Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,e...Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,exercisebehavior,lipofuscin content,antioxidative stress ability,swallowing frequency,body-bending frequency,and head-swinging ability of C.elegans.Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments,the effects of CGA on ROS levels,antioxidant enzyme activities,MDA content,mutant-strain lifespan,and anti-aging molecular signaling pathways were explored,as well as the underlying mechanisms.Results:CGA improved multiple indices of the nematode:body length was increased(all P<0.001),head-swing frequency and body-bending frequency were increased(all P<0.05),nematode longevity was prolonged(P=0.0021),lipofuscin deposition in nematodes was slowed down(all P<0.001),the chemotaxis index was improved(P=0.0012),ROS levels were reduced(all P<.001),and SOD activity and MDA content were reduced(SOD:P=0.0017 between the low-concentration group and the control group,P<.001 between the high-concentration and medium-concentration groups and the control group;MDA:P=0.0135 between the low-concentration group and the control group,and P<0.001 between the high-concentration and medium-concentration groups and the control group).In addition,CGA also activated the DAF-16 transcription factor,promoted DAF-16 nuclear translocation under oxidative stress conditions(both P<0.001 between the high-concentration and medium-concentration groups and the control group),and increased SOD-3 gene expression in nematodes(all P<0.001).Conclusion:CGA plays an anti-aging role in C.elegans.The underlying mechanisms include activation of the insulin/IGF-1 signaling pathway and enhancement of DAF-16 activity.This study lays a foundation for further research into the anti-aging effects of CGA.展开更多
BACKGROUND Left atrial(LA)enlargement is a marker of increased risk in the general population undergoing stress echocardiography.African American(AA)patients with hypertension are known to have less atrial remodeling ...BACKGROUND Left atrial(LA)enlargement is a marker of increased risk in the general population undergoing stress echocardiography.African American(AA)patients with hypertension are known to have less atrial remodeling than whites with hypertension.The prognostic impact of LA enlargement in AA with hypertension undergoing stress echocardiography is uncertain.AIM To investigate the prognostic value of LA size in hypertensive AA patients undergoing stress echocardiography.METHODS This retrospective outcomes study enrolled 583 consecutive hypertensive AA patients who underwent stress echocardiography over a 2.5-year period.Clinical characteristics including cardiovascular risk factors,stress and echocardiographic data were collected from the electronic health record of a large community hospital.Treadmill exercise and Dobutamine protocols were conducted based on standard practices.Patients were followed for all-cause mortality.The optimal cutoff value of antero-posterior LA diameter for mortality was assessed by receiver operating characteristic analysis.Cox regression was used to determine variables associated with outcome.RESULTS The mean age was 57±12 years.LA dilatation was present in 9%(54)of patients(LA anteroposterior≥2.4 cm/m^(2)).There were 85 deaths(15%)during 4.5±1.7 years of follow-up.LA diameter indexed for body surface area had an area under the curve of 0.72±0.03(optimal cut-point of 2.05 cm/m^(2)).Variables independently associated with mortality included age[P=0.004,hazard ratio(HR)1.34(1.10-1.64)],tobacco use[P=0.001,HR 2.59(1.51-4.44)],left ventricular hypertrophy[P=0.001,HR 2.14(1.35-3.39)],Dobutamine stress[P=0.003,HR 2.12(1.29-3.47)],heart failure history[P=0.031,HR 1.76(1.05-2.94)],LA diameter≥2.05 cm/m^(2)[P=0.027,HR 1.73(1.06-2.82)],and an abnormal stress echocardiogram[P=0.033,HR 1.67(1.04-2.68)].LA diameter as a continuous variable was also independently associated with mortality but LA size≥2.40 cm/m^(2) was not.CONCLUSION LA enlargement is infrequent in hypertensive AA patients when traditional reference values are used.LA enlargement is independently associated with mortality when a lower than“normal”threshold(≥2.05 cm/m^(2))is used.展开更多
Background: Cardiovascular involvement among patients with primary systemic amyloidosis (AL) is common and predicts poor prognosis. Different parameters have been used to predict outcome. We studied the prognostic sig...Background: Cardiovascular involvement among patients with primary systemic amyloidosis (AL) is common and predicts poor prognosis. Different parameters have been used to predict outcome. We studied the prognostic significance of clinical, ECG and echocardiographic parameters of 60 patients with tissue proven primary cardiac amyloidosis. Method and Results: Records of 60 patients with primary amyloidosis and cardiac involvement documented by endomyocardial tissue biopsy were retrospectively evaluated. Patients mean age was 57.9 ± 10.2 years. 71.6% were male and 86.6% Caucasian. Patients’ median survival was 12.2 ± 4.4 months with only 50% of patients survived for more than 1 year. 60% of patients had CHF (NYHA II-IV). CHF (NYHA II-IV), IVS, LVPW and LVEF were significant on univariate survival analysis展开更多
