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The association between vitamin D concentrations and the occurrence of diabetic foot ulcers (DFUs) remains a topic of ongoing debate. In order to provide a comprehensive and updated review, we conducted this meta‐analysis to further investigate the relationship between vitamin D concentrations and DFUs occurrence. The following databases, including Cochrane Library, EMBASE, Web of Science, PubMed, CBM, CNKI, WANFANG DATA and VIP Database, were systematically searched for studies published up to Dec. 20th, 2023. The combined estimation was calculated using both fixed-effects and random‐effects models. The overall effect size was reported as a weighted mean difference (WMD) with a corresponding 95% confidence interval (95%CI). Data analysis was performed utilizing Review Manager 5.4 and Stata 14. The Protocol has been registered in PROSPERO CRD42024503468. This updated meta-analysis, incorporating thirty-six studies encompassing 11,298 individuals with or without DFUs, demonstrated a significant association between vitamin D deficiency/insufficiency and an elevated risk of DFUs occurrence (< 25 nmol/L, OR 3.28, P < 0.00001; < 50 nmol/L, OR 2.25, P < 0.00001; < 75 nmol/L, OR 1.67, P = 0.0003). Vitamin D concentrations were significantly lower in individuals with DFUs compared to those without DFUs (P < 0.00001). Subgroup analyses consistently demonstrated this trend among the older population (> 50 years, P < 0.00001), individuals with long duration of diabetes (> 10 years, P < 0.00001), and those with poor glycemic control (mean HbA1c 8%-9% and > 9%, P < 0.00001). [ABSTRACT FROM AUTHOR]

Background: Benign paroxysmal positional vertigo is the most common neurootologic disorder, characterized by brief attacks of vertigo aggravated by certain head positions. During the last two decades, several studies were performed in different countries trying to find a relationship between benign paroxysmal positional vertigo and vitamin D3 (25 hydroxyvitamin D) deficiency. Objectives: This study aimed to find the relationship between vitamin D3 deficiency and total serum calcium with benign paroxysmal positional vertigo. Patients and methods: A case–control study conducted from January 2021 to December 2021, consisted of 62 participants; 30 patients with posterior canal benign paroxysmal positional vertigo and 32 healthy persons considered as a control group. The age and sex of both groups were matched, and diagnosis was made by history and examination (Dix-Hallpike's maneuver). A blood sample was taken to evaluate serum vitamin D level and total serum calcium. The results were compared between both groups. Results: The mean levels of vitamin D3 in patients and control groups were 18.57 ± 9.88 ng/ml and 64.12 ± 24.64 ng/ml, respectively, with a statistically significant difference at p ≤ 0.0001. Moreover, regarding vitamin D3 deficiency below 20 ng/ml between patients and control groups, there was a statistically significant difference p = 0.001. Furthermore, there was no significant difference regarding total serum calcium between the two groups, the mean of both groups was 8.57 ± 0.68 mg/dl and 8.93 ± 0.92 mg/dl for patients and control, respectively, at p = 0.084. Conclusion: There might be an association between benign paroxysmal positional vertigo and vitamin D3 deficiency. Moreover, there was no significant difference concerning total serum calcium levels between the patient and control groups. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is one of the complications of SARS-CoV-2 infection. This study aims to evaluate the clinical and laboratory characteristics, as well as treatment results, of MIS-C patients who received intravenous immunoglobulin (IVIG) monotherapy. Methods: This retrospective study included patients diagnosed with MIS-C. Demographic data, organ involvements at the admission, laboratory evaluations for diagnosis, treatment, and follow-up were recorded. We evaluated outcomes by the length of the intensive care unit stay, the total hospitalization period, complications, and mortality. Results: A total of 95 patients diagnosed with MIS-C were evaluated. The mean age was 118.8 (± 52.5) months. 76.8% of the patients had four or more organ systems involved. Seventy-nine patients (83%) were hospitalized in the pediatric intensive care unit (PICU) for a mean of 4.59 days. Seventy-seven (81%) patients received IVIG. A second dose of IVIG was administered to 66.3% of patients. All patients received vitamin D and C supplementation. Six patients who had cardiac involvement or cerebral infarction were treated with plasmapheresis. No patients received steroids. There was no mortality at the end of the follow-up. Conclusions: Favorable outcomes may be obtained with IVIG monotherapy in MIS-C patients. More clinical trials are needed to establish the role of supportive treatments like vitamin D and C in MIS-C management. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) due to vitamin D therapy for osteoporosis is encountered in clinical practice, but epidemiological studies are scarce. We aimed to determine the association between AKI and vitamin D therapy and to identify risk factors for AKI using the Japanese Adverse Drug Event Report database. We used reporting odds ratios (RORs) to detect signals and evaluate risk factors using multiple logistic regression analysis. Among 298,891 reports from April 2004 to September 2023, 1071 implicated active vitamin D3 analogs as suspect drugs for adverse events. There was a significant association between AKI and active vitamin D3 analogs (ROR [95% confidence interval {CI}], eldecalcitol: 16.75 [14.23–19.72], P < 0.001; alfacalcidol: 5.29 [4.07–6.87], P < 0.001; calcitriol: 4.46 [1.88–10.59], P < 0.001). The median duration of administration before AKI onset was 15.4 weeks. Multiple logistic regression analysis showed a significant association between AKI and age ≥ 70 years (odds ratio [95% CI], 1.47 [1.04–2.07]; P = 0.028), weight < 50 kg (1.55 [1.12–2.13]; P = 0.007), hypertension (1.90 [1.42–2.54]; P < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.58 [1.10–2.25], P = 0.012) and magnesium oxide (1.96 [1.38–2.78]; P < 0.001). Our results suggest that active vitamin D3 analogs are associated with AKI development. Physicians prescribing these medications to patients with risk factors should consider the possibility of AKI, especially during the first 6 months. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effect of vitamin D and/or synbiotics on the response to treatment, cytokines profile and hormonal biomarkers in breast cancer patients undergoing neoadjuvant therapy. A total of 76 patients were recruited and completed the course of the intervention between 2019 and 2021 in Kerman, Iran. breast cancer patients were randomly enrolled in this study. Patients divided into four groups to receive one of the following regimens: placebo, vitamin D, synbiotics and a combination of vitamin D and synbiotics. clinicopathologic parameters, inflammatory and anti-inflammatory biomarkers and hormonal levels were measured at the baseline and four months after intervention. The study results found no clear link between the interventions and achieving pathological complete response (pCR), and a similar trend was observed in Ki-67 index examination. After neoadjuvant therapy, TNF-α concentrations decreased, with vitamin D supplementation moderating this decline. Vitamin D supplemented groups showed a significant increase in serum IL-6 levels. While IL-10 levels decreased in the placebo group, all intervention groups were protected from this decline. Moreover, there was a notable increase in the anti-inflammatory index, particularly in the group receiving both vitamin D and synbiotic supplementation, suggesting potential synergistic anti-inflammatory effects from their combined administration. The outcomes suggest a potential anti-inflammatory function of this combination. Consequently, more extensive studies with prolonged follow-up periods and substantial sample sizes are warranted to thoroughly evaluate their potential benefits for breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence links vitamin D deficiency to oxidative stress (OS) and inflammation, posing ongoing risks to cardiovascular outcomes in hemodialysis (HD) patients. Despite this, current data are lacking regarding the optimal approach or schedule for administering vitamin D in this population. This study investigated the effectiveness of oral weekly versus oral monthly cholecalciferol supplementation on 25-hydroxy vitamin D (25(OH)D) levels, oxidative stress, inflammatory indicators, and secondary hyperparathyroidism in HD population. HD patients (N = 50) were randomly allocated to Group A (oral weekly 50,000 IU cholecalciferol) or Group B (oral monthly 200,000 IU cholecalciferol) for a 3 months duration. Serum levels of 25(OH)D, malondialdehyde (MDA), superoxide dismutase (SOD), high sensitivity C-reactive protein (HsCRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and intact parathyroid hormone (iPTH) were assessed at baseline and upon completion of the study. Results: A notable increase in serum 25(OH)D levels observed in both groups, with Group A showing a notably greater increase (p = 0.003). Group A demonstrated significant reductions in serum MDA and increases in SOD, along with declines in hsCRP and NLR levels, which were not observed in Group B. Moreover, Group A exhibited a greater drop in iPTH (ΔiPTH = − 30 pg/mL vs. − 3 pg/mL) compared to Group B. Clinicaltrial.gov: NCT05460338, registered 13/07/2022. Conclusions: Weekly oral 50,000 IU cholecalciferol supplementation emerges as a tolerable, safe and effective approach for restoring vitamin D levels in HD patients, while concurrently mitigating inflammation, OS, and secondary hyperparathyroidism. This finding suggests that the more frequent the administration of oral cholecalciferol, the higher the efficiency observed. [ABSTRACT FROM AUTHOR]

