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Vidal M, Lane NE. Vitamin D and Its Role in Rheumatic Diseases. Metabolites 2025; 15:259. [PMID: 40278388 PMCID: PMC12029499 DOI: 10.3390/metabo15040259] [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: 03/09/2025] [Revised: 03/31/2025] [Accepted: 04/04/2025] [Indexed: 04/26/2025] Open
Abstract
Vitamin D is a fat-soluble molecule with pleiotropic effects, acting as a steroid hormone on three main organs: the intestine, bone, and kidney. Among its best-known functions at the skeletal level are regulating bone metabolism and mineralization. In 1983, the presence of vitamin D receptors on the surface of immune cells was described, which led to the discovery of new functions on immunological and inflammatory processes. Currently, we know that vitamin D modulates the adaptative immune system by suppressing cells that produce inflammatory cytokines by downregulation, acting as an important regulator of immunity and the inflammatory response. In this article, we will review the synthesis, metabolic pathways, and the role of vitamin D in rheumatic autoimmune diseases.
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Affiliation(s)
- Maritza Vidal
- Centro de Diagnóstico de Osteoporosis y Enfermedades Reumáticas (CEDOR), Lima 15036, Peru
| | - Nancy E. Lane
- Center for Musculoskeletal Health, University of California at Davis School of Medicine, Sacramento, CA 95817, USA
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Ziada S, Wishahe A, Mabrouk N, Sahtout S. Vitamin D deficiency and oral health: a systematic review of literature. BMC Oral Health 2025; 25:468. [PMID: 40170041 PMCID: PMC11959803 DOI: 10.1186/s12903-025-05883-w] [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: 11/19/2024] [Accepted: 03/26/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Vitamin D (VD) levels are gaining increasing interest in dentistry due to their association with several oral diseases. OBJECTIVE This study aimed to evaluate the relationship between vitamin D deficiency and various oral disorders. MATERIALS AND METHODS A broad search on the MEDLINE database via the PubMed interface and on the Spring Link platform was carried out using keywords related to the subject. An additional electronic search of gray literature was conducted via Google Scholar. Inclusion criteria were listed for the selection of articles and a reading grid was designed for the extraction of data relating to the research question. The quality of included studies was assessed using JBI's critical appraisal tools. RESULTS A total of 57 studies were identified. After reading the full text, 16 studies were included and selected for qualitative analysis. There is an association between vitamin D deficiency and different oral disorders. Indeed, ten publications assessed the association between vitamin deficiency and periodontal disease, three examined the relationship between vitamin D deficit and dental caries, and one examined the intriguing relationship between vitamin D deficiency and tooth mineralization and two articles interested in vitamin D deficiency and stomatitis. CONCLUSION The analysis of these selected articles shows that Vitamin D deficiency can lead to various oral health disorders during growth and adulthood. Indeed, it can be linked to tooth mineralization defects and increasing the risk of dental caries. Severe Vitamin D deficiency also increases the prevalence of periodontitis and gingival inflammation. It may also be linked to certain oral pathology entities, such as oral cancers and jaw osteonecrosis.
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Affiliation(s)
- Saida Ziada
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia.
| | - Aws Wishahe
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Najet Mabrouk
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
| | - Souad Sahtout
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia
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Al Noman A, Afrosa H, Lihu IK, Sarkar O, Nabin NR, Datta M, Pathak R, Sharma H. Vitamin D and Neurological Health: Unraveling Risk Factors, Disease Progression, and Treatment Potential. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2025; 24:245-256. [PMID: 39440730 DOI: 10.2174/0118715273330972241009092828] [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: 06/08/2024] [Revised: 07/20/2024] [Accepted: 08/07/2024] [Indexed: 10/25/2024]
Abstract
This study explores the complex link between vitamin D and neurological illnesses, focusing on how vitamin D affects possible risk factors, therapeutic applications, and the trajectory of the disease. An epidemiological study has linked vitamin D insufficiency to several neurological conditions, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. It is hypothesized that immunomodulatory and anti-inflammatory properties of vitamin D contribute to its neuroprotective effects. Two major mechanisms in dementia include neuroinflammation and oxidative stress. Adequate levels of vitamin D have been shown in both animal models and human studies to enhance both clinical outcomes and the duration of illness in those who have it. Other ways that vitamin D contributes to its therapeutic potential include the production of neurotrophic factors, control over neurotransmitter synthesis, and preservation of the blood-brain barrier. Despite the encouraging outcomes, research is still being conducted to determine the optimal dosage and long-term benefits of vitamin D supplementation on brain function. In order to furnish precise directives and clarify the processes behind the neuroprotective impacts of vitamin D, future research must focus on large-scale randomized controlled studies. . This study highlights the significance of maintaining adequate levels of vitamin D as a modifiable risk factor for neurological disorders. Further study is also required to comprehend the possible medical benefits of this vitamin fully.
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Affiliation(s)
| | - Halima Afrosa
- School of Pharmacy, BRAC University, Dhaka, Bangladesh
| | | | | | | | - Monty Datta
- Department of Zoology, Government Tolaram College, National University Bangladesh, Gazipur 1704, Bangladesh
| | - Rashmi Pathak
- Department of Pharmacy, Invertis University, Bareilly (UP)-243123, India
| | - Himanshu Sharma
- Department of Pharmacy, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad (UP)-244001, India
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de Jorge‐Huerta L, Silva JT, Fernández‐Ruiz M, Rodríguez‐Goncer I, Pérez‐Jacoiste Asín MA, Ruiz‐Merlo T, Heredia‐Mena C, González‐Monte E, Polanco N, San Juan R, Andrés A, Aguado JM, López‐Medrano F. Novel intervention based on an individualized bundle of care to decrease infection in kidney transplant recipients. Transpl Infect Dis 2024; 26:e14354. [PMID: 39136146 PMCID: PMC11666872 DOI: 10.1111/tid.14354] [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: 02/10/2024] [Revised: 06/06/2024] [Accepted: 07/27/2024] [Indexed: 12/25/2024]
Abstract
BACKGROUND Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT. METHODS A single-center prospective cohort of 148 patients undergoing KT between February 2018 and September 2019 that received an individualized infection prevention strategy was compared to a preintervention cohort (n = 159). The bundle comprised a review of the patient's immunization history, infection risk by country of origin, screening for latent tuberculosis infection (LTBI), antimicrobial prophylaxis, and immunological assessment. Individualized recommendations were accordingly provided at a scheduled visit at day +30 after transplantation. RESULTS The intervention cohort showed a higher compliance rate with the recommended vaccine schedule, screening for geographically restricted infections and LTBI, and intravenous immunoglobulin and vitamin D supplementation (p values <.001). The 1-year incidence rate of infection was lower in the intervention cohort (42.6% vs. 57.9%; p value = .037), as was the rate of infection-related hospitalization (17.6% vs. 32.1%; p value = .003) and the incidence of severe bacterial infection. There were no differences in graft rejection or mortality rates between groups. CONCLUSIONS A multifaceted intervention, including a bundle of evidence-based practices, enhanced compliance with recommended preventive measures and was correlated with a reduction in the 12-month incidence of infection after KT.
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Affiliation(s)
- Lucía de Jorge‐Huerta
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - José Tiago Silva
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - Mario Fernández‐Ruiz
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)Instituto de Salud Carlos IIIMadridSpain
- Department of MedicineUniversidad Complutense de MadridMadridSpain
| | - Isabel Rodríguez‐Goncer
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - M. Asunción Pérez‐Jacoiste Asín
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - Tamara Ruiz‐Merlo
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - Carlos Heredia‐Mena
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - Esther González‐Monte
- Department of NephrologyHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - Natalia Polanco
- Department of NephrologyHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - Rafael San Juan
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)Instituto de Salud Carlos IIIMadridSpain
- Department of MedicineUniversidad Complutense de MadridMadridSpain
| | - Amado Andrés
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)Instituto de Salud Carlos IIIMadridSpain
- Department of MedicineUniversidad Complutense de MadridMadridSpain
- Department of NephrologyHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
| | - José María Aguado
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
- Department of MedicineUniversidad Complutense de MadridMadridSpain
| | - Francisco López‐Medrano
- Unit of Infectious DiseasesHospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12)MadridSpain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)Instituto de Salud Carlos IIIMadridSpain
- Department of MedicineUniversidad Complutense de MadridMadridSpain
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Bellavia D, Costa V, De Luca A, Maglio M, Pagani S, Fini M, Giavaresi G. Vitamin D Level Between Calcium-Phosphorus Homeostasis and Immune System: New Perspective in Osteoporosis. Curr Osteoporos Rep 2024; 22:599-610. [PMID: 27734322 DOI: 10.1007/s11914-016-0331-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Vitamin D is a key molecule in calcium and phosphate homeostasis; however, increasing evidence has recently shown that it also plays a crucial role in the immune system, both innate and adaptive. A deregulation of vitamin D levels, due also to mutations and polymorphisms in the genes of the vitamin D pathway, determines severe alterations in the homeostasis of the organism, resulting in a higher risk of onset of some diseases, including osteoporosis. This review gives an overview of the influence of vitamin D levels on the pathogenesis of osteoporosis, between bone homeostasis and immune system.
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Affiliation(s)
- Daniele Bellavia
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy
| | - Viviana Costa
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy
| | - Angela De Luca
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy
| | - Melania Maglio
- Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Stefania Pagani
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Milena Fini
- Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Gianluca Giavaresi
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy.
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Zhong K, Du X, Niu Y, Li Z, Tao Y, Wu Y, Zhang R, Guo L, Bi Y, Tang L, Dou T, Wang L. Progress in the mechanism of functional dyspepsia: roles of mitochondrial autophagy in duodenal abnormalities. Front Med (Lausanne) 2024; 11:1491009. [PMID: 39655235 PMCID: PMC11627220 DOI: 10.3389/fmed.2024.1491009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 11/12/2024] [Indexed: 12/12/2024] Open
Abstract
Mitochondria are the main source of energy for cellular activity. Their functional damage or deficiency leads to cellular deterioration, which in turn triggers autophagic reactions. Taking mitochondrial autophagy as a starting point, the present review explored the mechanisms of duodenal abnormalities in detail, including mucosal barrier damage, release of inflammatory factors, and disruption of intracellular signal transduction. We summarized the key roles of mitochondrial autophagy in the abnormal development of the duodenum and examined the in-depth physiological and pathological mechanisms involved, providing a comprehensive theoretical basis for understanding the pathogenesis of functional dyspepsia. At present, it has been confirmed that an increase in the eosinophil count and mast cell degranulation in the duodenum can trigger visceral hypersensitive reactions and cause gastrointestinal motility disorders. In the future, it is necessary to continue exploring the molecular mechanisms and signaling pathways of mitochondrial autophagy in duodenal abnormalities. A deeper understanding of mitochondrial autophagy provides important references for developing treatment strategies for functional dyspepsia, thereby improving clinical efficacy and patient quality of life.
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Affiliation(s)
- Kexin Zhong
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Xiaojuan Du
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yuanyuan Niu
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Zhengju Li
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yongbiao Tao
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yuqian Wu
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Ruiting Zhang
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Linjing Guo
- Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yurong Bi
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, School of Life Sciences, Lanzhou University, Lanzhou, China
| | - Lijuan Tang
- College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Tianyu Dou
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - Longde Wang
- Department of Gastroenterology, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, China
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Yin H, Zhang J, Chen Y, Guo J, Li Q, Dinnyes A, Sun Q, Liu X, He G, Zhu B, Liu Y, Xu P, Xu W, Xie J. Placenta-specific CYP11A1 overexpression lead to autism-like symptom in offspring with altered steroid hormone biosynthesis in the placenta-brain axis and rescued by vitamin D intervention. Brain Behav Immun 2024; 121:13-25. [PMID: 39025414 DOI: 10.1016/j.bbi.2024.07.012] [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: 04/10/2024] [Revised: 07/06/2024] [Accepted: 07/15/2024] [Indexed: 07/20/2024] Open
Abstract
Alterations in steroid hormone regulation have been implicated in the etiology and progression of autism spectrum disorders (ASD), with the enzyme cytochrome P450 family 11 subfamily A member 1 (CYP11A1)-a key catalyst in cholesterol side-chain cleavage, prominently expressed in the adrenal glands, ovaries, testes, and placenta-standing at the forefront of these investigations. The potential link between aberrations in placental Cyp11a1 expression and the resultant neurodevelopmental disorders, along with the mechanisms underpinning such associations, remains inadequately delineated. In this study, we employed a placental trophoblast-specific Cyp11a1 Hipp11 (H11) knock-in murine model to dissect the phenotypic manifestations within the placenta and progeny, thereby elucidating the underlying mechanistic pathways. Behavioral analyses revealed a diminution in social interaction capabilities alongside an augmented anxiety phenotype, as evidenced by open field and elevated plus maze assessments; both phenotypes were ameliorated after vitamin D3 supplementation. Electrophysiological assays underscored the augmented inhibition of paired-pulse facilitation, indicating impaired neuroplasticity in Cyp11a1 H11-modified mice. An elevation in progesterone concentrations was noted, alongside a significant upregulation of Th1-related cytokines (IL-6 and TNFα) across the plasma, placental, and frontal cortex-a pathological state mitigable through vitamin D3 intervention. Western blotting revealed a vitamin D-mediated rectification of vitamin D receptor and PGC-1α expression dysregulations. Immunofluorescence assays revealed microglial activation in the knock-in model, which was reversible upon vitamin D3 treatment. In conclusion, Cyp11a1 overexpression in the placenta recapitulated an autism-like phenotype in murine models, and vitamin D3 administration effectively ameliorated the resultant neurobehavioral and neuroinflammatory derangements. This study substantiates the application of Cyp11a1 as a biomarker in prenatal diagnostics and posits that prenatal vitamin D3 supplementation is a viable prophylactic measure against perturbations in steroid hormone metabolism associated with ASD pathogenesis.
