Search

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]

Background: Mitochondria are known to be involved in mediating the calorigenic effects of thyroid hormones. With an abundance of these hormones, alterations in energy metabolism and cellular respiration take place, leading to the development of cardiac hypertrophy. Vitamin D has recently gained attention due to its involvement in the regulation of mitochondrial function, demonstrating promising potential in preserving the integrity and functionality of the mitochondrial network. The present study aimed to investigate the therapeutic potential of Vitamin D on cardiac hypertrophy induced by hyperthyroidism, with a focus on the contributions of mitophagy and apoptosis as possible underlying molecular mechanisms. Methods and results: The rats were divided into three groups: control; hyperthyroid; hyperthyroid + Vitamin D. Hyperthyroidism was induced by Levothyroxine administration for four weeks. Serum thyroid hormones levels, myocardial damage markers, cardiac hypertrophy indices, and histological examination were assessed. The assessment of Malondialdehyde (MDA) levels and the expression of the related genes were conducted using heart tissue samples. Vitamin D pretreatment exhibited a significant improvement in the hyperthyroidism-induced decline in markers indicative of myocardial damage, oxidative stress, and indices of cardiac hypertrophy. Vitamin D pretreatment also improved the downregulation observed in myocardial expression levels of genes involved in the regulation of mitophagy and apoptosis, including PTEN putative kinase 1 (PINK1), Mitofusin-2 (MFN2), Dynamin-related Protein 1 (DRP1), and B cell lymphoma-2 (Bcl-2), induced by hyperthyroidism. Conclusions: These results suggest that supplementation with Vitamin D could be advantageous in preventing the progression of cardiac hypertrophy and myocardial damage. [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]

Background: Colorectal Cancer (CRC) has been molecularly classified into several subtypes according to tumor, stromal, and immune components. Here, we investigated whether the preventive effect of vitamin D on CRC varies with subtypes defined by Vitamin D receptor (VDR) expression in tumors and their surrounding stroma, along with the association of somatic mutations in CRC. Methods: In a population-based prospective study of 22,743 Japanese participants, VDR expression levels in tumors and their surrounding stroma were defined in 507 cases of newly diagnosed CRC using immunohistochemistry. Hazard ratios of CRC and its subtypes according to dietary vitamin D intake were estimated using multivariable Cox proportional hazards models. Results: Dietary vitamin D intake was not associated with CRC or its subtypes defined by VDR expression in tumors. However, an inverse association was observed for CRC with high VDR expression in the stroma (the highest tertile vs the lowest tertile: 0.46 [0.23–0.94], Ptrend = 0.03), but not for CRC with low VDR expression in the stroma (Pheterogeneity = 0.02). Furthermore, CRC with high VDR expression in the stroma had more somatic TP53 and BRAF mutations and fewer APC mutations than those with low VDR expression in the stroma. Conclusions: This study provides the first evidence that the preventive effect of vitamin D on CRC depends on VDR expression in the stroma rather than in the tumors. CRC with high VDR expression in the stroma is likely to develop through a part of the serrated polyp pathway, which tends to occur with BRAF but not with APC mutations. [ABSTRACT FROM AUTHOR]

