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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]

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]

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]

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]

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]

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]

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]

Abstract 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 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;

Abstract 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 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 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

Abstract Vitamin D modulates innate and adaptive immunity, the molecular mechanisms of which we aim to understand under human in vivo conditions. Therefore, we designed the study VitDHiD (NCT03537027) as a human investigation, in which 25 healthy individuals were supplemented with a single vitamin D3 bolus (80,000 IU). Transcriptome-wide differential gene expression analysis of peripheral blood mononuclear cells (PBMCs), which were isolated directly before and 24 h after supplementation, identified 452 genes significantly (FDR

Abstract 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 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 Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn’s disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level

Abstract 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 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 (

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]

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]

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]

Abstract Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.

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]

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]

Onoceroids are a rare family of triterpenes. One representative onoceroid is ambrein, which is the main component of ambergris used as a traditional medicine. We have previously identified the onoceroid synthase, BmeTC, in Bacillus megaterium and succeeded in creating ambrein synthase by introducing mutations into BmeTC. Owing to the structural similarity of ambrein to vitamin D, a molecule with diverse biological activities, we hypothesized that some of the activities of ambergris may be induced by the binding of ambrein to the vitamin D receptor (VDR). We demonstrated the VDR binding ability of ambrein. By comparing the structure–activity relationships of triterpenes with both the VDR affinity and osteoclastic differentiation-promoting activity, we observed that the activity of ambrein was not induced via the VDR. Therefore, some of the activities of ambergris, but not all, can be attributed to its VDR interaction. Additionally, six unnatural onoceroids were synthesized using the BmeTC reactions, and these compounds exhibited higher VDR affinity than that of ambrein. Enzymatic syntheses of onoceroid libraries will be valuable in creating a variety of bioactive compounds beyond ambergris. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P < 0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P = 0.01). Genes differentially associated with endogenous vitamin D by case–control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology. [ABSTRACT FROM AUTHOR]

The present study investigated primary care patients and compared self-reported sexual health in Swedes and Middle Easterners; analysed differences within and between the groups and analysed differences in 25-hydroxyvitamin D [25(OH)D] levels between the groups. 522 patients responded to a health questionnaire that included items on sexual health: 225 Middle Easterners from Iran, Iraq, and Turkey and 297 Swedes. Logistic regression was used to calculate the odds ratio (OR). Middle Easterners reported less sexual dysfunction than Swedes, and 75.8% of them and 18.9% of Swedes presented a 25(OH)D of < 50 nmol/L. The crude OR for reporting sexual dysfunction was 70% higher in Swedes compared to Middle Easterners (OR 1.70, 95% CI 1.15–2.50). This OR remained significant after adjustment for age, gender, waist circumference, and reported sexual desire. However, the significance disappeared after additional adjustment for 25(OH)D. In both groups, more females than males reported insufficient sexual desire. More female Middle Easterners reported sex life dissatisfaction. More female Swedes reported sexual dysfunction. Vitamin D could explain an association between gender and sex life dissatisfaction in Middle Easterners, and age could explain an association between gender and sexual dysfunction in Swedes. Age, waist circumference, and 25(OH)D levels were significant covariates in the logistic regression models. Results from the present study suggest that 25(OH)D variation partly explains differences in sexual dysfunction between the groups and between genders within the groups. Vitamin D therapy should be investigated to determine if these results are clinically useful. [ABSTRACT FROM AUTHOR]

Patients with osteoporosis are prone to fragility fractures. Evidence of the effects of active forms of vitamin D on hip fracture prevention is insufficient. We examined the association between vitamin D prescription and incidence of new fractures using the data of osteoporotic patients from the nationwide health insurance claims database of Japan. The follow-up period was 3 years after entry. The untreated patients were never prescribed vitamin D during follow-up (n = 422,454), and the treated patients had a vitamin D medication possession ratio of ≥ 0.5 at all time points (n = 169,774). Propensity score matching was implemented on these groups, yielding 105,041 pairs, and subsequently, the control and treatment groups were established and analyzed. The incidence of new fractures was significantly lower in the treatment group compared with the control group (6.25% vs. 5.69%, hazard ratio 0.936 [95% confidence interval 0.904–0.970], p < 0.001*). By site, hip fractures significantly decreased (0.89% vs. 0.42%, p < 0.001), but not vertebral and radial fractures. Subgroup analysis by vitamin D type showed a significantly lower incidence of total fractures only in alfacalcidol (hazard ratio 0.676 [95% confidence interval 0.628–0.728], p < 0.001*). The results suggest that vitamin D prescription was associated with a reduced incidence of hip fractures. [ABSTRACT FROM AUTHOR]

Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP. [ABSTRACT FROM AUTHOR]