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Affiliation(s)
- Heng Yin
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Chengdu Third People's Hospital, Chengdu 610041, China
| | - Jing Zhang
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Chengdu Third People's Hospital, Chengdu 610041, China
| | - Yajun Chen
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Juncen Guo
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Qing Li
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Andras Dinnyes
- BioTalentum Ltd., Gödöllő, Hungary; Department of Physiology and Animal Health, Institute of Physiology and Animal Nutrition, Hungarian University of Agriculture and Life Sciences, Gödöllő, Hungary
| | - Qun Sun
- Key Laboratory of Bio-Resource and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China
| | - Xinghui Liu
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Guolin He
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Bin Zhu
- School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, China
| | - Yan Liu
- Chengdu Third People's Hospital, Chengdu 610041, China
| | - Peng Xu
- School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, China.
| | - Wenming Xu
- Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
| | - Jiang Xie
- Chengdu Third People's Hospital, Chengdu 610041, China.
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Elnady M, Hafeez AA, Assal H, Zaid E, Abo Elwafa G. Serum vitamin D levels and the severity and clinical course of COVID-19. Monaldi Arch Chest Dis 2024. [PMID: 39324744 DOI: 10.4081/monaldi.2024.2978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 08/26/2024] [Indexed: 09/27/2024] Open
Abstract
Low vitamin D levels are associated with different pulmonary diseases, such as chronic obstructive pulmonary disease, bronchial asthma, and obstructive sleep apnea. In this study, we aimed to assess the relation between vitamin D levels and COVID-19 severity. Positive COVID-19 patients were subjected to clinical examination, computed tomography of the chest, and laboratory investigations. Serum vitamin D level was measured and correlated with the severity and the clinical course of the disease. The study included 72 patients, classified into four groups according to the severity of the disease. There was a statistically significant difference between the four groups regarding age, lymphocyte count, serum vitamin D, C-reactive protein, and lactate dehydrogenase levels. Serum vitamin D levels can be correlated with COVID-19 severity and clinical course.
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Affiliation(s)
- Mohamed Elnady
- Department of Chest Diseases, Faculty of Medicine, Cairo University.
| | | | - Hebatallah Assal
- Department of Chest Diseases, Faculty of Medicine, Cairo University.
| | | | - Gihan Abo Elwafa
- Department of Chest Diseases, Faculty of Medicine, Cairo University.
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Comas M, Zamora-Camacho FJ, Garrido-Bautista J, Moreno-Rueda G, Martín J, López P. Mounting an immune response reduces male attractiveness in a lizard. Integr Zool 2024. [PMID: 39219026 DOI: 10.1111/1749-4877.12889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Parasites impact host fitness and constitute an important selective pressure on the host's life history. According to parasite-mediated sexual selection, ornaments are presumed to honestly indicate immune capacity or resistance against parasites, and the chooser sex (typically females) obtains an advantage by selecting more ornamented, thus more immunocompetent mates. Therefore, signalers mounting an immune response must allocate resources from the sexual signal to the immune system, hence reducing the expression of the ornament and becoming less attractive to the choosing sex. Here, we test this idea in the lizard Psammodromus algirus. We inoculated a subsample of males with lipopolysaccharide (LPS) of the cell wall of Escherichia coli, while others served as sham controls. The inoculation of LPS decreased the proportion of ergosterol (pro-vitamin D2) in femoral secretions, and chemosensory tests showed that the scent of LPS-inoculated males was less attractive to females than the scent of control males. Given that ergosterol is a precursor of vitamin D, which has physiological functions as an immune modulator, immunocompromised males likely needed to divert vitamin D to the immune system, reducing the allocation of ergosterol to secretions. In this way, females could detect "sick" males, preferring the apparently healthy males. Overall, our study shows that mounting an immune response is costly in terms of reduced attractiveness. Moreover, we disentangle the underlying mechanism, which involves an honest signal based on vitamin D allocation.
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Affiliation(s)
- Mar Comas
- Department of Biological Sciences, Dartmouth College, Hanover, NH, USA
- Departamento de Zoología, Facultad de Ciencias, Universidad de Granada, Granada, Spain
| | - Francisco J Zamora-Camacho
- Departamento de Biogeografía y Cambio Global, Museo Nacional de Ciencias Naturales, C.S.I.C, Madrid, Spain
- Departamento de Biología de Organismos y Sistemas, Área de Zoología, Universidad de Oviedo, Oviedo, Spain
| | | | - Gregorio Moreno-Rueda
- Departamento de Zoología, Facultad de Ciencias, Universidad de Granada, Granada, Spain
| | - José Martín
- Departamento de Ecología Evolutiva, Museo Nacional de Ciencias Naturales, C.S.I.C, Madrid, Spain
| | - Pilar López
- Departamento de Ecología Evolutiva, Museo Nacional de Ciencias Naturales, C.S.I.C, Madrid, Spain
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Steigmann L, Kačarević ŽP, Khoury J, Nagy K, Feres M. Integration of precision medicine into the dental care setting. FRONTIERS IN DENTAL MEDICINE 2024; 5:1398897. [PMID: 39917647 PMCID: PMC11797757 DOI: 10.3389/fdmed.2024.1398897] [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: 03/11/2024] [Accepted: 07/09/2024] [Indexed: 01/03/2025] Open
Abstract
This narrative review aims to discuss the incorporation of novel medical concepts and tools into dental practice, with the goal of improving early diagnosis and exploring new personalized treatment options for oral pathologies, such as caries and periodontitis. Preventative dental approaches concentrate on the timely detection of oral infections and the integration of biomarker analysis to recognize pathogenic changes at early stage of disease. Likewise, periodic monitoring after the treatment is relevant to ensure the balance in the oral biofilms and prevent relapse. Additionally, more attention has shifted towards the contributing factors to disease development, such as essential nutrients. Sufficient levels of vitamin C, vitamin D and zinc pre- and post-operatively are employed to boost immune function and reduce the risk of postoperative infections. Omega-3 fatty acids, melatonin, and antioxidants like vitamin E, which have anti-inflammatory properties, are utilized to help minimize excessive inflammation and promote faster recovery. The data presented in this manuscript emphasize the crucial integration of innovative healthcare concepts and tools into dental practices. By adopting a more holistic view of the patient, clinicians can tailor treatments to each individual's predispositions, lifestyle, and oral health conditions. This review also highlights the potential of salivary biomarkers and point-of-care technologies in enhancing early diagnostic accuracy and personalizing treatment. Bridging the gap between oral and systemic health is the most effective approach to improving patient quality of life. These findings underscore the importance of continued interdisciplinary collaboration in dentistry.
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Affiliation(s)
- Larissa Steigmann
- Department of Oral Medicine, Infection, and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Boston, MA, United States
| | - Željka Perić Kačarević
- Department of Anatomy, Histology, Embryology, Pathology Anatomy and Pathology Histology, Faculty of Dental Medicine and Health Osijek, J.J. Strossmayer University of Osijek, Osijek, Croatia
| | - Jessica Khoury
- Department of Oral Biology, The Goldschleger School of Dental Medicine, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Katalin Nagy
- Department of Oral Surgery, Faculty of Dentistry, University of Szeged, Szeged, Hungary
| | - Magda Feres
- Department of Oral Medicine, Infection, and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Boston, MA, United States
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Wang J, Mei L, Hao Y, Xu Y, Yang Q, Dai Z, Yang Y, Wu Z, Ji Y. Contemporary Perspectives on the Role of Vitamin D in Enhancing Gut Health and Its Implications for Preventing and Managing Intestinal Diseases. Nutrients 2024; 16:2352. [PMID: 39064795 PMCID: PMC11279818 DOI: 10.3390/nu16142352] [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: 06/13/2024] [Revised: 07/11/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024] Open
Abstract
Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases.
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Affiliation(s)
- Jiaxin Wang
- State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; (J.W.); (L.M.); (Q.Y.); (Z.D.); (Y.Y.); (Z.W.)
| | - Lihua Mei
- State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; (J.W.); (L.M.); (Q.Y.); (Z.D.); (Y.Y.); (Z.W.)
| | - Yanling Hao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China;
| | - Yajun Xu
- Department of Nutrition and Food Hygiene, Peking University, Beijing 100083, China;
| | - Qing Yang
- State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; (J.W.); (L.M.); (Q.Y.); (Z.D.); (Y.Y.); (Z.W.)
| | - Zhaolai Dai
- State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; (J.W.); (L.M.); (Q.Y.); (Z.D.); (Y.Y.); (Z.W.)
| | - Ying Yang
- State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; (J.W.); (L.M.); (Q.Y.); (Z.D.); (Y.Y.); (Z.W.)
| | - Zhenlong Wu
- State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; (J.W.); (L.M.); (Q.Y.); (Z.D.); (Y.Y.); (Z.W.)
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China;
| | - Yun Ji
- State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; (J.W.); (L.M.); (Q.Y.); (Z.D.); (Y.Y.); (Z.W.)
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12
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Murdaca G, Tagliafico L, Page E, Paladin F, Gangemi S. Gender Differences in the Interplay between Vitamin D and Microbiota in Allergic and Autoimmune Diseases. Biomedicines 2024; 12:1023. [PMID: 38790985 PMCID: PMC11117902 DOI: 10.3390/biomedicines12051023] [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: 04/02/2024] [Revised: 04/22/2024] [Accepted: 05/01/2024] [Indexed: 05/26/2024] Open
Abstract
The synergic role of vitamin D and the intestinal microbiota in the regulation of the immune system has been thoroughly described in the literature. Vitamin D deficiency and intestinal dysbiosis have shown a pathogenetic role in the development of numerous immune-mediated and allergic diseases. The physiological processes underlying aging and sex have proven to be capable of having a negative influence both on vitamin D values and the biodiversity of the microbiome. This leads to a global increase in levels of systemic inflammatory markers, with potential implications for all immune-mediated diseases and allergic conditions. Our review aims to collect and analyze the relationship between vitamin D and the intestinal microbiome with the immune system and the diseases associated with it, emphasizing the effect mediated by sexual hormones and aging.
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Affiliation(s)
- Giuseppe Murdaca
- Department of Internal Medicine, University of Genova, 16132 Genova, Italy (E.P.)
- Allergology and Clinical Immunology Unit, San Bartolomeo Hospital, 19038 Sarzana, Italy
| | - Luca Tagliafico
- Department of Internal Medicine, University of Genova, 16132 Genova, Italy (E.P.)
- Ospedale Policlinico San Martino IRCCS, Largo Rosanna Benzi 10, 16132 Genova, Italy
| | - Elena Page
- Department of Internal Medicine, University of Genova, 16132 Genova, Italy (E.P.)
