The interaction between vitamin D and the immune system is perhaps the most well recognised extraskeletal facet of vitamin D, encompassing early studies of therapy for TB and leprosy through to more recent links with autoimmune disease. However, the spotlight on vitamin D and immune function has been particularly intense in the last five years following the COVID-19 pandemic. This was due, in part, to the many association studies of vitamin D status and COVID-19 infection and disease prognosis, as well as the smaller number of clinical trials of vitamin D supplementation. However, a potential role for vitamin D in COVID-19 also stemmed from the basic biology of vitamin D that provides a plausible mechanistic rationale for beneficial effects of vitamin D for improved immune health in the setting of respiratory infection. The aim of this review is to summarise the different strands of mechanistic evidence supporting a beneficial effect of vitamin D in COVID-19, how this was modified during the pandemic itself, and the potential new aspects of vitamin D and immune function that are likely to arise in the near future. Key topics that feature in this review are: antibacterial versus antiviral innate immune responses to 1,25-dihydroxyvitamin D (1,25(OH)2D); the function of immune 1α-hydroxylase (CYP27B1) activity and metabolism of 25-hydroxyvitamin D (25(OH)D) beyond antigen-presenting cells; advances in immune cell target gene responses to 1,25-dihydroxyvitamin D (notably changes in metabolic profile). Whilst much of the interest during the COVID-19 era has focused on vitamin D and public health, the continued evolution of our understanding of how vitamin D interacts with different components of the immune system continues to support a beneficial role for vitamin D in immune health.

The elderly population is prone to osteoporosis, owing to the deterioration of the skin, liver, and kidney functions. Vitamin D (VD) supplementation has a limited effect, and VD deficiency is mostly treated with medication. Several studies have shown that the gut microbiota alters intestinal VD metabolism and that probiotic supplements can influence circulating VD levels. Therefore, in the present study, we screened a strain of Bifidobacterium longum FSHHK13M1 that can increase the level of VD metabolites in the fermented supernatant species in vitro by modeling fecal bacterial fermentation. The results showed that FSHHK13M1 intervention significantly increased the serum levels of 1,25-dihydroxy VD and osteocalcin. It activated the expression of the VDR, OPG, Wnt10b/β-catenin, and Runx2/Osterix pathways and inhibited the expression of RANKL/RANK pathway. Furthermore, there was an enhancement in the quantity of bone trabeculae and the proportion of bone volume. Concurrently, the gut microbiota in mice with osteoporosis exhibited signs of imbalance. FSHHK13M1 intervention increased the relative abundance of specific bacteria, such as Faecalibaculum rodentium, Limosilactobacillus fermentum, Bifidobacterium pseudolongum, and Akkermansia muciniphila. These results suggest that B. longum FSHHK13M1 alleviates retinoic acid-induced osteoporosis symptoms by modulating related genes, regulating the intestinal flora and increasing the level of active VD.IMPORTANCEOsteoporosis is a systemic metabolic disease in which the patient's bone mass decreases for a variety of reasons, and the microstructure of the bone tissue is altered, leading to an increase in bone brittleness and susceptibility to fracture. Osteoporosis is almost always present in the elderly population, and fractures from falls are an important predisposing factor for mortality risk in the elderly population. Supplementation is quite limited for them as they are not able to utilize vitamin D well due to declining liver, kidney, and skin functions. In the present study, a strain of Bifidobacterium longum probiotic was found to increase the levels of the active form of vitamin D and ameliorate osteoporosis. This may play an important role in preventing osteoporosis and reducing fracture risk in the elderly.

Despite major advancements in the field of durable left ventricular assist devices (LVADs), driveline infection is a major source of morbidity and mortality. Risk factors have been proposed, but few are modifiable. We evaluated vitamin D deficiency as a potential modifiable risk factor for driveline infection.

This single-center, retrospective study included 134 LVAD recipients between 2010 and 2022. Patients were divided into two groups based on their pre-implant vitamin D levels: the vitamin D sufficient group (≥ 30 ng/mL) and the vitamin D deficient group (< 30 ng/mL). The Kaplan-Meier method estimated 18-month freedom from driveline infection. The Cox proportional hazards model estimated the effect of vitamin D deficiency on driveline infections. Kaplan-Meier estimates for infection-free survival were significantly higher in the sufficient group (90.5% vs. 69.6%, p = 0.014). Vitamin D deficiency (HR: 3.644, 95% CI: 1.271-10.448, p = 0.016) and obesity (HR: 3.190, 95% CI: 1.464-7.400, p = 0.004) were found to be independent risk factors for driveline infection.

Our findings support vitamin D deficiency as a potential modifiable risk factor for driveline infection. Obesity was also noted as a significant risk factor for infection. Further research is warranted to establish causality and assess the impact of vitamin D repletion on infection rates.

Schizophrenia (SCZ) is a complex and chronic psychiatric disorder that affects a significant proportion of the global population. Although the precise etiology of SCZ remains uncertain, recent studies have underscored the involvement of neuroinflammation and autophagy in its pathogenesis. Neuroinflammation, characterized by hyperactivated microglia and markedly elevated pro-inflammatory cytokines, has been observed in postmortem brain tissues of SCZ patients and is closely associated with disease severity. Autophagy, a cellular process responsible for eliminating damaged components and maintaining cellular homeostasis, is believed to play a pivotal role in neuronal health and the onset of SCZ. This review explores the roles and underlying mechanisms of neuroinflammation and autophagy in SCZ, with a particular focus on their intricate interplay. Additionally, we provide an overview of potential therapeutic strategies aimed at modulating neuroinflammation and autophagy, including nutritional interventions, anti-inflammatory drugs, antipsychotics, and plant-derived natural compounds. The review also addresses the dual effects of antipsychotics on autophagy. Our objective is to translate these insights into clinical practice, expanding the therapeutic options available to improve the overall health and well-being of individuals with SCZ.

Patients with hematologic malignancies (HM) are highly susceptible to bloodstream infection (BSI), particularly those undergoing treatments such as chemotherapy. A common and debilitating side effect of chemotherapy is oral and intestinal mucositis. These Patients are also at high risk of developing sepsis, which can arise from mucosal barrier injuries and significantly increases mortality in these patients. While conventional antibiotics are effective, their use can lead to antimicrobial resistance (AMR) and disrupt the gut microbiota (dysbiosis). In this review, we discuss utilizing host defense peptides (HDPs), key components of the innate immune system, and immune system inducers (ISIs) to maintain mucosal barrier integrity against infection, an underexplored host-directed therapy (HDT) approach to prevent BSI and sepsis. We advocate for the discovery of potent and safe ISIs for clinical use and call for further research into the mechanisms by which these ISIs induce HDPs and strengthen mucosal barriers.

