Obesity is an important risk factor for incidence and death for many types of cancer. Vitamin D reduces risk of incidence and death for many types of cancer. This review outlines the mechanisms by which obesity increases risk of cancer, how vitamin D reduces risk of cancer, and the extent to which vitamin D counters the effects of obesity in cancer. Vitamin D is a partial ally against some of obesity's pro-carcinogenic effects, notably by reducing inflammation and regulating sex hormone receptors, leptin resistance, cellular energy metabolism, the microbiome, and hypoxia. However, it can act stronger in against the renin-angiotensin system, insulin resistance, and oxidative stress in cancer. Additionally, excess fat tissue sequesters vitamin D and, along with its dilution in increased body volume, further reduces its bioavailability and serum concentration, limiting its protective effects against cancer. In conclusion, while vitamin D cannot reverse obesity, it plays a significant role in mitigating its pro-carcinogenic effects by targeting several mechanisms.

The role of vitamin D and its receptors (VDR) in PKDL and VL remains uncharacterized at genetic level. This study aimed to explore the single nucleotide polymorphism of VDR gene (rs1544410, rs7975232, rs731236) in association with PKDL and VL infection. A significant difference was observed among VL and PKDL patients versus healthy group (P ˂ 0.0001) for Bsm1 polymorphism. The comparison of VL and PKDL patients versus healthy control of VDR genotypes AA and GA were found highly significant (P˂0.0001). The risk for developing disease was 7.03 and 4.98 times greater in AA, while 2.49 and 2.97 times greater in GA in case of VL and PKDL patients, respectively. There was no statistical significant difference between VL and PKDL patients in VDR gene polymorphisms and allelic frequency (P > 0.05). The RNA expression profile of VDR gene and CYP27B1 gene were upregulated in pretreated PKDL (1.4-1.6 fold), but in VL patients, CYP27B1 (2-3 folds) and VDR (1.5 fold) expression were down regulated. Vitamin D levels in VL patients were significantly lower (22.41 ± 10.57 ng/ml), than PKDL patients (42.19 ± 10.84 ng/ml) (P˂0.01). However, no significant difference was observed in relation to the genetic data with age and sex for VL (P = 0.622) and PKDL (P = 0.786), clinical observations along with anthropometric indices. The Bsm1 gene polymorphisms may contribute in VL and PKDL infection as a risk factor.

- Granulomatous inflammation is a hallmark of several chronic inflammatory diseases, characterized by the formation of immune granulomas. The vitamin D receptor (VDR) and its ligands, such as paricalcitol, have demonstrated immunomodulatory effects on various immune cell subpopulations, including macrophages, dendritic cells, and T-cells. However, the precise role of VDR activation in granuloma formation and the associated immune regulatory pathways, including the PD-1/PD-L1 axis, remains poorly understood. This study aimed to evaluate the effects of paricalcitol, a selective VDR agonist, on granuloma formation and immune cell composition in an experimental model of superoxide dismutase A (SoDA)-induced inflammation, with a focus on antigen-presenting cells (including CD68 + and CD1a + cells), T- and B-cell populations, and PD-L1 expression.

- The study involved 90 male Wistar rats divided into control and experimental groups. Experimental animals received paricalcitol intraperitoneally at different time points relative to sensitization with SoDA and complete Freund's adjuvant. Granulomatous infiltrates were evaluated histologically, and the cellular composition was assessed via immunohistochemistry using markers such as CD68, CD3, CD1a, CD20, and PD-L1. Statistical analysis included quantitative morphometry and group comparisons.

- Paricalcitol administration significantly influenced granuloma development, with groups receiving treatment before (E1) or at the time of sensitization (E2) showing a reduction in immature granulomas and an increase in mature granulomas compared to the control groups. Enhanced macrophage differentiation, characterized by increased multinucleated giant cells and epithelioid cells, was observed. Additionally, there was a significant increase in PD-L1 expression in granulomatous infiltrates of treated groups, particularly in peripherally located immune cells. These effects were accompanied by a modulation of T-cell responses, including a reduction in CD3 + T-cell population.

- The findings suggest that paricalcitol promotes granuloma stabilization and maturation by modulating VDR-mediated immune pathways, including maturation and transformation of macrophages into epithelioid and giant multinucleated cells, increase in number of CD1a + cells, and PD-1/PD-L1 axis regulation. The ability of paricalcitol to enhance PD-L1 expression through the VDR-mediated pathways provides additional evidence for its role in preventing excessive immune responses and highlights the therapeutic potential of VDR agonists in managing granulomatous inflammation.

Inflammation is a critical part of innate immune response that is essential for exclusion of harmful stimuli and restoration of tissue homeostasis. Nonetheless, failure to resolve inflammation results in chronic inflammatory conditions, including autoimmune diseases. Conventionally, resolution of inflammation was deemed a passive process; however, evidence indicates that it entails active, highly regulated molecular and cellular events involving efferocytosis-driven macrophage reprogramming, post-transcriptional regulatory mechanisms and the production of specialized pro-resolving mediators (SPMs). These processes collectively restore tissue homeostasis and prevent chronic inflammation. Emerging therapeutic approaches targeting these pathways demonstrate promising results in preclinical studies and clinical trials, enhancing resolution and improving overall disease outcome. This resulted in a paradigm shift from conventional anti-inflammatory strategies to resolution-focused treatment. Yet, challenges remain due to the complexity of resolution mechanisms and tissue-specific differences. This review summarizes current advances in inflammation resolution, emphasizing emerging concepts of resolution pharmacology. By employing endogenous mechanisms facilitating resolution, novel therapeutic applications can effectively manage several chronic inflammatory disorders.

