Objective: To explore the effect and mechanism of angiotensin Ⅱ receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2...Objective: To explore the effect and mechanism of angiotensin Ⅱ receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan+ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43(Cx43) mR NA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group(SO), myocardial infarction group(MI), Irbesartan group and MI+ Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mR NA and protein level. Results: The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia(P<0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group(P<0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arerythmia between MI group and SO group(P<0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group(P<0.05). There was the significant difference in the overall score between MI+Irbesartan group and MI group(P<0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased(P<0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions: Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.展开更多
A new degraded sesquiterpene was isolated from the marine actinomycete Streptomyces sp. 0616208. Its structure was elucidated as (1α; 4aα; 5α, 7β, 8aβ)-5, 8a-dimethyl-decahydrona- phthalene-1, 4a, 7-triol on th...A new degraded sesquiterpene was isolated from the marine actinomycete Streptomyces sp. 0616208. Its structure was elucidated as (1α; 4aα; 5α, 7β, 8aβ)-5, 8a-dimethyl-decahydrona- phthalene-1, 4a, 7-triol on the basis of spectroscopic data.展开更多
Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),tog...Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),together with 16 known compounds(9-24),were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362.The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher’s method.Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring.A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin.The antimicrobial activity assay indicated that compounds 5,9,10,and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration(MIC)values in the range of 2.42-36.04μmol/L.While secalonic acid D(19)demonstrated signifcant antimicrobial activity against four strains of H.pylori with MIC values in the range of 0.20 to 1.57μmol/L.Furthermore,secalonic acid D(19)exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC_(50) values of 0.15 and 0.19μmol/L,respectively.The structure–activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H.pylori.The depsidone derivatives are promising leads to inhibit H.pylori and provide an avenue for further development of novel antibiotics.展开更多
Background: Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction;however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations betwee...Background: Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction;however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations between DC and stroke risk in paroxysmal atrial fibrillation (AF). We aimed to explore the influencing factors of abnormal DC and the relationships between DC and stroke risk in patients with paroxysmal AF. Methods: The study included hospitalized paroxysmal AF patients with DC measurements derived from 24-h Holter electrocardiography recordings taken between August 2015 and June 2016. Multivariable regression analysis was performed to evaluate the associations between correlated variables and abnormal DC values. The relationship between DC and ischemic stroke risk scores in patients with paroxysmal AF was analyzed. Results: We studied 259 hospitalized patients with paroxysmal AF (143 [55.2%] male, mean age 66.4 ± 12.0 years);38 patients of them showed abnormal DC values. In the univariate analysis, age, hypertension, heart failure, and previous stroke/transient ischemic attack (TIA) were significantly associated with abnormal DC values. Among these factors, a history of previous stroke/TIA (odds ratio = 2.861, 95% confidence interval: 1.356–6.039) were independently associated with abnormal DC values in patients with paroxysmal AF. The abnormal DC group showed a higher stroke risk with the score of congestive heart failure, hypertension, age >75 years, diabetes mellitus, previous stroke and TIA (CHADS2)(2.25 ± 1.48 vs. 1.40 ± 1.34, t =-4.907, P = 0.001) and CHA2DS2-vascular disease, age 65–74 years and female category (VASc)(3.76 ± 1.95 vs. 2.71 ± 1.87, t =-4.847, P = 0.001) scores. Correlation analysis showed that DC was negatively correlated with CHADS2 scores (r =-0.290, P < 0.001) and CHA2DS2-VASc scores (r =-0.263, P > 0.001). Conclusions: Lower DC is closely associated with previous stroke/TIA, and is also correlated negatively with higher stroke risk scores in patients with paroxysmal AF. It could be a potential indicator of stroke risk in paroxysmal AF patients.展开更多
Organic carbonates(OCs)are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups.They exist in either linear or cyclic forms,of which the majority encountered in nature adopt a pentacyclic s...Organic carbonates(OCs)are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups.They exist in either linear or cyclic forms,of which the majority encountered in nature adopt a pentacyclic structure.However,the enzymatic basis for pentacyclic carbonate ring formation remains elusive.Here,we reported that a four-protein metabolon(AlmUII-UV)assembled by a small peptide protein(AlmUV)appends a reactive N-hydroxylcarbamoyl moiety to the decarboxylated aldgamycins followed by a non-enzymatic condensation to give the pentacyclic carbonate ring.Our results have documented an unprecedent mechanism for carbonate formation.展开更多
基金supported by Research Topic of Department of Health of Jiangxi Province(No.20131074)Natural Science Fund of Jiangxi Province(No:20122BAB205028)
文摘Objective: To explore the effect and mechanism of angiotensin Ⅱ receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan+ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43(Cx43) mR NA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group(SO), myocardial infarction group(MI), Irbesartan group and MI+ Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mR NA and protein level. Results: The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia(P<0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group(P<0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arerythmia between MI group and SO group(P<0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group(P<0.05). There was the significant difference in the overall score between MI+Irbesartan group and MI group(P<0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased(P<0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions: Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.