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.

Vitamin D is a principal regulator of bone and mineral metabolism. Recent data have provided evidence that vitamin D is a polyfunctional hormone with actions that extend beyond its classical role as a nutrient for bone and mineral metabolism. These additional actions include its potential role to prevent infections and autoimmunity. This review will focus on the relationship between vitamin D and infections, specifically on tuberculosis (TB). The literature review was conducted on PubMed using the search terms "Vitamin D" and "Tuberculosis." As one of the most resilient infectious microorganisms on the planet, TB remains a public health concern because of the emergence of resistant strains, the burden, and side effects of treatment. Vitamin D plays an important role in the innate immune system that is the first line of defense against TB infection. Although there appears to be pathophysiological interplay between vitamin D and TB, more research is necessary to determine with certainty the extent of this relationship. Social determinants of health including population density, income, poverty, public assistance, unemployment, and education also play a role in estimating the prevalence of vitamin D deficiency and the burden of TB. This review explores the interplay between vitamin D and TB through factors including the immune system and social determinants of health.

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.

Background and Objectives: Vitamin D supplementation is effective for allergic rhinitis; however, its usefulness is unclear. We conducted a systematic review and meta-analysis to examine the conditions in which vitamin D supplementation was effective in allergic rhinitis management. Materials and Methods: Randomized controlled trials of vitamin D supplementation used for patients with allergic rhinitis were searched for across different databases. We extracted scores on patients' symptoms and the medication types used as the baseline treatments and performed a meta-analysis to evaluate the effect of vitamin D supplementation on allergic rhinitis symptoms. Meta-regression and subgroup analyses were performed for the average age, proportion of female participants, concomitant medications, vitamin D administration durations, and baseline serum 25-hydroxyvitamin D levels. Results: In total, 2389 articles were screened, and 5 randomized controlled trials (RCTs) were included in the meta-analysis. Compared with placebos, vitamin D supplementation alleviated allergic rhinitis symptoms, although the difference was not significant; there was significant heterogeneity among studies (standardized mean difference [SMD] = -2.69, 95% confidence interval [CI]: -6.20 to 0.82, I2 = 98%, p < 0.01). The proportion of female participants in the RCTs (slope: 0.21, p = 0.026) and concomitant corticosteroid use (slope: -9.16, p = 0.005) influenced the vitamin D response. Compared with the placebos, vitamin D supplementation without corticosteroids alleviated the allergic rhinitis symptoms (SMD = -0.56, 95% CI: -0.90 to -0.23). Combination treatment with corticosteroids also non-significantly alleviated symptoms. Additionally, the heterogeneity between studies was significant (SMD = -5.97, 95% CI: -13.55 to 1.16, I2 = 99%, p < 0.01). Conclusions: The study results suggest that vitamin D supplementation alleviates allergic rhinitis symptoms, although the effects differ according to the patient's sex and concomitant medications.

Aging is a complex and heterogeneous biological process characterized by telomere attrition, genomic instability, mitochondrial dysfunction, and disruption in nutrient sensing. Besides contributing to the progression of cancer, metabolic disorders, and neurodegenerative diseases, these manifestations of aging also adversely affect organ function. It is crucial to understand these mechanisms and identify interventions to modulate them to promote healthy aging and prevent age-related diseases. Vitamins have emerged as potential modulators of aging beyond their traditional roles in health maintenance. There is an increasing body of evidence that hormetic effects of vitamins are responsible for activating cellular stress responses, repair mechanisms, and homeostatic processes when mild stress is induced by certain vitamins. It is evident from this dual role that vitamins play a significant role in preventing frailty, promoting resilience, and mitigating age-related cellular damage. Moreover, addressing vitamin deficiencies in the elderly could have a significant impact on slowing aging and extending life expectancy. A review of recent advances in the role of vitamins in delaying aging processes and promoting multiorgan health is presented in this article. The purpose of this paper is to provide a comprehensive framework for using vitamins as strategic tools for fostering longevity and vitality. It offers a fresh perspective on vitamins' role in aging research by bridging biological mechanisms and clinical opportunities.

Warts are benign skin growths caused by variants of human papillomavirus that infect the superficial layers of the skin and penetrate epithelial cells, causing viral multiplication. Warts can be transmitted via skin-to-skin contact and cause significant discomfort and embarrassment. There are multiple treatment options for warts, including topical therapies, cryotherapy, laser vaporization, surgical excision, and oral agents (e.g., zinc, retinoid, levamisole). In recent years, immunotherapy with various antigens has successfully treated multiple lesions by combining a targeted approach with upregulation of the host's immune system. This study explores and compares the efficacy of two immunotherapy options to treat warts: vitamin D3 and the measles, mumps, and rubella (MMR) vaccine.

A randomized prospective comparative study was conducted to determine the efficacy of intralesional vitamin D3 and MMR vaccine in patients suffering from warts. The study population was categorized into two groups. The patients were divided into two equal groups, Group A (MMR; n=90) and Group B (vitamin D3; n=90), using a computer-generated random number table after applying the allocation concealment method to segregate participants and then allocated into either group using the sequentially numbered, opaque, sealed envelope (SNOSE) technique. One group received intralesional vitamin D3, and the other received intralesional MMR vaccine. Researchers followed up with patients for three months after completion of their therapy to notice any relapse. The outcomes considered in our study were recovery (complete, partial, and no recovery) and side effects such as pain, burning sensation, and desquamation. The statistical analysis was done using IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States).

At the end of the study, out of 150 subjects who reached the end, complete clearance was seen in 42/70 (60%) patients in Group A compared to only 26/80 (32.5%) patients showing clearance in Group B after completing six sessions of therapy in either group. Applying the chi-square test, the p-value comes to be 0.001323, so the result is significant at p<0.05. Hence, the MMR vaccine is better than an intralesional injection of vitamin D3 in treating warts.

Intralesional MMR vaccine showed a better response than injection of vitamin D3 in treating warts as an immunotherapeutic agent.