Epilepsy is a common neurological disorder, and the exploration of potential therapeutic drugs for its treatment is still ongoing. Vitamin D has emerged as a promising treatment due to its potential neuroprotective effects and anti-epileptic properties. This study aimed to investigate the effects of vitamin D on epilepsy and neuroinflammation in juvenile mice using network pharmacology and molecular docking, with a focus on the mammalian target of rapamycin (mTOR) signaling pathway. Experimental mouse models of epilepsy were established through intraperitoneal injection of pilocarpine, and in vitro injury models of hippocampal neurons were induced by glutamate (Glu) stimulation. The anti-epileptic effects of vitamin D were evaluated both in vivo and in vitro. Network pharmacology and molecular docking analysis were used to identify potential targets and regulatory pathways of vitamin D in epilepsy. The involvement of the mTOR signaling pathway in the regulation of mouse epilepsy by vitamin D was validated using rapamycin (RAPA). The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Gene and protein expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining was used to analyze the apoptosis of hippocampal neurons. In in vivo experiments, vitamin D reduced the Racine scores of epileptic mice, prolonged the latency of epilepsy, and inhibited the production of TNF-α, IL-1β, and IL-6 in the hippocampus. Furthermore, network pharmacology analysis identified RAF1 as a potential target of vitamin D in epilepsy, which was further confirmed by molecular docking analysis. Additionally, the mTOR signaling pathway was found to be involved in the regulation of mouse epilepsy by vitamin D. In in vitro experiments, Glu stimulation upregulated the expressions of RAF1 and LC3II/LC3I, inhibited mTOR phosphorylation, and induced neuronal apoptosis. Mechanistically, vitamin D activated the mTOR signaling pathway and alleviated mouse epilepsy via RAF1, while the use of the pathway inhibitor RAPA reversed this effect. Vitamin D alleviated epilepsy symptoms and neuroinflammation in juvenile mice by activating the mTOR signaling pathway via RAF1. These findings provided new insights into the molecular mechanisms underlying the anti-epileptic effects of vitamin D and further supported its use as an adjunctive therapy for existing anti-epileptic drugs. [ABSTRACT FROM AUTHOR]

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy. [ABSTRACT FROM AUTHOR]

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients. [ABSTRACT FROM AUTHOR]

Rationale: Probiotics have beneficial effects on the nervous system by modulating the gut-brain axis. Additionally, vitamin D supplementation presents a potential way for ameliorating neuropsychological disorders, particularly in regions with a high prevalence of vitamin D deficiency. Objectives: The current clinical trial aimed to investigate the role of co-administered supplementation of probiotics and Vitamin D on the different inflammatory aspects of patients with Parkinson's disease. Methods: Forty-six patients with PD were recruited From the Functional Neurosurgery Research Center, Tehran, Iran. These patients were randomly allocated to one of the two treatment groups: Group A, who received probiotic/vitamin D supplements (n = 23), and Group B who received placebo capsules (n = 23) for 12 weeks. As primary outcomes, Interferon-Gamma (IFN-γ), interleukin 1 beta (IL-1β), IL-6, IL-10, Tumor Necrosis Factor-Alpha (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in serum were evaluated at the baseline and the end of the trial. Moreover, Additional questionnaire-based factors including gastrointestinal symptom rating scale (GSRS), Beck Anxiety Inventory (BAI), and Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. Results: Our findings demonstrated that the consumption of probiotic/vitamin D supplements leads to a significant decrease in IL-1β, INF-γ, IL-6, and MDA levels, while showing a significant increase in IL-10 and TAC levels compared to the placebo group (P < 0.05). Additionally, it leads to a significant decrease in the disease severity, anxiety, and gastrointestinal problems in PD patients in comparison to the placebo group (P < 0.05). Conclusions: Given the acknowledged role of inflammation in the pathogenesis of Parkinson's disease on one hand, and the recognized anti-inflammatory and antioxidant effects associated with probiotics and vitamin D on the other hand, the concurrent administration of probiotics and vitamin D supplements emerges as a promising and potentially effective treatment option for individuals with PD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect and mechanism of 1,25(OH)2D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). Methods: A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining. Mouse PSCs were extracted, co-cultured with mouse insulinoma β cells (MIN6 cells) and treated with 1,25(OH)2D3. ELISA detection of inflammatory factor expression. Tissue reactive oxygen species (ROS) levels were also measured. Immunofluorescence or Western blotting were used to measure fibrosis and inflammation-related protein expression. Results: PSCs activation and islets fibrosis in T2DM mice. Elevated blood glucose was accompanied by significant increases in serum inflammatory cytokines and tissue ROS levels. 1,25(OH)2D3 attenuated islet fibrosis by reducing hyperglycemia, ROS levels, and inflammatory factors expression. Additionally, the co-culture system confirmed that 1,25(OH)2D3 inhibited PSCs activation, reduced the secretion of pro-inflammatory cytokines, down-regulated the expression of fibrosis and inflammation-related proteins, and promoted insulin secretion. Conclusion: Our findings identify that PSCs activation contributes to islet fibrosis and β-cell dysfunction. 1,25(OH)2D3 exerts beneficial effects on T2DM potentially by inhibiting PSCs activation and inflammatory response, highlighting promising control strategies of T2DM by vitamin D. Highlights: PSCs activation leads to islet fibrosis in T2DM mice. TGF- β, IL-1 β, TNF-α, ROS induce PSCs activation, thereby inhibiting MIN6 cell proliferation and function. 1,25(OH)2D3 inhibits PSCs activation by downregulating the expression of factors such as TGF-β, protecting β cell function. [ABSTRACT FROM AUTHOR]

