目的:探讨Wnt蛋白生成抑制剂2(the inhibitor of Wnt production 2,IWP2)对非小细胞肺癌细胞迁移与侵袭能力的影响。方法:体外培养非小细胞肺癌H1299和95C细胞,分为对照组(无血清培养基)及实验组(应用10μmol/L IWP2处理24或48 h)。采...目的:探讨Wnt蛋白生成抑制剂2(the inhibitor of Wnt production 2,IWP2)对非小细胞肺癌细胞迁移与侵袭能力的影响。方法:体外培养非小细胞肺癌H1299和95C细胞,分为对照组(无血清培养基)及实验组(应用10μmol/L IWP2处理24或48 h)。采用划痕实验和未铺Matrigel胶的Transwell迁移实验检测IWP2对细胞迁移能力的影响;铺有Matrigel胶的Transwell侵袭实验检测IWP2对细胞侵袭能力的影响;Western blot实验检测IWP2对非小细胞肺癌细胞中β-catenin及上皮间充质转化(EMT)相关蛋白ZEB1、Snail表达的影响。结果:划痕实验结果显示,经10μmol/L IWP2处理24 h后,与对照组比较,实验组H1299和95C细胞的划痕愈合面积均明显降低(P<0.01);在Transwell迁移实验中,实验组过膜细胞数明显降低(P<0.01);Transwell侵袭实验结果显示,实验组细胞表现出更低的侵袭能力(P<0.01)。Western blot结果表明,H1299和95C细胞在经IWP2作用后,与对照组比较,β-catenin的表达水平分别降低41.3%和36.1%(P均<0.01);IWP2也抑制了EMT相关蛋白ZEB1、Snail的表达,与对照组比较,实验组H1299和95C细胞中,ZEB1的表达水平分别降低51.8%和40.9%,Snail表达水平分别降低43.2%和30.7%,差异均具有统计学意义(P均<0.01)。结论:IWP2抑制β-catenin的表达并抑制非小细胞肺癌细胞发生EMT,从而降低细胞的迁移与侵袭能力。展开更多
A novel coronavirus,known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has surfaced and caused global concern owing to its ferocity.SARS-CoV-2 is the causative agent of coronavirus disease 2019;howev...A novel coronavirus,known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has surfaced and caused global concern owing to its ferocity.SARS-CoV-2 is the causative agent of coronavirus disease 2019;however,it was only discovered at the end of the year and was considered a pandemic by the World Health Organization.Therefore,the develop-ment of novel potent inhibitors against SARS-CoV-2 and future outbreaks is urgently required.Numerous naturally occurring bioactive substances have been studied in the clinical setting for diverse disorders.The intricate infection and replication mechanism of SARS-CoV-2 offers diverse therapeutic drug targets for developing antiviral medicines by employing natural products that are safer than synthetic compounds.Marine natural products(MNPs)have received increased attention in the development of novel drugs owing to their high diversity and availability.Therefore,this review article investigates the infection and replication mechanisms,including the function of the SARS-CoV-2 genome and structure.Furthermore,we highlighted anti-SARS-CoV-2 therapeutic intervention efforts utilizing MNPs and predicted SARS-CoV-2 inhibitor design.展开更多
For the past 2 years,the coronavirus responsible for the COVID-19 infection has become a world pandemic,ruining the lives and economies of several nations in the world.This has scaled up research on the virus and the ...For the past 2 years,the coronavirus responsible for the COVID-19 infection has become a world pandemic,ruining the lives and economies of several nations in the world.This has scaled up research on the virus and the resulting infection with the goal of developing new vaccines and therapies.Natural products are known to be a rich source of lead compounds for drug discovery,including against infectious diseases caused by microbes(viruses,bacteria and fungi).In this review article,we conducted a literature survey aimed at identifying natural products with inhibitory concentrations against the coronaviruses or their target proteins,which lie below 10μM.This led to the identification of 42 compounds belonging to the alkaloid,flavonoid,terpenoid,phenolic,xanthone and saponin classes.The cut off concentration of 10μM was to limit the study to the most potent chemical entities,which could be developed into therapies against the viral infection to make a contribution towards limiting the spread of the disease.展开更多
The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics.Dietary supplements,especially natural...The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics.Dietary supplements,especially natural products that are edible and safe for human use,are a good source of drug discovery with potential for uncovering novel applications,In this study,we tested 40 natural products of dietary supplements and identified capsaicin,a common dietary supplement abundant in chili peppers,as an inhibitor of Lassa virus(LASV)entry with EC5,of 6.9-10.0μmol/L using an HIV based pseudo virus platform.Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus(LCMV),showing a preferential activity against LASV.Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide(SSP)-GP2 transmembrane(GP2TM)region of the LASV surface glycoprotein.Mutational study revealed the key residues Ala25,Val431,Phe434 and Val435 in SsP-CP2TM region in capsaicin’s antiviral effect.This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV,providing detailed interaction hot spots in the unique SSP-GP2TMinterface of LASV glycoprotein that is crucial in fusion inhibition,and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.展开更多
Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15（1） and mycalenitrile-16（2）,along with five known related ones（3-7）,were isolated from the South China Sea sponge Mycale lissochela.The structu...Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15（1） and mycalenitrile-16（2）,along with five known related ones（3-7）,were isolated from the South China Sea sponge Mycale lissochela.The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those reported in the literature.In bioassay,compounds 1 and 7 exhibited significant PTPIB（Protein-tyrosine phosphatase 1B,a recognized target for diabetes and obesity） inhibitory activities with IC（50） values of 8.6 and 3.1 μmoI/L,respectively.A preliminary SAR analysis of the isolated compounds with their PTP1 B inhibitory effects was described.展开更多