Restless legs syndrome (RLS) and acute ischemic stroke are prevalent conditions in neurology. Several studies have indicated a relationship between RLS, acute ischemic stroke, and vitamin D levels. This study aimed to evaluate vitamin D levels in patients with RLS after acute ischemic stroke, compared to those with only acute ischemic stroke, to determine if there is a significant association. A case-control study included 270 patients with acute ischemic stroke and 53 patients who developed RLS following acute ischemic stroke. The International Restless Legs Syndrome Study Group (IRLSSG) scale was used to assess RLS severity, and vitamin D levels were measured (levels below 20 ng/ml were considered insufficient). Patients with RLS after acute ischemic stroke had significantly lower vitamin D levels (P < 0.001) and a higher incidence of vitamin D insufficiency (P < 0.001) compared to those with only acute ischemic stroke. The multivariate logistic regression model adjusted for the age, female, smoking status, alcohol consumption, history of hypertension, history of diabetes, low density lipoprotein-cholesterol (LDL-C), Homocysteine (HCY), vitamin D, vitamin D (OR = 0.673, 95% CI: 0.610-0.743, P < 0.001) and sex remained (OR = 4.217, 95% CI: 1.390-12.791, P = 0.011) significantly associated with RLS following acute ischemic stroke. Among RLS patients, those with (extremely) severe RLS had lower vitamin D levels than those with mild to moderate RLS (P < 0.001). Vitamin D levels were negatively correlated with IRLSSG scores after adjusting for confounding factors. The area under the curve (AUC) was 0.915 (95% CI 0.873-0.958), and the cut-off value for vitamin D was 18.15 ng/ml, with a sensitivity of 84.4% and specificity of 90.6%. Adults with acute post-ischemic stroke RLS generally have lower vitamin D levels than those with ischemic stroke alone, and lower vitamin D levels are linked to more severe RLS symptoms. Vitamin D levels and sex are important influencing factors for the occurrence of RLS following acute ischemic stroke. Vitamin D level is an independent predictor of RLS after acute ischemic stroke and has high predictive value.

The current definition of a postbiotic is a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Postbiotics can be mainly classified as metabolites, derived from intestinal bacterial fermentation, or structural components, as intrinsic constituents of the microbial cell. Secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) are bacterial metabolites generated by the enzymatic modifications of primary bile acids by microbial enzymes. Secondary bile acids function as receptor ligands modulating the activity of a family of bile-acid-regulated receptors (BARRs), including GPBAR1, Vitamin D (VDR) receptor and RORγT expressed by various cell types within the entire human body. Secondary bile acids integrate the definition of postbiotics, exerting potential beneficial effects on human health given their ability to regulate multiple biological processes such as glucose metabolism, energy expenditure and inflammation/immunity. Although there is evidence that bile acids might be harmful to the intestine, most of this evidence does not account for intestinal dysbiosis. This review examines this novel conceptual framework of secondary bile acids as postbiotics and how these mediators participate in maintaining host health.

Vitamin D plays a key role in regulating the immune system and vaccine response, and hypovitaminosis D is a known risk factor for mortality. However, its potential influence on mortality in SARS-CoV-2 vaccinated older adults remains underexplored. This study aims to examine survival differences between unvaccinated and vaccinated older adults with varying vitamin D levels, and to assess the impact of vitamin D on mortality.

We recruited patients aged 65 and over from the Geriatrics Unit of Azienda Ospedale - Università Padova. Clinical, pharmacological data, including vaccination status and vitamin D levels, were collected at admission, alongside mortality data 12 months post-hospitalization. Participants were divided into three groups: unvaccinated, vaccinated with vitamin D levels of 25-50 nmol/L, and vaccinated with levels > 50 nmol/L.

A total of 126 participants were included (56% women, mean age 83 years). No significant differences were found in COVID-19 severity among the three groups. After 12 months, 24 deaths were recorded: 17% in unvaccinated, 19% in vaccinated with low vitamin D, and 20% in vaccinated with high vitamin D (p = 0.94). Kaplan-Meier curves showed that mortality risk for vaccinated individuals with low vitamin D was similar to unvaccinated patients but significantly higher than vaccinated individuals with high vitamin D (p = 0.04). Vitamin D levels of 25-50 nmol/L were associated with a threefold increased risk of 12-month mortality (HR: 3.79, p < 0.001).

Vitamin D levels can impact mortality in older vaccinated individuals. Early correction of vitamin D deficiency could potentially enhance outcomes.

Rheumatoid arthritis (RA) is a chronic inflammatory multisystemic disorder that can cause significant deformity and disability. Vitamin D has a role in Th1-medicated autoimmune diseases like RA. Furthermore, some observational studies have concluded that Vitamin D supplementation reduces the severity of RA.

This study aimed to find out any correlation between Vitamin D levels and severity of early RA.

This study settings and design were a cross-sectional single-center observational study.

This was an observational study. All patients with early RA were screened and evaluated as per protocol. No extra tests were done.

Pearson's Chi-square test for independence of attributes/Fisher's exact test was used to find the association between the categorical variables as appropriate.

We found that all patients of early RA had moderate-tosevere disease activity without any relation with their Vitamin D level ( P > 0.05).

Asthma and allergies have emerged as some of the most common chronic diseases, particularly in developed countries. Epidemiological studies have consistently demonstrated that children growing up in farming/rural environments are less likely to develop these conditions. Over the past three decades, China has experienced unprecedented economic development and urbanisation, accompanied by a rapid rise in the prevalence of allergic disorders. Despite the substantial number of affected individuals, allergy management in China remains inconsistent and often inadequate, compounded by variations in diagnostic criteria and limited healthcare access in less developed regions. Furthermore, the vast population, regional disparities, and methodological inconsistencies in data collection have hindered the acquisition of comprehensive, large-scale epidemiological data. This review examines the factors contributing to asthma and allergies from their early origins, focusing on modifiable factors from a specific perspective of China. Factors related to traditional lifestyle, such as early-life exposure to agricultural farming and poultry, diverse dietary patterns, and early introduction of allergenic foods, appear to offer protection against allergies. Conversely, exposure to open-fire cooking, incense burning, tobacco smoke, as well as early-life antibiotic use and perinatal factors like Caesarean section delivery and prematurity may represent potential risks. A clear understanding of the role of these factors would pave the way for developing effective interventions to mitigate the substantial health and socioeconomic burdens associated with asthma and allergies.

The prevalence of cardiometabolic diseases is rising, and this is fuelled by inflammation, which tends to be worse in individuals with vitamin D (VD) deficiency. While non-steroidal anti-inflammatory interventions are available, they present with coagulation events. Hence, alternative therapy in the form of VD supplements is gaining research interest. This study reviewed the effect of VD supplementation on inflammation, focusing on nuclear factor kappa-beta (NF-κβ), tumour necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) across different cardiometabolic disease. Thirty-seven studies, 16 rodent models and 21 clinical studies were evaluated. The study considered evidence from rodent models to understand the effect of VD on these markers of inflammation and its translatability to clinical studies. While the potential benefits of VD were notable in rodents, these effects were less consistent in clinical studies. Notably, rodent models showed a more pronounced impact of VD in reducing NF-κβ and TNF-α; however, clinical trials reported conflicting findings. Furthermore, the VD was important in reducing MCP-1 across different rodent models; this was partially demonstrated in clinical trials. Based on these findings, VD modulates inflammation in cardiometabolic disease by inhibiting the activation of NF-κβ and suppressing the production of TNF-α and MCP-1. Although VD has some possible benefits in rodent models, the translatability of these findings in clinical trials is limited. Hence, the presented evidence in this study calls for further randomised controlled trials to assess the effect of VD on inflammation in patients living with different conditions as a therapy to curb the inflammation and the risk thereof. Future trials should also focus on exploring the VD dose-response, optimal dose, and duration of VD intervention among these patients that may offer optimal benefits on inflammation.