Background: Endocrine regulation of bone metabolisms is the focus of the "Skeletal Endocrinology" series of meetings. Aims: To report on the outcome of the discussion on the role of vitamin D/PTH axis in endocrine osteopathies held during the 10th Skeletal Endocrinology Meeting which took place in Stresa (Italy) in March 2023. Outcomes: Vitamin D/PTH axis has relevant influence on several outcomes in the general population and in patients affected by endocrinopathies such as hypoparathyroidism and secreting pituitary adenomas. Conclusions: Assessing the status of the vitamin D/PTH axis and using vitamin D and PTH as therapeutic agents is mandatory in several endocrine-related bone metabolic conditions. [ABSTRACT FROM AUTHOR]

Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2 years were treated with Denosumab, 42% with 120 mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70 mg. To avoid ADRs 500 mg of calcium and 400 IU of vitamin D orally were used. Initial effective response was reported after 1–3 months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120 mg, 60 or 70 mg in patients < 45 or 50 kg for ≥ 12 months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy. [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]

Purpose: With dairy products and fish being major sources of iodine in Switzerland, the growing popularity of plant-based alternatives may impact iodine nutrition. This study aimed to assess the iodine content in plant-based dairy and fish alternatives available in the Swiss market and compare them with conventional products. Methods: In 2022, a market survey was conducted in Zurich, Switzerland, to identify the plant-based dairy and fish alternatives available and assess their iodine content. To evaluate the impact of plant-based alternatives on iodine consumption in Switzerland, we modeled dietary scenarios by substituting the intake of dairy and fish items with plant-based alternatives. In addition, we investigated fortification with calcium, vitamins B2, B12, and D. Results: Out of 477 identified products, only four milk-alternative products were iodine fortified (median iodine concentration: 22.5 μg/100 ml). The median iodine concentration in unfortified plant-based alternatives was negligible compared to conventional dairy and fish products (milk: 0.21 vs 9.5 μg/100 ml; yogurt 0.36 vs 6.1 μg/100 g; cheese: 0.10 vs 20 μg/100 g; fish 0.50 vs 44 μg/100 g). Three portions of dairy per day as recommended by the Swiss Food Pyramid provide 25% of the RDA for iodine (150 μg/day), whereas substituting those with unfortified alternatives provides only 0.7% of the RDA. Conclusion: Only four out of 477 plant-based alternative products are iodine fortified in the Swiss market. Thus, the risk for consumers to miss out on the ca. 25% of the RDA for iodine by consuming plant-based alternatives is high, placing them at a risk for inadequate iodine intake. [ABSTRACT FROM AUTHOR]

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied. Aims: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp. Methods: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography. Results: Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01). Conclusions: Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction. [ABSTRACT FROM AUTHOR]

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. Summary: This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification. [ABSTRACT FROM AUTHOR]

