Environmental factors contribute to approximately 41% of the risk of rheumatoid arthritis (RA). Previous studies have focused on anthropogenic environmental factors, while much less attention has been given to natural environmental factors. Our study explored the potential influence of natural environmental factors at birth on the risk of RA.

This large retrospective study utilized data from the China Kadoorie Biobank. A restricted cubic spline (RCS) model was employed to explore nonlinear relationships between natural environmental factors and the risk of RA. Additionally, a multivariable Cox regression model, adjusted for confounding factors, was used to examine correlations between season of birth, geographic, climate, and the risk of RA.

A total of 512,715 participants were included in this study, of which 2889 (0.56%) were diagnosed with RA. The RCS analysis revealed that the monthly average temperature at birth (p < 0.001), the latitude (p = 0.027) of the birthplace, and the sunshine rate (p < 0.001) exhibited a nonlinear relationship with the risk of RA. Multivariable Cox regression analysis revealed that participants born in Spring and Summer (HR 1.13, 95% CI 1.05-1.23) had an increased risk of RA compared to those born in Autumn and Winter. Additionally, participants born at latitudes ≤ 24°N (HR 1.49, 95% CI 1.32-1.68), with sunshine rate ≤ 28% (HR 2.00, 95% CI 1.75-2.29) or ≥ 60% (HR 1.22, 95% CI 1.08-1.38) had an increased risk of RA. Being born in regions with a monthly average temperature ≥ 27 °C (HR 0.82, 95% CI 0.72-0.95) was associated with a decreased risk of RA.

Being born in Spring and Summer, as well as early-life exposure to low-latitude regions and extreme sunlight environments increases the risk of RA. Our study revealed significant associations between the risk of RA and natural environmental factors at birth, emphasizing the impact of the early-life environment on the onset of RA.

Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the "Hallmarks of ageing". Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition.

Anti-tumor immunity, including innate and adaptive immunity is critical in inhibiting tumorigenesis and development of tumor. The adaptive immunity needs specific lymph organs such as tertiary lymphoid structures (TLSs), which are highly correlated with improved survival outcomes in many cancers. In recent years, with increasing attention on the TLS in tumor microenvironment, TLSs have emerged as a novel target for anti-tumor therapy. Excitingly, studies have shown the contribution of TLSs to the adaptive immune responses. However, it is unclear how TLSs to form and how to more effectively defense against tumor through TLS formation. Recent studies have shown that the inflammation plays a critical role in TLS formation. Interestingly, studies have also found that gut microbiota can regulate the occurrence and development of inflammation. Therefore, we here summarize the potential effects of gut microbiota- mediated inflammation or immunosuppression on the TLS formation in tumor environments. Meanwhile, this review also explores how to manipulate mature TLS formation through regulating gut microbiota/metabolites or gut microbiota associated signal pathways for anti-tumor immunity, which potentially lead to a next-generation cancer immunotherapy.

A growing body of evidence suggests a correlation among immune cells, serum micronutrient levels, and neuropathic pain. However, previous studies have been limited in scope, hindering the establishment of conclusive findings. Therefore, this study employs mendelian randomization (MR) analysis to investigate the genetic perspectives on the causal relationships among these factors. Initially, the relationship between five serum micronutrient levels (specifically, four vitamin levels and zinc levels) and neuropathic pain was examined using a bidirectional MR design. Subsequently, positive results identified through the inverse variance weighted (IVW) method prompted further analysis, using immune cells as exposures to explore their causal links with neuropathic pain. As a result, a two-step MR analysis demonstrated that serum vitamin levels mediate the relationship between immune cells and neuropathic pain, quantifying both direct impacts and mediation effects. This study revealed that low serum levels of vitamin D and 25-hydroxyvitamin D increased the risk of postherpetic neuralgia and thoracic spine pain. Reverse MR analysis suggested that neuropathic pain does not contribute to a reduction in the serum levels of vitamin D and 25-hydroxyvitamin D. Furthermore, significant associations were observed between 27 immune cells and postherpetic neuralgia, as well as between 22 immune cells and thoracic spine pain. Additionally, the mediation analysis identified causal relationships between immune cells and serum micronutrient levels, confirming the "immune cells-serum micronutrient levels-neuropathic pain" pathway. This study provides valuable insights into the potential mechanisms by which vitamin D and 25-hydroxyvitamin D regulate the interaction between the immune system and neuropathic pain. These findings are crucial for the timely detection, treatment, and management of neuropathic pain, offering new perspectives on how vitamin levels influence immune cell behavior and neuropathic pain susceptibility.

Inflammatory Bowel Disease (IBD) is an autoimmune disease characterized by chronic relapsing inflammation of the intestinal tract. Gut microbiota (GM) and CD4+T cells are important in the development of IBD. A lot of studies have shown that GM and their metabolites like short-chain fatty acids, bile acids and tryptophan can be involved in the differentiation of CD4+T cells through various mechanisms, which in turn regulate the immune homeostasis of the IBD patients. Therefore, regulating CD4+T cells through GM may be a potential therapeutic direction for the treatment of IBD. Many studies have shown that Traditional Chinese Medicine (TCM) formulas and some herbal extracts can affect CD4+T cell differentiation by regulating GM and its metabolites. In this review, we mainly focus on the role of GM and their metabolites in regulating the differentiation of CD4+T cells and their correlation with IBD. We also summarize the current research progress on the regulation of this process by TCM.