We aimed to investigate the preventive effect of vitamin D2 on COVID-19 and the improvement of symptoms after COVID-19 infection. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to vitamin D2 or non-intervention at a ratio 1:1. Subjects recorded PCR or antigen tests and the symptoms of COVID-19 twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines were measured. The rates of COVID-19 infection were 50.5% in the vitamin D2 group and 52.4% in the non-intervention group (P = 0.785). There was no difference in the COVID-19 symptoms between the two groups. The mean 25(OH)D level significantly increased from 14.1 to 31.1 ng/mL after administration (P < 0.001). The difference between the two groups was not significant for the concentrations of CRP, C1q and inflammatory cytokines on the thirtieth day of the trial. According to the second level of vitamin D, there was a 14.3% difference in positive infection rates between the vitamin D adequate (> 30 ng/mL) and deficient groups (< 20 ng/mL). Adequate vitamin D had a tendency to prevent COVID-19. Trial registration: ClinicalTrials.gov NCT05673980, dated: 12/2022. [ABSTRACT FROM AUTHOR]

Context: The structural, electronic, and nonlinear optical properties of Verdoocridone A (Ver A) and B (Ver B) are examined theoretically in this study. The results showed that Ver A and B exhibit good electronic properties and can be used as new materials in NLO applications. According to their maximum absorption wavelength, Ver A (λmax = 313 nm) enables production of vitamin D, while Ver B (λmax = 319.55 nm) can help skin pigmentation. Methods: All calculations were performed at the DFT/B3LYP-D3/6–311 + G(d,p) level of theory using the Gaussian 16 software package. Excited states were simulated using the TD-DFT method at the CAM-B3LYP combined with 6–311 + (d,p) basis set. Also, the solvent effect was studied in water and benzene phases by the solvation model based on density (SMD) method. [ABSTRACT FROM AUTHOR]

This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

Purpose: The assessment of sarcoma during clinical practice is primarily based on imaging examination, with no effective biomarkers available. Although it has been established that 1,25(OH)2D3 is abnormally expressed in patients with sarcoma, it remains unclear whether 1,25(OH)2D3 level could be used as an evaluation marker in these patient population. Methods: This real-world study investigated 1,25(OH)2D3 level and its association with clinical features in sarcoma patients. Data on 1,25(OH)2D3, parathyroid hormone, calcium, and calcitonin were collected from 331 patients with sarcoma, while the imaging results and the variation in 1,25(OH)2D3 among 213 patients with sarcoma before and after treatment was further analyzed. Results: We found that the serum 1,25(OH)2D3 level was predominantly decreased in patients with sarcoma, with a mean of 45.68 nmol/L. 1,25(OH)2D3 was significantly correlated with the gender and age of sarcoma patients, with more substantial reductions in women and younger patients. Among sarcoma patients, those with progressive disease exhibited a 7.08 nmol/L (−13.73%) decrease in serum 1,25(OH)2D3 levels compared to baseline, while patients with non-progressive disease showed a 1.11 nmol/L (+ 7.0%) increase. Conclusion: The variation of serum 1,25(OH)2D3 can predict the disease status of patients with sarcoma. Decreased serum 1,25(OH)2D3 levels are indicative of disease progression in sarcoma patients, suggesting its potential for application as a prognostic marker for disease assessment in this patient population. [ABSTRACT FROM AUTHOR]

Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups; < 36.2 nmol/L. The vitamin D levels in Group DMS were significantly lower than that in Group Non-DMS (41.74 ± 14.60 vs. 47.19 ± 13.01, P < 0.05). After adjusting confounder factors including sex, age, vitamin D levels, HbA1c, ALB, HDLC, eGFR, diabetes microvascular complications and macrovascular, there was an independent association between risk of DMS and age (OR value = 1.160, 95% CI 1.091–1.234, P = 0.000), HbA1c(OR value = 1.262, 95% CI 1.046–1.532, P = 0.015), and vitamin D deficiency (< 36.2 nmol/L) (OR value = 2.990, 95% CI 1.284–6.964, P = 0.011). Our findings suggest that low levels of vitamin D are a predictor of DMS in middle-aged and elderly patients with poor control of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Insufficient vitamin D (VD) levels have been linked to a higher vulnerability to acute respiratory infections and the severity of COVID-19 sickness. Objective: The purpose of this research is to investigate whether or not there is a connection between the amounts of VD produced by patients from Egypt and the severity of COVID-19, as well as the consequences of the disease. Methods: This research used a case–control design and included a total of 90 adult patients who had been diagnosed with COVID-19, as well as 90 healthy controls who were matched in terms of age and sex. Patients were classified into mild, moderate, and severe categories according to clinical and radiological criteria. The study included measuring levels of VD and analyzing their relationships with illness severity, inflammatory markers, radiological findings, and outcomes. Results: COVID-19 patient(s) had notably reduced levels of serum VD versus the control group (11.78 ± 3.24 ng/mL vs. 20.88 ± 7.76 ng/mL, p < 0.001). Lower VD levels were associated with more severe disease (p < 0.001), dyspnea (p < 0.001), radiological abnormalities (p = 0.001), and higher mortality (p < 0.001). A serum VD level ≤ 14.8 ng/mL could differentiate COVID-19 patients from controls with 86.67% sensitivity and 77.78% specificity (AUC = 0.881). Conclusions: COVID-19 patients often had a deficiency of VD, which was linked to more severe illness, respiratory issues, aberrant radiological findings, and higher fatality rates. VD levels may be used as a biological surrogate marker to assess the risk and predict the outcome of COVID-19. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is increasingly common in systemic lupus erythematosus (SLE) patients and is associated with the disease activity and proteinuria. Recently, alterations in metabolism have been recognized as key regulators of SLE pathogenesis. Our objective was to identify differential metabolites in the serum metabolome of SLE with vitamin D deficiency. In this study, serum samples from 31 SLE patients were collected. Levels of 25(OH)D3 were assayed by ELISA. Patients were divided into two groups according to their vitamin D level (20 ng/ml). Untargeted metabolomics were used to study the metabolite profiles in serum by high-performance liquid chromatography-tandem mass spectrometry. Subsequently, we performed metabolomics profiling analysis to identify 52 significantly altered metabolites in vitamin D deficient SLE patients. The area under the curve (AUC) from ROC analyses was calculated to assess the diagnostic potential of each candidate metabolite biomarker. Lipids accounted for 66.67% of the differential metabolites in the serum, highlighted the disruption of lipid metabolism. The 52 differential metabolites were mapped to 27 metabolic pathways, with fat digestion and absorption, as well as lipid metabolism, emerging as the most significant pathways. The AUC of (S)-Oleuropeic acid and 2-Hydroxylinolenic acid during ROC analysis were 0.867 and 0.833, respectively, indicating their promising diagnostic potential. In conclusion, our results revealed vitamin D deficiency alters SLE metabolome, impacting lipid metabolism, and thrown insights into the pathogenesis and diagnosis of SLE. [ABSTRACT FROM AUTHOR]