Little is known about the impact of vitamin D supplementation on hand grip strength (HGS) and health-related quality of life (HRQoL) in children and adolescents with sickle cell disease (SCD). We aimed to evaluate the safety and efficacy of monthly high-dose vitamin D3 supplementation and its implications on bone mineral density (BMD), HGS, and HRQoL in patients with SCD and healthy controls. The study included 42 children with SCD and 42 healthy matched controls. The study participants were supplemented with high-dose monthly oral vitamin D3. Changes in the serum level of 25(OH) vitamin D3, maximum HGS, and BMD from baseline to 6 months were assessed, and the HRQoL questionnaire and Childhood Health Assessment Questionnaire (CHAQ) were used to evaluate the functional capacity. At baseline, SCD subjects had poorer growth status indicated by negative Z scores. Suboptimal BMD was detected by significantly lower Z score, and lower HGS and worse HRQL parameters were found compared to the controls (P < 0.001). Median 25(OH) vitamin D3 was significantly lower in SCD patients compared to controls (16.5 vs. 28 ng/mL, respectively (P < 0.001)). After 6 months of vitamin D supplementation, there was significant improvement in the DEXA Z-score (P < 0.001), limitation of physical health (P = 0.02), pain scores (P < 0.001), and CHAQ grades (P = 0.01) in SCD patients. A significant improvement in HGS (P < 0.001 and P = 0.005) as well as the CHAQ score (P < 0.001 and P = 0.003) was detected in the SCD group and controls, respectively. There were no reported clinical adverse events (AEs) or new concomitant medications (CMs) during the study duration, and safe levels of Ca and 25 (OH) D3 were observed at 3 and 6 months for both groups. There was a significant positive correlation between HGS and total physical score (r = 0.831, P < 0.001) and a negative correlation with CHAQ score (r = − 0.685, P < 0.001). We also detected a significant positive correlation between vitamin D levels at 6 months and HGS (r = 0.584, P < 0.001), pain score (r = 0.446, P < 0.001), and a negative correlation with CHAQ score (r = − 0.399, P < 0.001). Conclusion: Monthly oral high-dose vitamin D supplementation was safe and effective in improving vitamin D levels, HGS, and HRQoL in SCD children and healthy subjects, and BMD scores in SCD patients. Further randomized controlled trials are warranted to assess an optimal dosing strategy and to investigate the impact on clinically significant outcomes in children and adolescents with SCD and their healthy counterparts. Trial registration: ClinicalTrials.gov, identifier NCT06274203, date of registration: 23/02/2024, retrospectively registered. What is known: • Several studies have reported a high prevalence of vitamin D deficiency and suboptimal bone mineral density (BMD) in sickle cell disease (SCD) patients. • Musculoskeletal dysfunction is reported in SCD patients with a negative impact on physical activity and health-related quality of life (HRQL). • Little is known regarding the impact of vitamin D3 supplementation in children and adolescents with SCD. What is new: • We found that monthly oral high-dose vitamin D3 supplementation was safe, tolerated, and effective in improving serum vitamin D levels, HGS, BMD scores, and HRQL in SCD patients. [ABSTRACT FROM AUTHOR]

Telogen effluvium is characterized by excessive hair shedding usually following a stressful event. Ferritin has been used in clinical practice as a biomarker of nonanemic iron deficiency in cases of telogen effluvium. During the years of the COVID19 pandemic, telogen effluvium was reported as a part of post covid manifestations. As ferritin was also a biomarker for inflammation in cases with covid infection, this study was designed to evaluate the value of ferritin in cases with postcovid telogen effluvium one hundred patients recovering from covid 19 for 4–12 weeks were included in the study, detailed drug and laboratory history was obtained and serum ferritin level was measured. the mean serum level of ferritin among telogen effluvium patients was significantly lower than controls (68.52 ± 126 and 137 ± 137.597 ug/L respectively). Patients with telogen effluvium used significantly more azithromycin and ivermectin and significantly less vitamin C, D, lactoferrin and zinc than the controls Although serum ferritin is lower among telogen effluvium patients, it was still higher than the cutoff value for diagnosing nonanemic iron deficiency, we suggest that it will not be a good biomarkers in these cases. Our secondary outcomes showed that dietary supplements used during active infection such as vitamin C, D, lactoferrin and zinc might have a preventive value on postcovid hair loss, while azithromycin and ivermectin could have a negative long term effect on telogen effluvium. [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]

