Regulation Of Vitamin Research Articles

Effects of solubility of Supercritical-CO2 solvent and mass transfer property on extraction of vitamin E from canola seeds

This study is to explore the solubility of the targeted Vitamin E from canola seeds in supercritical-CO2 (SC–CO2)solvent and their intricate relationship through the developed modelling approach. The study investigated the impact of pressure and temperature on the efficiency of Vitamin E extraction through the regulation of Vitamin E solubility and yield in SC-CO2 solvent. These parameters played a crucial role in determining extraction efficiency. Pressures enhanced the solubility and density of Vitamin E, while elevated temperatures facilitated total Vitamin E extraction yield by promoting solvent diffusion and mass transfer through viscosity reduction. The optimal separation process of Vitamin E was achieved at 75ׄ°C, 18 MPa. The Vitamin E concentration in extracted oil is 12 times higher than Vitamin E contents in regular canola seed oil. The mathematical modeling revealed fundamental mechanisms governing the extraction process and offers useful information for optimizing extraction protocols in industrial applications.

Investigating Vitamin D-Binding Protein's Role in Childhood Health and Development.

Vitamin D-binding protein (DBP), also known as Gc-globulin, is a protein that affects several physiological processes, including the transport and regulation of vitamin D metabolites. Genetic polymorphisms in the DBP gene have a significant impact on vitamin D levels and may have implications for disease risk. DBP polymorphisms are linked to differential immune responses, which could influence the onset of juvenile diseases. This narrative review examines the various roles of DBP, with a focus on bone health, immunological regulation, and lipid metabolism in children. Chronic disorders affected by DBP polymorphisms include bone abnormalities, autoimmune diseases, cardiovascular issues, childhood asthma, allergies, cystic fibrosis, acute liver failure, celiac disease, inflammatory bowel disease, and chronic kidney disease. Future research should focus on identifying the processes that underpin the many roles that DBP plays and developing customized therapeutics to improve health outcomes in the juvenile population.

Non-Classical Effects of FGF23: Molecular and Clinical Features.

This article reviews the role of fibroblast growth factor 23 (FGF23) protein in phosphate metabolism, highlighting its regulation of vitamin D, parathyroid hormone, and bone metabolism. Although it was traditionally thought that phosphate-calcium homeostasis was controlled exclusively by parathyroid hormone (PTH) and calcitriol, pathophysiological studies revealed the influence of FGF23. This protein, expressed mainly in bone, inhibits the renal reabsorption of phosphate and calcitriol formation, mediated by the α-klotho co-receptor. In addition to its role in phosphate metabolism, FGF23 exhibits pleiotropic effects in non-renal systems such as the cardiovascular, immune, and metabolic systems, including the regulation of gene expression and cardiac fibrosis. Although it has been proposed as a biomarker and therapeutic target, the inhibition of FGF23 poses challenges due to its potential side effects. However, the approval of drugs such as burosumab represents a milestone in the treatment of FGF23-related diseases.

Gene expression profiling of vitamin D metabolism enzymes in leukemia and lymphoma patients: molecular aspect interplay of VDR, CYP2R1, and CYP24A1.

Vitamin D deficiency is prevalent among the Indonesian population, particularly in individuals diagnosed with leukemia-lymphoma. The regulation of vitamin D metabolism is influenced by the expression of several enzymes, such as CYP2R1, CYP24A1, and the vitamin D receptor (VDR). This study aimed to scrutinize the gene expression profiles in both mRNA and protein levels of VDR, CYP2R1, and CYP24A1 in leukemia and lymphoma patients. The research was a cross-sectional study conducted at Cipto Mangunkusumo Hospital (RSCM) in Jakarta, Indonesia. The study included a total of 45 patients aged over 18years old who have received a diagnosis of lymphoma or leukemia. Vitamin D status was measured by examining serum 25 (OH) D levels. The analysis of VDR, CYP2R1, and CYP24A1 mRNA expression utilized the qRT-PCR method, while protein levels were measured through the ELISA method. The study revealed a noteworthy difference in VDR protein levels between men and women. The highest mean CYP24A1 protein levels were observed in the age group > 60years. This study found a significant, moderately positive correlation between VDR protein levels and CYP24A1 protein levels in the male and vitamin D sufficiency groups. In addition, a significant positive correlation was found between VDR mRNA levels and CYP2R1 mRNA levels, VDR mRNA levels and CYP2R1 mRNA levels, and CYP2R1 mRNA levels and CYP24A1 mRNA levels. However, the expression of these genes does not correlate with the protein levels of its mRNA translation products in blood circulation.