Sepsis and septic shock are major complications of febrile neutropenia (FN) in pediatric patients with cancer (PPCs). The aim of the present study was to determine the association of vitamin D (VD) and cathelicidin levels with sepsis and septic shock in PPCs with FN. A prospective cohort of PPCs with FN who had previously received cytotoxic chemotherapy was analyzed. At baseline, the plasma levels of VD and cathelicidin were quantified. Patients with sepsis and septic shock were compared with patients with FN without complications. Relative risks (RRs) were calculated with 95% confidence intervals (95% CIs) to determine associations. Multiple logistic regression analysis was performed to adjust the results for the identified confounders. A total of 78 episodes of FN were included; 35 (44.8%) completed their FN treatment without complications, 19 (24.4%) presented with sepsis and 24 (30.8%) progressed to septic shock. The median plasma VD level was 15.2 ng/ml, while the median plasma cathelicidin level was 27.9 ng/ml. Patients with severe VD deficiency (RR, 2.34; 95% CI, 1.17-4.70) and patients with cathelicidin levels >41.5 ng/ml (RR, 2.44; 95% CI, 1.07-5.56) exhibited a higher risk of developing sepsis compared with the control group. Patients with severe VD deficiency had a higher risk of septic shock (RR, 1.96; 95% CI, 1.02-3.79) compared with patients without complications, while cathelicidin levels were not associated with septic shock. After adjusting for confounders, cathelicidin levels >41.5 ng/ml (odds ratio, 5.52; 95% CI, 1.17-26.06) remained as an independent risk factor for progressing to sepsis. In patients who developed septic shock, the multivariate model revealed <700 leukocytes/mm3 and glucose levels >100 mg/dl as independent risk factors. In conclusion, higher plasma cathelicidin levels were independently associated with progression to sepsis in PPCs with FN.

Macrophages destroy bacteria and other microorganisms through phagocytosis-coupled antimicrobial responses, such as the generation of reactive oxygen species and the delivery of hydrolytic enzymes from lysosomes to the phagosome. However, many intracellular bacteria subvert these responses, escaping to other cellular compartments to survive and/or replicate. Such bacterial subversion strategies are countered by a range of additional direct antibacterial responses that are switched on by pattern-recognition receptors and/or host-derived cytokines and other factors, often through inducible gene expression and/or metabolic reprogramming. Our understanding of these inducible antibacterial defence strategies in macrophages is rapidly evolving. In this Review, we provide an overview of the broad repertoire of antibacterial responses that can be engaged in macrophages, including LC3-associated phagocytosis, metabolic reprogramming and antimicrobial metabolites, lipid droplets, guanylate-binding proteins, antimicrobial peptides, metal ion toxicity, nutrient depletion, autophagy and nitric oxide production. We also highlight key inducers, signalling pathways and transcription factors involved in driving these different antibacterial responses. Finally, we discuss how a detailed understanding of the molecular mechanisms of antibacterial responses in macrophages might be exploited for developing host-directed therapies to combat antibiotic-resistant bacterial infections.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. They occur in the urinary system when a microorganism, commonly present on the perineal skin or rectum, reaches the bladder through the urethra, and adheres to the luminal surface of uroepithelial cells, forming biofilms. The treatment of UTIs includes antibiotics, but their indiscriminate use has favored the development of multidrug-resistant bacteria strains, which represent a serious challenge to today's microbiology. The pathogenesis of the infection and antibiotic resistance synergistically contribute to hindering the eradication of the disease while favoring the establishment of persistent infections. The repeated requirement for antibiotic treatment and the limited therapeutic options have further contributed to the increase in antibiotic resistance and the occurrence of potential relapses by therapeutic failure. To limit antimicrobial resistance and broaden the choice of non-antibiotic preventive approaches, this review reports studies focused on the bacteriostatic/bactericidal activity, inhibition of bacterial adhesion and quorum sensing, restoration of uroepithelial integrity and immune response of molecules, vitamins, and compounds obtained from plants. To date, different supplementations are recommended by the European Association of Urology for the management of UTIs as an alternative approach to antibiotic treatment, while a variety of bioactive compounds are under investigation, mostly at the level of in vitro and preclinical studies. Although the evidence is promising, they are far from being included in the clinical practice of UTIs.

Vitamin D receptor [VDR] expression promotes LL37 expression, possibly contributing to host defense. The hypothesis was that an increase in 25 hydroxyvitamin D [25vitD] could lead to enhanced VDR expression and increased LL-37 production, thereby contributing to improved prognosis in critically ill patients. Methods: A nonblinded, randomized controlled trial was conducted. A total of 207 patients admitted to ICU with severe SARS-CoV-2 pneumonia were included and received different doses of cholecalciferol (500 MU, 3 MU/day, no cholecalciferol) during their ICU and hospital stay. 25vitD levels as well as LL37 and monocytes' VDR gene expression were evaluated on admission and after. Clinical evolution, ICU mortality, hospital mortality, and 60-day mortality were evaluated. Results: The median age was 57.7 years and the majority of patients were Caucasian [87.4%] and male [70.5%]. There was a significant difference in 25vitD levels between groups on the third [p = 0.002] and seventh [p < 0.001] days. Patients supplemented with 500 MU of cholecalciferol had a very significant increase in monocytes' VDR gene expression and showed a better clinical evolution in the ICU, with a significant correlation to evolution factors. Higher LL37 on admission had a significant negative association with hospital and ICU mortality, lost after adjustment for comorbidities to a nearly significant association with ICU, hospital, and 60-day mortality. Conclusion: Supplementation with higher doses of cholecalciferol may contribute to a significant increase in 25vitD levels but not in LL37 levels. Higher LL37 levels on admission may be related to a decrease in ICU, hospital, and 60-day mortality. VDR gene expression in monocytes is much higher in patients supplemented with higher doses of cholecalciferol.

Despite a large number of published studies, the effect of vitamin D3 supplementation on mortality in hospitalized patients, as well as the recommended dose and duration of therapy, is unclear. In our retrospective study, we aimed to investigate the impact of vitamin D deficiency and moderately high-dose vitamin D3 supplementation on mortality and disease outcomes in patients with COVID-19 infection.

We analyzed data from 148 COVID-19-infected hospitalized patients in two different departments, Internal Medicine and Oncology, at Semmelweis University. The severity of COVID-19 and the treatment used were the same except at one of the departments, where patients received circa 90,000 IU of vitamin D3. We compared in-hospital mortality rates between the groups. In a subgroup analysis, we evaluated the efficacy and safety of vitamin D3 supplementation by assessing 25(OH)D and 1,25(OH)2D concentrations on days 0, 4, and 8.

