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Huang YK, Chen CW, Renn TY, Shen MY, Klimenkov IV, Sudakov NP, Singh SK, Chang HM. Post-operative supplementation with vitamin D after mucogingival surgery significantly enhances autophagy and improves life quality following feline chronic gingivostomatitis. Int J Vet Sci Med 2025; 13:1-9. [PMID: 40290667 PMCID: PMC12024499 DOI: 10.1080/23144599.2025.2487751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 03/08/2025] [Accepted: 03/11/2025] [Indexed: 04/30/2025] Open
Abstract
Oral mucositis is a complex inflammatory and ulcerative condition frequently associated with a heightened risk of infections, malnutrition and diminished quality of life in both humans and animals. Despite the availability of various preventive and therapeutic interventions, their overall efficacy remains unclear. Considering that vitamin D exhibits pronounced anti-inflammatory properties by modulating autophagic pathways via activation of the vitamin D receptor (VDR), the present study aims to determine whether supplementation with vitamin D after the mucogingival replacement surgery (MGRS) would effectively enhance autophagy, and therefore, protect the integrity of mucosal lining in cases of severe oral mucositis. Adult domestic cats suffered from feline chronic gingivostomatitis and undergoing MGRS were used in this study. After MGRS, experimental cats were orally administered either fat-soluble or water-soluble vitamin D at a dose of 200 ng/kg twice daily for 6 weeks. Quantitative analysis revealed that in cats with oral mucositis and received MGRS, post-operative supplementation of both types of vitamin D greatly improved the quality of life and increased the anti-inflammatory reactivity. Moreover, both types of vitamin D considerably enhanced the expression of VDR and light chain 3B (LC3B, a biochemical marker for autophagy) within the affected tissues, with the most notable change observed in cats that received fat-soluble vitamin D. Based on these findings, incorporating vitamin D into the post-operative care regimens may enhance the therapeutic efficacy of surgical interventions targeting severe mucosal injury. This strategy may also hold a novel promise for improving the overall management of oral mucositis and associated complications.
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Affiliation(s)
- Yung-Kai Huang
- School of Oral Hygiene, College of Oral Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | - Ting-Yi Renn
- Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ming-Yi Shen
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan
| | - Igor V. Klimenkov
- Department of Cell Ultrastructure, Limnological Institute, Siberian Branch of the Russian Academy of Sciences, Irkutsk, Russia
| | - Nikolay P. Sudakov
- Department of Cell Ultrastructure, Limnological Institute, Siberian Branch of the Russian Academy of Sciences, Irkutsk, Russia
| | - Sandeep Kumar Singh
- Department of Medical Biotechnology, All India Institute of Medical Sciences, Nagpur, India
| | - Hung-Ming Chang
- Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Lu W, Shi X, Liu Y, Zhang H, Yuan Z, Han Y, Weng Q. 1α,25(OH) 2D 3 improves 17β-estradiol secretion and potentially alleviates endoplasmic reticulum stress in muskrat granulosa cells. Biochem Pharmacol 2025; 232:116696. [PMID: 39647606 DOI: 10.1016/j.bcp.2024.116696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/12/2024] [Accepted: 12/03/2024] [Indexed: 12/10/2024]
Abstract
Vitamin D3 plays an essential regulatory role in female reproduction. However, the studies on the correlation between vitamin D3 and muskrat reproduction are limited. This study aims to determine the role of the active form of vitamin D3, 1α,25-dihydroxytamin D3 [1α,25(OH)2D3], on muskrat ovarian granulosa cells (MGCs). The results showed that vitamin D receptor (VDR) was prominently localized in MGCs and 1α,25(OH)2D3 supplementation increased VDR signaling of MGCs. Meanwhile, 10 nM of 1α,25(OH)2D3 stimulated MGCs to secrete 17β-estradiol and enhanced the mRNA expression of steroidogenic enzymes. 1α,25(OH)2D3 also remarkably down-regulated MGCs endoplasmic reticulum stress according to the expression of GRP78, p-PERK, ATF4, and CHOP. In addition, RNA-seq analysis revealed that 10 nM of 1α,25(OH)2D3 activated the PI3K/Akt/mTOR and TNF pathways that contributed to the inhibition of MGCs apoptosis. Taken together, these findings suggest that 1α,25(OH)2D3-induced VDR signaling improves 17β-estradiol secretion and potentially alleviate MGCs endoplasmic reticulum stress through the PERK-ATF4-CHOP pathway.
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Affiliation(s)
- Wenjing Lu
- College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, PR China
| | - Xinjing Shi
- College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, PR China
| | - Yuning Liu
- College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, PR China
| | - Haolin Zhang
- College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, PR China
| | - Zhengrong Yuan
- College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, PR China
| | - Yingying Han
- College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, PR China.
| | - Qiang Weng
- College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, PR China.
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Jiang Y, Li M, Yu Y, Liu H, Li Q. Correlation Between Vitamin D, Inflammatory Markers, and T Lymphocytes With the Severity of Chronic Obstructive Pulmonary Disease and its Effect on the Risk of Acute Exacerbation: A Single Cross-sectional Study. Clin Ther 2025; 47:44-54. [PMID: 39516115 DOI: 10.1016/j.clinthera.2024.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/24/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE Chronic obstructive pulmonary disease (COPD) will become the fourth largest cause of death of chronic diseases in the world in 2030. The incidence of COPD ranked top among chronic diseases in the world. At present, there is a lack of simple and effective drugs for the treatment of COPD and for slowing the progression of the disease. The application of vitamin D as a drug in clinical treatment has been a research hotspot. In this study, we investigated the correlation between serum 25-hydroxyvitamin D (25(OH)D), inflammatory markers, and T lymphocytes with the severity of COPD and its effect on the risk of acute exacerbation. METHODS In this study, we recruited hospital inpatients and outpatient clinic patients with COPD. Their levels of 25(OH)D, inflammatory markers, and T lymphocytes were assessed. We built a nomogram model to evaluate the risk of acute exacerbation of COPD. FINDINGS The inflammatory mediators were higher in patients with acute exacerbation of COPD (AECOPD) than those in patients with COPD, but 25(OH)D showed the opposite phenomenon. In logistic regression analysis, high levels of neutrophil-lymphocyte ratio, C-reactive protein, and partial pressure of carbon dioxide and low levels of vitamin D, partial pressure of oxygen, and forced expiratory volume in the first as a percentage of predicted were regarded as independent risk factors for AECOPD. These variables were used for the construction of the nomogram model. The AUCs of the model were 0.971 (95% CI, 0.952-0.989), and 0.981 (95% CI, 0.959-1.000) in the training and testing set respectively, demonstrating that the model exhibited high accuracy for the prediction of the risk of acute exacerbation of COPD. The calibration curve of the nomogram found a high degree of consistency between the expected and actual values. The decision curve analysis and clinical impact curve indicated that the nomogram has clinical applicable for patients with COPD. IMPLICATIONS A considerable percentage of patients with COPD were found to have insufficient vitamin D levels. Patients with AECOPD reported more symptoms than those with COPD. The variables neutrophil-lymphocyte ratio, C-reactive protein, partial pressure of carbon dioxide, 25(OH)D, partial pressure of oxygen, and forced expiratory volume in the first as a percentage of predicted can be used for the prediction of AECOPD. Accordingly, this study provided experimental rationales for the role of 25(OH)D in the prevention and the potential anti-inflammatory mechanisms involved in the control of the COPD process.
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Affiliation(s)
- Yeqian Jiang
- Department of Respiratory and Critical Care Medicine, Anqing First People's Hospital of Anhui Medical University, Anqing, China; The Fifth Clinical College of Anhui Medical University, Hefei, China
| | - Mingzhu Li
- Department of Respiratory and Critical Care Medicine, Anqing First People's Hospital of Anhui Medical University, Anqing, China; The Fifth Clinical College of Anhui Medical University, Hefei, China
| | - Yan Yu
- Department of Respiratory and Critical Care Medicine, Anqing First People's Hospital of Anhui Medical University, Anqing, China
| | - Hejun Liu
- Department of Respiratory and Critical Care Medicine, Anqing First People's Hospital of Anhui Medical University, Anqing, China
| | - Qianbing Li
- Department of Respiratory and Critical Care Medicine, Anqing First People's Hospital of Anhui Medical University, Anqing, China.
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Zhang M, Chen X, Zhang Y. Mechanisms of Vitamins Inhibiting Ferroptosis. Antioxidants (Basel) 2024; 13:1571. [PMID: 39765898 PMCID: PMC11673384 DOI: 10.3390/antiox13121571] [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: 11/20/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
Ferroptosis is an iron-dependent form of cell death, which is characterized by the uncontrolled and overwhelming peroxidation of cell membrane lipids. Ferroptosis has been implicated in the progression of various pathologies, including steatotic liver, heart failure, neurodegenerative diseases, and diabetes. Targeted inhibition of ferroptosis provides a promising strategy to treat ferroptosis-related diseases. Multivitamins, including vitamins A, B, C, D, E, and K, have shown a good ability to inhibit ferroptosis. For example, vitamin A significantly upregulated the expression of several key ferroptotic gatekeepers genes through nuclear retinoic acid receptors and retinoic X receptors (RAR/RXR). Vitamin B6 could compensate for the impaired glutathione (GSH) levels and restore Glutathione peroxidase 4 (GPX4) expression in cells, ultimately inhibiting ferroptosis. Vitamin D could up-regulate the expression of several anti-ferroptosis proteins by activating vitamin D receptors. Vitamin E and hydroquinone vitamin K (VKH2) can directly inhibit the propagation of lipid peroxidation, thereby inhibiting ferroptosis. In this review, we summarize the currently understood mechanisms by which vitamins inhibit ferroptosis to provide reference information for future research on the development of ferroptosis inhibitors.
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Affiliation(s)
- Meng Zhang
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (M.Z.); (X.C.)
| | - Xin Chen
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (M.Z.); (X.C.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| | - Yumei Zhang
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (M.Z.); (X.C.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
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Parenti M, Melough MM, Lapehn S, MacDonald J, Bammler T, Firsick EJ, Choi HY, Derefinko KJ, Enquobahrie DA, Carroll KN, LeWinn KZ, Bush NR, Zhao Q, Sathyanarayana S, Paquette AG. Associations Between Prenatal Vitamin D and Placental Gene Expression. J Nutr 2024; 154:3603-3614. [PMID: 39401684 DOI: 10.1016/j.tjnut.2024.10.019] [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: 05/31/2024] [Revised: 09/16/2024] [Accepted: 10/10/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Vitamin D is a hormone that regulates gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D. OBJECTIVES We investigated the association between prenatal vitamin D concentrations and placental gene expression in a large, prospective pregnancy cohort. METHODS Participants were recruited from Shelby County, TN, United States, in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at midpregnancy (16-28 wk) and delivery. RNA was sequenced from placental samples collected at birth. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene coexpression network analysis. RESULTS The median 25(OH)D of participants was 21.8 ng/mL at midpregnancy (N = 774; IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (n = 753; IQR: 16.8-29.1 ng/mL). Placental expression of 17 DEGs was associated with 25(OH)D at midpregnancy, but only 1 DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and transcriptional regulation. We identified 2 weighted gene coexpression network analysis gene modules whose expression was associated with 25(OH)D at midpregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function and were regulated by transcription factors including ARNT2 and FOSL2. We also identified 12 modules associated with 25(OH)D in females and 1 module in males. CONCLUSIONS 25(OH)D during midpregnancy, but not at delivery, is associated with placental gene expression at birth. Future research is needed to investigate a potential role of vitamin D in modulating placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.