The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice.

Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expression and function. In turn, legumain alters VD3 bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP). Active VD3 (1,25(OH)2D3) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Upregulation of legumain was also observed in vivo, evidenced by increased legumain mRNA in the liver and spleen, as well as increased legumain activity in kidneys from wild-type mice treated with 25(OH)D3 (50 µg/kg, subcutaneously) for 8 days compared to a control. In addition, the serum level of legumain was also increased. We further showed that active legumain cleaved purified VDBP (55 kDa) in vitro, forming a 45 kDa fragment. In vivo, no VDBP cleavage was found in kidneys or liver from legumain-deficient mice (Lgmn-/-), whereas VDBP was cleaved in wild-type control mice (Lgmn+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D3 and total VD3 and altered expression of key renal enzymes involved in VD3 metabolism (CYP24A1 and CYP27B1). In conclusion, a regulatory interplay between VD3 and legumain is suggested.

Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease-a comprehensive review from the ERA CKD-MBD working group.

Klotho, a multifunctional protein, acts as a co-receptor in fibroblast growth factor 23 and exerts its impact through various molecular pathways, including Wnt, hypoxia-inducible factor and insulin-like growth factor 1 pathways. The physiological significance of Klotho is the regulation of vitamin D and phosphate metabolism as well as serving as a vital component in aging and neurodegeneration. The role of Klotho in aging and neurodegeneration in particular has gained considerable attention. In this narrative review we highlight several key insights into the molecular basis and physiological function of Klotho and synthesize current research on the role of Klotho in neurodegeneration and aging. Klotho deficiency was associated with cognitive impairment, reduced growth, diminished longevity and the development of age-related diseases in vivo. Serum Klotho levels showed a decline in individuals with advanced age and those affected by chronic kidney disease, establishing its potential diagnostic significance. Additionally, multiple medications have been demonstrated to influence Klotho levels. Therefore, this comprehensive review suggests that Klotho could open the door to novel interventions aimed at addressing the challenges of aging and neurodegenerative disorders.

Isochromosome 12p Formation Regulates Vitamin D Metabolism in Testicular Cancer.

Isochromosome 12p (iChr12p) is typical in almost all invasive testicular cancers. Increased copy number of genes on 12p is associated with the development of a clinically manifest tumor; however, the causative genes have not yet been identified. Chromosome 12 harbors many genes involved in Vitamin D metabolism. RNAseq analysis of Vitamin D receptor (VDR) genes from the TCGA cohort revealed that clustering of VDR expression signatures could differentiate between pure seminomas and non-seminomatous germ cell tumors (NSGCT). Using TCGA mRNA expression of anabolic (CYP2R1, CYP27A1 and CYP27B1) and catabolic (CYP24A1) Vitamin D enzymes, positive (PTHLH, IFNG, and TNF) and negative (FGF23) feedback regulators could also clearly distinguish between pure seminomas and NSGCT. We hypothesize that the regulation of Vitamin D metabolism might be disturbed through iChr12p formation, influencing testicular carcinogenesis via increased FGF23 and PTHLH expression. While FGF23 represses CYP27B1 and activates catabolism of active hormone, increased PTHLH secretion can lead to hypercalcemia via inactivation of VDR. In conclusion, testicular cancer is associated with extensive modifications in intratesticular Vitamin D homeostasis. Further research is needed to clarify whether Vitamin D deficiency causes the formation of iChr12p and whether Vitamin D deficiency via iChr12p genomic aberration is involved in testicular carcinogenesis.

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines.

Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

ABCG5 and ABCG8 Are Involved in Vitamin K Transport.