- Ospedale Policlinico San Martino IRCCS, Largo Rosanna Benzi 10, 16132 Genova, Italy
| | - Francesca Paladin
- Elderly and Disabeld Department, San Paolo Hospital, 17100 Savona, Italy
| | - Sebastiano Gangemi
- School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
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13
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Felipin KP, Paloschi MV, Silva MDS, Ikenohuchi YJ, Santana HM, Setúbal SDS, Rego CMA, Lopes JA, Boeno CN, Serrath SN, De Medeiros EHRT, Pimentel IF, Oliveira AER, Cupolillo E, Cantanhêde LM, Ferreira RDGM, Zuliani JP. Transcriptomics analysis highlights potential ways in human pathogenesis in Leishmania braziliensis infected with the viral endosymbiont LRV1. PLoS Negl Trop Dis 2024; 18:e0012126. [PMID: 38743668 PMCID: PMC11093365 DOI: 10.1371/journal.pntd.0012126] [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: 05/16/2023] [Accepted: 04/01/2024] [Indexed: 05/16/2024] Open
Abstract
The parasite Leishmania (Viannia) braziliensis is widely distributed in Brazil and is one of the main species associated with human cases of different forms of tegumentary leishmaniasis (TL) such as cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). The mechanisms underlying the pathogenesis of TL are still not fully understood, but it is known that factors related to the host and the parasite act in a synergistic and relevant way to direct the response to the infection. In the host, macrophages have a central connection with the parasite and play a fundamental role in the defense of the organism due to their ability to destroy intracellular parasites and present antigens. In the parasite, some intrinsic factors related to the species or even the strain analyzed are fundamental for the outcome of the disease. One of them is the presence of Leishmania RNA Virus 1 (LRV1), an endosymbiont virus that parasitizes some species of Leishmania that triggers a cascade of signals leading to a more severe TL phenotype, such as ML. One of the strategies for understanding factors associated with the immune response generated after Leishmania/host interaction is through the analysis of molecular patterns after infection. Thus, the gene expression profile in human monocyte-derived macrophages obtained from healthy donors infected in vitro with L. braziliensis positive (LbLRV1+) and negative (LbLRV1-) for LRV1 was evaluated. For this, the microarray assay was used and 162 differentially expressed genes were identified in the comparison LbLRV1+ vs. LbLRV1-, 126 upregulated genes for the type I and II interferons (IFN) signaling pathway, oligoadenylate synthase OAS/RNAse L, non-genomic actions of vitamin D3 and RIG-I type receptors, and 36 down-regulated. The top 10 downregulated genes along with the top 10 upregulated genes were considered for analysis. Type I interferon (IFNI)- and OAS-related pathways results were validated by RT-qPCR and Th1/Th2/Th17 cytokines were analyzed by Cytometric Bead Array (CBA) and enzyme-linked immunosorbent assay (ELISA). The microarray results validated by RT-qPCR showed differential expression of genes related to IFNI-mediated pathways with overexpression of different genes in cells infected with LbLRV1+ compared to LbLRV1- and to the control. No significant differences were found in cytokine levels between LbLRV1+ vs. LbLRV1- and control. The data suggest the activation of gene signaling pathways associated with the presence of LRV1 has not yet been reported so far. This study demonstrates, for the first time, the activation of the OAS/RNase L signaling pathway and the non-genomic actions of vitamin D3 when comparing infections with LbLRV1+ versus LbLRV1- and the control. This finding emphasizes the role of LRV1 in directing the host's immune response after infection, underlining the importance of identifying LRV1 in patients with TL to assess disease progression.
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Affiliation(s)
- Kátia Paula Felipin
- Laboratório de Epidemiologia Genética, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Mauro Valentino Paloschi
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Milena Daniela Souza Silva
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Yoda Janaina Ikenohuchi
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Hallison Mota Santana
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Sulamita da Silva Setúbal
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Cristina Matiele Alves Rego
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Jéssica Amaral Lopes
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Charles Nunes Boeno
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | - Suzanne Nery Serrath
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | | | - Iasmin Ferreira Pimentel
- Laboratório de Epidemiologia Genética, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
| | | | - Elisa Cupolillo
- Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
- Instituto Nacional de Epidemiologia da Amazônia Ocidental, EpiAmO, Porto Velho, Brazil
| | - Lilian Motta Cantanhêde
- Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
- Instituto Nacional de Epidemiologia da Amazônia Ocidental, EpiAmO, Porto Velho, Brazil
| | - Ricardo de Godoi Matos Ferreira
- Laboratório de Epidemiologia Genética, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
- Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
- Instituto Nacional de Epidemiologia da Amazônia Ocidental, EpiAmO, Porto Velho, Brazil
| | - Juliana Pavan Zuliani
- Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil
- Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho, Brazil
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Napiórkowska-Baran K, Treichel P, Czarnowska M, Drozd M, Koperska K, Węglarz A, Schmidt O, Darwish S, Szymczak B, Bartuzi Z. Immunomodulation through Nutrition Should Be a Key Trend in Type 2 Diabetes Treatment. Int J Mol Sci 2024; 25:3769. [PMID: 38612580 PMCID: PMC11011461 DOI: 10.3390/ijms25073769] [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: 02/09/2024] [Revised: 03/21/2024] [Accepted: 03/23/2024] [Indexed: 04/14/2024] Open
Abstract
An organism's ability to function properly depends not solely on its diet but also on the intake of nutrients and non-nutritive bioactive compounds that exert immunomodulatory effects. This principle applies both to healthy individuals and, in particular, to those with concomitant chronic conditions, such as type 2 diabetes. However, the current food industry and the widespread use of highly processed foods often lead to nutritional deficiencies. Numerous studies have confirmed the occurrence of immune system dysfunction in patients with type 2 diabetes. This article elucidates the impact of specific nutrients on the immune system function, which maintains homeostasis of the organism, with a particular emphasis on type 2 diabetes. The role of macronutrients, micronutrients, vitamins, and selected substances, such as omega-3 fatty acids, coenzyme Q10, and alpha-lipoic acid, was taken into consideration, which outlined the minimum range of tests that ought to be performed on patients in order to either directly or indirectly determine the severity of malnutrition in this group of patients.
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Affiliation(s)
- Katarzyna Napiórkowska-Baran
- Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland;
| | - Paweł Treichel
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Marta Czarnowska
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Magdalena Drozd
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Kinga Koperska
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Agata Węglarz
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Oskar Schmidt
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Samira Darwish
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Bartłomiej Szymczak
- Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland; (P.T.); (M.C.); (M.D.); (K.K.); (A.W.); (O.S.); (S.D.); (B.S.)
| | - Zbigniew Bartuzi
- Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, 85-067 Bydgoszcz, Poland;
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15
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Nireeksha, Hegde MN, Kumari N S. Potential role of salivary vitamin D antimicrobial peptide LL-37 and interleukins in severity of dental caries: an exvivo study. BMC Oral Health 2024; 24:79. [PMID: 38218769 PMCID: PMC10787980 DOI: 10.1186/s12903-023-03749-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 12/08/2023] [Indexed: 01/15/2024] Open
Abstract
INTRODUCTION Vitamin D performs various functions as a hormone by promoting calcium absorption but plays a major role in innate immunity,cell differentiation, cell maturation through its genomic effects via vitamin D receptor. The immune response also plays a major role in tooth surface and supporting structure destruction and playing a major factor in high caries formation. The inflammatory cytokines are released has proinflammatory cytokines and stimulate cells in disease process. Therefore, in the present study we have evaluated the association of salivary vitamin D, LL-37, interleukins 6 and 17A in various levels of severity of dental caries. METHOD Ethical approval was obtained (NU/CEC/2020/0339), 377 individuals reporting to department of conservative dentistry and endodontics, AB Shetty memorial institute of dental sciences were included based on inclusion criteria. The individuals were further divided into caries free(N = 105) and caries active(N = 272) based on their caries prevalence. The salivary were collected and evaluated for vitamin D, LL-37,IL-17A and IL-6.Results were statistically analysed with SPSS vs 22 (IBM Corp, USA). Normally distributed data were expressed as mean ± SD. Skewed data were expressed as median and interquartile range. To compare (mean) outcome measures between the two groups unpaired independent t-test was applied and for values in median IQR, Mann Whitney U test was used. All statistical analysis for P value were two-sided and significance was set to P ≤ 0.05. RESULTS The study showed that, the salivary vitamin D statistically decreased with increasing severity of caries which showed that vitamin D plays an important role in prevention of caries. Antimicrobial peptide LL-37 was higher in caries free group but was not statistically significant, salivary IL-6 level was higher in caries active group but intergroup comparison did not show significant difference. Salivary IL-17A did not show statistically significant between caries active and caries free group. CONCLUSION The salivary levels of vitamin D may play a vital role in prevalence of dental caries and its severity which can be a underlying cause in presence of other etiological factors.
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Affiliation(s)
- Nireeksha
- Department of Conservative Dentistry and Endodontics, AB Shetty Memorial Institute of Dental Sciences, Nitte (deemed to be) University, Mangaluru, India.
| | - Mithra N Hegde
- Department of Conservative Dentistry and Endodontics, AB Shetty Memorial Institute of Dental Sciences, Nitte (deemed to be) University, Mangaluru, India
| | - Suchetha Kumari N
- Department of Biochemistry, KS Hegde Medical Academy, Nitte (deemed to be) University, Mangaluru, India
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16
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Wu D, Khan FA, Zhang K, Pandupuspitasari NS, Negara W, Guan K, Sun F, Huang C. Retinoic acid signaling in development and differentiation commitment and its regulatory topology. Chem Biol Interact 2024; 387:110773. [PMID: 37977248 DOI: 10.1016/j.cbi.2023.110773] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/11/2023] [Accepted: 10/20/2023] [Indexed: 11/19/2023]
Abstract
Retinoic acid (RA), the derivative of vitamin A/retinol, is a signaling molecule with important implications in health and disease. It is a well-known developmental morphogen that functions mainly through the transcriptional activity of nuclear RA receptors (RARs) and, uncommonly, through other nuclear receptors, including peroxisome proliferator-activated receptors. Intracellular RA is under spatiotemporally fine-tuned regulation by synthesis and degradation processes catalyzed by retinaldehyde dehydrogenases and P450 family enzymes, respectively. In addition to dictating the transcription architecture, RA also impinges on cell functioning through non-genomic mechanisms independent of RAR transcriptional activity. Although RA-based differentiation therapy has achieved impressive success in the treatment of hematologic malignancies, RA also has pro-tumor activity. Here, we highlight the relevance of RA signaling in cell-fate determination, neurogenesis, visual function, inflammatory responses and gametogenesis commitment. Genetic and post-translational modifications of RAR are also discussed. A better understanding of RA signaling will foster the development of precision medicine to improve the defects caused by deregulated RA signaling.
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Affiliation(s)
- Di Wu
- Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
| | - Faheem Ahmed Khan
- Research Center for Animal Husbandry, National Research and Innovation Agency, Jakarta Pusat, 10340, Indonesia
| | - Kejia Zhang
- Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
| | | | - Windu Negara
- Research Center for Animal Husbandry, National Research and Innovation Agency, Jakarta Pusat, 10340, Indonesia
| | - Kaifeng Guan
- School of Advanced Agricultural Sciences, Peking University, Beijing, 100871, China.
| | - Fei Sun
- Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China.
| | - Chunjie Huang
- Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China.
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17
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Johnson CR, Thacher TD. Vitamin D: immune function, inflammation, infections and auto-immunity. Paediatr Int Child Health 2023; 43:29-39. [PMID: 36857810 DOI: 10.1080/20469047.2023.2171759] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 10/12/2022] [Indexed: 03/03/2023]
Abstract
Vitamin D plays an active role beyond mineral metabolism and skeletal health, including regulation of the immune system. Vitamin D deficiency is widely prevalent, and observational studies link low vitamin D status to a risk of infections and auto-immune disorders. Reports indicate an inverse relationship between vitamin D status and such conditions. This review details vitamin D signalling interactions with the immune system and provides experimental and clinical evidence evaluating vitamin D status, vitamin D supplementation and host susceptibility to infections, inflammation and auto-immunity. The published literature including related reviews, systematic reviews, meta-analyses, randomised controlled trials (RCTs), observational studies and basic science reports have been synthesised. Meta-analyses of observational studies have demonstrated a link between low vitamin D status and risk of acute respiratory infections, COVID-19 disorders, multiple sclerosis, type 1 diabetes (T1DM), inflammatory bowel disease (IBD), systemic lupus erythematosus and other auto-immune disorders. Observational studies suggest that vitamin D supplementation may protect against several infectious and auto-immune conditions. Meta-analyses of RCTs had mixed results, demonstrating a small protective role for vitamin D supplementation against acute respiratory infections, especially in those with vitamin D deficiency and children, and providing modest benefits for the management of T1DM and IBD. Vitamin D status is inversely associated with the incidence of several infectious and auto-immune conditions. Supplementation is recommended for those with vitamin D deficiency or at high risk of deficiency, and it might provide additional benefit in acute respiratory infections and certain auto-immune conditions.
