scholarly journals Vitamin D3 Modulates NF-kB/p65, 17β-Estradiol, and Vitamin D Receptors Expression at Estrogen Deficiency

Author(s):  
Alexandra Koshkina ◽  
Olga Volkova ◽  
Julia Fedotova
Author(s):  
Patrick J. McCullough ◽  
Jeffrey Amend ◽  
William P. McCullough ◽  
Steven J. Repas ◽  
Jeffrey B. Travers ◽  
...  

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.


2016 ◽  
Vol 57 (1) ◽  
pp. 23-32
Author(s):  
Kumi Futawaka ◽  
Tetsuya Tagami ◽  
Yuki Fukuda ◽  
Rie Koyama ◽  
Ayaka Nushida ◽  
...  

The active form of vitamin D3 (1α,25(OH)2D3, also known as calcitriol) controls the expression of target genes via the vitamin D receptor (VDR). Vitamin D-dependent rickets type II (VDDRII) is a congenital disease caused by inactivating mutations in the VDR. The condition is treated with high doses of calcitriol, but the therapeutic effects of other synthetic VD3 analogs have not yet been investigated. In the present study, we analyzed the transcriptional activity of seven different VD3 analogs with VDRs carrying ligand-binding domain mutations identified in VDDRII patients. Wild-type VDR (WT-VDR) and seven mutant VDRs were expressed in TSA201 human embryonic kidney cells, HepG2 human liver cancer cells, and MC3T3-E1 mouse calvaria cells, and their transcriptional activation with VD3 analogs were analyzed by performing transient expression assays, western blotting, and quantitative real-time PCR. The results demonstrated that falecalcitriol stimulated significantly higher transcriptional activation of the WT-VDR and some mutant VDRs than did calcitriol. Calcitriol showed almost no transcriptional activation of the VDR with the I268T mutation identified in a severe case of VDDRII, whereas falecalcitriol caused a dose-dependent increase in the activation of this mutant VDR. Our findings demonstrate that falecalcitriol has a VDR activation profile distinct from that of calcitriol and may exhibit therapeutic effects even on difficult-to-treat VDDRII cases resistant to calcitriol. It is also possible that VDDRII patients responding to high doses of calcitriol could be appropriately treated with low doses of falecalcitriol.


Author(s):  
Sangeeta Chowdhary ◽  
Mala Shukla ◽  
Ruchi Joshi

Background: Fibroid uterus or leiomyoma is a benign tumour composed mainly of unicellular smooth muscle cells with varying amounts of fibrous connective tissue. UF are associated with significant morbidity as it presents in form of abnormal uterine bleeding, anaemia, pelvic pain, subfertility, and obstetric complications and causes financial burden on the patient. Recent studies have shown the critical role that vitamin D plays in fibroid formation, with individual fibroids expressing lower levels of vitamin D receptors than adjacent healthy tissue, making vitamin D deficiency a crucial, yet preventable risk factor.Methods: This was cross-sectional observational study. It was conducted on 140 female patients aged (18 to 50 years) presenting to the OPD of department of obstetrics and gynecology at NDMC & Hindu Rao Hospital during July 2019 to June 2020. 70 women had uterine fibroids on ultrasound and treated as cases and rest healthy women without fibroids served as controls. All women were subjected to ultrasound examination of uterus followed by serum vitamin D3 levels.Results: The mean value of vitamin D levels in cases was 12.81±8.56 ng/ml and in controls it was 19.83±9.21 ng/ml with p value<0.0001. Thus, it was statistically significant lower in cases of fibroid uterus as compared to controls. Secondary incidental outcomes were found between vitamin D3 level and BMI as fibroids occur statistically significantly more often in patient having of BMI ≥25 kg/m2. Also, menorrhagia and dysmenorrhea were the major complaints in 62.5% of cases followed by lowers abdominal pain and dyspareunia.Conclusions: Our study reached significance in the inverse correlation between fibroids and vitamin D levels at the primary outcome level. Larger prospective longitudinal studies drawing on more number and eliminating confounding variables are needed.


2021 ◽  
Vol 22 (17) ◽  
pp. 9287
Author(s):  
Carmela Conte ◽  
Samuela Cataldi ◽  
Cataldo Arcuri ◽  
Alessandra Mirarchi ◽  
Andrea Lazzarini ◽  
...  

The release of exosomes can lead to cell–cell communication. Nutrients such as vitamin D3 and sphingolipids have important roles in many cellular functions, including proliferation, differentiation, senescence, and cancer. However, the specific composition of sphingolipids in exosomes and their changes induced by vitamin D3 treatment have not been elucidated. Here, we initially observed neutral sphingomyelinase and vitamin D receptors in exosomes released from HN9.10 embryonic hippocampal cells. Using ultrafast liquid chromatography tandem mass spectrometry, we showed that exosomes are rich in sphingomyelin species compared to whole cells. To interrogate the possible functions of vitamin D3, we established the optimal conditions of cell treatment and we analyzed exosome composition. Vitamin D3 was identified as responsible for the vitamin D receptor loss, for the increase in neutral sphingomyelinase content and sphingomyelin changes. As a consequence, the generation of ceramide upon vitamin D3 treatment was evident. Incubation of the cells with neutral sphingomyelinase, or the same concentration of ceramide produced in exosomes was necessary and sufficient to stimulate embryonic hippocampal cell differentiation, as vitamin D3. This is the first time that exosome ceramide is interrogated for mediate the effect of vitamin D3 in inducing cell differentiation.


2017 ◽  
Vol 21 (2) ◽  
pp. 166-175
Author(s):  
Sapna Singh ◽  
Binita Goswami ◽  
Rashmi Verma ◽  
Bhawna Singh ◽  
Santosh K Gupta

ABSTRACT Introduction The active vitamin D3—1,25 dihydroxy cholecalciferol—is the key player in calcium and phosphorus metabolism and skeletal growth and functions. However, recent new developments have revealed its role in other tissues as well, referred to as the nonclassical actions of vitamin D. Not only the endocrinal effects, evidence indicates that vitamin D3 also has autocrine and paracrine functions due to its extrarenal synthesis by many cells, including the immune cells. All cells of the immune system have vitamin D receptors and show wide-ranging effects to it. It impacts both the innate and adaptive immune systems and the overall influence points to anti-infective, anti-inflammatory, immunosuppressive, and regulatory roles. It shows a significant role in chronic inflammatory and autoimmune diseases as well in susceptibility to infections. In this review, newer developments on the role of vitamin D in immunity and the underlying mechanism are discussed with possible future reflections. How to cite this article Verma R, Singh S, Singh B, Goswami B, Gupta SK. Role of Active Vitamin D3 in Immunity. Indian J Med Biochem 2017;21(2):166-175.


2006 ◽  
Vol 175 (4S) ◽  
pp. 520-521
Author(s):  
Ajay K. Nangia ◽  
Vince Memoli ◽  
Alan Schned ◽  
Oya Hill ◽  
Catherine E. Schwender

Author(s):  
Giuseppe Derosa ◽  
Angela D’Angelo ◽  
Chiara Martinotti ◽  
Maria Chiara Valentino ◽  
Sergio Di Matteo ◽  
...  

Abstract. Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.


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