文摘A new degraded sesquiterpene was isolated from the marine actinomycete Streptomyces sp. 0616208. Its structure was elucidated as (1α; 4aα; 5α, 7β, 8aβ)-5, 8a-dimethyl-decahydrona- phthalene-1, 4a, 7-triol on the basis of spectroscopic data.
基金This research was funded by grants from National Key Research and Development Program of China(2018YFC0311002)High-Level Talent Special Support Plan of Zhejiang Province(2019R52009).
文摘Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),together with 16 known compounds(9-24),were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362.The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher’s method.Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring.A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin.The antimicrobial activity assay indicated that compounds 5,9,10,and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration(MIC)values in the range of 2.42-36.04μmol/L.While secalonic acid D(19)demonstrated signifcant antimicrobial activity against four strains of H.pylori with MIC values in the range of 0.20 to 1.57μmol/L.Furthermore,secalonic acid D(19)exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC_(50) values of 0.15 and 0.19μmol/L,respectively.The structure–activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H.pylori.The depsidone derivatives are promising leads to inhibit H.pylori and provide an avenue for further development of novel antibiotics.
基金This study was supported by the grants from the National Natural Science Foundation of China (No. 81370288, No. 8153000545)National Basic Research Program of China (973 Program 2013CB531103)Jiangxi Science Foundation (Nos. 20121BBG70030, 20161BAB215241).
文摘Background: Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction;however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations between DC and stroke risk in paroxysmal atrial fibrillation (AF). We aimed to explore the influencing factors of abnormal DC and the relationships between DC and stroke risk in patients with paroxysmal AF. Methods: The study included hospitalized paroxysmal AF patients with DC measurements derived from 24-h Holter electrocardiography recordings taken between August 2015 and June 2016. Multivariable regression analysis was performed to evaluate the associations between correlated variables and abnormal DC values. The relationship between DC and ischemic stroke risk scores in patients with paroxysmal AF was analyzed. Results: We studied 259 hospitalized patients with paroxysmal AF (143 [55.2%] male, mean age 66.4 ± 12.0 years);38 patients of them showed abnormal DC values. In the univariate analysis, age, hypertension, heart failure, and previous stroke/transient ischemic attack (TIA) were significantly associated with abnormal DC values. Among these factors, a history of previous stroke/TIA (odds ratio = 2.861, 95% confidence interval: 1.356–6.039) were independently associated with abnormal DC values in patients with paroxysmal AF. The abnormal DC group showed a higher stroke risk with the score of congestive heart failure, hypertension, age >75 years, diabetes mellitus, previous stroke and TIA (CHADS2)(2.25 ± 1.48 vs. 1.40 ± 1.34, t =-4.907, P = 0.001) and CHA2DS2-vascular disease, age 65–74 years and female category (VASc)(3.76 ± 1.95 vs. 2.71 ± 1.87, t =-4.847, P = 0.001) scores. Correlation analysis showed that DC was negatively correlated with CHADS2 scores (r =-0.290, P < 0.001) and CHA2DS2-VASc scores (r =-0.263, P > 0.001). Conclusions: Lower DC is closely associated with previous stroke/TIA, and is also correlated negatively with higher stroke risk scores in patients with paroxysmal AF. It could be a potential indicator of stroke risk in paroxysmal AF patients.
基金financially supported by grants from National Key Research and Development Program of China(2018YFA0903200/2018YFA0903201)the National Natural Science Foundation of China(81925037,31870032,31761143016 and 31670036)+7 种基金the 111 Project of Ministry of Education of the People’s Republic of China(B13038)Chang Jiang Scholars Program(Young Scholar)from the Ministry of Education of China(Hao Gao,2017)National High-level Personnel of Special Support Program(2017RA2259,China)the Guangdong Natural Science Funds for Distinguished Young Scholar(2019B151502014,China)Guangdong Special Support Program(2016TX03R280,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036,China)K.C.Wong Education Foundation(Hao Gao,2016,China)China Postdoctoral Science Foundation(2019M663192)
文摘Organic carbonates(OCs)are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups.They exist in either linear or cyclic forms,of which the majority encountered in nature adopt a pentacyclic structure.However,the enzymatic basis for pentacyclic carbonate ring formation remains elusive.Here,we reported that a four-protein metabolon(AlmUII-UV)assembled by a small peptide protein(AlmUV)appends a reactive N-hydroxylcarbamoyl moiety to the decarboxylated aldgamycins followed by a non-enzymatic condensation to give the pentacyclic carbonate ring.Our results have documented an unprecedent mechanism for carbonate formation.