After a century of extensive scientific investigations, there is still no curative or disease-modifying treatment available that can provide long-lasting remission for patients diagnosed with type 1 diabetes (T1D). Although T1D has historically been regarded as a classic autoimmune disorder targeting and destroying pancreatic islet β-cells, significant research has recently demonstrated that β-cells themselves also play a substantial role in the disease's progression, which could explain some of the unfavorable clinical outcomes. We offer a thorough review of scientific and clinical insights pertaining to molecular mechanisms behind pathogenesis and the different therapeutic interventions in T1D covering over 20 possible pharmaceutical intervention treatments. The interventions are categorized as immune therapies, treatments targeting islet endocrine dysfunctions, medications with dual modes of action in immune and islet endocrine cells, and combination treatments with a broader spectrum of activity. We suggest that these collective findings can provide a valuable platform to discover new combinatorial synergies in search of the curative disease-modifying intervention for T1D. SIGNIFICANCE STATEMENT: This research delves into the underlying causes of T1D and identifies critical mechanisms governing β-cell function in both healthy and diseased states. Thus, we identify specific pathways that could be manipulated by existing or new pharmacological interventions. These interventions fall into several categories: (1) immunomodifying therapies individually targeting immune cell processes, (2) interventions targeting β-cells, (3) compounds that act simultaneously on both immune cell and β-cell pathways, and (4) combinations of compounds simultaneously targeting immune and β-cell pathways.

The importance of vitamin D for a well-functioning immune system is becoming increasingly evident. Nevertheless, the other fat-soluble vitamins A, E and K also seem to play a central role regarding the adequate function of immune cells and to counteract excessive immune reactions and inflammatory processes. However, recognizing hidden hunger, particularly micronutrient deficiencies in vulnerable groups like the elderly, is crucial because older adults often lack sufficient micronutrients for various reasons. This review summarizes the latest findings on the immune modulating functions of fat-soluble vitamins in a physiological and pathophysiological context, provides a graphical comparison of the Recommended Daily Allowances between Deutschland, Austria, Confoederatio Helvetica (D-A-CH; eng. GSA, Germany, Switzerland, Austria), Deutsche Gesellschaft für Ernährung (DGE; eng. German Nutrition Society) and National Institutes of Health (NIH) across all age groups and, in particular, addresses the question regarding the benefits of supplementation of the respective micronutrients for the aging population of industrialized nations to strengthen the immune system. The following review highlights the importance of fat-soluble vitamins A, D, E and K which play critical roles in maintaining immune system function and, in some cases, in preventing excessive immune activation. Therefore, a better understanding of the relevance of adequate blood levels and consequently potential supplementation strategies may contribute to the prevention and management of infectious diseases as well as better overall health of the elderly.

Calcitriol, beyond its well-established role in calcium and phosphate homeostasis, contributes to immunological processes. No known vitamin D dosage regimen effectively corrects the deficiency while accounting for immunoregulatory effects. Therefore, the purpose of this assessment was to determine whether regular administration of low doses of vitamin D might correct deficiency and have immunoregulatory effects.

A total of 35 healthy volunteers were asked to supplement with vitamin D daily at a dosage of 500 or 1000 IU, depending on the degree of deficiency, for 12 months. At the beginning of the study and after the end of the supplementation period, concentrations of 25(OH)D; PTH; total calcium; inorganic phosphorus; and the inflammatory cytokines IL-17, IL-10, TGF-β, and IFN-γ were determined in all participants.

Correction of vitamin D deficiency was achieved with accompanying decreases in PTH and pro-inflammatory cytokine concentrations, while the concentration of anti-inflammatory cytokines remained stable.

Therefore, regular vitamin D supplementation, even in small doses, effectively corrected the deficiency and had immunomodulatory effects.

The etiology of systemic lupus erythematosus (SLE) is complex, involving both environmental and genetic factors. Previous research has indicated a potential link between autoimmune diseases, such as SLE, and variations in the vitamin D receptor gene (VDR). This study intended to explore the relationship between VDR SNPs, susceptibility to SLE, clinical parameters, and prognosis in the Chinese Han SLE population.

Totally, 461 healthy individuals and 503 patients were recuited SLE diagnoses were chosen. Data on clinical symptoms, scores from the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and results from clinical examinations were collected. The study analyzed four variations in the VDR gene (FokI, BsmI, ApaI, TaqI) using MassARRAY® Iplex GOLD SNP genotyping.

The dominant model showed significant correlations between susceptibility to SLE and the FokI (P < 0.001) and ApaI (P < 0.001) SNPs. Additionally, mucosal ulcer was linked to FokI, while hematologic disorder, rash, photosensitivity, and anti-dsDNA positivity were associated with ApaI. Subsequent studies indicated that the FokI SNP was connected to a poorer prognosis in SLE patients.

This research indicates that VDR SNPs could potentially contribute to the susceptibility of SLE, as well as impacting the clinical presentation and outlook for Chinese individuals with SLE. (Protocol No. 2016-027, registered retrospectively).

During the COVID-19 pandemic, several observational studies proved a certain efficacy of nutraceuticals, herbal products, and other dietary supplements as adjuvant therapies used alongside antiviral drugs. Although their use has not been widespread in Italy, according to preliminary evidence, many supplements with demonstrated immunomodulatory effects, such as vitamins C and D, herbal medicines and essential oils, might relieve the respiratory symptoms of COVID-19, since SARS-CoV-2 can activate inflammasome-mediated inflammatory signaling pathways. Other observational studies have shown that herbal treatments, such as Echinacea purpurea and ginseng, help alleviate respiratory symptoms and reduce serum levels of inflammatory cytokines, which are typically overexpressed in both adult and pediatric SARS-CoV-2 patients. Further, vitamins C and D can attenuate the immune response thanks to their cytokine suppression ability and to their known antimicrobial activity and potential to modulate T helper cell response. The strong immune response triggered by SARS-CoV-2 infection is responsible for the severity of the disease. Preliminary data have also shown that L-arginine, an endothelial-derived relaxing factor, is able to modulate endothelial damage, which appears to be one of the main targets of this systemic disease. Finally, some essential oils and their isolated compounds, such as eucalyptol, may be helpful in reducing many of the respiratory symptoms of COVID-19, although others, such as menthol, are not recommended, since it can lead to an undervaluation of the clinical status of a patient. In this narrative review, despite the lack of strong evidence in this field, we aimed to give an overview of the current available literature (mainly observational and cross-sectional studies) regarding herbal products and dietary supplements and their use in the treatment of mild disease from SARS-CoV-2 infection. Obviously, dietary supplements and herbal products do not constitute a standardized treatment for COVID-19 disease, but they could represent an adjunctive and useful treatment when used together with antivirals.