Targeting optimal glycemic control based on hemoglobin A1c (A1c) values reduces but does not abolish the onset of diabetic kidney disease and its progression to chronic kidney disease (CKD). This suggests that factors other than the average glucose contribute to the residual risk. Vitamin D deficiency and frequent episodes of acute hyperglycemia (AH) are associated with the onset of albuminuria and CKD progression in diabetes. This study aimed to determine if moderate levels of AH harm podocytes directly or promote a pro-inflammatory monocyte/macrophage phenotype that leads to podocyte apoptosis, and whether vitamin D deficiency accelerates these processes. We found that AH (16.7 mM D- glucose) didn't induce podocyte apoptosis directly, but it did promote a pro-inflammatory response in human monocytes and macrophages, resulting in an increased TNF-α secretion causing podocyte apoptosis. The AH-induced monocyte TNF-α secretion was inversely correlated with healthy donors' serum 25(OH)D levels. AH induced monocyte TNF-α release by increasing oxidative and ER stress, which in turn increased ADAM17 (A Disintegrin And Metalloprotease 17) and iRhom2 (inactive Rhomboid protein 2) expression, both essential for TNF-α secretion. Additionally, monocyte activation of glucagon-like peptide-1 receptor (GLP-1R), using a GLP-1R agonist, downregulated ADAM17/iRhom2 expression, decreasing TNF-α release and reducing podocyte apoptosis. These results show that a normal vitamin D status may attenuate a mechanism by which AH contributes to podocyte apoptosis and CKD progression and might enhance a novel anti-inflammatory role of GLP-1 to prevent AH-driven CKD progression in diabetes.

Vitamin D was discovered as the cure for nutritional rickets, a disease of bone growth arising from inadequate intestinal calcium absorption, and for much of the 20th century, it was studied for its critical role in calcium homeostasis. However, we now recognize that the vitamin D receptor and vitamin D metabolic enzymes are expressed in numerous tissues unrelated to calcium homeostasis. Notably, vitamin D signaling can induce cellular differentiation and cell cycle arrest. Moreover, the vitamin D receptor and the enzyme CYP27B1, which produces the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), are expressed throughout the immune system. In addition, CYP27B1 expression in immune cells is regulated by physiological inputs independent of those controlling its expression in calcium homeostatic tissues. These observations have driven the development of 1,25D-like secosteroidal analogs and nonsecosteroidal analogs to separate the effects of vitamin D on cell differentiation and function from its calcemic activities. Notably, some of these analogs have had considerable success in the clinic in the treatment of inflammatory and immune-related disorders. In this review, we described in detail the mechanisms of vitamin D signaling and the physiological signals controlling 1,25D synthesis and catabolism, with a focus on the immune system. We also surveyed the effects of 1,25D and its analogs on the regulation of immune system function and their implications for human immune-related disorders. Finally, we described the potential of vitamin D analogs as anticancer therapeutics, in particular, their use as adjuncts to cancer immunotherapy. SIGNIFICANCE STATEMENT: Vitamin D signaling is active in both the innate and adaptive arms of the immune system. Numerous vitamin D analogs, developed primarily to minimize the dose-limiting hypercalcemia of the active form of vitamin D, have been used widely in preclinical and clinical studies of immune system regulation. This review presents a description of the mechanisms of action of vitamin D signaling, an overview of analog development, and an in-depth discussion of the immunoregulatory roles of vitamin D analogs.

The health benefits of vitamin D are far beyond bone mineral metabolism. Vitamin D has immunomodulator and anti-inflammatory properties and its role in critically ill patients is controversial. The purpose of the study is to understand whether high doses of vitamin D supplementation are beneficial in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia hospitalized in a polyvalent intensive care unit (ICU) and correlate to all-cause mortality, need for invasive mechanical ventilation, and duration of hospitalization.

A retrospective study was conducted at a single polyvalent ICU, comparing patients supplemented with vitamin D with nonsupplemented patients. Eligible participants were adults with SARS-CoV-2 pneumonia admitted in this unit between April 14, 2020, and October 31, 2020. Demographic and clinical characteristics, comorbidities, and disease-related outcomes were extracted from electronic medical records.

No statistically significant differences were observed between the groups in terms of need for invasive mechanical ventilation or duration of hospitalization. Supplementation with vitamin D was associated with lower all-cause ICU, intrahospital, and total mortality.

High-dose vitamin D supplementation was associated with a reduction of mortality in patients with severe SARS-CoV-2 pneumonia. Randomized clinical trials are needed to confirm these findings and to assess the optimal dosage of supplementation.

The SARS-CoV-2 vaccine is an important keystone in fighting against the virus. The vaccination alone could not prevent all SARS-CoV-2 viral infections or even its spread, especially after the emergence of newly mutant strains. The immune response to the SARS-CoV-2 vaccines varies greatly from one person to another. Age, along with adequate micronutrients, especially vitamin D, are major factors influencing immunity. We aimed to analyze SARS-CoV-2 vaccine neutralization potency and the total IgG antibodies along with 25-hydroxy-cholecalciferol concentrations in a cohort of healthy Egyptian vaccinated adults. 196 individuals were included; 145 females and 51 males, with an age range between 22 and 59 years old, from the first time of vaccination and over 16 weeks long. Three blood samples were taken from each individual at three time points; before the 1st dose of vaccination, before the 2nd dose of vaccination, and after 8 weeks of complete vaccination. The samples were analyzed using a chemiluminescent immunoassay to measure vitamin D level and titer of neutralizing and IgG antibodies. A lower level of neutralizing antibodies was detected in deficient and insufficient vitamin D-vaccinated individuals. However, a sufficient titer was detected in individuals with normal vitamin D. Vitamin D deficiency is associated with a suppressed immune response against SARS-CoV-2 despite vaccination. Thus, we made inquiries about using vitamin D as an adjuvant to SARS-CoV-2 vaccination, and its relation with the production of anti-SARS-CoV-2 antibodies.