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Affiliation(s)
- Mariana Parenti
- Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States.
| | - Melissa M Melough
- Department of Health Behavior and Nutrition Sciences, University of Delaware, Newark, DE, United States
| | - Samantha Lapehn
- Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States
| | - James MacDonald
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States
| | - Theo Bammler
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States
| | - Evan J Firsick
- Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States
| | - Hyo Young Choi
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States
| | - Karen J Derefinko
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States; Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Sciences Center, Memphis, TN, United States
| | - Daniel A Enquobahrie
- Department of Epidemiology, University of Washington, Seattle, WA, United States
| | - Kecia N Carroll
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Kaja Z LeWinn
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Nicole R Bush
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States
| | - Qi Zhao
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States
| | - Sheela Sathyanarayana
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States; Department of Epidemiology, University of Washington, Seattle, WA, United States; Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States
| | - Alison G Paquette
- Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States
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Cirilo MADS, Ribeiro FPB, Lima NKDS, Silva JK, Gomes JADS, Albuquerque JSS, Siqueira LCDS, Santos VBDS, Carvalho JMD, Tenorio FDCAM, Vieira LD. Paricalcitol prevents renal tubular injury induced by ischemia-reperfusion: Role of oxidative stress, inflammation and AT 1R. Mol Cell Endocrinol 2024; 594:112349. [PMID: 39233041 DOI: 10.1016/j.mce.2024.112349] [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: 04/19/2024] [Revised: 08/30/2024] [Accepted: 08/31/2024] [Indexed: 09/06/2024]
Abstract
The vitamin D receptor (VDR) is associated with antioxidative and anti-inflammatory effects and modulation of the renin-angiotensin-aldosterone system. This study evaluated whether VDR agonist paricalcitol protects renal ischemia-reperfusion (IR) induced tubular injury in rats by evaluating: 1) ATP-dependent tubular Na+ transport; 2) renal redox signaling; 3) renal content of proinflammatory cytokines TNF-α and IL-6; and 4) renal content of renin and angiotensin II receptor type 1 (AT1R). Paricalcitol prevented IR-induced tubular injury, evidenced by the prevention of histopathological changes and renal fibrosis with preservation of the activity of ATP-dependent Na+ transporters in the renal cortex. Paricalcitol decreased renal oxidative stress by reducing NADPH oxidase activity and increasing catalase. Paricalcitol also decreased the renal content of TNF-α, IL-6, and AT1R. The NADPH oxidase inhibitor apocynin did not present additive protection to paricalcitol-induced effects. The protective effects of paricalcitol on tubular injury induced by renal IR may dependent on the modulation of redox and proinflammatory signaling and renal angiotensin II/AT1R signaling.
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Affiliation(s)
| | | | | | - Jeoadã Karollyne Silva
- Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
| | - José Anderson da Silva Gomes
- Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil; Department of Histology and Embriology, Federal University of Pernambuco, Recife, Brazil.
| | | | | | | | | | | | - Leucio Duarte Vieira
- Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
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7
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Rezano A, Rezkiawan D, Lie V, Srisadono A, Rivaldo RM, Purba AR, Adha MJ, Tanojo TD, Pramesti MPBD. The effect of vitamin D in vitro supplementation on sperm deoxyribonucleic acid fragmentation. Arch Ital Urol Androl 2024; 96:12891. [PMID: 39692423 DOI: 10.4081/aiua.2024.12891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 08/26/2024] [Indexed: 12/19/2024] Open
Abstract
OBJECTIVE This study aimed to identify the direct effect of vitamin D on sperm DNA integrity after swim-up preparation. MATERIALS AND METHODS Normozoospermia samples were gathered from 12 men and assessed for their baseline characteristics, including DNA Fragmentation Index (DFI). Each sample was then prepared using the swim-up method. Half of the samples were incubated with vitamin D, while the other half were incubated with a standard sperm-washing medium. RESULTS Vitamin D significantly reduced the DFI compared to the baseline (5.5 ± 3.4% versus 17.6 ± 4.2%; p < 0.001) and the swim-up-only group (5.5 ± 3.4% versus 12.0 ± 4.2%; p < 0.001). Microscopic examination reflected these results, showing a reduction in the number of small halos and no halos with an increased appearance of large to medium-sized halos. CONCLUSIONS These results suggest that vitamin D incubation is valuable in protecting sperm from DNA damage that develops during sperm preparation. However, additional investigation is warranted to explore other preparation methods and to elucidate the underlying mechanisms.
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Affiliation(s)
- Andri Rezano
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java.
| | - Ditto Rezkiawan
- Andrology Study Program, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java.
| | - Vellyana Lie
- Andrology Study Program, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java.
| | - Arya Srisadono
- Andrology Study Program, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java.
| | - Rafly Mochamad Rivaldo
- Medical Study Program, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java.
| | - Amelia Reta Purba
- Medical Study Program, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java.
| | | | - Tjahjo Djojo Tanojo
- Andrology Study Program, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java.
| | - Maria P B D Pramesti
- Andrology Study Program, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java.
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Shadid ILC, Guchelaar HJ, Weiss ST, Mirzakhani H. Vitamin D beyond the blood: Tissue distribution of vitamin D metabolites after supplementation. Life Sci 2024; 355:122942. [PMID: 39134205 PMCID: PMC11371480 DOI: 10.1016/j.lfs.2024.122942] [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: 05/02/2024] [Revised: 07/24/2024] [Accepted: 08/04/2024] [Indexed: 08/25/2024]
Abstract
Vitamin D3's role in mineral homeostasis through its endocrine function, associated with the main circulating metabolite 25-hydroxyvitamin D3, is well characterized. However, the increasing recognition of vitamin D3's paracrine and autocrine functions-such as cell growth, immune function, and hormone regulation-necessitates examining vitamin D3 levels across different tissues post-supplementation. Hence, this review explores the biodistribution of vitamin D3 in blood and key tissues following oral supplementation in humans and animal models, highlighting the biologically active metabolite, 1,25-dihydroxyvitamin D3, and the primary clearance metabolite, 24,25-dihydroxyvitamin D3. While our findings indicate significant progress in understanding how circulating metabolite levels respond to supplementation, comprehensive insight into their tissue concentrations remains limited. The gap is particularly significant during pregnancy, a period of drastically increased vitamin D3 needs and metabolic alterations, where data remains sparse. Within the examined dosage ranges, both human and animal studies indicate that vitamin D3 and its metabolites are retained in tissues selectively. Notably, vitamin D3 concentrations in tissues show greater variability in response to administered doses. In contrast, its metabolites maintain a more consistent concentration range, albeit different among tissues, reflecting their tighter regulatory mechanisms following supplementation. These observations suggest that serum 25-hydroxyvitamin D3 levels may not adequately reflect vitamin D3 and its metabolite concentrations in different tissues. Therefore, future research should aim to generate robust human data on the tissue distribution of vitamin D3 and its principal metabolites post-supplementation. Relating this data to clinically appropriate exposure metrics will enhance our understanding of vitamin D3's cellular effects and guide refinement of clinical trial methodologies.
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Affiliation(s)
- Iskander L C Shadid
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Henk-Jan Guchelaar
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Scott T Weiss
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Hooman Mirzakhani
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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Zhou Z, Zhang L, Wei X, Wang A, Hu Y, Xiao M, Zheng Y. 1,25(OH) 2D 3 inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM. Endocrine 2024; 85:1193-1205. [PMID: 38656750 DOI: 10.1007/s12020-024-03833-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/11/2024] [Indexed: 04/26/2024]
Abstract
PURPOSE To evaluate the effect and mechanism of 1,25(OH)2D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). METHODS A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining. Mouse PSCs were extracted, co-cultured with mouse insulinoma β cells (MIN6 cells) and treated with 1,25(OH)2D3. ELISA detection of inflammatory factor expression. Tissue reactive oxygen species (ROS) levels were also measured. Immunofluorescence or Western blotting were used to measure fibrosis and inflammation-related protein expression. RESULTS PSCs activation and islets fibrosis in T2DM mice. Elevated blood glucose was accompanied by significant increases in serum inflammatory cytokines and tissue ROS levels. 1,25(OH)2D3 attenuated islet fibrosis by reducing hyperglycemia, ROS levels, and inflammatory factors expression. Additionally, the co-culture system confirmed that 1,25(OH)2D3 inhibited PSCs activation, reduced the secretion of pro-inflammatory cytokines, down-regulated the expression of fibrosis and inflammation-related proteins, and promoted insulin secretion. CONCLUSION Our findings identify that PSCs activation contributes to islet fibrosis and β-cell dysfunction. 1,25(OH)2D3 exerts beneficial effects on T2DM potentially by inhibiting PSCs activation and inflammatory response, highlighting promising control strategies of T2DM by vitamin D.
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Affiliation(s)
- Zhengyu Zhou
- Laboratory Animal Center of Suzhou Medical college, Soochow University, Suzhou, China.
| | - Lewen Zhang
- Laboratory Animal Center of Suzhou Medical college, Soochow University, Suzhou, China
| | - Xun Wei
- Center of Laboratory Animal, Shanghai Jiao Tong University, Shanghai, China
| | - Aiqing Wang
- Suzhou Medical college of Soochow University, Suzhou, China
| | - Yudie Hu
- Laboratory Animal Center of Suzhou Medical college, Soochow University, Suzhou, China
| | - Min Xiao
- Laboratory Animal Center of Suzhou Medical college, Soochow University, Suzhou, China
| | - Yuxuan Zheng
- Laboratory Animal Center of Suzhou Medical college, Soochow University, Suzhou, China
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10
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Mainardi E, Corino C, Rossi R. The Effect of Vitamins on the Immune Systems of Pigs. Animals (Basel) 2024; 14:2126. [PMID: 39061588 PMCID: PMC11273632 DOI: 10.3390/ani14142126] [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: 06/27/2024] [Revised: 07/18/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024] Open
Abstract
In modern pig farming, there are many environmental, physiological or social stresses that weaken the immune response and increase susceptibility to disease. Nutritional management has a significant impact on the efficiency of the immune system in pigs. Among the various nutrients, vitamins have been shown to have specific effects on immune system activity. However, the needs of modern genetic types are not met by the dietary recommendations for vitamins in pig diets. The present study therefore summarises the data on dietary integration with supranutritional doses of vitamins in gestating and lactating sows and post-weaning piglets in terms of the immune response. The present data highlight that high doses of dietary vitamins are an effective way to improve the immune system, antioxidant status and gut health. Further studies are needed to deepen the understanding of the role of dietary supplementation with vitamins in pigs on immune system and gut functionality.
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Affiliation(s)
| | | | - Raffaella Rossi
- Department of Veterinary Medicine and Animal Science, Università Degli Studi di Milano, Via Dell’Università 6, 26900 Lodi, Italy; (E.M.); (C.C.)
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11
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Liu J, Bitsue HK, Yang Z. Skin colour: A window into human phenotypic evolution and environmental adaptation. Mol Ecol 2024; 33:e17369. [PMID: 38713101 DOI: 10.1111/mec.17369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/13/2024] [Accepted: 04/17/2024] [Indexed: 05/08/2024]
Abstract
As modern humans ventured out of Africa and dispersed around the world, they faced novel environmental challenges that led to geographic adaptations including skin colour. Over the long history of human evolution, skin colour has changed dramatically, showing tremendous diversity across different geographical regions, for example, the majority of individuals from the expansive lands of Africa have darker skin, whereas the majority of people from Eurasia exhibit lighter skin. What adaptations did lighter skin confer upon modern humans as they migrated from Africa to Eurasia? What genetic mechanisms underlie the diversity of skin colour observed in different populations? In recent years, scientists have gradually gained a deeper understanding of the interactions between pigmentation gene and skin colour through population-based genomic studies of different groups around the world, particularly in East Asia and Africa. In this review, we summarize our current understanding of 26 skin colour-related pigmentation genes and 48 SNPs that influence skin colour. Important pigmentation genes across three major populations are described in detail: MFSD12, SLC24A5, PDPK1 and DDB1/CYB561A3/TMEM138 influence skin colour in African populations; OCA2, KITLG, SLC24A2, GNPAT and PAH are key to the evolution of skin pigmentation in East Asian populations; and SLC24A5, SLC45A2, TYR, TYRP1, ASIP, MC1R and IRF4 significantly contribute to the lightening of skin colour in European populations. We summarized recent findings in genomic studies of skin colour in populations that implicate diverse geographic environments, local adaptation among populations, gene flow and multi-gene interactions as factors influencing skin colour diversity.