The frequency and risk factors for the development of diastolic dysfunction (DD) in patients with CPPD and OA have not been studied. The objective of this study was to determine the frequency and identify risk factors (RF) for the development of DD of the left and right ventricles (LV and RV) in patients with calcium pyrophosphate crystal deposition disease (CPPD) and osteoarthritis (OA). The study included 26 patients with CPPD and with knee OA 18–65 years old, matched in age and gender, without cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and rheumatic diseases. Conventional risk factors (TRF) of CVD were assessed, and echocardiography was performed. The frequency of DD in patients with CPPD and OA was quite high and almost did not differ in both groups: it was detected in 19 patients, of which 11 (42%) had CPPD and 8 (31%) had OA (p = 0.39). Type 1 LV DD was detected in 10 (39%) patients with CPPD and in 8 (31%) with OA (p = 0.11); type 1RV DD was detected in 8 (31%) patients with CPPD and in 7 (27%) patients with OA (p = 0.17); and type 1 LV DD and RV DD was detected in 7 (27%) patients with both CPPD and with OA. DD types 2 and 3 were not detected in both groups. There were no differences in both groups in CV risk factors, except for the level of CRP (it was higher in CPPD) (p = 0.03). In the CPPD group, mean values of LV E/E' (p = 0.02), LVDT (p = 0.03), LVMI (p = 0.04) were significantly higher than in patients with OA. On the contrary, in patients with OA, indices EDV (p = 0.004) and TVC (p = 0.02) were higher. There were direct correlations between diastolic function indices and the following factors in CPPD: LVL, PWLV and PTH level (r = 0.7, p <0.005), LV E' and PTH level (r = 0.7, p < 0.005). Inverse correlations were found between the level of PTH and IS (r = –0.5, p < 0.005), LVMI (r = –0.5, p < 0.005), and the level of vitamin D and VDDT (r = –0.6, p < 0.005). Direct correlations in OA were found between the level of CRP and PVAdiast (r = 0.6, p < 0.005), and the level of sUA (r = 0.7, p < 0.005), and the level of vitamin D and E/E'LV (r = 0.6, p < 0.005). A high prevalence of LV and RV DD was found in patients with CPPD and OA. The presence of DD in CPPD was associated with lower vitamin D levels, and in OA with a higher level of sUA and a lower level of PTH. [ABSTRACT FROM AUTHOR]

Previous studies, including our own, have demonstrated that arsenic exposure can induce liver fibrosis, while the underlying mechanism remains unclear and there is currently no effective pharmacological intervention available. Recent research has demonstrated that vitamin D supplementation can ameliorate liver fibrosis caused by various etiologies, potentially through modulation of the Nrf2 signaling pathways. However, it remains unclear whether vitamin D intervention can mitigate arsenic-caused liver fibrosis. As is known hepatic stellate cells (HSCs) activation and extracellular matrix (ECM) deposition are pivotal in the pathogenesis of liver fibrosis. In this study, we investigated the intervention effect of calcitriol (a form of active vitamin D) on arsenite-triggered Lx-2 cells (a human hepatic stellate cell line) activation and ECM oversecretion. Additionally, we also elucidated the role and mechanism of Nrf2 antioxidant signaling pathway. Our results demonstrated that calcitriol intervention significantly inhibits Lx-2 cell activation and ECM oversecretion induced by arsenite exposure. Additionally, calcitriol activates Nrf2 and its downstream antioxidant enzyme expression in Lx-2 cells, thereby reducing ROS overproduction caused by arsenite exposure. Further investigation reveals that calcitriol activates the Nrf2 signaling pathway and inhibits arsenite-triggered Lx-2 cell activation and ECM oversecretion by targeting vitamin D receptor (VDR). In conclusion, this study has demonstrated that vitamin D intervention can effectively inhibit HSC activation and ECM oversecretion triggered by arsenite exposure through its antioxidant activity. This provides a novel strategy for targeted nutritional intervention in the treatment of arsenic-induced liver fibrosis. [ABSTRACT FROM AUTHOR]

