Vitamin D3 deficiency and insufficiency are becoming a common global issue for us, especially in the most industrially developed countries. The only acknowledged activity of vitamin D3 in vertebrates is to promote the absorption of calcium and, therefore, allow for the mineralization of bones. Accordingly, its deficiency is associated with diseases such as rickets. Other numerous vital functions associated with vitamin D3 are yet to be considered, and the function of vitamin D2 in plants is unknown. Thus, 100 years after its discovery, the importance of vitamin D still seems to be unacknowledged (except for rickets), with little attention given to its decrease throughout the world. In this review, I suggest that vitamin D deficiency and insufficiency may be linked to the westernized lifestyle in more developed countries. Furthermore, I suggest that, rather than the calcemic activity, the main function of vitamin D is, in general, that of strengthening living organisms. I conclude with the hypothesis that vitamin D deficiency may represent a marker for a greater risk of chronic inflammatory diseases and a shorter life expectancy.

BACKGROUND: COVID-19 is strongly linked to cardiovascular disease, with direct myocardial injury and systemic inflammation as common mechanisms. Pre-existing or infection-induced cardiovascular disease worsens the outcomes for COVID-19 patients.
METHODS: To estimate the serum electrolytes (Na+, K+, Ca++, Zn) and vitamin D3, the study depended on ichroma ii device for Vitamin D3 and Chemistry Analyzer for electrolytes in patient samples.
RESULTS: A study was conducted on 192 individuals diagnosed with COVID-19, including 35 critical cases, 53 severe cases, 54 moderate cases, and 50 individuals in a control group. The age group with the highest prevalence of infection was between 50‒69 years, while the lowest prevalence was observed in those under 30 years. The study found significant decreases in calcium, potassium, sodium, zinc, and vitamin D3 levels among COVID-19 patients compared to the control group. Zinc and vitamin D3 levels showed a significant correlation with sex, with males experiencing a decline in zinc levels and females having lower vitamin D3 levels. The concentration of calcium, sodium, and zinc showed a negative correlation with age, with older patients having the lowest levels. COVID-19 patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease also had a detrimental impact on electrolyte levels, zinc, and vitamin D3, with critical cases showing the lowest levels. The complications such as heart failure were associated with lower levels of potassium, sodium, and zinc.
CONCLUSIONS: In conclusion, the study revealed significant associations between COVID-19 and decreased electrolyte levels, zinc, and vitamin D3. Sex and age were found to be correlated with these markers. Patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease was also linked to lower electrolyte levels, zinc, and vitamin D3. Complications such as heart failure were associated with decreased levels of potassium, sodium, and zinc.
Введение. COVID-19 тесно связан с сердечно-сосудистыми заболеваниями, общими механизмами которых являются прямое повреждение миокарда и системное воспаление. Ранее существовавшие или вызванные инфекцией сердечно-сосудистые заболевания ухудшают исходы для пациентов с COVID-19. Материалы и методы. В образцах сыворотки крови пациентов проводили количественное определение электролитов (Na+, K+, Ca++, Zn) с помощью биохимического анализатора и витамина D3 с помощью устройства ichroma ii. Результаты. В исследовании приняли участие 142 пациента с диагнозом COVID-19, включая 35 критических случаев, 53 тяжелых случая, 54 среднетяжелых случая, а также 50 человек в контрольной группе. Возрастная группа с наибольшей распространенностью инфекции составила 50‒69 лет, а наименьшая распространенность наблюдалась среди лиц моложе 30 лет. Исследование выявило значительное снижение уровней кальция, калия, натрия, цинка и витамина D3 среди пациентов с COVID-19 по сравнению с контрольной группой. Уровни цинка и витамина D3 продемонстрировали значительную корреляцию с полом: у мужчин наблюдалось снижение уровня цинка, а у женщин ‒ более низкий уровень витамина D3. Концентрация кальция, натрия и цинка имела отрицательную корреляцию с возрастом, при этом у пожилых пациентов наблюдалась самая низкая концентрация. У пациентов с COVID-19 с хроническими заболеваниями сердца и высоким кровяным давлением наблюдались самые низкие уровни этих маркеров. Тяжесть заболевания также оказывала пагубное влияние на уровень электролитов, цинка и витамина D3, при этом в критических случаях COVID-19 наблюдались самые низкие уровни. Такие осложнения, как сердечная недостаточность, были связаны с более низким уровнем калия, натрия и цинка. Вывод. Исследование выявило значительную связь между COVID-19 и снижением уровней электролитов, цинка и витамина D3. Было обнаружено, что пол и возраст коррелируют с этими маркерами. У пациентов с хроническими сердечно-сосудистыми заболеваниями и высоким кровяным давлением наблюдались самые низкие уровни этих маркеров. Тяжесть заболевания COVID-19 также была связана с более низким уровнем электролитов, цинка и витамина D3. Такие осложнения, как сердечная недостаточность, были связаны со снижением уровней калия, натрия и цинка.

BACKGROUND: Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated.
METHODS: An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis.
RESULTS: Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells\' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function.
CONCLUSIONS: Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.