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Affiliation(s)
- Jiuming Liu
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Habtom K Bitsue
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Zhaohui Yang
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
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12
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Pereira F, Fernández-Barral A, Larriba MJ, Barbáchano A, González-Sancho JM. From molecular basis to clinical insights: a challenging future for the vitamin D endocrine system in colorectal cancer. FEBS J 2024; 291:2485-2518. [PMID: 37699548 DOI: 10.1111/febs.16955] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 08/03/2023] [Accepted: 09/11/2023] [Indexed: 09/14/2023]
Abstract
Colorectal cancer (CRC) is one of the most life-threatening neoplasias in terms of incidence and mortality worldwide. Vitamin D deficiency has been associated with an increased risk of CRC. 1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D metabolite, is a pleiotropic hormone that, through its binding to a transcription factor of the nuclear receptor superfamily, is a major regulator of the human genome. 1,25(OH)2D3 acts on colon carcinoma and stromal cells and displays tumor protective actions. Here, we review the variety of molecular mechanisms underlying the effects of 1,25(OH)2D3 in CRC, which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D3 supplementation conducted in both healthy individuals and CRC patients.
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Affiliation(s)
- Fábio Pereira
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Servicio de Oncología Radioterápica, Complejo Hospitalario Universitario de Ourense, Spain
| | - Asunción Fernández-Barral
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
| | - María Jesús Larriba
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
| | - Antonio Barbáchano
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
| | - José Manuel González-Sancho
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
- Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain
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13
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Parenti M, Melough MM, Lapehn S, MacDonald J, Bammler T, Firsick EJ, Choi HY, Derefinko KJ, Enquobahrie DA, Carroll KN, LeWinn KZ, Bush NR, Zhao Q, Sathyanarayana S, Paquette AG. Associations Between Prenatal Vitamin D and Placental Gene Expression. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.10.593571. [PMID: 38765981 PMCID: PMC11100832 DOI: 10.1101/2024.05.10.593571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Background Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To date, studies of vitamin D and placental gene expression have focused on a limited number of candidate genes. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D. Objective We investigated the association between prenatal vitamin D levels and placental gene expression in a large, prospective pregnancy cohort. Methods Participants were recruited in Shelby County, Tennessee in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D level (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at mid-pregnancy (16-28 weeks' gestation) and delivery. Placenta samples were collected at birth. RNA was isolated and sequenced. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene co-expression network analysis (WGCNA). Results The median 25(OH)D of participants was 21.8 ng/mL at mid-pregnancy (N=774, IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (N=753, IQR: 16.8-29.1 ng/mL). Placental expression of 25 DEGs was associated with 25(OH)D at mid-pregnancy, but no DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and RNA transcription. Using WGCNA, we identified 2 gene modules whose expression was associated with 25(OH)D at mid-pregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function, and were regulated by transcription factors including ARNT2, BHLHE40, FOSL2, JUND, and NFKB1. Conclusions Our results indicate that 25(OH)D during mid-pregnancy, but not at delivery, is associated with placental gene expression at birth. Future research is needed to investigate a potential role of vitamin D in programming placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.
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Affiliation(s)
- Mariana Parenti
- Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA, United States
| | - Melissa M. Melough
- Department of Health Behavior and Nutrition Sciences, University of Delaware, Newark, DE, United States
| | - Samantha Lapehn
- Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA, United States
| | - James MacDonald
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States
| | - Theo Bammler
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States
| | - Evan J. Firsick
- Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA, United States
| | - Hyo Young Choi
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States
| | - Karen J. Derefinko
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States
- Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Sciences Center, Memphis, TN, United States
| | | | - Kecia N. Carroll
- Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Kaja Z. LeWinn
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Nicole R. Bush
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States
- Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States
| | - Qi Zhao
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States
| | - Sheela Sathyanarayana
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States
- Department of Epidemiology, University of Washington, Seattle, WA, United States
- Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, Seattle, WA, United States
- Department of Pediatrics, University of Washington, Seattle, WA, United States
| | - Alison G. Paquette
- Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA, United States
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States
- Department of Pediatrics, University of Washington, Seattle, WA, United States
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14
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Pludowski P, Grant WB, Karras SN, Zittermann A, Pilz S. Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population. Nutrients 2024; 16:391. [PMID: 38337676 PMCID: PMC10857599 DOI: 10.3390/nu16030391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 01/26/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
Vitamin D deficiency is considered a public health problem due to its worldwide high prevalence and adverse clinical consequences regarding musculoskeletal health. In addition, vitamin D may also be crucial for the prevention of certain extraskeletal diseases. Despite decades of intensive scientific research, several knowledge gaps remain regarding the precise definition of vitamin D deficiency and sufficiency, the health benefits of improving vitamin D status, and the required vitamin D intakes. Consequently, various societies and expert groups have released heterogeneous recommendations on the dosages for vitamin D supplementation. In this brief narrative review, we outline and discuss recent advances regarding the scientific evidence arguing for a daily vitamin D supplementation with 2000 international units (IU) (50 µg) of vitamin D3 to prevent and treat vitamin D deficiency. According to data from randomized controlled trials (RCTs), such a dose may improve some health outcomes and is sufficient to raise and maintain serum 25(OH)D concentrations above 50 nmol/L (20 ng/mL) and above 75 nmol/L (30 ng/mL) in >99% and >90% of the general adult population, respectively. According to large vitamin D RCTs, there are no significant safety concerns in supplementing such a dose for several years, even in individuals with an already sufficient vitamin D status at baseline. A daily vitamin D supplementation with 2000 IU (50 µg) may be considered a simple, effective, and safe dosage to prevent and treat vitamin D deficiency in the adult general population.
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Affiliation(s)
- Pawel Pludowski
- Department of Clinical Biochemistry, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - William B. Grant
- Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA;
| | - Spyridon N. Karras
- Laboratory of Biological Chemistry, Medical School, Aristotle University, 54636 Thessaloniki, Greece;
| | - Armin Zittermann
- Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW), Ruhr University Bochum, 32545 Bad Oeynhausen, Germany;
| | - Stefan Pilz
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
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15
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van Driel M, Muñoz A, van Leeuwen JP. Overview of vitamin D actions in cancer. FELDMAN AND PIKE'S VITAMIN D 2024:679-718. [DOI: 10.1016/b978-0-323-91338-6.00034-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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16
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Wierzbicka A, Semik-Gurgul E, Świątkiewicz M, Szmatoła T, Steg A, Oczkowicz M. Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol. Int J Mol Sci 2023; 25:464. [PMID: 38203636 PMCID: PMC10778667 DOI: 10.3390/ijms25010464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 12/22/2023] [Accepted: 12/26/2023] [Indexed: 01/12/2024] Open
Abstract
Maintaining an appropriate concentration of vitamin D is essential for the proper functioning of the body, regardless of age. Nowadays, there are more and more indications that vitamin D supplementation at higher than standard doses may show protective and therapeutic effects. Our study identified differences in the body's response to long-term supplementation with cholecalciferol at an increased dose. Two groups of pigs were used in the experiment. The first group received a standard dose of cholecalciferol (grower, 2000 IU/kg feed, and finisher, 1500 IU/kg feed), and the second group received an increased dose (grower, 3000 IU/kg feed, and finisher, 2500 IU/kg feed). After slaughter, lung samples were collected and used for RRBS and mRNA sequencing. Analysis of the methylation results showed that 2349 CpG sites had significantly altered methylation patterns and 1116 (47.51%) identified DMSs (Differentially Methylated Sites) were related to genes and their regulatory sites. The mRNA sequencing results showed a significant change in the expression of 195 genes. The integrated analysis identified eleven genes with DNA methylation and mRNA expression differences between the analyzed groups. The results of this study suggested that an increased vitamin D intake may be helpful for the prevention of lung cancer and pulmonary fibrosis. These actions may stem from the influence of vitamin D on the expression of genes associated with collagen production, such as SHMT1, UGT1A6, and ITIH2.The anti-cancer properties of vitamin D are also supported by changes in KLHL3 and TTPA gene expression.
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Affiliation(s)
- Alicja Wierzbicka
- Department of Animal Molecular Biology, National Research Institute of Animal Production, ul. Krakowska 1, 32-083 Balice, Poland; (A.W.); (E.S.-G.); (T.S.); (A.S.)
| | - Ewelina Semik-Gurgul
- Department of Animal Molecular Biology, National Research Institute of Animal Production, ul. Krakowska 1, 32-083 Balice, Poland; (A.W.); (E.S.-G.); (T.S.); (A.S.)
| | - Małgorzata Świątkiewicz
- Department of Animal Nutrition and Feed Science, National Research Institute of Animal Production, ul. Krakowska 1, 32-083 Balice, Poland;
| | - Tomasz Szmatoła
- Department of Animal Molecular Biology, National Research Institute of Animal Production, ul. Krakowska 1, 32-083 Balice, Poland; (A.W.); (E.S.-G.); (T.S.); (A.S.)
- Center for Experimental and Innovative Medicine, The University of Agriculture in Kraków, Rędzina 1c, 30-248 Kraków, Poland
| | - Anna Steg
- Department of Animal Molecular Biology, National Research Institute of Animal Production, ul. Krakowska 1, 32-083 Balice, Poland; (A.W.); (E.S.-G.); (T.S.); (A.S.)
| | - Maria Oczkowicz
- Department of Animal Molecular Biology, National Research Institute of Animal Production, ul. Krakowska 1, 32-083 Balice, Poland; (A.W.); (E.S.-G.); (T.S.); (A.S.)
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17
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Hrabia A, Kamińska K, Socha M, Grzesiak M. Vitamin D 3 Receptors and Metabolic Enzymes in Hen Reproductive Tissues. Int J Mol Sci 2023; 24:17074. [PMID: 38069397 PMCID: PMC10707381 DOI: 10.3390/ijms242317074] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 11/28/2023] [Accepted: 12/01/2023] [Indexed: 12/18/2023] Open
Abstract
In recent years, vitamin D3 has been revealed as an important regulator of reproductive processes in humans and livestock; however, its role in the female reproductive system of poultry is poorly known. The aim of this study was to examine vitamin D3 receptor (VDR and PDIA3) and metabolic enzyme (1α-hydroxylase and 24-hydroxylase) mRNA transcript and protein abundances, and protein localization within the hen ovary, oviductal shell gland, pituitary, liver, and kidney. We demonstrated, for the first time, the patterns of the relative mRNA and protein abundances of examined molecules in the ovary, dependent on follicle development and the layer of follicle wall, as well as in other examined organs. Immunohistochemically, PDIA3, 1α-hydroxylase, and 24-hydroxylase are localized in follicular theca and granulosa layers, luminal epithelium and tubular glands of the shell gland, pituitary, liver, and kidney. These results indicate that reproductive tissues have both receptors, VDR, primarily involved in genomic action, and PDIA3, probably participating in the rapid, non-genomic effect of vitamin D3. The finding of 1α-hydroxylase and 24-hydroxylase expression indicates that the reproductive system of chickens has the potential for vitamin D3 synthesis and inactivation, and may suggest that locally produced vitamin D3 can be considered as a significant factor in the orchestration of ovarian and shell gland function in hens. These results provide a new insight into the potential mechanisms of vitamin D3 action and metabolism in the chicken ovary and oviduct.