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Affiliation(s)
- Casey R Johnson
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Tom D Thacher
- Department of Family Medicine, Mayo Clinic, Rochester, New York, USA
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18
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Li Z, Wei X, Shao Z, Liu H, Bai S. Correlation between vitamin D levels in serum and the risk of dental caries in children: a systematic review and meta-analysis. BMC Oral Health 2023; 23:768. [PMID: 37858104 PMCID: PMC10585927 DOI: 10.1186/s12903-023-03422-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 09/18/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND Vitamin D plays a crucial role in oral health, and its deficiency is associated to significant changes in oral health diseases. We aimed to explore the relationship between levels of 25-hydroxyvitamin D (25(OH) D) and dental caries in children. METHODS Four electronic databases were searched by two investigators including PubMed, Embase, Web of Science, and Cochrane Library. Dental caries results were presented as either prevalence or based on the index of primary and permanent teeth/surfaces with decaying, missing, and filled areas, while vitamin D levels were determined through laboratory testing. Two researchers independently selected studies, collected information, assessed risk of bias, and evaluated the study quality. Any disagreements were resolved through discussion. RESULTS A total of 13 studies were included, comprising 5 cross-sectional studies, 5 cohort studies, 3 case-control studies, all of which had high methodological quality. Our meta-analysis showed that children with vitamin D deficiency had a 22% higher risk of dental caries than those with normal vitamin D levels, with a relative risk (RR) of 1.22 and a 95% confidence interval (CI) of 1.18 to 1. 25. Further subgroup analysis according to the three types of studies showed that the risk of dental caries in children with vitamin D deficiency was higher than that in normal vitamin D level group (cohort studies: 62%; cross-sectional studies, 19%; and case-control studies, 5%). Additionally, according to age, subgroup analysis also showed that the risk of dental caries in children with vitamin D deficiency was higher than that in normal vitamin D level group (permanent teeth studies, 28%; deciduous teeth studies, 68%; and mixed dentition studies 8%). CONCLUSIONS Levels of 25 (OH) D have been found negatively associated with dental caries in children, indicating that low vitamin D levels may be considered a potential risk factor to this dental disease.
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Affiliation(s)
- Zizhan Li
- College of Basic Medical Sciences, Army Medical University, Chongqing, 400038, China
- Department of Stomatology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China
| | - Xiao Wei
- Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Zhongjun Shao
- Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Huan Liu
- Department of Stomatology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
| | - Shizhu Bai
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Digital Center of School of Stomatology, Air Force Medical University, Xi'an, 710032, Shaanxi, China.
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19
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Kawagoe F, Mototani S, Mendoza A, Takemoto Y, Uesugi M, Kittaka A. Structure-activity relationship studies on vitamin D-based selective SREBP/SCAP inhibitor KK-052. RSC Med Chem 2023; 14:2030-2034. [PMID: 37859714 PMCID: PMC10583829 DOI: 10.1039/d3md00352c] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 08/09/2023] [Indexed: 10/21/2023] Open
Abstract
Vitamin D3 metabolites block lipid biosynthesis by promoting degradation of the complex of sterol regulatory element-binding protein (SREBP) and SREBP cleavage-activating protein (SCAP) independent of their effects on the vitamin D receptor (VDR). We previously reported the development of KK-052, the first vitamin D-based SREBP inhibitor that mitigates hepatic lipid accumulation without VDR-mediated calcemic action in mice. Herein we extend our previous work to synthesize KK-052 analogues. Various substituents were introduced to the phenyl ring of KK-052, and two KK-052 analogues were found to exhibit more potent SREBP/SCAP inhibitory activity than KK-052, whereas they all lack VDR activity. These new KK-052 analogues may be suited for further development as VDR-silent SREBP/SCAP inhibitors.
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Affiliation(s)
- Fumihiro Kawagoe
- Faculty of Pharmaceutical Sciences, Teikyo University Itabashi-ku Tokyo 173-8605 Japan
| | - Sayuri Mototani
- Faculty of Pharmaceutical Sciences, Teikyo University Itabashi-ku Tokyo 173-8605 Japan
| | - Aileen Mendoza
- Institute for Chemical Research and Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Uji Kyoto 611-0011 Japan
| | - Yasushi Takemoto
- Institute for Chemical Research and Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Uji Kyoto 611-0011 Japan
| | - Motonari Uesugi
- Institute for Chemical Research and Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Uji Kyoto 611-0011 Japan
- School of Pharmacy, Fudan University Shanghai 201203 China
| | - Atsushi Kittaka
- Faculty of Pharmaceutical Sciences, Teikyo University Itabashi-ku Tokyo 173-8605 Japan
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20
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Gao M, Liu M, Chen J, Zhu Z, Chen H. Association of serum 25-hydroxyvitamin D concentrations with all-cause mortality among individuals with kidney stone disease: the NHANES database prospective cohort study. Front Endocrinol (Lausanne) 2023; 14:1207943. [PMID: 37854198 PMCID: PMC10579890 DOI: 10.3389/fendo.2023.1207943] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 09/08/2023] [Indexed: 10/20/2023] Open
Abstract
Background The purpose of this study was to investigate the correlation between serum 25(OH)D concentrations and all-cause mortality in patients with kidney stone disease (KSD) as the effects of a deficiency in 25-hydroxyvitamin D on KSD patients are currently unclear. Methods For our prospective cohort study, we included 2,916 participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The National Death Index (NDI) was utilized to identify all causes of death and cause-specific mortality until December 31, 2018. We calculated hazard ratios (HR) and 95% confidence intervals (CIs) using multivariate Cox regression models. Results During the 18,859 person-years of follow-up, a total of 375 fatalities occurred, including 83 deaths from cardiovascular disease (CVD) and 79 deaths from cancer. At baseline, individuals with higher blood 25(OH)D concentrations had lower levels of glucose, glycohemoglobin, CRP, and insulin, as well as higher levels of HDL cholesterol (P < 0.01). In the fully adjusted model (Model 3), compared to the group with the lowest 25(OH)D concentrations, those with serum 25(OH)D concentrations ≥75 nmol/L had hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.48 (0.26, 0.87) for all-cause mortality (P=0.02, P for trend = 0.02). The association between serum 25(OH)D concentrations and all-cause mortality in KSD patients was found to be significantly non-linear. A 7% decrease in the risk of death from all causes was observed for each unit-nmol/L increase in serum 25(OH)D concentrations when the concentrations were below 27.7 nmol/L (P < 0.05). Conclusion Based on the findings, KSD patients with insufficient serum 25(OH)D concentrations were at a higher risk of all-cause mortality. Therefore, it is crucial to maintain sufficient blood 25(OH)D concentrations and prevent 25(OH)D insufficiency in order to extend the lifespan of KSD patients.
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Affiliation(s)
- Meng Gao
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Minghui Liu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Zewu Zhu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Hequn Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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21
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Mehrani Y, Morovati S, Tieu S, Karimi N, Javadi H, Vanderkamp S, Sarmadi S, Tajik T, Kakish JE, Bridle BW, Karimi K. Vitamin D Influences the Activity of Mast Cells in Allergic Manifestations and Potentiates Their Effector Functions against Pathogens. Cells 2023; 12:2271. [PMID: 37759494 PMCID: PMC10528041 DOI: 10.3390/cells12182271] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/11/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Mast cells (MCs) are abundant at sites exposed to the external environment and pathogens. Local activation of these cells, either directly via pathogen recognition or indirectly via interaction with other activated immune cells and results in the release of pre-stored mediators in MC granules. The release of these pre-stored mediators helps to enhance pathogen clearance. While MCs are well known for their protective role against parasites, there is also significant evidence in the literature demonstrating their ability to respond to viral, bacterial, and fungal infections. Vitamin D is a fat-soluble vitamin and hormone that plays a vital role in regulating calcium and phosphorus metabolism to maintain skeletal homeostasis. Emerging evidence suggests that vitamin D also has immunomodulatory properties on both the innate and adaptive immune systems, making it a critical regulator of immune homeostasis. Vitamin D binds to its receptor, called the vitamin D receptor (VDR), which is present in almost all immune system cells. The literature suggests that a vitamin D deficiency can activate MCs, and vitamin D is necessary for MC stabilization. This manuscript explores the potential of vitamin D to regulate MC activity and combat pathogens, with a focus on its ability to fight viruses.
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Affiliation(s)
- Yeganeh Mehrani
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada; (Y.M.); (S.T.); (S.V.); (J.E.K.)
- Department of Clinical Sciences, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad 91779-48974, Iran;
| | - Solmaz Morovati
- Division of Biotechnology, Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz 71557-13876, Iran;
| | - Sophie Tieu
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada; (Y.M.); (S.T.); (S.V.); (J.E.K.)
| | - Negar Karimi
- Department of Clinical Sciences, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad 91779-48974, Iran;
| | - Helia Javadi
- Department of Medical Sciences, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 3K7, Canada;
| | - Sierra Vanderkamp
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada; (Y.M.); (S.T.); (S.V.); (J.E.K.)
| | - Soroush Sarmadi
- Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran 14174-66191, Iran;
| | - Tahmineh Tajik
- Department of Pathobiology, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad 91779-48974, Iran;
| | - Julia E. Kakish
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada; (Y.M.); (S.T.); (S.V.); (J.E.K.)
| | - Byram W. Bridle
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada; (Y.M.); (S.T.); (S.V.); (J.E.K.)
| | - Khalil Karimi
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada; (Y.M.); (S.T.); (S.V.); (J.E.K.)
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22
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Daryabor G, Gholijani N, Kahmini FR. A review of the critical role of vitamin D axis on the immune system. Exp Mol Pathol 2023; 132-133:104866. [PMID: 37572961 DOI: 10.1016/j.yexmp.2023.104866] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 08/05/2023] [Accepted: 08/08/2023] [Indexed: 08/14/2023]
Abstract
In recent years, the physiological and molecular functions of vitamin D (Vit-D) have been deeply investigated. At first, Vit-D was considered a regulator of mineral and skeletal homeostasis. However, due to the extensive-expression pattern of Vit-D receptor (VDR) in almost every non-skeletal cell, Vit-D is considered mainly a multifunctional agent with broad effects on various tissues, notably the immune system. The expression of VDR in immune cells such as dendritic cells, monocyte/macrophage, neutrophils, B cells and T cells has been well demonstrated. Besides, such immune cells are capable of metabolizing the active form of Vit-D which means that it can module the immune system in both paracrine and autocrine manners. Vit-D binding protein (DBP), that regulates the levels and homeostasis of Vit-D, is another key molecule capable of modulating the immune system. Recent studies indicate that dysregulation of Vit-D axis, variations in the DBP and VDR genes, and Vit-D levels might be risk factors for the development of autoimmune disease. Here, the current evidence regarding the role of Vit-D axis on the immune system, as well as its role in the development of autoimmune disease will be clarified. Further insight will be given to those studies that investigated the association between single nucleotide polymorphisms of DBP and VDR genes with autoimmune disease susceptibility.
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Affiliation(s)
- Gholamreza Daryabor
- Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasser Gholijani
- Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Rezaei Kahmini
- Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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23
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Abo-Amer YEE, Mohamed AA, Elhoseeny MM, Rezk SM, Abdel-Salam S, Alrohaimi AH, Abdelgeliel AS, Alzahrani SS, Jafri I, Alqahtani LS, Fayad E, Fakhry M, Soliman MY. Association Between Vitamin D Receptor Polymorphism and the Response to Helicobacter Pylori Treatment. Infect Drug Resist 2023; 16:4463-4469. [PMID: 37449247 PMCID: PMC10337687 DOI: 10.2147/idr.s414186] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/10/2023] [Indexed: 07/18/2023] Open
Abstract
Background & Aims This research aimed to determine how variations in the vitamin D receptor gene affected the response of H. pylori infections to eradication therapy. Patients and Methods On 105 adult H. Pylori-positive patients, a prospective cohort study was carried out. PCR was used to genotype all patients' VDR gene polymorphisms. The patients in the study received standard triple eradication medication (clarithromycin 500 mg, amoxicillin 1000 mg, and omeprazole 20 mg) twice daily for 14 days. A stool test for H. pylori Ag was conducted 4 weeks following the end of treatment. Results In our study, the usual triple therapy's H. pylori eradication rate was 75.2%. The successful eradication of H. pylori and VDR rs 2228570 gene polymorphisms was more prevalent in CT gene polymorphism (64.6%) compared to non-responders (19.2%), while treatment failure was more prevalent in CC gene polymorphism (73.1% in non-responders compared to responders 24.1%), which is statistically significant. In regards to the eradication of H. pylori and VDR rs7975232 gene polymorphisms, the success of eradication was more prevalent in AC gene polymorphism (54.4%) vs non-responders (30.4%), while all patients (14) with gene AA (17.7%) are responders to standard treatment, while the failure of treatment was more prevalent in CC gene polymorphism (69.2% in non-responder vs 27.8% in responders) which is statistically significant. Our findings demonstrated a strong correlation between patients' responses to H. pylori treatment and polymorphisms in the VDR gene (ApaI and TaqI) (P 0.05). Conclusion As far as we are aware, this is the first study to identify a potential link between the FokI and Apal VDR polymorphism and treatment response in H pylori-positive patients. To evaluate the findings, more research with larger number of patients and different population is required.