Vitamin D inadequacy is a global problem in all age groups. Although there are various studies of vitamin D status in pregnant women in Southeast Asia, to date there are few studies from Southeast Asia examining vitamin D status in non-pregnant women of reproductive age. To examine the prevalence of vitamin D insufficiency (VDI) in healthy non-pregnant women of reproductive age in Southern Thailand, 120 healthy non-pregnant women aged 18–42 years were enrolled. Demographic and lifestyle data relevant to vitamin D assessment (sunlight exposure, nutritional intake, type of dress, sunscreen use) and biochemical studies (serum 25-hydroxyvitamin D or 25OHD, parathyroid hormone, calcium, phosphate) were obtained. VDI was classified as serum 25OHD < 20 ng/mL. The average serum 25OHD level was 23.1 ± 6.0 ng/mL. The overall prevalence of VDI was 34.1%. The average dietary intake of calcium, phosphorus and vitamin D and the average duration of sunlight exposure per week were not significantly different between the VDI women and the vitamin D sufficient (VDS) women. Logistic regression analysis found that the significant risk factors for VDI were greater body mass index and higher family income (p-values 0.01 and 0.02, respectively). The prevalence of VDI in non-pregnant women was high at 34%. As the dietary sources of vitamin D are limited and cutaneous vitamin D synthesis is limited by avoidance of sunlight exposure, vitamin D fortification in common daily foods would be an alternative option to reach the recommended vitamin D intake generally of at least 800 IU/day. [ABSTRACT FROM AUTHOR]

Can brucellosis-related biochemical and immunological parameters be used as diagnostic and treatment indicators? The goal of this project was to look at biochemical parameters, trace elements, and inflammatory factors in the acute and chronic stages of brucellosis after treatment with streptomycin and hydroxychloroquine-loaded solid lipid nanoparticles (STR-HCQ-SLN). The double emulsion method was used for the synthesis of nanoparticles. Serum levels of trace elements, vitamin D, CRP, and biochemical parameters were measured in rats involved in brucellosis. The therapeutic effect of STR-HCQ-SLN was compared with that of free drugs. In both healthy and infected rats, serum concentrations of copper, zinc, iron, magnesium, potassium, and biochemical parameters of the liver were significantly different. By altering the serum levels of the aforementioned factors, treatment with STR-HCQ-SLN had a positive therapeutic effect on chronic brucellosis. Vitamin D levels declined (46.4%) and CRP levels rose (from 7.5 mg to less than 1 mg) throughout the acute and chronic stages of brucellosis. This study showed that by comparing the biochemical parameters and the levels of trace elements in the serum of healthy and diseased mice in the acute and chronic stages of brucellosis, it is possible to get help from other routine methods for diagnosis. [ABSTRACT FROM AUTHOR]

Recent evidence has demonstrated that both acute and chronic exposure to particulate air pollution are risk factors for respiratory tract infections and increased mortality from sepsis. There is therefore an urgent need to establish the impact of ambient particulate matter (PM) on innate immune cells and to establish potential strategies to mitigate against adverse effects. PM has previously been reported to have potential adverse effects on neutrophil function. In the present study, we investigated the impact of standard urban PM (SRM1648a, NIST) and PM2.5 collected from Chiang Mai, Thailand, on human peripheral blood neutrophil functions, including LPS-induced migration, IL-8 production, and bacterial killing. Both NIST and the PM2.5, being collected in Chiang Mai, Thailand, increased IL-8 production, but reduced CXCR2 expression and migration of human primary neutrophils stimulated with Escherichia coli LPS. Moreover, PM-pretreated neutrophils from vitamin D-insufficient participants showed reduced E. coli-killing activity. Furthermore, in vitro vitamin D3 supplementation attenuated IL-8 production and improved bacterial killing by cells from vitamin D-insufficient participants. Our findings suggest that provision of vitamin D to individuals with insufficiency may attenuate adverse acute neutrophilic responses to ambient PM. [ABSTRACT FROM AUTHOR]

