Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The ...Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The pathway analyses for the collection of anticancer targets screened were carried out based on the KEGG pathway database, followed by the forecast of potential pharmacological activities and pathways of the effects of cryptotanshinone, and verification of some of the targets screened using whole cell tests. The results showed that a total of eight targets with anticancer potential were screened, including MAP2K1, RARα, RXRα, PDK1, CHK1, AR, Ang-1 R, and Kif11. These targets are mainly related to four aspects of the cancer growth: the cell cycle, angiogenesis, apoptosis, and androgen receptor. The cell tests showed that cryptotanshinone can inhibit the viability of human hepatoma cells SMMC-7721, which is related to the reduction of expression of MAP2K1 mRNA. This method provides a strong clue for the study of the anticancer effects and mechanisms of action of cryptotanshinone in the future.展开更多
Cancer screening is a strategy focused on highrisk populations rather than universal populationwide screening, based on a comprehensive evaluation of epidemiological principles and practical feasibility. The effective...Cancer screening is a strategy focused on highrisk populations rather than universal populationwide screening, based on a comprehensive evaluation of epidemiological principles and practical feasibility. The effectiveness of screening depends on factors such as disease prevalence, as well as the sensitivity and specificity of the screening technology employed.展开更多
’97 Wuhan International Screen Special Printing Technology Exhibition was held from May 21—24, 1997 in Wuhan city,the capital of Hubei Province. 120 famous exhibitors from China, USA, Canada, Holland, Japan, Korea, ...’97 Wuhan International Screen Special Printing Technology Exhibition was held from May 21—24, 1997 in Wuhan city,the capital of Hubei Province. 120 famous exhibitors from China, USA, Canada, Holland, Japan, Korea, and Hong Kong, Taiwan districts attended the Exhibition. The booth area was more than 5000 m^2.展开更多
Advancements in screening technologies employing small organisms have enabled deep profiling of compounds in vivo.However,current strategies for phenotyping of behaving animals,such as zebrafish,typically involve tedi...Advancements in screening technologies employing small organisms have enabled deep profiling of compounds in vivo.However,current strategies for phenotyping of behaving animals,such as zebrafish,typically involve tedious manipulations.Here,we develop and validate a fully automated in vivo screening system(AISS)that integrates microfluidic technology and computer-vision-based control methods to enable rapid evaluation of biological responses of non-anesthetized zebrafish to molecular gradients.Via precise fluidic control,the AISS allows automatic loading,encapsulation,transportation and immobilization of single-larva in droplets for multi-organ imaging and chemical gradients generation inaccessible in previous systems.Using this platform,we examine the cardiac sensitivity of an antipsychotic drug with multiple concentration gradients,and reveal dramatic diversity and complexity in the accurate chemical regulation of cardiac functions in vivo.This proposed system expands the arsenal of tools available for in vivo screening and facilitates comprehensive profiling of pharmaceuticals.展开更多
Sepsis is a life-threatening syndrome characterized by dysregulated host responses to infection,leading to severe organ dysfunction and a high mortality rate.Reducing the incidence of sepsis is of paramount importance...Sepsis is a life-threatening syndrome characterized by dysregulated host responses to infection,leading to severe organ dysfunction and a high mortality rate.Reducing the incidence of sepsis is of paramount importance.Given that sepsis-associated drugs largely fail in clinical trials,in this project,we devised and validated a novel long-acting C5a-blocking cyclic peptide drug(Cp1)via phage screening technology to block the upstream“bottleneck molecule”C5a-mediated amplification cascade of the inflammatory response.In the early stage of infection,we utilized the efficient neutralization of Cp1 against C5a to effectively curb the“waterfall effect”of inflammatory factors and mitigate the progression to dysregulated systemic inflammation,thereby providing effective prevention and therapeutic intervention for sepsis.First,in vitro and in vivo studies collectively demonstrated the optimal binding affinity and blocking selectivity of Cp1.The excellent plasma stability of Cp1 further endows it with antibodylike systemic circulation.In the CLP-induced sepsis model,Cp1 significantly suppressed the expression of inflammatory factors and chemokines in both plasma and peritoneal lavage fluid(PLF).Additionally,Cp1 potently inhibited innate immune injury.Ultimately,after a single administration of Cp1,the CLP-induced septic mice presented a significant reduction in bacterial burden,evident amelioration of organ dysfunction,and notable prolongation of survival time.Overall,the novel cyclic peptide drug Cp1 developed in this study is a highly promising and cost-competitive therapeutic option for sepsis prophylaxis and therapy.展开更多
基金supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.11KJB360004)the Jiangsu Provincial Natural Science Foundation of China(No.BK2012458),the National Natural Science Foundation of China(Nos.81373232,81173174,81270514)+1 种基金the National Key Technology R&D Program during the 11th Five-Year Plan Period(No.2008BAI51B02)the Doctoral Fund of Ministry of Education of China(No.20113237110008)
文摘Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The pathway analyses for the collection of anticancer targets screened were carried out based on the KEGG pathway database, followed by the forecast of potential pharmacological activities and pathways of the effects of cryptotanshinone, and verification of some of the targets screened using whole cell tests. The results showed that a total of eight targets with anticancer potential were screened, including MAP2K1, RARα, RXRα, PDK1, CHK1, AR, Ang-1 R, and Kif11. These targets are mainly related to four aspects of the cancer growth: the cell cycle, angiogenesis, apoptosis, and androgen receptor. The cell tests showed that cryptotanshinone can inhibit the viability of human hepatoma cells SMMC-7721, which is related to the reduction of expression of MAP2K1 mRNA. This method provides a strong clue for the study of the anticancer effects and mechanisms of action of cryptotanshinone in the future.
