Objective Statins inhibit hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase activity and lower total serum cholesterol levels. We investigated the effects of Pravastatin on neuroprotection and neurogenesis in the...Objective Statins inhibit hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase activity and lower total serum cholesterol levels. We investigated the effects of Pravastatin on neuroprotection and neurogenesis in the dentate gyrus （DG）, subventricular zone （SVZ） and striatum after cerebral ischemia in rats. Methods The filament method was used for temporary middle cerebral artery occlusion （tMCAO）. Pravastatin or saline post-ischemically were administered at subsequent time points： 6 h after tMCAO, and then on every subsequent day up to day 14 after tMCAO. Neurological outcome was investigated by using a neuroscore, the beam balance test and the rotarod test. Cholesterol and triglycerides levels were determined by blood sample analysis prior to sacrifice. Infarct area was calculated by microtubule-associated protein 2 （MAP2） staining. Neurogenesis was evaluated by triple staining with bromodeoxyuridine （BrdU）, doublecortin （DCX）, and neuronal nuclei （NeuN）. Results Compared with the control groups, Pravastatin treated animals were significantly improved in neurological outcome in rotarod test, with smaller infarct size. Pravastatin increased BrdU- positive cells number in the DG （P = 0.0029） and the SVZ （P = 0.0280） but not in the striatum （P = 0.3929）. Furthermore, Pravastatin increased BrdU-labeled DCX positive cells number in the DG （P = 0.0031）, SVZ （P = 0.0316） and striatum （P = 0.0073）. We also observed a DCX-positive cells stream from the SVZ to the striatum, suggesting a migration route of those immature neurons. No significant differences of total serum cholesterol and triglycerides were observed between groups. Conclusion The Pravastatin administration strategy is safe and could promote neurological recovery in ischemic stroke. Pravastatin induces neurogenesis in the DG and SVZ, and increases the number of migration cells in the striatum. These effects are independent of the cholesterol-lowering property of Pravastatin.展开更多
Background:Individuals at risk of suffering cardiovascular disease(CVD) present with larger increases in blood trigyceride(TG) concentration after a high-fat meal than do healthy individuals.These postprandial hypertr...Background:Individuals at risk of suffering cardiovascular disease(CVD) present with larger increases in blood trigyceride(TG) concentration after a high-fat meal than do healthy individuals.These postprandial hypertriglyceride levels are an independent risk factor for CVD.Prescription of statins and a bout of prolonged exercise are both effective in lowering postprandial hypertriglyceride levels.We aimed to evaluate the comparative effectiveness of statins vs.a bout of aerobic exercise in reducing fasting and postprandial TG(PPTG) concentrations in indiv、duals at high nsk of developing CVD.Methods:Thirty-seven sltudies from a systematic literature search of the PubMed,EMBASE,and Cochrane databases were included in this review.The selected studies conducted trials involving statin therapy(n=20) or a bout of aerobic exercise(n=19) and measured their impact on PPTG levels as the outcome.Two studies analyzed both treatments and were included in duplicate.The meta-analysis was constructed using a random-effects model to calculate the mean difference(MD).The Student t test was used to compare the data sets for statins vs.exercise.Results:Overall,statin and exercise interventions showed similar reductions in PPTG levels,with an MD of-0.65 mmol/L for statins(95% confidence interval(95%CI):-0.54 to-0.77;p <0.001) and-0.46 mmol/L for exercise(95%CI:-0.21 to-0.71;p <0.01).However,statins lowered fasting TG levels more than exercise(MD=-1.54 mmol/L,95%CI:-2.25 to-0.83;p=0.009).Conclusion:Although aerobic exercise is effective in lowering blood TG levels,statins seem to be more efficient,especially in the fasted state.A combination of exercise and statins might reveal a valuable approach to the treatment and prevention of CVD.More studies are required to determine the underlying mechanisms and the possible additive effects of these interventions.展开更多
BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus(T2DM).Statin and metformin are commonly used medications in T2DM patients,and some studies showed statin-or metformin-induced neuropat...BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus(T2DM).Statin and metformin are commonly used medications in T2DM patients,and some studies showed statin-or metformin-induced neuropathy.AIM To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies.METHODS Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used.Patients with T2DM and no complications were divided into statin/metformin/statin+metformin users and non-users.Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems,10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants.Logistic regression analyses were conducted to examine the associations between statin/metformin/statin+metformin therapies and the incidence of neuropathy.Propensity score(PS)matching was performed on the basis of age,sex and comorbidities.RESULTS Overall,34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017,respectively.Statin therapy was associated with increased risks of neuropathy in 2016 and 2017[PS-matched odds ratio(OR)=1.22,95%confidence interval(CI):1.08-1.38;PS-matched OR=1.17,95%CI:1.03-1.33,respectively].Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017(PS-matched OR=0.30,95%CI:0.21-0.42;PSmatched OR=0.44,95%CI:0.32-0.60,respectively).Combined statin+metformin therapy was not significantly associated with neuropathy in 2016 or 2017(PSmatched OR=0.85,95%CI:0.61-1.19;PS-matched OR=0.95,95%CI:0.66-1.38,respectively).CONCLUSION Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM,but metformin therapy showed the opposite association.展开更多