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Affiliation(s)
| | - Amal Ahmed Mohamed
- National Hepatology & Tropical Medicine Research Institute, Department of Biochemistry, Cairo, Egypt
| | | | - Samar M Rezk
- Department of Clinical Nutrition, Mahalla Hepatology Teaching Hospital, El-Mahalla El-Kubra, Elgharbia, Egypt
| | - Sherief Abdel-Salam
- Department of Tropical Medicine, Hepatology & Gastroenterology Unit, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Abdulmohsen H Alrohaimi
- Department of Pharmacy Practice, College of Pharmacy, Shaqra University, Shaqra, 11961, Saudi Arabia
| | - Asmaa Sayed Abdelgeliel
- Department of Botany & Microbiology, Faculty of Science, South Valley University, Qena, 83523, Egypt
| | - Seham Saeed Alzahrani
- Department of Biotechnology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Ibrahim Jafri
- Department of Biotechnology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Leena S Alqahtani
- Department of Biochemistry, College of Science, University of Jeddah, Jeddah, 23445, Saudi Arabia
| | - Eman Fayad
- Department of Biotechnology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Mohamed Fakhry
- Department of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Asyut, Egypt
| | - Moataz Yousry Soliman
- Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
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Ciarambino T, Crispino P, Minervini G, Giordano M. Vitamin D: Can Gender Medicine Have a Role? Biomedicines 2023; 11:1762. [PMID: 37371857 PMCID: PMC10296422 DOI: 10.3390/biomedicines11061762] [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: 04/19/2023] [Revised: 06/15/2023] [Accepted: 06/19/2023] [Indexed: 06/29/2023] Open
Abstract
This narrative review aims to shed light on the role of gender differences, on the biological and molecular functions in the main pathological mechanisms that recognize the role of vitamin D. Vitamin D deficiency is widespread worldwide, but it is still very controversial whether the amount of vitamin D taken daily is actually the only problem related to its biological functions. Currently, the plasma concentration of 25-hydroxyvitamin D represents the only indicator of the circulating blood quota. The concept is that the biological function of vitamin D is not only linked to its circulating levels, but it is hypothesized that its biological functions depend, above all, on its total bioavailability. In particular, vitamin D circulates for the most part linked to albumin and vitamin D binding protein (DBP), which depend on various pathological conditions and physiologically, above all, the function of the latter is regulated by estrogens, glucocorticoids, and inflammatory cytokines. During her life, women undergo various changes in the hormonal and sexual sphere concerning menarche, possible pregnancies, and breastfeeding but also the use of contraceptives and, finally, the transition from the period of fertility to menopause. Each of these phases presents specific needs and, consequently, sometimes also specific criticalities. Studies on young women have shown that vitamin D deficiency is present in 58 to 91% of cases. Obesity, metabolic disorders, and variation in estrogen contraction may affect vitamin D deficiency due to the decreased bioavailability from dietary sources due to deposition in body fat compartments.
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Affiliation(s)
- Tiziana Ciarambino
- Internal Medicine Department, Hospital of Marcianise, ASL Caserta, 81037 Caserta, Italy
| | - Pietro Crispino
- Internal Medicine Department, Hospital of Latina, ASL Latina, 04100 Latina, Italy
| | - Giovanni Minervini
- Emergency Department, Hospital of Lagonegro, AOR San Carlo, 85042 Lagonegro, Italy
| | - Mauro Giordano
- Advanced Medical and Surgical Sciences Department, University of Campania, L. Vanvitelli, 81100 Naples, Italy;
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Liu MC, Weng PW, Chen SC, Liu TH, Huang HW, Huang CT, Yang CT, Mishra VK, Yang MT. Immunologic, Anti-Inflammatory, and Anti-Muscle Damage Profile of Supplemented Vitamin D 3 in Healthy Adults on Strenuous Endurance Exercise. BIOLOGY 2023; 12:biology12050657. [PMID: 37237471 DOI: 10.3390/biology12050657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 04/19/2023] [Accepted: 04/25/2023] [Indexed: 05/28/2023]
Abstract
Reportedly, strenuous endurance exercise can depress the immune system and induce inflammation and muscle damage. Therefore, this double-blinded, matched-pair study aimed to investigate the impact of vitamin D3 supplementation on immune response (leukocyte, neutrophil, lymphocyte, CD4+, CD8+, CD19+, and CD56+ counts), inflammatory profile (TNF-α and IL-6), muscle damage (CK and LDH levels), as well as aerobic capacity after strenuous endurance exercise in 18 healthy men taking 5000 IU of vitamin D3 (n = 9) or placebo (n = 9) daily for 4 weeks. Total and differential blood leukocyte counts, levels of cytokines, and muscle damage biomarkers were determined before, immediately after, and 2, 4, and 24 h after exercise. The IL-6, CK, and LDH levels were significantly lower in vitamin D3 group at 2, 4, and 24 h post exercise (p < 0.05). Maximal and average heart rates during exercise were also significantly lower (p < 0.05). In the vitamin D3 group, the CD4+/CD8+ ratio after 4 weeks of supplementation was only significantly lower at post-0 than at baseline and significantly higher at post-2 than at baseline and post-0 (all p < 0.05). Taken together, 5000 IU of daily vitamin D3 supplementation for 4 weeks exhibited positive effects in terms of increased blood 25(OH)D levels, CD4+/CD8+ ratio (immune response), and aerobic capacity while inhibiting inflammatory cytokines and CK and LDH (muscle damage) in people performing strenuous endurance exercise.
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Affiliation(s)
- Ming-Che Liu
- School of Dental Technology, Taipei Medical University, Taipei 110301, Taiwan
- Clinical Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan
- Department of Urology, Taipei Medical University Hospital, Taipei 110301, Taiwan
- Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 110301, Taiwan
- Research Center of Urology and Kidney, Taipei Medical University, Taipei 110301, Taiwan
| | - Pei-Wei Weng
- School of Medicine, Taipei Medical University, Taipei 110301, Taiwan
- Department of Orthopaedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, Taiwan
- International Ph.D. Program in Biomedical Engineering, Taipei Medical University, Taipei 110301, Taiwan
| | - Sheng-Chang Chen
- School of Medicine, Taipei Medical University, Taipei 110301, Taiwan
| | - Ting-Hao Liu
- Center for General Education, Taipei Medical University, Taipei 110301, Taiwan
| | - Hsiang-Wei Huang
- Department of Medical Education, E-DA Hospital, Kaohsiung 824005, Taiwan
| | - Chang-Ti Huang
- Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 110301, Taiwan
| | - Cheng-Tse Yang
- Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 110301, Taiwan
| | | | - Ming-Ta Yang
- Clinical Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan
- Center for General Education, Taipei Medical University, Taipei 110301, Taiwan
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The Effect of Weekly 50,000 IU Vitamin D 3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency. Nutrients 2023; 15:nu15051188. [PMID: 36904187 PMCID: PMC10005440 DOI: 10.3390/nu15051188] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/03/2023] Open
Abstract
This research aimed to evaluate the effects of high-dose cholecalciferol (VD3) supplements (50,000 IU/week) on selected circulating cytokines associated with cytokine storms in adults with vitamin D deficiency. This clinical trial, based in Jordan, included 50 participants receiving vitamin D3 supplements (50,000 IU/week) for 8 weeks; the exact number was assigned to the control group. Interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrotic factor-α (TNF-α), and leptin were measured in serum at baseline and 10 weeks (wash out: 2 weeks). Our results revealed that vitamin D3 supplementation significantly increased the serum levels of 25OHD, IL-6, IL-10, IL-1β, and leptin compared with baseline. In contrast, the serum level of TNF-α insignificantly increased in the group receiving vitamin D3 supplementation. Although the observations of this trial may refer to a potential negative effect of VD3 supplementation during cytokine storms, further trials are required to clarify the potential benefits of VD3 supplement during cytokine storms.
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Evaluation of biochemical variables in patients with recurrent aphthous stomatitis. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2023; 124:101294. [PMID: 36162803 DOI: 10.1016/j.jormas.2022.09.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/09/2022] [Accepted: 09/20/2022] [Indexed: 11/21/2022]
Abstract
PURPOSE We investigated the effects of various biochemical agents on the etiopathogenesis of recurrent aphthous stomatitis (RAS). METHODS We enrolled 70 RAS patients and 70 healthy volunteers. Peripheral venous blood samples were collected. We performed complete blood counts, then measured the levels of ferritin, vitamin B12, iron, magnesium, phosphorus, calcium, thyroid-stimulating hormone, T3, T4, and 25-hydroxy D3. RESULTS The groups did not differ in terms of age (p = 0.912) or sex (p = 0.612). The levels of ferritin and 25-hydroxy vitamin D were significantly lower in RAS patients (both p ˂ 0.05). CONCLUSION Vitamin D and/or ferritin deficiency may induce RAS. Measurements of vitamin D and ferritin may assist diagnosis and follow-up.
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Plantone D, Primiano G, Manco C, Locci S, Servidei S, De Stefano N. Vitamin D in Neurological Diseases. Int J Mol Sci 2022; 24:87. [PMID: 36613531 PMCID: PMC9820561 DOI: 10.3390/ijms24010087] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/16/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Vitamin D may have multiple effects on the nervous system and its deficiency can represent a possible risk factor for the development of many neurological diseases. Recent studies are also trying to clarify the different effects of vitamin D supplementation over the course of progressive neurological diseases. In this narrative review, we summarise vitamin D chemistry, metabolism, mechanisms of action, and the recommended daily intake. The role of vitamin D on gene transcription and the immune response is also reviewed. Finally, we discuss the scientific evidence that links low 25-hydroxyvitamin D concentrations to the onset and progression of severe neurological diseases, such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, migraine, diabetic neuropathy and amyotrophic lateral sclerosis. Completed and ongoing clinical trials on vitamin D supplementation in neurological diseases are listed.
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Affiliation(s)
- Domenico Plantone
- Centre for Precision and Translational Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Guido Primiano
- Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Carlo Manco
- Centre for Precision and Translational Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Sara Locci
- Centre for Precision and Translational Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Serenella Servidei
- Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Nicola De Stefano
- Centre for Precision and Translational Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
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Abdrabbo AlYafei N, Fathima Jaleel BN, Abdel-Salam ASG, Ali Al-Saadi H, Al Abdulla SA. Association of Serum Vitamin D level and COVID-19 infection: A Case-control Study. Qatar Med J 2022; 2022:48. [PMID: 36504923 PMCID: PMC9720159 DOI: 10.5339/qmj.2022.48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 08/22/2022] [Indexed: 12/07/2022] Open
Abstract
BACKGROUND Vitamin D is considered a potent modulator of the immune system, albeit its role in COVID-19 infection is a matter of debate. The present study aimed to estimate the association between serum vitamin D levels and COVID-19 among people in Qatar. METHODS This case-control study, approved by the Institutional Review Board of Primary Health Care Corporation (PHCC) Qatar, retrospectively evaluated the principal public healthcare sector population data repository retrieved from the cloud-based Electronic Health Record (EHR) software-Cerner, during April 2020-2021. The health records of all adult patients aged >18 years who had undergone the reverse transcription-polymerase chain reaction (RT-PCR) test and whose medical records had documented serum 25-hydroxyvitamin D [25 (OH)D] levels were analyzed. RESULTS A total of 924,173 EHRs were extracted, of which 62,451 EHR comprised of 16,446 (26.3%) COVID-19 patients and 46,005 (73.7%) negative-control group patients met the inclusion criteria. The odds ratio (OR) among different categories of vitamin D deficiency (VDD) revealed that people with mild/moderate VDD were 1.18 times (95% CI 1.126-1.258) and those with severe VDD were 1.90 times (95% CI 1.116-1.251) more likely to have COVID-19 infection when compared to the people with optimal serum vitamin D level. On applying multiple logistic regression, the odds of having COVID-19 infection were found to be 1.27 times (95% CI 1.184-1.371) higher among those with mild/moderate VDD and 1.32 times (95% CI 1.206-1.405) higher among those with severe VDD when compared to people with optimal vitamin D level (p < 0.001). CONCLUSION Our findings demonstrated a significant association between the suboptimal serum vitamin D level and COVID-19 infection. Further studies are required to determine the effects of VDD on the severity and outcomes of COVID-19 infections.