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Affiliation(s)
- Anna Hrabia
- Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, Al. Mickiewicza 21, 31-120 Krakow, Poland;
| | - Kinga Kamińska
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland;
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland
| | - Magdalena Socha
- Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, Al. Mickiewicza 21, 31-120 Krakow, Poland;
| | - Małgorzata Grzesiak
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland
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18
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Singh S, Gaur S. Virtually selected phytochemicals from edible seeds as possible potential medicaments for hypercholesterolemia: an in silico approach. J Biomol Struct Dyn 2023; 41:8690-8700. [PMID: 36259535 DOI: 10.1080/07391102.2022.2135604] [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: 12/06/2021] [Accepted: 10/08/2022] [Indexed: 10/24/2022]
Abstract
Hypercholesterolemia is one of the major health concerns in today's time. Bioactive compounds from various sources have been implicated in managing the conditions of Hypercholesterolemia. With advancements in research, several edible seeds have been explored in managing the disease. This study employs in silico approach to gain insights into the binding interactions of the bioactive compounds which are reportedly present in Edible seeds, against the protein HMG-CoA reductase, which plays a crucial role in cholesterol metabolism. The bioactive compounds were virtually screened and selected based on molecular docking studies which revealed the strong binding interactions of HMG-CoA reductase with Acacetin (-7.6 kcal/mol), Irilone (-7.5 kcal/mol), Orobanchol (-7.5 kcal/mol), Diadzein (-7.4 kcal/mol) and Malvidin (-7.4 kcal/mol). These compounds largely conformed to drug likeliness criteria and ADME properties with lesser mutagenic, hepatotoxic effects and higher absorption percentage in human intestine. Moreover, we performed molecular dynamics simulation studies for docked complexes to explore their stability under simulated conditions. Data gathered from this study will support the future in vitro and in vivo research in development of potential medicaments using the bioactive compounds from edible seeds for management of hypercholesterolemia.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Shubhi Singh
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Smriti Gaur
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
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Al-Smadi K, Ali M, Alavi SE, Jin X, Imran M, Leite-Silva VR, Mohammed Y. Using a Topical Formulation of Vitamin D for the Treatment of Vitiligo: A Systematic Review. Cells 2023; 12:2387. [PMID: 37830601 PMCID: PMC10572240 DOI: 10.3390/cells12192387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/21/2023] [Accepted: 09/26/2023] [Indexed: 10/14/2023] Open
Abstract
Vitamin D is one significant prohormone substance in human organ systems. It is a steroidal hormone produced in the skin upon exposure to UVB rays. This paper presents a systematic review of the utilization of topical vitamin D, specifically cholecalciferol, calcipotriol, and tacalcitol, in the treatment of vitiligo. It considers the role of vitamin D in stimulating the synthesis of melanin and melanogenesis, which can help with the process of repigmentation. The inclusion of calcipotriol or tacalcitol in Narrowband Ultraviolet Phototherapy (NB-UVB) has shown the potential to enhance therapeutic outcomes for vitiligo. However, their effectiveness in combination with Psoralens Long Wave Ultraviolet Radiation (PUVA) and Monochromatic Excimer Light (MEL) treatment for vitiligo is limited. In contrast, combining topical corticosteroids with vitamin D analogues has demonstrated superior efficacy in treating vitiligo compared to using vitamin D analogues alone, while also providing the added benefit of reducing corticosteroid-related adverse effects. In addition, treating stable vitiligo with topical cholecalciferol and microneedling has shown success. Future studies are needed to ascertain an efficient method of administering vitamin D topically as an anti-vitiligo agent.
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Affiliation(s)
- Khadeejeh Al-Smadi
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (K.A.-S.); (M.I.)
| | - Masood Ali
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (K.A.-S.); (M.I.)
| | - Seyed Ebrahim Alavi
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (K.A.-S.); (M.I.)
| | - Xuping Jin
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (K.A.-S.); (M.I.)
- School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia
| | - Mohammad Imran
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (K.A.-S.); (M.I.)
| | - Vania R. Leite-Silva
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (K.A.-S.); (M.I.)
- Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, UNIFESP-Diadema, São Paulo 09913-030, Brazil
| | - Yousuf Mohammed
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (K.A.-S.); (M.I.)
- School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia
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20
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Liu X, Dai B, Chuai Y, Hu M, Zhang H. Associations between vitamin D levels and periodontal attachment loss. Clin Oral Investig 2023; 27:4727-4733. [PMID: 37291391 DOI: 10.1007/s00784-023-05100-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 05/29/2023] [Indexed: 06/10/2023]
Abstract
OBJECTIVES Periodontitis is accompanied by attachment loss and alveolar bone resorption. Vitamin D (VD) deficiency was closely associated with bone loss or osteoporosis. The study aims to investigate the potential relationship between different VD levels and severe periodontal attachment loss in American adults. METHODS A cross-sectional analysis was conducted including 5749 participants in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. The association of periodontal attachment loss progression with total VD, vitamin D3 (VD3), and vitamin D2 (VD2) levels was assessed using multivariable linear regression models, hierarchical regression, fitted smoothing curves, and generalized additive models. RESULTS Based on the indicators of 5749 subjects, we found that severe attachment loss tended to occur in the elderly or males and was accompanied by less total VD levels, or VD3 levels, as well as a lower poverty-income ratio (PIR). Total VD (below the inflection point: 111 nmol/L) or VD3 were negatively associated with the progression of attachment loss in each multivariable regression model. In threshold analysis, VD3 is linearly correlated with the progression of attachment loss (β = - 0.0183, 95% CI: - 0.0230 to - 0.0136). The relationship between VD2 and attachment loss progression was an S-shaped curve (inflection point: 5.07 nmol/L). CONCLUSION Increasing total VD (below 111 nmol/L) and VD3 levels may be beneficial to periodontal health. VD2 levels above 5.07 nmol/L were a risk factor for severe periodontitis. CLINICAL RELEVANCE The present study reports that different vitamin D levels may serve as different associations with periodontal attachment loss progression.
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Affiliation(s)
- Xiaoyun Liu
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Bichong Dai
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Yuanyuan Chuai
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Menglin Hu
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Hengguo Zhang
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.
- Department of Dental Implantology, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.
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Gospodarska E, Ghosh Dastidar R, Carlberg C. Intervention Approaches in Studying the Response to Vitamin D 3 Supplementation. Nutrients 2023; 15:3382. [PMID: 37571318 PMCID: PMC10420637 DOI: 10.3390/nu15153382] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 07/20/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
Vitamin D intervention studies are designed to evaluate the impact of the micronutrient vitamin D3 on health and disease. The appropriate design of studies is essential for their quality, successful execution, and interpretation. Randomized controlled trials (RCTs) are considered the "gold standard" for intervention studies. However, the most recent large-scale (up to 25,000 participants), long-term RCTs involving vitamin D3 did not provide any statistically significant primary results. This may be because they are designed similarly to RCTs of a therapeutic drug but not of a nutritional compound and that only a limited set of parameters per individual were determined. We propose an alternative concept using the segregation of study participants into different groups of responsiveness to vitamin D3 supplementation and in parallel measuring a larger set of genome-wide parameters over multiple time points. This is in accordance with recently developed mechanistic modeling approaches that do not require a large number of study participants, as in the case of statistical modeling of the results of a RCT. Our experience is based on the vitamin D intervention trials VitDmet, VitDbol, and VitDHiD, which allowed us to distinguish the study participants into high, mid, and low vitamin D responders. In particular, investigating the vulnerable group of low vitamin D responders will provide future studies with more conclusive results both on the clinical and molecular benefits of vitamin D3 supplementation. In conclusion, our approach suggests a paradigm shift towards detailed investigations of transcriptome and epigenome-wide parameters of a limited set of individuals, who, due to a longitudinal design, can act as their own controls.
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Affiliation(s)
- Emilia Gospodarska
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, PL-10-748 Olsztyn, Poland; (E.G.); (R.G.D.)
| | - Ranjini Ghosh Dastidar
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, PL-10-748 Olsztyn, Poland; (E.G.); (R.G.D.)
| | - Carsten Carlberg
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, PL-10-748 Olsztyn, Poland; (E.G.); (R.G.D.)
- School of Medicine, Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland
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22
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Huang D, Guo Y, Li X, Pan M, Liu J, Zhang W, Mai K. Vitamin D 3/VDR inhibits inflammation through NF-κB pathway accompanied by resisting apoptosis and inducing autophagy in abalone Haliotis discus hannai. Cell Biol Toxicol 2023; 39:885-906. [PMID: 34637036 DOI: 10.1007/s10565-021-09647-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/16/2021] [Indexed: 01/08/2023]
Abstract
Vitamin D3 is believed to be a contributing factor to innate immunity. Vitamin D receptor (VDR) has a positive effect on inhibiting nuclear factor κB (NF-κB)-mediated inflammation. The underlying molecular mechanisms remain unclear, particularly in mollusks. Consequently, this study will investigate the process of vitamin D3/VDR regulating NF-κB pathway and further explore their functions on inflammation, autophagy, and apoptosis in abalone Haliotis discus hannai. Results showed that knockdown of VDR by using siRNA and dsRNA of VDR in vitro and in vivo led to more intense response of NF-κB signaling to lipopolysaccharide and higher level of apoptosis and autophagy. In addition, 1,25(OH)2D3 stimulation after VDR silencing could partially alleviate apoptosis and induce autophagy. Overexpression of VDR restricted the K48-polyubiquitin chain-dependent inhibitor of κB (IκB) ubiquitination and apoptosis-associated speck-like protein containing CARD (ASC) oligomerization. Besides, VDR silencing resulted in increase of ASC speck formation. In further mechanistic studies, we showed that VDR can directly bind to IκB and IKK1 in vitro and in vivo. In the feeding trial, H&E staining, TUNEL, and electron microscope results showed that vitamin D3 deficiency (0 IU/kg) could recruit more basophilic cells and increase more TUNEL-positive apoptotic cells and lipid droplets (LDs) than vitamin D3 supplement (1000 IU/kg and 5000 IU/kg). In summary, abalone VDR plays a negative regulator role in NF-κB-mediated inflammation via interacting with IκB and inhibiting ubiquitin-dependent degradation of IκB. Vitamin D3 in combination with VDR is essential to establish a delicate balance between autophagy and apoptosis in response to inflammation.
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Affiliation(s)
- Dong Huang
- The Key Laboratory of Mariculture (Ministry of Education), The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Fisheries College, Ocean University of China, Qingdao, 266003, China
| | - Yanlin Guo
- The Key Laboratory of Mariculture (Ministry of Education), The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Fisheries College, Ocean University of China, Qingdao, 266003, China
| | - Xinxin Li
- The Key Laboratory of Mariculture (Ministry of Education), The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Fisheries College, Ocean University of China, Qingdao, 266003, China
| | - Mingzhu Pan
- The Key Laboratory of Mariculture (Ministry of Education), The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Fisheries College, Ocean University of China, Qingdao, 266003, China
| | - Jiahuan Liu
- The Key Laboratory of Mariculture (Ministry of Education), The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Fisheries College, Ocean University of China, Qingdao, 266003, China
| | - Wenbing Zhang
- The Key Laboratory of Mariculture (Ministry of Education), The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Fisheries College, Ocean University of China, Qingdao, 266003, China.
| | - Kangsen Mai
- The Key Laboratory of Mariculture (Ministry of Education), The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Fisheries College, Ocean University of China, Qingdao, 266003, China
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23
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Wimalawansa SJ. Physiological Basis for Using Vitamin D to Improve Health. Biomedicines 2023; 11:1542. [PMID: 37371637 PMCID: PMC10295227 DOI: 10.3390/biomedicines11061542] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/11/2023] [Accepted: 05/11/2023] [Indexed: 06/29/2023] Open
Abstract
Vitamin D is essential for life-its sufficiency improves metabolism, hormonal release, immune functions, and maintaining health. Vitamin D deficiency increases the vulnerability and severity of type 2 diabetes, metabolic syndrome, cancer, obesity, and infections. The active enzyme that generates vitamin D [calcitriol: 1,25(OH)2D], CYP27B1 (1α-hydoxylase), and its receptors (VDRs) are distributed ubiquitously in cells. Once calcitriol binds with VDRs, the complexes are translocated to the nucleus and interact with responsive elements, up- or down-regulating the expression of over 1200 genes and modulating metabolic and physiological functions. Administration of vitamin D3 or correct metabolites at proper doses and frequency for longer periods would achieve the intended benefits. While various tissues have different thresholds for 25(OH)D concentrations, levels above 50 ng/mL are necessary to mitigate conditions such as infections/sepsis, cancer, and reduce premature deaths. Cholecalciferol (D3) (not its metabolites) should be used to correct vitamin D deficiency and raise serum 25(OH)D to the target concentration. In contrast, calcifediol [25(OH)D] raises serum 25(OH)D concentrations rapidly and is the agent of choice in emergencies such as infections, for those who are in ICUs, and for insufficient hepatic 25-hydroxylase (CYP2R1) activity. In contrast, calcitriol is necessary to maintain serum-ionized calcium concentration in persons with advanced renal failure and hypoparathyroidism. Calcitriol is, however, ineffective in most other conditions, including infections, and as vitamin D replacement therapy. Considering the high costs and higher incidence of adverse effects due to narrow therapeutic margins (ED50), 1α-vitamin D analogs, such as 1α-(OH)D and 1,25(OH)2D, should not be used for other conditions. Calcifediol analogs cost 20 times more than D3-thus, they are not indicated as a routine vitamin D supplement for hypovitaminosis D, osteoporosis, or renal failure. Healthcare workers should resist accepting inappropriate promotions, such as calcifediol for chronic renal failure and calcitriol for osteoporosis or infections-there is no physiological rationale for doing so. Maintaining the population's vitamin D sufficiency (above 40 ng/mL) with vitamin D3 supplements and/or daily sun exposure is the most cost-effective way to reduce chronic diseases and sepsis, overcome viral epidemics and pandemics, and reduce healthcare costs. Furthermore, vitamin D sufficiency improves overall health (hence reducing absenteeism), reduces the severity of chronic diseases such as metabolic and cardiovascular diseases and cancer, decreases all-cause mortality, and minimizes infection-related complications such as sepsis and COVID-19-related hospitalizations and deaths. Properly using vitamin D is the most cost-effective way to reduce chronic illnesses and healthcare costs: thus, it should be a part of routine clinical care.