Background The survival ratio of implanted mesenchymal stem cells （MSCs） in the infarcted myocardium is low.Autophagy is a complex self-eating process and can be utilized for cell survival. We have found that atorva...Background The survival ratio of implanted mesenchymal stem cells （MSCs） in the infarcted myocardium is low.Autophagy is a complex self-eating process and can be utilized for cell survival. We have found that atorvastatin （ATV）can effectively activate autophagy to enhance MSCs survival during hypoxia and serum deprivation （H/SD）. The mitogen-activated protein kinase/extracellular signal-regulated kinase （MEK/ERK） pathway is a non-canonical autophagy pathway.We hypothesized that the MEK/ERK pathway mediated ATV-induced autophagy of MSCs under H/SD.展开更多
Background Well designed randomized trials and meta-analyses have clearly shown that statins reduce the risk of major vascular events, including ischemic stroke, in a wide range of patients and their routine use is re...Background Well designed randomized trials and meta-analyses have clearly shown that statins reduce the risk of major vascular events, including ischemic stroke, in a wide range of patients and their routine use is recommended for patients at an increased cardiovascular risk. Survivors of a first ischemic stroke are at a risk of recurrence and of other vascular events and statins are generally recommended to reduce this risk. This study investigated how widely statins were being used for such patients in China. Methods Totally 6422 patients with a history of ischemic stroke were identified by reviewing medical records at 51 highest-ranking hospitals in 14 cities in China, and invited to attend a screening clinic to assess eligibility for a randomized trial. Their current statin and other drug uses were recorded alongside clinical and demographic characteristics. Univariate chi-square test and multivariate Logistic regression were used to determine the factors associated with treatment. Results Only 24% of these patients reported currently taking a statin. The most important predictor of statin use among these patients was prior history of coronary heart disease. History of diabetes or hypertension, as well as treated in university affiliated hospitals is related to increased use. The status had improved significantly during a 2-year period. Atorvastatin （40%） and simvastatin （39%） were the most commonly used. Conclusions In China, statins are still underused for secondary prevention among survivors of ischemic stroke. Reasons for this Door use need to be understood in order to increase use of these evidence based therapies.展开更多
文摘Objective Statins inhibit hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase activity and lower total serum cholesterol levels. We investigated the effects of Pravastatin on neuroprotection and neurogenesis in the dentate gyrus （DG）, subventricular zone （SVZ） and striatum after cerebral ischemia in rats. Methods The filament method was used for temporary middle cerebral artery occlusion （tMCAO）. Pravastatin or saline post-ischemically were administered at subsequent time points： 6 h after tMCAO, and then on every subsequent day up to day 14 after tMCAO. Neurological outcome was investigated by using a neuroscore, the beam balance test and the rotarod test. Cholesterol and triglycerides levels were determined by blood sample analysis prior to sacrifice. Infarct area was calculated by microtubule-associated protein 2 （MAP2） staining. Neurogenesis was evaluated by triple staining with bromodeoxyuridine （BrdU）, doublecortin （DCX）, and neuronal nuclei （NeuN）. Results Compared with the control groups, Pravastatin treated animals were significantly improved in neurological outcome in rotarod test, with smaller infarct size. Pravastatin increased BrdU- positive cells number in the DG （P = 0.0029） and the SVZ （P = 0.0280） but not in the striatum （P = 0.3929）. Furthermore, Pravastatin increased BrdU-labeled DCX positive cells number in the DG （P = 0.0031）, SVZ （P = 0.0316） and striatum （P = 0.0073）. We also observed a DCX-positive cells stream from the SVZ to the striatum, suggesting a migration route of those immature neurons. No significant differences of total serum cholesterol and triglycerides were observed between groups. Conclusion The Pravastatin administration strategy is safe and could promote neurological recovery in ischemic stroke. Pravastatin induces neurogenesis in the DG and SVZ, and increases the number of migration cells in the striatum. These effects are independent of the cholesterol-lowering property of Pravastatin.