Immunotherapies aimed at preserving residual beta cell function in type 1 diabetes have been successful, although the effect has been limited, or raised safety concerns. Transient effects often observed may necessitate redosing to prolong the effect, although this is not always feasible or safe. Treatment with intralymphatic GAD-alum has been shown to be tolerable and safe in persons with type 1 diabetes and has shown significant efficacy to preserve C-peptide with associated clinical benefit in individuals with the human leukocyte antigen DR3DQ2 haplotype. To further explore the feasibility and advantages of redosing with intralymphatic GAD-alum, six participants who had previously received active treatment with intralymphatic GAD-alum and carried HLA DR3-DQ2 received one additional intralymphatic dose of 4 μg GAD-alum in the pilot trial DIAGNODE-B. The participants also received 2000 U/day vitamin D (Calciferol) supplementation for two months, starting one month prior to the GAD-alum injection. During the 12-month follow-up, residual beta cell function was estimated with Mixed-Meal Tolerance Tests, and clinical and immune responses were observed. C-peptide decreased minimally, and most patients showed stable HbA1c and IDAA1c. The mean % TIR increased while the mean daily insulin dose decreased at month 12 compared to the baseline. Redosing with GAD-alum seems to be safe and tolerable, and may prolong the disease modification elicited by the original GAD-alum treatment.

Chronic periodontitis is one of the most common inflammatory diseases worldwide. Micronutrients play a significant impact on health and periodontal disease progression. However, there is still a lack of conclusive studies confirming the causal association of micronutrients with chronic periodontitis.

Genome-wide association study pooled data on chronic periodontitis were collected from the FinnGen consortium, and 14 micronutrients (calcium, copper, zinc, potassium, magnesium, selenium, iron, carotenoids, vitamin B6, B12, C, D, E and folate) were obtained from the OpenGWAS and UK Biobank Study. Instrumental variables were screened by strict criteria. Five Mendelian randomization (MR) methods were used. Finally, the robustness of the findings was verified by sensitivity analyses.

We found that vitamin D reduced the risk of chronic periodontitis (OR: 0.605, 95%CI: 0.398-0.921, P = 0.019). However, we had no evidence of a significant association between other micronutrients and chronic periodontitis. Multiple sensitivity analyses confirmed the robustness of the findings. A variety of sensitivity analysis methods confirmed the reliability of the results.

In this study, we found a potential causal relationship between vitamin D and chronic periodontitis by MR analysis, whereas we did not find an association between 13 other micronutrients and chronic periodontitis. This result might provide new ideas for the prevention and treatment of chronic periodontitis to some extent. However, despite the rigorous analytical methods used in this study, this finding needs to be interpreted with caution. Further randomized controlled studies might provide more in-depth references to the findings of this study.

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.

Vaginitis is a common disease of the reproductive system in women, causing discomfort in daily life. Many reports indicate that the causes of vaginitis are related to vaginal microecological disturbances. Therefore, treatment strategies to restore microecological balance have shown promising results in both basic research and clinical settings. Recent studies have highlighted the potential adjuvant role of vitamin D in the treatment of vaginitis while illustrating its role in maintaining microecological balance. Therefore, this study focused on the therapeutic effects of vitamin D on vaginitis.

The study provided a statistical description of 5978 vaginitis patients who visited Shaanxi Provincial People's Hospital, presenting data in absolute numbers (%) and mean ± standard deviation (median quartiles were used for non-normally distributed variables). The chi-square test and analysis of variance were employed to analyze the distribution of vitamin D levels among patients, factors influencing vitamin D levels, and the association between recurrence rates and vitamin D levels.

Vitamin D deficiency (57.74%) or insufficiency (22.20%) is prevalent among patients with vaginitis. Furthermore, vitamin D levels have an impact on the dominant bacterial species in the vagina, as well as catalase, acetylglucosaminidase, and the overall vaginal microecological status. Age and BMI have correlations with vitamin D levels. It is hypothesized that this relationship may be attributed to clinicians utilizing vitamin D as a supplementary treatment.

This study examined the statistical findings of vitamin D-related data from 5978 vaginitis patients, revealing a positive correlation between vitamin D deficiency and vaginitis occurrence. Patients with vitamin D deficiency/severe deficiency showed weakly positive levels of catalase and mostly weakly positive levels of acetylglucosaminidase, and most of these vaginitis are trichomonas vaginalis (TV). Furthermore, older individuals and those with higher BMI were found to be more susceptible to symptoms of vitamin D deficiency.

This meta-analysis explores the impact of vitamin D supplementation on antibiotic utilization.

We systematically searched for relevant randomized controlled trials (RCTs) in PubMed, Web of Science, EMBASE, and Science Direct from inception to April 2024. These trials compared antibiotic use rates between groups receiving vitamin D supplements and placebo.