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Affiliation(s)
- Sunil J Wimalawansa
- Medicine, Endocrinology & Nutrition, Cardio Metabolic Institute, (Former) Rutgers University, North Brunswick, NJ 08901, USA
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24
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Carlberg C, Raczyk M, Zawrotna N. Vitamin D: A master example of nutrigenomics. Redox Biol 2023; 62:102695. [PMID: 37043983 PMCID: PMC10119805 DOI: 10.1016/j.redox.2023.102695] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023] Open
Abstract
Nutrigenomics attempts to characterize and integrate the relation between dietary molecules and gene expression on a genome-wide level. One of the biologically active nutritional compounds is vitamin D3, which activates via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) the nuclear receptor VDR (vitamin D receptor). Vitamin D3 can be synthesized endogenously in our skin, but since we spend long times indoors and often live at higher latitudes where for many winter months UV-B radiation is too low, it became a true vitamin. The ligand-inducible transcription factor VDR is expressed in the majority of human tissues and cell types, where it modulates the epigenome at thousands of genomic sites. In a tissue-specific fashion this results in the up- and downregulation of primary vitamin D target genes, some of which are involved in attenuating oxidative stress. Vitamin D affects a wide range of physiological functions including the control of metabolism, bone formation and immunity. In this review, we will discuss how the epigenome- and transcriptome-wide effects of 1,25(OH)2D3 and its receptor VDR serve as a master example in nutrigenomics. In this context, we will outline the basis of a mechanistic understanding for personalized nutrition with vitamin D3.
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25
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Hamza FN, Daher S, Fakhoury HMA, Grant WB, Kvietys PR, Al-Kattan K. Immunomodulatory Properties of Vitamin D in the Intestinal and Respiratory Systems. Nutrients 2023; 15:nu15071696. [PMID: 37049536 PMCID: PMC10097244 DOI: 10.3390/nu15071696] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 03/28/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body’s first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.
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Affiliation(s)
- Fatheia N. Hamza
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
| | - Sarah Daher
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
| | - Hana M. A. Fakhoury
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
- Correspondence:
| | - William B. Grant
- Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA
| | - Peter R. Kvietys
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
| | - Khaled Al-Kattan
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
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26
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Nemeth Z, Patonai A, Simon-Szabó L, Takács I. Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism-Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer. Int J Mol Sci 2023; 24:ijms24076154. [PMID: 37047134 PMCID: PMC10094444 DOI: 10.3390/ijms24076154] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/13/2023] [Accepted: 03/16/2023] [Indexed: 04/14/2023] Open
Abstract
The importance of the prevention and control of non-communicable diseases, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer, is increasing as a requirement of the aging population in developed countries and the sustainability of healthcare. Similarly, the 2013-2030 action plan of the WHO for the prevention and control of non-communicable diseases seeks these achievements. Adequate lifestyle changes, alone or with the necessary treatments, could reduce the risk of mortality or the deterioration of quality of life. In our recent work, we summarized the role of two central factors, i.e., appropriate levels of vitamin D and SIRT1, which are connected to adequate lifestyles with beneficial effects on the prevention and control of non-communicable diseases. Both of these factors have received increased attention in relation to the COVID-19 pandemic as they both take part in regulation of the main metabolic processes, i.e., lipid/glucose/energy homeostasis, oxidative stress, redox balance, and cell fate, as well as in the healthy regulation of the immune system. Vitamin D and SIRT1 have direct and indirect influence of the regulation of transcription and epigenetic changes and are related to cytoplasmic signaling pathways such as PLC/DAG/IP3/PKC/MAPK, MEK/Erk, insulin/mTOR/cell growth, proliferation; leptin/PI3K-Akt-mTORC1, Akt/NFĸB/COX-2, NFĸB/TNFα, IL-6, IL-8, IL-1β, and AMPK/PGC-1α/GLUT4, among others. Through their proper regulation, they maintain normal body weight, lipid profile, insulin secretion and sensitivity, balance between the pro- and anti-inflammatory processes under normal conditions and infections, maintain endothelial health; balance cell differentiation, proliferation, and fate; and balance the circadian rhythm of the cellular metabolism. The role of these two molecules is interconnected in the molecular network, and they regulate each other in several layers of the homeostasis of energy and the cellular metabolism. Both have a central role in the maintenance of healthy and balanced immune regulation and redox reactions; therefore, they could constitute promising targets either for prevention or as complementary therapies to achieve a better quality of life, at any age, for healthy people and patients under chronic conditions.
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Affiliation(s)
- Zsuzsanna Nemeth
- Department of Internal Medicine and Oncology, Semmelweis University, Koranyi S. u 2/a, 1083 Budapest, Hungary
| | - Attila Patonai
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Ulloi u. 78, 1082 Budapest, Hungary
| | - Laura Simon-Szabó
- Department of Molecular Biology, Semmelweis University, Tuzolto u. 37-47, 1094 Budapest, Hungary
| | - István Takács
- Department of Internal Medicine and Oncology, Semmelweis University, Koranyi S. u 2/a, 1083 Budapest, Hungary
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27
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Zheng J, Wu F, Wang F, Cheng J, Zou H, Li Y, Du J, Kan J. Biomarkers of Micronutrients and Phytonutrients and Their Application in Epidemiological Studies. Nutrients 2023; 15:nu15040970. [PMID: 36839326 PMCID: PMC9959711 DOI: 10.3390/nu15040970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/21/2023] [Accepted: 02/08/2023] [Indexed: 02/17/2023] Open
Abstract
Nutritional biomarkers can be used as important indicators of nutritional status and play crucial roles in the prevention as well as prognosis optimization of various metabolism-related diseases. Measuring dietary with the deployment of biomarker assessments provides quantitative nutritional information that can better predict the health outcomes. With the increased availability of nutritional biomarkers and the development of assessment tools, the specificity and sensitivity of nutritional biomarkers have been greatly improved. This enables efficient disease surveillance in nutrition research. A wide range of biomarkers have been used in different types of studies, including clinical trials, observational studies, and qualitative studies, to reflect the relationship between diet and health. Through a comprehensive literature search, we reviewed the well-established nutritional biomarkers of vitamins, minerals, and phytonutrients, and their association with epidemiological studies, to better understand the role of nutrition in health and disease.
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Affiliation(s)
- Jianheng Zheng
- Nutrilite Health Institute, 720 Cailun Road, Shanghai 201203, China
| | - Feng Wu
- Sequanta Technologies Co., Ltd., 240 Hedan Road, Shanghai 200131, China
| | - Feijie Wang
- Nutrilite Health Institute, 720 Cailun Road, Shanghai 201203, China
| | - Junrui Cheng
- Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695, USA
| | - Hong Zou
- Sequanta Technologies Co., Ltd., 240 Hedan Road, Shanghai 200131, China
| | - Yuan Li
- Sequanta Technologies Co., Ltd., 240 Hedan Road, Shanghai 200131, China
| | - Jun Du
- Nutrilite Health Institute, 720 Cailun Road, Shanghai 201203, China
| | - Juntao Kan
- Nutrilite Health Institute, 720 Cailun Road, Shanghai 201203, China
- Correspondence: ; Tel.: +86-21-2305-6982
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28
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Lucock MD. The evolution of human skin pigmentation: A changing medley of vitamins, genetic variability, and UV radiation during human expansion. AMERICAN JOURNAL OF BIOLOGICAL ANTHROPOLOGY 2023; 180:252-271. [PMID: 36790744 PMCID: PMC10083917 DOI: 10.1002/ajpa.24564] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 05/19/2022] [Accepted: 05/25/2022] [Indexed: 04/12/2023]
Abstract
This review examines putative, yet likely critical evolutionary pressures contributing to human skin pigmentation and subsequently, depigmentation phenotypes. To achieve this, it provides a synthesis of ideas that frame contemporary thinking, without limiting the narrative to pigmentation genes alone. It examines how geography and hence the quality and quantity of UV exposure, pigmentation genes, diet-related genes, vitamins, anti-oxidant nutrients, and cultural practices intersect and interact to facilitate the evolution of human skin color. The article has a strong focus on the vitamin D-folate evolutionary model, with updates on the latest biophysical research findings to support this paradigm. This model is examined within a broad canvas that takes human expansion out of Africa and genetic architecture into account. A thorough discourse on the biology of melanization is provided (includes relationship to BH4 and DNA damage repair), with the relevance of this to the UV sensitivity of folate and UV photosynthesis of vitamin D explained in detail, including the relevance of these vitamins to reproductive success. It explores whether we might be able to predict vitamin-related gene polymorphisms that pivot metabolism to the prevailing UVR exposome within the vitamin D-folate evolutionary hypothesis context. This is discussed in terms of a primary adaptive phenotype (pigmentation/depigmentation), a secondary adaptive phenotype (flexible metabolic phenotype based on vitamin-related gene polymorphism profile), and a tertiary adaptive strategy (dietary anti-oxidants to support the secondary adaptive phenotype). Finally, alternative evolutionary models for pigmentation are discussed, as are challenges to future research in this area.
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Affiliation(s)
- Mark D. Lucock
- School of Environmental & Life SciencesUniversity of NewcastleOurimbahNew South WalesAustralia
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29
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Maurya VK, Shakya A, Bashir K, Jan K, McClements DJ. Fortification by design: A rational approach to designing vitamin D delivery systems for foods and beverages. Compr Rev Food Sci Food Saf 2023; 22:135-186. [PMID: 36468215 DOI: 10.1111/1541-4337.13066] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 10/04/2022] [Accepted: 10/10/2022] [Indexed: 12/09/2022]
Abstract
Over the past few decades, vitamin D deficiency has been recognized as a serious global public health challenge. The World Health Organization has recommended fortification of foods with vitamin D, but this is often challenging because of its low water solubility, poor chemical stability, and low bioavailability. Studies have shown that these challenges can be overcome by encapsulating vitamin D within well-designed delivery systems containing nanoscale or microscale particles. The characteristics of these particles, such as their composition, size, structure, interfacial properties, and charge, can be controlled to attain desired functionality for specific applications. Recently, there has been great interest in the design, production, and application of vitamin-D loaded delivery systems. Many of the delivery systems reported in the literature are unsuitable for widespread application due to the complexity and high costs of the processing operations required to fabricate them, or because they are incompatible with food matrices. In this article, the concept of "fortification by design" is introduced, which involves a systematic approach to the design, production, and testing of colloidal delivery systems for the encapsulation and fortification of oil-soluble vitamins, using vitamin D as a model. Initially, the challenges associated with the incorporation of vitamin D into foods and beverages are reviewed. The fortification by design concept is then described, which involves several steps: (i) selection of appropriate vitamin D form; (ii) selection of appropriate food matrix; (iii) identification of appropriate delivery system; (iv) identification of appropriate production method; (vii) establishment of appropriate testing procedures; and (viii) system optimization.
