Post-resuscitation myocardial dysfunction(PRMD)is the most severe myocardial ischemia-reperfusion injury(MIRI)and is characterized by difficult treatment and poor prognosis.Research has shown the protective effects of...Post-resuscitation myocardial dysfunction(PRMD)is the most severe myocardial ischemia-reperfusion injury(MIRI)and is characterized by difficult treatment and poor prognosis.Research has shown the protective effects of the rational use of ivabradine(IVA)against PRMD,however,the molecular mechanisms of IVA remain unknown.In this study,an ischemia-reperfusion injury(IRI)model was established using hypoxic chambers.The results demonstrated that pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis.IVA attenuated mitochondrial damage,eliminated excess reactive oxygen species(ROS),suppressed IRI-induced ATP and NAD+,and increased the AMP/ATP ratio.We further found that IVA increased the mRNA levels of sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α)and upregulated the expression levels of phosphorylated AMP-activated protein kinase(p-AMPK)/AMPK,SIRT1,and PGC-1αproteins.Interestingly,no change in AMPK mRNA levels was observed.Cardiomyocyte energy metabolism significantly changed after IRI.The aim of this study was to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1αsignaling pathway in myocardial ischemia/reperfusion injury-induced in H9c2 cell.展开更多
Many common diseases are characterized by polygenic architectures in which a single variant has only a small effect on phenotype.Genome-wide association studies and next generation sequencing have identified thousands...Many common diseases are characterized by polygenic architectures in which a single variant has only a small effect on phenotype.Genome-wide association studies and next generation sequencing have identified thousands of genetic variants of disease susceptibility.Recently,non-coding variants identified by genome-wide association studies have been systematically reviewed.Here,we review disease-causing coding variants and their relevance to clinical medicine.展开更多
studies have suggested that non-optimal temperatures may increase the risk of injury,epidemiological studies focusing on the association between temperature and non-fatal injury among children and adolescents are limi...studies have suggested that non-optimal temperatures may increase the risk of injury,epidemiological studies focusing on the association between temperature and non-fatal injury among children and adolescents are limited.Therefore,we investigated the short-term effect of ambient temperature on non-fatal falls and road traffic injuries(RTIs)among students across Jiangsu Province,China.Meteorological data and records of non-fatal outdoor injuries due to falls and RTIs among students aged 6–17 were collected during 2018–2020.We performed a time-stratified case-crossover analysis with a distributed lag nonlinear model to examine the effect of ambient temperature on the risk of injury.Individual meteorological exposure was estimated based on the address of the selected school.We also performed stratified analyses by sex,age,and area.A total of 57322 and 5455 cases of falls and RTIs were collected,respectively.We observed inverted U-shaped curves for temperatureinjury associations,with maximum risk temperatures at 18℃(48th of daily mean temperature distribution)for falls and 22℃(67th of daily mean temperature distribution)for RTIs.The corresponding odds ratios(95%confidence intervals)were 2.193(2.011,2.391)and 3.038(1.988,4.644)for falls and RTIs,respectively.Notably,there was a significant age-dependent trend in which the temperature effect on falls was greater in older students(P-trend<0.05).This study suggests a ignificant association between ambient temperature and students’outdoor falls and RTIs.Our findings may help advance tailored strategies to reduce the incidence of outdoor falls and RTIs in children and adolescents.展开更多
基金the National Natural Science Foundation Youth Science Foundation(No.81601661)the Science Foundation for Post-doctoral researchers in Anhui Province of China(No.2016B140).
文摘Post-resuscitation myocardial dysfunction(PRMD)is the most severe myocardial ischemia-reperfusion injury(MIRI)and is characterized by difficult treatment and poor prognosis.Research has shown the protective effects of the rational use of ivabradine(IVA)against PRMD,however,the molecular mechanisms of IVA remain unknown.In this study,an ischemia-reperfusion injury(IRI)model was established using hypoxic chambers.The results demonstrated that pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis.IVA attenuated mitochondrial damage,eliminated excess reactive oxygen species(ROS),suppressed IRI-induced ATP and NAD+,and increased the AMP/ATP ratio.We further found that IVA increased the mRNA levels of sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α)and upregulated the expression levels of phosphorylated AMP-activated protein kinase(p-AMPK)/AMPK,SIRT1,and PGC-1αproteins.Interestingly,no change in AMPK mRNA levels was observed.Cardiomyocyte energy metabolism significantly changed after IRI.The aim of this study was to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1αsignaling pathway in myocardial ischemia/reperfusion injury-induced in H9c2 cell.
基金This work was financially supported by the National Natural Science Foundation of China(No.81130031).
文摘Many common diseases are characterized by polygenic architectures in which a single variant has only a small effect on phenotype.Genome-wide association studies and next generation sequencing have identified thousands of genetic variants of disease susceptibility.Recently,non-coding variants identified by genome-wide association studies have been systematically reviewed.Here,we review disease-causing coding variants and their relevance to clinical medicine.
文摘studies have suggested that non-optimal temperatures may increase the risk of injury,epidemiological studies focusing on the association between temperature and non-fatal injury among children and adolescents are limited.Therefore,we investigated the short-term effect of ambient temperature on non-fatal falls and road traffic injuries(RTIs)among students across Jiangsu Province,China.Meteorological data and records of non-fatal outdoor injuries due to falls and RTIs among students aged 6–17 were collected during 2018–2020.We performed a time-stratified case-crossover analysis with a distributed lag nonlinear model to examine the effect of ambient temperature on the risk of injury.Individual meteorological exposure was estimated based on the address of the selected school.We also performed stratified analyses by sex,age,and area.A total of 57322 and 5455 cases of falls and RTIs were collected,respectively.We observed inverted U-shaped curves for temperatureinjury associations,with maximum risk temperatures at 18℃(48th of daily mean temperature distribution)for falls and 22℃(67th of daily mean temperature distribution)for RTIs.The corresponding odds ratios(95%confidence intervals)were 2.193(2.011,2.391)and 3.038(1.988,4.644)for falls and RTIs,respectively.Notably,there was a significant age-dependent trend in which the temperature effect on falls was greater in older students(P-trend<0.05).This study suggests a ignificant association between ambient temperature and students’outdoor falls and RTIs.Our findings may help advance tailored strategies to reduce the incidence of outdoor falls and RTIs in children and adolescents.