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Affiliation(s)
- Najat Abdrabbo AlYafei
- Primary Health Care Corporation, Qatar. Email & ORCID ID: & https://orcid.org/0000-0002-8071-3646
| | | | - Abdel-Salam G Abdel-Salam
- Department of Mathmatics, Statistics and Physics, College of Art and Sciences, Qatar unitversity, Doha, Box. 2713, Qatar
| | - Hamda Ali Al-Saadi
- Primary Health Care Corporation, Qatar. Email & ORCID ID: & https://orcid.org/0000-0002-8071-3646
| | - Samya Ahmad Al Abdulla
- Primary Health Care Corporation, Qatar. Email & ORCID ID: & https://orcid.org/0000-0002-8071-3646
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Effect of vitamin D receptor gene polymorphisms on the risk of chronic and aggressive periodontitis: A systematic review and meta-analysis of the Chinese population. Arch Oral Biol 2022; 144:105566. [DOI: 10.1016/j.archoralbio.2022.105566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 09/27/2022] [Accepted: 09/30/2022] [Indexed: 11/18/2022]
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Al-Jaberi FAH, Crone CG, Lindenstrøm T, Arildsen NS, Lindeløv ES, Aagaard L, Gravesen E, Mortensen R, Andersen AB, Olgaard K, Hjaltelin JX, Brunak S, Bonefeld CM, Kongsbak-Wismann M, Geisler C. Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report. Front Immunol 2022; 13:1038960. [PMID: 36405761 PMCID: PMC9672840 DOI: 10.3389/fimmu.2022.1038960] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 10/18/2022] [Indexed: 01/11/2025] Open
Abstract
Tuberculosis (TB) presents a serious health problem with approximately a quarter of the world's population infected with Mycobacterium tuberculosis (M. tuberculosis) in an asymptomatic latent state of which 5-10% develops active TB at some point in their lives. The antimicrobial protein cathelicidin has broad antimicrobial activity towards viruses and bacteria including M. tuberculosis. Vitamin D increases the expression of cathelicidin in many cell types including macrophages, and it has been suggested that the vitamin D-mediated antimicrobial activity against M. tuberculosis is dependent on the induction of cathelicidin. However, unraveling the immunoregulatory effects of vitamin D in humans is hampered by the lack of suitable experimental models. We have previously described a family in which members suffer from hereditary vitamin D-resistant rickets (HVDRR). The family carry a mutation in the DNA-binding domain of the vitamin D receptor (VDR). This mutation leads to a non-functional VDR, meaning that vitamin D cannot exert its effect in family members homozygous for the mutation. Studies of HVDRR patients open unique possibilities to gain insight in the immunoregulatory roles of vitamin D in humans. Here we describe the impaired ability of macrophages to produce cathelicidin in a HVDRR patient, who in her adolescence suffered from extrapulmonary TB. The present case is a rare experiment of nature, which illustrates the importance of vitamin D in the pathophysiology of combating M. tuberculosis.
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Affiliation(s)
- Fatima A. H. Al-Jaberi
- The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Cornelia Geisler Crone
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Lindenstrøm
- Department of infectious disease immunology, Statens Serum Institut, Copenhagen, Denmark
| | - Nicolai Skovbjerg Arildsen
- The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Emilia Sæderup Lindeløv
- The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Louise Aagaard
- The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Eva Gravesen
- Department of Nephrology, University of Copenhagen, Rigshospitalet and Faculty of Health and Medical Sciences, Copenhagen, Denmark
| | - Rasmus Mortensen
- Department of infectious disease immunology, Statens Serum Institut, Copenhagen, Denmark
| | - Aase Bengaard Andersen
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Klaus Olgaard
- Department of Nephrology, University of Copenhagen, Rigshospitalet and Faculty of Health and Medical Sciences, Copenhagen, Denmark
| | - Jessica Xin Hjaltelin
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
| | - Søren Brunak
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
| | - Charlotte Menné Bonefeld
- The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Martin Kongsbak-Wismann
- The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Carsten Geisler
- The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Clinical Effect of Preoperative 25-OH-Vitamin D3 Level in Liver Transplant Recipients. Transplant Proc 2022; 54:2301-2306. [DOI: 10.1016/j.transproceed.2022.08.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/02/2022] [Accepted: 08/26/2022] [Indexed: 11/07/2022]
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Xiao M, Yang S, Zhou A, Li T, Liu J, Chen Y, Luo Y, Qian C, Yang F, Tang B, Li C, Su N, Li J, Jiang M, Yang S, Lin H. MiR-27a-3p and miR-30b-5p inhibited-vitamin D receptor involved in the progression of tuberculosis. Front Microbiol 2022; 13:1020542. [PMID: 36304947 PMCID: PMC9593098 DOI: 10.3389/fmicb.2022.1020542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 09/20/2022] [Indexed: 11/28/2022] Open
Abstract
Background MicroRNAs (miRNAs) play a vital role in tuberculosis (TB). Vitamin D receptor (VDR), an miRNA target gene, and its ligand, vitamin D3 (VitD3), have been reported to exert protective effects against TB. However, whether miRNAs can affect the progression of TB by targeting VDR has not been reported. Materials and methods Research subjects were selected according to defined inclusion criteria. A clinical database of 360 samples was established, including the subjects’ demographic information, miRNA expression profiles and cellular experimental results. Two candidate miRNAs, miR-27a-3p, and miR-30b-5p, were identified by a high-throughput sequencing screen and validated by qRT–PCR assays. Univariate and multivariate statistical analyses were performed. VDR and NF-kB p65 protein levels were detected by Western blot assays. Proinflammatory cytokine expression levels were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase assays and fluorescence-activated cell sorting (FACS) were further applied to elucidate the detailed mechanisms. Results Differential miRNA expression profiles were obtained, and miR-27a-3p and miR-30b-5p were highly expressed in patients with TB. These results showed that the two miRNAs were able to induce M1 macrophage differentiation and inhibit M2 macrophage differentiation. Further experiments showed that the two miRNAs decreased the VDR protein level and increased proinflammatory cytokine secretion by macrophages. Mechanistically, the miRNAs targeted the 3′ untranslated region (3′UTR) of the VDR mRNA and thereby downregulated VDR protein levels by post-transcriptional regulation. Then, due to the reduction in VDR protein levels, the NF-kB inflammatory cytokine signaling pathway was activated, thus promoting the progression of TB. Conclusion Our study not only identified differentially expressed miRNAs between the TB and control groups but also revealed that miR-27a-3p and miR-30b-5p regulate proinflammatory cytokine secretion and macrophage differentiation through VDR in macrophages. Thus, these two miRNAs influence the progression of TB.
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Affiliation(s)
- Min Xiao
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Song Yang
- Chongqing Public Health Medical Center, Southwest University, Chongqing, China
| | - An Zhou
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Tongxin Li
- Chongqing Public Health Medical Center, Southwest University, Chongqing, China
| | - Jingjing Liu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Yang Chen
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Ya Luo
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Chunfang Qian
- Chongqing Public Health Medical Center, Southwest University, Chongqing, China
| | - Fuping Yang
- Chongqing Public Health Medical Center, Southwest University, Chongqing, China
| | - Bo Tang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Chunhua Li
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Na Su
- Chongqing Public Health Medical Center, Southwest University, Chongqing, China
| | - Jing Li
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Mingying Jiang
- Chongqing Public Health Medical Center, Southwest University, Chongqing, China
- *Correspondence: Mingying Jiang,
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
- Shiming Yang,
| | - Hui Lin
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
- Hui Lin,
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Mărginean CO, Meliț LE, Borka Balas R, Văsieșiu AM, Fleșeriu T. The Crosstalk between Vitamin D and Pediatric Digestive Disorders. Diagnostics (Basel) 2022; 12:diagnostics12102328. [PMID: 36292016 PMCID: PMC9600444 DOI: 10.3390/diagnostics12102328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/18/2022] [Accepted: 09/23/2022] [Indexed: 11/22/2022] Open
Abstract
Vitamin D is a cyclopentane polyhydrophenanthrene compound involved mainly in bone health and calcium metabolism but also autophagy, modulation of the gut microbiota, cell proliferation, immune functions and intestinal barrier integrity. The sources of vitamin D include sunlight, diet and vitamin D supplements. Vitamin D3, the most effective vitamin D isoform is produced in the human epidermis as a result of sunlight exposure. Vitamin D undergoes two hydroxylation reactions in the liver and kidney to reach its active form, 1,25-dihydroxyvitamin D. Recent studies highlighted a complex spectrum of roles regarding the wellbeing of the gastrointestinal tract. Based on its antimicrobial effect, it was recently indicated that vitamin D supplementation in addition to standard eradication therapy might enhance H. pylori eradication rates. Moreover, it was suggested that low levels of vitamin D might also be involved in the acquisition of H. pylori infection. In terms of celiac disease, the negative effects of vitamin D deficiency might begin even during intrauterine life in the setting of maternal deficiency. Moreover, vitamin D is strongly related to the integrity of the gut barrier, which represents the core of the pathophysiology of celiac disease onset, in addition to being correlated with the histological findings of disease severity. The relationship between vitamin D and cystic fibrosis is supported by the involvement of this micronutrient in preserving lung function by clearing airway inflammation and preventing pathogen airway colonization. Moreover, this micronutrient might exert anticatabolic effects in CF patients. Inflammatory bowel disease patients also experience major benefits if they have a sufficient level of circulating vitamin D, proving its involvement in both induction and remission in these patients. The findings regarding the relationship between vitamin D, food allergies, diarrhea and constipation remain controversial, but vitamin D levels should be monitored in these patients in order to avoid hypo- and hypervitaminosis. Further studies are required to fill the remaining gaps in term of the complex impact of vitamin D on gastrointestinal homeostasis.
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Affiliation(s)
- Cristina Oana Mărginean
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No 38, 540136 Târgu Mureș, Romania
| | - Lorena Elena Meliț
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No 38, 540136 Târgu Mureș, Romania
- Correspondence:
| | - Reka Borka Balas
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No 38, 540136 Târgu Mureș, Romania
| | - Anca Meda Văsieșiu
- Department of Infectious Disease, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No 38, 540136 Târgu Mureș, Romania
| | - Tudor Fleșeriu
- Department of Infectious Disease, County Clinical Hospital Târgu Mureș, Gheorghe Doja Street No 89, 540394 Târgu Mureș, Romania
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Crescioli C. Vitamin D, exercise, and immune health in athletes: A narrative review. Front Immunol 2022; 13:954994. [PMID: 36211340 PMCID: PMC9539769 DOI: 10.3389/fimmu.2022.954994] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 08/22/2022] [Indexed: 11/23/2022] Open
Abstract
Vitamin D exerts important extra-skeletal effects, exhibiting an exquisite immune regulatory ability, affecting both innate and adaptive immune responses through the modulation of immunocyte function and signaling. Remarkably, the immune function of working skeletal muscle, which is fully recognized to behave as a secretory organ with immune capacity, is under the tight control of vitamin D as well. Vitamin D status, meaning hormone sufficiency or insufficiency, can push toward strengthening/stabilization or decline of immune surveillance, with important consequences for health. This aspect is particularly relevant when considering the athletic population: while exercising is, nowadays, the recommended approach to maintain health and counteract inflammatory processes, “too much” exercise, often experienced by athletes, can increase inflammation, decrease immune surveillance, and expose them to a higher risk of diseases. When overexercise intersects with hypovitaminosis D, the overall effects on the immune system might converge into immune depression and higher vulnerability to diseases. This paper aims to provide an overview of how vitamin D shapes human immune responses, acting on the immune system and skeletal muscle cells; some aspects of exercise-related immune modifications are addressed, focusing on athletes. The crossroad where vitamin D and exercise meet can profile whole-body immune response and health.
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Dai T, Jiao L, Tao X, Lu J, Jin M, Sun P, Zhou Q. Effects of dietary vitamin D 3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae. Br J Nutr 2022; 128:793-801. [PMID: 34879881 DOI: 10.1017/s0007114521004931] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
An 8-week feeding trial was conducted to investigate the effects of dietary vitamin D3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae. A total of 720 shrimp (initial weight 0·50 ± 0·01 g) were randomly distributed into six treatments, each of which had three duplicates of forty shrimp per duplicate. Six isonitrogenous and isolipidic diets were formulated to contain graded vitamin D3 (0·18, 0·23, 0·27, 0·48, 0·57 and 0·98 mg/kg of vitamin D3, measured) supplementation levels. The results revealed that L. vannamei fed diet containing 0·48 mg/kg of vitamin D3 achieved the best growth performance. Compared with the control group, supplementing 0·48 mg/kg of vitamin D3 significantly increased (P < 0·05) the activities of catalase, total antioxidative capacity, alkaline phosphatase and acid phosphatase in serum and hepatopancreas. Expression levels of antioxidant and immune-related genes were synchronously increased (P < 0·05). Carapace P and Ca concentrations were increased (P < 0·05) with the increased vitamin D3 supplementation levels. Further analysis of lipid metabolism-related genes expression showed that shrimp fed 0·48 mg of vitamin D3 per kg diet showed the highest value in the expression of lipid synthesis-related genes, while shrimp fed 0·98 mg of vitamin D3 per kg diet showed the highest value in the expression of lipolysis-related genes. In conclusion, the results of present study indicated that dietary supplementation of 0·48 mg/kg of vitamin D3 could increase Ca and P concentrations, improve antioxidant capacity and immune response, and influence lipid metabolism in L. vannamei.
