目的系统评价5-HTR2A 102T>C基因多态性与抗精神病药物疗效的相关性。方法计算机检索Web of Science、Pub Med、中国学术期刊全文数据库(CNKI)、万方数据库、维普数据库中研究5-HTR2A 102T>C基因多态性与抗精神病药物疗效的研究,...目的系统评价5-HTR2A 102T>C基因多态性与抗精神病药物疗效的相关性。方法计算机检索Web of Science、Pub Med、中国学术期刊全文数据库(CNKI)、万方数据库、维普数据库中研究5-HTR2A 102T>C基因多态性与抗精神病药物疗效的研究,检索年限从建库至2017年5月2日。按纳入与排除标准筛选文献、提取资料并评价纳入研究的方法学质量后,采用Stata 12.0软件进行Meta分析。结果共纳入10项研究,Meta-分析结果表明,5-HTR2A 102T>C基因多态性与抗精神病药物疗效在等位基因模型、共显性基因模型、显性基因模型中均无统计学意义(P>0.05):等位基因模型OR=1.16,95%CI(1.00~1.36);共显性基因(TT vs CC)模型OR=1.23,95%CI(0.91~1.65);共显性基因(TT vs TC)模型OR=0.90,95%CI(0.68~1.19);显性基因模型OR=1.04,95%CI(0.80~1.34);而隐性基因模型和超显性基因模型具有统计学意义(P<0.05):隐性基因模型OR=1.37,95%CI(1.09~1.72);超显性基因模型OR=0.78,95%CI(0.62~0.96)。结论 5-HTR2A 102T>C基因多态性与抗精神病药物疗效有关联性。展开更多
目的应用meta分析明确5-羟色胺2A受体(5-HTR2A)基因rs6311(-1438A>G)和rs6313(102T>C)位点多态性与抗精神分裂症药物疗效的相关性。方法计算机检索PubMed、Embase、ScienceDirect、Web of Science和中国知网、万方、维普、中国生...目的应用meta分析明确5-羟色胺2A受体(5-HTR2A)基因rs6311(-1438A>G)和rs6313(102T>C)位点多态性与抗精神分裂症药物疗效的相关性。方法计算机检索PubMed、Embase、ScienceDirect、Web of Science和中国知网、万方、维普、中国生物医学文献数据库,获取近20年有关5-HTR2A基因多态性与抗精神分裂症药物疗效关系的相关文献,提取数据。采用Review Manager 5.3软件进行meta分析。结果共纳入27篇文献。分别对5-HTR2A基因rs6311、rs6313位点的等位基因和基因型多态性与抗精神分裂症药物治疗有效率、减分率的关联性进行meta分析,并以时间、药物、地区3种因素分别进行亚组分析。rs6311位点有效率数据合并显示,等位基因A>G多态性与抗精神病药疗效无关,而亚组分析显示中国人群中等位基因A患者的有效率更高;减分率数据合并显示AG基因型患者的抗精神病药物减分率高于GG。对于rs6313位点,等位基因T>C多态性与抗精神病药有效率无关,而与基因型多态性存在关联,TC基因型患者的氯丙嗪有效率高于TT基因型患者;减分率数据也显示TC患者的药物减分率比TT患者高,亚组分析显示在中国群体中基因型TC患者减分率高于TT患者,而其他国家群体中CC基因型患者减分率高于TT患者,在利培酮和1999—2009群体中TC基因型患者的减分率均高于CC基因型患者。结论5-HTR2A基因多态性与抗精神分裂症药物疗效的关联受时间、药物、地区的影响,但总体而言rs6311位点AG基因型、rs6313位点TC基因型是抗精神分裂症药物疗效好的预测因子。展开更多
Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been...Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
文摘目的系统评价5-HTR2A 102T>C基因多态性与抗精神病药物疗效的相关性。方法计算机检索Web of Science、Pub Med、中国学术期刊全文数据库(CNKI)、万方数据库、维普数据库中研究5-HTR2A 102T>C基因多态性与抗精神病药物疗效的研究,检索年限从建库至2017年5月2日。按纳入与排除标准筛选文献、提取资料并评价纳入研究的方法学质量后,采用Stata 12.0软件进行Meta分析。结果共纳入10项研究,Meta-分析结果表明,5-HTR2A 102T>C基因多态性与抗精神病药物疗效在等位基因模型、共显性基因模型、显性基因模型中均无统计学意义(P>0.05):等位基因模型OR=1.16,95%CI(1.00~1.36);共显性基因(TT vs CC)模型OR=1.23,95%CI(0.91~1.65);共显性基因(TT vs TC)模型OR=0.90,95%CI(0.68~1.19);显性基因模型OR=1.04,95%CI(0.80~1.34);而隐性基因模型和超显性基因模型具有统计学意义(P<0.05):隐性基因模型OR=1.37,95%CI(1.09~1.72);超显性基因模型OR=0.78,95%CI(0.62~0.96)。结论 5-HTR2A 102T>C基因多态性与抗精神病药物疗效有关联性。
文摘目的应用meta分析明确5-羟色胺2A受体(5-HTR2A)基因rs6311(-1438A>G)和rs6313(102T>C)位点多态性与抗精神分裂症药物疗效的相关性。方法计算机检索PubMed、Embase、ScienceDirect、Web of Science和中国知网、万方、维普、中国生物医学文献数据库,获取近20年有关5-HTR2A基因多态性与抗精神分裂症药物疗效关系的相关文献,提取数据。采用Review Manager 5.3软件进行meta分析。结果共纳入27篇文献。分别对5-HTR2A基因rs6311、rs6313位点的等位基因和基因型多态性与抗精神分裂症药物治疗有效率、减分率的关联性进行meta分析,并以时间、药物、地区3种因素分别进行亚组分析。rs6311位点有效率数据合并显示,等位基因A>G多态性与抗精神病药疗效无关,而亚组分析显示中国人群中等位基因A患者的有效率更高;减分率数据合并显示AG基因型患者的抗精神病药物减分率高于GG。对于rs6313位点,等位基因T>C多态性与抗精神病药有效率无关,而与基因型多态性存在关联,TC基因型患者的氯丙嗪有效率高于TT基因型患者;减分率数据也显示TC患者的药物减分率比TT患者高,亚组分析显示在中国群体中基因型TC患者减分率高于TT患者,而其他国家群体中CC基因型患者减分率高于TT患者,在利培酮和1999—2009群体中TC基因型患者的减分率均高于CC基因型患者。结论5-HTR2A基因多态性与抗精神分裂症药物疗效的关联受时间、药物、地区的影响,但总体而言rs6311位点AG基因型、rs6313位点TC基因型是抗精神分裂症药物疗效好的预测因子。
基金the Ministry of Science and Technology of China(2018YFA0507402)the National Natural Science Foundation of China(32000667)+5 种基金the Shanghai Science and Technology Innovation Action(21ZR1470600)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2022264)the National Natural Science Foundation of China(81771465 and 81930033)the Science and Technology Project of the Department of Education of Jiangxi Province(GJJ211248)the Division of Intramural Research,National Institute of Allergy and Infectious Diseases,National Institutes of Health(grant 1ZIA-Al-001169)the US-China Biomedical Collaborative Research Program(grant Al-129775).
文摘Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