As a result of the supplementation, the deficiency was resolved in 4 days in deficient patients, and none of the 25(OH)D or 1,25(OH)2D concentrations exceeded the normal range. Mortality was significantly lower and decreased 67% in the group receiving vitamin D3 supplementation, regardless of baseline 25(OH)D concentrations.

The supplemental dosage, 3 × 30,000 IU of vitamin D3, is effective and safe and may reduce mortality in COVID-19 infection.

On September 27, 2024, a discussion-based working meeting on the issue of vitamin D deficiency in patients with overweight and obesity was held in Vladikavkaz.The meeting aimed to evaluate the relationship between vitamin D deficiency, overweight, and associated comorbidities, as well as to explore modern strategies and practical approaches for managing such patients in endocrinology practice. The resolution of the meeting was developed by its participants, comprising leading endocrinologists.

Patients with vitamin D deficiency are susceptible to increased microbial infection and increased risk of mortality. However, whether vitamin D supplementation would improve their prognosis remains uncertain.

We conducted a retrospective cohort study using data from MIMIC-IV database, a publicly available database containing clinical information on patients admitted to the ICU at Beth Israel Deaconess Medical Center (BIDMC) from 2008 to 2019. Adult patients with sepsis were included in the analysis. The exposure factor was vitamin D supplementation during the ICU stay. The primary outcome was 28-day all-cause mortality. Both propensity score matching (PSM) and stepwise regression analyses were employed to adjust for potential confounders.

A total of 20230 eligible patients were enrolled in the entire unmatched cohort, and 8710 patients were included in the matched cohort. In PSM analysis, the 28-day all-cause mortality rate was 14.04% (250/1780) in the vitamin D group and 22.31% (1546/6930) in the no vitamin D group. Vitamin D supplementation was associated with decreased 28-day all-cause mortality (HR, 0.56; 95% CI, 0.49-0.64; p < 0.001). Subgroup analyses showed consistent benefits regardless of the baseline vitamin D status (deficiency: HR, 0.70; 95% CI, 0.33-1.50; p = 0.36; insufficiency: HR, 0.10; 95% CI, 0.03-0.34; p < 0.001; sufficiency: HR, 0.33; 95% CI, 0.12-0.88; p = 0.03). Additionally, vitamin D supplementation was associated with decreased ICU mortality (OR, 0.37; 95% CI, 0.29-0.48; p < 0.001) and reduced in-hospital mortality (OR, 0.57; 95% CI, 0.48-0.68; p < 0.001). Sensitivity analysis using the unmatched cohort confirmed these findings (HR, 0.57; 95% CI, 0.43-0.76; p < 0.001).

Vitamin D supplementation may reduce mortality in critically ill patients with sepsis. However, further high-quality prospective studies are still needed to validate these findings.

Randomised trials conducted from 2006 to 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, larger randomised trials published in 2022 did not confirm the health benefits of VDS in COVID-19 patients.

To examine through a systematic review with meta-analysis the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and of randomised trials on VDS for the prevention of ARI.

A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al. 2021. Groups were formed including trials with total numbers of patients below or above the median size of all trials. The associations between VDS vs no VDS, and admission to ICU were evaluated using random-effects models from which summary odds ratios (SOR) and 95% confidence intervals (CI) were obtained. Meta-analyses were done for all trials and for each group of trials, which allowed testing a possible effect modification of trial size. Publication bias was assessed using the Louis-Furuya-Kanaruori (LFK) index (no bias if index between -1 and +1) and the trim and fill method.

Nine trials on VDS for preventing admission to ICU were identified, including 50 to 548 patients. The summary odds ratio (SOR) was 0.61 (95% CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (interaction p = 0.04). The LFK index was -3.79, and after trim and fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention included 25 to 16,000 patients. The SOR was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (interaction p = 0.0001). The LFK index was -3.11, and after trim and fill, the SOR was 0.96 (0.88-1.05).

Strong publication bias affected small randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.

Vitamin D offers numerous under-recognized health benefits beyond its well-known role in musculoskeletal health. It is vital for extra-renal tissues, prenatal health, brain function, immunity, pregnancy, cancer prevention, and cardiovascular health. Existing guidelines issued by governmental and health organizations are bone-centric and largely overlook the abovementioned extra-skeletal benefits and optimal thresholds for vitamin D. In addition, they rely on randomized controlled trials (RCTs), which seldom show benefits due to high baseline 25-hydroxyvitamin D [25(OH)D] concentrations, moderate supplementation doses, and flawed study designs. This review emphasizes the findings from prospective cohort studies showing that higher 25(OH)D concentrations reduce the risks of major diseases and mortality, including pregnancy and birth outcomes. Serum concentrations > 30 ng/mL (75 nmol/L) significantly lower disease and mortality risks compared to <20 ng/mL. With 25% of the U.S. population and 60% of Central Europeans having levels <20 ng/mL, concentrations should be raised above 30 ng/mL. This is achievable through daily supplementation with 2000 IU/day (50 mcg/day) of vitamin D3, which prevent diseases and deaths. Furthermore, a daily dose between 4000 and 6000 IU of vitamin D3 to achieve serum 25(OH)D levels between 40 and 70 ng/mL would provide greater protection against many adverse health outcomes. Future guidelines and recommendations should integrate the findings from observational prospective cohort studies and well-designed RCTs to improve public health and personalized care.

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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized for inducing severe respiratory symptoms like cough, and shortness of breathing. Although symptom severity varies, some individuals remain asymptomatic. This virus has sparked a global pandemic, imposing a substantial rate of mortality or morbidity, with extended periods of illness reported. People with underlying medical issues and the elderly are more likely to experience adverse results. The virus's frequent mutations pose challenges for medical professionals, necessitating adaptable therapeutic and preventive strategies. Vitamin D, a versatile regulatory molecule, not only influences physiological processes such as serum calcium regulation but also exhibits immunomodulatory functions. Calcium ions play a crucial role as secondary signal transduction molecules, impacting diverse cellular functions and maintaining homeostasis through ion channel regulation. Parathormone, another key regulator of serum calcium, often acts antagonistically to vitamin D. This review delves into the interplay of vitamin D, calcium, and parathormone, exploring their possible influence on the progression of COVID-19. The intricate signaling involving these elements contributes to adverse prognosis, emphasizing the need for comprehensive understanding. Monitoring and controlling these physiological factors and associated pathways have shown the potential to alter disease outcomes, underscoring the importance of a holistic approach.