We first established percentile reference curves for infant length and head circumference in Hainan Province based on gender and age in months and compared them with the 2022 national standards and World Health Organization (WHO) standards. This cross-sectional survey involved 2736 infants (1471 boys and 1265 girls) in 18 cities and counties in Hainan Province. Standardized instruments were used to measure head circumference and length. Reference values for Hainan infants' length and head circumference were determined using the LMS method. Curves were generated using the LMS Chart Maker software. According to the newly established reference curves, the length and head circumference of Hainan infants exhibited a consistent trend of steady growth. However, the average head circumference was below the 2022 national reference values and WHO standards. The mean length was lower than the new national reference values but roughly consistent with the WHO standards. Differences exist in infant length and head circumference in Hainan compared to national and global averages. To enhance infant length and head circumference growth, the health department should encourage exclusive breastfeeding for the first 6 months, ensure infants' sleep needs at night, and promote the regularity of vitamin D supplementation during the perinatal period. [ABSTRACT FROM AUTHOR]

Cardiometabolic risk factors increase the chance of developing cardiovascular disease (CVD) and type 2 diabetes. Most CVD risk factors are influenced by total and regional obesity. A higher risk of developing CVD may be linked to vitamin D deficiency, which is more prevalent in the older population. With the goal of evaluating the association between vitamin D and cardiometabolic risk factors and total and regional obesity in older adults, this research included 25 (OH) vitamin D3 concentrations and biochemical markers associated with cardiometabolic diseases, as well as total and regional adiposity, which was measured by DXA. A total of 1991 older participants in the PoCOsteo study were included. Overall, 38.5% of participants had vitamin D deficiency. After adjusting for confounders, the results of multiple linear and logistic regression suggested an inverse association between vitamin D and body mass index (P = 0.04), waist circumference (P = 0.001), total fat (P = 0.02), android fat (P = 0.001), visceral fat (P < 0.001), subcutaneous fat (P = 0.01), trunk fat (P = 0.006), arm fat (P = 0.03), high systolic blood pressure (P = 0.004), high total cholesterol (P < 0.001), high LDL-cholesterol (P < 0.001), high serum triglycerides (P = 0.001), and high fasting glucose (P < 0.001). Additionally, higher vitamin D concentrations decreased the risk of dyslipidemia by 2%. Our results showed a significant association between serum vitamin D and a number of cardiometabolic risk factors, including total and regional obesity. [ABSTRACT FROM AUTHOR]

One of the leading causes of mortality worldwide is cardiovascular disease, which is influenced by some variables, including calcium and vitamin D. This study aimed to assess the relationship between Angiopoietin-Like 3 (ANGPTL3) gene polymorphisms with vitamin D and calcium levels in cardiovascular disease (CVD) patients. In this research, 1002 people participated. Participants' anthropometric parameters, and FBG, calcium, and vitamin D were assessed. Blood samples were used to extract DNA. Taqman®-based polymerase chain reaction (PCR) was used to conduct genetic analysis for the rs10789117 and rs17458195. Statistical analysis was applied to determine differences across subgroups and the relationship between polymorphisms and disease. Age, body mass index (BMI), fasting Blood Sugar (FBG), phenylalanine ammonia-lyase (PAL), and smoking history were significantly correlated with CVD. Vitamin D was statistically associated with rs10789117 and rs17458195 in non-CVD individuals. In the moderate group, individuals with the C allele in rs10789117 showed a tenfold increase in vitamin D deficiency compared to those with the A allele. However, in rs11207997, individuals with the T allele had 5 to 6 times higher vitamin D deficiency than those with the C allele in all groups. This research demonstrates the relationship between some ANGPTL3 gene polymorphisms and complement levels in CVD patients. It may be concluded that individuals carrying these variants would likely benefit from using vitamin D and calcium supplements to avoid CVD. [ABSTRACT FROM AUTHOR]

Skin pigmentation is negatively associated with circulating vitamin D (VD) concentration. Therefore, genetic factors involved in skin pigmentation could influence the risk of vitamin D deficiency (VDD). We evaluated the impact genetic variants related to skin pigmentation on VD in Mexican population. This cross-sectional analysis included 848 individuals from the Health Worker Cohort Study (ratio males to females ~ 1:3). Eight genetic variants: rs16891982 (SLC45A2), rs12203592 (IRF4), rs1042602 and rs1126809 (TYR), rs1800404 (OCA2), rs12913832 (HERC2), rs1426654 (SLC24A5), and rs2240751 (MFSD12); involved in skin pigmentation were genotyped. Skin pigmentation was assessed by self-report. Linear and logistic regression were used to assess the association between the variants of interest and VD and VDD, as appropriate. In our study, eight genetic variants were associated with skin pigmentation. A genetic risk score built with the variants rs1426654 and rs224075 was associated with lower VD levels (β = − 1.38, 95% CI − 2.59, − 0.17, p = 0.025). Nevertheless, when examining gene–gene interactions, we observed that rs2240751 × rs12203592 were associated with VD levels (P interaction = 0.021). Whereas rs2240751 × rs12913832 (P interaction = 0.0001) were associated with VDD. Our results suggest that skin pigmentation-related gene variants are associated with lower VD levels in Mexican population. These results underscore the importance of considering genetic interactions when assessing the impact of genetic polymorphisms on VD levels. [ABSTRACT FROM AUTHOR]

Vitamin D3 is clinically used for the treatment of vitamin D3 deficiency or osteoporosis, partially because of its role in regulating phosphate (Pi) and calcium (Ca2+) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in Pi homeostasis; however, the role of vitamin D3 in hypophosphatemia has never been investigated. We administered vehicle or vitamin D3 to wild-type (WT) mice or hypophosphatemic Npt2a−/− mice. In contrast to WT mice, vitamin D3 treatment increased plasma Pi levels in Npt2a−/− mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca2+ was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary Pi and Ca2+/creatinine ratios, in Npt2a−/− mice, Pi/creatinine was unchanged and Ca2+/creatinine drastically decreased, coinciding with the highest kidney Ca2+ content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a−/− mice, vitamin D3 treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a−/− only, the latter might facilitate the increase in plasma Pi in Npt2a−/− mice. Npt2a might function as regulator between renal Ca2+ excretion and reabsorption in response to vitamin D3. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders are rapidly increasing in prevalence and have been linked to various environmental risk factors. Mounting evidence suggests a potential role of vitamin D in child neurodevelopment, though the causal mechanisms remain largely unknown. Here, we investigate how vitamin D deficiency affects children's communication development, particularly in relation to Autism Spectrum Disorder (ASD). We do so by developing an integrative network approach that combines metabolomic profiles, clinical traits, and neurodevelopmental data from a pediatric cohort. Our results show that low levels of vitamin D are associated with changes in the metabolic networks of tryptophan, linoleic, and fatty acid metabolism. These changes correlate with distinct ASD-related phenotypes, including delayed communication skills and respiratory dysfunctions. Additionally, our analysis suggests the kynurenine and serotonin sub-pathways may mediate the effect of vitamin D on early life communication development. Altogether, our findings provide metabolome-wide insights into the potential of vitamin D as a therapeutic option for ASD and other communication disorders. [ABSTRACT FROM AUTHOR]

White adipose tissue (WAT) has been recognized as a fundamental and crucial organ of interest in research focusing on inflammation during obesity or aging. WAT is also proposed as a significant component of cholecalciferol and 25-hydroxyvitamin D (25(OH)D) storage, which participates in the decrease of 25(OH)D plasma levels reported during aging and obesity. In the present study, we evaluated WAT and plasma cholecalciferol and 25(OH)D content together with inflammatory status to highlight the putative relationship between vitamin D status and inflammatory process during aging alone or combined with obesity. Circulating cholecalciferol and 25(OH)D and the stored quantity of cholecalciferol and 25(OH)D in WAT were quantified in young and old mice fed a control or obesogenic diet. The inflammation was assessed by measuring plasma inflammatory cytokines, mRNA, and microRNAs inflammatory-associated in WAT. The combination of aging and obesity decreased 25(OH)D plasma levels but did not modify circulating inflammatory markers. A cumulative effect of aging and obesity was observed in WAT, with rising mRNA inflammatory cytokines, notably Ccl5 and Tnf. Interestingly, aging and obesity-associated were also characterized by increased inflammatory microRNA expression. The inflammatory parameters in WAT were negatively correlated with the plasma 25(OH)D but positively correlated with the quantity of cholecalciferol and 25(OH)D in WAT. These results support the cumulative effect of obesity and aging in aggravation of WAT inflammation and suggest that accumulation of cholecalciferol and 25(OH)D in WAT could constitute a mechanism to counteract WAT inflammation during aging and obesity. [ABSTRACT FROM AUTHOR]