We included seven RCTs involving 35,160 participants. There was no significant difference in antibiotic use between the two groups in the general population (Odds Ratio [OR] = 0.98, p = 0.232), including elderly participants (OR = 0.98, p = 0.295). However, antibiotic use was lower in the intervention group compared to the placebo group among participants under 70 years of age (OR = 0.95, p = 0.015), those with relative vitamin D deficiency [25(OH)D < 75 nmol/L, OR = 0.95, p = 0.024; 25(OH)D < 50 nmol/L, OR = 0.96, p = 0.026], and those with respiratory tract infections (RTIs) (OR = 0.51, 95% CI: 0.24-1.08, p = 0.080), although these differences were not statistically significant for RTIs.

Vitamin D supplementation does not affect antibiotic use in the general population. However, it does reduce antibiotic utilization in individuals with RTIs, relative vitamin D deficiency, or aged below 70 years.

This meta-analysis adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and is registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42024543246.

Interactions between genetic and environmental variables contribute to the autoimmune inflammatory process in multiple sclerosis (MS). Elevated homocysteine levels, and vitamin D, vitamin B12, and folate deficiencies are some of the environmental factors associated with the pathogenesis of MS. Considering that the relationship between MTHFR 677C>T (rs1801133) genetic variant, homocysteine, and folate in patients with MS remains unclear and that their role were not extensively explored in the clinical course of the disease, we investigated whether this variant and plasma homocysteine and folate levels are associated with MS susceptibility, disability, disability progression, and inflammatory biomarkers.

The case-control study included 163 patients with MS categorized using the Expanded Disability Status Scale (EDSS) as mild (EDSS<3) and moderate/high (EDSS≥3) disability, and 226 healthy controls (HC). Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS) and the MTHFR 677C>T variant was genotyped using real time polymerase chain reaction. The plasma levels of some inflammatory biomarkers were determined. Two new composed scores were proposed: the first, namely as inflammatory activity index (IAI), was entered as a latent vector extracted from the macrophage M1 + T helper (Th)1 + Th17 + Th2 + T regulatory (Treg) cytokines, + tumor necrosis factor (TNF)-α+ soluble TNF receptor (sTNFR)-1 + sTNFR2. The second score, namely MS-severity index was entered as a latent vector extracted from the EDSS + MSSS scores + MS diagnosis.

Patients with MS showed higher homocysteine and folate than controls (p < 0.001); homocysteine, and the M1, Th1, Th17, and Th2 Treg cytokine values were different between the three study groups and increased from HC to MS patients with mild disability and to MS patients with moderate/high disability (p < 0.0001). The levels of TNF-α and their soluble receptors sTNFR1 and sTNFR2 were higher in MS patients with EDSS≥3 than in the two other groups (EDSS<3 and HC) (p < 0.001). There was no association between the MTHFR 677 C > T genotypes and MS susceptibility, disability and disability progression (p > 0.05). Moreover, 21.8 % of the disability variance was explained by age, IAI and C-reactive protein (CRP) (all positively associated); 10.9 % of the disability progression variance was predicted by IAI and CRP (both positively) and 25-hydroxyvitamin D (negatively), whereas 54.4 % of the severity index (MS-EDSS-MSSS) was explained by the regression on age, IAI, homocysteine, folate, and CRP (all positively), and adiponectin, body mass index, and 25-hydroxyvitamin D (all negatively), female sex, and the MTHFR 677 TT genotype. In patients and controls, 16.6 % of the variance in the homocysteine was explained by the MTHFR 677 TT genotype and age (both positively), folate (negatively) and male sex.

The MTHFR 677C>T variant has an indirect effect on the increase in disability in patients with MS, which also depends on factors such as age, sex, ad folate status.

Previous studies have shown the anti-inflammatory effect of 25-hydroxyvitamin D (25(OH)D) and the crucial roles of high-sensitive C reactive protein (hsCRP) and novel inflammatory markers (red blood cell distribution width-platelet count ratio (RDWPCR), mean platelet volume-platelet count ratio (MPVPCR), neutrophil-lymphocyte ratio (NLR) and white blood cell-neutrophil ratios (WBCNR)) in several diseases, but scarce data explored the associations of 25(OH)D with hsCRP and novel inflammatory markers. This study aimed to investigate these associations in children.

Cross-sectional study.

Children in China.

10141 children (mean age 14.6 months) were included.

HsCRP, red blood cell distribution width, platelet count, mean platelet volume, neutrophil, lymphocyte and white blood cell were measured.

Overall, serum 25(OH)D was inversely associated with hsCRP and novel inflammatory biomarkers. In multivariable analysis, serum 25(OH)D was inversely associated with hsCRP and novel inflammatory biomarkers (Q quartile (Q) 4 vs Q1: 1129.75 vs 2090.99 for hsCRP; 4246.94 vs 6829.89 for RDWPCR; 4863.57 vs 5545.66 for MPVPCR; 4345.76 vs 6507.46 for NLR; 2418.84 vs 2868.39 for WBCNR). Similar results also were observed in stratified analyses by sex (boys and girls). Moreover, serum 25(OH)D was inversely associated with elevated inflammation levels. After adjustment for other potential covariates, inverse associations between serum 25(OH)D and elevated inflammation levels were still observed. The corresponding ORs (95% CI) were 0.05 (0.04, 0.06) for hsCRP, 0.13 (0.11, 0.15) for RDWPCR, 0.74 (0.64, 0.85) for MPVPCR, 0.11 (0.09, 0.13) for NLR and 0.57 (0.49, 0.66) for WBCNR in the fourth quartile compared with the first quartile, respectively.

