Changchun, China
| | - Yueqi Guan
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
| | - Jingyue Liu
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
| | - Sushan Wang
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
| | - Haoran Li
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
| | - Wenyou Zhang
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
| | - Hao Han
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
| | - Ming Zhang
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
- *Correspondence: Ming Zhang, ; Li Chen,
| | - Li Chen
- Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China
- *Correspondence: Ming Zhang, ; Li Chen,
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28
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Ateeq H, Zia A, Husain Q, Khan MS, Ahmad M. Effect of inflammation on bones in diabetic patients with periodontitis via RANKL/OPG system-A review. J Diabetes Metab Disord 2022; 21:1003-1009. [PMID: 35673491 PMCID: PMC9167386 DOI: 10.1007/s40200-021-00960-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/14/2021] [Indexed: 01/31/2023]
Abstract
Purpose Diabetes mellitus and periodontitis are inflammatory diseases, the severity of inflammation results in the progression and persistence of both the disorders and affects bones. Diabetic complications aggravate in diabetic subjects having periodontitis; similarly, diabetic patients are more prone to developing gingivitis and periodontitis. Periodontal and diabetic inflammation disturbs bone homeostasis, which possibly involves both innate and adaptive immune responses. The pathogenic processes that link the two diseases are the focus of much research and it is likely that upregulated inflammation arising from each condition adversely affects the other. RANKL/OPG pathway plays a prominent role in periodontal and diabetic inflammation and bone resorption. Method This review article summarises the literature on the link between inflammatory cytokines and the prevalence of disturbed bone homeostasis in diabetic patients with periodontitis. An extensive search was done in PubMed, Scopus, Medline and Google Scholar databases between April 2003 and May 2021. Result A total of 27 articles, including pilot studies, case-control studies, cross-sectional studies, cohort studies, randomized control trials, longitudinal studies, descriptive studies and experimental studies, were included in our literature review. Conclusion Since RANKL/OPG are cytokines and have immune responses, regulating these cytokines expression will help control diabetes, periodontitis and bone homeostasis. The growing evidence of bone loss and increased fracture risk in diabetic patients with periodontitis makes it imperative that health professionals carry out planned treatment focusing on monitoring oral health in diabetic patients; bone markers should also be evaluated in patients with chronic periodontitis with an impaired glycemic state.
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Affiliation(s)
- Hira Ateeq
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh-202002, India
- Dr. Ziauddin Ahmad Dental College, Aligarh Muslim University, Aligarh-202002, India
| | - Afaf Zia
- Dr. Ziauddin Ahmad Dental College, Aligarh Muslim University, Aligarh-202002, India
| | - Qayyum Husain
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh-202002, India
| | - Mohd Sajid Khan
- Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh-202002, India
| | - Mohd Ahmad
- Dr. Ziauddin Ahmad Dental College, Aligarh Muslim University, Aligarh-202002, India
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Rosinha PMO, Inácio IMR, de Moura Teixeira SM, do Amaral CS, da Silva MHCP. Hyperglycemia in hospitalized patients of a tertiary care hospital: prevalence and treatment in two cross-sectional evaluations (2011-2020). ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 66:214-221. [PMID: 35315989 PMCID: PMC9832891 DOI: 10.20945/2359-3997000000452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Objective A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. Methods We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). Results A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Conclusion Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.
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Maslinic Acid Protects against Streptozotocin-Induced Diabetic Retinopathy by Activating Nrf2 and Suppressing NF-κB. J Ophthalmol 2022; 2022:3044202. [PMID: 35265366 PMCID: PMC8901311 DOI: 10.1155/2022/3044202] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 01/15/2022] [Accepted: 01/19/2022] [Indexed: 12/17/2022] Open
Abstract
This study tested the protective effect of maslinic acid (MA) against diabetic retinopathy (DR) in rats with type 1 diabetes mellitus (T1DM) and investigated possible mechanisms of action. DM was introduced by streptozotocin (STZ) (65 mg/kg, i.p.). Control and STZ (T1DM) were divided into 2 subgroups, which received either the vehicle or MA (80 mg/kg). Serum, pancreases, and retinas were collected for further use. MA significantly reduced fasting glucose levels in the control and T1DM rats but enhanced fasting insulin levels and partially increased the size of the islets of Langerhans and the number of β-cells in T1DM rats. In addition, MA significantly improved the retina structure by preventing the reduction in the area between the inner and outer limiting membranes (ILM and OLM, respectively) and increasing the number of cells forming the ganglion cell layer (GCL), inner nuclear layer (INL), and outer nuclear layer (ONL). Associated with these effects, MA significantly reduced the total levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as the nuclear levels of NF-κB p65, mRNA levels of Bax, and protein levels of cleaved caspase-3 in the retinas of T1DM rats. However, MA significantly lowered levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but significantly increased the nuclear levels of Nrf2, protein levels of Bcl2, and total levels of superoxide dismutase (SOD) and reduced glutathione (GSH) in the retinas of the control and T1DM rats. In conclusion, MA prevents DR by antioxidant potential mediated by the activation of Nrf2.