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Affiliation(s)
- Vaibhav Kumar Maurya
- Centre for Food Research and Analysis, National Institute of Food Technology Entrepreneurship and Management, Sonepat, India
| | - Amita Shakya
- Agriculture and Environmental Sciences, National Institute of Food Technology Entrepreneurship and Management, Sonepat, India
| | - Khalid Bashir
- Department of Food Technology, Jamia Hamdard, New Delhi, India
| | - Kulsum Jan
- Department of Food Technology, Jamia Hamdard, New Delhi, India
| | - David Julian McClements
- Department of Food Science, University of Massachusetts, Amherst, Massachusetts, USA.,Department of Food Science & Bioengineering, Zhejiang Gongshang University, Hangzhou, China
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30
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Carlberg C. A Pleiotropic Nuclear Hormone Labelled Hundred Years Ago Vitamin D. Nutrients 2022; 15:171. [PMID: 36615828 PMCID: PMC9823827 DOI: 10.3390/nu15010171] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 12/21/2022] [Indexed: 01/01/2023] Open
Abstract
This year we are celebrating 100 years of the naming of vitamin D, but the molecule is, in fact, more than one billion years old [...].
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Affiliation(s)
- Carsten Carlberg
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, PL-10-748 Olsztyn, Poland;
- School of Medicine, Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland
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31
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Shao R, Liu J, Lan Y, Liao X, Zhang J, Xu W, Mai K, Ai Q, Wan M. Vitamin D impacts on the intestinal health, immune status and metabolism in turbot ( Scophthalmus maximus L.). Br J Nutr 2022; 128:2083-2096. [PMID: 35057874 DOI: 10.1017/s0007114522000125] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Vitamin D (VD) plays a vital role in various physiological processes in addition to its classic functions on maintaining the balance of Ca and P metabolism. However, there still are gaps to understand in depth the issues on the precise requirement, metabolic processes and physiological functions of VD in fish. In this study, we investigated the effects of VD on the growth, intestinal health, host immunity and metabolism in turbot (Scophthalmus maximus L.), one important commercial carnivorous fish in aquaculture, through the supplementation of different doses of dietary VD3 (0, 200, 400, 800 and 1600 μg VD3/kg diet). According to our results, the optimal VD3 level in the feed for turbot growth was estimated to be around 400 IU/kg, whereas VD3 deficiency or overdose in diets induced the intestinal inflammation, lowered the diversity of gut microbiota and impaired the host resistance to bacterial infection in turbot. Moreover, the level of 1α,25(OH)2D3, the active metabolite of VD3, reached a peak value in the turbot serum in the 400 μg group, although the concentrations of Ca and phosphate in the turbot were stable in all groups. Finally, the deficiency of dietary VD3 disturbed the nutritional metabolism in turbot, especially the metabolism of lipids and glucose. In conclusion, this study evaluated the optimal dose of dietary VD3 for turbot and provided the evidence that VD has a significant impact on intestinal health, host immunity and nutritional metabolism in fish, which deepened our understanding on the physiological functions and metabolism of VD3 in fish.
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Affiliation(s)
- Rui Shao
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
| | - Jiayu Liu
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
| | - Yawen Lan
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
| | - Xinmeng Liao
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
| | - Jinjin Zhang
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
| | - Weiqi Xu
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
| | - Kangsen Mai
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
- Pilot National Laboratory of Marine Science and Technology, Qingdao266237, People's Republic of China
| | - Qinghui Ai
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
- Pilot National Laboratory of Marine Science and Technology, Qingdao266237, People's Republic of China
| | - Min Wan
- Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao266003, People's Republic of China
- Pilot National Laboratory of Marine Science and Technology, Qingdao266237, People's Republic of China
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32
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Żmijewski MA. Nongenomic Activities of Vitamin D. Nutrients 2022; 14:nu14235104. [PMID: 36501134 PMCID: PMC9737885 DOI: 10.3390/nu14235104] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 12/04/2022] Open
Abstract
Vitamin D shows a variety of pleiotropic activities which cannot be fully explained by the stimulation of classic pathway- and vitamin D receptor (VDR)-dependent transcriptional modulation. Thus, existence of rapid and nongenomic responses to vitamin D was suggested. An active form of vitamin D (calcitriol, 1,25(OH)2D3) is an essential regulator of calcium-phosphate homeostasis, and this process is tightly regulated by VDR genomic activity. However, it seems that early in evolution, the production of secosteroids (vitamin-D-like steroids) and their subsequent photodegradation served as a protective mechanism against ultraviolet radiation and oxidative stress. Consequently, direct cell-protective activities of vitamin D were proven. Furthermore, calcitriol triggers rapid calcium influx through epithelia and its uptake by a variety of cells. Subsequently, protein disulfide-isomerase A3 (PDIA3) was described as a membrane vitamin D receptor responsible for rapid nongenomic responses. Vitamin D was also found to stimulate a release of secondary massagers and modulate several intracellular processes-including cell cycle, proliferation, or immune responses-through wingless (WNT), sonic hedgehog (SSH), STAT1-3, or NF-kappaB pathways. Megalin and its coreceptor, cubilin, facilitate the import of vitamin D complex with vitamin-D-binding protein (DBP), and its involvement in rapid membrane responses was suggested. Vitamin D also directly and indirectly influences mitochondrial function, including fusion-fission, energy production, mitochondrial membrane potential, activity of ion channels, and apoptosis. Although mechanisms of the nongenomic responses to vitamin D are still not fully understood, in this review, their impact on physiology, pathology, and potential clinical applications will be discussed.
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Affiliation(s)
- Michał A Żmijewski
- Department of Histology, Faculty of Medicine, Medical University of Gdańsk, PL-80211 Gdańsk, Poland
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Grzesiak M, Tchurzyk M, Socha M, Sechman A, Hrabia A. An Overview of the Current Known and Unknown Roles of Vitamin D 3 in the Female Reproductive System: Lessons from Farm Animals, Birds, and Fish. Int J Mol Sci 2022; 23:ijms232214137. [PMID: 36430615 PMCID: PMC9693557 DOI: 10.3390/ijms232214137] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/18/2022] Open
Abstract
Recent studies have clearly shown that vitamin D3 is a crucial regulator of the female reproductive process in humans and animals. Knowledge of the expression of vitamin D3 receptors and related molecules in the female reproductive organs such as ovaries, uterus, oviduct, or placenta under physiological and pathological conditions highlights its contribution to the proper function of the reproductive system in females. Furthermore, vitamin D3 deficiency leads to serious reproductive disturbances and pathologies including ovarian cysts. Although the influence of vitamin D3 on the reproductive processes of humans and rodents has been extensively described, the association between vitamin D3 and female reproductive function in farm animals, birds, and fish has rarely been summarized. In this review, we provide an overview of the role of vitamin D3 in the reproductive system of those animals, with special attention paid to the expression of vitamin D3 receptors and its metabolic molecules. This updated information could be essential for better understanding animal physiology and overcoming the incidence of infertility, which is crucial for optimizing reproductive outcomes in female livestock.
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Affiliation(s)
- Malgorzata Grzesiak
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Gronostajowa 9, 30-387 Krakow, Poland
- Correspondence: ; Tel.: +48-12-664-5025
| | - Marcelina Tchurzyk
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Gronostajowa 9, 30-387 Krakow, Poland
| | - Magdalena Socha
- Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, al. Mickiewicza 21, 31-120 Krakow, Poland
| | - Andrzej Sechman
- Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, al. Mickiewicza 21, 31-120 Krakow, Poland
| | - Anna Hrabia
- Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, al. Mickiewicza 21, 31-120 Krakow, Poland
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Vitamin D 3 promotes longevity in Caenorhabditis elegans. GeroScience 2022; 45:345-358. [PMID: 36001277 PMCID: PMC9886739 DOI: 10.1007/s11357-022-00637-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 07/30/2022] [Indexed: 02/03/2023] Open
Abstract
Vitamin D deficiency is associated with a variety of age-related diseases and is becoming increasingly more prevalent in the population over time. Some diseases associated with deficiency are cardiovascular disease, cancer, and neurodegeneration. This association, as well as the fact that vitamin D has been demonstrated to play an important role in a variety of extraskeletal processes, has led some to claim that vitamin D is an essential longevity vitamin. However, the role of vitamin D in healthy aging has been difficult to determine. In order to study vitamin D in the context of aging, the model organism, Caenorhabditis elegans (C. elegans), was employed. To study vitamin D's impact on aging and age-related disease, lifespan and health span were measured across three different genetic strains of C. elegans. Strains investigated were wildtype (N2), worms with a mutant vitamin D receptor ortholog (nhr-8), and worms engineered to represent Alzheimer disease (gnals2). Bioinformatic analysis of available public data was also performed in order to identify the transcriptional response produced in N2 worms treated with vitamin D3. Treatment with vitamin D3 significantly extended the lifespan of N2 worms and rescued nhr-8 worms, which typically have decreased lifespans compared to N2. Treatment with vitamin D3 minimally extended the lifespan of gnals2 worms. Similar results were obtained for measures of health span, quantified as motility through time. Differentially expressed genes upon treatment with vitamin D3 were largely associated with biological processes such as the innate immune response and metabolism of xenobiotic compounds in the worms, which may explain the observed increase in lifespan and health span.
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Vitamin D in the Context of Evolution. Nutrients 2022; 14:nu14153018. [PMID: 35893872 PMCID: PMC9332464 DOI: 10.3390/nu14153018] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 07/18/2022] [Accepted: 07/21/2022] [Indexed: 12/12/2022] Open
Abstract
For at least 1.2 billion years, eukaryotes have been able to synthesize sterols and, therefore, can produce vitamin D when exposed to UV-B. Vitamin D endocrinology was established some 550 million years ago in animals, when the high-affinity nuclear receptor VDR (vitamin D receptor), transport proteins and enzymes for vitamin D metabolism evolved. This enabled vitamin D to regulate, via its target genes, physiological process, the first of which were detoxification and energy metabolism. In this way, vitamin D was enabled to modulate the energy-consuming processes of the innate immune system in its fight against microbes. In the evolving adaptive immune system, vitamin D started to act as a negative regulator of growth, which prevents overboarding reactions of T cells in the context of autoimmune diseases. When, some 400 million years ago, species left the ocean and were exposed to gravitation, vitamin D endocrinology took over the additional role as a major regulator of calcium homeostasis, being important for a stable skeleton. Homo sapiens evolved approximately 300,000 years ago in East Africa and had adapted vitamin D endocrinology to the intensive exposure of the equatorial sun. However, when some 75,000 years ago, when anatomically modern humans started to populate all continents, they also reached regions with seasonally low or no UV-B, i.e., and under these conditions vitamin D became a vitamin.