Cathelicidins are a group of cationic, amphipathic peptides that play a vital role in the innate immune response of many vertebrates, including humans. Produced by immune and epithelial cells, they serve as natural defenses against a wide range of pathogens, including bacteria, viruses, and fungi. In humans, the cathelicidin LL-37 is essential for wound healing, maintaining skin barrier integrity, and combating infections. Cathelicidins of different origins have shown potential in treating various skin conditions, including melanoma, acne, and diabetic foot ulcers. Despite their promising therapeutic potential, cathelicidins face significant challenges in clinical application. Many peptide-based therapies have failed in clinical trials due to unclear efficacy and safety concerns. Additionally, the emergence of bacterial resistance, which contradicts initial claims of non-resistance, further complicates their development. To successfully translate cathelicidins into effective clinical treatments, therefore, several obstacles must be addressed, including a better understanding of their mechanisms of action, sustainable large-scale production, optimized formulations for drug delivery and stability, and strategies to overcome microbial resistance. This review examines the current knowledge of cathelicidins and their therapeutic applications and discusses the challenges that hinder their clinical use and must be overcome to fully exploit their potential in medicine.

Despite being one of the most common infectious diseases, urinary tract infections (UTIs) still represent a challenge for clinicians to diagnose and treat, especially in the era of growing antibiotic resistance among uropathogenic bacteria. Recent studies investigating the pathophysiology of UTIs have discovered the prominent role of antimicrobial peptides in the urinary tract defense system. Cathelicidin is an evolutionary conserved antimicrobial peptide encoded by one single gene in humans. Except for being stored in neutrophil cytoplasmic granules, cathelicidin is produced by uroepithelial cells rapidly upon contact with a uropathogen, even before leukocytes invade the urinary tract. In addition to its bactericidal effect, cathelicidin acts as a chemoattractant for multiple immune cells and a potent inductor of numerous cytokine synthesis. Such a crucial role in the initial pathogenesis of a UTI makes cathelicidin a potential biomarker for an early UTI diagnosis. Indeed, multiple studies over the last two decades have proved the potential clinical utility of cathelicidin as a UTI diagnostic biomarker. Furthermore, since patients after the resolution of a UTI have been found to express a lower urinary cathelicidin level than healthy controls, decreased cathelicidin levels have been suggested as a risk factor for developing UTI recurrence. Therefore, measuring cathelicidin levels in urine might help in distinguishing patients with a higher risk for a recurrent UTI. Interestingly, except in UTIs, cathelicidin has also been evaluated in other urinary tract diseases and proposed as a biomarker for diagnosing severe vesicoureteral reflux (VUR) and for recognizing renal scar development in patients with VUR. Finally, a prominent role in UTI pathogenesis also makes cathelicidin an attractive therapeutic target for treating UTIs and, lately, different therapeutic agents up-regulating cathelicidin expression have been investigated in this matter. Therefore, the present review aims to summarize the current body of knowledge on the diagnostic, prognostic and therapeutic potential of cathelicidin in urinary tract diseases. For this purpose, three databases (Scopus, Medline and Web of Science) were extensively searched to cover all the published articles. This exhaustive review will update clinicians on the contemporary state of knowledge about the potential clinical utility of cathelicidin in urinary tract diseases and hopefully encourage further research, resulting in improvement in the current management of urinary tract diseases.

Vitamin D is a key molecule in calcium and phosphate homeostasis; however, increasing evidence has recently shown that it also plays a crucial role in the immune system, both innate and adaptive. A deregulation of vitamin D levels, due also to mutations and polymorphisms in the genes of the vitamin D pathway, determines severe alterations in the homeostasis of the organism, resulting in a higher risk of onset of some diseases, including osteoporosis. This review gives an overview of the influence of vitamin D levels on the pathogenesis of osteoporosis, between bone homeostasis and immune system.

Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients?

Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women.

EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels.

We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients.

A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients were divided into two groups: the <50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs.

Of all patients, 23.8% (740/3107) were vitamin D deficient (<50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with <50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smooth curve fitting model showed a nonlinear correlation between 25(OH)D levels and risk of EPs (nonlinear P-value = 0.020), with an optimal threshold of 51.8 nmol/l for 25(OH)D levels. Moreover, subgroup smooth curve fitting models showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients aged <35 years (nonlinear P-value = 0.010), whereas a linear correlation between 25(OH)D levels and polyp risk was found in patients aged ≥35 years (nonlinear P-value = 0.682).

Caution should be exercised in interpreting our findings as this is a correlational study and causality cannot be inferred from our results. In addition, because of strict inclusion and exclusion criteria, our results may not be generalizable to unselected populations, including premenopausal women or women of other races.

This study demonstrated for the first time that vitamin D deficiency is an independent risk factor for the incidence of EPs in infertile patients. Identifying modifiable risk factors (e.g. vitamin D deficiency) can help in the development of new strategies for treating polyps or to protect against polyp development. Further clinical intervention trials and laboratory studies are needed to evaluate the effect of vitamin D on the development of EPs and to elucidate the mechanisms.

The study was funded by the National Natural Science Foundation of China (82101718) and Natural Science Foundation of Guangdong Province, China (2022A1515010776). No competing interest was involved in this study.

N/A.

Several studies have suggested an association between vitamin deficiency and the development of tuberculosis; however, the precise impact remains unclear. This study aimed to elucidate the relationship between distinct vitamin statuses and the occurrence of tuberculosis.

Retrieval was conducted using several databases without language restrictions to capture the eligible studies on tuberculosis and vitamin status. Pooled odds ratios (ORs), relative risks (RRs), and hazard ratios (HRs) were used with 95% confidence intervals (CIs) to clarify the relationship between the different vitamin statuses (A, B, D, and E) and the occurrence of tuberculosis. Subgroup analysis, sensitivity analysis, meta-regression analysis, and Galbraith plot were performed to determine sources of heterogeneity. Potential publication biases were detected using Begg's test, Egger's test, and the trim-and-fill test.

We identified 10,266 original records from our database searches, and 69 eligible studies were considered in this study. The random-effect model showed that people with tuberculosis may exhibit vitamin A deficiency (OR = 10.66, 95%CI: 2.61-43.63, p = .001), while limited cohort studies showed that vitamin A supplementation may reduce tuberculosis occurrence. Additionally, vitamin D deficiency was identified as a risk factor for tuberculosis development (RR = 1.69, 95%CI: 1.06-2.67, p = .026), and people with tuberculosis generally had lower vitamin D levels (OR = 2.19, 95%CI: 1.76-2.73, p < .001) compared to other groups. No publication bias was detected.