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Dwivedi PSR, Patil R, Khanal P, Gurav NS, Murade VD, Hase DP, Kalaskar MG, Ayyanar M, Chikhale RV, Gurav SS. Exploring the therapeutic mechanisms of Cassia glauca in diabetes mellitus through network pharmacology, molecular docking and molecular dynamics. RSC Adv 2021; 11:39362-39375. [PMID: 35492478 PMCID: PMC9044434 DOI: 10.1039/d1ra07661b] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 11/16/2021] [Indexed: 12/30/2022] Open
Abstract
Cassia glauca is reported as anti-diabetic medicinal plant and is also used as an ethnomedicine. However, its mode of action as an anti-diabetic agent has not been clearly elucidated. Hence, the present study investigated the probable mechanism of action of C. glauca to manage diabetes mellitus via network pharmacology and molecular docking and simulations studies. The reported bioactives from C. glauca were retrieved from an open-source database, i.e. ChEBI, and their targets were predicted using SwissTargetPrediction. The proteins involved in the pathogenesis of diabetes were identified from the therapeutic target database. The targets involved in diabetes were enriched in STRING, and the pathways involved in diabetes were identified concerning the KEGG. Cytoscape was used to construct the network among bioactives, proteins, and probably regulated pathways, which were analyzed based on edge count. Similarly, molecular docking was performed using the Glide module of the Schrodinger suite against majorly targeted proteins with their respective ligands. Additionally, the drug-likeness score and ADMET profile of the individual bioactives were predicted using MolSoft and admetSAR2.0 respectively. The stability of these complexes were further studied via molecular dynamics simulations and binding energy calculations. Twenty-three bio-actives were retrieved from the ChEBI database in which cassiarin B was predicted to modulate the highest number of proteins involved in diabetes mellitus. Similarly, GO analysis identified the PI3K-Akt signaling pathway to be primarily regulated by modulating the highest number of gene. Likewise, aldose reductase (AKR1B1) was majorly targeted via the bioactives of C. glauca. Similarly, docking study revealed methyl-3,5-di-O-caffeoylquinate (docking score -9.209) to possess the highest binding affinity with AKR1B1. Additionally, drug-likeness prediction identified cassiaoccidentalin B to possess the highest drug-likeness score, i.e. 0.84. The molecular dynamics simulations and the MMGBSA indicate high stability and greater binding energy for the methyl-3,5-di-O-caffeoylquinate (ΔG bind = -40.33 ± 6.69 kcal mol-1) with AKR1B1, thus complementing results from other experiments. The study identified cassiarin B, cassiaoccidentalin B, and cinnamtannin A2 as lead hits for the anti-diabetic activity of C. glauca. Further, the PI3K-Akt and AKR1B1 were traced as majorly modulated pathway and target, respectively.
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Affiliation(s)
- Prarambh S R Dwivedi
- Department of Pharmacology, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University) Mangalore-575018 India
| | - Rajesh Patil
- Sinhgad Technical Education Society's, Sinhgad College of Pharmacy Vadgaon (Bk) Pune-411041 Maharashtra India
| | - Pukar Khanal
- Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER) Belagavi-590010 India
| | - Nilambari S Gurav
- Ponda Education Society's Rajaram and Tarabai Bandekar College of Pharmacy India
| | - Vaishali D Murade
- Department of Chemistry, Padmashri Vikhe Patil College Pravarangar, Loni Ahmednagar Maharashtra India
| | - Dinesh P Hase
- Department of Pharmacognosy, Amrutvahini College of Pharmacy Sangamner Maharashtra India
| | - Mohan G Kalaskar
- R C Patel Institute of Pharmaceutical Education and Research Shirpur India
| | - Muniappan Ayyanar
- Department of Botany, A. V. V. M. Sri Pushpam College (Autonomous), Affiliated to Bharathidasan University Poondi Thanjavur India
| | - Rupesh V Chikhale
- School of Pharmacy, University of East Anglia Norwich Research Park Norwich UK
| | - Shailendra S Gurav
- Department of Pharmacognosy and Phytochemistry, Goa College of Pharmacy Panaji, Goa University Goa-403001 India
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Von Dentz M, Gambato G, Ferrari A, Fontana RC, Rodrigues E, Salvador M, Camassola M, Jahn MP. Antihyperlipidemic effect of the hydroalcoholic extract of Basidiomycete Pycnoporus sanguineus (Fr.) Murr. in streptozotocin-induced diabetic rats. ADVANCES IN TRADITIONAL MEDICINE 2021. [DOI: 10.1007/s13596-020-00459-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Extracts from the Leaves of Cissus verticillata Ameliorate High-Fat Diet-Induced Memory Deficits in Mice. PLANTS 2021; 10:plants10091814. [PMID: 34579347 PMCID: PMC8468243 DOI: 10.3390/plants10091814] [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: 06/16/2021] [Revised: 08/25/2021] [Accepted: 08/27/2021] [Indexed: 11/17/2022]
Abstract
We investigated the effects of Cissus verticillata leaf extract (CVE) on a high-fat diet (HFD)-induced obesity and memory deficits. Male mice (5 weeks of age) were fed vehicle (distilled water), or 30, 100, or 300 mg/kg of CVE once a day for 8 weeks with an HFD. Treatment with CVE resulted in lower body weight and glucose levels in a concentration- and feeding time-dependent manner. LDL cholesterol and triglyceride levels were significantly lower in the CVE-treated HFD group than in the vehicle-treated HFD group. In contrast, high-density lipoprotein cholesterol levels did not show any significant changes. Lipid droplets and ballooning were reduced depending on the concentration of CVE treatment compared to the HFD group. Treatment with CVE ameliorated the increase in glucagon and immunoreactivities in the pancreas, and novel object recognition memory was improved by 300 mg/kg CVE treatment compared to the HFD group. More proliferating cells and differentiated neuroblasts were higher in mice treated with CVE than in vehicle-treated HFD-fed mice. Brain-derived neurotrophic factor (BDNF) levels were significantly decreased in the HFD group, which was facilitated by treatment with 300 mg/kg CVE in hippocampal homogenates. These results suggest that CVE ameliorates HFD-induced obesity and memory deficits in mice, associated with increased BDNF levels in the hippocampus.