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Mazanova A, Shymanskyi I, Lisakovska O, Labudzynskyi D, Khomenko A, Veliky M. The link between vitamin D status and NF-κB-associated renal dysfunction in experimental diabetes mellitus. Biochim Biophys Acta Gen Subj 2022; 1866:130136. [DOI: 10.1016/j.bbagen.2022.130136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/19/2022] [Accepted: 03/25/2022] [Indexed: 10/18/2022]
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Homayouni-Meymandi M, Sotoodehnejadnematalahi F, Nasr-Esfahani MH. Relationship between Serum Vitamin D in Male, Sperm Function and Clinical Outcomes in Infertile Men Candidate for ICSI: A Cohort Study. INTERNATIONAL JOURNAL OF FERTILITY & STERILITY 2022; 16:115-121. [PMID: 35639649 PMCID: PMC9108299 DOI: 10.22074/ijfs.2021.522049.1067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 08/04/2021] [Indexed: 11/04/2022]
Abstract
Background Today, vitamin D deficiency (VDD) is one of the major health issues around the world and VDD is associated with several diseases. This study was conducted to find the relationship between vitamin D status in male's serum with sperm function and clinical outcomes in infertile men candidate for intracytoplasmic sperm injection (ICSI). Materials and Methods In this cohort study, different parameters of male fertility such as sperm parameters, oxidative stress, and sperm chromatin status were evaluated in sperm samples of 30 infertile couples candidate for ICSI. Clinical outcomes like fertilization, embryo quality, and implantation were also assessed. Data were analyzed using SPSS Statistics 25.0 software. Besides, assessment of the correlation between aforementioned parameters with the level of serum vitamin D, in this study, ICSI candidates were divided into three groups [individuals with sufficient vitamin D levels (>30 ng/ml), insufficient vitamin D levels (between 20-29 ng/ml), and VDD (<20 ng/ml)]. The aforementioned parametesr were also compared between these study groups. Results Analysis of all the data revealed a significant correlation between the level of vitamin D with sperm concentration (P=0.000, r=0.5), sperm count (P=0.03, r=0.31) and sperm reactive oxygen species (ROS) level (P=0.000, r=-0.77). Moreover, comparing clinical outcomes within study groups showed a significant difference in implantation rate between sufficient and other groups (insufficient and deficient) (P=0.02). Conclusion Considering the association between sperm concentration and level of ROS with vitamin D and, higher implantation rate in individuals with vitamin D sufficient group compared to other two groups, our data call for vitamin D supplementation as part of male infertility treatment. But considering our sample size, further research is needed to verify these findings.
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Affiliation(s)
| | | | - Mohammad Hossein Nasr-Esfahani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
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Sigüeiro R, Bianchetti L, Peluso-Iltis C, Chalhoub S, Dejaegere A, Osz J, Rochel N. Advances in Vitamin D Receptor Function and Evolution Based on the 3D Structure of the Lamprey Ligand-Binding Domain. J Med Chem 2022; 65:5821-5829. [PMID: 35302785 DOI: 10.1021/acs.jmedchem.2c00171] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
1α,25-dihydroxyvitamin D3 (1,25D3) regulates many physiological processes in vertebrates by binding to the vitamin D receptor (VDR). Phylogenetic analysis indicates that jawless fishes are the most basal vertebrates exhibiting a VDR gene. To elucidate the mechanism driving VDR activation during evolution, we determined the crystal structure of the VDR ligand-binding domain (LBD) complex from the basal vertebratePetromyzon marinus, sea lamprey (lVDR). Comparison of three-dimensional crystal structures of the lVDR-1,25D3 complex with higher vertebrate VDR-1,25D3 structures suggests that 1,25D3 binds to lVDR similarly to human VDR, but with unique features for lVDR around linker regions between H11 and H12 and between H9 and H10. These structural differences may contribute to the marked species differences in transcriptional responses. Furthermore, residue co-evolution analysis of VDR across vertebrates identifies amino acid positions in H9 and the large insertion domain VDR LBD specific as correlated.
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Affiliation(s)
- Rita Sigüeiro
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France.,Institut National de La Santé et de La Recherche Médicale (INSERM), U1258, 67400 Illkirch, France.,Centre National de Recherche Scientifique (CNRS), UMR7104, 67400 Illkirch, France.,Université de Strasbourg, 67400 Illkirch, France
| | - Laurent Bianchetti
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France.,Institut National de La Santé et de La Recherche Médicale (INSERM), U1258, 67400 Illkirch, France.,Centre National de Recherche Scientifique (CNRS), UMR7104, 67400 Illkirch, France.,Université de Strasbourg, 67400 Illkirch, France
| | - Carole Peluso-Iltis
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France.,Institut National de La Santé et de La Recherche Médicale (INSERM), U1258, 67400 Illkirch, France.,Centre National de Recherche Scientifique (CNRS), UMR7104, 67400 Illkirch, France.,Université de Strasbourg, 67400 Illkirch, France
| | - Sandra Chalhoub
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France.,Institut National de La Santé et de La Recherche Médicale (INSERM), U1258, 67400 Illkirch, France.,Centre National de Recherche Scientifique (CNRS), UMR7104, 67400 Illkirch, France.,Université de Strasbourg, 67400 Illkirch, France
| | - Annick Dejaegere
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France.,Institut National de La Santé et de La Recherche Médicale (INSERM), U1258, 67400 Illkirch, France.,Centre National de Recherche Scientifique (CNRS), UMR7104, 67400 Illkirch, France.,Université de Strasbourg, 67400 Illkirch, France
| | - Judit Osz
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France.,Institut National de La Santé et de La Recherche Médicale (INSERM), U1258, 67400 Illkirch, France.,Centre National de Recherche Scientifique (CNRS), UMR7104, 67400 Illkirch, France.,Université de Strasbourg, 67400 Illkirch, France
| | - Natacha Rochel
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France.,Institut National de La Santé et de La Recherche Médicale (INSERM), U1258, 67400 Illkirch, France.,Centre National de Recherche Scientifique (CNRS), UMR7104, 67400 Illkirch, France.,Université de Strasbourg, 67400 Illkirch, France
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Li Y, Qi W, Shi Y. miR‑150‑5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR. Exp Ther Med 2022; 23:283. [PMID: 35317439 PMCID: PMC8908459 DOI: 10.3892/etm.2022.11213] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 12/16/2021] [Indexed: 11/05/2022] Open
Abstract
Dysregulated microRNAs (miRNAs or miRs) serve potential roles in inflammatory systemic disease, including ankylosing spondylitis (AS). The aim of the present study was to investigate the potential function of miR-150-5p in osteogenic differentiation of AS fibroblasts and its underlying mechanism. The expression of miR-150-5p and vitamin D receptor (VDR) in AS joint capsules and fibroblasts was detected by reverse transcription-quantitative (RT-q)PCR and western blotting. Following overexpression of miR-150-5p, the alteration in osteogenic gene expression was detected by RT-qPCR, western blotting and alkaline phosphatase activity assay, as well as alizarin red staining. The association between miR-150-5p and VDR was confirmed by luciferase assay and rescue experiments were performed. Patients with AS exhibited decreased expression of miR-150-5p in joint capsules. Treatment with bone morphogenic protein 2 (BMP-2) and transforming growth factor-β1 (TGF-β1) led to downregulation of miR-150-5p in AS fibroblasts. Enforced expression of miR-150-5p attenuated osteogenic differentiation of AS fibroblasts. These results demonstrated that miR-150-5p inhibited osteogenic differentiation of AS fibroblasts by targeting VDR. miR-150-5p overexpression decreased osteogenic transformation of fibroblasts by decreasing VDR expression in AS.
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Affiliation(s)
- Yuan Li
- Department of Rheumatology and Immunology, Tianjin First Central Hospital, Tianjin 300192, P.R. China
| | - Wufang Qi
- Department of Rheumatology and Immunology, Tianjin First Central Hospital, Tianjin 300192, P.R. China
| | - Yuquan Shi
- Department of Rheumatology and Immunology, Tianjin First Central Hospital, Tianjin 300192, P.R. China
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Gilani SJ, Bin-Jumah MN, Nadeem MS, Kazmi I. Vitamin D attenuates COVID-19 complications via modulation of proinflammatory cytokines, antiviral proteins, and autophagy. Expert Rev Anti Infect Ther 2022; 20:231-241. [PMID: 34112047 PMCID: PMC8477590 DOI: 10.1080/14787210.2021.1941871] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 06/09/2021] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Global emergence of coronavirus disease-19 (COVID-19) has clearly shown variable severity, mortality, and frequency between and within populations worldwide. These striking differences have made many biological variables attractive for future investigations. One of these variables, vitamin D, has been implicated in COVID-19 with rapidly growing scientific evidence. AREAS COVERED The review intended to systematically explore the sources, and immunomodulatory role of vitamin D in COVID-19. Search engines and data sources including Google Scholar, PubMed, NCBI, Scopus, and Web of Science were used for data collection. The search terms used were Vitamin D, COVID-19, immune system, and antiviral mechanism. Overall, 232 sources of information were collected and 188 were included in this review. EXPERT OPINION Interaction of vitamin D and vitamin D receptor (VDR) triggers the cellular events to modulate the immune system by regulation of many genes. Vitamin D operates as a double-edged sword against COVID-19. First, in macrophages, it promotes the production of antimicrobial and antiviral proteins like β-defensin 2 and cathelicidin, and these proteins inhibit the replication of viral particles and promote the clearance of virus from the cells by autophagy. Second, it suppresses cytokine storm and inflammatory processes in COVID-19.
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Affiliation(s)
- Sadaf Jamal Gilani
- Department of Basic Health Sciences, Preparatory Year, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - May Nasser Bin-Jumah
- Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
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Critical Appraisal of Large Vitamin D Randomized Controlled Trials. Nutrients 2022; 14:nu14020303. [PMID: 35057483 PMCID: PMC8778517 DOI: 10.3390/nu14020303] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 12/11/2022] Open
Abstract
As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.
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The Brain-Skin Axis in Psoriasis-Psychological, Psychiatric, Hormonal, and Dermatological Aspects. Int J Mol Sci 2022; 23:ijms23020669. [PMID: 35054853 PMCID: PMC8776235 DOI: 10.3390/ijms23020669] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/05/2022] [Accepted: 01/06/2022] [Indexed: 02/04/2023] Open
Abstract
Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.
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Rozha SO, Hawraz FM, Harseen MR, Hassan AH, Rebin KM, Dyary HO, Lava MS, Soz MM. Green Walnut Husk Ameliorating the Adverse Effects Induced by High Fat Diet in Rats. THE IRAQI JOURNAL OF VETERINARY MEDICINE 2021. [DOI: 10.30539/ijvm.v45i2.1286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
This study was designed to investigate the ameliorating effect of methanolic extract of green walnut husk (GWH) in hypercholesterolemic rats. A total of thirty male Albino Wistar rats (Rattus norvegicus domestica) were divided randomly into six equal groups. Group 1, negative control, fed on a standard rat diet whereas groups 2–6, hypercholesterolemic rats, fed a high-fat diet (1% cholesterol in a standard diet). Group 2, positive control, was left untreated, whereas the groups 3–5 treated orally with methanolic extract of GWH at 200, 400, and 800 mg/kg/day BW, respectively. Group 6, treatment control, received atorvastatin intraperitoneally at a dosage rate of 0.8 mg/kg/day. The treatment lasted for 84 days. Lipid profiles, biomarkers for liver and kidney functions, some hematological parameters, and liver histopathological assessment were performed. No significant variation was observed on lipid profile values after 42 days of GWH intake; while after 84 days, there was significant reduction (P<0.05) in cholesterol, LDL, and triglycerides and significant increase (P<0.05) in HDL. On day 42, the GWH intake revealed no ameliorating effect on ALT, AST, ALP, serum creatinine, and blood urea nitrogen (BUN); while on day 84, the GWH at 400 and 800 mg/kg BW reduced liver injury enzymes and serum creatinine levels but not the BUN. The GWH showed no significant effect on RBC, HGH, HCV, MCH, and MCHC counts; however, the WBCs count of all experimental groups showed significant (P<0.05) increase when compared to negative control. In comparison with other experimental groups, the 800 mg/kg GWH group and the treatment control group exhibited significant decrease (P<0.05) in HCT. The histopathological findings of the liver showed that the 800 mg/kg BW dosage rate of GWH was efficient in ameliorating the adverse tissue changes noticed in the positive control and other experimental groups. It can be inferred that GWH at dosage rate 200, 400, and 800 mg/kg BW have a potential antidyslipidemic effect in dose and period dependent manner. Further investigation to identify the safety of GWH for long standing using against hyperlipidemic patients is required.
