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) mRNA 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 pathomorpholouy 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 mRNA and protein level. Results: The intervention of lrbesartan 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(US) 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
Two new epimeric pairs of iridoid scyphiphin A1 （la）, A2 （lb） and scyphiphin B 1 （2a）, B2 （2b） were isolated from Scyphiphora hydrophyllacea Gaertn. F. Their structures were elucidated by spectroscopic methods...Two new epimeric pairs of iridoid scyphiphin A1 （la）, A2 （lb） and scyphiphin B 1 （2a）, B2 （2b） were isolated from Scyphiphora hydrophyllacea Gaertn. F. Their structures were elucidated by spectroscopic methods. The mixture of scyphiphin B 1 and scyphiphin B2 showed moderate cytotoxicity against human hepatoma SMMC-7721 cell line in vitro by MTT method.展开更多
Azalomycin F4a 2-ethylpentyl ester,a new 36-membered macrocyclic lactone antibiotic,was isolated from mangrove actinomycete Streptomyces sp.211726.Its structure was elucidated on the basis of spectroscopic data.The co...Azalomycin F4a 2-ethylpentyl ester,a new 36-membered macrocyclic lactone antibiotic,was isolated from mangrove actinomycete Streptomyces sp.211726.Its structure was elucidated on the basis of spectroscopic data.The compound showed broad-spectrum antifungal activity and moderate cytotoxicity against human colon tumor cell HCT-116.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
An investigation of the mangrove-derived fungus Penicillium sp.DM27 led to the isolation of 19 new compounds,including three pairs of piperidinone enantiomers(±)-1,(±)-2,and(±)-3,two pairs of pyrrolidin...An investigation of the mangrove-derived fungus Penicillium sp.DM27 led to the isolation of 19 new compounds,including three pairs of piperidinone enantiomers(±)-1,(±)-2,and(±)-3,two pairs of pyrrolidinone enantiomers(±)-4 and(±)-5,and nine pyrrolidine derivatives 6−14.The structures of 1−14 were elucidated through NMR and HRESIMS analysis,coupled with experimental and calculated ECD spectroscopy and the modified Mosher method.Quantitative real time PCR and Western bolt analyses revealed that 11 blocked EMT in TGF-β1-treated HK-2 cells and suppressed fibroblast activation in TGF-β1-stimulated NIH-3T3 cells.Molecular simulations demonstrated that compound 11 could dock ADAM17,showing a high negative binding affinity.Additionally,the overexpression of ADAM17 by lentiviral infection triggered renal tubular EMT,while compound 11 suppressed this process.Overall,our research suggests that pyrrolidine derivatives may be potential therapeutic agents for the treatment of fibrotic kidney disease.展开更多
Objectives Ischemia induced arrhythmia(ventricular tachycardia/ventricular fibrillation) is one of the major causes of death.Potassium channels change are likely to be responsible for the ischemia-related arrhythmias....Objectives Ischemia induced arrhythmia(ventricular tachycardia/ventricular fibrillation) is one of the major causes of death.Potassium channels change are likely to be responsible for the ischemia-related arrhythmias.Cardiac potassium current is the major outward current involved in cardiac repolarization.The properties of potassium channels have been intensively studied.Here,we investigated the association between ischemia induced arrhythmia and potassium channels genetic variations.Methods 23 patients with ventricular tachycardia/ventricular fibrillation induced by ischemia were selected as objects.5ML peripheral blood were taken from each person,from which DNA was extracted us- ing a standard enzymatic phenol-chloroform method.Candidate genes(HERG、KCNJ2、KCNQ1、Mink、Mirp1、Kir2.1、KV4.3、Kir3.1、KV1.5、Kir6.1、Kir6.2、Kir2.1) Were screened for potassium channels gene mutations with direct sequencing methods.Results Here 4 potassium channels gene mutations have been discovered.In the gene coding for the ATP-sensitive K^+ channels subunit Kir6.2,there is a change from valine to isoleucine at the position of 326(V326I).At the position 448,arginine substitutes proline(P448R) in the KC-NQ1 gene.In the gene KCNJ2 two mutations have been found(P156L,Q193H).Conclusions This study implicated that there is a high relationship between ischemia induced arrhythmia and the mutation of potassium channels.In order to identify the precisely relationship there is need functional analysis.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 between DC...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(CHADS_(2))(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 CHADS_(2) 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
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
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) mRNA 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 pathomorpholouy 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 mRNA and protein level. Results: The intervention of lrbesartan 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(US) 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Two new epimeric pairs of iridoid scyphiphin A1 （la）, A2 （lb） and scyphiphin B 1 （2a）, B2 （2b） were isolated from Scyphiphora hydrophyllacea Gaertn. F. Their structures were elucidated by spectroscopic methods. The mixture of scyphiphin B 1 and scyphiphin B2 showed moderate cytotoxicity against human hepatoma SMMC-7721 cell line in vitro by MTT method.