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Bai A, Tao J, Tao L, Liu J. Prevalence and risk factors of diabetes among adults aged 45 years or older in China: A national cross-sectional study. Endocrinol Diabetes Metab 2021; 4:e00265. [PMID: 34277988 PMCID: PMC8279593 DOI: 10.1002/edm2.265] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/14/2021] [Accepted: 04/30/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Although there is preponderance of literature on disease burden of diabetes in developed countries, limited investigations have been conducted in less developed regions including China. This study aimed to explore the current prevalence and risk factors for diabetes, pre-diabetes, awareness, treatment and control of diabetes in China. METHODS We included 12,458 adults from the China Health and Retirement Longitudinal Study. We estimated prevalence of diabetes and pre-diabetes in the overall sample and by socio-demographics. Bivariate associations of diabetes, pre-diabetes, awareness, control and treatment of diabetes with health and function measures were evaluated by chi-squared test and multivariate logistic regression analysis. RESULTS We found that the prevalence of diabetes and pre-diabetes was 13.21% and 25.16%. The prevalence of diabetes increased with advanced age (12.37%, 15.98% and 16.52% among persons who were 45 to 55, 55 to 65 and ≥65 years old, respectively), educational background (14.52%, 15.52% and 15.58% among persons who were illiterate, had primary education and had secondary or above education) and weight (8.18%, 17.05% and 22.54% among persons with a body mass index of 18.5 to 24.9, 25.0 to 29.9 and ≥30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (19.04% vs. 12.85%). We also observed that aged between 55 and 65 years, obesity, history of hypertension and coronary heart disease, and inactivity were significant risk factors of awareness of diabetes. CONCLUSION Our results indicated that diabetes is high prevalent in adults aged 45 years or above in China. The potentially modifiable risk factors should be further studied to develop interventions and strategies aimed at prevention and treatment of diabetes among middle-aged and older Chinese adults.
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Affiliation(s)
- Anying Bai
- School of Public HealthPeking UniversityBeijingChina
| | - Jing Tao
- College of Rehabilitation MedicineFujian University of Traditional Chinese MedicineFujianChina
| | - Liyuan Tao
- Research Center of Clinical EpidemiologyPeking University Third HospitalBeijingChina
| | - Jue Liu
- School of Public HealthPeking UniversityBeijingChina
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Hamasaki-Matos AJ, Cóndor-Marín KM, Aquino-Ortega R, Carrillo-Ng H, Ugarte-Gil C, Silva-Caso W, Aguilar-Luis MA, Del Valle-Mendoza J. Characterization of the gut microbiota in diabetes mellitus II patients with adequate and inadequate metabolic control. BMC Res Notes 2021; 14:238. [PMID: 34167557 PMCID: PMC8223318 DOI: 10.1186/s13104-021-05655-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 06/14/2021] [Indexed: 12/12/2022] Open
Abstract
Objective The objective of this study was to characterize the composition of the gut microbiota in type 2 Diabetes Mellitus (T2DM) patients with adequate and inadequate metabolic control, and its relationship with fiber consumption. Results A total of 26 patients with type 2 diabetes mellitus (T2DM) were enrolled, of which 7 (26.9%) cases had adequate metabolic control (HbA1c < 7%) and 19 (73.1%) inadequate metabolic control (HbA1c ≥ 7%). It was observed that among patients with controlled T2DM, 2 (28.6%) cases presented good intake of fiber and 5 (71.4%) cases a regular intake. In contrast, in patients with uncontrolled T2DM, 13 (68.4%) patients reported a regular intake and 6 (31.6%) a poor intake. In relation to the identification of the gut microbiota, both groups presented a similar characterization. There were differences in the population of bacteria identified in both groups, however, the results were not statistically significant. The most frequently identified bacteria in controlled and uncontrolled T2DM patients were Prevotella (71.4% vs 52.6%), followed by Firmicutes (71.4% vs 42.1%), Proteobacteria (71.4% vs 36.8%) and Bacteroidetes (57.1% vs 37.8%). On the other hand, Fusobacterium, Actinobacteria were not identified in either of the two groups of study. Supplementary Information The online version contains supplementary material available at 10.1186/s13104-021-05655-z.
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Affiliation(s)
| | | | - Ronald Aquino-Ortega
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Hugo Carrillo-Ng
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Cesar Ugarte-Gil
- School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Wilmer Silva-Caso
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Miguel Angel Aguilar-Luis
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Juana Del Valle-Mendoza
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. .,School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. .,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru.
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Zhang X, Zhao L, Jin R, Li M, Li MS, Li R, Liang X. CRISPR/Cas9-Mediated α-ENaC Knockout in a Murine Pancreatic β-Cell Line. Front Genet 2021; 12:664799. [PMID: 33868391 PMCID: PMC8047203 DOI: 10.3389/fgene.2021.664799] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 03/08/2021] [Indexed: 12/27/2022] Open
Abstract
Many ion channels participate in controlling insulin synthesis and secretion of pancreatic β-cells. Epithelial sodium channel (ENaC) expressed in human pancreatic tissue, but the biological role of ENaC in pancreatic β-cells is still unclear. Here, we applied the CRISPR/Cas9 gene editing technique to knockout α-ENaC gene in a murine pancreatic β-cell line (MIN6 cell). Four single-guide RNA (sgRNA) sites were designed for the exons of α-ENaC. The sgRNA1 and sgRNA3 with the higher activity were constructed and co-transfected into MIN6 cells. Through processing a series of experiment flow included drug screening, cloning, and sequencing, the α-ENaC gene-knockout (α-ENaC−/−) in MIN6 cells were obtained. Compared with the wild-type MIN6 cells, the cell viability and insulin content were significantly increased in α-ENaC−/− MIN6 cells. Therefore, α-ENaC−/− MIN6 cells generated by CRISPR/Cas9 technology added an effective tool to study the biological function of α-ENaC in pancreatic β-cells.