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Guo Y, Jiang F, Yang W, Shi W, Wan J, Li J, Pan J, Wang P, Qiu J, Zhang Z, Li B. Effect of 1α,25(OH) 2D 3-Treated M1 and M2 Macrophages on Cell Proliferation and Migration Ability in Ovarian Cancer. Nutr Cancer 2021; 74:2632-2643. [PMID: 34894920 DOI: 10.1080/01635581.2021.2014903] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The biological active form of vitamin D3, 1α,25-dehydroxyvitamin D3 [1α,25(OH)2D3], exerts pleiotropic effects including bone mineralization, anti-tumor, as well as immunomodulator. This study aimed to explore the potential impact of 1α,25(OH)2D3 on tumor-associated macrophages (TAMs) infiltration in ovarian cancer. Firstly, human monocytic THP-1 cells were differentiated into macrophages (M0) in the presence of phorbol 12-myristate 13-acetate (PMA). In Vivo, 1α,25(OH)2D3 not only reversed the polarization of M2 macrophages, but also decreased the proliferation and migration abilities of ovarian cancer cells induced by M2 macrophages supernatant. Furthermore, 1α,25(OH)2D3 dramatically decreased the secretion of TGF-β1 and MMP-9 in M2 macrophages. However, no significant effect was observed in 1α,25(OH)2D3 treated M1 macrophages. In Vivo, vitamin D3 had an inhibitive effect of 1α,25(OH)2D3-treated M2 macrophages on tumorigenesis. In addition, we conducted the association of TAMs with the poor prognosis of patients with ovarian cancer by meta-analysis, which suggested the higher proportion of M2 macrophages was related to the poorer prognosis in ovarian cancer. Collectively, these results identified distinct roles of 1α,25(OH)2D3 treated M1 and M2 macrophages on cell proliferation and migration abilities in ovarian cancer.
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Affiliation(s)
- Yi Guo
- Medical College of Soochow University, Suzhou, China.,Jiangpu Community Healthcare Service, Suzhou, Kunshan, China
| | - Fei Jiang
- Medical College of Soochow University, Suzhou, China
| | - Wenqing Yang
- Medical College of Soochow University, Suzhou, China
| | - Weiqiang Shi
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jianmei Wan
- Medical College of Soochow University, Suzhou, China
| | - Jie Li
- Medical College of Soochow University, Suzhou, China
| | - Jinjing Pan
- Medical College of Soochow University, Suzhou, China
| | - Ping Wang
- Medical College of Soochow University, Suzhou, China
| | - Junlan Qiu
- Medical College of Soochow University, Suzhou, China.,Department of Oncology and Hematology, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Zengli Zhang
- Medical College of Soochow University, Suzhou, China
| | - Bingyan Li
- Medical College of Soochow University, Suzhou, China
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Parameters of Oxidative Stress, Vitamin D, Osteopontin, and Melatonin in Patients with Lip, Oral Cavity, and Pharyngeal Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:2364931. [PMID: 34721756 PMCID: PMC8550860 DOI: 10.1155/2021/2364931] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/07/2021] [Indexed: 12/16/2022]
Abstract
Lip, oral cavity, and pharyngeal cancers (LOCP) constitute a group of rare neoplasms with unfavorable prognosis. So far, not much is known about the role of vitamin D and oxidative stress in the pathogenesis of LOCP in the European population. The aim of the study was to determine the concentrations of vitamin D, osteopontin, melatonin, and malondialdehyde (MDA) as markers of oxidative stress and/or inflammation, as well as the activities of antioxidant enzymes in the course of LOCP. The vitamin D, melatonin, and osteopontin concentrations in blood serum, the MDA levels in erythrocytes and blood plasma, and the activities of superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GPx) in erythrocytes were measured in blood samples taken from 25 LOCP patients of middle age (YCG), 20 LOCP elderly patients (OCG), and 25 healthy middle-aged volunteers. In both cancer groups, decreases in vitamin D and CAT, as well as increases in osteopontin and blood plasma MDA, were observed. An increase in GPx activity in YCG and a decrease in melatonin level in OCG were found. The results indicate the vitamin D deficiency and disturbed oxidant-antioxidant homeostasis in LOCP patients. Osteopontin seems to be associated with LOCP carcinogenesis and requires further research.
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Young AR, Morgan KA, Harrison GI, Lawrence KP, Petersen B, Wulf HC, Philipsen PA. A revised action spectrum for vitamin D synthesis by suberythemal UV radiation exposure in humans in vivo. Proc Natl Acad Sci U S A 2021; 118:e2015867118. [PMID: 34580202 PMCID: PMC8501902 DOI: 10.1073/pnas.2015867118] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2021] [Indexed: 11/24/2022] Open
Abstract
Action spectra are important biological weighting functions for risk/benefit analyses of ultraviolet (UV) radiation (UVR) exposure. One important human benefit of exposure to terrestrial solar UVB radiation (∼295 to 315 nm) is the cutaneous synthesis of vitamin D3 that is initiated by the photoconversion of 7-dehydrocholesterol to previtamin D3 An action spectrum for this process that is followed by other nonphotochemical steps to achieve biologically active vitamin D3 has been established from ex vivo data and is widely used, although its validity has been questioned. We tested this action spectrum in vivo by full- or partial-body suberythemal irradiation of 75 healthy young volunteers with five different polychromatic UVR spectra on five serial occasions. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels, as the most accurate measure of vitamin D3 status, were assessed before, during, and after the exposures. These were then used to generate linear dose-response curves that were different for each UVR spectrum. It was established that the previtamin D3 action spectrum was not valid when related to the serum 25(OH)D3 levels, as weighting the UVR doses with this action spectrum did not result in a common regression line unless it was adjusted by a blue shift, with 5 nm giving the best fit. Such a blue shift is in accord with the published in vitro action spectra for vitamin D3 synthesis. Thus, calculations regarding the risk (typically erythema) versus the benefit of exposure to solar UVR based on the ex vivo previtamin D3 action spectrum require revision.
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Affiliation(s)
- Antony R Young
- St. John's Institute of Dermatology, School of Basic and Biomedical Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom;
| | - Kylie A Morgan
- St. John's Institute of Dermatology, School of Basic and Biomedical Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom
| | - Graham I Harrison
- St. John's Institute of Dermatology, School of Basic and Biomedical Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom
| | - Karl P Lawrence
- St. John's Institute of Dermatology, School of Basic and Biomedical Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, United Kingdom
| | - Bibi Petersen
- Global Medical Affairs, LEO Pharma, 2750 Ballerup, Denmark
| | - Hans Christian Wulf
- Department of Dermatology D92, Copenhagen University Hospital - Bispebjerg, DK-2400 Copenhagen, Denmark
| | - Peter A Philipsen
- Department of Dermatology D92, Copenhagen University Hospital - Bispebjerg, DK-2400 Copenhagen, Denmark
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Lazzara F, Amato R, Platania CBM, Conti F, Chou TH, Porciatti V, Drago F, Bucolo C. 1α,25-dihydroxyvitamin D 3 protects retinal ganglion cells in glaucomatous mice. J Neuroinflammation 2021; 18:206. [PMID: 34530842 PMCID: PMC8444391 DOI: 10.1186/s12974-021-02263-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 08/30/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice). METHODS DBA/2J mice were randomized to 1,25(OH)2D3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA. RESULTS DBA/2J mice treated with 1,25(OH)2D3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)2D3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)2D3-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF. CONCLUSIONS 1,25(OH)2D3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)2D3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.
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Affiliation(s)
- Francesca Lazzara
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Catania, Italy
- Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Rosario Amato
- Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
- Department of Biology, University of Pisa, Pisa, Italy
| | - Chiara Bianca Maria Platania
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Catania, Italy
| | - Federica Conti
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Catania, Italy
| | - Tsung-Han Chou
- Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Vittorio Porciatti
- Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Catania, Italy
- Center for Research in Ocular Pharmacology - CERFO, University of Catania, Catania, Italy
| | - Claudio Bucolo
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Catania, Italy.
- Center for Research in Ocular Pharmacology - CERFO, University of Catania, Catania, Italy.
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Lucock MD, Jones PR, Veysey M, Thota R, Garg M, Furst J, Martin C, Yates Z, Scarlett CJ, Jablonski NG, Chaplin G, Beckett EL. Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation. Am J Hum Biol 2021; 34:e23667. [PMID: 34418235 DOI: 10.1002/ajhb.23667] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/28/2021] [Accepted: 07/29/2021] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation." METHODS Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D3 were measured by immunoassay and HPLC, respectively. RESULTS Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and β-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3 . CONCLUSION New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.
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Affiliation(s)
- Mark D Lucock
- School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia
| | - Patrice R Jones
- School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia
| | | | - Rohith Thota
- Nutraceuticals Research Group, University of Newcastle, Callaghan, New South Wales, Australia.,Metabolism and Nutrition, Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Manohar Garg
- Nutraceuticals Research Group, University of Newcastle, Callaghan, New South Wales, Australia
| | - John Furst
- Maths and Physical Sciences, University of Newcastle, Ourimbah, New South Wales, Australia
| | - Charlotte Martin
- School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia
| | - Zoe Yates
- Biomedical Sciences and Pharmacy, University of Newcastle, Ourimbah, New South Wales, Australia
| | - Christopher J Scarlett
- School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia
| | - Nina G Jablonski
- Anthropology Department, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - George Chaplin
- Anthropology Department, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Emma L Beckett
- School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia
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Vitamin D and the risk for cancer: A molecular analysis. Biochem Pharmacol 2021; 196:114735. [PMID: 34411566 DOI: 10.1016/j.bcp.2021.114735] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/12/2021] [Accepted: 08/12/2021] [Indexed: 02/08/2023]
Abstract
Uncontrolled overgrowth of cells, such as in cancer, is an unavoidable risk in life that affects nearly every second individual in industrialized countries. However, in part this risk can be controlled through lifestyle adjustments, such as the avoidance of smoking, unhealthy diet, obesity, physical inactivity and other cancer risk factors. A low vitaminD status is a risk in particular for cancers of colon, prostate, breast and leukocytes. VitaminD3 is produced non-enzymatically, when the cholesterol precursor 7-dehydrocholesterol is exposed to UV-B from sunlight, i.e., all cholesterol synthesizing species, including humans, can make vitaminD3. VitaminD endocrinology started some 550million years ago, when the metabolite 1α,25-dihydroxyvitaminD3 and the transcription factor vitaminD receptor teamed up for regulating the expression of hundreds of target genes in a multitude of different tissues and cell types. Initially, these genes were focused on the control of energy homeostasis, which later also involved energy-demanding innate and adaptive immunity. Rapidly growing cells of the immune system as well as those of malignant tumors rely on comparable genes and pathways, some of which are modulated by vitaminD. Accordingly, vitaminD has anti-cancer effects both directly via controling the differentiation, proliferation and apoptosis of neoplastic cells as well as indirectly through regulating immune cells that belong to the microenvironment of malignant tumors. This review discusses effects of vitaminD on the epigenome and transcriptome of stromal and tumor cells, inter-individual variations in vitaminD responsiveness and their relation to the prevention and possible therapy of cancer.
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Bhutia SK. Vitamin D in autophagy signaling for health and diseases: Insights on potential mechanisms and future perspectives. J Nutr Biochem 2021; 99:108841. [PMID: 34403722 DOI: 10.1016/j.jnutbio.2021.108841] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 06/08/2021] [Accepted: 08/10/2021] [Indexed: 02/07/2023]
Abstract
Vitamin D regulates the pleiotropic effect to maintain cellular homeostasis and epidemiological evidence establishes an association between vitamin D deficiency and various human diseases. Here, the role of autophagy, the cellular self-degradation process, in vitamin D-dependent function is documented in different cellular settings and discussed the molecular aspects for treating chronic inflammatory, infectious diseases, and cancer. Vitamin D activates autophagy through a genomic and non-genomic signaling pathway to influence a wide variety of physiological functions of different body organs along with bone health and calcium metabolism. Moreover, it induces autophagy as a protective mechanism to inhibit oxidative stress and apoptosis to regulate cell proliferation, differentiation, and immune modulation. Furthermore, vitamin D and its receptor regulate autophagy signaling to control inflammation and host immunity by activating antimicrobial defense mechanisms. Vitamin D has been revealed as a potent anticancer agent and induces autophagy to increase the response to radiation and chemotherapeutic drugs for potential cancer therapy. Increasing vitamin D levels in the human body through timely exposure to sunlight or vitamin D supplements could activate autophagy as part of the homeostasis mechanism to prevent multiple human diseases and aging-associated dysfunctions.
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Affiliation(s)
- Sujit Kumar Bhutia
- Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, 769008, India.
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