ATP-binding cassette protein G5 (ABCG5)/ABCG8 heterodimer exports cholesterol from cells, while Niemann-Pick C1-like 1 (NPC1L1) imports cholesterol and vitamin K. We examined whether ABCG5/ABCG8 transports vitamin K similar to NPC1L1. Since high concentrations of vitamin K3 show cytotoxicity, the cytoprotective effects of ABCG5/ABCG8 were examined. BHK cells expressing ABCG5/ABCG8 were more resistant to vitamin K3 cytotoxicity than control cells, suggesting that ABCG5/ABCG8 transports vitamin K3 out of cells. The addition of vitamin K1 reversed the effects of ABCG5/ABCG8, suggesting that vitamin K1 competitively inhibits the transport of vitamin K3. To examine the transport of vitamin K1 by ABCG5/ABCG8, vitamin K1 levels in the medium and cells were measured. Vitamin K1 levels in cells expressing ABCG5/ABCG8 were lower than those in control cells, while vitamin K1 efflux increased in cells expressing ABCG5/ABCG8. Furthermore, the biliary vitamin K1 concentration in Abcg5/Abcg8-deficient mice was lower than that in wild-type mice, although serum vitamin K1 levels were not affected by the presence of Abcg5/Abcg8. These findings suggest that ABCG5 and ABCG8 are involved in the transport of sterols and vitamin K. ABCG5/ABCG8 and NPC1L1 might play important roles in the regulation of vitamin K absorption and excretion.

LBODP016 Lithocholic Acid Induced 25-hydroxyvitamin D-1alpha Hydroxylase (cyp27b1) Expression And Activities In Vitro And In Vivo

Abstract Our previous study reported that oleanolic acid, a natural agonist for bile acid membrane receptor Takeda G protein coupled receptor 5 (TGR5), could exert bone protective effects, increase circulating 1, 25(OH)2D3 level and induce renal CYP27B1 expression and activities. However, it is unclear if bile acids, as the endogenous agonist of bile acid receptors, could regulate CYP27B1 expression and activities in kidney and bone tissues. The present study aimed to characterize the effects of lithocholic acid (LCA), a secondary bile acid, on CYP27B1 expression and activities in vitro using human proximal tubule (HKC-8) and osteosarcoma (MG-63) and in vivo using mature (6-month-old) male C57BL/6 mice. HKC-8 and MG-63 cells were treated with either LCA (10-10 to 10-5 M), PTH (10-7M), or its vehicle for 4 hours. For MG-63 cells, LCA significantly induced CYP27B1 protein expression at 10-10 and 10-9M (P<0. 001) and CYP27B1 mRNA expression at 10-9M (P<0. 001). For HKC-8 cells, LCA significantly induced CYP27B1 protein expression at 10-10 to 10-6M (P<0. 01) and CYP27B1 mRNA expression at 10-10M (P<0. 001). In addition, LCA significantly induced CYP27B1 activity in MG-63 cells (10-10M) (P<0. 05) and in HKC-8 cells (10-6M) (P<0. 01). For the in vivo study, male C57BL/6 mice were fed with 25mg/kg LCA or its vehicle for three consecutive days and sacrificed 5 hours after the last gavage. Serum, kidney, and iliac crests were collected for subsequent analysis. LCA significantly induced circulating 1,25(OH)2D3 levels (P<0. 01) and CYP27B1 protein expression in both kidney and iliac crests in mice (P <0. 05). In addition, the time-dependent change (2, 5, 8 hours) in serum 1,25(OH)2D3 levels were determined upon feeding the male mice with a single dose of 25mg/kg LCA. LCA significantly increased serum 1,25(OH)2D3 levels in male mice at 2 and 5 hours (P <0. 01 and P <0. 05, respectively), and serum 1,25(OH)2D3 levels returned to basal level by 8 hours. LCA significantly increased CYP27B1 protein expression in kidney in mice at 8 hours after treatment (vs. control group, P<0. 05). In summary, our results showed that LCA significantly induced circulating 1,25(OH)2D3 levels, possibly by its actions to induce CYP27B1 expressions and activities in renal and extra-renal (bone) tissues. The study indicated that bile acids and other TGR5 ligands might play an important role in the regulation of vitamin D metabolism. Presentation: No date and time listed

ESTIMATION OF THE FREQUENCY OF GENETIC VARIANTS ASSOCIATED WITH VITAMIN D LEVELS AND OSTEOPOROSIS IN THE POPULATION OF UKRAINE