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Affiliation(s)
- Xue Zhang
- Department of Pathophysiology, Nanjing Medical University, Nanjing, China
| | - Lihua Zhao
- Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China
| | - Runbing Jin
- Department of Pathophysiology, Nanjing Medical University, Nanjing, China
| | - Min Li
- Department of Pathophysiology, Nanjing Medical University, Nanjing, China
| | - Mei-Shuang Li
- Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China
| | - Rongfeng Li
- Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China
| | - Xiubin Liang
- Department of Pathophysiology, Nanjing Medical University, Nanjing, China.,Department of Nephrology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China
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Park EH, Kim HJ, Cha DS. Protective effects of black bamboo leaves on the glucose-induced toxicity in Caenorhabditis elegans. JOURNAL OF HERBMED PHARMACOLOGY 2021. [DOI: 10.34172/jhp.2021.25] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Introduction: Previous studies have suggested that high glucose (HG) condition shortens the lifespan of worms by increasing glycolytic flux followed by accelerating reactive oxygen species (ROS) production, termed glucose toxicity. This study was designed to investigate the protective effects of the leaves of black bamboo (Phyllostachys nigra var. henosis) on the HG-induced toxicity using Caenorhabditis elegans model system. Methods: To determine the effect of black bamboo leaf extract (BLE) against HG-induced toxicity, lifespan assay was carried out with wild-type and daf-16 null mutant worms under 2% glucose condition. The involvement of DAF-16 was further confirmed by observing fluorescence signal of transgenic mutant carrying DAF-16::GFP transgene. ROS levels and glucose concentration of worms were analyzed using fluorescent probe H2DCF-DA and glucose meter, respectively. Nile-red staining was carried out to evaluate the lipid storage of worms. Intercellular lipid accumulation was measured using Oil-Red O staining method. Results: BLE strongly extended the lifespan of worms under not only normal culture condition but also HG condition. Our additional studies suggested that DAF-16 activation was responsible for BLE-mediated longevity and protective action against glucose toxicity. In addition, HG-fed worms showed increased ROS generation, and it was completely normalized by BLE treatment. Moreover, BLE reduced body glucose concentration and lipid accumulation in HG-fed worms. We further confirmed the inhibitory effect of BLE on lipid storage under HG condition using 3T3-L1 adipocytes. Conclusion: These therapeutic values of BLE on glucose toxicity raise the possibility that BLE might have beneficial effects on the pathogenesis of diabetes mellitus.
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Affiliation(s)
- Eun Hye Park
- College of Pharmacy, Woosuk University, Jeonbuk 55338, Republic of Korea
| | - Hong Jun Kim
- Department of Korean Medicine, Woosuk University, Jeonbuk 55338, Republic of Korea
| | - Dong Seok Cha
- College of Pharmacy, Woosuk University, Jeonbuk 55338, Republic of Korea
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Xia M, Liu K, Feng J, Zheng Z, Xie X. Prevalence and Risk Factors of Type 2 Diabetes and Prediabetes Among 53,288 Middle-Aged and Elderly Adults in China: A Cross-Sectional Study. Diabetes Metab Syndr Obes 2021; 14:1975-1985. [PMID: 33976558 PMCID: PMC8104985 DOI: 10.2147/dmso.s305919] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 04/09/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Diabetes is a metabolic disorder that causes a heavy burden on healthcare systems worldwide. The aim of this study was to determine the prevalence of type 2 diabetes and prediabetes and its associated factors among eight communities in Nanchong, China. METHODS This was an observational cross-sectional study conducted throughout eight communities in Nanchong, China. The participants were 53,288 individuals aged 45 years or older. The participants' characteristics, comorbidities, health behaviors, family history, and dietary intake were assessed. Multinomial logistic regression models were fitted to identify factors associated with type 2 diabetes and prediabetes. RESULTS The prevalence of diabetes and prediabetes was 13.9% (95% confidence interval [CI], 13.6-14.2) and 3.1% (95% CI, 2.9-3.2) of the population, respectively. After adjusting for other risk factors, advanced age, overweight, obesity, abdominal obesity, comorbidities, smoking, a family history of diabetes, and Chinese cooking vegetable intake were associated with an increased risk of type 2 diabetes and prediabetes. CONCLUSION The prevalence of type 2 diabetes in the Chinese population is rising compared with data from the past. The risk factors of type 2 diabetes and prediabetes identified in this study will aid the identification of individuals at a high-risk of diabetes and the implementation of effective health promotion programs and campaigns. CLINICAL TRIAL REGISTRY NUMBER ChiCTR-HOC-17013200.
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Affiliation(s)
- Mengdi Xia
- Department of Nephrology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital) and Nanchong Key Laboratory of Basic Science & Clinical Research on Chronic Kidney Disease, Nanchong, Sichuan, People’s Republic of China
| | - Kaixiang Liu
- Department of Nephrology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China
| | - Jie Feng
- Department of Nephrology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital) and Nanchong Key Laboratory of Basic Science & Clinical Research on Chronic Kidney Disease, Nanchong, Sichuan, People’s Republic of China
| | - Zaiqiong Zheng
- Department of Nephrology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital) and Nanchong Key Laboratory of Basic Science & Clinical Research on Chronic Kidney Disease, Nanchong, Sichuan, People’s Republic of China
| | - Xisheng Xie
- Department of Nephrology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital) and Nanchong Key Laboratory of Basic Science & Clinical Research on Chronic Kidney Disease, Nanchong, Sichuan, People’s Republic of China
- Correspondence: Xisheng Xie Department of Nephrology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), South Renmin Road 97, Shunqing District, Nanchong, Sichuan Province, 637000, People’s Republic of ChinaTel +86 158 8170 0265 Email
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Shin SA, Joo BJ, Lee JS, Ryu G, Han M, Kim WY, Park HH, Lee JH, Lee CS. Phytochemicals as Anti-Inflammatory Agents in Animal Models of Prevalent Inflammatory Diseases. Molecules 2020; 25:E5932. [PMID: 33333788 PMCID: PMC7765227 DOI: 10.3390/molecules25245932] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/07/2020] [Accepted: 12/11/2020] [Indexed: 02/06/2023] Open
Abstract
Phytochemicals are known to have anti-inflammatory effects in vitro and in vivo, such as in inflammatory disease model systems. Inflammation is an essential immune response to exogenous stimuli such as infection and injury. Although inflammation is a necessary host-defense mechanism, chronic inflammation is associated with the continuous local or systemic release of inflammatory mediators, non-cytokine mediators, such as ROS and NO, and inflammatory cytokines are strongly implicated in the pathogenesis of various inflammatory disorders. Phytochemicals that exhibit anti-inflammatory mechanisms that reduce sustained inflammation could be therapeutic candidates for various inflammatory diseases. These phytochemicals act by modulating several main inflammatory signaling pathways, including NF-κB, MAPKs, STAT, and Nrf-2 signaling. Here, we discuss the characteristics of phytochemicals that possess anti-inflammatory activities in various chronic inflammatory diseases and review the molecular signaling pathways altered by these anti-inflammatory phytochemicals, with a focus on transcription factor pathways. Furthermore, to evaluate the phytochemicals as drug candidates, we translate the effective doses of phytochemicals in mice or rat disease models into the human-relevant equivalent and compare the human-relevant equivalent doses of several phytochemicals with current anti-inflammatory drugs doses used in different types of chronic inflammatory diseases.