Vitamin D is activated into 1α,25(OH)2D through two hydroxylation steps that are primarily catalyzed by 25-hydroxylase in the liver and 1α-hydroxylase in the kidneys. The active form of vitamin D regulates myriads of cellular functions through its nuclear receptor, vitamin D receptor (VDR). Vitamin D metabolizing enzymes and VDR are expressed in adipose tissues and vitamin D regulates multiple aspects of adipose biology including the recruitment and differentiation of adipose stem cells into adipocytes and metabolic, endocrine, and immune properties. Obesity is associated with low vitamin D status, which is thought to be explained by its sequestration in large mass of adipose tissues as well as dysregulated vitamin D metabolism. Low vitamin D status in obesity may negatively impact adipose biology leading to adipose tissue dysfunctions, the major pathological factors for cardiometabolic diseases in obesity. In this review, the current understanding of vitamin D metabolism and its molecular mechanisms of actions, focusing on vitamin D-VDR regulation of adipose biology with their implications on obesity-associated diseases, is discussed. Whether improving vitamin D status leads to reductions in adiposity and risks for cardiometabolic diseases is also discussed.

This study explores the complex link between vitamin D and neurological illnesses, focusing on how vitamin D affects possible risk factors, therapeutic applications, and the trajectory of the disease. An epidemiological study has linked vitamin D insufficiency to several neurological conditions, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. It is hypothesized that immunomodulatory and anti-inflammatory properties of vitamin D contribute to its neuroprotective effects. Two major mechanisms in dementia include neuroinflammation and oxidative stress. Adequate levels of vitamin D have been shown in both animal models and human studies to enhance both clinical outcomes and the duration of illness in those who have it. Other ways that vitamin D contributes to its therapeutic potential include the production of neurotrophic factors, control over neurotransmitter synthesis, and preservation of the blood-brain barrier. Despite the encouraging outcomes, research is still being conducted to determine the optimal dosage and long-term benefits of vitamin D supplementation on brain function. In order to furnish precise directives and clarify the processes behind the neuroprotective impacts of vitamin D, future research must focus on large-scale randomized controlled studies. . This study highlights the significance of maintaining adequate levels of vitamin D as a modifiable risk factor for neurological disorders. Further study is also required to comprehend the possible medical benefits of this vitamin fully.

Several nutrients are crucial in enhancing the immune system and preserving the structural integrity of bodily tissue barriers. Vitamin D (VD) and zinc (Zn) have received considerable interest due to their immunomodulatory properties and ability to enhance the body's immune defenses. Due to their antiviral, anti-inflammatory, antioxidative, and immunomodulatory properties, the two nutritional powerhouses VD and Zn are crucial for innate and adaptive immunity. As observed with COVID-19, deficiencies in these micronutrients impair immune responses, increasing susceptibility to viral infections and severe disease. Ensuring an adequate intake of VD and Zn emerges as a promising strategy for fortifying the immune system. Ongoing clinical trials are actively investigating their potential therapeutic advantages. Beyond the immediate context of the pandemic, these micronutrients offer valuable tools for enhancing immunity and overall well-being, especially in the face of future viral threats. This analysis emphasizes the enduring significance of VD and Zn as both treatment and preventive measures against potential viral challenges beyond the current health crisis. The overview delves into the immunomodulatory potential of VD and Zn in combating viral infections, with particular attention to their effects on animals. It provides a comprehensive summary of current research findings regarding their individual and synergistic impacts on immune function, underlining their potential in treating and preventing viral infections. Overall, this overview underscores the need for further research to understand how VD and Zn can modulate the immune response in combatting viral diseases in animals.

The role of vitamin D in regulating calcium metabolism and skeletal growth and disease is widely recognized. Indeed, current recommendations for serum vitamin D concentrations are based on these parameters. A serum vitamin D <20 ng/mL is considered deficient, concentrations between 20 and 30 ng/mL are insufficient, and >30 ng/mL is adequate. However, over the past number of years, epidemiological studies, randomized clinical trials, and preclinical animal and cell culture-based research have demonstrated that vitamin D modulates immune function. Cardiovascular disease (CVD), the leading cause of morbidity and mortality in the United States and in industrialized nations, is mediated in part by chronic inflammation as well as by other well-established risk factors including dyslipidemia, hypertension, obesity, and diabetes. Vitamin D deficiency (<20 ng/mL or <50 nM) is associated with increased CVD risk. As described in this review, several recent systematic reviews and meta-analyses provide some evidence that vitamin D administration to individuals with vitamin D deficiency may have little effect on CVD-related mortality. Many well-designed randomized clinical trials in the general population as well as in people at risk for CVD-related complication later in life provide evidence that treatment may be beneficial. These latter studies as well as the paucity of information regarding the optimal vitamin D concentration required for optimizing immune function in patients indicate that more research is needed to address whether vitamin D supplements may be a cost-effective intervention for preventing CVD.

Vitamin D (VD) is a vital lipophilic secosteroid hormone known for its essential role in maintaining skeletal health and regulating calcium and phosphate metabolism. Recent evidence has begun to illuminate its significance beyond bone health, particularly in relation to thrombosis-a condition characterized by blood clot formation within the vascular system that can lead to serious cardiovascular events such as myocardial infarction and stroke. VD deficiency, defined as a plasma 25-hydroxyVD level below 25 nmol/L, affects a substantial portion of the global population, with prevalence rates ranging from 8% to 18%. This study systematically explores the relationships between VD levels and the risk of thrombosis, investigating the underlying mechanisms including VD's anticoagulant properties, influence on inflammatory pathways, and interactions with endothelial cells. Epidemiological data suggest that low serum levels of VD correlate with an increased risk of venous thromboembolism (VTE), although the reported findings remain inconsistent. Mechanisms that potentially link VD to thrombotic risk include modulation of thrombomodulin and tissue factor expression, as well as enhancement of anti-inflammatory cytokines. Given the prevalence of VD insufficiency, particularly among populations with limited exposure to sunlight, this research highlights the urgent need for strategies to increase VD levels through dietary modifications and supplementation in order to prevent thrombotic events.

Melatonin and vitamin D are associated with the immune system and have important functions as antioxidants. Numerous attempts have been made to identify up to date activities of these molecules in various physiological conditions. The biosynthetic pathways of melatonin and vitamin D are correlated to sun exposure in an inverse manner. Vitamin D is biosynthesized when the skin is exposed to the sun's UV radiation, while melatonin synthesis occurs in the pineal gland principally during night. Additionally, vitamin D is particularly associated with intestinal absorption, metabolism, and homeostasis of ions including calcium, magnesium. However, melatonin has biological marks and impacts on the sleep-wake cycle. The roles of vitamin D and melatonin are opposed to each other individually, but either of them is implicated in the immune system. Recently studies have shown that melatonin and vitamin D have their specific set of aberrations in different cell signaling pathways, such as serine/threonine-specific protein kinase (Akt), phosphoinositide 3-kinase (PI3K), nuclear factor-κB (NF-κB), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and Notch. The aim of this review is to clarify the common biological functions and molecular mechanisms through which melatonin and vitamin D could deal with different signaling pathways.