Experimental, clinical and epidemiologic studies have provided strong evidence that physical training has beneficial effects on cardiovascular health. Numerous investigations have demonstrated that exercise increases ...Experimental, clinical and epidemiologic studies have provided strong evidence that physical training has beneficial effects on cardiovascular health. Numerous investigations have demonstrated that exercise increases coronary blood flow and myocardial perfusion. Importantly, training also can stimulate angiogenesis and accelerate collateral vessel growth in animal models with coronary artery occlusion. Cardiac adaptation such as increased vascularity or capillary density has been evidenced after regular endurance exercises. More recently, several studies indicate that physical training induces high levels of myocardial heat shock protein and antioxidant protein expression, which may play an important role in myocardial protection against ischemia-reperfusion injury.展开更多
Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac m uscle involvement. The aim of the present study was to determine whether familia l clustering is observed in the severity of muscle involv...Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac m uscle involvement. The aim of the present study was to determine whether familia l clustering is observed in the severity of muscle involvement in DM1. We evalua ted 51 sibling groups constituting 112 patients with geneticallyverified DM1. Th e siblings were similar to each other in age, cytosine-thymine-guanine (CTG) r epeat length, age at disease onset, muscular impairment rating score, and electr ocardiographic markers of cardiac conduction disease. After adjusting for the si milarities between siblings in age and CTG repeat length, the siblings remained similar to each other in measures of both skeletal and cardiac muscle involvemen t. These results suggest that factors other than CTG repeat length play a role i n the severity and progression of the degenerative skeletal and cardiac muscle d isease in DM1.展开更多
Background: Despite new therapies, the prevalence of heart failure continues to escalate. The prevalence of diabetes, a risk factor for heart failure, also continues to rise. To further understand the increasing preva...Background: Despite new therapies, the prevalence of heart failure continues to escalate. The prevalence of diabetes, a risk factor for heart failure, also continues to rise. To further understand the increasing prevalence of heart failure, we compared trends in the prevalence of diabetes among individuals with diagnosed heart failure versus those in the general population. Methods: Fourteen randomized trials between 1989 and 1999 including subjects with heart failure(n=34,633)were reviewed. For each trial, the enrollment date was used to estimate the yearly prevalence of diabetes among study participants with heart failure. The prevalence of diabetes in the general population was estimated based on United State’s Center for Disease Control statistics from 1989 to 1999. The prevalence of diabetes between heart failure subjects and the general population was compared using a two-sample t-test for independent samples with unequal variances. Results: The prevalence of diabetes increased from 2.6%to 4.0%from 1989 to 1999 in the general U.S. population. Among patients with heart failure, the prevalence of diabetes increased from 13%to 47%. Diabetes prevalence estimates varied significantly(p< 0.001) between the general population and individuals with heart failure during the study period. Conclusions: The rising prevalence of diabetes may partially explain the growing epidemic of heart failure. Increased efforts targeting diabetes and other cardiovascular risk factors are warranted in attenuating the rising prevalence of heart failure.展开更多
Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulat...Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown.Based on a screening panel,IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19.Supporting clinical data,administration of SARS-CoV-2 Spike 1(S1)glycoprotein or receptor-binding domain(RBD)proteins into human angiotensin-converting enzyme 2(hACE2)transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation(pNF-κB)and cardiopulmonary-derived IL-18 and NLRP3 expression.IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1-or RBD-exposed hACE2 mice.Through in vivo and in vitro work,both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species.Enhancing mitophagy prevented Spike protein-mediated IL-18 expression.Moreover,IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability.Overall,the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.展开更多
基金This study was supported by the Key Research Project Fund of Beijing University of Chinese Medicine(2021JYB2002001)the National Natural Science Foundation of Tibetan medicine Collabo-rative Innovation(82130113).
