PMID: 

Arch Physiol Biochem. 2019 Jul 10:1-15. Epub 2019 Jul 10. PMID: 31291127

Abstract Title: 

Health implication of vitamin D on the cardiovascular and the renal system.

Abstract: 

Vitamin D regulates the calcium and phosphorus balance in the body. The activated form of vitamin D (1α,25-dihydroxyvitamin D) binds to vitamin D receptor which regulates genes that control cell proliferation, differentiation and apoptosis. In the cardiovascular system, the vitamin D receptor is present in cardiomyocytes and the arterial wall. A clear correlation between vitamin D level and cardiovascular diseases is established. Vitamin D deficiency affects the renin-angiotensin system leading to ventricular hypertrophy and eventually to stroke. While clinical trials highlighted the positive effects of vitamin D supplements on cardiovascular disease these still need to be confirmed. This review outlines the association between vitamin D and cardiovascular and renal disease summarising the experimental data of selective cardiovascular disorders.

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PMID: 

CNS Drugs. 2019 Dec ;33(12):1187-1199. PMID: 31686407

Abstract Title: 

An Update on Vitamin D and Disease Activity in Multiple Sclerosis.

Abstract: 

Vitamin D and its main active metabolite 1,25-dihydroxyvitamin D serve a crucial role in maintenance of a healthy calcium metabolism, yet have additional roles in immune and central nervous system cell homeostasis. Serum levels of 25-hydroxyvitamin D are a biomarker of future disease activity in patients with early relapsing-remitting multiple sclerosis (RRMS), and vitamin D supplementation in patients with low circulating 25-dihydroxyvitamin D levels has been anticipated as a potential efficacious treatment strategy. The results of the first large randomized clinical trials (RCTs), the SOLAR and CHOLINE studies, have now been published. The SOLAR study compared 14,000 IU of vitamin D(cholecalciferol) per day with placebo for 48 weeks in 232 randomized patients, whereas CHOLINE compared vitamin D100,000 IU every other week with placebo for 96 weeks in 129 randomized patients. All patients in both studies also used interferon-β-1a. None of the studies met their primary endpoints, which were no evidence of disease activity (NEDA-3) at 48 weeks in SOLAR and annualized relapse rate at 96 weeks inCHOLINE. Both studies did, however, suggest modest effects on secondary endpoints. Thus, vitamin D reduced the number of new or enlarging lesions and new T2 lesions in SOLAR, and the annualized relapse rate and number of new T1 lesions, volume of hypointense T1 lesions, and disability progressionin the 90 patients who completed 96 weeks' follow-up in CHOLINE. We conclude that none of the RCTs on vitamin supplementation in MS have met their primary clinical endpoint in the intention to treat cohorts. This contrasts the observation studies, where each 25 nmol/l increase in 25-hydroxyvitaminD levels were associated with 14-34% reduced relapse risk and 15-50% reduced risk of new lesions on magnetic resonnance imaging. This discrepancy may have several explanations, including confounding and reverse causality in the observational studies. The power calculations of the RCTs have been based on the observational studies, and the RCTs may have been underpowered to detect less prominent yet important effects of vitamin D supplementation. Although the effect of vitamin D supplementation is uncertain and less pronounced than suggested by observational studies, current evidence still support that people with MS should avoid vitamin D insufficiency, and preferentially aim for vitamin D levels around 100 nmol/L or somewhat higher.

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PMID: 

Nutrients. 2020 Jan 30 ;12(2). Epub 2020 Jan 30. PMID: 32019160

Abstract Title: 

Effects of 1,25-dihydroxyvitamin D3 on the Inflammatory Responses of Stromal Vascular Cells and Adipocytes from Lean and Obese Mice.

Abstract: 

Vitamin D status has been implicated in obesity and adipose tissue inflammation. In the present study, we explored the effects of dietary vitamin D supplementation on adipose tissue inflammation and immune cell population, and the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) treatment on pro-inflammatory cytokine production by stromal vascular cells (SVCs) and adipocytes in lean and high-fat diet-induced obese mice. The results show that epididymal fat Mcp-1 and Rantes mRNA levels, which were higher in obese mice compared with lean mice, were significantly down-regulated by vitamin D supplementation. While obese mice had higher numbers of macrophages and natural killer (NK) cells within adipose tissue, these remained unaltered by vitamin D supplementation. In accordance with these in vivo findings, the in vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, and IL-1β production by SVCs from obese mice, but not by adipocytes. In addition, 1,25(OH)2D3 treatment significantly decreased Tlr2 expression and increased mRNA levels of Iba and Dusp1 in SVCs. These findings suggest that vitamin D supplementation attenuates inflammatory response in adipose tissue, especially in SVCs, possibly through inhibiting NF-κB and MAPK signaling pathways in SVCs but not by the inhibition of macrophage infiltration.

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PMID: 

Cell Prolif. 2018 Oct ;51(5):e12461. Epub 2018 Apr 24. PMID: 29687949

Abstract Title: 

1,25(OH)Dinhibited Th17 cells differentiation via regulating the NF-κB activity and expression of IL-17.