UNASSIGNED: Kawasaki Disease (KD) is a pediatric vasculitic disorder characterized by systemic small vasculitis, notably coronary arteritis, with unclear pathogenesis. This explorative case-control study investigated the association between folic acid (FA), vitamin D3 (VD3), and vitamin B12 (VB12) levels and the different types of Kawasaki Disease, as well as the incidence of coronary artery lesions (CALs).
UNASSIGNED: In this explorative case control study, 365 KD children admitted to our hospital from January 1, 2022 to June 30, 2023 were included as the KD group. Simultaneously, 365 healthy children who received physical examination during the same period were included as the control group. The KD group was divided into typical KD group and incomplete KD group (IKD group), CALs group and non-CALS group, and IVIG sensitive group and IVIG resistant group. The children with CALs were divided into small tumor group, medium tumor group and large tumor group. Serum levels of FA, VB12, and VD3 were compared across all groups.
UNASSIGNED: Serum levels of FA and VD3 were significantly decreased in both the KD and CALs groups (p < 0.05), and both factors were identified as independent risk factors for KD and CALs. Similarly, reduced serum VD3 levels were observed in the IKD and IVIG-resistant groups (p < 0.05), with VD3 also being an independent risk factor for both IKD and IVIG resistance. Additionally, lower serum FA levels were noted in the group with large aneurysms (p < 0.05), establishing FA as an independent risk factor for aneurysm size.
UNASSIGNED: Serum levels of folic FA and vitamin VD3 were significantly reduced in children with KD. Furthermore, these reductions were more pronounced in children with IKD and CALs. This pattern suggests that lower FA and VD3 levels may increase the risk of more severe coronary lesions in KD patients. Therefore, monitoring these biomarkers could provide valuable insights for early clinical diagnosis and intervention.

Increasing bone diseases and anomalies significantly challenge bone regeneration, necessitating the development of innovative implantable devices for effective healing. This study explores the potential of 3D-printed calcium phosphate (CaP) scaffolds functionalized with natural medicine to address this issue. Specifically, quercetin and vitamin D3 (QVD) encapsulated solid lipid nanoparticles (QVD-SLNs) are incorporated into the scaffold to enhance bone regeneration. The melt emulsification method is utilized to achieve high drug encapsulation efficiency (~98%) and controlled biphasic release kinetics. The process-structure-property performance of these systems allows more controlled release while maintaining healthy cell-material interactions. The functionalized scaffolds show ~1.3- and ~-1.6-fold increase in osteoblast cell proliferation and differentiation, respectively, as compared with the control. The treated scaffold demonstrates a reduction in osteoclastic activity as compared with the control. The QVD-SLN-loaded scaffolds show ~4.2-fold in vitro chemopreventive potential against osteosarcoma cells. Bacterial assessment with both Staphylococcus aureus and Pseudomonas aeruginosa shows a significant reduction in bacterial colony growth over the treated scaffold. These findings summarize that the release of QVD-SLNs through a 3D-printed CaP scaffold can treat various bone-related disorders for low or non-load-bearing applications.

Mucosal-associated invariant T (MAIT) cells, a subset of Vα7.2+ T cells, are a crucial link between innate and adaptive immunity, responding to various stimuli through TCR-dependent and independent pathways. We investigated the responses of MAIT cells and Vα7.2+/CD161- T cells to different stimuli and evaluated the effects of Cyclosporin A (CsA) and Vitamin D3 (VitD). Peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with various agents (PMA/Ionomycin, 5-OP-RU, 5-OP-RU/IL-12/IL-33) with or without CsA and VitD. Flow cytometric analysis assessed surface markers and intracellular cytokine production. Under steady-state conditions, MAIT cells displayed elevated expression of CCR6 and IL-13. They showed upregulated activation and exhaustion markers after activation, producing IFNγ, TNFα, and TNFα/GzB. CsA significantly inhibited MAIT cell activation and cytokine production. Conversely, Vα7.2+/CD161- T cells exhibited distinct responses, showing negligible responses to 5-OP-RU ligand but increased cytokine production upon PMA stimulation. Our study underscores the distinct nature of MAIT cells compared to Vα7.2+/CD161- T cells, which resemble conventional T cells. CsA emerges as a potent immunosuppressive agent, inhibiting proinflammatory cytokine production in MAIT cells. At the same time, VitD supports MAIT cell activation and IL-13 production, shedding light on potential therapeutic avenues for immune modulation.