Recent evidence suggests the mechanistic role of mitochondria and oxidative stress in the development of celecoxib-induced cardiotoxicity. On the other, it has reported the positive effects of vitamin D on oxidative stress and the maintenance of mitochondrial functions. This current study examined the cardiac effects of celecoxib, doxorubicin, vitamin D, and a combination of them in rats. The effect of 10 days of celecoxib (100 mg/kg/day), doxorubicin (2.5 mg/kg), vitamin D (60,000 U/kg), and their combination was studied on cardiac function according to serum lactate dehydrogenase (LDH), creatine kinase (CK), glutathione (GSH), and malondialdehyde (MDA) levels as well as mitochondrial succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS) production, mitochondrial swelling, and mitochondrial membrane potential (MMP). Results showed that celecoxib and its combination with doxorubicin led to abnormality in paws and limbs, increased pressure in the eyes, blindness and animal death (in about 75% of the animals under study). Moreover, celecoxib and its combination with doxorubicin significantly increased cardiotoxicity biomarkers, oxidative stress markers (GSH and MDA), and mitochondrial toxicity parameters (SDH, ROS formation, MMP collapse, mitochondrial swelling). However, the combination of vitamin D with celecoxib and celecoxib + doxorubicin caused a significant reversal of deformity in paws and limbs, increased pressure in the eye, blindness, and animal death, as well as cardiotoxicity, oxidative stress, and mitochondrial parameters. This study proved for the first time the beneficial effect of vitamin D on celecoxib-induced cardiotoxicity, which is aggravated in the presence of doxorubicin through the maintenance of mitochondrial functions and its antioxidant potential. [ABSTRACT FROM AUTHOR]

Aims: Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture. Methods: An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray. Results: Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures. Conclusions: In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures. [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]

Vitamin D deficiencies are linked to multiple human diseases. Optimizing its synthesis, physicochemical properties, and delivery systems while minimizing side effects is of clinical relevance and is of great medical and industrial interest. Biotechnological techniques may render new modified forms of vitamin D that may exhibit improved absorption, stability, or targeted physiological effects. Novel modified vitamin D derivatives hold promise for developing future therapeutic approaches and addressing specific health concerns related to vitamin D deficiency or impaired metabolism, such as avoiding hypercalcemic effects. Identifying and engineering key enzymes and biosynthetic pathways involved, as well as developing efficient cultures, are therefore of outmost importance and subject of intense research. Moreover, we elaborate on the critical role that microbial bioconversions might play in the a la carte design, synthesis, and production of novel, more efficient, and safer forms of vitamin D and its analogs. In summary, the novelty of this work resides in the detailed description of the physiological, medical, biochemical, and epidemiological aspects of vitamin D supplementation and the steps towards the enhanced and simplified industrial production of this family of bioactives relying on microbial enzymes. Key points: • Liver or kidney pathologies may hamper vitamin D biosynthesis • Actinomycetes are able to carry out 1α- or 25-hydroxylation on vitamin D precursors [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]

Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic respiratory symptoms due to inflammatory and destructive changes of the lung leading to progressive airflow obstruction. Fragility fractures associated with osteoporosis are among major comorbidities and have significant impacts on quality of life and prognosis of patients with COPD. Evidence suggests that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility and resultant fractures in COPD. Although various clinical risk factors of osteoporosis have been described, mechanisms of COPD-associated osteoporosis are still largely unknown. In addition, its specific treatment has not been established, either. Previous studies have suggested involvement of low BMI and sarcopenia in the pathogenesis of COPD-associated osteoporosis. In this narrative review, we will propose critical roles of vitamin D deficiency and inflammation, both of which are often present in COPD and may underlie the development of osteosarcopenia and impaired bone quality, ultimately causing fractures in COPD patients. [ABSTRACT FROM AUTHOR]