文摘Cancer screening is a strategy focused on highrisk populations rather than universal populationwide screening, based on a comprehensive evaluation of epidemiological principles and practical feasibility. The effectiveness of screening depends on factors such as disease prevalence, as well as the sensitivity and specificity of the screening technology employed.
文摘’97 Wuhan International Screen Special Printing Technology Exhibition was held from May 21—24, 1997 in Wuhan city,the capital of Hubei Province. 120 famous exhibitors from China, USA, Canada, Holland, Japan, Korea, and Hong Kong, Taiwan districts attended the Exhibition. The booth area was more than 5000 m^2.
基金supported by the National Natural Science Foundation of China(82372088)the National Natural Science Foundation of Guangdong Province(2021A1515010266)+2 种基金the Shenzhen Science and Technology Program(202206193000001,20220816161126002)the Foundation of Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument(2020B1212060077)2021 Foshan Science and Technology Innovation Team for Young-Top Talents(2120001010795).
文摘Advancements in screening technologies employing small organisms have enabled deep profiling of compounds in vivo.However,current strategies for phenotyping of behaving animals,such as zebrafish,typically involve tedious manipulations.Here,we develop and validate a fully automated in vivo screening system(AISS)that integrates microfluidic technology and computer-vision-based control methods to enable rapid evaluation of biological responses of non-anesthetized zebrafish to molecular gradients.Via precise fluidic control,the AISS allows automatic loading,encapsulation,transportation and immobilization of single-larva in droplets for multi-organ imaging and chemical gradients generation inaccessible in previous systems.Using this platform,we examine the cardiac sensitivity of an antipsychotic drug with multiple concentration gradients,and reveal dramatic diversity and complexity in the accurate chemical regulation of cardiac functions in vivo.This proposed system expands the arsenal of tools available for in vivo screening and facilitates comprehensive profiling of pharmaceuticals.
基金supported by grants from the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-076)the Shanghai Top Priority Research Center Project(2023ZZ02013)the Research Initiation Fund for High-caliber PhD Talent of the First Affiliated Hospital of Naval Medical University(2023).
文摘Sepsis is a life-threatening syndrome characterized by dysregulated host responses to infection,leading to severe organ dysfunction and a high mortality rate.Reducing the incidence of sepsis is of paramount importance.Given that sepsis-associated drugs largely fail in clinical trials,in this project,we devised and validated a novel long-acting C5a-blocking cyclic peptide drug(Cp1)via phage screening technology to block the upstream“bottleneck molecule”C5a-mediated amplification cascade of the inflammatory response.In the early stage of infection,we utilized the efficient neutralization of Cp1 against C5a to effectively curb the“waterfall effect”of inflammatory factors and mitigate the progression to dysregulated systemic inflammation,thereby providing effective prevention and therapeutic intervention for sepsis.First,in vitro and in vivo studies collectively demonstrated the optimal binding affinity and blocking selectivity of Cp1.The excellent plasma stability of Cp1 further endows it with antibodylike systemic circulation.In the CLP-induced sepsis model,Cp1 significantly suppressed the expression of inflammatory factors and chemokines in both plasma and peritoneal lavage fluid(PLF).Additionally,Cp1 potently inhibited innate immune injury.Ultimately,after a single administration of Cp1,the CLP-induced septic mice presented a significant reduction in bacterial burden,evident amelioration of organ dysfunction,and notable prolongation of survival time.Overall,the novel cyclic peptide drug Cp1 developed in this study is a highly promising and cost-competitive therapeutic option for sepsis prophylaxis and therapy.