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Affiliation(s)
- Seong Ah Shin
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 52828, Korea; (S.A.S.); (B.J.J.); (J.S.L.); (G.R.); (M.H.)
| | - Byeong Jun Joo
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 52828, Korea; (S.A.S.); (B.J.J.); (J.S.L.); (G.R.); (M.H.)
| | - Jun Seob Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 52828, Korea; (S.A.S.); (B.J.J.); (J.S.L.); (G.R.); (M.H.)
| | - Gyoungah Ryu
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 52828, Korea; (S.A.S.); (B.J.J.); (J.S.L.); (G.R.); (M.H.)
| | - Minjoo Han
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 52828, Korea; (S.A.S.); (B.J.J.); (J.S.L.); (G.R.); (M.H.)
| | - Woe Yeon Kim
- Division of Applied Life Science (BK21), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Life Sciences (RILS), Gyeongsang National University, Jinju 52828, Korea;
| | - Hyun Ho Park
- College of Pharmacy, Chung-Ang University, Seoul 06974, Korea;
| | - Jun Hyuck Lee
- Research Unit of Cryogenic Novel Material, Korea Polar Research Institute, Incheon 21990, Korea;
- Department of Polar Sciences, University of Science and Technology, Incheon 21990, Korea
| | - Chang Sup Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 52828, Korea; (S.A.S.); (B.J.J.); (J.S.L.); (G.R.); (M.H.)
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Assessment of Absorption of Glycated Nail Proteins in Patients with Diabetes Mellitus and Diabetic Retinopathy. ACTA ACUST UNITED AC 2020; 56:medicina56120658. [PMID: 33260342 PMCID: PMC7760767 DOI: 10.3390/medicina56120658] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/17/2020] [Accepted: 11/27/2020] [Indexed: 12/12/2022]
Abstract
Background and objectives: Glycation occurs in a variety of human tissues and organs. Knowledge about the relationship between predictive biochemical factors such as absorption of glycated nail proteins and severity of type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) remains limited. Materials and Methods: The study group consisted of patients with type 2 DM and DR (n = 32) and a control group (n = 28). Each patient underwent a comprehensive ophthalmic examination. The glycation process in nail clippings was evaluated in stages of in vitro glycation and deglycation stages. ATR–FTIR spectroscopy was used to calculate the infrared absorption in the region of interest. The absorption of solutions with nail clippings was evaluated by NanoDrop spectrophotometry. Absorption spectra differences before and after the exposure to fructosamine 3-kinase were compared between DM patients with DR and the control group. Results: The absorption of glycated nail protein greater than 83.00% increased the chance of developing DM and DR (OR = 15.909, 95% CI 3.914–64.660, p < 0.001). Absorption of glycated nail protein by ATR–FTIR spectroscopy in patients with DM and DR in vitro glycation was statistically significantly higher than in the control group; also absorption of solution with nails by NanoDrop spectroscopy was statistically significantly higher than in controls in vitro glycation and in vitro deglycation. After exposure to fructosamine 3-kinase, absorption of nail protein in DM + severe/proliferative DR group was statistically significantly lower in comparison with DM + mild/moderate group DR. Conclusions: Evaluation of glycated nail protein could be applied to evaluate the risk of having DM and for long-term observation of DM control.
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Pandey S, Dvorakova MC. Future Perspective of Diabetic Animal Models. Endocr Metab Immune Disord Drug Targets 2020; 20:25-38. [PMID: 31241444 PMCID: PMC7360914 DOI: 10.2174/1871530319666190626143832] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 04/06/2019] [Accepted: 04/17/2019] [Indexed: 12/15/2022]
Abstract
Objective The need of today’s research is to develop successful and reliable diabetic animal models for understanding the disease susceptibility and pathogenesis. Enormous success of animal models had already been acclaimed for identifying key genetic and environmental factors like Idd loci and effects of microorganisms including the gut microbiota. Furthermore, animal models had also helped in identifying many therapeutic targets and strategies for immune-intervention. In spite of a quite success, we have acknowledged that many of the discovered immunotherapies are working on animals and did not have a significant impact on human. Number of animal models were developed in the past to accelerate drug discovery pipeline. However, due to poor initial screening and assessment on inequivalent animal models, the percentage of drug candidates who succeeded during clinical trials was very low. Therefore, it is essential to bridge this gap between pre-clinical research and clinical trial by validating the existing animal models for consistency. Results and Conclusion In this review, we have discussed and evaluated the significance of animal models on behalf of published data on PUBMED. Amongst the most popular diabetic animal models, we have selected six animal models (e.g. BioBreeding rat, “LEW IDDM rat”, “Nonobese Diabetic (NOD) mouse”, “STZ RAT”, “LEPR Mouse” and “Zucker Diabetic Fatty (ZDF) rat” and ranked them as per their published literature on PUBMED. Moreover, the vision and brief imagination for developing an advanced and robust diabetic model of 21st century was discussed with the theme of one mice-one human concept including organs-on-chips.
