BACKGROUND Obesity and type 2 diabetes mellitus(T2DM)are frequent co-occurring disorders that affect regular metabolic functions.Obesity has also been linked to an inc-reased risk of developing diabetes.Obesity and di...BACKGROUND Obesity and type 2 diabetes mellitus(T2DM)are frequent co-occurring disorders that affect regular metabolic functions.Obesity has also been linked to an inc-reased risk of developing diabetes.Obesity and diabetes are on the rise,increa-sing healthcare costs and raising mortality rates.Research has revealed that the expression profile of microRNAs(miRNAs)changes as diabetes progresses.Fur-thermore,vitamin D may have an anti-obesity effect and inverse association with body weight and body mass index(BMI).Low vitamin D levels do not solely cause obesity,which could be a factor in the etiology of T2DM.METHODS This study included 210 participants,of which,82 were obese(BMI>30 kg/m2)without T2DM,28 were obese with T2DM,and 100 were healthy controls.BMI was evaluated and both fasting and postprandial blood glucose were used to confirm T2DM.Exosomal miRNA-200a and miRNA-200b expression were analyzed using real-time PCR using Taqman probes,and vitamin-D levels were evaluated using an electrochemiluminescence-based immunoassay technique.All data analyses were performed using SPSS 20.0 and GraphPad Prism 5 software.RESULTS Overall,a 2.20-and 4.40-fold increase in miRNA-200a and miRNA-200b expression was observed among participants compared to healthy controls.MiRNA-200a and miRNA-200b expression among obese participants increased 2.40-fold and 3.93-fold,respectively,while in obese T2DM participants these values were 2.67-fold,and 5.78-fold,respectively,and these differences were found to be statistically significant(P=0.02)(P<0.0001).Obese participants showed a vitamin D level of 34.27 ng/mL,while in obese-T2DM participants vitamin D level was 22.21 ng/mL(P<0.0001).Vitamin D was negatively correlated with miRNA-200a(r=-0.22,P=0.01)and miRNA-200b(r=-0.19,P=0.04).MiRNA-200a sensitivity was 75%,and specificity was 57%,with a cutoff value of 2.07-fold.MiRNA-200b sensitivity was 75%,and specificity was 71%with a cutoff value of 4.12-fold,suggesting that miRNA-200a and miRNA-200b with an increased expression of 2.07-and 4.12-fold could be predictive indicators for the risk of diabetes in obese participants.CONCLUSION MiRNA-200a and miRNA-200b were higher in diabetic obese participants vs non-diabetic obese participants,and insufficient vitamin D levels in obese T2DM participants may be involved in poor clinical outcome.展开更多
No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues...No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD patients.Thereby,the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.Total extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs.VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques.VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice.The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.展开更多
基金Supported by The Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia,for funding this research work through the project number ISP-24.,Jazan University,Jazan 82817,Saudi Arabia.
文摘BACKGROUND Obesity and type 2 diabetes mellitus(T2DM)are frequent co-occurring disorders that affect regular metabolic functions.Obesity has also been linked to an inc-reased risk of developing diabetes.Obesity and diabetes are on the rise,increa-sing healthcare costs and raising mortality rates.Research has revealed that the expression profile of microRNAs(miRNAs)changes as diabetes progresses.Fur-thermore,vitamin D may have an anti-obesity effect and inverse association with body weight and body mass index(BMI).Low vitamin D levels do not solely cause obesity,which could be a factor in the etiology of T2DM.METHODS This study included 210 participants,of which,82 were obese(BMI>30 kg/m2)without T2DM,28 were obese with T2DM,and 100 were healthy controls.BMI was evaluated and both fasting and postprandial blood glucose were used to confirm T2DM.Exosomal miRNA-200a and miRNA-200b expression were analyzed using real-time PCR using Taqman probes,and vitamin-D levels were evaluated using an electrochemiluminescence-based immunoassay technique.All data analyses were performed using SPSS 20.0 and GraphPad Prism 5 software.RESULTS Overall,a 2.20-and 4.40-fold increase in miRNA-200a and miRNA-200b expression was observed among participants compared to healthy controls.MiRNA-200a and miRNA-200b expression among obese participants increased 2.40-fold and 3.93-fold,respectively,while in obese T2DM participants these values were 2.67-fold,and 5.78-fold,respectively,and these differences were found to be statistically significant(P=0.02)(P<0.0001).Obese participants showed a vitamin D level of 34.27 ng/mL,while in obese-T2DM participants vitamin D level was 22.21 ng/mL(P<0.0001).Vitamin D was negatively correlated with miRNA-200a(r=-0.22,P=0.01)and miRNA-200b(r=-0.19,P=0.04).MiRNA-200a sensitivity was 75%,and specificity was 57%,with a cutoff value of 2.07-fold.MiRNA-200b sensitivity was 75%,and specificity was 71%with a cutoff value of 4.12-fold,suggesting that miRNA-200a and miRNA-200b with an increased expression of 2.07-and 4.12-fold could be predictive indicators for the risk of diabetes in obese participants.CONCLUSION MiRNA-200a and miRNA-200b were higher in diabetic obese participants vs non-diabetic obese participants,and insufficient vitamin D levels in obese T2DM participants may be involved in poor clinical outcome.
基金supported by the National Natural Science Key Foundation of China(No.81830040 and 82130042 to ZJ Zhang)China Science and Technology Innovation 2030-Major Project(China)(No.2022ZD0211701,2022ZD0211700 and 2021ZD0200700 to ZJ Zhang)+2 种基金Science and Technology Program of Guangdong,China(No.2018B030334001 to ZJ Zhang)Science and Technology Program of Shenzhen,China(No.GJHZ20210705141400002,KCXFZ20211020164543006,JCYJ20220818101615033 and ZDSYS20220606100606014 to ZJ Zhang)The National Natural Science Foundation of China(No.U20A6005 to ZQM).
文摘No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD patients.Thereby,the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.Total extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs.VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques.VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice.The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.
