Here,a dopa decarboxylase(DDC)from Harmonia axyridis was heterogeneously expressed in Escherichia coli for the efficient biosynthesis of dopamine.For the production of recombinant DDC,the cultivation conditions includ...Here,a dopa decarboxylase(DDC)from Harmonia axyridis was heterogeneously expressed in Escherichia coli for the efficient biosynthesis of dopamine.For the production of recombinant DDC,the cultivation conditions including IPTG concentration,temperature and induction time were optimized and obtained an optimal specific enzyme activity of 51.72 U·mg^(-1) crude extracts.After the purification of DDC with a recovery yield of 68.79%,its activity was further characterized.The Vmax,Km,Kcat,and Kcat/Km of DDC for d ihyd roxy pheny la la nine(dopa)were 0.02 mmol·ml^(-1)·s^(-1),2.328 mmol·ml^(-1),10435.90 s^(-1) and4482.77 ml,mmol respectively.The highest DDC activity was observed at the condition of pH 7.5 and 45℃.With the purified DDC,the feasibility to produce dopamine from L-dopa was evaluated.The optimal yield was determined at the following bioconversion conditions:pH of 7,0,the reaction temperature of 40℃,0.4 mmol·L^(-1) of PLP and 4 g·L^(-1) of L-dopa,Subsequently,a fed-batch process for the production of dopamine was developed and the effect of oxygen was evaluated.The titer,yield and productivity of dopamine reached up to 21.99 g·L^(-1)80.88%and 14.66 g·L^(-1)·h^(-1) at 90 min under anaerobic condition.展开更多
Traditional Chinese medicine Buyi Ganshen therapy combined with dopa preparation in the therapy of Parkinson’s disease could enhance the clinical safety and efficacy compared with dopa preparation along.The exact mec...Traditional Chinese medicine Buyi Ganshen therapy combined with dopa preparation in the therapy of Parkinson’s disease could enhance the clinical safety and efficacy compared with dopa preparation along.The exact mechanism of how Buyi Ganshen works combined with dopa preparation still unknown and the enrolled articles quality was relatively inadequate,yet it could provide the reference in the clinical application and further studies.Background:To research the influence of“Buyi Ganshen”,a traditional Chinese medicine that commonly used in“Tonifying the Liver and the Kidney”,added dopa preparation for the therapy of Parkinson’s disease.Methods:This meta-analysis examined existing literature by searching 7 electronic databases(CNKI,WanFang,EMBASE,PubMed,Medline,the Cochrane Library,and the VIP database)from inception to December 2019.Randomized controlled trials evaluating the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease were identified.The main results were clinical efficacy,UPDRS I(mental score),total unified Parkinson’s disease ratingscale score,UPDRS III(motor score),UPDRS II(activities of daily life),and UPDRS IV(complications of treatment).The subordinate results were the SPOCA-AUT scores,traditional Chinese medicine syndromes and other adverse reactions.The Review Manager 5.3 software was used to calculate the pooled estimate effect.The outcomes were showed as relative ratio with 95%confidence interval.The fixed or random model was elected based on the level of homogeneity among researches.The I2 was used to detected heterogeneity.The quality of the researches was also assessed.Results:The meta-analysis include 2,241 individuals from a total of 30 studies.These data suggested that the therapy of Parkinson’s disease with the combination of“Buyi Ganshen”and dopa preparation were more effective compared to dopa preparation alone.Conclusion:“Buyi Ganshen”combined with dopa preparation exists,in some degree,to enhance clinical safety and effectiveness in the cure of Parkinson’s disease,compared with dopa preparation along.As most of the studies included were with low quality,this conclusion must be considered with caution.Thus,more multi-center,high-quality,prospective randomized controlled trials with large enough sample sizes are required to further illuminate the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease.展开更多
不宁腿综合征(restless legs syndrome,RLS)是一种常见的神经系统疾病,特点是不舒服的腿部冲动,在运动或起身行走时缓解,并在夜间症状加重。RLS的发病机制仍不清楚,但随着病理生理学研究的进展,发现可能涉及中枢神经系统的多巴胺功能障...不宁腿综合征(restless legs syndrome,RLS)是一种常见的神经系统疾病,特点是不舒服的腿部冲动,在运动或起身行走时缓解,并在夜间症状加重。RLS的发病机制仍不清楚,但随着病理生理学研究的进展,发现可能涉及中枢神经系统的多巴胺功能障碍,以及其他未确定的促进机制,特别是缺铁和慢性肾功能障碍。有家族史的遗传易感性很常见。RLS增强的特点是症状的严重性更强,症状发生的时间更早,而且常常是症状从腿部扩散至手臂或身体其他区域。一些RLS患者通过非药物措施,如按摩和温水浴,可以充分控制症状。一线治疗方案包括对体内铁储存减少的人进行铁补充治疗,或使用加巴喷丁、普瑞巴林,以及多巴胺激动剂,如普拉克索、罗匹尼罗和罗替戈汀。二线疗法包括曲马多、羟考酮和美沙酮等阿片类药物。RLS严重影响患者的生活质量,且仍是一个非常需要创新的治疗领域,需要有更多新的、有生物依据的治疗方法。展开更多
In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of...In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.展开更多
基金funded by the National Natural Science Foundation of China(21576134 and 21706126)the National Key Research and Development Program(2016YFA0204300)。
文摘Here,a dopa decarboxylase(DDC)from Harmonia axyridis was heterogeneously expressed in Escherichia coli for the efficient biosynthesis of dopamine.For the production of recombinant DDC,the cultivation conditions including IPTG concentration,temperature and induction time were optimized and obtained an optimal specific enzyme activity of 51.72 U·mg^(-1) crude extracts.After the purification of DDC with a recovery yield of 68.79%,its activity was further characterized.The Vmax,Km,Kcat,and Kcat/Km of DDC for d ihyd roxy pheny la la nine(dopa)were 0.02 mmol·ml^(-1)·s^(-1),2.328 mmol·ml^(-1),10435.90 s^(-1) and4482.77 ml,mmol respectively.The highest DDC activity was observed at the condition of pH 7.5 and 45℃.With the purified DDC,the feasibility to produce dopamine from L-dopa was evaluated.The optimal yield was determined at the following bioconversion conditions:pH of 7,0,the reaction temperature of 40℃,0.4 mmol·L^(-1) of PLP and 4 g·L^(-1) of L-dopa,Subsequently,a fed-batch process for the production of dopamine was developed and the effect of oxygen was evaluated.The titer,yield and productivity of dopamine reached up to 21.99 g·L^(-1)80.88%and 14.66 g·L^(-1)·h^(-1) at 90 min under anaerobic condition.