Nutrient pattern analysis is an easy way to compare nutrient intakes across different nations due to the universality of nutrients nature. The purpose of this study was to examine the relationship between dietary nutrient patterns (NPs) and circulating 25(OH)D concentrations with sleep duration and sleep quality among Iranian adults. We used a multistage cluster random sampling method to enroll 535 adults in this cross-sectional investigation. A validated food frequency questionnaire was applied to evaluate typical dietary intakes. Fasting blood samples were obtained to determine levels of circulating 25(OH)D. Sleep characteristics were assessed using the Pittsburgh Sleep Quality Index (PSQI). Participants had a mean age of 42.57 years and 51.2% of them had insufficient or deficient levels of serum vitamin D. Three NPs were identified: "high animal protein", "high vegetable" and "high carbohydrate". After adjustments for potential confounders, no significant associations were observed between "high animal protein" pattern and short sleeping or sleep quality. Greater adherence to "high vegetable" NP was associated with lower odds of short sleeping (OR 0.24; 95% CI 0.10, 0.54) and poor sleep quality (OR 0.45; 95% CI 0.20, 1.05). Stratified analysis revealed that these associations were stronger in normal-weight participants. Greater adherence to "high carbohydrate" NP, on the other hand, was connected to higher odds of short sleeping (OR 2.83; 95% CI 1.20, 6.72). Low adherence to "high vegetable" pattern and vitamin D insufficiency/deficiency were jointly associated with increased odds of short sleeping (OR 3.42, 95% CI 1.42, 6.64). High adherence to pattern comprising mainly of vegetable nutrients was associated with a reduced likelihood of being short sleepers and having poor sleep quality in Iranian adults, especially among those with a normal weight. Lower adherence to vegetable NP and insufficient/deficient vitamin D levels were synergistically associated with greater likelihood of being short sleepers. Greater adherence to carbohydrate NP was associated with an increased likelihood of short sleeping. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that vitamin D deficiency could play an important role in the development of non-skeletal diseases, including cancer. Vitamin D also affects the function of the reproductive system. In the present study, the relationship between 25(OH)D levels with oocyte quality in Breast Cancer (BC) women and control group have been investigated. After initial evaluations, ovarian stimulation began with the GnRH antagonist protocol in the BC group (N = 16) and control group (N = 16). The serum and follicular fluid (FF) 25(OH)D levels were measured at the time of oocyte retrieval and their relationship to oocyte quality was examined. The mean levels of serum and FF 25(OH)D in BC women were significantly lower than in the control group (22.26 ± 7.98 vs. 29.61 ± 9.12, P = 0.02, 21.65 ± 7.59 vs. 28.00 ± 9.05, P = 0.04, respectively). There was a significant correlation between the levels of 25(OH)D in FF and serum in BC women (r = 0.873, P < 0.001). But there was no correlation between the serum or FF 25(OH)D levels with the parameters related to oocytes (P > 0.05). In the BC women, the number of dysmorph and highly dysmorph oocytes was higher than in the control group (P < 0.001). Women with BC referring to infertility centers for fertility preservation are more likely to be deficient in serum 25(OH)D level; this subsequently affects the FF 25(OH)D level. However, serum and FF 25(OH)D levels may not be suitable indicators for examining maturity and quality of oocytes in terms of morphology in BC women, and the poor morphological quality of oocytes in BC women may be due to other factors. [ABSTRACT FROM AUTHOR]

Type II rickets is a hereditary disease caused by a mutation in the vitamin D receptor (VDR) gene. The main symptoms of this disease are bone dysplasia and alopecia. Bone dysplasia can be ameliorated by high calcium intake; however, there is no suitable treatment for alopecia. In this study, we verified whether gene therapy using an adenoviral vector (AdV) had a therapeutic effect on alopecia in Vdr-KO rats. The VDR-expressing AdV was injected into six 7-week-old female Vdr-KO rats (VDR-AdV rats). On the other hand, control-AdV was injected into 7-week-old female rats (control-AdV rats); non-infected Vdr-KO rats (control rats) were also examined. The hair on the backs of the rats was shaved with hair clippers, and VDR-AdV or control-AdV was intradermally injected. Part of the back skin was collected from each rat after AdV administration. Hair follicles were observed using hematoxylin and eosin staining, and VDR expression was examined using immunostaining and western blotting. VDR-AdV rats showed significant VDR expression in the skin, enhanced hair growth, and low cyst formation, whereas control-AdV and non-infected rats did not show any of these effects. The effect of VDR-AdV lasted for nearly 60 days. These results indicate that gene therapy using VDR-AdV may be useful to treat alopecia associated with type II rickets, if multiple injections are possible after a sufficient period of time. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common cancer with a rising incidence among white-skinned individuals. A number of epidemiological studies have suggested that obesity and serum 25-hydroxy-vitamin D (25(OH)D) levels may affect the arising of BCC. To address this, we selected 443 and 96 single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and serum level of 25(OH)D from large-scale genome-wide association studies (GWAS), respectively. The univariable and multivariable two-sample Mendelian randomization (MR) analyses were conducted with a series of sensitivity analyses to ensure the results were reliable and reproducible. The results of univariable two-sample MR analysis showed that higher BMI was related to lower risk for BCC (Odds ratio(OR) = 0.90; 95% confidence interval (CI),[0.81,0.99]; p = 0.02). In addition, this causal effect of BMI on BCC still remained (OR = 0.88; 95%CI,[− 0.22, − 0.03], p-value = 0.008) after adjusting for 25(OH)D level in the multivariable MR analysis. However, the results suggested that 25(OH)D level was not associated with BCC(OR = 1.02; 95%CI, [0.94,1.09], p-value = 0.67). In conclusion, similar to the conclusions of retrospective observational studies, the MR results indicate that high BMI is an independent protective factor for BCC. Meanwhile, vitamin D levels may not be causally associated with the risk of basal cell carcinoma and increasing vitamin D supplementation is unlikely to reduce the risk. [ABSTRACT FROM AUTHOR]