Arsenic, a well-known environmental endocrine disruptor, exerts interference on the body's endocrine system. Our previous investigations have demonstrated that chronic exposure to sodium arsenite (NaAsO2) can induce thyroid damage and dysfunction in Sprague-Dawley (SD) rats. Vitamin D (VD) is an indispensable fat-soluble vitamin that plays a crucial role in maintaining thyroid health. In recent years, numerous studies have demonstrated the association between VD deficiency and the development of various thyroid disorders. However, the precise intervention roles and mechanisms of VD in arsenic-induced thyroid injury remain elusive. This study aimed to investigate the intervention effect of VD on NaAsO2-induced thyroid dysfunction in SD rats. The results demonstrated that exposure to NaAsO2 activates the TLR4/NF-κB signaling pathway in thyroid tissue of rats, leading to apoptosis of thyroid cells and subsequent inflammatory damage and disruption of serum thyroid hormone secretion. Supplementation with TAK-242 (a TLR4 inhibitor) and VD effectively inhibits the activation of the TLR4/NF-κB signaling pathway in rat thyroid tissue exposed to NaAsO2, thereby reducing the inflammatory damage and dysfunction caused by arsenic exposure. In conclusion, the findings of this study offer innovative insights into the application of VD in the prevention and treatment of thyroid dysfunction caused by arsenic exposure.

As of the 7th of July 2024, 775,754,322 confirmed cases of COVID-19, including 7,053,902 deaths worldwide, had been reported to the WHO (World Health Organization). Nevertheless, untill the 15th of July 2024, a total of 13,578,710,228 vaccine doses had been administered, with almost no country spared from COVID-19 attacks. The pathophysiology of this virus is complicated, and several symptoms require a deep understanding of the actual mechanisms. It is unclear why some patients develop severe symptoms while others do not, although literature suggests a role for vitamin D. Vitamin D plays a crucial role in the infection or in ameliorating the severity of symptoms. The mechanism of action of vitamin D and vitamin D deficiency (VDD) is well understood. VDD is associated with increased hospitalization of severely ill patients and increased levels of COVID-19-caused mortality. Recent studies suggest that vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene significantly impact the severity and outcomes of COVID-19, especially in the infections caused by Delta and Omicron variants. Furthermore, VDD causes immune system dysregulation upon infection with SARS-CoV-2, indicating that vitamin D sufficiency is crucial in fighting against COVID-19 infection. The therapeutic effect of vitamin D raises interest in its potential role as a prophylactic and treatment adjunct. We evaluate the immunomodulatory effects of vitamin D and its ability to enhance the efficacy of new antiviral drugs like molnupiravir and paxlovid against SARS-CoV-2. This review discusses the role of vitamin D sufficiency and VDD in COVID-19 initiation and progression, emphasizing the molecular mechanisms by which vitamin D exerts its actions as a proactive step for the next pandemic. However, there is still no clear evidence of vitamin D's impact on prevention and treatment, leading to contradictory findings. Therefore, large-scale randomized trials are required to reach a definitive conclusion. A bibliometric analysis of publications related to vitamin D, immunity, and COVID-19 revealed a significant increase in research activity in this area, particularly in 2020-2024, underscoring the growing recognition of vitamin D's potential role in the context of the pandemic.

Earlier studies about the influence of vitamin D (Vit D) supplementation on patients with inflammatory bowel disease (IBD) reported inconsistent results. Current comprehensive systematic review and meta-analysis was conducted to assess the effect of Vit D supplementation on clinical and subclinical factors in patients with IBD.

PubMed, Scopus, and Web of Science databases were searched for relevant randomized controlled trials (RCTs) on the effect of Vit D supplementation in IBD patients, published up to March 2023. Data were analyzed by the random-effect model. Heterogeneity was assessed by Cochran's Q test and I-square (I 2) statistic. The mean differences (MDs) were calculated as the summary effect size.

We included nine related articles, and our findings indicated that vitamin D administration increased serum vitamin D levels compared to placebo (weighted mean difference (WMD): 12.08; 95% confidence interval (95% CI): 9.06, 15.09; I 2 = 97.01%; P < 0.001) in IBD patients. However, it had no significant influence on disease activity (standardized mean difference (SMD): 0.27; 95% CI: -0.42, 0.95; I2 = 91.7%; P < 0.001) or serum levels of C-reactive protein (CRP) (WMD: -1.42; 95% CI: -3.90, 1.06; I2 = 41.9%; P = 0.262).

Current meta-analysis showed a significant effect of Vit D supplementation on increasing serum cholecalciferol. However, no significant effects of Vit D supplementation on the disease activity and serum levels of CRP were seen. Further studies are needed to expand current knowledge in this issue and found a significant increment in serum 25-hydroxy cholecalciferol concentrations following Vit D supplementation in IBD patients.

Vitamin D (VD), a crucial micronutrient, regulates bone health and immune responses. Recent studies suggest that VD may confer protective effects against chronic inflammatory diseases. Additionally, plant-based peptides can show biological activities. Furthermore, the supplementation of protein hydrolysates with VD could potentially enhance the bioactivity of peptides, leading to synergistic effects. In this study, THP-1 cells were exposed to low concentrations of Lipopolysaccharide (LPS) to induce inflammation, followed by treatment with vitamin D at different concentrations (10, 25, or 50 nM) or a chickpea protein hydrolysate ("H30BIO") supplemented with VD. The cytotoxicity of VD was evaluated using viability assay to confirm its safety. The cytokine secretion of TNF-α, IL-1β, and IL6 was assessed in the cell supernatant, and the gene expression of TNF-α, IL-1β, IL6, IL8, CASP-1, COX2, NRF2, NF-ĸB, NLRP3, CCL2, CCR2, IP10, IL10, and RANTES was quantified by qRT-PCR. Treatment with VD alone significantly decreased the expression of the pro-inflammatory genes TNF-α and IL6, as well as their corresponding cytokine levels in the supernatants. While IL-1β gene expression remained unchanged, a reduction in its cytokine release was observed upon VD treatment. No dose-dependent effects were observed. Interestingly, the combination of VD with H30BIO led to an increase in TNF-α expression and secretion in contrast with the LPS control, coupled with a decrease in IL-1β levels. Additionally, genes such as IP10, NF-κB, CCL2, COX2, NRF2, and CASP-1 exhibited notable modulation, suggesting that the combination treatment primarily downregulates NF-κB-related gene activity. This study demonstrates a synergistic interaction between VD and H30BIO, suggesting that this combination may enhance pathways involving TNF-α, potentially aiding in the resolution and modulation of inflammation through adaptive processes. These findings open new avenues for research into the therapeutic applications of enriched protein hydrolysates with VD to manage low-grade inflammatory-related conditions.