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Affiliation(s)
- Shashank Pandey
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Magdalena C Dvorakova
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.,Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
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Al-Zawawi AS, Bukhari IA, Bello-Correa FO, Sheikh SA, Albaijan R, Vohra F. Influence of root debridement with adjunct photodynamic therapy on periodontal parameters and gingival crevicular fluid cortisol levels among patients with and without type-2 diabetes mellitus. Photodiagnosis Photodyn Ther 2020; 32:102076. [PMID: 33152543 DOI: 10.1016/j.pdpdt.2020.102076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 10/24/2020] [Accepted: 10/26/2020] [Indexed: 01/10/2023]
Abstract
OBJECTIVE The aim of the present study was to assess the influence of scaling and root planing (SRP) with adjunct antimicrobial photodynamic therapy (aPDT) on periodontal parameters and gingival crevicular fluid (GCF) cortisol levels in type-2 diabetic and non-diabetic patients with periodontitis. METHODS One hundred and twenty-eight patients with periodontitis (64 with and 64 without type-2 diabetes mellitus, respectively) were included. In the test- and control-groups, patients underwent SRP with and without aPDT, respectivey. In both groups, plaque and gingival indices (PI and GI), probing depth (PD), clinical attachment loss (CAL), marginal bone loss (MBL) and GCF volume and cortisol levels were assessed at baseline and three and six-months after SRP with or without aPDT. The aPDT was performed at baseline using methylene blue and photobiomodulation. The Kruskall-Wallis test was used to assess data normality; and group-comparisons were done. P-values, which were below 0.01 indicated statistical significance. RESULTS Sixty-four type-2 diabetic patients with and 64 non-diabetic patients with periodontitis were included. All individuals had Stage-III/Grade-C periodontitis. Among patients with type-2 diabetes mellitus (DM), there was no statistically significant difference in hemoblobin A1c, PI, GI, PD, CAL and MBL at baseline and at 3- and 6-months intervals. Amongst diabetic patietns, there was no difference in the GCF volume and cortisol levels in the test- and control-groups at all time intervals. In non-diabetic patients, there was a significqnt reductionin GCF volume and cortisol levels when SRP was done with aPDT than when SRP was carried out as the sole treatment strategy CONCLUSION: Among non-diabetic patients, SRP with aPDT helps reduce periodontal inflammation and GCF cortisol levels for up to 6-months; however poorly-controlled DM compromises the beneficial effects of this treatment strategy.
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Affiliation(s)
- Abeer S Al-Zawawi
- Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Ishfaq A Bukhari
- Department of Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Fernanda O Bello-Correa
- Department of Dentistry, Life Sciecnes Institute, Federal University of Juiz de Fora, Governador Valadares, MG, Brazil
| | - Saeed A Sheikh
- Department of Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Refal Albaijan
- Department of Prosthetic Dental Science, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Fahim Vohra
- Department of Prosthetic Dental Science, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
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Cao Z, Yao F, Lang Y, Feng X. Elevated Circulating LINC-P21 Serves as a Diagnostic Biomarker of Type 2 Diabetes Mellitus and Regulates Pancreatic β-cell Function by Sponging miR-766-3p to Upregulate NR3C2. Exp Clin Endocrinol Diabetes 2020; 130:156-164. [PMID: 33007789 DOI: 10.1055/a-1247-4978] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE The purpose of this study was to evaluate the clinical value and biological function of long non-coding RNA (lncRNA) LINC-P21 in type 2 diabetes mellitus (T2DM), and explore the underlying mechanisms. METHODS The expression of LINC-P21 was estimated using quantitative real-time PCR. The functional role of LINC-P21 was explored by gain- and loss-of-function experiments. INS-1 cell proliferation was analyzed using a cell counting kit-8 (CCK-8)assay, and the glucose-stimulated insulin secretion was measured using an ELISA kit. The miRNAs that might be sponged by LINC-P21 were analyzed, and the subsequent target genes were predicted and assessed in INS-1 cells. RESULTS Serum expression of LINC-P21 was elevated in T2DM patients, which was correlated with fasting blood glucose levels and disease diagnosis. The glucose-stimulated insulin secretion and the proliferation of INS-1 cells were enhanced by LINC-P21 knockdown, but the overexpression of LINC-P21 led to opposite effects. miR-766-3p could be directly inhibited by LINC-P21 in INS-1 cells and reverse the effects of LINC-P21 on β-cell function. Additionally, NR3C2 was determined as a target of miR-766-3p, which could be positively regulated by LINC-P21 and had same effects with LINC-P21 on INS-1 cell proliferation and insulin secretion. CONCLUSION All the data demonstrated that serum elevated LINC-P21 and decreased miR-766-3p serve as candidate diagnostic biomarkers in T2DM patients. LINC-P21 acts as a potential regulator in insulin secretion and proliferation of pancreatic β-cells through targeting miR-766-3p to upregulate NR3C2.
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Affiliation(s)
- Zhibin Cao
- Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong
| | - Fuwang Yao
- Department of Anesthesiology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong
| | - Yuqin Lang
- Department of Endoscopic Outpatient Operating Room, Affiliated Hospital of Weifang Medical University, Weifang, Shandong
| | - Xueqiang Feng
- Vascular Intervention Department, Affiliated Hospital of Weifang Medical University, Weifang, Shandong
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Ahmed SM, Johar D, Ali MM, El-Badri N. Insights into the Role of DNA Methylation and Protein Misfolding in Diabetes Mellitus. Endocr Metab Immune Disord Drug Targets 2019; 19:744-753. [DOI: 10.2174/1871530319666190305131813] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 10/25/2018] [Accepted: 11/29/2018] [Indexed: 12/24/2022]
Abstract
Background:
Diabetes mellitus is a metabolic disorder that is characterized by impaired
glucose tolerance resulting from defects in insulin secretion, insulin action, or both. Epigenetic modifications,
which are defined as inherited changes in gene expression that occur without changes in gene
sequence, are involved in the etiology of diabetes.
Methods:
In this review, we focused on the role of DNA methylation and protein misfolding and their
contribution to the development of both type 1 and type 2 diabetes mellitus.
Results:
Changes in DNA methylation in particular are highly associated with the development of
diabetes. Protein function is dependent on their proper folding in the endoplasmic reticulum. Defective
protein folding and consequently their functions have also been reported to play a role. Early treatment
of diabetes has proven to be of great benefit, as even transient hyperglycemia may lead to pathological
effects and complications later on. This has been explained by the theory of the development of a
metabolic memory in diabetes. The basis for this metabolic memory was attributed to oxidative stress,
chronic inflammation, non-enzymatic glycation of proteins and importantly, epigenetic changes. This
highlights the importance of linking new therapeutics targeting epigenetic mechanisms with traditional
antidiabetic drugs.
