We enrolled 23 Japanese men (age: 76.0 ± 8.7) and 17 women (age: 78.3 ± 9.3) in this study. The physical function of even a person getting on a wheelchair could be tested in all subjects. Blood was collected...We enrolled 23 Japanese men (age: 76.0 ± 8.7) and 17 women (age: 78.3 ± 9.3) in this study. The physical function of even a person getting on a wheelchair could be tested in all subjects. Blood was collected by venipuncture and the serum 1, 25-hydroxy vitamin D (1, 25OHD) concentration was measured. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment-Japanese version (MoCA-J) was used for the cognitive function test. Physical function was measured objectively using the Timed UP and Go (TUG) and 4-m walking test (4MWS). A significant positive correlation was found between serum 1, 25OHD and MMSE or MoCA-J. It is expected that an elderly person can maintain a mean serum 1, 25OHD level of about 100 pg/mL for preventing early cognitive disorder. In the present study, a significant positive correlation was found between urinary 25-hydroxy vitamin D (25OHD)/creatinine and MMSE or MoCA-J. Our results showed that urinary 25OHD might be a useful biomarker for predicting cognitive disorder. There was a significant negative correlation between serum 1, 25OHD and TUG or 4MWS. These findings suggest that serum 1, 25OHD levels might serve as a useful index to improve cognitive and physical functional impairment.展开更多
AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incub...AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25（OH）2D3 or with 1 umol/L 1α-25（OH）2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25（OH）2D3 or 1α-25（OH）2D3. 1α-25（OH）2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25（OH）2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS： Both butyrate and 1α-25（OH）2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25（OH）2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25（OH）2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION： Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25（OH）2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25（OH）2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.展开更多
Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D...Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.展开更多
BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship bet...BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce.AIM To explore a possible causal link between cataracts and vitamin D.METHODS In this study,we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization.Our analytical approach included inverse-variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode methods.The primary analyses utilized IVW with random effects,supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger.MR-Egger was also applied for pleiotropy testing.Additionally,a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms.RESULTS The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts(OR=1.11,95%CI:1.00-1.22;P=0.032).The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity(P>0.05),and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis(P>0.05).Furthermore,a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms.CONCLUSION There is a potential causal link between 25-(OH)D levels and the development of cataracts,suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation.Further experimental research is required to confirm these findings.展开更多
Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Le...Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Leukoaraiosis(LA)is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses.This study aimed to investigate the impact of vitamin D on the severity of LA.Methods:Patients with LA were categorized based on 3.0 T brain MRI findings into mild(N=43),moderate(N=40),or severe groups(N=29)using the Fazekas scale(scoring 1-6).A control group consisting of 41 healthy individuals was included.Serum fibrinogen C,homocysteine,plasma 25-hydroxyvitamin D,and intercellular cell adhesion molecule-1(ICAM-1)levels were measured using ELISA.Results:All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group,with a more pronounced decrease observed as LA severity increased.Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA(P<0.05)according to Multiple logistic regression analysis.Additionally,a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1.Conclusions:Disease severity positively correlated with levels of the inflammatory marker ICAM-1,worsening as plasma 25-hydroxyvitamin D concentration decreased.Low 25-hydroxyvitamin D emerged as an independent risk factor for LA,potentially exacerbating the inflammatory response.These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.展开更多
Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T...Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.展开更多
文摘We enrolled 23 Japanese men (age: 76.0 ± 8.7) and 17 women (age: 78.3 ± 9.3) in this study. The physical function of even a person getting on a wheelchair could be tested in all subjects. Blood was collected by venipuncture and the serum 1, 25-hydroxy vitamin D (1, 25OHD) concentration was measured. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment-Japanese version (MoCA-J) was used for the cognitive function test. Physical function was measured objectively using the Timed UP and Go (TUG) and 4-m walking test (4MWS). A significant positive correlation was found between serum 1, 25OHD and MMSE or MoCA-J. It is expected that an elderly person can maintain a mean serum 1, 25OHD level of about 100 pg/mL for preventing early cognitive disorder. In the present study, a significant positive correlation was found between urinary 25-hydroxy vitamin D (25OHD)/creatinine and MMSE or MoCA-J. Our results showed that urinary 25OHD might be a useful biomarker for predicting cognitive disorder. There was a significant negative correlation between serum 1, 25OHD and TUG or 4MWS. These findings suggest that serum 1, 25OHD levels might serve as a useful index to improve cognitive and physical functional impairment.
基金Supported by the Else Kroner-Fresenius Foundation, Bad Homburg, Germany
文摘AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25（OH）2D3 or with 1 umol/L 1α-25（OH）2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25（OH）2D3 or 1α-25（OH）2D3. 1α-25（OH）2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25（OH）2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS： Both butyrate and 1α-25（OH）2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25（OH）2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25（OH）2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION： Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25（OH）2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25（OH）2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.
基金funded by the Nactional Natural Science Foundation of China(81872618)。
文摘Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.
文摘BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce.AIM To explore a possible causal link between cataracts and vitamin D.METHODS In this study,we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization.Our analytical approach included inverse-variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode methods.The primary analyses utilized IVW with random effects,supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger.MR-Egger was also applied for pleiotropy testing.Additionally,a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms.RESULTS The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts(OR=1.11,95%CI:1.00-1.22;P=0.032).The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity(P>0.05),and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis(P>0.05).Furthermore,a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms.CONCLUSION There is a potential causal link between 25-(OH)D levels and the development of cataracts,suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation.Further experimental research is required to confirm these findings.
基金This work was supported by the National Natural Science Foundation of Heilongjiang Province of China(No.LH2020H051)Key R&D projects of Natural Science Foundation of Heilongjiang Province(No.2023ZX06C03)Foundation of Harbin Science Technology Bureau of China(No.2014RFQGJ042).
文摘Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Leukoaraiosis(LA)is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses.This study aimed to investigate the impact of vitamin D on the severity of LA.Methods:Patients with LA were categorized based on 3.0 T brain MRI findings into mild(N=43),moderate(N=40),or severe groups(N=29)using the Fazekas scale(scoring 1-6).A control group consisting of 41 healthy individuals was included.Serum fibrinogen C,homocysteine,plasma 25-hydroxyvitamin D,and intercellular cell adhesion molecule-1(ICAM-1)levels were measured using ELISA.Results:All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group,with a more pronounced decrease observed as LA severity increased.Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA(P<0.05)according to Multiple logistic regression analysis.Additionally,a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1.Conclusions:Disease severity positively correlated with levels of the inflammatory marker ICAM-1,worsening as plasma 25-hydroxyvitamin D concentration decreased.Low 25-hydroxyvitamin D emerged as an independent risk factor for LA,potentially exacerbating the inflammatory response.These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.
基金supported by the National Natural Science Foundation of China(No.82120108008,No.91857117)the Project of Biobank(No.YBKA201909)from Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicinea grant from Shanghai Jiaotong University School of Medicine(No.19XJ11007).
文摘Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.