文摘Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,exercisebehavior,lipofuscin content,antioxidative stress ability,swallowing frequency,body-bending frequency,and head-swinging ability of C.elegans.Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments,the effects of CGA on ROS levels,antioxidant enzyme activities,MDA content,mutant-strain lifespan,and anti-aging molecular signaling pathways were explored,as well as the underlying mechanisms.Results:CGA improved multiple indices of the nematode:body length was increased(all P<0.001),head-swing frequency and body-bending frequency were increased(all P<0.05),nematode longevity was prolonged(P=0.0021),lipofuscin deposition in nematodes was slowed down(all P<0.001),the chemotaxis index was improved(P=0.0012),ROS levels were reduced(all P<.001),and SOD activity and MDA content were reduced(SOD:P=0.0017 between the low-concentration group and the control group,P<.001 between the high-concentration and medium-concentration groups and the control group;MDA:P=0.0135 between the low-concentration group and the control group,and P<0.001 between the high-concentration and medium-concentration groups and the control group).In addition,CGA also activated the DAF-16 transcription factor,promoted DAF-16 nuclear translocation under oxidative stress conditions(both P<0.001 between the high-concentration and medium-concentration groups and the control group),and increased SOD-3 gene expression in nematodes(all P<0.001).Conclusion:CGA plays an anti-aging role in C.elegans.The underlying mechanisms include activation of the insulin/IGF-1 signaling pathway and enhancement of DAF-16 activity.This study lays a foundation for further research into the anti-aging effects of CGA.
文摘BACKGROUND Left atrial(LA)enlargement is a marker of increased risk in the general population undergoing stress echocardiography.African American(AA)patients with hypertension are known to have less atrial remodeling than whites with hypertension.The prognostic impact of LA enlargement in AA with hypertension undergoing stress echocardiography is uncertain.AIM To investigate the prognostic value of LA size in hypertensive AA patients undergoing stress echocardiography.METHODS This retrospective outcomes study enrolled 583 consecutive hypertensive AA patients who underwent stress echocardiography over a 2.5-year period.Clinical characteristics including cardiovascular risk factors,stress and echocardiographic data were collected from the electronic health record of a large community hospital.Treadmill exercise and Dobutamine protocols were conducted based on standard practices.Patients were followed for all-cause mortality.The optimal cutoff value of antero-posterior LA diameter for mortality was assessed by receiver operating characteristic analysis.Cox regression was used to determine variables associated with outcome.RESULTS The mean age was 57±12 years.LA dilatation was present in 9%(54)of patients(LA anteroposterior≥2.4 cm/m^(2)).There were 85 deaths(15%)during 4.5±1.7 years of follow-up.LA diameter indexed for body surface area had an area under the curve of 0.72±0.03(optimal cut-point of 2.05 cm/m^(2)).Variables independently associated with mortality included age[P=0.004,hazard ratio(HR)1.34(1.10-1.64)],tobacco use[P=0.001,HR 2.59(1.51-4.44)],left ventricular hypertrophy[P=0.001,HR 2.14(1.35-3.39)],Dobutamine stress[P=0.003,HR 2.12(1.29-3.47)],heart failure history[P=0.031,HR 1.76(1.05-2.94)],LA diameter≥2.05 cm/m^(2)[P=0.027,HR 1.73(1.06-2.82)],and an abnormal stress echocardiogram[P=0.033,HR 1.67(1.04-2.68)].LA diameter as a continuous variable was also independently associated with mortality but LA size≥2.40 cm/m^(2) was not.CONCLUSION LA enlargement is infrequent in hypertensive AA patients when traditional reference values are used.LA enlargement is independently associated with mortality when a lower than“normal”threshold(≥2.05 cm/m^(2))is used.