Circulating vitamin D levels and the risk of osteoporosis have significant inheritance. Single nucleotide polymorphisms (SNPs) in the GC, DHCR7/NADSYN1, CYP2R1, CYP24A1, and SEC23A genes have shown significant association with these conditions in previous genome-wide association studies (GWAS). Objective: to study the frequency of alleles associated with circulating levels of vitamin D and osteoporosis in the cohort of Ukrainians, as well as to compare the frequencies of these variants with individuals of Western and Northern European origin. Materials and Methods. This paper presents the results of the study of the frequencies of genomic variants associated with vitamin D levels and osteoporosis in a cohort of 97 Ukrainians based on genome data obtained by whole genome sequencing (WGS), as well as comparing their frequencies with the combined European population (CEU) of the "1000 genomes" project (persons of Western and Northern European ancestry). Files with the primary publicly available genomic data of Ukrainians were annotated using ANNOVAR and SNPEff software using the reference database of the human genome version hg38. Comparison of allele frequencies between populations was performed using Fisher's exact test using the number of alleles in the two studied populations and the construction of conjugated 2x2 tables. Results. It was found that of the 22 single nucleotide polymorphisms included in the analysis, 10, namely rs2282679; rs4855; rs10033936; rs3755967; rs17467825; rs12639968; rs1155563; rs17216707; rs10745742; rs180119, significantly differ in the Ukrainian cohort comparatively to CEU. Using correlation analysis, we also found that the genotypes of SNPs rs3755967, rs17467825, rs2282679 and rs4855 in Ukrainians are completely correlated with each other (r = 1), which means that they are in a state of complete linkage in Ukrainians of the given cohorts. Conclusion. Such findings may be the evidence of evolutionary and adaptation processes in the regulation of vitamin D levels and bone mineral density in the population of Ukraine and requires further studies of phenotype-genotype relationship.

Fibroblast Growth Factor 23 as Regulator of Vitamin D Metabolism.

Fibroblast growth factor 23 (FGF23) is a hormone produced by osteocytes in bone that acts on the kidneys to regulate phosphate and vitamin D metabolism.FGF23 levels were shown to be increased in the early stage of chronic kidney disease (CKD), with a slight decline in estimated glomerular filtration rate (eGFR) even when the range was restricted to above 60mL/min/1.73m2, indicating that subtle phosphate load is a stimulator of FGF23 in serum. FGF23 is also known to inhibit vitamin D activation from 25-hydroxyvitamin D (25-OH-D) to 1,25-dihydroxyvitamin D [1,25(OH)2D], while it stimulates its degradation from 25-OH-D to 24,25-dihydroxyvitamin D [24,25(OH)2D]. Previously, we demonstrated a significant and negative association of serum FGF23 with serum 1,25(OH)2D and 1,25(OH)2D/25-OH-D ratio, a putative parameter for CYP27B1, and confirmed the physiological effects of FGF23 on phosphate and vitamin D metabolism in non-CKD subjects. Elevated FGF23 by itself is reported to be associated with various adverse outcomes, including left ventricular hypertrophy, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system, leading to increased mortality even in non-CKD individuals. On the other hand, our previous study showed that the impaired incremental response of serum FGF23 in response to oral phosphate load in diabetic patients can help to significantly increase serum phosphate (Yoda et al., J Clin Endocrinol Metab 97:E2036-43, 2012) and thus may contribute to progression of vascular calcification in those patients (personal observation). It is suggested that increased serum FGF23 might be an important indicator of adverse outcomes in non-CKD as well as CKD patients.

Might Routine Vitamin A Monitoring in Cystic Fibrosis Patients Reduce Virus-Mediated Lung Pathology?

Cystic fibrosis (CF) is an autosomal recessive gene disorder that affects tens of thousands of patients worldwide. Individuals with CF often succumb to progressive lung disease and respiratory failure following recurrent infections with bacteria. Viral infections can also damage the lungs and heighten the CF patient’s susceptibility to bacterial infections and long-term sequelae. Vitamin A is a key nutrient important for immune health and epithelial cell integrity, but there is currently no consensus as to whether vitamin A should be monitored in CF patients. Here we evaluate previous literature and present results from a CF mouse model, showing that oral vitamin A supplements significantly reduce lung lesions that would otherwise persist for 5-6 weeks post-virus exposure. Based on these results, we encourage continued research and suggest that programs for the routine monitoring and regulation of vitamin A levels may help reduce virus-induced lung pathology in CF patients.