This meta-analysis indicated that people with tuberculosis exhibited low levels of vitamins A and D, while vitamin D deficiency was identified as a risk factor for tuberculosis. More randomized controlled interventions at the community levels should be recommended to determine the association between specific vitamin supplementation and tuberculosis onset.

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 status, the vitamin D receptor (VDR), and the ability to produce active vitamin D [1,25(OH)2D, regulated by Cyp27b1] regulate fetal and adult hematopoiesis. Transgenic reporter mice that express the tdTomato RFP as an indication of Vdr expression were used to identify immune cells that express the Vdr. Vdr/tdTomato+ hematopoietic progenitors were identified as early as embryonic day (E)15.5, establishing that these cells have expressed the Vdr and are vitamin D targets. Maternal vitamin D deficiency [D-; serum 25(OH)D < 20 ng/ml] or Vdr knockout or Cyp27b1 knockout resulted in embryos with fewer fetal progenitors. Vdr/tdTomato+ expression was found to increase with age in CD8+ T cells and innate lymphoid cells (ILCs)1 and ILC3, suggesting that initial Vdr expression in these cells is dependent on environmental factors immediately postbirth. In adult tissues, the frequencies of mature T cells and ILCs as well as Vdr/tdTomato expression were reduced by D-. Maternal D- resulted in fewer progenitors that expressed Vdr/tdTomato+ at E15.5 and fewer Vdr/tdTomato+ immune cells in the adult spleen than offspring from D+ mice. We challenged D- mice with H1N1 influenza infection and found that D- mice were more susceptible than D+ mice. Treating D- mice with vitamin D restored Vdr/tdTomato+ expression in splenic T cells and partially restored resistance to H1N1 infection, which shows that developmental D- results in lingering effects on Vdr expression in the adult immune system that compromise the immune response to H1N1 infection. Vitamin D and the Vdr regulate hematopoiesis in both fetal and postnatal phases of immune cell development that impact the immune response to a viral infection.

Genetic factors are reported to be connected with tuberculosis (TB) infection. Studies have shown that genetic variations in genes involved in the vitamin D pathway influence the levels of vitamin D found in the bloodstream (serum). Cyp27b1 (1α-hydroxylase) is an enzyme that activates the synthesis of bioactive vitamin D3 by hydroxylation of 25(OH)D3.The in vitro studies reported rare gene variants of Cyp27b1 such as rs118204011 and rs118204012, associated with loss of Cyp27b1 function and lower serum vitamin D levels. Globally, a critical gap exists in understanding the link between these gene variants with TB and vitamin D levels. Hence, the study objective is to comprehend the association of Cyp27b1 rs118204009 (G/A), rs118204011 (C/T), and rs118204012 (A/G) with tuberculosis susceptibility/protection and to assess the influence of gene variants on vitamin D levels in both healthy controls (HCs) and those with pulmonary tuberculosis (PTB) in South India.

Genomic DNA extraction was performed by salting-out procedure and subsequently genotyped through polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Vitamin D level was measured by Enzyme-Linked Immunosorbent Assay (ELISA).

In rs118204012 (A/G), a substantial association was found with PTB susceptibility in allele 'A' [Odds Ratio (OR): 1.52 (1.02-2.26); p = 0.044] and 'AA' genotype [OR: 1.69 (1.02-2.81); p = 0.040] through the dominant model. Allele 'G' [OR: 0.66 (0.44-0.98); p = 0.044) was found to be associated with protection against TB. Males were associated with increased susceptibility towards TB compared to females in the rs118204011 "CC" [OR: 3.94 (1.94-7.98); p = 0.002] and rs118204012 'AA' [OR: 4.57 (2.13-9.79); p = 0.0001] genotypes. Vitamin D insufficiency (<30 ng/ml) was more prevalent in PTB patients (66.67 %) with the rs118201012 'AA' genotype compared with healthy controls (57.14 %). This genotype was associated with disease susceptible odds ratio of 1.5.

Cyp27b1 rs118204012 'AA' genotype was found to have association with vitamin D insufficiency and TB susceptibility. In terms of gender, our findings suggest that male individuals are correlated with a higher TB risk. This suggest that the gene variants may be involved in the downstream processing of serum Vitamin D levels and its association with the disease.

Background. According to the World Health Organization, neglected tropical diseases (NTDs) affect over two billion people worldwide. While the links between nutrition and many diseases have become clear over recent decades, NTDs have lagged behind and the linkage with nutrition is largely unknown. We conducted this systematic review with meta-analysis to determine the current knowledge on the association between NTDs and malnutrition. Methodology. PubMed, Embase, Scopus and African Journals Online databases were searched using predefined search terms. We included all original articles with a case-control design and at least one NTD. The studies had to compare nutritional parameters between infected cases and control participants. Articles that did not report original data were excluded. The quality of the studies was assessed using the Newcastle-Ottawa scale. Pooled estimates were conducted using the random effect model. The publication bias of the studies was determined by funnel plots. Q and I 2 statistics were used to assess the heterogeneity of the studies. Results. After screening 1294 articles, only 16 qualified for the systematic review and 12 for meta-analysis. These predominately had a focus on soil-transmitted helminthiasis (ascariasis, hookworm diseases and trichuriasis) and schistosomiasis, with a minority concerning leishmaniasis and leprosy. Pooled estimates showed an association between intestinal parasites and stunting in children [odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.14-1.66, I 2 = 0%, tau2 = 0]. We also identified a moderate association established between serum iron deficiency (OR = 4.67, 95% CI: 1.91-11.44, tau2 = 0) and intestinal parasites. Conclusions/significance. Of the 20 NTDs, the links between diet and disease have been explored for only 4. There is a paucity of data from low- and middle-income countries and least-developed countries where the NTD burden is high. Therefore, more research into the role of malnutrition in NTDs other than intestinal parasites, leishmaniasis and leprosy is needed.

The function of keratinocytes (KCs) to form a barrier and produce cytokines is well-known, but recent progress has revealed many different roles for KCs in regulation of skin immunity. In this review, we provide an update on the current understanding of how KCs communicate with microbes, immunocytes, neurons, and other cells to form an effective immune barrier. We catalog the large list of genes and metabolites of KCs that participate in host defense and discuss the mechanisms of immune crosstalk, addressing how KCs simultaneously form a physical barrier, communicate with fibroblasts, and control immune signals. Overall, the signals sent and received by KCs are an exciting group of therapeutic targets to explore in the treatment of dermatologic disorders.