文摘Background: Cardiovascular involvement among patients with primary systemic amyloidosis (AL) is common and predicts poor prognosis. Different parameters have been used to predict outcome. We studied the prognostic significance of clinical, ECG and echocardiographic parameters of 60 patients with tissue proven primary cardiac amyloidosis. Method and Results: Records of 60 patients with primary amyloidosis and cardiac involvement documented by endomyocardial tissue biopsy were retrospectively evaluated. Patients mean age was 57.9 ± 10.2 years. 71.6% were male and 86.6% Caucasian. Patients’ median survival was 12.2 ± 4.4 months with only 50% of patients survived for more than 1 year. 60% of patients had CHF (NYHA II-IV). CHF (NYHA II-IV), IVS, LVPW and LVEF were significant on univariate survival analysis
文摘Experimental, clinical and epidemiologic studies have provided strong evidence that physical training has beneficial effects on cardiovascular health. Numerous investigations have demonstrated that exercise increases coronary blood flow and myocardial perfusion. Importantly, training also can stimulate angiogenesis and accelerate collateral vessel growth in animal models with coronary artery occlusion. Cardiac adaptation such as increased vascularity or capillary density has been evidenced after regular endurance exercises. More recently, several studies indicate that physical training induces high levels of myocardial heat shock protein and antioxidant protein expression, which may play an important role in myocardial protection against ischemia-reperfusion injury.
文摘Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac m uscle involvement. The aim of the present study was to determine whether familia l clustering is observed in the severity of muscle involvement in DM1. We evalua ted 51 sibling groups constituting 112 patients with geneticallyverified DM1. Th e siblings were similar to each other in age, cytosine-thymine-guanine (CTG) r epeat length, age at disease onset, muscular impairment rating score, and electr ocardiographic markers of cardiac conduction disease. After adjusting for the si milarities between siblings in age and CTG repeat length, the siblings remained similar to each other in measures of both skeletal and cardiac muscle involvemen t. These results suggest that factors other than CTG repeat length play a role i n the severity and progression of the degenerative skeletal and cardiac muscle d isease in DM1.
文摘Background: Despite new therapies, the prevalence of heart failure continues to escalate. The prevalence of diabetes, a risk factor for heart failure, also continues to rise. To further understand the increasing prevalence of heart failure, we compared trends in the prevalence of diabetes among individuals with diagnosed heart failure versus those in the general population. Methods: Fourteen randomized trials between 1989 and 1999 including subjects with heart failure(n=34,633)were reviewed. For each trial, the enrollment date was used to estimate the yearly prevalence of diabetes among study participants with heart failure. The prevalence of diabetes in the general population was estimated based on United State’s Center for Disease Control statistics from 1989 to 1999. The prevalence of diabetes between heart failure subjects and the general population was compared using a two-sample t-test for independent samples with unequal variances. Results: The prevalence of diabetes increased from 2.6%to 4.0%from 1989 to 1999 in the general U.S. population. Among patients with heart failure, the prevalence of diabetes increased from 13%to 47%. Diabetes prevalence estimates varied significantly(p< 0.001) between the general population and individuals with heart failure during the study period. Conclusions: The rising prevalence of diabetes may partially explain the growing epidemic of heart failure. Increased efforts targeting diabetes and other cardiovascular risk factors are warranted in attenuating the rising prevalence of heart failure.
基金National Key Research and Development Program of China(2019YFE0119400)Natural Science Foundation of China(81770059,81970052 and 82000055)+4 种基金NIH NHLBI Grant(R01HL136603 to A.A.D.)National Science Foundation CCF PIPP Grant(2200138 to J.S.C.)ZHONGNANSHAN MEDICAL FOUNDATION OF GUANGDONG PROVINCE(ZNSA-2020013)Shenzhen Science and Technology Program(JCYJ20210324122410028)Open Project of State Key Laboratory of Respiratory Disease(SKLRD-OP-202301/202114).
文摘Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown.Based on a screening panel,IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19.Supporting clinical data,administration of SARS-CoV-2 Spike 1(S1)glycoprotein or receptor-binding domain(RBD)proteins into human angiotensin-converting enzyme 2(hACE2)transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation(pNF-κB)and cardiopulmonary-derived IL-18 and NLRP3 expression.IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1-or RBD-exposed hACE2 mice.Through in vivo and in vitro work,both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species.Enhancing mitophagy prevented Spike protein-mediated IL-18 expression.Moreover,IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability.Overall,the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.