Staying and climbing in high mountains (>2,500 m) involves changes in diet due to poor access to fresh food, lack of appetite, food poisoning, environmental conditions and physiological changes. The purpose of this review is to summarize the current knowledge on the principles of nutrition, hydration and supplementation in high-altitude conditions and to propose practical recommendations/solutions based on scientific literature data. Databases such as Pubmed, Scopus, ScienceDirect and Google Scholar were searched to find studies published from 2000 to 2023 considering articles that were randomized, double-blind, placebo-controlled trials, narrative review articles, systematic reviews and meta-analyses. The manuscript provides recommendations for energy supply, dietary macronutrients and micronutrients, hydration, as well as supplementation recommendations and practical tips for mountaineers. In view of the difficulties of being in high mountains and practicing alpine climbing, as described in the review, it is important to increase athletes' awareness of nutrition and supplementation in order to improve well-being, physical performance and increase the chance of achieving a mountain goal, and to provide the appropriate dietary care necessary to educate mountaineers and personalize recommendations to the needs of the individual.

Numerous studies have shown that vitamin D may play an important role in modulating the inflammatory process. This study aimed to evaluate the effect of vitamin D supplementation on inflammatory markers in patients with orthopedic disorders and obesity. Thirty-three obese subjects were included in the study and were divided into two groups based on their medical condition: acute orthopedic diseases and chronic orthopedic diseases. Inclusion criteria for the research included age 18-75 years, BMI > 30 kg/m2, vitamin D deficiency, and no previous vitamin D supplementation. Samples were collected before and after 3 months of 4000 IU/day vitamin D supplementation. The study used enzyme-linked immunosorbent assay (ELISA) and measured serum levels of markers such as chitinase-3-like protein 1 (YKL-40), interleukin 6 (IL-6), interleukin 17 (IL-17), tumor necrosis factor (TNF-α), and adiponectin. After 3 months of vitamin D supplementation, a statistically significant increase in vitamin D and IL-17 levels was observed in the group with acute orthopedic diseases. Similarly, after supplementation, a statistically significant increase in vitamin D, IL-6 and TNF-α levels was observed in the group with chronic orthopedic diseases. Moreover, after vitamin D supplementation, statistically significantly higher adiponectin levels were observed in the chronic orthopedic group than in the acute orthopedic group. Despite high-dose vitamin D supplementation, inflammatory markers increased in acute and chronic orthopedic conditions. Based on our study, vitamin D does not reduce inflammation in patients with orthopedic conditions and obesity.

The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses in circulation and mitigating inflammation. While SARS-CoV-2 reduces ACE-2 expression, vitamin D increases it, counteracting the virus's harmful effects. Vitamin D's beneficial actions are mediated through complex molecular mechanisms involving innate and adaptive immune systems. Meanwhile, vitamin D status [25(OH)D concentration] is inversely correlated with severity, complications, and mortality rates from COVID-19. This study explores mechanisms through which vitamin D inhibits SARS-CoV-2 replication, including the suppression of transcription enzymes, reduced inflammation and oxidative stress, and increased expression of neutralizing antibodies and antimicrobial peptides. Both hypovitaminosis D and SARS-CoV-2 elevate renin levels, the rate-limiting step in the renin-angiotensin-aldosterone system (RAS); it increases ACE-1 but reduces ACE-2 expression. This imbalance leads to elevated levels of the pro-inflammatory, pro-coagulatory, and vasoconstricting peptide angiotensin-II (Ang-II), leading to widespread inflammation. It also causes increased membrane permeability, allowing fluid and viruses to infiltrate soft tissues, lungs, and the vascular system. In contrast, sufficient vitamin D levels suppress renin expression, reducing RAS activity, lowering ACE-1, and increasing ACE-2 levels. ACE-2 cleaves Ang-II to generate Ang(1-7), a vasodilatory, anti-inflammatory, and anti-thrombotic peptide that mitigates oxidative stress and counteracts the harmful effects of SARS-CoV-2. Excess ACE-2 molecules spill into the bloodstream as soluble receptors, neutralizing and facilitating the destruction of the virus. These combined mechanisms reduce viral replication, load, and spread. Hence, vitamin D facilitates rapid recovery and minimizes transmission to others. Overall, vitamin D enhances the immune response and counteracts the pathological effects of SARS-CoV-2. Additionally, data suggests that widely used anti-hypertensive agents-angiotensin receptor blockers and ACE inhibitors-may lessen the adverse impacts of SARS-CoV-2, although they are less potent than vitamin D.

Temporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration.

Mice ablated for Vdr (Vdr-/-res) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr-/- chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined.

Vdr-/-res mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr-/-res mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr-/-res mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr-/- chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr-/- chondrocytes.

VD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ.

Oxidative stress and inflammation play a vital function in the pathophysiology of polycystic ovary syndrome (PCOS) and infertility. The aim of this work was to control the impacts of vitamin D intake on metabolic profiles in infertile subjects with PCOS.

This randomized, double-blinded, placebo-controlled clinical trial was carried out among 40 infertile women with PCOS. Subjects were randomly divided into two intervention groups to take either 50 000 IU vitamin D (n=20) or placebo (n=20) weekly for 8 weeks. Metabolic profiles and few inflammatory cytokines expression evaluated on peripheral blood mononuclear cells (PBMCs) of participants, using real-time polymerase chain reaction (RT-PCR) method.

Vitamin D intake decreased high-sensitivity C-reactive protein (hs-CRP) (-0.9±1.1 vs. 0.3±0.9 mg/l, P=0.002) and elevated total antioxidant capacity (TAC) levels (49.2±60.2 vs. -50.6±161.8 mmol/l, P=0.02) compared with placebo; but no significant effects on other metabolic parameters were observed. Moreover, a significant downregulation of tumor necrosis factor alpha (TNF-α) expression (P=0.03) was observed after taking vitamin D compared with the placebo.

Overall, vitamin D intake for eight weeks had beneficial impacts on hs-CRP, TAC, and TNF-α among infertile women with PCOS.