Observational studies have shown a negative correlation between Vitamin D level and the likelihood of developing insulin resistance (IR) and/or diabetes over time, yet evidence remains inconsistent. In this meta-analysis and systematic review, we strive to define the potential association between serum or supplemental Vitamin D Levels and insulin resistance respectively, as well as the contribution of Vitamin D to type 2 diabetes, and to summarize the biologic plausibility of Vitamin D. Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched for this Systematic Literature Review (SLR) to find appropriate observational studies and clinical trials published in English through to July 2022. EndNote (version X9) is used to manage the literature search results. We calculated Standard Mean Differences (SMDs) and Risk Ratios (RRs) with their 95% Confidence Intervals (CIs), separately, for continuous and dichotomous outcomes. The correlation coefficients were normalized to z values through Fisher's z-transformation to calculate the relevant statistics. Meta-analyses were carried out for all comparisons, based on a random-effects pooling model. Data analysis was performed using RevMan (version 5.3) and STATA (version 15.1). All statistical tests were two-sided, with P < 0.05 were regarded as significant. In our current meta-analysis, there are 18 RCTs and 20 observational studies including 1243 and 11,063 participants respectively. In the overall analysis, the diabetic with Vitamin D supplement treatment group showed significantly improve serum insulin (SMD = − 0.265, 95% CI − 0.394 to − 0.136, P < 0.05), glucose (SMD = − 0.17, 95% CI − 0.301to − 0.039, P < 0.05) and HOMA-IR (SMD = − 0.441, 95% CI − 0.582 to − 0.3, P < 0.05) compared with the routine treatment group. Correlation analysis results showed that all three outcomes were significantly correlated in a negative manner with raised Vitamin D (insulin: r = − 0.08 95% = − 0.12 to − 0.04; glucose: r = − 0.06 95% = − 0.11 to − 0.01; HOMA-IR: r = − 0.08 95% = − 0.09 to − 0.06). Results of overall analysis proved that vitamin D has shown significant effect on regulates insulin resistance, and there is a significant inverse association between serum Vitamin D level and IR. Vitamin D supplementation is expected to be integrated into conventional medical approaches to prevent type 2 diabetes and to mitigate the burden of diabetes for individuals and society. PROSPERO registration number: CRD42022348295. [ABSTRACT FROM AUTHOR]

Beneficial and adverse associations with arrhythmias have been reported for omega-3 fatty acids (omega-3 FA) and Vitamin D. The 12 lead electrocardiogram (ECG) contains quantitative measures reflecting diverse aspects of electrophysiology that might provide insights into mechanisms underlying these associations. In a pre-specified ancillary study of the VITaminD and omegA-3 (VITAL) trial, we examined the effect of 1 g of marine omega-3 FA per day, comprised of 460 mg eicosapentanoic acid and 380 mg of docosahexaenoic acid, and 2000 IU VitaminD3 per day on ECG characteristics associated with atrial and ventricular arrhythmias among individuals age 50 years or greater. A total of 911 study participants underwent ECGs at baseline and again at 2 years after the randomization. Individuals randomized to active omega-3 FA demonstrated significant net increase in PR-interval duration (p = 0.005) and P-wave duration (p = 0.03) as well significant net decrease in P-wave amplitude (p = 0.037) as compared to placebo. RMSSD increased to a greater extent in the omega-3 FA arm compared to placebo (p = 0.040). For Vitamin D3, the Cornell voltage increased to a lesser extent in the participants assigned to active treatment as compared to placebo (p = 0.044). There were no other significant differences in QRS, QTc, Cornell voltage or heart rate. Thus, randomized treatment with omega-3 FA supplements resulted in changes on the ECG that are potentially reflective of heightened vagal tone and/or slowing of intraatrial and AV conduction. Vitamin D3 supplementation resulted in modest reductions in progressive LV voltage suggestive of a potential antihypertrophic effect. Trial registration ClinicalTrials.gov Identifiers: NCT01169259, NCT02178410 (06/26/2010 and 06/30/2014). [ABSTRACT FROM AUTHOR]