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Affiliation(s)
- Tianmeng Dai
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Lefei Jiao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Xinyue Tao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Jingjing Lu
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Min Jin
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Peng Sun
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Qicun Zhou
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
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Yang J, Chen D, Tian G, Mao X, He J, Zheng P, Yu J, Luo Y, Luo J, Huang Z, Wu A, Yan H, Yu B. 1,25-Dihydroxyvitamin D3 Negatively Regulates the Inflammatory Response to Porcine Epidemic Diarrhea Virus Infection by Inhibiting NF-κB and JAK/STAT Signaling Pathway in IPEC-J2 Porcine Epithelial Cells. Int J Mol Sci 2022; 23:ijms231810603. [PMID: 36142545 PMCID: PMC9504568 DOI: 10.3390/ijms231810603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/06/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea and vomiting in piglets. The pathogenesis of PEDV infection is related to intestinal inflammation. It is known that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent anti-inflammatory activity, but it is unknown whether 1,25(OH)2D3 can inhibit the PEDV-induced inflammatory response and the underlying mechanism. We used transcriptome analysis, gene and protein expression, RNA interference and overexpression, and other techniques to study the anti-inflammatory effects of 1,25(OH)2D3 on PEDV infection in IPEC-J2 cells. The results showed that interleukin 19 (IL-19) and C-C motif chemokine ligand 20 (CCL20) gene expression were enhanced with the increase in PEDV infection time in IPEC-J2 cells. Interestingly, 1,25(OH)2D3 supplementation obviously inhibited IL-19 and CCL20 expression induced by PEDV. Meanwhile, we also found that 1,25(OH)2D3 reduced p-NF-κB, p-STAT1, and p-STAT3 protein levels induced by PEDV at 24 h post-infection. IκBα and SOCS3, NF-κB, and STAT inhibitor respectively, were increased by 1,25(OH)2D3 supplementation upon PEDV infection. In addition, 1,25(OH)2D3 supplementation inhibited ISG15 and MxA expression induced by PEDV. Although 1,25(OH)2D3 suppressed the JAK/STAT signal pathway and antiviral gene expression, it had no significant effects on PEDV replication and IFN-α-induced antiviral effects. In addition, when the vitamin D receptor (VDR) was silenced by siRNA, the anti-inflammatory effect of 1,25(OH)2D3 was inhibited. Meanwhile, the overexpression of VDR significantly downregulated IL-19 and CCL20 expression induced by PEDV infection. Together, our results provide powerful evidence that 1,25(OH)2D3 could alleviate PEDV-induced inflammation by regulating the NF-κB and JAK/STAT signaling pathways through VDR. These results suggest that vitamin D could contribute to inhibiting intestinal inflammation and alleviating intestinal damage in PEDV-infected piglets, which offers new approaches for the development of nutritional strategies to prevent PEDV infection in piglets.
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Megalin and Vitamin D Metabolism—Implications in Non-Renal Tissues and Kidney Disease. Nutrients 2022; 14:nu14183690. [PMID: 36145066 PMCID: PMC9506339 DOI: 10.3390/nu14183690] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/02/2022] [Accepted: 09/06/2022] [Indexed: 11/17/2022] Open
Abstract
Megalin is an endocytic receptor abundantly expressed in proximal tubular epithelial cells and other calciotropic extrarenal cells expressing vitamin D metabolizing enzymes, such as bone and parathyroid cells. The receptor functions in the uptake of the vitamin D-binding protein (DBP) complexed to 25 hydroxyvitamin D3 (25(OH)D3), facilitating the intracellular conversion of precursor 25(OH)D3 to the active 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). The significance of renal megalin-mediated reabsorption of 25(OH)D3 and 1,25(OH)2D3 has been well established experimentally, and other studies have demonstrated relevant roles of extrarenal megalin in regulating vitamin D homeostasis in mammary cells, fat, muscle, bone, and mesenchymal stem cells. Parathyroid gland megalin may regulate calcium signaling, suggesting intriguing possibilities for megalin-mediated cross-talk between calcium and vitamin D regulation in the parathyroid; however, parathyroid megalin functionality has not been assessed in the context of vitamin D. Within various models of chronic kidney disease (CKD), megalin expression appears to be downregulated; however, contradictory results have been observed between human and rodent models. This review aims to provide an overview of the current knowledge of megalin function in the context of vitamin D metabolism, with an emphasis on extrarenal megalin, an area that clearly requires further investigation.
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Røyrvik EC, Husebye ES. The genetics of autoimmune Addison disease: past, present and future. Nat Rev Endocrinol 2022; 18:399-412. [PMID: 35411072 DOI: 10.1038/s41574-022-00653-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/21/2022] [Indexed: 12/23/2022]
Abstract
Autoimmune Addison disease is an endocrinopathy that is fatal if not diagnosed and treated in a timely manner. Its rarity has hampered unbiased studies of the predisposing genetic factors. A 2021 genome-wide association study, explaining up to 40% of the genetic susceptibility, has revealed new disease loci and reproduced some of the previously reported associations, while failing to reproduce others. Credible risk loci from both candidate gene and genome-wide studies indicate that, like one of its most common comorbidities, type 1 diabetes mellitus, Addison disease is primarily caused by aberrant T cell behaviour. Here, we review the current understanding of the genetics of autoimmune Addison disease and its position in the wider field of autoimmune disorders. The mechanisms that could underlie the effects on the adrenal cortex are also discussed.
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Affiliation(s)
- Ellen C Røyrvik
- Department of Clinical Science, University of Bergen, Bergen, Norway.
- K.G. Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway.
| | - Eystein S Husebye
- Department of Clinical Science, University of Bergen, Bergen, Norway
- K.G. Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Zhang M, Huang X, Song M, Mi L, Yin Y, Wang F, Chen M, Zhang T, Yang J, Cui X. A novel LC-MS/MS method for the simultaneous analysis of selected fat-soluble vitamins in serum obtained from pediatric patients with pneumonia. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2022; 14:2511-2521. [PMID: 35703250 DOI: 10.1039/d2ay00491g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Several observational studies have reported associations between low levels of fat-soluble vitamins (A, D and E) and the incidence of pneumonia. Whether infection affects or negatively regulates serum vitamin levels remains controversial. Our aims were to develop and validate a simple-pretreatment and fast method to determine the serum levels of selected fat-soluble vitamins, namely vitamin A (retinol), vitamin D (25-OH-D3, 25-OH-D2, and 3-epi-25-OH-D3), and vitamin E (α-tocopherol), in children suffering from pneumonia during the acute phase and after inflammatory marker recovery. The sample preparation procedure involving protein precipitation and filtration was finished in one step, and separation took 8 min per sample. The calibrations were linear, with R2 > 0.99. Both the intra-run (n = 6) and inter-run (n = 3) precision (relative standard deviation, RSD%) values were below 14.61%. The spiked recoveries at 3 concentrations ranged from 80.97 to 111.91%. Accuracies were calibrated using both National Institute of Standards and Technology serum (NIST 968f) and external quality assurance (EQA) samples offered by the National Center of Clinical Laboratories of China, and the relative error (RE%) values ranged from -13.17% to 12.53%. Clinical sample analysis revealed that infection did alter the serum retinol concentration and it did not alter the 25-OH-D and α-tocopherol levels in young children with pneumonia.
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Affiliation(s)
- Min Zhang
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing 100020, China
| | - XiaoLan Huang
- Clinical Central Laboratory, Capital Institute of Pediatrics, Beijing 100020, China.
| | - MeiYan Song
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China
| | - Lala Mi
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China
| | - Yan Yin
- Department of Integrated Early Childhood Development, Capital Institute of Pediatrics, Beijing 100020, China
| | - Fang Wang
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing 100020, China
| | - Min Chen
- Clinical Central Laboratory, Capital Institute of Pediatrics, Beijing 100020, China.
| | - Ting Zhang
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing 100020, China
| | - Jian Yang
- Department of Neurology, Capital Institute of Pediatrics, Beijing 100020, China.
| | - XiaoDai Cui
- Clinical Central Laboratory, Capital Institute of Pediatrics, Beijing 100020, China.
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Buonsenso D, Pata D, Turriziani Colonna A, Ferrari V, Salerno G, Valentini P. Vitamin D and tuberculosis in children: a role in the prevention or treatment of the disease? Monaldi Arch Chest Dis 2022; 92. [PMID: 35352542 DOI: 10.4081/monaldi.2022.2112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 03/24/2022] [Indexed: 11/23/2022] Open
Abstract
Despite the growing number of published studies, the role of vitamin D in the prevention or treatment of tuberculosis remains unclear. In this review we analyze current scientific literature to provide evidence about the relationship between vitamin D and TB, with a special focus on the pediatric population. While in vitro studies have shown relevant antimycobacterial immune-stimulatory and immunosuppressive effects of vitamin D, this has not panned out in vivo with active TB. On the contrary, there is some evidence that this tool could work as prevention - both against TB infection as well as progression from latent to active infection. However, only a few studies have evaluated this correlation in children. The potential link between tuberculosis and vitamin D levels is promising. If effective, vitamin D supplementation of at-risk populations would be an affordable public health intervention, particularly in light of the worldwide increase in identified TB cases and drug-resistance. Vitamin D might represent a new, affordable, safe and easy to access drug for the prevention and treatment of TB. For stronger evidence, considering the features of infection (relative low incidence of reactivation of latent infection in immunocompetent patients) we need clinical trials with large numbers of participants conducted in endemic regions with a prolonged follow-up time.
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Affiliation(s)
- Danilo Buonsenso
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli", Rome.
| | - Davide Pata
- Institute of Pediatrics, Catholic University of Sacred Heart, Rome.
| | | | - Vittoria Ferrari
- Institute of Pediatrics, Catholic University of Sacred Heart, Rome.
| | - Gilda Salerno
- Institute of Pediatrics, Catholic University of Sacred Heart, Rome.
| | - Piero Valentini
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli", Rome; Institute of Pediatrics, Catholic University of Sacred Heart, Rome.
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Albergamo A, Apprato G, Silvagno F. The Role of Vitamin D in Supporting Health in the COVID-19 Era. Int J Mol Sci 2022; 23:3621. [PMID: 35408981 PMCID: PMC8998275 DOI: 10.3390/ijms23073621] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 02/06/2023] Open
Abstract
The genomic activity of vitamin D is associated with metabolic effects, and the hormone has a strong impact on several physiological functions and, therefore, on health. Among its renowned functions, vitamin D is an immunomodulator and a molecule with an anti-inflammatory effect, and, recently, it has been much studied in relation to its response against viral infections, especially against COVID-19. This review aims to take stock of the correlation studies between vitamin D deficiency and increased risks of severe COVID-19 disease and, similarly, between vitamin D deficiency and acute respiratory distress syndrome. Based on this evidence, supplementation with vitamin D has been tested in clinical trials, and the results are discussed. Finally, this study includes a biochemical analysis on the effects of vitamin D in the body's defense mechanisms against viral infection. In particular, the antioxidant and anti-inflammatory functions are considered in relation to energy metabolism, and the potential, beneficial effect of vitamin D in COVID-19 is described, with discussion of its influence on different biochemical pathways. The proposed, broader view of vitamin D activity could support a better-integrated approach in supplementation strategies against severe COVID-19, which could be valuable in a near future of living with an infection becoming endemic.
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Affiliation(s)
- Alice Albergamo
- Department of Oncology, University of Torino, 10126 Torino, Italy
| | - Giulia Apprato
- Department of Oncology, University of Torino, 10126 Torino, Italy
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Newton DA, Baatz JE, Chetta KE, Walker PW, Washington RO, Shary JR, Wagner CL. Maternal Vitamin D Status Correlates to Leukocyte Antigenic Responses in Breastfeeding Infants. Nutrients 2022; 14:1266. [PMID: 35334923 PMCID: PMC8952362 DOI: 10.3390/nu14061266] [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: 02/17/2022] [Revised: 03/10/2022] [Accepted: 03/15/2022] [Indexed: 02/04/2023] Open
Abstract
It is unknown if vitamin D (vitD) sufficiency in breastfeeding mothers can lead to physiological outcomes for their children that are discernible from infant vitD sufficiency per se. In a 3-month, randomized vitD supplementation study of mothers and their exclusively breastfeeding infants, the effects of maternal vitD sufficiency were determined on infant plasma concentrations of 25-hydroxyvitamin D (i.e., vitD status) and 11 cytokines. An inverse correlation was seen between maternal vitD status and infant plasma TNF concentration (r = −0.27; p < 0.05). Infant whole blood was also subjected to in vitro antigenic stimulation. TNF, IFNγ, IL-4, IL-13, and TGFβ1 responses by infant leukocytes were significantly higher if mothers were vitD sufficient but were not as closely correlated to infants’ own vitD status. Conversely, IL-10 and IL-12 responses after antigenic challenge were more correlated to infant vitD status. These data are consistent with vitD-mediated changes in breast milk composition providing immunological signaling to breastfeeding infants and indicate differential physiological effects of direct-infant versus maternal vitD supplementation. Thus, consistent with many previous studies that focused on the importance of vitD sufficiency during pregnancy, maintenance of maternal sufficiency likely continues to affect the health of breastfed infants.