The COVID-19 pandemic has promoted an intensive investigation into the pathophysiological mechanisms of SARS-CoV-2 infection, risk factors, and its impact on disease severity. Vitamin D has generated significant attention for its potential role in viral prevention and immune defense due to its pleiotropic functions, including immunomodulation and antimicrobial effects. This study aimed to assess serum 25(OH)D3 levels in patients with COVID-19 compared to those with other viral respiratory infections and to evaluate associations of vitamin D levels with symptomatology, clinical characteristics, presence of comorbidities and laboratory investigation.

The study included 78 patients admitted to a hospital with COVID-19 (52 patients) or other viral respiratory infections (26 patients). Routine blood biomarkers, markers of inflammation, markers of endothelial dysfunction, serum 25(OH)D3 were analyzed, and patients were classified according to vitamin D levels and presence of comorbidities.

Most patients had vitamin D levels <30 ng/mL and there was no significant difference in 25(OH)D3 levels between patients with and without COVID-19 (p=0.768). Aging and comorbidity prevalence were significantly increased in the COVID-19 than in the non-COVID-19 group (p<0.001; p=0.049). A significant positive correlation was determined between endocan level and serum ferritin concentration in patients with COVID-19 and vitamin D deficiency. A borderline significantly elevated NLR was observed in patients with COVID-19 who were also vitamin D deficient, compared with the similar non-COVID-19 subgroup (p=0.05). In patients with COVID-19 and insufficient vitamin D, levels of 25(OH)D negatively correlated with endocan. Interestingly, COVID-19 patients with diabetes exhibited significantly lower 25(OH)D3 levels compared to non-diabetic patients (p=0.003), along with higher ferritin levels, suggesting a potential association between vitamin D deficiency and diabetes in COVID-19.

These findings contribute to the understanding of the complex interplay between vitamin D status, comorbidities, and COVID-19 outcomes, emphasizing the need for further research to elucidate their underlying mechanisms and clinical implications.

The impact of nutrient availability on the survival of Mycobacterium leprae and the development of leprosy remains largely unknown. Iron is essential for the survival and replication of pathogens, while vitamin D has been involved with pathogen elimination and immunoregulation.

We evaluated the influence of dietary iron and vitamin D supplementation and restriction on the inflammatory response of mouse immune cells in vitro.

After 30 days of standard or modified diets, peritoneal cells and splenocytes were stimulated with the alive microorganisms and sonicated antigens of M. leprae, respectively. The production of inflammatory cytokines, reactive oxygen species, and cell proliferation were evaluated.

In peritoneal cells, vitamin D supplementation and iron restriction reduced the production of IL-6 and TNF in response to M. leprae, while splenocytes presented a reduction in TNF production under the same conditions. Lower levels of IFN-γ and TNF were observed in both iron-supplemented and iron-deficient splenocytes. Besides, iron supplementation also reduced the production of IL-6 and IL-10. No changes in the production of reactive oxygen species or in cell proliferation were observed related to different diets.

Taken together, these data point to an interference of the status of these nutrients on the interaction between the host and M. leprae, with the potential to interfere with the progression of leprosy. Our results highlight the impact of nutritional aspects on this neglected disease, which is significantly associated with unfavourable social conditions.

Bile acids are steroids formed at the interface of host metabolism and intestinal microbiota. While primary bile acids are generated in the liver from cholesterol metabolism, secondary bile acids represent the products of microbial enzymes. Close to 100 different enzymatic modifications of bile acids structures occur in the human intestine and clinically guided metagenomic and metabolomic analyses have led to the identification of an extraordinary number of novel metabolites. These chemical mediators make an essential contribution to the composition and function of the postbiota, participating to the bidirectional communications of the intestinal microbiota with the host and contributing to the architecture of intestinal-liver and -brain and -endocrine axes. Bile acids exert their function by binding to a group of cell membrane and nuclear receptors collectively known as bile acid-regulated receptors (BARRs), expressed in monocytes, tissue-resident macrophages, CD4+ T effector cells, including Th17, T regulatory cells, dendritic cells and type 3 of intestinal lymphoid cells and NKT cells, highlighting their role in immune regulation. In this review we report on how bile acids and their metabolitesmodulate the immune system in inflammations and cancers and could be exploiting for developing novel therapeutic approaches in these disorders.

To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults.

We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis.

After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups.

Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; 24: 554-562.

Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke.

A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke.

A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR: .85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10).

Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

VDX-111 (also identified as AMPI-109) is a vitamin D derivative which has shown anticancer activity. To further assess the function of this compound against multiple cancer types, we examined the efficacy of VDX-111 against a panel of 30 well characterized canine cancer cell lines. Across a variety of cancer types, VDX-111 induced widely variable growth inhibition, cell death, and migration inhibition, at concentrations ranging from 10 nM to 1 μM. Growth inhibition sensitivity did not correlate strongly with tumor cell histotype; however, it was significantly correlated with the expression of genes in multiple cell signaling pathways, including the MAPK and PI3K-AKT pathways. We confirmed inhibition of these signaling pathways as likely participants in the effects of VDX-111. These results suggest that a subset of canine tumors may be sensitive to treatment with VDX-111, and suggests possible predictive markers of drug sensitivity and pharmacodynamic biomarkers of drug exposure that could be employed in future clinical trials.

Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels and maintaining bone health. However, it was later discovered that many organs express vitamin D metabolizing enzymes and have a ligand for vitamin D, which regulates the expression of an extensive assortment of genes. As a result, vitamin D is indispensable for the proper function of organs, and its deficiency is believed to be a critical factor in symptoms and disorders such as cardiovascular diseases, autoimmune diseases, and cancers. The significance of vitamin D in reproductive tissues was recognized later, and studies have revealed its crucial role in male and female fertility, as well as proper reproductive function during pregnancy. Vitamin D deficiency has been identified as a risk factor for infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, and endometriosis. However, data investigating the association between vitamin D levels and reproductive disorders, including endometriosis, have encountered inconsistencies. Therefore, the present study aims to review existing research on the effect of vitamin D on proper reproductive function, and the role of deficiency in reproductive diseases and specifically focuses on endometriosis.

Higher 25-hydroxyvitamin D (25(OH)D) concentrations in serum has a positive association with pulmonary function. Investigating genome-wide interactions with 25(OH)D may reveal new biological insights into pulmonary function.

We aimed to identify novel genetic variants associated with pulmonary function by accounting for 25(OH)D interactions.