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

Introduction: Transient hypercalcaemia due to teriparatide occurs in up to 11% of patients though delayed hypercalcaemia (> 24 h post injection) is rare. We report the case of a female who developed significant delayed hypercalcaemia after teriparatide treatment for osteoporosis and review other cases in the literature to date. Case report: A 72-year-old female on teriparatide for the treatment of osteoporosis was found to have hypercalcaemia (3.30 mmol/l) on routine testing approximately 3 months after starting therapy. Serum calcium pretreatment was normal at 2.39 mmol/l. She was admitted to the hospital for investigations which identified a serum 25-hydroxyvitamin D of 94 nmol/l, a low parathyroid hormone of 6.0 pg/ml, and normal test results for 1,25 dihydroxyvitamin D (115 pmol/l), parathyroid hormone-related peptide (< 1.4 pmol/ml), serum electrophoresis and angiotensin-converting enzyme (39 IU/l). CT abdomen, pelvis, and thorax revealed no evidence of malignancy and an isotope bone scan ruled out skeletal metastases. Serum calcium normalised (2.34 mmol/l) several days after stopping teriparatide and calcium supplements and administering intravenous fluid. On restarting teriparatide, delayed hypercalcaemia reoccurred and treatment was switched to denosumab. Discussion: Delayed moderate to severe hypercalcaemia (serum calcium > 3.0 mmol/l) due to teriparatide is rare but may lead to therapy withdrawal. The underlying predisposing risk factors remain unclear and highlight the importance of a routine serum calcium assessment on therapy. [ABSTRACT FROM AUTHOR]

Summary: Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. Purpose: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. Methods: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. Results: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06–0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04–0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. Conclusion: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future. [ABSTRACT FROM AUTHOR]

Rosacea is a common inflammatory skin condition displaying symptoms like flushing, erythema, papules, and pustules. Oral antibiotics, despite long-term adverse effects, are often used due to topical treatment limitations, underscoring the need for cost-effective choices like dietary modifications. Our review investigates the role of vitamins and minerals in rosacea, and provides evidence-based recommendations for supplementation and topical treatment of these nutrients for rosacea. An online search was performed on PubMed, Web of Science, Science Direct, Google Scholar, and ClinicalTrials.gov from 1998 to 2023. Included studies were summarized and assessed for quality and relevance in rosacea management. Varied outcomes emerged concerning the impact of essential vitamins and minerals on rosacea treatment. Vitamin A derivatives, specifically oral isotretinoin, demonstrated significant efficacy, with a 90% reduction in lesions, complete remission in 24% of patients, and marked improvement in 57% of patients. Vitamin B3 derivatives, such as topical 1-methylnicotinamide 0.25% and NADH 1%, improved symptoms in 76.4% (26/34) and 80% of patients, respectively. Outcomes for vitamin D, vitamin C, and zinc supplementation varied across studies. However, zinc sulfate solution 5% significantly reduced acne rosacea severity for patients with 40% and 60% exhibiting a moderate or good response, respectively. Omega-3 fatty acids showed significant improvement in alleviating xerophthalmia in 64% of patients with ocular rosacea. Vitamins and minerals hold potential in managing rosacea symptoms, offering a safe and cost-effective alternative or adjunctive treatment option. Currently, there are no established recommendations regarding their supplementation for rosacea. Studies assessing serum levels of vitamins and minerals in relation to rosacea are warranted, as this avenue holds potential for future advancements in the field. [ABSTRACT FROM AUTHOR]

This study evaluated the health-related weighted ultraviolet radiation (UVR) due to the total ozone content (TOC) and the aerosol optical depth (AOD) changes. Clear-sky Ultraviolet Index (UVI), daily doses, and exposure times for erythema induction (Dery and Tery) and vitamin D synthesis (DvitD and TvitD) were computed by a radiative transfer estimator. TOC and AOD data were provided by six Earth System Models (ESMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6). For projections, we consider four Shared Socioeconomic Pathways scenarios—SSPs (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5)—and two time-slices (near: 2041–2060 and far future: 2081–2100). UVR projections showed pronounced changes for the summer hemispheres in the far future. TOC increases in mid- and high latitudes of the Southern Hemisphere caused decreases in UVR at the summer solstice. However, projections did not indicate sun-safe exposure conditions in South America, Australia, and Southern Africa. On the contrary, exposure around solar noon from 10 to 20 min will still be sufficient to induce erythema in skin type III individuals throughout this century. In southern Argentina and Chile, the UVR insufficiency for vitamin D synthesis at solar noon in skin type III remains the same during this century at the winter solstice. In the Northern Hemisphere, UVI and Dery at the summer solstice should remain high (UVI ≥ 8; Dery ~ 7.0 kJ m−2) in highly populated locations. Above 45 °N, UVR levels cannot be enough to synthesize vitamin D in skin type III during the boreal winter. Our results show that climate change will affect human health through excess or lack of solar UVR availability. [ABSTRACT FROM AUTHOR]