基金funded by a grant from the Spanish Ministry of Economy and Competitiveness (DEP-2017-83244R)the European Economic Community。
文摘Background:Individuals at risk of suffering cardiovascular disease(CVD) present with larger increases in blood trigyceride(TG) concentration after a high-fat meal than do healthy individuals.These postprandial hypertriglyceride levels are an independent risk factor for CVD.Prescription of statins and a bout of prolonged exercise are both effective in lowering postprandial hypertriglyceride levels.We aimed to evaluate the comparative effectiveness of statins vs.a bout of aerobic exercise in reducing fasting and postprandial TG(PPTG) concentrations in indiv、duals at high nsk of developing CVD.Methods:Thirty-seven sltudies from a systematic literature search of the PubMed,EMBASE,and Cochrane databases were included in this review.The selected studies conducted trials involving statin therapy(n=20) or a bout of aerobic exercise(n=19) and measured their impact on PPTG levels as the outcome.Two studies analyzed both treatments and were included in duplicate.The meta-analysis was constructed using a random-effects model to calculate the mean difference(MD).The Student t test was used to compare the data sets for statins vs.exercise.Results:Overall,statin and exercise interventions showed similar reductions in PPTG levels,with an MD of-0.65 mmol/L for statins(95% confidence interval(95%CI):-0.54 to-0.77;p <0.001) and-0.46 mmol/L for exercise(95%CI:-0.21 to-0.71;p <0.01).However,statins lowered fasting TG levels more than exercise(MD=-1.54 mmol/L,95%CI:-2.25 to-0.83;p=0.009).Conclusion:Although aerobic exercise is effective in lowering blood TG levels,statins seem to be more efficient,especially in the fasted state.A combination of exercise and statins might reveal a valuable approach to the treatment and prevention of CVD.More studies are required to determine the underlying mechanisms and the possible additive effects of these interventions.
基金Supported by the Konkuk University Medical Center Research Grant 2020.
文摘BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus(T2DM).Statin and metformin are commonly used medications in T2DM patients,and some studies showed statin-or metformin-induced neuropathy.AIM To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies.METHODS Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used.Patients with T2DM and no complications were divided into statin/metformin/statin+metformin users and non-users.Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems,10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants.Logistic regression analyses were conducted to examine the associations between statin/metformin/statin+metformin therapies and the incidence of neuropathy.Propensity score(PS)matching was performed on the basis of age,sex and comorbidities.RESULTS Overall,34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017,respectively.Statin therapy was associated with increased risks of neuropathy in 2016 and 2017[PS-matched odds ratio(OR)=1.22,95%confidence interval(CI):1.08-1.38;PS-matched OR=1.17,95%CI:1.03-1.33,respectively].Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017(PS-matched OR=0.30,95%CI:0.21-0.42;PSmatched OR=0.44,95%CI:0.32-0.60,respectively).Combined statin+metformin therapy was not significantly associated with neuropathy in 2016 or 2017(PSmatched OR=0.85,95%CI:0.61-1.19;PS-matched OR=0.95,95%CI:0.66-1.38,respectively).CONCLUSION Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM,but metformin therapy showed the opposite association.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81170129 and No. 81000091）, the China Health Medical Development Foundation （No. 2011-H25）, the Research Fund of Capital Medical Development （No. 2007-2018）, 863 Program of China （No. 2011AA020110）, and the Postgraduates＇ Innovative Research Foundation of Peking Union Medical College （2012-1002-31）.
文摘Background The survival ratio of implanted mesenchymal stem cells （MSCs） in the infarcted myocardium is low.Autophagy is a complex self-eating process and can be utilized for cell survival. We have found that atorvastatin （ATV）can effectively activate autophagy to enhance MSCs survival during hypoxia and serum deprivation （H/SD）. The mitogen-activated protein kinase/extracellular signal-regulated kinase （MEK/ERK） pathway is a non-canonical autophagy pathway.We hypothesized that the MEK/ERK pathway mediated ATV-induced autophagy of MSCs under H/SD.
文摘Background Well designed randomized trials and meta-analyses have clearly shown that statins reduce the risk of major vascular events, including ischemic stroke, in a wide range of patients and their routine use is recommended for patients at an increased cardiovascular risk. Survivors of a first ischemic stroke are at a risk of recurrence and of other vascular events and statins are generally recommended to reduce this risk. This study investigated how widely statins were being used for such patients in China. Methods Totally 6422 patients with a history of ischemic stroke were identified by reviewing medical records at 51 highest-ranking hospitals in 14 cities in China, and invited to attend a screening clinic to assess eligibility for a randomized trial. Their current statin and other drug uses were recorded alongside clinical and demographic characteristics. Univariate chi-square test and multivariate Logistic regression were used to determine the factors associated with treatment. Results Only 24% of these patients reported currently taking a statin. The most important predictor of statin use among these patients was prior history of coronary heart disease. History of diabetes or hypertension, as well as treated in university affiliated hospitals is related to increased use. The status had improved significantly during a 2-year period. Atorvastatin （40%） and simvastatin （39%） were the most commonly used. Conclusions In China, statins are still underused for secondary prevention among survivors of ischemic stroke. Reasons for this Door use need to be understood in order to increase use of these evidence based therapies.