Abstract: 

OBJECTIVES: The role of vitamin D (VD) in innate and adaptive immune responses to tuberculosis is still unclear. Our research was aimed to uncover the effect of VD on Th17 cells and elucidate potential molecular mechanism.MATERIALS AND METHODS: VDR-deficient and wild-type mice were used to obtain CD4 T cells. Th17 cells were induced and activated by Bacillus Calmette Guerin. Flow cytometry was used to analyse the apoptosis rate and degree of differentiation of Th17 cells in the treatment of 1,25(OH)D. The interaction between P65 and Rorc was determined by immunofluorescence assay, luciferase reporter assay, EMSA-Super-shelf assay and ChIP assay. Co-IP assay was carried out to test the interaction between VDR and NF-κB family proteins. qRT-PCR and Western blot were also performed to detect the levels of P65, RORγt and IL-17.RESULTS: The Th17 cells differentiation was suppressed by 1,25(OH)Din vitro. We confirmed that Rorc was a downstream gene of the transcription factor P65. VDR interacts with P105/P50, P100/P52 and P65 NF-κB family proteins. 1,25(OH)Dinhibited the expression of RORγt/IL-17 by suppressing p65 transcription factor translocating to nucleus. In vivo experiments, the expression of IL-17 and RANKL was suppressed by 1,25(OH)Dby VD receptor. Moreover, 1,25(OH)Dsuppressed the inflammatory infiltrates and inhibited the expression of P65, RORγt and IL-17 in the spleen tissues of model mice.CONCLUSIONS: Together, 1,25(OH)Dsuppressed the differentiation of Th17 cells via regulating the NF-κB activity.

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PMID: 

Int J Mol Sci. 2020 Apr 28 ;21(9). Epub 2020 Apr 28. PMID: 32354174

Abstract Title: 

Vitamin D as a Potential Therapy for Multiple Sclerosis: Where Are We?

Abstract: 

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and is caused by an aberrant immune response to myelin sheath. Disease-modifying medications, which mainly aim to suppress such aberrant immune response, have significantly improved MS treatment. However, the disease severity continues to worsen. In contrast, progressively more data suggest that 1,25-dihydroxyvitamin D or 1,25(OH)D, i.e., the active vitamin D, suppresses the differentiation of potentially pathogenic T cells associated with MS, enhances the differentiation of regulatory T cells that suppress the pathogenic T cells, and promotes remyelination. These novel 1,25(OH)D functions have encouraged investigators to develop vitamin D as a potential therapy for MS. However, because of the hypercalcemia that is associated with high 1,25(OH)D concentrations, supplementation of native vitamin D has been a major focus in clinical trials for the treatment of MS, but such trials have produced mixed data. In this article, we will review current progress in the supplementation of different vitamin D forms for the treatment of experimental autoimmune encephalomyelitis (i.e., an MS animal model) as well as MS. Furthermore, we will review alternative strategies that our laboratory and others are pursuing in an attempt to circumvent the hurdles that are hampering the effective use of vitamin D as a potential therapy for MS.

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Astonishingly, in spite of being only 80 miles from the coast of China with over 400,000 of its 24 million citizens working in China, as of mid-April, Taiwan only has 400 cases of COVID, 6 deaths

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PMID: 

Nutrients. 2020 Apr 16 ;12(4). Epub 2020 Apr 16. PMID: 32316365

Abstract Title: 

The Study of Correlation Between Serum Vitamin DConcentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients.

Abstract: 

Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D(vitamin D) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin Dsufficiency. We assigned vitamin Dstatus as either normal (≥30 ng/mL), insufficient (20-30 ng/mL), or deficient (

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PMID: 

Nutrients. 2020 Apr 19 ;12(4). Epub 2020 Apr 19. PMID: 32325790

Abstract Title: 

Key Vitamin D Target Genes with Functions in the Immune System.

Abstract: 

The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D(1,25(OH)D), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)D, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin Dbolus. The led to the genes,,,,,,,,,,,,,and. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.

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PMID: 

Clin Psychopharmacol Neurosci. 2020 May 31 ;18(2):203-213. PMID: 32329301

Abstract Title: 

Vitamin D Supplementation is Beneficial for Children with Autism Spectrum Disorder: A Meta-analysis.

Abstract: 

Objective: We conducted a meta-analysis of randomized controlled trials to explore whether vitamin D supplementation is beneficial for symptom improvement in children with autism spectrum disorder.Methods: We systematically searched the PubMed database, EMBASE, Cochrane Library, Web of Science, Sino-Med, Wanfang Data, and China National Knowledge Infrastructure mainly up to September 2019. Using a fixed effects model, we calculated the standard mean difference with 95% confidence interval. Furthermore, we analyzed baseline serum 25-hydroxyvitamin D levels and outcome scores including the Social Responsiveness Scale and Child Autism Rating Scale scores after vitamin D supplementation.Results: There was no significant difference in baseline serum 25-hydroxyvitamin D levels among 203 children included from three studies in the meta-analysis. After vitamin D supplementation, the outcome scores in the experimental group were dramatically elevated compared with those in the control group (= 0.03).Conclusion: Vitamin D supplementation improves the typical symptoms of autism spectrum disorder, as indicated by reduced Social Responsiveness Scale and Child Autism Rating Scale scores; thus, it is beneficial for children with autism spectrum disorder.

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