The microgravity environment aboard the International Space Station (ISS) provides a unique stressor that can help understand underlying cellular and molecular drivers of pathological changes observed in astronauts with the ultimate goals of developing strategies to enable long- term spaceflight and better treatment of diseases on Earth. We used this unique environment to evaluate the effects of microgravity on kidney proximal tubule epithelial cell (PTEC) response to serum exposure and vitamin D biotransformation capacity. To test if microgravity alters the pathologic response of the proximal tubule to serum exposure, we treated PTECs cultured in a microphysiological system (PT-MPS) with human serum and measured biomarkers of toxicity and inflammation (KIM-1 and IL-6) and conducted global transcriptomics via RNAseq on cells undergoing flight (microgravity) and respective controls (ground). Given the profound bone loss observed in microgravity and PTECs produce the active form of vitamin D, we treated 3D cultured PTECs with 25(OH)D3 (vitamin D) and monitored vitamin D metabolite formation, conducted global transcriptomics via RNAseq, and evaluated transcript expression of CYP27B1, CYP24A1, or CYP3A5 in PTECs undergoing flight (microgravity) and respective ground controls. We demonstrated that microgravity neither altered PTEC metabolism of vitamin D nor did it induce a unique response of PTECs to human serum, suggesting that these fundamental biochemical pathways in the kidney proximal tubule are not significantly altered by short-term exposure to microgravity. Given the prospect of extended spaceflight, more study is needed to determine if these responses are consistent with extended (>6 months) exposure to microgravity. [ABSTRACT FROM AUTHOR]

Background: Epileptic children can pose an additional risk of poor bone health; this study aimed to evaluate the influence of anti-seizure medications (ASMs) on vitamin D level and sclerostin as a bone turnover biomarker in children with epilepsy. Subject and methods: This case–control comparative study was conducted on 180 children aged from 5–18 years diagnosed with epilepsy according to the definition of the International League Against Epilepsy on ASMs for more than 3 months and were classified into 90 epileptic children on ASM monotherapy and 90 epileptic children on ASM polytherapy, in addition to 90 healthy children age- and sex-matched who served as controls. After obtaining basic data, laboratory investigations were performed, including serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, vitamin D, and serum sclerostin. Results: When we compared epileptic patients to the control group, there was a statistically significant low level of vitamin D, calcium, and phosphorus and a high level of sclerostin among both epileptic groups with mono or polytherapy. Sclerostin has a statistically significant negative correlation with vitamin D, alkaline phosphatase and parathyroid hormone. Additionally, it has a negative correlation with serum phosphorus, but without a significant correlation. On the other hand, sclerostin has a statistically positive correlation with age and serum calcium, but without a significant correlation. Multiple linear regression analyses were conducted to predict the contributing factors of sclerostin. Only duration of treatment and BMI were significant predictors of high levels of sclerostin. In contrast, the other factors failed to show any significant contribution. Conclusion: The present study showed that ASMs modulate the serum levels of sclerostin and vitamin D hence, might be involved in their adverse effects on bone. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vitamin D status has been shown to be associated with prediabetes risk. However, epidemiologic evidence on whether sex modulates the association between vitamin D and prediabetes is limited. The present study investigated sex-specific associations between vitamin D and prediabetes. Subjects/Methods: The Kuwait Wellbeing Study, a population-based cross-sectional study, enrolled nondiabetic adults. Prediabetes was defined as 5.7 ≤ HbA1c% ≤6.4; 25-hydroxyvitamin D (25(OH)D) was measured in venous blood and analyzed as a continuous, dichotomous (deficiency: <50 nmol/L vs. insufficiency/sufficiency ≥50 nmol/L), and categorical (tertiles) variable. Associations were evaluated by estimating adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), while stratifying by sex. Results: A total of 384 participants (214 males and 170 females) were included in the current analysis, with a median age of 40.5 (interquartile range: 33.0–48.0) years. The prevalence of prediabetes was 35.2%, and 63.0% of participants had vitamin D deficiency. Assessments of statistical interaction between sex and 25(OH)D status were statistically significant (PSex × 25(OH)D Interaction < 0.05). In the sex-stratified analysis, after adjustment for confounding factors, decreased 25(OH)D levels were associated with increased prevalence of prediabetes in males (aPRDeficiency vs. In-/Sufficiency: 2.35, 95% CI: 1.36–4.07), but not in females (aPRDeficiency vs. In-/Sufficiency: 1.03, 95% CI: 0.60–1.77). Moreover, the prevalence of prediabetes differed between males and females at 25(OH)D levels of ≤35 nmol/L, with a higher prevalence of prediabetes in males compared to females. Such a sex-specific difference was not observed at 25(OH)D levels of >35 nmol/L. Conclusions: Sex modified the association between vitamin D levels and prediabetes, with an inverse association observed among males, but not among females. Moreover, the observed sex-disparity in the prevalence of prediabetes was only pronounced at 25(OH)D levels of ≤35 nmol/L. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate whether vitamin D deficiency is a common finding in autism spectrum disorder (ASD) children and whether such deficiency is related to ASD severity and language age or not. Methods: A cross-sectional observational study was conducted on ASD children aged 2-6 years. The participants were 80 Egyptian children with ASD. All participants were assessed using DSM-V, the Childhood Autism Rating Scale (CARS), language assessment, and assessment of serum vitamin D using ADVIA Centaur Vit D assay. Results: About 63.8% of ASD children have vitamin D insufficiency, 28.8 % have vitamin D deficiency, and 7.4% have normal serum levels. No correlation was found between serum vitamin D and language age (r = -0.085, P = 0.451), DSM 5 severity levels (r = 0.015,P= 0.894), and CARS scores (r= 0.075, P= 0.511). Conclusion: ASD children have lower serum vitamin D levels, which may be one of the environmental factors contributing to ASD development in genetically susceptible individuals, and its correction may be helpful as adjuvant therapy for ASD. [ABSTRACT FROM AUTHOR]

Poor birth outcomes in low- and middle income countries are associated with maternal vitamin D deficiency and chronic helminth infections. Here, we investigated whether maternal Schistosoma haematobium affects maternal or cord vitamin D status as well as birth outcomes. In a prospective cross-sectional study of pregnant women conducted in Lambaréné, Gabon, we diagnosed maternal parasitic infections in blood, urine and stool. At delivery we measured vitamin D in maternal and cord blood. S. haematobium, soil-transmitted helminths, and microfilariae were found at prevalences of 30.2%, 13.0%, and 8.8%, respectively. Insufficient vitamin D and calcium levels were found in 28% and 15% of mothers, and in 11.5% and 1.5% of newborns. Mothers with adequate vitamin D had lower risk of low birthweight babies (aOR = 0.11, 95% CI 0.02–0.52, p = 0.01), whilst offspring of primipars had low cord vitamin D levels, and low vitamin D levels increased the risk of maternal inflammation. Maternal filariasis was associated with low calcium levels, but other helminth infections affected neither vitamin D nor calcium levels in either mothers or newborns. Healthy birth outcomes require maintenance of adequate vitamin D and calcium levels. Chronic maternal helminth infections do not disrupt those levels in a semi-rural setting in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Low serum 25(OH)D levels (< 30 nmol/L) have been associated with increased depressive symptom scores over time, and it is believed that functionality may play a mediating role in the relationship between 25(OH)D and depressive symptoms. To comprehend the association between these factors could have significant implications for public health policy. The aim of this study was to verify the association between simultaneous vitamin D insufficiency and depressive symptoms, and functional disability in community-dwelling older adults. This was a cross-sectional study with data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), collected between 2015 and 2016. The outcomes were functional disability assessed through basic activities of daily living (ADL) and instrumental activities of daily living (IADL). The exposures were vitamin D insufficiency (< 30 nmol/L) and depressive symptoms (≥ 4 points in 8-item version of the Center for Epidemiological Studies-Depression). Crude and adjusted Poisson regression was performed to estimate associations. A total of 1781 community-dwelling older adults included in this study, 14.6% had disability in ADL and 47.9% in IADL; 59.7% had vitamin D insufficient levels, and 33.2% depressive symptoms. The concomitant presence of vitamin D insufficient and depressive symptoms increased the prevalence of ADL by 2.20 (95% CI: 1.25; 3.86) and IADL by 1.54 (95% CI: 1.24; 1.91), respectively. Therefore, preventive strategies to keep older adults physically and socially active, with a good level of vitamin D, are essential to avoid depression and functional disability. [ABSTRACT FROM AUTHOR]