基金This study was financially supported by TCM Administration Project of Guangdong Province,China(No.20203010)Science and Technology Program of Guangdong,China(No.2020A151501325).
文摘Traditional Chinese medicine Buyi Ganshen therapy combined with dopa preparation in the therapy of Parkinson’s disease could enhance the clinical safety and efficacy compared with dopa preparation along.The exact mechanism of how Buyi Ganshen works combined with dopa preparation still unknown and the enrolled articles quality was relatively inadequate,yet it could provide the reference in the clinical application and further studies.Background:To research the influence of“Buyi Ganshen”,a traditional Chinese medicine that commonly used in“Tonifying the Liver and the Kidney”,added dopa preparation for the therapy of Parkinson’s disease.Methods:This meta-analysis examined existing literature by searching 7 electronic databases(CNKI,WanFang,EMBASE,PubMed,Medline,the Cochrane Library,and the VIP database)from inception to December 2019.Randomized controlled trials evaluating the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease were identified.The main results were clinical efficacy,UPDRS I(mental score),total unified Parkinson’s disease ratingscale score,UPDRS III(motor score),UPDRS II(activities of daily life),and UPDRS IV(complications of treatment).The subordinate results were the SPOCA-AUT scores,traditional Chinese medicine syndromes and other adverse reactions.The Review Manager 5.3 software was used to calculate the pooled estimate effect.The outcomes were showed as relative ratio with 95%confidence interval.The fixed or random model was elected based on the level of homogeneity among researches.The I2 was used to detected heterogeneity.The quality of the researches was also assessed.Results:The meta-analysis include 2,241 individuals from a total of 30 studies.These data suggested that the therapy of Parkinson’s disease with the combination of“Buyi Ganshen”and dopa preparation were more effective compared to dopa preparation alone.Conclusion:“Buyi Ganshen”combined with dopa preparation exists,in some degree,to enhance clinical safety and effectiveness in the cure of Parkinson’s disease,compared with dopa preparation along.As most of the studies included were with low quality,this conclusion must be considered with caution.Thus,more multi-center,high-quality,prospective randomized controlled trials with large enough sample sizes are required to further illuminate the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease.
基金Research and Agricultural Project of Zhejiang Technology Department(2008C22026,2009C32016)Key Project of Zhejiang Education Department(20070430)Xin-Miao Project of Zhejiang Technology Department(2008R40G2110002)
基金Supported by Research and Agricultural Project of Science and Technology Department of Zhejiang Province(No.2008C22026)Key Project of Education Department of Zhejiang Province(No.20070430)~~
文摘不宁腿综合征(restless legs syndrome,RLS)是一种常见的神经系统疾病,特点是不舒服的腿部冲动,在运动或起身行走时缓解,并在夜间症状加重。RLS的发病机制仍不清楚,但随着病理生理学研究的进展,发现可能涉及中枢神经系统的多巴胺功能障碍,以及其他未确定的促进机制,特别是缺铁和慢性肾功能障碍。有家族史的遗传易感性很常见。RLS增强的特点是症状的严重性更强,症状发生的时间更早,而且常常是症状从腿部扩散至手臂或身体其他区域。一些RLS患者通过非药物措施,如按摩和温水浴,可以充分控制症状。一线治疗方案包括对体内铁储存减少的人进行铁补充治疗,或使用加巴喷丁、普瑞巴林,以及多巴胺激动剂,如普拉克索、罗匹尼罗和罗替戈汀。二线疗法包括曲马多、羟考酮和美沙酮等阿片类药物。RLS严重影响患者的生活质量,且仍是一个非常需要创新的治疗领域,需要有更多新的、有生物依据的治疗方法。
基金supported by SIP-IPN,CONACYT (CB-168116)FIS/IMSS (FIS/IMSS/PROT/G11-2/1013)
文摘In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.