Generally, the graded and inverse associations of serum 25(OH)D with hsCRP and four novel inflammatory markers (RDWPCR, MPVPCR, NLR and WBCNR) were observed. The present study provided further support for the anti-inflammatory effects of 25(OH)D.

Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients.

To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers.

We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD).

Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation.

Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

Gut microbiota contributes to the homeostasis of immune system and is related to various diseases such as tumorigenesis. Ferroptosis, a new type of cell death, is also involved in the disease pathogenesis. Recent studies have found the correlations of gut microbiota mediated ferroptosis and immune cell death. Gut microbiota derived immunosuppressive metabolites, which can promote differentiation and function of immune cells, tend to inhibit ferroptosis through their receptors, whereas inflammatory metabolites from gut microbiota also affect the differentiation and function of immune cells and their ferroptosis. Thus, it is possible for gut microbiota to regulate immune cell ferroptosis. Indeed, gut microbiota metabolite receptor aryl hydrocarbon receptor (AhR) can affect ferroptosis of intestinal intraepithelial lymphocytes, leading to disease pathogenesis. Since immune cell ferroptosis in tumor microenvironment (TME) affects the occurrence and development of tumor, the modulation of gut microbiota in these cell ferroptosis might influence on the tumorigenesis, and also immunotherapy against tumors. Here we will summarize the recent advance of ferroptosis mediated by gut microbiota metabolites, which potentially acts as regulator(s) on immune cells in TME for therapy against tumor.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, mortality rates of coronavirus disease 2019 (COVID-19) have significantly decreased. However, a variable proportion of patients exhibit persistent prolonged symptoms of COVID-19 infection (long COVID). This virus primarily attacks respiratory system, but numerous individuals complain persistent skeletal muscle pain or worsening pre-existing muscle pain post COVID-19, which severely affects the quality of life and recovery. Currently, there is limited research on the skeletal muscle pain in long COVID. In this brief review, we review potential pathological mechanisms of skeletal muscle pain in long COVID, and summarize the various auxiliary examinations and treatments for skeletal muscle pain in long COVID. We consider abnormal activation of inflammatory response, myopathy, and neurological damages as pivotal pathological mechanisms of skeletal muscle pain in long COVID. A comprehensive examination is significantly important in order to work out effective treatment plans and relieve skeletal muscle pain. So far, rehabilitation interventions for myalgia in long COVID contain but are not limited to drug, nutraceutical therapy, gut microbiome-targeted therapy, interventional therapy and strength training. Our study provides a potential mechanism reference for clinical researches, highlighting the importance of comprehensive approach and management of skeletal muscle pain in long COVID. The relief of skeletal muscle pain will accelerate rehabilitation process, improve activities of daily living and enhance the quality of life, promoting individuals return to society with profound significance.

Idiopathic pulmonary fibrosis remains a relevant problem of the healthcare system with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the damage of the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD-mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of new approaches aimed at regulating the immune response, cellular aging processes, programmed cell death, and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential targets, and effects of vitamin D and its metabolites.

Vaccination is the effective strategy for coronavirus disease 2019 (COVID-19). However, few studies have investigated the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)G and vitamin D.

This study aimed to investigate the association between SARS-CoV-2 IgG and active vitamin D analogs in hemodialysis patients. Blood samples were collected four times: before vaccination and 30, 60, and 90 days after vaccination, BNT162b2 (Pfizer©).

A total of 418 patients were enrolled. The mean age was 71.1 ± 12 years. Almost two thirds of the patients were prescribed active vitamin D analogs. The distribution of SARS-CoV-2 IgG before vaccination was 235 (93-454) AU/mL. After multiple regression analyses, active vitamin D analog use was found to be associated with higher SARS-CoV-2 IgG levels from prevaccination to 90 days postvaccination.

This study demonstrated an association between higher SARS-CoV-2 IgG and active vitamin D analog use in hemodialysis patients.

The study information was registered in the UMIN-CTR (UMIN 000046906).

In December 2019, Corona Virus Disease 2019 (COVID-19) was first identified and designated as a pandemic in March 2020 due to rapid spread of the virus globally. At the beginning of the pandemic, only a few treatment options, mainly focused on supportive care and repurposing medications, were available. Due to its effects on immune system, vitamin D was a topic of interest during the pandemic, and researchers investigated its potential impact on COVID-19 outcomes. However, the results of studies about the impact of vitamin D on the disease are inconclusive. In the present narrative review, different roles of vitamin D regarding the COVID-19 have been discussed to show that vitamin D supplementation should be recommended carefully.

Vitamin D possesses a crucial role in preserving bone health, modulating the immune system responses, and supporting various physiological functions throughout the body. Chronic atrophic autoimmune gastritis (CAAG) constitutes an autoimmune condition marked by inflammation and damage to the stomach cells, often resulting in a decreased ability to absorb certain nutrients, including vitamin B12 and iron. Although, vitamin D is not directly affected by this condition, the sufficiency of this micronutrient seems to have important implications for overall health and management of the disease. The aim of the current review was to assess the incidence and related features of vitamin D deficiency in patients with CAAG and to elucidate the complex regulatory role of this nutrient, in an effort to improve patient outcomes. Vitamin D greatly contributes to the regulation of the immune system. In patients with CAAG, the immune system attacks the stomach lining; thus, the maintenance of a healthy and balanced immune response is important. In autoimmune conditions such as CAAG, where inflammation plays a decisive role in disease progression, vitamin D could potentially exert a role in managing and controlling the associated symptoms. Adequate vitamin D levels may help in regulating the immune response and reducing inflammation. In addition, patients with CAAG are at risk of nutrient deficiencies, including vitamin B12 and iron, which can lead to anemia and bone health issues. As vitamin D is critical for calcium absorption and bone health, assurance of sufficient levels of this micronutrient can be beneficial in preventing or mitigating bone-related complications. In conclusion, regular monitoring of vitamin D levels, among other nutrients, and appropriate supplementation, when necessary, can help improve overall health and well-being in these patients.