Conclusion:
Although new data is evolving on the relation between DNA methylation, protein misfolding,
and the etiology of diabetes, more studies are required for developing new relevant diagnostics
and therapeutics.
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Affiliation(s)
- Sara M. Ahmed
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, Egypt
| | - Dina Johar
- Biomedical Sciences Program, Zewail City of Science and Technology, Giza, Egypt
| | - Mohamed Medhat Ali
- Biomedical Sciences Program, Zewail City of Science and Technology, Giza, Egypt
| | - Nagwa El-Badri
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, Egypt
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Rittiphairoj T, Pongpirul K, Mueller NT, Li T. Probiotics for glycemic control in patients with type 2 diabetes mellitus: protocol for a systematic review. Syst Rev 2019; 8:227. [PMID: 31481125 PMCID: PMC6720889 DOI: 10.1186/s13643-019-1145-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 08/22/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a major public health problem worldwide. It is characterized by the increased concentration of glucose in the blood and leads to damage of the body system, especially blood vessels and nerves. Lifestyle modification is often combined with anti-diabetic therapy as the standard of care for T2DM to maintain the proper blood glucose and to prevent long-term diabetic complications. The role of probiotics in improving glycemic control has been investigated in several randomized controlled trials (RCTs). Previous systematic reviews and meta-analyses, including different sets of trials have concluded an overall beneficial effect of probiotics in patients with T2DM. At least two RCTs with a longer treatment duration have been published since the publication of existing reviews. METHODS We will conduct a systematic review of RCTs that evaluated the effectiveness and safety of probiotics for glycemic control in T2DM patients. Primary outcomes are fasting blood glucose and glycosylated hemoglobin (A1c). Secondary outcomes are plasma insulin, blood lipid profile, adverse events, and cost associated with the intervention and hospital visits. We will search PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, and trial registries. Two reviewers will independently screen titles and abstracts, review full texts, extract information, and assess the risk of bias. We will summarize the results both qualitatively and statistically. We will use random-effects model for meta-analysis. DISCUSSION This systematic review aims to examine whether probiotics are effective and safe for glycemic control in T2DM patients. Evidence generated from this review will inform clinical and public health practice and future research. SYSTEMATIC REVIEW REGISTRATION CRD42019121682.
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Affiliation(s)
- Thanitsara Rittiphairoj
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 USA
- Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, 1873 Rama IV Road, Pathumwan, Bangkok, 10330 Thailand
| | - Krit Pongpirul
- Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, 1873 Rama IV Road, Pathumwan, Bangkok, 10330 Thailand
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 USA
| | - Noel T. Mueller
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 USA
- Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, MD 21205 USA
| | - Tianjing Li
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 USA
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Long noncoding RNA: an emerging player in diabetes and diabetic kidney disease. Clin Sci (Lond) 2019; 133:1321-1339. [PMID: 31221822 DOI: 10.1042/cs20190372] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 05/16/2019] [Accepted: 05/29/2019] [Indexed: 02/07/2023]
Abstract
Diabetic kidney disease (DKD) is among the most common complications of diabetes mellitus (DM), and remains the leading cause of end-stage renal diseases (ESRDs) in developed countries, with no definitive therapy yet available. It is imperative to decipher the exact mechanisms underlying DKD and identify novel therapeutic targets. Burgeoning evidence indicates that long non-coding RNAs (lncRNAs) are essential for diverse biological processes. However, their roles and the mechanisms of action remain to be defined in disease conditions like diabetes and DKD. The pathogenesis of DKD is twofold, so is the principle of treatments. As the underlying disease, diabetes per se is the root cause of DKD and thus a primary focus of therapy. Meanwhile, aberrant molecular signaling in kidney parenchymal cells and inflammatory cells may directly contribute to DKD. Evidence suggests that a number of lncRNAs are centrally involved in development and progression of DKD either via direct pathogenic roles or as indirect mediators of some nephropathic pathways, like TGF-β1, NF-κB, STAT3 and GSK-3β signaling. Some lncRNAs are thus likely to serve as biomarkers for early diagnosis or prognosis of DKD or as therapeutic targets for slowing progression or even inducing regression of established DKD. Here, we elaborated the latest evidence in support of lncRNAs as a key player in DKD. In an attempt to strengthen our understanding of the pathogenesis of DKD, and to envisage novel therapeutic strategies based on targeting lncRNAs, we also delineated the potential mechanisms of action as well as the efficacy of targeting lncRNA in preclinical models of DKD.
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Huber J, Smeikal M, Saely CH, Stingl H, Lechleitner M, Fasching P. Geriatrische Aspekte bei Diabetes mellitus (Update 2019). Wien Klin Wochenschr 2019; 131:236-245. [DOI: 10.1007/s00508-019-1463-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Jung SH, Han JH, Park HS, Lee DH, Kim SJ, Cho HS, Kang JS, Myung CS. Effects of unaltered and bioconverted mulberry leaf extracts on cellular glucose uptake and antidiabetic action in animals. Altern Ther Health Med 2019; 19:55. [PMID: 30841887 PMCID: PMC6404318 DOI: 10.1186/s12906-019-2460-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Accepted: 02/15/2019] [Indexed: 12/29/2022]
Abstract
Background Mulberry is a Korean medicinal herb that shows effective prevention and treatment of obesity and diabetes. Bioconversion is the process of producing active ingredients from natural products using microorganisms or enzymes. Methods In this study, we prepared bioconverted mulberry leaf extract (BMLE) with Viscozyme L, which we tested in insulin-sensitive cells (i.e., skeletal muscle cells and adipocytes) and insulin-secreting pancreatic β-cells, as well as obese diabetic mice induced by co-administration of streptozotocin (100 mg/kg, IP) and nicotinamide (240 mg/kg, IP) and feeding high-fat diet, as compared to unaltered mulberry leaf extract (MLE). Results BMLE increased the glucose uptake in C2C12 myotubes and 3 T3-L1 adipocytes and increased glucose-stimulated insulin secretion in HIT-T15 pancreatic β-cells. The fasting blood glucose levels in diabetic mice treated with BMLE or MLE (300 and 600 mg/kg, PO, 7 weeks) were significantly lower than those of the vehicle-treated group. At the same concentration, BMLE-treated mice showed better glucose tolerance than MLE-treated mice. Moreover, the blood concentration of glycated hemoglobin (HbA1C) in mice treated with BMLE was lower than that in the MLE group at the same concentration. Plasma insulin levels in mice treated with BMLE or MLE tended to increase compared to the vehicle-treated group. Treatment with BMLE yielded significant improvements in insulin resistance and insulin sensitivity. Conclusion These results indicate that in the management of diabetic condition, BMLE is superior to unaltered MLE due to at least, in part, high concentrations of maker compounds (trans-caffeic acid and syringaldehyde) in BMLE. Electronic supplementary material The online version of this article (10.1186/s12906-019-2460-5) contains supplementary material, which is available to authorized users.