Functional constituents are the main concern in food production and consumption. Because foods rich in functional constituents have antioxidant capacity and are important in keeping consumers healthy. Pleurotus ostreatus is among foods rich in functional constituents. However, its functional constituents are affected by various factors. This study compared the antioxidant capacity of P. ostreatus grown on different substrates: straws of tef (Trt1), barley (Trt2), and wheat (Trt3), husks of faba bean (Trt4), and field pea (Trt5), sawdust (Trt6), and the mixture of the above with 1:1 w/w (Trt7). Trt7 had significantly higher radical scavenging activity (RSA) (73.27%), vitamin C (10.61 mg/100 g), and vitamin D (4.92 mg/100 g) compared to other treatments. Whereas the lowest values of RSA (44.24%), vitamin C (5.39 mg/100 g), and vitamin D (1.21 mg/100 g) were found in Trt2. The results indicated that mixed substrate may be a good growth substrate for functionally beneficial P. ostreatus and could be a promising source of natural antioxidants. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 outbreak has increased awareness of vitamin D's (Vit-D) potential advantages for both prevention and treatment. Adequate vitamin D levels are necessary for health of the immune system, which can help with cellular response and protection against the severity of microbial infection. Purpose: To evaluate Vit-D levels and their association with illness severity in Egyptian COVID-19-infected individuals. Methods: This case–control investigation was performed at the Alexandria Main University Hospital on 80 subjects divided into 2 groups: 40 COVID-19 patients and 40 healthy persons to measure the Vit-D levels of the Egyptian cohort. Results: There was a statistically insignificant difference in the Vit-D serum levels of the studied groups (P = 1.000). The age of the Vit-D insufficient patients was significantly higher than that of Vit-D sufficient patients (P = 0.006). There was a statistically insignificant rise in the CRP level in the Vit-D insufficient patients (P = 0.862) compared to patients with sufficient Vit-D. Also, the D-dimer levels in Vit-D-insufficient patients were considerably higher (P = 0.015). Patients with sufficient Vit-D exhibited significantly lower levels of IL-6 than Vit-D insufficient patients. (P = 0.037). Patients in the Vit-D-insufficient subgroup needed substantially more breathing support than those in the Vit-D-sufficient group (P = 0.020). Conclusion: Although there was no association between both levels of Vit-D and the COVID-19 infection risk, insufficiency of Vit-D was related to more severe infection. [ABSTRACT FROM AUTHOR]

Background: Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. Methods: DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. Results: 1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. Conclusions: The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women. In recent years, the effects of vitamin D receptor (VDR) gene variants and VitD3 levels on clinical features of PCOS have been frequently described. In this study, we aimed to determine the relationship between VDR ApaI, TaqI and Cdx2 gene variants and VitD3 levels in PCOS patients. Patients were divided into two groups: BMI<25 and BMI≥25. VDR genotypes were determined by real-time polymerase chain reaction (PCR) and serum VitD3 levels were examined by ELISA. We observed that frequencies of the Apa1 AC genotype, C allele and Cdx2 T allele are increased in the BMI≥25 group compared to BMI<25 group. Also, the ApaI C allele, Taq1 AA genotype and A allele, Cdx2 CC genotype and C allele are associated with increased triglyceride, total cholesterol, LDL-cholesterol levels in patients with BMI≥25. When examining the relationship between VitD3 levels and clinical profiles in all PCOS patients, regardless of BMI distinction, it is determined that there is a positive correlation between LDL-cholesterol and ftestosterone levels. The present findings suggest that VDR variants are one of the most important risk factors for PCOS, especially for patients with BMI≥25. [ABSTRACT FROM AUTHOR]

Objective: To compare the proportion of exclusively breastfed (EBF) infants having severe vitamin D deficiency (25(OH)D concentration <11 ng/mL) at 6 months of age when mothers were supplemented with 300,000 IU vitamin D3 or placebo during the third trimester of pregnancy. Methods: In this randomized double-blind placebo-controlled trial, we recruited 100 pregnant women (who were willing to exclusively breastfeed their babies for 6 months) at 30–32 weeks gestation and the infants born to them. Pregnant women were randomized to receive either oral vitamin D3 60,000 IU or placebo, given weekly for 5 weeks during the third trimester. Serum 25(OH)D, calcium, phosphorus and alkaline phosphatase concentration were measured in all participants at recruitment, in the cord blood at delivery, and in infants at 6 months of age. The proportion of infants developing severe vitamin D deficiency and rickets at 6 months was assessed. Results: A total 72 mother-infant dyads were followed-up till 6 months. At enrollment, the mean (SD) serum 25(OH)D concentration (ng/mL) were comparable in mothers in the intervention and control groups [12.9 (5.8) vs 12.8 (5.9), P = 0.96]. The mean (SD) 25(OH)D concentration (ng/mL) in the cord blood was significantly higher in the intervention group compared to the control group [42.1 (17.1) vs 12.7 (6.3); P = 0.002]. Serum 25(OH)D levels (ng/mL) in the infants at 6 months age were higher in the intervention group compared to the control group [31.8 (10.9) vs 12.5 (5.7); P < 0.001]. No infant in the intervention group had severe vitamin D deficiency at 6 months age compared to 54.3% infants in the control group (P < 0.001). No infant in the intervention group developed rickets. Conclusion: Oral supplementation of vitamin D3 to pregnant women in the third trimester prevents severe hypovitaminosis D in the EBF infants at 6 months of age. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency and insufficiency pose global public health challenges, yet research on serum vitamin D levels in the 0–17-year-old age group in southeastern China remains limited. This study aimed to fill this gap by investigating serum 25(OH)D levels in children in the region aged 0–17 years, contributing crucial data for understanding vitamin D nutritional status. Liquid chromatography‒mass spectrometry/mass spectrometry (LC‒MS/MS) technology was used. Vitamin D testing was integrated into routine diagnostic procedures for 11,116 children in Wujiang District, Suzhou City. Among the 0–17-year age group, comprising 6348 boys and 4768 girls, the prevalence of serum 25(OH)D deficiency and insufficiency was 21.4% and 31.0%, respectively. The median serum 25(OH)D concentration was 29.72 ng/mL (21.84–39.84 ng/mL) in boys compared to 28.48 ng/mL (20.65–39.23 ng/mL) in girls. Seasonal variations were observed, with median serum 25(OH)D concentrations of 29.02 ng/mL (20.73–39.72 ng/mL) in spring, 28.79 ng/mL (21.53–39.37 ng/mL) in summer, 30.12 ng/mL (22.00–39.70 ng/mL) in autumn, and 28.58 ng/mL (19.97–39.46 ng/mL) in winter. Statistically significant differences were noted in the serum 25(OH)D levels during autumn and winter. In conclusion, the rate of adequate vitamin D levels in local children was 47.5%, revealing a relatively high prevalence of vitamin D deficiency (21.4%) and insufficiency (31.0%), especially during the post-preschool period. Advocating for vitamin D supplementation in children is crucial for ensuring adequate vitamin D support. [ABSTRACT FROM AUTHOR]