We included 211,264 participants from the observational United Kingdom Biobank study with pulmonary function tests (PFTs), genome-wide genotypes, and 25(OH)D concentrations from 4 ancestral backgrounds-European, African, East Asian, and South Asian. Among PFTs, we focused on forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) because both were previously associated with 25(OH)D. We performed genome-wide association study (GWAS) analyses that accounted for variant×25(OH)D interaction using the joint 2 degree-of-freedom (2df) method, stratified by participants' smoking history and ancestry, and meta-analyzed results. We evaluated interaction effects to determine how variant-PFT associations were modified by 25(OH)D concentrations and conducted pathway enrichment analysis to examine the biological relevance of our findings.

Our GWAS meta-analyses, accounting for interaction with 25(OH)D, revealed 30 genetic variants significantly associated with FEV1 or FVC (P2df <5.00×10-8) that were not previously reported for PFT-related traits. These novel variant signals were enriched in lung function-relevant pathways, including the p38 MAPK pathway. Among variants with genome-wide-significant 2df results, smoking-stratified meta-analyses identified 5 variants with 25(OH)D interactions that influenced FEV1 in both smoking groups (never smokers P1df interaction<2.65×10-4; ever smokers P1df interaction<1.71×10-5); rs3130553, rs2894186, rs79277477, and rs3130929 associations were only evident in never smokers, and the rs4678408 association was only found in ever smokers.

Genetic variant associations with lung function can be modified by 25(OH)D, and smoking history can further modify variant×25(OH)D interactions. These results expand the known genetic architecture of pulmonary function and add evidence that gene-environment interactions, including with 25(OH)D and smoking, influence lung function.

Low-grade systemic inflammation measured as high sensitivity C-reactive protein (hs-CRP) has been associated with non-communicable disease risk. We assessed whether prenatal inflammation and early-childhood vitamin D are associated with inflammation until age 6-8.

We analyzed blood hs-CRP and 25-hydroxy vitamin D [25(OH)D] in pregnancy, at birth from umbilical cord blood (UCB), from offspring at ages 1, 2, and 6-8 years in the Vitamin D Intervention in Infants (VIDI) study. VIDI was a randomized-controlled trial of vitamin D supplementation of 10 μg/day or 30 μg/day from age 2 weeks until 2 years in 975 infants recruited in 2013-14, with follow-up at age 6-8 in 2019-21 (n = 283).

Pregnancy hs-CRP was associated with UCB hs-CRP (r = 0.18, p < 0.001) but not independently with childhood hs-CRP (Estimate [95% CI] 0.04 [<-0.00, 0.09]). Higher UCB hs-CRP was associated independently with higher hs-CRP until 6-8 years (0.20 [0.12, 0.29]). Infant vitamin D dose had no effect on longitudinal hs-CRP (6-8 years, 0.11 [-0.04, 0.25]). Childhood 25(OH)D were associated positively with hs-CRP until age 6-8 (0.01 [>0.00, 0.01]).

Our results indicate that in children, inflammation, assessed by hs-CRP, persists from birth until 6-8 years. We observed positive associations between 25(OH)D and hs-CRP in vitamin D-sufficient children.

High sensitivity C-reactive protein (hs-CRP) concentrations tract from birth to age 8 years Our novel finding suggests a long-lasting pro-inflammatory phenotype in the child Higher vitamin D concentration - but not dose - is associated with higher childhood hs-CRP Chronic disease risk related to inflammation may in part originate from the prenatal period or early childhood Further studies are needed to investigate the effects of inflammation on long-term clinical health outcomes.

Human patients with type 1 diabetes mellitus (T1DM) are susceptible to several long-term complications that are related to glycemic control and immune dysregulation. Immune function remains relatively unexplored in dogs with naturally occurring diabetes mellitus (NODM). Calcitriol improves various aspects of immune function in a variety of species, but its effect in diabetic dogs remains unexplored. Therefore, the objectives of this study were to (i) evaluate immune function in dogs with NODM and determine if differences exist based on the level of clinical control and (ii) assess the immunomodulatory effects of calcitriol. Twenty diabetic dogs (clinically controlled, n = ten, not controlled, n = ten) and 20 non-diabetic, healthy control dogs were included in this prospective, case-control study. Whole blood was incubated with calcitriol (10-7 M) or negative control, after which the samples were divided for phagocytosis and leukocyte cytokine response experiments. The phagocytosis of opsonized Escherichia coli (E. coli) was evaluated with flow cytometry. The samples for leukocyte cytokine response evaluations were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate buffer solution (PBS; negative control), and tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured in supernatant using a canine-specific multiplex bead-based assay. The leukocytes from diabetic dogs produced higher concentrations of IL-10 (p = 0.01), IL-6 (p < 0.0001), and IL-8 (p < 0.0001) than the control dogs while controlling for the intervention and stimulant. Calcitriol decreased the supernatant concentrations of TNF-α (p < 0.001) and IL-8 (p = 0.04) with concomitant increases in IL-6 (p = 0.005). Diabetic dogs had a lower percentage of leukocytes undergoing phagocytosis (p < 0.0001) but a higher number of bacteria phagocytized per cell (p = 0.001) when compared to the control dogs. Calcitriol had no effect on phagocytic capacity. Lastly, the status of clinical control in diabetic dogs did not yield differences in immune function. These results support that dogs with NODM exhibit immune dysregulation and warrant additional investigation.

Diabetes is a common chronic metabolic disease with complex causes and pathogenesis. As an immunomodulator, vitamin D has recently become a research hotspot in the occurrence and development of diabetes and its complications. Many studies have shown that vitamin D can reduce the occurrence of diabetes and delay the progression of diabetes complications, and vitamin D can reduce oxidative stress, inhibit iron apoptosis, promote Ca2+ influx, promote insulin secretion, and reduce insulin resistance. Therefore, the prevention and correction of vitamin D deficiency is very necessary for diabetic patients, but further research is needed to confirm what serum levels of vitamin D3 are maintained in the body. This article provides a brief review of the relationship between vitamin D and diabetes, including its acute and chronic complications.

Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear.

We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target.

The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy.

This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

Vitamin D3 replacement in older insufficient adults significantly improves their antigen-specific varicella zoster virus (VZV) cutaneous immunity. However, the mechanisms involved in this enhancement of cutaneous immunity are not known. Here, we show for the first time that vitamin D3 blocks the senescence-associated secretory phenotype (SASP) production by senescent fibroblasts by partially inhibiting the p38 MAPK pathway. Furthermore, transcriptomic analysis of skin biopsies from older subjects after vitamin D3 supplementation shows that vitamin D3 inhibits the same inflammatory pathways in response to saline as the specific p38 inhibitor, losmapimod, which also enhances immunity in the skin of older subjects. Vitamin D3 supplementation therefore may enhance immunity during ageing in part by blocking p38 MAPK signalling and in turn inhibit SASP production from senescent cells in vivo.