2021年2月12日,北京大学药学院天然药物及仿生药物国家重点实验室、分子与细胞药理学系刘涛课题组和南开大学化学学院刘育课题组合作在学术期刊《Angewandte Chemie International Edition》发表了题为"A general supramolecular a...2021年2月12日,北京大学药学院天然药物及仿生药物国家重点实验室、分子与细胞药理学系刘涛课题组和南开大学化学学院刘育课题组合作在学术期刊《Angewandte Chemie International Edition》发表了题为"A general supramolecular approach to regulate protein functions by cucurbit uril and unnatural amino acid recognition"(葫芦脲7和非天然氨基酸主客体识别介导的通用超分子策略用于蛋白质功能调控)的研究工作。展开更多
2021年2月11日,国际著名期刊Angew.Chem.Int.Ed.(IF 12.959)在线刊登了北京大学药学院天然药物及仿生药物国家重点实验室刘涛研究员的最新研究成果"Expanding the structure diversity of protein building blocks with biosynthes...2021年2月11日,国际著名期刊Angew.Chem.Int.Ed.(IF 12.959)在线刊登了北京大学药学院天然药物及仿生药物国家重点实验室刘涛研究员的最新研究成果"Expanding the structure diversity of protein building blocks with biosynthesized noncanonical amino acids from aromatic thiols"。自然界蛋白质一般是由20种天然氨基酸组成,但是随着研究的深入,有限的天然氨基酸的结构类型限制了对蛋白质功能和药物应用的拓展。展开更多
In the present study,we studied the effects of 3,4-dihydroxybenzaldehyde,derived from Salvia miltiorrhiza Bunge,on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by...In the present study,we studied the effects of 3,4-dihydroxybenzaldehyde,derived from Salvia miltiorrhiza Bunge,on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by cyclophosphamide in vivo.3,4-Dihydroxybenzaldehyde(0.01,0.1,and 1 mg/m L)improved sperm survival rate and sperm membrane integrity in separated mouse sperm(all P<0.05).In cyclophosphamide-treated male mice(60 mg/kg/d through intraperitoneal injection for 5 d),3,4-dihydroxybenzaldehyde(40 mg/kg/d through intragastric gavage for 35 d)increased the testis index,epididymis index,and sperm nuclear maturity(all P<0.05).3,4-Dihydroxybenzaldehyde also improved testis morphology characterized by orderly arranged layers of spermatogenic cells,numbers of sperm in the lumen,normal mesenchymal cells,and close and tidy arrangement of the seminiferous tubules.3,4-Dihydroxybenzaldehyde also increased testicular superoxide dismutase activity and elevated DJ-1 expression.In addition,it decreased the expression of ICAM-1 and enhanced the expressions of VCAM-1,PEDF,VEGF,and PPARγ.These findings indicated that 3,4-dihydroxybenzaldehyde increased mouse sperm survival and sperm membrane integrity in vitro and reduced mouse reproductive damage induced by cyclophosphamide via DJ-1 and other targets in vivo.3,4-Dihydroxybenzaldehyde might thus be useful for treating male reproductive damage and antineoplastic cyclophosphamide-induced reproductive toxicity.展开更多
A series of 2-arylamino-1,3,5-triazine derivatives(4a–4g),which were designed and synthesized via Sonogashira coupling reaction,were evaluated using two-electrode voltage clamp(TEVC)recordings of humanα7 nAChR expre...A series of 2-arylamino-1,3,5-triazine derivatives(4a–4g),which were designed and synthesized via Sonogashira coupling reaction,were evaluated using two-electrode voltage clamp(TEVC)recordings of humanα7 nAChR expressed in Xenopus ooctyes.Compound 4g as a positive allosteric modulator(PAM)showed better efficacy than lead compound 3(HZZ-A-11)with an EC50 value of 1.23±0.41μM.Further pharmacological evaluation of compound 4g might lead to the developmental potential for therapy of cognitive deficits commonly shared by neuropsychiatric disorders,such as schizophrenia and Alzheimer’s disease.展开更多
Ela tablets contain an optimized extract of a Chinese herbal prescription. The original prescription has been used to treat erectile dysfunction(ED), while the detailed indications and specific treatment mechanisms of...Ela tablets contain an optimized extract of a Chinese herbal prescription. The original prescription has been used to treat erectile dysfunction(ED), while the detailed indications and specific treatment mechanisms of Ela tablets remain unclear. In the present study, we aimed to investigate whether Ela tablets could protect mice from ED caused by repeated restraint stress and to explore the possible mechanisms. Mice were restrained daily in centrifuge tubes with venting holes for 14 consecutive days and administered Ela tablets at 1 h before restraining. On the 14 th night, mating experiments were conducted. Thereafter, blood, testicular, and penile samples were collected. Serum testosterone levels were measured using a kit. Testicular tissue morphology was observed by H&E staining. The PDE5 expression in the corpus cavernosum was measured by Western blotting analysis. The results indicated that Ela tablets significantly shortened the sexual arousal time, increased the number of sexual encounters, maintained the normal morphology of testicular tissue, increased the serum testosterone levels, and decreased the PDE5 expression in the corpus cavernosum. Our data showed that Ela tablets elicited protective effects on the sexual ability of mice exposed to repeated restraint stress. Moreover, the underlying mechanism was related to the preservation of testicular tissue morphology, maintenance of testosterone levels, and inhibition of penile PDE5 expression.展开更多