Effectiveness of vitamin D supplements in the patients suffering from Alzheimer disease

Introduction: Vitamin D is a steroid hormone. It crosses the blood brain barrier and binds with receptors present in neurons and glial cells of various parts of central nervous system like hippocampus, cortex, sub-cortex etc. Due to its antioxidant property and regulating intra-neuronal calcium homeostasis, it can be hypothesized that vitamin D has a role to play in preventing age related cognitive decline. Materials and Methods: Total of 160 patients were included in the study. MMSE is useful for evaluating the subjects having dementia syndrome because these subjects cooperate well only for short duration. Mini Mental state examination score was used for the assessment of dementia. They were included in the study on the basis of serum vitamin D level and MMSE score. Results: The collected data showed that mean serum vitamin D levels were found to be lower in group A when compared to group B. After 3 months of treatment with supplements, the score of post treatment MMSE was found to be higher in group A as compared to group B. After 6 months of treatment with supplements, the score of post treatment MMSE was found to be higher in group A as compared to group B. Discussion & Conclusion: Vitamin D acts like a neurosteroid hormone in areas of neurotransmission and neuro-immunomodulation. Patients on medical therapy for dementia has also shown improve results with regulation of vitamin D. It has also exhibited neuro-protective properties against glutamate toxicity through antioxidant effects thus preventing apoptosis. The present study is one of on-going steps in the direction of establishing role of Vitamin D in prevention and treatment of senile dementia.

Effect of dietary vitamins C and E on the risk of Parkinson's disease: A meta-analysis

A neuroprotective effect of dietary vitamins C and E on Parkinson's disease (PD) has been suggested, however, several human studies have reported controversial results. Therefore, we conducted a meta-analysis on the effect of vitamins C and E on the risk of Parkinson's disease.A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases for studies published up to January 23, 2021. We included studies that reported (1) intake of vitamins C and E using validated methods; (2) assessment of odds ratio (OR), relative risk (RR), or hazard ratio (HR); and (3) patients with PD identified by a neurologist, hospital records, or death certificates. The Comprehensive Meta-Analysis Software 2 program was used for statistical analyses of the pooled data.A total of 12 studies (four prospective cohort and eight case-control studies) were included in our meta-analysis. No significant risk reduction was observed in the high vitamin C intake group compared to low intake group. On the other hand, the high vitamin E intake group showed a significantly lower risk of development of PD than the low intake group (pooled OR = 0.799. 95% CI = 0.721 to 0.885).We conclude that vitamin E might have a protective effect against PD, while vitamin C does not seem to have such an effect. However, the exact mechanism of the transport and regulation of vitamin E in the CNS remains elusive, and further studies would be necessary in this field.

Regulation of Vitamin C Accumulation for Improved Tomato Fruit Quality and Alleviation of Abiotic Stress.

Ascorbic acid (AsA) is an essential multifaceted phytonutrient for both the human diet and plant growth. Optimum levels of AsA accumulation combined with balanced redox homeostasis are required for normal plant development and defense response to adverse environmental stimuli. Notwithstanding its moderate AsA levels, tomatoes constitute a good source of vitamin C in the human diet. Therefore, the enhancement of AsA levels in tomato fruit attracts considerable attention, not only to improve its nutritional value but also to stimulate stress tolerance. Genetic regulation of AsA concentrations in plants can be achieved through the fine-tuning of biosynthetic, recycling, and transport mechanisms; it is also linked to changes in the whole fruit metabolism. Emerging evidence suggests that tomato synthesizes AsA mainly through the l-galactose pathway, but alternative pathways through d-galacturonate or myo-inositol, or seemingly unrelated transcription and regulatory factors, can be also relevant in certain developmental stages or in response to abiotic factors. Considering the recent advances in our understanding of AsA regulation in model and other non-model species, this review attempts to link the current consensus with novel technologies to provide a comprehensive strategy for AsA enhancement in tomatoes, without any detrimental effect on plant growth or fruit development.

The blood-cerebrospinal fluid barrier, an important regulator of vitamin D metabolite concentrations in the central nervous system

The blood-cerebrospinal fluid barrier, an important regulator of vitamin D metabolite concentrations in the central nervous system