Long noncoding small nucleolar RNA (LncRNA) host gene 16 (SNHG16) is associated with certain diseases, including cancers. However, its role and mechanism in Mycobacterium tuberculosis (Mtb) infection remain unclear. Here, we demonstrated that SNHG16 expression levels were suppressed in peripheral blood mononuclear cells (PBMCs) and CD14+ monocytes of tuberculosis (TB) patients. SNHG16 was up-regulated by acute Mtb infection of PBMCs from healthy control (HC) subjects. Such TB suppression of SNHG16 was consistent with an immunosuppressive-like state driven by IL-10 signaling as seen in TB patients. Notably, SNHG16 limited Mtb growth in macrophages/monocytes through autophagy and vitamin D receptor (VDR)-dependent cathelicidin (CAMP) antimicrobial pathways. Concurrently, SNHG16 was highly expressed in lymphocytes, including CD8+ and Vγ2 Vδ2 T-cell subsets in HCs. SNHG16 overexpression in lymphocytes allowed them to control Mtb infection in macrophages, and SNHG16 epigenetically increased the expression of anti-Mtb effector cytokines in lymphocytes by developing more accessible chromatin states in gene loci encoding IFN-γ, TNF-α, and Granzyme B. Furthermore, the adoptive transfer of SNHG16-overexpressing human PBMCs into Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, SNHG16 drove the induction of pleiotropic effector functions that inhibited intracellular Mtb growth in vitro and in vivo, serving as an immunotherapy target in TB.

Gut microbiome plays a vital role in the intestinal ecosystem and has close association with metabolites. Due to the development of metabolomics and microbiomics, recent studies have observed that alteration of either the gut microbiome or metabolites may have effects on the progression of pancreatitis. Several new treatments based on the gut microbiome or metabolites have been studied extensively in recent years. Gut microbes, such as Bifidobacterium, Akkermansia, and Lactobacillus, and metabolites, such as short-chain fatty acids, bile acids, vitamin, hydrogen sulfide, and alcohol, have different effects on pancreatitis. Some preliminary studies about new intervention measures were based on the gut microbiome and metabolites such as diet, prebiotic, herbal medicine, and fecal microbiota transplantation. This review aims to summarize the recent advances about the gut microbiome, metabolites, and pancreatitis in order to determine the potential beneficial role of the gut microbiome and metabolites in pancreatitis.

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.

Despite their relatively short lifespan, neutrophils are tasked with counteracting pathogens through various functions, including phagocytosis, production of reactive oxygen species, neutrophil extracellular traps (NETs), and host defense peptides. Regarding the latter, small cationic cathelicidins present a conundrum in neutrophil function. Although primarily recognized as microbicides with an ability to provoke pores in microbial cell walls, the ability of cathelicidin to modulate key neutrophil functions is also of great importance, including the release of chemoattractants, cytokines, and reactive oxygen species, plus prolonging neutrophil lifespan. Cumulative evidence indicates a less recognized role of cathelicidin as an "immunomodulator"; however, this term is not always explicit, and its relevance in neutrophil responses during infection and inflammation is seldom discussed. This review compiles and discusses studies of how neutrophils use cathelicidin to respond to infections, while also acknowledging immunomodulatory aspects of cathelicidin through potential crosstalk between sources of the peptide.

Background: Critically ill patients with sepsis have a high incidence of vitamin D deficiency. Vitamin D promotes the synthesis of human cathelicidin antimicrobial peptide, a precursor of LL-37, which is a part of the innate immune system. This study investigated the effectiveness and safety of the early administration of high-dose enteral vitamin D3 in comparison with low-dose vitamin D3 in patients with sepsis requiring mechanical ventilation (MV). Methods: Eighty adult patients with sepsis requiring MV with known vitamin D deficiency were randomly assigned to receive either an enteral 50 000 IU (Group I) or 5000 IU (Group II) vitamin D supplementation. Clinical and laboratory parameters were evaluated at baseline and on days 4 and 7 between the study groups. The change in serum procalcitonin (PCT) levels on day 7 was the primary outcome, while the change in serum LL-37 levels on day 7, changes in sequential organ failure assessment (SOFA) score, and clinical pulmonary infection score on day 7, MV duration, and hospital length of stay (LOS) were the secondary outcomes. Results: The (day 7-day 0) change in serum PCT and LL-37 levels and SOFA score were significantly different in Group I (P = .010, P < .001, and P < .001, respectively). The SOFA score was significantly different on days 4 and 7 in Group I (P < .001 and P < .001, respectively). The incidence of early ventilator-associated pneumonia was significantly different between both treatment groups (P = .025). The hospital LOS was shorter in Group I (P < .001). No 25-hydroxyvitamin-D toxicity was observed in either group. Conclusions: Early enteral administration of high-dose vitamin D3 in critically ill patients with sepsis requiring MV along with standard treatment for sepsis decreased serum procalcitonin levels, increased serum LL-37 levels, and ameliorated illness severity scores.

Acne is an inflammatory condition of the pilosebaceous unit. Previous studies have established a link between acne and vitamin D deficiency and the potential effectiveness of vitamin D supplementation in treatment. However, the efficacy of vitamin D as an adjuvant treatment for acne remains unknown.

To evaluate the efficacy of weekly vitamin D2 oral administration as an adjunctive treatment to standard topical care for acne.

This study was a randomized, double-blind, placebo-controlled trial including subjects with mild-to-moderate acne. Topical 2.5% benzoyl peroxide was applied twice daily for 12 weeks to all subjects. Subjects were randomly allocated to receive either oral vitamin D2 40,000 IU weekly or placebo weekly during the treatment period. No additional treatment was administered during the 4-week follow-up period.

A total of 44 subjects were included in this study. All of them had inadequate 25(OH)D levels. Both regimens showed significant improvement in acne during the treatment period. Weekly vitamin D2 supplementation significantly prevented the relapse of inflammatory acne lesions (P = .048) at the follow-up visit. No adverse effects or biochemical changes were observed.

There were no subjects of severe acne vulgaris.

Adjunctive weekly vitamin D2 supplementation to standard topical benzoyl peroxide could reduce relapses of inflammatory lesions in mild-to-moderate acne.