Background and objective: This study aims to investigate the role of Vitamin D (VD) in regulating the stemness and survival of CD133+/CD44 + breast cancer stem cells, and to explore the role of NLRP3 in this process. Methods: Breast cancer tissues were collected for RXRα and VDR expression analysis. A triple-negative breast cancer cell line was cultured and stem-like cells (CD133 + CD44+) isolated using flow cytometry. These cells were treated with VD, analyzing their stem-like properties, apoptosis and proliferation, as well as P65 nuclear expression and NLRP3 expression. After NLRP3 inflammasome activator treatment, the parameters were reassessed. RXRα and VDR interaction was confirmed using co-immunoprecipitation (CoIP). Finally, a subcutaneous xenograft model of triple-negative breast cancer was treated with VD and subsequently analyzed for stem-like properties, proliferation, apoptosis, and NLRP3 expression levels. Results: CD133+/CD44 + stem cells expressed high levels of SOX2 and OCT4. VD treatment resulted in a significant decrease in SOX2 and OCT4 expression, fewer sphere-forming colonies, lower proliferation ability, and more apoptosis. Additionally, VD treatment inhibited NF-κB signaling and reduced NLRP3 expression. The NLRP3 activator BMS-986,299 counteracted the effects of VD in vitro. In vivo, VD inhibited the growth of breast cancer stem cells, reducing both tumor volume and weight, and decreased NLRP3, SOX2, and OCT4 expression within tumor tissues. Conclusion: Findings elucidate that VD mediates the modulation of stemness in CD133+/CD44 + breast cancer stem cells through the regulation of NLRP3 expression. The research represents novel insights on the implications for the application of VD in cancer therapies. [ABSTRACT FROM AUTHOR]

The management of malocclusion has developed greatly in terms of treatment simulation and biomechanics, but treatment duration has been a great concern to the clinician as well as the patient. 1-25dihydroxycholecalciferol (biologically active form of Vitamin D) stimulates both osteoclasts and osteoblasts and was found to be the most significant in Orthodontic Tooth Movement acceleration. Inflammatory cytokines like IL-17A also play an important role in osteoclastogenesis and can enhance the rate of Orthodontic Tooth Movement. To perform a simultaneous evaluation of pro-inflammatory salivary cytokine IL-17A and salivary 1-25dihydroxycholecalciferol and to correlate their role on orthodontic tooth movement. A prospective cohort study was conducted among n = 97 patients. Saliva samples were collected from the patients at three phases of the orthodontic treatment, centrifuged and stored at 4℃ for evaluation of salivary 1-25dihydroxycholecalciferol levels and Pro-inflammatory cytokine IL-17A using ELISA. The mean salivary 1-25dihydoxycholecalciferol levels were 41.250 ng/ml, 33.246 ng/ml and 35.043 ng/ml during the initial phase, lag phase and post lag phase of orthodontic treatment. The mean pro-inflammatory cytokine IL-17 A levels were 107.79 pg/ml, 102.98 pg/ml and 66.156 pg/ml during the initial phase, lag phase and post lag phase of orthodontic treatment. There was a correlation between the salivary 1-25dihydroxycholecalciferol level and salivary cytokine IL-17A levels during the various phases of orthodontic treatment using Spearman's correlation rho test and linear regression analysis. There was no significant difference (p > 0.05) between 1-25dihydroxycholecalciferol levels and gender during the various phases (initial phase, lag phase and post lag phase) of Orthodontic treatment. There was a negative correlation between salivary 1-25dihydroxycholecalciferol level and salivary cytokine IL-17A levels during the various phases of orthodontic treatment. The level of 1-25dihydroxycholecalciferol and salivary cytokine IL-17A have been quantified during the various phases of Orthodontic treatment and this can be used clinically for the supplementation of Vitamin D in patients with low vitamin D levels and can enhance the treatment duration for the patient with less damaging effects to the surrounding tissues. [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]