BACKGROUND: The COVID-19 pandemic has highlighted the vulnerability of particular patient groups to SARS-CoV-2 infection, including those with cardiovascular diseases, hypertension, and intestinal dysbiosis. COVID-19 affects the gut, suggesting diet and vitamin D3 supplementation may affect disease progression.
OBJECTIVE: To evaluate levels of Ang II and Ang-(1-7), cytokine profile, and gut microbiota status in patients hospitalized for mild COVID-19 with a history of cardiovascular disease and treated with daily doses of vitamin D3.
METHODS: We recruited 50 adult patients. We screened 50 adult patients and accessed pathophysiology study 22, randomized to daily oral doses of 10,000IU vitamin D3 (n=11) or placebo (n=11). Plasma levels of Ang II and Ang-(1-7) were determined by radioimmunoassay, TMA and TMAO were measured by liquid chromatography and interleukins (ILs) 6, 8, 10 and TNF-α by ELISA.
RESULTS: The Ang-(1-7)/Ang II ratio, as an indirect measure of ACE2 enzymatic activity, increased in the vitamin D3 group (24±5pg/mL vs. 4.66±2pg/mL, p<0.01). Also, in the vitamin D3-treated, there was a significant decline in inflammatory ILs and an increase in protective markers, such as a substantial reduction in TMAO (5±2μmoles/dL vs. 60±10μmoles/dL, p<0.01). In addition, treated patients experienced less severity of infection, required less intensive care, had fewer days of hospitalization, and a reduced mortality rate. Additionally, improvements in markers of cardiovascular function were seen in the vitamin D3 group, including a tendency for reductions in blood pressure in hypertensive patients.
CONCLUSIONS: Vitamin D3 supplementation in patients with COVID-19 and specific conditions is associated with a more favourable prognosis, suggesting therapeutic potential in patients with comorbidities such as cardiovascular disease and gut dysbiosis.

Various adjuvants have been tested clinically for patients with problems with embryo implantation during in vitro fertilization (IVF)-embryo transfer (ET). Vitamin D3, an essential modulator of various physiological processes, has received attention as an important adjuvant for successful pregnancy, as many studies have shown a strong association between vitamin D deficiency and implantation failure and fetal growth restriction. However, vitamin D has been widely utilized in different protocols, resulting in non-reproducible and debatable outcomes. In the present study, we demonstrated that cyclic intrauterine administration of vitamin D3 increased endometrial receptivity and angiogenesis, which could be attributed to increased recruitment of uterus-resident natural killer cells. In particular, cyclic treatment of vitamin D3 promoted stable attachment of the embryo onto endometrial cells in vitro, suggesting its merit during the early stage of embryo implantation to support the initial maternal-fetal interactions. Our findings suggest that women with repeated implantation failure may benefit from the use of vitamin D3 as a risk-free adjuvant prior to IVF-ET procedures to improve the uterine environment, and make it favorable for embryo implantation.

BACKGROUND: Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma. It is identified by the excessive production of abnormal monoclonal immunoglobulins, which can result in various clinical symptoms such as destructive bone lesions, renal dysfunction, anemia, and immunodeficiency. The current study aims to evaluate the serum levels of carboxy-terminal collagen crosslinks 1 (CTX-1), Fibulin-1, vitamin D3, LDH, and albumin in MM patients and their significance for early diagnosis.
METHODS: This study included 30 healthy controls (11 males, 19 females) and 60 patients with multiple myeloma (37 males and 23 females), aged between 40-60 years. Five-milliliter blood samples were collected and stored at -20°C. Afterward, enzyme-linked immunosorbent assay (ELISA) kits were used to estimate the concentrations of CTX-1, Fibulin-1, and vitamin D3. Additionally, LDH and albumin levels were determined using the automated biochemistry analyzer.
RESULTS: This study revealed that the majority of patients with multiple myeloma are between the ages of 51 and 60 years. The serum concentrations of CTX-1, Fibulin-1, and LDH were significantly increased in the multiple myeloma patients compared to the healthy control group. In contrast, the serum level of vitamin D3 was significantly decreased in patients with MM.
CONCLUSIONS: Our results indicate that the incidence of multiple myeloma is higher in males than in females. Additionally, the serum concentrations of CTX-1 and Fibulin-1 were significantly higher in the multiple myeloma patients compared to the healthy control group, indicating their potential for early detection and as therapeutic targets.

Since the beginning of the COVID-19 pandemic, vitamin D has attracted interest due to its immunomodulatory properties. Numerous studies show a correlation between vitamin D levels and COVID-19 cases and mortality. Therefore, we conducted a meta-analysis in order to assess the relationship between vitamin D3 supplementation and COVID-19 severity. We included 13 randomized clinical trials that contained the analyzed endpoints: length of COVID-19 hospitalization, number of intensive care unit (ICU) admissions, length of stay in the ICU, number of cases requiring any supplemental oxygenation, duration of any supplemental oxygenation, number of overall mortality and number of deaths associated with COVID-19. The relative risk with 95% confidence interval (CI) and the mean difference with 95% CI were calculated to compare the effect. A random effects model was used to calculate effect sizes. Our meta-analysis showed a positive effect of vitamin D3 supplementation on ICU admission (RR = 0.73; 95% CI [0.57; 0.95], p = 0.02, I2 = 19.6%) and mortality associated with COVID-19 among patients (RR = 0.56; 95% CI [0.34; 0.91]; p = 0.02; I2 = 0%). Vitamin D3 supplementation may potentially reduce the risk of ICU admission and death associated with COVID-19.