Sodium glucose cotransporter 2 inhibitors (SGLT2is) are a newly developed class of anti-diabetics which exert potent hypoglycemic effects in the diabetic milieu. However, the evidence suggests that they also have extra-glycemic effects. The renin-angiotensin-aldosterone system (RAAS) is a hormonal system widely distributed in the body that is important for water and electrolyte homeostasis as well as renal and cardiovascular function. Therefore, modulating RAAS activity is a main goal in patients, notably diabetic patients, which are at higher risk of complications involving these organ systems. Some studies have suggested that SGLT2is have modulatory effects on RAAS activity in addition to their hypoglycemic effects and, thus, these drugs can be considered as promising therapeutic agents for renal and cardiovascular disorders. However, the exact molecular interactions between SGLT2 inhibition and RAAS activity are not clearly understood. Therefore, in the current study we surveyed the literature for possible molecular mechanisms by which SGLT2is modulate RAAS activity.

25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further.

4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model. In addition, subgroup and sensitivity analyses were employed.

1255 participants died during a mean follow-up period of 70 months. Compared with the 25(OH)D-deficient group, the fully adjusted hazard ratios and 95% confidence intervals for the 25(OH)D-adequate group were 0.631 (0.545, 0.730) for all-cause mortality, 0.569 (0.435, 0.743) for cardiovascular mortality, 0.637 (0.461, 0.878) for hypertension mortality, and cancer mortality was 0.596 (0.426, 0.834). The inflection points of serum 25(OH)D concentration affecting all-cause and cardiovascular mortality were 89 nmol/L, and 107 nmol/L, respectively. Subgroup analyses and interaction tests suggested that the effects varied across populations. The results of sensitivity analyses indicated a reliable correlation.

We found an association between serum 25(OH)D concentrations and the prognosis of patients with CKD as a reliable predictor of early intervention and intensive care.

COPD is a common, preventable and treatable airway disease, and is currently the third leading cause of death worldwide. About one billion people worldwide are estimated to have vitamin D deficiency or insufficiency. Vitamin D deficiency is common among people with COPD, and has been reported to be associated with reduced lung function and increased risk of acute exacerbations of COPD. Several clinical trials of vitamin D to prevent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and improve COPD control have been conducted, but an up-to-date meta-analysis of all double-blind, randomised, placebo-controlled trials of this intervention is lacking.

To assess the effects of vitamin D for the management of acute exacerbations and symptoms for people with COPD.

We searched the Cochrane Airways Trials Register and reference lists of articles. We also searched trial registries directly, and contacted the authors of studies in order to identify additional trials. The date of the last search was 24 August 2022.

We included double-blind, randomised, placebo-controlled trials of vitamin D or its hydroxylated metabolites, for adults with a clinical diagnosis of chronic obstructive pulmonary disease based on the presence of characteristic symptoms and irreversible airflow obstruction. We did not impose restrictions regarding disease severity or baseline vitamin D status, in order to maximise generalisability.

We used standard Cochrane methods. The primary outcome was the rate of moderate or severe exacerbations (requiring systemic corticosteroids, antibiotics or both). We also performed subgroup analyses to determine whether the effect of vitamin D on the rate of moderate or severe exacerbations was modified by baseline vitamin D status, COPD severity or regular inhaled corticosteroid use. The main secondary outcomes of interest were the proportion of participants experiencing one or more exacerbations (moderate or severe), the change in forced expiratory volume in one second (FEV1, % predicted) and the proportion of participants with one or more serious adverse events of any cause, mortality (all-cause) and quality of life. We used GRADE to assess the certainty of evidence for each outcome.

We included 10 double-blind, randomised, placebo-controlled trials in this review, involving a total of 1372 adults. Five studies contributed to the primary outcome analysis of the rate of moderate or severe exacerbations requiring systemic corticosteroids, antibiotics or both. The duration of studies ranged from six weeks to 40 months, and all investigated the effects of administering cholecalciferol (vitamin D3). One study included two intervention arms, one where vitamin D3 was given and one where calcitriol (1,25-dihydroxyvitamin D) was given. The majority of participants had mild to moderate COPD, and profound vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) < 25 nmol/L) at baseline was rare (123 participants contributing data to subgroup analysis). Administration of vitamin D or its hydroxylated metabolites results in little to no change in the overall rate of exacerbations requiring systemic corticosteroids, antibiotics or both (rate ratio (RR) 0.98, 95% CI 0.86 to 1.11; 5 studies, 980 participants; high-certainty evidence). Vitamin D supplementation did not influence any meta-analysed secondary outcomes. These were all based on moderate- or high-certainty evidence aside from adverse events and quality of life, which were based on low-certainty evidence. We observed little to no change in the proportion of participants experiencing one or more moderate or severe exacerbations (odds ratio (OR) 0.94, 95% CI 0.72 to 1.24; 5 studies, 980 participants; high-certainty evidence). Additionally, vitamin D probably results in little to no difference in the inter-arm mean change in FEV1 (% predicted) (mean difference 2.82 higher in intervention arm, 95% CI -2.42 to 8.06; 7 studies, 1063 participants; moderate-certainty evidence). There was also probably no effect of vitamin D on the incidence of serious adverse events due to any cause; although we identified an anticipated absolute effect of 36 additional adverse events per 1000 people, the confidence interval included the null hypothesis of no effect (OR 1.19, 95% CI 0.82 to 1.71; 5 studies, 663 participants; moderate-certainty evidence). Vitamin D may have little to no effect on mortality (OR 1.13, 95% CI 0.57 to 2.21; 6 studies, 1019 participants; low-certainty evidence). It also may have little to no effect on quality of life as measured by validated instruments (narrative findings; 5 studies, 663 participants; low-certainty evidence). We assessed one study as being at high risk of bias in at least one domain; this did not contribute data to the meta-analysis of the primary outcome reported above. Sensitivity analysis that excluded this study from the meta-analysed outcome to which it contributed, the inter-arm mean change in FEV1, did not change the findings.

We found that administration of vitamin D results in little to no effect on the rate of moderate or severe exacerbations requiring systemic corticosteroids, antibiotics or both or the proportion of participants experiencing one or more exacerbations (moderate or severe) (both high-certainty evidence). Further, vitamin D probably has no effect on the inter-arm difference in change in lung volumes and the proportion of participants with one or more serious adverse event of any cause (both moderate-certainty evidence), and may make little to no difference to mortality or quality of life (both low-certainty evidence). We recommend further research on the balance of benefits and harms of vitamin D supplements in COPD for those with very low or very high starting vitamin D levels, because we assessed the available evidence as low-certainty for these groups.