In recent years, the relationship between vitamin D and allergic diseases has received widespread attention. As a fat-soluble vitamin, vitamin D plays a crucial role in regulating the immune system and may influence the onset and progression of diseases such as atopic dermatitis, allergic rhinitis, and asthma. To understand the underlying mechanisms, we have summarized the current research on the association between vitamin D and allergic diseases. We also discuss the impact of vitamin D on the immune system and its role in the course of allergic diseases, particularly focusing on how vitamin D supplementation affects the treatment outcomes of these conditions. We aim to provide a theoretical basis and practical guidance for optimizing the management and treatment of allergic diseases by modulating vitamin D levels.

It is well known that vitamin D has a profound effect on calcium and bone metabolism, but its influence on other organs (extraskeletal effect) has been proposed. Consistently, vitamin D deficiency is associated with an increased incidence of various diseases, including type 1 and type 2 diabetes, as reported by many observational studies. However, there has been no consensus on whether vitamin D deficiency is a causative factor in the incidence of diabetes mellitus. There have been no randomized controlled trials (RCTs) aimed at preventing the onset of type 1 diabetes with vitamin D intake. In addition, the results of RCTs evaluating the preventive effect of vitamin D supplementation on type 2 diabetes development have been inconsistent. The recent observational studies, randomized controlled trials, and meta-analyses are confirming that vitamin D or active vitamin D administration is effective in preventing the incident of type 1 and type 2 diabetes.

The immune benefits of vitamin D3 supplementation beyond calcium and phosphate maintenance are highly clinically debated. Kidney expression of CYP27B1 is the source of endocrine, circulating 1,25(OH)2D3 (active form of vitamin D) that maintains serum calcium and phosphate. 1,25(OH)2D3 may also be made by the CYP27B1 enzyme in nonrenal cells, like immune cells, in a process driven by cellular availability of 25(OH)D3 and inflammation. Due to the endocrine nature of 1,25(OH)2D3 in circulation, it is difficult to discern between these 2 sources. We recently created a regulatory deletion model of Cyp27b1 (M1/M21-DIKO) where mice have normal inflammatory-regulated Cyp27b1 expression in nonrenal tissues (unlike global Cyp27b1-KO) but no expression within the kidney. Here, utilizing on-tissue chemical derivatization and matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), we investigated the distribution of 1,25(OH)2D3 and 25(OH)D3 in the kidney, liver, spleen, and thymus. MALDI-MSI demonstrated increased 1,25(OH)2D3 in nonrenal tissues such as the spleen after vitamin D3 supplementation in M1/M21-DIKO mice. Additionally, from this, we found increased Il4 and decreased Tnfa in the spleen after vitamin D3 supplementation. Taken together, these data demonstrate nonrenal production of 1,25(OH)2D3 in vivo and provide a consequence of vitamin D3 supplementation and nonrenal 1,25(OH)2D3 production in cytokine changes.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The occurrence and development of CRC are related to multiple risk factors such as gut microbiota. Indeed, gut microbiota plays an important role in the different phases of colorectal cancers (CRCs) from oncogenesis to metastasis. Some specific bacteria such as Fusobacterium nucleatum (F. nucleatum) associated with CRCs have been found. However, recently identified bile acid and tryptophan metabolites as well as short chain fatty acids (SCFAs), which are derived from gut microbiota, can also exert effects on the CRCs such as that SCFAs directly inhibit CRC growth. Importantly these metabolites also modulate immune responses to affect CRCs. They not only act as tumor inhibiting factor(s) but also promotor(s) in the occurrence, development, and metastasis of CRCs. While gut microbiota metabolites (GMMs) inhibit immunity against CRCs, some of them also improve immune responses to CRCs. Notably, GMMs also potentially affect the shaping of immune-privileged metastatic niches through direct roles or immune cells such as macrophages and myeloid-derived suppressive cells. These findings offer new insights for clinical application of gut microbiota in precise and personalized treatments of CRCs. Here, we will mainly discuss direct and indirect (via immune cells) effects of GMMs, especially SCFAs, bile acid and tryptophan metabolites on the occurrence, development and metastasis of CRCs.

The synergic role of vitamin D and the intestinal microbiota in the regulation of the immune system has been thoroughly described in the literature. Vitamin D deficiency and intestinal dysbiosis have shown a pathogenetic role in the development of numerous immune-mediated and allergic diseases. The physiological processes underlying aging and sex have proven to be capable of having a negative influence both on vitamin D values and the biodiversity of the microbiome. This leads to a global increase in levels of systemic inflammatory markers, with potential implications for all immune-mediated diseases and allergic conditions. Our review aims to collect and analyze the relationship between vitamin D and the intestinal microbiome with the immune system and the diseases associated with it, emphasizing the effect mediated by sexual hormones and aging.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.

International and observational epidemiological studies provide evidence that vitamin D deficiency may confer increased risk of influenza and respiratory tract infection. This study was undertaken to evaluate the prevalence of vitamin D deficiency in pneumonia in children, and to assess its relationship with the severity.