This study aims to examine whether hypovitaminosis D was associated with cognitive impairment among chronic kidney patients with different level of albuminuria. This population-based cross-sectional study was conducted on elderly (over 60 years old) with urine albumin to creatinine ratio (UACR) ≥ 30 mg/g from 2011 to 2014 in the US National Health and Nutrition Examination Survey (NHANES). Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning (CERAD). Subjects were divided into 2 groups according to the absence or presence of cognitive impairment and a propensity score matching (PSM) was further conducted. The association was assessed with Spearman correlation and logistic regression analysis. The positive association of 25-hydroxyvitamin D3 (25(OH)D3) and cognitive score was presented. PSM analysis revealed that a higher level of 25(OH)D3 correlated to a better cognitive function in CKD patients with albuminuria, especially in patients with 30 mg/g ≤ UACR < 300 mg/g. This study indicated that a low 25(OH)D3 level was associated with poor cognitive performance, especially in patients with microalbuminuria. Thus, early diagnosis of vitamin D insufficiency and an effective intervention might be a useful therapeutic strategy to prevent cognitive decline in patients with the progression of renal dysfunction. [ABSTRACT FROM AUTHOR]

Vitamin D (VitD) is a naturally occurring, fat-soluble vitamin which regulates calcium and phosphate homeostasis in the human body and is also known to have a neuroprotective role. VitD deficiency has often been associated with impaired cognition and a higher risk of dementia. In this study, we aimed to explore the relationship between levels of VitD and cognitive functioning in adult individuals. 982 cognitively healthy adults (≥ 45 years) were recruited as part of the CBR-Tata Longitudinal Study for Aging (TLSA). Addenbrooke's cognitive examination-III (ACE-III) and Hindi mental status examination (HMSE) were used to measure cognitive functioning. 25-hydroxyvitamin D [25(OH)D] levels were measured from the collected serum sample and classified into three groups— deficient (< 20 ng/ml), insufficient (20–29 ng/ml) and normal (≥ 30 ng/ml). Statistical analysis was done using IBM SPSS software, version 28.0.1.1(15). The mean age of the participants was 61.24 ± 9 years. Among 982 participants, 572 (58%) were deficient, 224 (23%) insufficient and only 186 (19%) had normal levels of VitD. Kruskal–Wallis H test revealed a significant difference in age (p = 0.015) and education (p = 0.021) across VitD levels and the Chi-square test revealed a significant association between gender (p = 0.001) and dyslipidemia status (p = 0.045) with VitD levels. After adjusting for age, education, gender and dyslipidemia status, GLM revealed that individuals with deficient (p = 0.038) levels of VitD had lower scores in ACE-III verbal fluency as compared to normal. Additionally, we also found that 91.2% individuals who had VitD deficiency were also having dyslipidemia. It is concerning that VitD deficiency impacts lipid metabolism. Lower levels of VitD also negatively impacts verbal fluency in adult individuals. Verbal fluency involves higher order cognitive functions and this result provides us with a scope to further investigate the different domains of cognition in relation to VitD deficiency and other associated disorders. [ABSTRACT FROM AUTHOR]

COVID-19, caused by SARS-CoV-2, can lead to a severe inflammatory disease characterized by significant lymphopenia. However, the underlying cause for the depletion of T-cells in COVID-19 patients remains incompletely understood. In this study, we assessed the presence of different T-cell subsets in the progression of COVID-19 from mild to severe disease, with a focus on TCF1 expressing progenitor T-cells that are needed to replenish peripheral T-cells during infection. Our results showed a preferential decline in TCF1+ progenitor CD4 and CD8+ T-cells with disease severity. This decline was seen in various TCF1+ subsets including naive, memory and effector-memory cells, and surprisingly, was accompanied by a loss in cell division as seen by a marked decline in Ki67 expression. In addition, TCF1+ T-cells showed a reduction in pro-survival regulator, BcL2, and the appearance of a new population of TCF1 negative caspase-3 expressing cells in peripheral blood from patients with severe disease. The decline in TCF1+ T-cells was also seen in a subgroup of severe patients with vitamin D deficiency. Lastly, we found that sera from severe patients inhibited TCF1 transcription ex vivo which was attenuated by a blocking antibody against the cytokine, interleukin-12 (IL12). Collectively, our findings underscore the potential significance of TCF1+ progenitor T-cells in accounting for the loss of immunity in severe COVID-19 and outline an array of markers that could be used to identify disease progression. This study shows that severity of disease in COVID-19 patients is characterized by the preferential loss of TCF1+ progenitor T-cells needed to self-renew and replenish the immune system. [ABSTRACT FROM AUTHOR]

A former work conducted in our Lab, lead to in a effective scale up of vitamin D3 bioconversion into calcitriol by Actinomyces (A.) hyovaginalis isolate CCASU-A11-2 in Lab fermenter (14 L) resulting in 32.8 µg/100 mL of calcitriol. However, the time needed for such a bioconversion process was up to 5 days. Therefore, the objective of this study was to shorten the bioconversion time by using cell-free lysate and studying different factors influencing bioconversion. The crude cell lysate was prepared, freeze-dried, and primarily fractionated into nine fractions, of which, only three fractions, 50, 100, and 150 mM NaCl elution buffers showed 22, 12, and 2 µg/10 mL, calcitriol production, respectively. Ammonium sulfate was used for protein precipitation, and it did not affect the bioconversion process except at a concentration of 10%w/v. Secondary fractionation was carried out using 80 mL of the 50 mM NaCl elution buffer and the results showed the 80 mL eluent volume was enough for the complete elution of the active protein. The pH 7.8, temperature 28 °C, and 6 h reaction time were optimum for maximum calcitriol production (31 µg/10 mL). In conclusion, the transformation of vitamin D3 into calcitriol was successfully carried out within 6 h and at pH 7.8 and 28 °C using fractionated cell lysate. This process resulted in a 10-fold increase in calcitriol as compared to that produced in our previous study using a 14 L fermenter (32.8 µg/100 mL). Therefore, cell-free lysate should be considered for industrial and scaling up vitamin D3 bioconversion into calcitriol. Key points: Biotransformation of vitamin D into calcitriol has been achieved within 6 h using a cell-free lysate of A. hyovaginalis isolate CCASU-A11-2. pH 7.8 and incubation temperatures 28 °C were optimum for maximum calcitriol production using the cell-free lysate. This study results in a 10-fold (31 µL/10 mL) to that obtained using a 14 L Lab fermenter. Bioconversion using cell-free lysate should be considered for industrial production of calcitriol. [ABSTRACT FROM AUTHOR]

The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health, Office of Dietary Supplements (NIH ODS), introduced the first Standard Reference Material® (SRM) for determining vitamin D metabolites in 2009 motivated by significant concerns about the comparability and accuracy of different assays to assess vitamin D status. After 14 years, a suite of five serum matrix SRMs and three calibration solution SRMs are available. Values were also assigned for vitamin D metabolites in five additional SRMs intended primarily to support measurements of other clinical diagnostic markers. Both the SRMs and the certification approach have evolved from significant exogenous serum content to primarily endogenous content and from value assignment by combining the results of multiple analytical methods to the use of measurements exclusively from reference measurement procedures (RMPs). The impact of the availability of these SRMs can be assessed by both the distribution information (sales) and by reports in the scientific literature describing their use for method validation, quality control, and research. In this review, we describe the development of these SRMs, the evolution in design and value assignment, the expansion of information reported, and SRM use in validating analytical methods and providing quality assurance within the vitamin D measurement community. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic brain injury (HIBI) results in part from excess reactive oxygen species and iron-dependent lipid peroxidation (i.e. ferroptosis). The vitamin D precursor 7-dehydrocholesterol (7-DHC) may inhibit iron-dependent lipid peroxidation. Primary neurons underwent oxygen and glucose deprivation (OGD) injury and treatment with 7-DHC-elevating medications such as cariprazine (CAR) or vehicle. Postnatal day 9 mice underwent sham surgery or carotid artery ligation and hypoxia and received intraperitoneal CAR. In neurons, CAR administration resulted in significantly increased cell survival compared to vehicle controls, whether administered 48 h prior to or 30 min after OGD, and was associated with increased 7-DHC. In the mouse model, malondialdehyde and infarct area significantly increased after HIBI in the vehicle group, which were attenuated by post-treatment with CAR and were negatively correlated with tissue 7-DHC concentrations. Elevating 7-DHC concentrations with CAR was associated with improved cellular and tissue viability after hypoxic-ischemic injury, suggesting a novel therapeutic avenue. [ABSTRACT FROM AUTHOR]