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Stefanaki C, Bacopoulou F, Michos A. The impact of probiotics' administration on glycemic control, body composition, gut microbiome, mitochondria, and other hormonal signals in adolescents with prediabetes - A randomized, controlled trial study protocol. Contemp Clin Trials Commun 2018; 11:55-62. [PMID: 30003169 PMCID: PMC6041374 DOI: 10.1016/j.conctc.2018.06.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 05/20/2018] [Accepted: 06/01/2018] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Recent studies have demonstrated that a significant proportion of adolescents exhibit abdominal obesity in early-middle adolescence, and impaired glucose metabolism. Dysregulation of glucose metabolism is aggravated by the existing osteosarcopenia not only in obese but also in overweight youth. Biochemical inflammation, derived from glucose metabolism dysregulation, in combination with increased stress levels lead to the accumulation of reactive oxygen species, also known as ROS, which seem to afflict the integrity of the gastrointestinal wall, gut mucosa, and commensal, intestinal gut microflora. The current scientific protocol aims to assess the administration of probiotics in prediabetic adolescents in relation with their glycemic control, body composition, and intestinal microbiome. METHODS/DESIGN This is a study protocol of a two-armed RCT, that recruits adolescents with prediabetes, who will receive either a 4-month, life-style intervention, or a life-style intervention along with a probiotic supplement. The primary outcome is the differences in gut microbiome synthesis, body composition analysis parameters, and concentrations of hormones, before and after the intervention. DISCUSSION This study aims to halt the progression of obesity and diabetes and aspires to contribute new evidence for upgraded treatment of obesity and diabetes. TRIAL REGISTRATION Australian New Zealand Clinical Trial Registry (ACTRN12615000470594).
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Affiliation(s)
- Charikleia Stefanaki
- Choremeion Research Laboratory, First Department of Pediatrics, Faculty of Medicine, National and Kapodistrian University of Athens, “Aghia Sophia” Children's Hospital, Athens, Greece
| | - Flora Bacopoulou
- Choremeion Research Laboratory, First Department of Pediatrics, Faculty of Medicine, National and Kapodistrian University of Athens, “Aghia Sophia” Children's Hospital, Athens, Greece
- Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, Faculty of Medicine, National and Kapodistrian University of Athens, “Aghia Sophia” Children's Hospital, Athens, Greece
| | - Athanasios Michos
- Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, Faculty of Medicine, National and Kapodistrian University of Athens, “Aghia Sophia” Children's Hospital, Athens, Greece
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Xu H, Wang Q, Sun Q, Qin Y, Han A, Cao Y, Yang Q, Yang P, Lu J, Liu Q, Xiang Q. In type 2 diabetes induced by cigarette smoking, activation of p38 MAPK is involved in pancreatic β-cell apoptosis. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2018; 25:9817-9827. [PMID: 29372523 DOI: 10.1007/s11356-018-1337-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Accepted: 01/18/2018] [Indexed: 06/07/2023]
Abstract
Type 2 diabetes (T2D) is a chronic disease caused by pancreatic β-cell dysfunction and insulin resistance. Exposure to smoke is a risk factor for diabetes; however, its mechanisms are unclear. In an epidemiological study, we determined the relationship between cigarette smoking and β-cell function. T2D patients had a history of heavier smoking than people without T2D, and heavy smokers had more abnormal glucose metabolism. For various smoking populations, there was a dose-effect relationship between decreases of homeostatic model assessment (HOMA)-β levels or the increases of HOMA-insulin resistance (IR) levels and amount of smoking (pack-years), which indicated that smoking induced β-cell dysfunction. For MIN6 cells, cigarette smoke extract (CSE) decreased insulin secretion and content; enhanced apoptosis, as illustrated by decreases of BCL-2 levels, increases of BAX and cleaved caspase-3 levels, and an increased apoptotic index; and activated the p38 MAPK pathway. For MIN6 cells, inhibition of p-p38 MAPK by SB203580 prevented enhanced apoptosis and the dysfunction of insulin secretion induced by CSE. In sum, activation of p38 MAPK is involved in the apoptosis of pancreatic β-cells induced by cigarette smoking, which is a possible mechanism for induction of T2D by cigarette smoke.
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Affiliation(s)
- Hui Xu
- Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China
- The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China
| | - Qiushi Wang
- School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, People's Republic of China
| | - Qian Sun
- Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China
- The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China
| | - Yu Qin
- Institute of Chronic Non-Communicable Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, Jiangsu, People's Republic of China
| | - Aohan Han
- School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, People's Republic of China
| | - Ye Cao
- School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, People's Republic of China
| | - Qianlei Yang
- Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China
- The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China
| | - Ping Yang
- School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 510182, Guangdong, People's Republic of China
| | - Jiachun Lu
- School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 510182, Guangdong, People's Republic of China
| | - Qizhan Liu
- Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
- The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
| | - Quanyong Xiang
- Institute of Chronic Non-Communicable Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, Jiangsu, People's Republic of China.
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