Study group included children aged between 2 months to 5 years of age admitted as inpatients who presented with clinical features of pneumonia as per WHO Classification. Detailed clinical assessment and physical examination was done at the time of admission and patients were enrolled and relevant findings were noted in prestructured proforma. Vitamin D levels <30 nmol/L (<12 ng/mL) were defined as deficient, 30-50 nmol/L (12-20 ng/mL) as insufficient, and >125 nmol/L (>50 ng/mL) as sufficient. Outcomes of the patients admitted were recorded in terms of duration of hospitalization, Intensive Care Unit (ICU) stay, oxygen requirement, antibiotic need and duration, need for upgradation of antibiotics, nebulization need with drugs used, ventilator need and other parameters. Statistical analysis was performed using statistical package for social sciences software (SPSS Inc., Chicago, IL, USA). A P value of <0.05 was considered statistically significant.

Out of 101 patients, 100% presented with fever, cough and fast breathing, 42.6% with grunting, 41 (40.5%) with noisy breathing, 5.7% with bluish discoloration, and 4.3% with apnea. Forty-one (40.5%) patients had crepitation, 53 (52.4%) patients had rhonchi, while 7 (6%) presented with bronchial breathing. Chest radiography features at admission helped to differentiate between presumed viral and presumed bacterial infection. Vitamin D deficient patients had significantly longer duration of hospital stay as compared to vitamin D sufficient group (P<0.001). The need for upgradation of antibiotics between the three groups were found to be significant (P<0.001). This showed that vitamin D deficiency is directly proportional to the need of upgradation of antibiotics. Bacterial pneumonia presents mostly as alveolar infiltrates and/or pleural effusion while viral pneumonia presents as interstitial infiltrates and/or hyperinflation. Cases with presumed bacterial pneumonia (based on X-ray, 38 out of 48, 79.1%) were more often vitamin D deficient as compared to case with presumed viral pneumonia (32 out of 52, 61.5%, P=0.05).

Vitamin D is widely prevalent in Indian children with pneumonia. Vitamin D deficient patients needed a longer duration of hospitalization, more upgradation of antibiotics, and PICU admissions; moreover, it had more CPAP requirement, longer duration of PICU stay and longer duration of CPAP requirements as compared to vitamin D sufficient group.

Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)-the most common variant of CTCL-often presents with skin lesions around the abdomen and buttocks ("bathing suit" distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin D induces apoptosis and inhibits the expression of cytokines in malignant T cells. Furthermore, CTCL patients often display vitamin D deficiency, whereas phototherapy induces vitamin D and has beneficial effects in CTCL, suggesting that light and vitamin D have beneficial/protective effects in CTCL. Inversely, vitamin D promotes T helper 2 (Th2) cell specific cytokine production, regulatory T cells, tolerogenic dendritic cells, as well as the expression of immune checkpoint molecules, all of which may have disease-promoting effects by stimulating malignant T-cell proliferation and inhibiting anticancer immunity. Studies on vitamin D treatment in CTCL patients showed conflicting results. Some studies found positive effects, others negative effects, while the largest study showed no apparent clinical effect. Taken together, vitamin D may have both pro- and anticancer effects in CTCL. The balance between the opposing effects of vitamin D in CTCL is likely influenced by treatment and may change during the disease course. Therefore, it remains to be discovered whether and how the effect of vitamin D can be tilted toward an anticancer response in CTCL.

The active metabolite of vitamin D 1,25(OH)2D is well known for its role in regulating calcium-phosphate homeostasis of the human body. However, the immunomodulating activity of 1,25(OH)2D has been known for many years. There are numerous reports correlating low vitamin D levels in blood serum with the onset of autoimmune diseases and with the severe course of acute infections. In this chapter, we address the role of 1,25(OH)2D in these diseases, and we discuss the possible mechanisms of action of 1,25(OH)2D in immune cells.

Helicobacter pylori (HP) infections affect approximately one-third of children worldwide. In China, the incidence of HP infection in children ranges from approximately 30% to 60%. In addition to damaging the gastrointestinal tract mucosa, HP infection in children can negatively affect their growth and development, hematology, respiratory and hepatobiliary system, skin, nutritional metabolism, and autoimmune system. However, the rate of HP eradication also fell considerably from the previous rate due to the presence of drug-resistant HP strains and the limited types of antibiotics that can be used in young patients. Vitamin D3 (VitD3) is a steroid hormone that can reduce inflammation in the stomach mucosa induced by HP and can alleviate and eradicate HP through a variety of pathways and mechanisms, including immune regulation and the stimulation of antimicrobial peptide (AMP) secretion and Ca2+ influx, to reestablish lysosomal acidification; thus, these results provide new strategies and ideas for the eradication of drug-resistant HP strains.

Tumor cells can evade immune surveillance by expressing immune checkpoint molecule ligands, resulting in effective immune cell inactivation. Immune checkpoint blockades (ICBs) have dramatically improved survival of patients with multiple types of cancers. However, responses to ICB immunotherapy are heterogeneous with lower patient response rates. The advances have established that the gut microbiota can be as a promising target to overcome resistance to ICB immunotherapy. Furthermore, some bacterial species have shown to promote improved responses to ICBs. However, gut microbiota is critical in maintaining gut and systemic immune homeostasis. It not only promotes differentiation and function of immunosuppressive immune cells but also inhibits inflammatory cells via gut microbiota derived products such as short chain fatty acids (SCFAs), tryptophan (Trp) and bile acid (BA) metabolites, which play an important role in tumor immunity. Since the gut microbiota can either inhibit or enhance immune against tumor, it should be a double-edged sword in ICBs against tumor. In this review, we discuss the effects of gut microbiota on immune cells and also tumor cells, especially enhances of gut microbiota on ICB immunotherapy. These discussions can hopefully promote the development of ICB immunotherapy.