基金supported by The National High Technology Development Project(863)(No. 2007AA09Z415)The National Natural Science Foundation of China(No.U0633008)
文摘Azalomycin F4a 2-ethylpentyl ester,a new 36-membered macrocyclic lactone antibiotic,was isolated from mangrove actinomycete Streptomyces sp.211726.Its structure was elucidated on the basis of spectroscopic data.The compound showed broad-spectrum antifungal activity and moderate cytotoxicity against human colon tumor cell HCT-116.
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supported by the National Key Research and Development Program of China(No.2021YFC2100600),the National Natural Science Foundation of China(Nos.81973201,82200773,82370696,82204225,82200807),the Natural Science Foundation of Hubei Province(Nos.2021CFB347,2021CFB061),the Fundamental Research Funds for Central University(2042022kf1140),the Program of Excellent Doctoral(Postdoctoral)of Zhongnan Hospital of Wuhan University(ZNYB2021029),the Hubei Province Health and Family Planning Scientific Research Project(WJ2019MB103),the Clinical Research Project for Wu Jieping Medical Foundation(320.6750.19089-58),and the Research Fund from Medical Sci-Tech Innovation Platform of Zhongnan Hospital,Wuhan University(PTXM2020028,XKJS202035).We thank Dr.Ran Zhang from the Core Facility of Wuhan University and Dr.Xue Zhou from the Core Research Facilities of CCMS(WHU)for their assistance with NMR analysis.
文摘An investigation of the mangrove-derived fungus Penicillium sp.DM27 led to the isolation of 19 new compounds,including three pairs of piperidinone enantiomers(±)-1,(±)-2,and(±)-3,two pairs of pyrrolidinone enantiomers(±)-4 and(±)-5,and nine pyrrolidine derivatives 6−14.The structures of 1−14 were elucidated through NMR and HRESIMS analysis,coupled with experimental and calculated ECD spectroscopy and the modified Mosher method.Quantitative real time PCR and Western bolt analyses revealed that 11 blocked EMT in TGF-β1-treated HK-2 cells and suppressed fibroblast activation in TGF-β1-stimulated NIH-3T3 cells.Molecular simulations demonstrated that compound 11 could dock ADAM17,showing a high negative binding affinity.Additionally,the overexpression of ADAM17 by lentiviral infection triggered renal tubular EMT,while compound 11 suppressed this process.Overall,our research suggests that pyrrolidine derivatives may be potential therapeutic agents for the treatment of fibrotic kidney disease.
文摘Objectives Ischemia induced arrhythmia(ventricular tachycardia/ventricular fibrillation) is one of the major causes of death.Potassium channels change are likely to be responsible for the ischemia-related arrhythmias.Cardiac potassium current is the major outward current involved in cardiac repolarization.The properties of potassium channels have been intensively studied.Here,we investigated the association between ischemia induced arrhythmia and potassium channels genetic variations.Methods 23 patients with ventricular tachycardia/ventricular fibrillation induced by ischemia were selected as objects.5ML peripheral blood were taken from each person,from which DNA was extracted us- ing a standard enzymatic phenol-chloroform method.Candidate genes(HERG、KCNJ2、KCNQ1、Mink、Mirp1、Kir2.1、KV4.3、Kir3.1、KV1.5、Kir6.1、Kir6.2、Kir2.1) Were screened for potassium channels gene mutations with direct sequencing methods.Results Here 4 potassium channels gene mutations have been discovered.In the gene coding for the ATP-sensitive K^+ channels subunit Kir6.2,there is a change from valine to isoleucine at the position of 326(V326I).At the position 448,arginine substitutes proline(P448R) in the KC-NQ1 gene.In the gene KCNJ2 two mutations have been found(P156L,Q193H).Conclusions This study implicated that there is a high relationship between ischemia induced arrhythmia and the mutation of potassium channels.In order to identify the precisely relationship there is need functional analysis.
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(CHADS_(2))(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 CHADS_(2) 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.