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Affiliation(s)
- Danforth A. Newton
- Department of Pediatrics/Neonatology, Shawn Jenkins Children’s Hospital, Medical University of South Carolina, Charleston, SC 29425, USA; (J.E.B.); (K.E.C.); (P.W.W.); (R.O.W.); (J.R.S.); (C.L.W.)
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Influence of exercise and vitamin D on the immune system against Covid-19: an integrative review of current literature. Mol Cell Biochem 2022; 477:1725-1737. [PMID: 35258807 PMCID: PMC8902492 DOI: 10.1007/s11010-022-04402-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 02/23/2022] [Indexed: 10/26/2022]
Abstract
Respiratory infections of viral origin have become the leading cause of infectious diseases in the world. In 2020, the World Health Organization (WHO) declared a pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Coronavirus Disease 2019 (Covid-19). The pandemic caused by the new coronavirus has challenged the entire global health system, since Covid-19 has a high rate of morbidity and mortality. The immune response to the virus depends on factors such as age, genetics, nutritional status, physical status, as well as environmental factors. Despite scientific advances, so far, there is still no specific therapy for the disease. Thus, this study aims to analyze the contribution of physical exercise and maintenance and/or supplementation of vitamin D to the strengthening of the immune system against viral infections, among them, Covid-19. Regular practice of moderate-intensity physical activity is responsible for promoting a reduction in the concentrations of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β), as well as triggering the increase in the production of anti-inflammatory cytokines (IL-4 and IL-10). In addition, hypovitaminosis D predisposes to the development of chronic diseases and infections. Therefore, in patients affected by Covid-19, the maintenance of vitamin D levels contributes significantly to the 0prevention of the cytokine storm. Thus, the association between maintaining vitamin D levels and performing moderate-intensity physical exercise is responsible for strengthening the immune system and, therefore, triggering a defense mechanism against infections by intracellular microorganisms, in which SARS -CoV-2.
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Infante M, Buoso A, Pieri M, Lupisella S, Nuccetelli M, Bernardini S, Fabbri A, Iannetta M, Andreoni M, Colizzi V, Morello M. Low Vitamin D Status at Admission as a Risk Factor for Poor Survival in Hospitalized Patients With COVID-19: An Italian Retrospective Study. J Am Coll Nutr 2022; 41:250-265. [PMID: 33600292 PMCID: PMC7899172 DOI: 10.1080/07315724.2021.1877580] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 01/08/2021] [Accepted: 01/12/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Preliminary findings suggest a relationship between lower serum 25-hydroxyvitamin D [25(OH)D] levels and incidence and severity of COVID-19. The aim of this study was to evaluate the relationship between vitamin D status at admission and different markers of inflammation, coagulation, and sepsis in hospitalized patients with COVID-19. METHOD We conducted a retrospective study on 137 consecutive patients with SARS-CoV-2 infection and available data on serum 25(OH)D levels, who were admitted to our Institution between March 1 and April 30, 2020. Patients were divided into two groups: survivors (n = 78; 57%) and non-survivors (n = 59; 43%). RESULTS At admission, all patients showed hypovitaminosis D. Median total serum 25(OH)D levels at admission were significantly higher in survivors than non-survivors (12 ng/mL vs 8 ng/mL; p < 0.01). Non-survivors exhibited significantly higher median levels of white blood cell (WBC) count, neutrophil-to-lymphocyte count ratio (NLR), high-sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6), D-dimer, fibrinogen, and procalcitonin (PCT) compared to survivors at three different time points during hospitalization. In a multivariate analysis performed by a logistic regression model, serum 25(OH)D levels were significantly inversely associated with risk of COVID-19-related in-hospital mortality (odds ratio, 0.91; 95% confidence interval, 0.85-0.98; p = 0.01). According to receiver operating characteristic curve analysis, hsCRP, NLR, ferritin, and D-dimer were the best predictive biomarkers for poor prognosis of COVID-19, whereas IL-6, PCT, fibrinogen, 25(OH)D, WBC count, and tumor necrosis factor alpha (TNF-α) may serve as supportive biomarkers for worse clinical course of the disease. CONCLUSIONS We found a markedly high prevalence (100%) of hypovitaminosis D in patients admitted to hospital with COVID-19, suggesting a possible role of low vitamin D status in increasing the risk of SARS-CoV-2 infection and subsequent hospitalization. The inverse association between serum 25(OH)D levels and risk of in-hospital mortality observed in our cohort suggests that a lower vitamin D status upon admission may represent a modifiable and independent risk factor for poor prognosis in COVID-19.
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Affiliation(s)
- Marco Infante
- Department of Systems Medicine, Diabetes Research Institute Federation (DRIF), CTO Hospital ASL Roma 2, University of Rome Tor Vergata, Rome, Italy
- UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Rome, Italy
| | - Andrea Buoso
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Infectious Disease Clinic, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Massimo Pieri
- Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Santina Lupisella
- Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Marzia Nuccetelli
- Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Sergio Bernardini
- Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Andrea Fabbri
- Department of Systems Medicine, Diabetes Research Institute Federation (DRIF), CTO Hospital ASL Roma 2, University of Rome Tor Vergata, Rome, Italy
| | - Marco Iannetta
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Infectious Disease Clinic, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Massimo Andreoni
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Infectious Disease Clinic, Tor Vergata University Hospital (PTV), Rome, Italy
| | - Vittorio Colizzi
- UNESCO Chair of Biotechnology & Bioethics, University of Rome Tor Vergata, Rome, Italy
| | - Maria Morello
- Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
- Clinical Biochemistry Department, Tor Vergata University Hospital (PTV), Rome, Italy
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Calcaterra V, Nappi RE, Farolfi A, Tiranini L, Rossi V, Regalbuto C, Zuccotti G. Perimenstrual Asthma in Adolescents: A Shared Condition in Pediatric and Gynecological Endocrinology. CHILDREN 2022; 9:children9020233. [PMID: 35204953 PMCID: PMC8870409 DOI: 10.3390/children9020233] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/04/2022] [Accepted: 02/07/2022] [Indexed: 12/12/2022]
Abstract
Asthma is a frequent medical condition in adolescence. The worsening of the most common symptoms perimenstrually is defined as perimenstrual asthma (PMA). The cause of PMA remains unclear, but a role for hormonal milieu is plausible. Data on PMA in adolescents are limited, and its management is not fully established. We aimed to discuss the PMA phenomenon in young females from pathophysiology to preventive strategies, focusing on the relationship with the hormonal pattern. The fluctuation of estrogens at ovulation and before menstruation and the progesterone secretion during the luteal phase and its subsequent withdrawal seem to be the culprits, because the deterioration of asthma is cyclical during the luteal phase and/or during the first days of the menstrual cycle. Conventional asthma therapies are not always effective for PMA. Preventive strategies may include innovative hormonal contraception. Even a possible beneficial effect of other hormonal treatments, including estrogens, progestogens, and androgens, as well as leukotriene receptor antagonists and explorative approach using microbial-directed therapy, is considered. The underlying mechanisms, through which sex-hormone fluctuations influence asthma symptoms, represent a challenge in the clinical management of such a distressing condition. Further studies focused on young females are mandatory to promote adolescent health.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
- Correspondence:
| | - Rossella Elena Nappi
- Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (R.E.N.); (L.T.)
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
| | - Andrea Farolfi
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
| | - Lara Tiranini
- Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (R.E.N.); (L.T.)
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
| | - Virginia Rossi
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
| | - Corrado Regalbuto
- Pediatric Unit, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy;
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milano, 20157 Milano, Italy
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Herrera MT, Juárez E, Guzmán-Beltrán S, Torres M, Luna-Morales VA, Villalana-Alvarez LD, González Y. High Vitamin D Concentrations Restore the Ability to Express LL37 by M. tuberculosis-Infected Human Macrophages. Biomolecules 2022; 12:biom12020268. [PMID: 35204769 PMCID: PMC8961537 DOI: 10.3390/biom12020268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/27/2022] [Accepted: 01/30/2022] [Indexed: 11/16/2022] Open
Abstract
Vitamin D has an immunomodulatory function and is involved in eliminating pathogens. Vitamin D deficiencies reported in Type 2 diabetes mellitus (T2DM) patients make them more susceptible to developing tuberculosis (TB). The macrophages are the immune cells that control intracellular pathogens by producing the antimicrobial peptide cathelicidin-LL37. This pathway involves TLR activation by pathogens, vitamin D receptor (VDR) ligation, and the enzyme 1α-hydroxylase Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). However, it is not clear whether the biological actions of vitamin D are affected by high glucose concentrations. This study aimed to evaluate the vitamin D contribution in the expression of VDR and CYP27B1, involved in the conversion of an inactive to an active form of vitamin D in the infected macrophages using M. tuberculosis as an infection model. The expression of LL37 and the nucleus translocation of VDR were evaluated as the readout of the response of vitamin D and determined if those processes are affected by glucose concentrations. Macrophages from healthy donors were cultured under glucose concentrations of 5.5, 15, or 30 mM, stimulated with vitamin D in inactive (25(OH)D3) or active (1,25(OH)2D3) forms, and infected with M. tuberculosis. The vitamin D-dependent induction of LL37 and the expression of VDR and CYP27B1 genes were analyzed by qPCR, and VDR translocation was analyzed in nuclear protein extracts by ELISA. M. tuberculosis downregulated the expression of LL37 regardless of the glucose concentration, whereas VDR and CYP27B1 upregulated it regardless of the glucose concentration. After evaluating two concentrations of vitamin D, 1 nM or 1 μM, the high concentration (1 μM) was necessary to restore the induction of LL37 expression in M. tuberculosis-infected macrophages. High concentrations of the inactive form of vitamin D restore the infected macrophages’ ability to express LL37 regardless of the glucose concentration. This finding supports the idea that vitamin D administration in patients with T2DM could benefit TB control and prevention.
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Affiliation(s)
- María Teresa Herrera
- Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City 14080, Mexico; (M.T.H.); (E.J.); (S.G.-B.)
| | - Esmeralda Juárez
- Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City 14080, Mexico; (M.T.H.); (E.J.); (S.G.-B.)
| | - Silvia Guzmán-Beltrán
- Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City 14080, Mexico; (M.T.H.); (E.J.); (S.G.-B.)
| | - Martha Torres
- Biomedical Research Sub Direction, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City 14080, Mexico;
| | - Victor Adrián Luna-Morales
- Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City 14080, Mexico; (V.A.L.-M.); (L.D.V.-A.)
| | | | - Yolanda González
- Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City 14080, Mexico; (M.T.H.); (E.J.); (S.G.-B.)
- Correspondence: ; Tel.: +(52)-55-5487-1734; Fax: +(52)-55-5487-1700 (ext. 5117)
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Khodaei B, Seyedpour S, Gholami B, Garmarudi G, Nasimi M. Seasonal and gender variation in skin disease: A cross-sectional study of 3120 patients at Razi hospital. Int J Womens Dermatol 2022; 7:799-802. [PMID: 35028385 PMCID: PMC8714557 DOI: 10.1016/j.ijwd.2021.09.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 11/29/2022] Open
Abstract
Objective: We aimed to determine the prevalence of different skin diseases and their seasonal variations at the Razi dermatology hospital from 2019 to 2020. Methods: In this cross-sectional study, we obtained data from the medical records of 3120 patients visiting the dermatology clinic of Razi hospital. The prevalence of skin diseases was evaluated using meteorologically defined seasons. We looked for significant equally distributed results during each season. Results: During all seasons, women were referred to our clinic more frequently than men. Some diseases demonstrated significant seasonality with a peak during the winter, including acne, eczema, wart, seborrheic dermatitis, nevus, vitiligo, lentigo, and dermatophytosis. Atopic dermatitis was more frequent during the spring and winter compared with other seasons (p < .05). Actinic keratosis and lichen planus showed a significant seasonal trend with a peak during the summer (p < .05). Infections, including viral, bacterial, and fungal skin diseases, were more frequent during the winter than the summer (p = .001). Conclusion: This study provides an overview of the seasonal distribution of dermatology visits at our referral hospital, which will aid in developing better policies to prevent and manage skin disorders in outpatient visits.
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Affiliation(s)
- Behzad Khodaei
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Nanomedicine Research Association, Universal Scientific Education and Research Network, Tehran, Iran
| | - Simin Seyedpour
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Nanomedicine Research Association, Universal Scientific Education and Research Network, Tehran, Iran
| | - Bahare Gholami
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Gholamreza Garmarudi
- Health Promotion and Education Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Nasimi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
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White JH. Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity. Nutrients 2022; 14:284. [PMID: 35057465 PMCID: PMC8779757 DOI: 10.3390/nu14020284] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/04/2022] [Accepted: 01/08/2022] [Indexed: 02/06/2023] Open
Abstract
Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.
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Affiliation(s)
- John H White
- Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
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50
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Severe COVID-19 patients have severe vitamin D deficiency in Northeast Mexico. NUTR HOSP 2022; 39:393-397. [DOI: 10.20960/nh.03731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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