A feasible yet effective electrochemical aptasensor for the detection of 25-hydroxyvitamin D3 (25-OHD3) has been devised based on gold-modified mesoporous silica-zeolitic imidazolate framework-8 (MSS-Z8) composite. The physical as well as electrochemical aspects of Au/MSS/FTO, Au/Z8/FTO, and Au/MSS-Z8/FTO were thoroughly investigated, and Au/MSS-Z8/FTO displayed enhanced electrochemical and electrokinetic performance. Therefore, Au/MSS-Z8/FTO platform has been utilized for electrochemical biosensing of 25-OHD3 by employing 5' thiolated aptamer specific to 25-OHD3 as biorecognition element. The efficacy of resultant aptasensor was evaluated in [Fe(CN)6]3−/4− redox mediator using differential pulse voltammetry technique. The Apt/Au/MSS-Z8/FTO displayed a highly sensitive (39.1 µA (pg mL−1)−1 cm−2) and selective voltammetric response towards 25-OHD3 within 0.001 to 106 pg mL−1 concentration range with experimental and theoretical detection limit of 0.001 and 0.084 pg mL−1, respectively. Also, the aptasensor performed reliably with both spiked serum samples (Recovery = 97.56–102.1%, RSD = 0.89–2.80%) as well as real serum samples as evident by consistency of results with those obtained from ELISA analysis of real serum samples. [ABSTRACT FROM AUTHOR]

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment. [ABSTRACT FROM AUTHOR]

The mucosa of the respiratory system is an essential site for local vitamin D synthesis, degradation, and signaling. It modulates the inflammatory and immune response by saving the integrity of the mucosal barrier and killing the invading pathogen through the induction of antimicrobial peptides. The proper functioning of the immune system within the respiratory system is influenced by the complex interactions of numerous immune pathways, including the gut-lung axis. Recent research has indicated that the gut microbiota is vital in developing and progressing chronic inflammatory chest conditions, such as asthma and chronic obstructive pulmonary disease (COPD). Furthermore, the immune-modulating function of vitamin D operates through the gut mucosa; hence, the vitamin D receptor is expressed to regulate the antimicrobial peptide. The potential protective role of vitamin D and its correlation with COPD has garnered significant interest. It is currently under exploration as a possible adjuvant therapy to aid in managing frequent exacerbation of COPD. In this review, we explored the connection between vitamin D and the immune system, as well as its relationship with microbiota. We also summarized some novel mechanisms of action of vitamin D supplementation that can impact disease exacerbation. [ABSTRACT FROM AUTHOR]

Quantitative analysis of the biologically-active metabolites of vitamin D (VitD), which are crucial in regulating various physiological and pathological processes, is important for clinical investigations. Liquid chromatography-tandem mass spectrometry (LC-MS) has been widely used for this purpose but existing LC-MS methods face challenges in achieving highly sensitive and accurate quantification of low-abundance VitD metabolites while maintaining high throughput and robustness. Here we developed a novel pipeline that combines a trapping-micro-LC-(T-µLC) with narrow-window-isolation selected-reaction monitoring MS(NWI-SRM) for ultra-sensitive, robust and high-throughput quantification of VitD metabolites in serum samples after derivatization. The selective-trapping and delivery approach efficiently removes matrix components, enabling high-capacity sample loading and enhancing sensitivity, throughput, and robustness. The NWI-SRM further improves the sensitivity by providing high selectivity. The lower limits of quantification (LOQs) achieved were markedly lower than any existing LC-MS methods: 1.0 pg/mL for 1,25(OH)2D3, 5.0 pg/mL for 24,25(OH)2D3, 30 pg/mL for both 25(OH)D2 and 25(OH)D3, all within a 9-min cycle. The method is applied to quantify VitD metabolites from 218 patients with multiple sclerosis. This study revealed negative correlations(r=− 0.44 to − 0.51) between the levels of 25(OH)D2 and all the three D3 metabolites in multiple sclerosis patients. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is widely prevalent among the elderly, posing significant health risks. This study aims to determine the global prevalence of vitamin D deficiency in the elderly. Methods: A systematic review and meta-analysis was conducted, examining databases including Scientific Information Database (SID), Medline (PubMed), ScienceDirect, Scopus, Embase, and Google Scholar until January 2023. The publication bias of the studies was assessed using the I2 test of heterogeneity and the Egger test. Results: The prevalence of vitamin D deficiency, defined as levels below 20 ng or 50 nmol was found to be 59.7% (95% CI 45.9–72.1). Furthermore, a review of six studies involving 6748 elderly individuals showed a prevalence of 27.5% (95% CI 21.8–34.1) for deficiency defined between 20 and 30 ng or 50–75 nmol. Additionally, a meta-analysis of seven studies with a sample size of 6918 elderly individuals reported a prevalence of 16% (95% CI 10.2–24.1) for deficiency defined above 30 nmol or 75 nmol. Conclusion: The results of the present study reveal that the prevalence of vitamin D deficiency among the elderly is high and requires the attention of health policymakers at the World Health Organization to prioritize extensive information dissemination and screening to mitigate the adverse effects on their quality of life. [ABSTRACT FROM AUTHOR]

Background: The incidence of type 1 diabetes (T1D) is showing a rising trend all over the world, and these patients are living longer than before. With increasing longevity, they are at increased risk of chronic complications including fractures. However, the bone mineral density (BMD) data in T1D patients are conflicting and variable across the studies. Here, we aimed to study the BMD in adult patients with T1D and delineate its predictors. Material and methods: We recruited 40 T1D patients and equal number of age- and sex-matched control subjects. Clinical, biochemical, hormonal, and densitometric assessments were performed for each of the participants and compared between the two groups. Results: The median age of T1D and control subjects was 23.5 (21–27.75) years and 24 (22–26) years, respectively. The median duration of diabetes in T1D patients was 12.5 (9–15.75) years with a mean HbA1C of 8.7 ± 1.9%. The serum corrected calcium, phosphorous, alkaline phosphatase, creatinine, and plasma 25-hydroxyvitamin D and iPTH levels were comparable between the groups. In T1D subjects, the mean lumbar spine and left hip BMD were 0.876 ± 0.154 gm/cm2 and 0.780 ± 0.112 gm/cm2, respectively, which corresponded to mean Z-scores of -1.5 ± 1.4 and -1.4 ± 0.9, respectively, which were significantly lower compared to control group. Multiple linear regression analyses showed that BMI and serum albumin were significant determinant of lumbar spine and hip BMD, respectively, in patients with T1D. Conclusion: Patients of T1D have apparently reduced BMD, which is being influenced by BMI and serum albumin level. [ABSTRACT FROM AUTHOR]

Solar ultraviolet (UV) radiation is a part of sunlight that enables vitamin D production in the human body. Vitamin D production depends on many factors, including exposure time, amount of radiation on the Earth's surface, and even personal factors (i.e., skin type, age, and lifestyle). In this work, maps of long-term monthly average hourly vitamin D–weighted solar UV radiation over Thailand using a semi-empirical model with ground-based and satellite-based input data were developed. These input data consist of ozone, cloud, aerosol, solar zenith angle, air mass, and extraterrestrial UV irradiance. The 2-year dataset (2014 and 2016) was used for model development, and that between 2017 and 2018 was utilized for model validation. For mapping process, the proposed model was used to estimate the vitamin D–weighted solar UV radiation over Thailand using 10-year period (2012–2021) of data. The spatial distributions of radiation over Thailand were presented as maps of long-term monthly average hourly from 0830 to 1630 local time. The maps show the influences of geography and the monsoons blowing through the country. [ABSTRACT FROM AUTHOR]