Tomatidine ameliorates obesity-induced nonalcoholic fatty liver disease in mice

Tomatidine is isolated from the leaves and green fruits of some plants in the Solanaceae family, and has been reported to have anti-inflammatory and antitumor effects. Previous studies have found that tomatidine decreases hepatic lipid accumulation via regulation of vitamin D receptor and activation of AMP-activated protein kinase (AMPK) phosphorylation. However, whether tomatidine reduces weight gain and improves nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated how tomatidine ameliorates NAFLD in obese mice and evaluated the regulatory mechanism of lipogenesis in hepatocytes. Male C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity and NAFLD, and treated with tomatidine via intraperitoneal injection. In vitro, FL83B hepatocytes were incubated with oleic acid and treated with tomatidine to evaluate lipid metabolism. Our results demonstrate that tomatidine significantly decreases body weight and fat weight compared to HFD-fed mice. In addition, tomatidine decreased hepatic lipid accumulation and improved hepatocyte steatosis in HFD-induced obese mice. We also found that tomatidine significantly regulated serum total cholesterol, fasting blood glucose, low-density lipoprotein, and triglyceride levels, but the serum high-density lipoprotein and adiponectin concentrations were higher than in the HFD-fed obese mice. In vivo and in vitro, tomatidine significantly suppressed the expression of fatty acid synthase and transcription factors involved in lipogenesis, and increased the expression of adipose triglyceride lipase. Tomatidine promoted the sirtuin 1 (sirt1)/AMPK signaling pathway to increase lipolysis and β-oxidation in fatty liver cells. These findings suggest that tomatidine potentially ameliorates obesity and acts against hepatic steatosis by regulating lipogenesis and the sirt1/AMPK pathway.

New insights into vitamin D regulation: is there a role for alkaline phosphatase?

PurposeThe diagnosis of vitamin D deficiency is based on the determination of total plasma 25-hydroxyvitamin D (25-OHD) concentrations, but the regulation of vitamin D 25-hydroxylation is not a major consideration and very little information is available on this activity.To check what factors could interfere with the activity of vitamin D-25-hydroxylase and thus alter the 25-OHD concentrations, we looked for potential correlations between 25-OHD and results of liver function tests in healthy adults.MethodsThis single-centre study was retrospective and consisted of evaluating the correlations between 25-OHD and the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and bone alkaline phosphatase (BALP) in 349 healthy subjects aged from 18 to 65 years. In particular, in Group 1 (n = 119), we looked for correlations between 25OHD and all liver function tests and in Group 2 (n = 230) the correlation between 25OHD and BALP.ResultsIn Group 1, we found no correlation between 25OHD and AST (r = − 0.03; p = 0.8), ALT (r = − 0.02; p = 0.91), GGT (r = − 0.08; p = 0.68), direct bilirubin (r = − 0.02; p = 0.89), indirect bilirubin (r = − 0.24; p = 0.21), and total bilirubin (r = − 0.24; p = 0.21) but one between 25OHD and ALP (r = − 0.2; p = 0.007); in Group 2, we found a significant negative correlation between 25-OHD and BALP (r = − 0.2; p = 0.0008).ConclusionsThe correlations that we found suggest that ALP and BALP might be involved in the regulation of vitamin D-25-hydroxylase activity, but further studies are mandatory to confirm our assumptions.

Association of Fibroblast Growth Factor 23 With Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study.

Fibroblast growth factor 23 (FGF23), which is involved in the regulation of vitamin D, is an emerging independent risk factor for cardiovascular diseases. Previous studies have demonstrated a positive association between FGF23 and stroke. In this study, we aimed to assess the association of FGF23 with ischemic stroke and its subtypes by applying a Mendelian randomization (MR) framework. Five genetic variants obtained from a genome-wide association study involving 16,624 European subjects were used as valid instruments of circulating FGF23 levels. MR was applied to infer the causality of FGF23 levels and the risk of ischemic stroke using data from the MEGASTROKE consortium. Subsequently, several MR analyses, including inverse-variance weighted meta-analysis, MR-Egger, weighted median estimate (WME), MR Pleiotropy Residual Sum and Outlier were performed. The heterogeneity test analysis, including Cochran’s Q, I2 test and leave-one-out analysis were also applied. Furthermore, potential horizontal/vertical pleiotropy was assessed. Lastly, the power of MR analysis was tested. Three validated variants were found to be associated with circulating FGF23 levels and were used for further investigation. We found that high expression level of FGF23 was not associated with any ischemic stroke. However, a causal association between genetically predicted FGF23 levels and the risk of large-artery atherosclerotic stroke (LAS) was significant, with an odds ratio of 1.74 (95% confidence interval = 1.08–2.81) per standard deviation increase in circulating FGF23 levels. Our findings provide support for the causal association between FGF23 and LAS, and therefore, offer potential therapeutic targets for LAS. The specific roles of FGF23 in LAS and associated molecules require further investigation.