文摘2021年2月12日,北京大学药学院天然药物及仿生药物国家重点实验室、分子与细胞药理学系刘涛课题组和南开大学化学学院刘育课题组合作在学术期刊《Angewandte Chemie International Edition》发表了题为"A general supramolecular approach to regulate protein functions by cucurbit uril and unnatural amino acid recognition"(葫芦脲7和非天然氨基酸主客体识别介导的通用超分子策略用于蛋白质功能调控)的研究工作。
文摘2021年2月11日,国际著名期刊Angew.Chem.Int.Ed.(IF 12.959)在线刊登了北京大学药学院天然药物及仿生药物国家重点实验室刘涛研究员的最新研究成果"Expanding the structure diversity of protein building blocks with biosynthesized noncanonical amino acids from aromatic thiols"。自然界蛋白质一般是由20种天然氨基酸组成,但是随着研究的深入,有限的天然氨基酸的结构类型限制了对蛋白质功能和药物应用的拓展。
基金Science and Technology Program of the Beijing Municipal Education Commission(Grant No.KM201810025002)National Natural Science Foundation of China(Grant No.81801522)Natural Science Foundation of Hebei Province(Grant No.H2018209342)。
文摘In the present study,we studied the effects of 3,4-dihydroxybenzaldehyde,derived from Salvia miltiorrhiza Bunge,on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by cyclophosphamide in vivo.3,4-Dihydroxybenzaldehyde(0.01,0.1,and 1 mg/m L)improved sperm survival rate and sperm membrane integrity in separated mouse sperm(all P<0.05).In cyclophosphamide-treated male mice(60 mg/kg/d through intraperitoneal injection for 5 d),3,4-dihydroxybenzaldehyde(40 mg/kg/d through intragastric gavage for 35 d)increased the testis index,epididymis index,and sperm nuclear maturity(all P<0.05).3,4-Dihydroxybenzaldehyde also improved testis morphology characterized by orderly arranged layers of spermatogenic cells,numbers of sperm in the lumen,normal mesenchymal cells,and close and tidy arrangement of the seminiferous tubules.3,4-Dihydroxybenzaldehyde also increased testicular superoxide dismutase activity and elevated DJ-1 expression.In addition,it decreased the expression of ICAM-1 and enhanced the expressions of VCAM-1,PEDF,VEGF,and PPARγ.These findings indicated that 3,4-dihydroxybenzaldehyde increased mouse sperm survival and sperm membrane integrity in vitro and reduced mouse reproductive damage induced by cyclophosphamide via DJ-1 and other targets in vivo.3,4-Dihydroxybenzaldehyde might thus be useful for treating male reproductive damage and antineoplastic cyclophosphamide-induced reproductive toxicity.
基金National Natural Science Foundation of China aw arded to Q.Sun(NSFC,Grant No.81973169,21572011)and K.W.Wang(NSFC,Grant No.81537410)the Ministry of Science and Technology of China to K.W.Wang(Grant No.2014ZX09507003-006-004)。
文摘A series of 2-arylamino-1,3,5-triazine derivatives(4a–4g),which were designed and synthesized via Sonogashira coupling reaction,were evaluated using two-electrode voltage clamp(TEVC)recordings of humanα7 nAChR expressed in Xenopus ooctyes.Compound 4g as a positive allosteric modulator(PAM)showed better efficacy than lead compound 3(HZZ-A-11)with an EC50 value of 1.23±0.41μM.Further pharmacological evaluation of compound 4g might lead to the developmental potential for therapy of cognitive deficits commonly shared by neuropsychiatric disorders,such as schizophrenia and Alzheimer’s disease.
基金National Major Scientific and Technological Special Project for "Significant New Drugs Development" during the Thirteenth Five-year Plan Period,China (Grant No.2017ZX09101003-009-006)the Major Science and Technology Projects of Xinjiang Uyghur Autonomous Region (Grant No.2016 A03005-3)+3 种基金the Key Laboratory of Plant Resources and Chemistry in Arid RegionsChinese Academy of Sciences (Grant No.2008DP173091-2017-X,2008DP173091-2017-2)the National Natural Science Foundation of China (Grant No.U1603128)the Research and Development of New Ethnic Medicine Varities and Their Innovative Technologies (Grant No.2017ZX009301045)。
文摘Ela tablets contain an optimized extract of a Chinese herbal prescription. The original prescription has been used to treat erectile dysfunction(ED), while the detailed indications and specific treatment mechanisms of Ela tablets remain unclear. In the present study, we aimed to investigate whether Ela tablets could protect mice from ED caused by repeated restraint stress and to explore the possible mechanisms. Mice were restrained daily in centrifuge tubes with venting holes for 14 consecutive days and administered Ela tablets at 1 h before restraining. On the 14 th night, mating experiments were conducted. Thereafter, blood, testicular, and penile samples were collected. Serum testosterone levels were measured using a kit. Testicular tissue morphology was observed by H&E staining. The PDE5 expression in the corpus cavernosum was measured by Western blotting analysis. The results indicated that Ela tablets significantly shortened the sexual arousal time, increased the number of sexual encounters, maintained the normal morphology of testicular tissue, increased the serum testosterone levels, and decreased the PDE5 expression in the corpus cavernosum. Our data showed that Ela tablets elicited protective effects on the sexual ability of mice exposed to repeated restraint stress. Moreover, the underlying mechanism was related to the preservation of testicular tissue morphology, maintenance of testosterone levels, and inhibition of penile PDE5 expression.