In the last decade, an immuno-modulatory effect of vitamin D supplementation have emerged as a potential therapeutic approach for some inflammatory and autoimmune diseases. As previously reported, vitamin D deficiency was strongly linked to several diseases as Behçet's disease (BD). BD is a chronic systemic inflammatory disorder with autoimmunity, genetic and environmental factors involvement. The aim of our current study is to set up a new therapeutic strategy in BD, combining conventional therapy and vitamin D supplementation.

Blood samples were collected from active and inactive BD patients and healthy controls (HC) to evaluate 25(OH) vitamin D levels using an electrochemiluminescence method. All deficient and insufficient vitamin D BD patients' were supplemented with vitamin D3 (CHOLECALCIFEROL, 200 000 UI/1 ml). In this context, NO, IL-17A and IL-10 levels were evaluated in patients and HC in vivo and ex vivo using Griess and ELISA methods respectively.

Before supplementation, we noted with interest that BD patients had vitamin D deficiency, associated with elevated in vivo and ex vivo NO and IL-17A levels compared to HC. Conversely, low IL-10 levels were observed in the same BD patients in comparison to HC. Interestingly, restored vitamin D status in supplemented BD patients was related to the decreased NO levels. In the same way, the IL-10/IL-17A ratio was improved.

Collectively, our data suggest that vitamin D supplementation in combination with conventional treatments has a beneficial effect and could constitute a good therapeutic candidate for alleviating inflammatory responses during Behçet disease.

Vitamin D is known for its role in modulating calcium and phosphate homeostasis and is implicated both in bone mineralization and immune system regulation. The immune-modulatory role of vitamin D and its impact on multiple sclerosis (MS) courses are still debated. The aim of this review was to check the effect of vitamin D supplementation on cytokine profile regulation in people with MS. A significant increase in serum concentrations of interleukin (IL)-10 and Transforming growth factor (TGF)-β1 after vitamin D supplementation was demonstrated in most studies, with some of them reporting a reduction in disability scores after vitamin D supplementation and an inverse correlation between IL-10 levels and disability. The effect of vitamin D on the serum levels of IL-17 and IL-6 was controversial; different results across studies could be explained by a variability in the treatment duration, route, and frequency of administration, as well as the dosage of vitamin D supplementation, responses to vitamin D treatment and the serum levels reached with supplementation, including the methods used for cytokine analysis and the different cell types investigated, the MS phenotype, the disease phase (active vs. non-active) and duration, and concomitant treatment with disease-modifying therapies. Nevertheless, the significant increase in the serum concentrations of IL-10 and TGF-β1, demonstrated in most studies, suggests an anti-inflammatory effect of vitamin D supplementation.

Vitamin D has been suggested to influence the immune system, and vitamin D metabolites and the vitamin D receptor (VDR) are generated and expressed in white blood cells (WBC). Moreover, vitamin D status has been associated with incidence and prognosis of some respiratory tract infections (RTI). Therefore, we investigated the effect of vitamin D3 supplementation on WBC, acute phase reactants (APR), and the risk of developing RTIs.

A double-blinded, randomized, placebo-controlled clinical trial of 307 infertile men with multiple secondary immunological endpoints. The vitamin D3 group (n = 151) initially received 300,000 IU (7,500 µg) cholecalciferol once - followed by 1,400 IU (35 µg) daily for 150 days. The placebo group (n = 156) did not receive active ingredients.

At baseline, stratification into clinically relevant groups of vitamin D status (< 25; 25-50; 50-75; >75 nmol/L), showed an inverse association with total leucocyte concentrations (7.0 vs. 6.0 vs. 6.0 vs. 5.5 (109/L); p = 0.007), lymphocytes (2.4 vs. 2.1 vs. 2.0 vs. 2.0 (109/L); p = 0.048), CRP (2.0 vs. 1.7 vs. 1.2 vs. 1.2 (mg/L); p = 0.037), and orosomucoid (0.82 vs. 0.77 vs. 0.76 vs. 0.70 (g/L); p = 0.015). After 150 days, no differences were detected in WBC counts or APRs between the vitamin D3 and the placebo group. However, vitamin D3 treated men had a higher prevalence of self-reported RTIs compared with the placebo group (55% vs. 39%; p = 0.005).

High-dose vitamin D3 supplementation did not alter WBCs or APRs, but a higher prevalence of respiratory infections was observed in the vitamin D3 group. Serum 25(OH)D3 was negatively correlated with most WBCs, indicating that vitamin D status may be linked with inflammation and WBC turnover, but not an important determinant of developing RTIs.

NCT01304927 (ClinicalTrials.gov). Registered February 20, 2011.

Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors.

Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol (1, 25(OH)2D3) at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes' expression levels were measured using real-time PCR.

Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFβ) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFNϒ) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFNϒ and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation.

The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT.

Vitamin D is implicated in many processes in the central nervous system (CNS), such as neurogenesis, neurotransmitter synthesis, synaptogenesis and protection against oxidative stress, thereby exerting a neuroprotective effect.

In the present review, we aimed to evaluate the potential benefit(s) of vitamin D supplementation for CNS aging in different clinical contexts.

We performed a literature search, looking for clinical trials and randomized clinical trials evaluating the effect of vitamin D supplementation on different endpoints related to cognitive outcomes.

Firstly, we identified 16 papers dealing with the impact of vitamin D supplementation on cognitive function in healthy subjects; the current literature suggests a real role for vitamin D supplementation in the prevention of cognitive decay in this clinical setting. Conversely, two papers suggest that vitamin D supplementation may be beneficial in patients with mild cognitive impairment (MCI). Finally, current data on vitamin D in Alzheimer's disease are contradictory.

Vitamin D supplementation may improve the cognitive outcomes of patients with MCI, whereas there is no evidence that it may prevent dementia or modulate the course of Alzheimer's disease.