This study assesses the prevalence of Vitamin D deficiency and its potential association with cardiometabolic risk factors among South African adults residing in the Eastern Cape province. In this cross-sectional study, 1244 healthcare workers (HCWs) completed a self-administered questionnaire and venous blood samples were drawn at two academic hospitals in the Eastern Cape. History of hypertension and diabetes mellitus were self-reported. Participants were categorised as obese if their body mass index (BMI) ≥ 30 kg/m2. Participants were classified as having metabolic syndrome if they had hypertension, diabetes mellitus and obesity. Vitamin D [25(OH)D] deficiency was defined as venous blood concentrations < 50 nmol/L. Associations between vitamin D deficiency and participants' characteristics were assessed using multivariate logistic regression model analysis. The prevalence of vitamin D deficiency was 28.5% (n = 355), of whom 292 were female. Among the participants who were deficient in vitamin D, the prevalence of obesity, diabetes mellitus, hypertension, chronic kidney disease, and metabolic syndrome was 64.9% (n = 230), 9% (n = 32), 16.6% (n = 59), 2.3% (n = 8) and 18% (n = 64), respectively. In the adjusted multivariate logistic regression model, black Africans (AOR = 2.87; 95% CI 1.52–5.43) and individuals ≥ 42 years (AOR = 1.37; 95% CI 1.07–1.77) were more likely to exhibit vitamin D deficiency. However, there was no significant association by age, sex, and cardiometabolic markers. More than one in four healthcare workers was deficient in vitamin D among the study sample, especially the black Africans and older individuals. Further studies are needed at the population level to elucidate on the vitamin D status in the region. [ABSTRACT FROM AUTHOR]

Vitamin D-binding protein (VDBP) deficiency is a recently discovered apparently benign biochemical disorder that can masquerade as treatment-resistant vitamin D deficiency and is likely underrecognized. We present the case of a child with persistently low 25OH vitamin D levels despite replacement therapy. Exome sequencing revealed a novel homozygous nonsense variant in the GC gene, leading to undetectable levels of VDBP. Interestingly, exome sequencing also revealed a homozygous loss-of-function variant in ZNF142, which likely explains the additional clinical features of recurrent febrile convulsions and global developmental delay. Our findings corroborate the two previously reported patients with autosomal recessive VDBP deficiency caused by biallelic GC variants and emphasize the importance of measuring VDBP levels in cases of apparent vitamin D deficiency that is treatment-resistant. We also urge caution in concluding "atypical" presentations without careful investigation of a potential dual molecular diagnosis. [ABSTRACT FROM AUTHOR]

Background: Evaluation of hypercalcaemia in a patient with chronic kidney disease (CKD) is challenging, especially in low-resource settings. Hormone assays should be interpreted with caution as CKD affects both parathyroid hormone (PTH) and vitamin D. Therapies such as bisphosphonates are contraindicated in CKD, while fluid resuscitation can lead to volume overload. We report the diagnostic workup of a patient with stage V CKD who presented with symptomatic hypercalcaemia and discuss the diagnostic pitfalls and therapeutic challenges. Case presentation: A 72-year-old Sri Lankan woman with stage V, non-oliguric CKD presented with a 2-week history of worsening lassitude, increased thirst and constipation. She was clinically euvolemic and did not have signs of uraemia. Bilateral lung fields had occasional coarse crepitations. The rest of the physical examination was normal. Her serum creatinine level was similar to her baseline (4.7 mg/dl, eGFR 9 ml/min). She was found to have a high serum calcium (14.3 mg/dl) and phosphate (5.0 mg/dl) levels. Her PTH level was 24.1 pg/ml (15–68), and she was deficient in 25-hydroxycholecalciferol (9 mg/ml (30–100)). She was not on calcium or vitamin D supplementation. Disseminated tuberculosis was diagnosed after detecting granulomata in the lungs and abdomen in the contrast-enhanced computed tomography (CECT) and mycobacterial DNA in sputum. She was hydrated with 0.9% NaCl with meticulous use of frusemide. The effect of frusemide waned off by the 10th day, requiring haemodialysis to control the hypercalcaemia. Vitamin D was replaced intramuscularly with 200,000 IU, after which the calcium levels increased. She was treated with IV pamidronate 30 mg, and the calcium levels started reducing drastically. Antituberculous therapy (ATT) was initiated 7 days after pamidronate treatment. The calcium levels normalised 2 days after ATT and sustained beyond 2 months. Conclusion: Interpretation of PTH and phosphate levels should be done with caution when evaluating hypercalcaemia in patients with advanced chronic kidney disease. First- and second-generation assays detect PTH fragments which accumulate in CKD, leading to false positives. Hypophosphataemic effects of PTH/PTHrP can be masked by accumulation of phosphate in CKD. Bisphosphonates might have a role in treating calcitriol-induced hypercalcaemia, although this needs further evaluation. [ABSTRACT FROM AUTHOR]

Severe infections frequently require admission to the intensive care unit and cause life-threatening complications in critically ill patients. In this setting, severe infections are acknowledged as prerequisites for the development of sepsis, whose pathophysiology implies a dysregulated host response to pathogens, leading to disability and mortality worldwide. Vitamin D is a secosteroid hormone that plays a pivotal role to maintain immune system homeostasis, which is of paramount importance to resolve infection and modulate the burden of sepsis. Specifically, vitamin D deficiency has been widely reported in critically ill patients and represents a risk factor for the development of severe infections, sepsis and worse clinical outcomes. Several studies have demonstrated the feasibility, safety and effectiveness of vitamin D supplementation strategies to improve vitamin D body content, but conflictual results support its benefit in general populations of critically ill patients. In contrast, small randomised clinical trials reported that vitamin D supplementation may improve host-defence to pathogen invasion via the production of cathelicidin and specific cytokines. Nonetheless, no large scale investigations have been designed to specifically assess the impact of vitamin D supplementation on the outcome of critically ill septic patients admitted to the intensive care unit. [ABSTRACT FROM AUTHOR]

Background Diversity of risk factors, namely, vitamin D and lipid panel abnormalities, are connected to multiple sclerosis (MS) etiology and may possess an influential role on disease course. In a cross-sectional study, we correlated the demographic, clinical and radiological characteristics of 111 relapsing-remitting MS (RRMS) patients with their serum levels of vitamin D and lipid profile to evaluate the consequences of their abnormalities on disease activity and/or its progression. Results In the study group, the mean serum level of vitamin D was 18.93 ± 9.85 ng/mL, over 80% had insufficient level (< 30 ng/mL) and significantly lower in females (P = 0.011). Insufficient vitamin D significantly associated with high relapse frequency (P = 0.005). Measurement the direction of this association showed that each 1 ng/mL increase in vitamin D was correlated with both decrease in annualized relapse rate (ARR) of 0.02 relapse/year (P = 0.017) and with decrease in number of relapses during last 2 years of 0.02 relapse (P = 0.045). Analysis of serum lipid panel showed a direct link between higher levels of TC and LDL to increased total number of relapses (P < 0.001 and 0.003, respectively) and EDSS (P = 0.001 and 0.022), also between higher TG and EDSS (P = 0.001). This link became indirect between HDL and both total number of relapse and EDSS (P = 0.001 and 0.001). Radiologically, positively linked confluent brain lesion to elevated TC and TG levels (P = 0.001 and 0.002, respectively) and cord lesions to elevated TC (P = 0.007). Longer disease duration positively associated with all lipids-related variables. As a direct effect on lipid metabolism, each 1 ng/mL increase in vitamin D was associated with reduction in serum TC of 1.48 mg/dL (P = 0.002) and rise in HDL of 0.35 mg/dL (P = 0.028). Conclusions Management of vitamin D insufficiency may decrease risk of higher ARR and the same for dyslipidemia in reduction of disability and confluent brain T2 lesion. Increasing vitamin D was positively correlated with HDL but negatively with TC. [ABSTRACT FROM AUTHOR]