Nitrogen(N) losses in cropland resulting from the application of synthetic fertilizers decrease crop productivity and exacerbate environmental pollution.Mitigation measures, such as reduction in N fertilizer applicati...Nitrogen(N) losses in cropland resulting from the application of synthetic fertilizers decrease crop productivity and exacerbate environmental pollution.Mitigation measures, such as reduction in N fertilizer application rates, can have unintentional adverse effects on crop yield. We conducted a meta-analysis of soil N_(2)O emissions from agricultural fields across China under contrasting mitigation scenarios as a novel approach to identify the most effective strategy for the mitigation of emissions of N_(2)O derived from N fertilizer use in China. Current standard agricultural practice was used as a baseline scenario(BS), and 12 potential mitigation scenarios(S1–S12) were derived from the available literature and comprised single and combinations of management scenarios that accounted for crop yield. Mitigation scenarios S6(nitrification inhibitor 3,4-dimethylpyrazole phosphate) and S11(20% reduction in N application rate plus nitrification inhibitor dicyandiamide) in maize, rice, and wheat crops led to an average 56.0% reduction in N_(2)O emissions at the national level, whereas scenario S4(nitrification inhibitor dicyandiamide) led to yield optimization, with a 14.0% increase for maize and 8.0% increase for rice as compared to the BS. Implementation of these most effective mitigation scenarios(S4, S6, and S11) might help China, as a signatory to the 2015 United Nations Framework Convention on Climate Change(Paris Agreement), to achieve a 30% reduction in N_(2)O emissions by 2030.展开更多
基金part of the project“Develop-ment of functional food products with natural materials derived from marine resources(no.20170285)”,funded by the Ministry of Oceans and Fisheries,Korea.
文摘A novel coronavirus,known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has surfaced and caused global concern owing to its ferocity.SARS-CoV-2 is the causative agent of coronavirus disease 2019;however,it was only discovered at the end of the year and was considered a pandemic by the World Health Organization.Therefore,the develop-ment of novel potent inhibitors against SARS-CoV-2 and future outbreaks is urgently required.Numerous naturally occurring bioactive substances have been studied in the clinical setting for diverse disorders.The intricate infection and replication mechanism of SARS-CoV-2 offers diverse therapeutic drug targets for developing antiviral medicines by employing natural products that are safer than synthetic compounds.Marine natural products(MNPs)have received increased attention in the development of novel drugs owing to their high diversity and availability.Therefore,this review article investigates the infection and replication mechanisms,including the function of the SARS-CoV-2 genome and structure.Furthermore,we highlighted anti-SARS-CoV-2 therapeutic intervention efforts utilizing MNPs and predicted SARS-CoV-2 inhibitor design.
文摘For the past 2 years,the coronavirus responsible for the COVID-19 infection has become a world pandemic,ruining the lives and economies of several nations in the world.This has scaled up research on the virus and the resulting infection with the goal of developing new vaccines and therapies.Natural products are known to be a rich source of lead compounds for drug discovery,including against infectious diseases caused by microbes(viruses,bacteria and fungi).In this review article,we conducted a literature survey aimed at identifying natural products with inhibitory concentrations against the coronaviruses or their target proteins,which lie below 10μM.This led to the identification of 42 compounds belonging to the alkaloid,flavonoid,terpenoid,phenolic,xanthone and saponin classes.The cut off concentration of 10μM was to limit the study to the most potent chemical entities,which could be developed into therapies against the viral infection to make a contribution towards limiting the spread of the disease.
基金financially supported by the National Natural Science Foundation of China(Nos.81473256 and 81273561)the CAMS Innovation Fund for Medical Sciences(No.2016-I2M-1014,China)+3 种基金the Science and Technology Program of Beijing(No.Z151100000115008,China)the Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study(No.BZ0150,China)the Drug Innovation Major Project(Nos.2015ZX09102-023 and 2018ZX09711001-003-002,China)the Disciplines Construction Project(No.201920200802,China)
文摘The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics.Dietary supplements,especially natural products that are edible and safe for human use,are a good source of drug discovery with potential for uncovering novel applications,In this study,we tested 40 natural products of dietary supplements and identified capsaicin,a common dietary supplement abundant in chili peppers,as an inhibitor of Lassa virus(LASV)entry with EC5,of 6.9-10.0μmol/L using an HIV based pseudo virus platform.Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus(LCMV),showing a preferential activity against LASV.Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide(SSP)-GP2 transmembrane(GP2TM)region of the LASV surface glycoprotein.Mutational study revealed the key residues Ala25,Val431,Phe434 and Val435 in SsP-CP2TM region in capsaicin’s antiviral effect.This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV,providing detailed interaction hot spots in the unique SSP-GP2TMinterface of LASV glycoprotein that is crucial in fusion inhibition,and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.
基金financially supported by the National Natural Science Foundation of China(Nos.41476063,81520108028,81273430,41306130 81302692,41676073,81603022)SCTSM Project from Shanghai Science and Technology Committee,Shanghai,China(Nos.14431901100,15431901000)+4 种基金The project from Institutes for Drug Discovery and Development,Chinese Academy of Sciences,China(No.CASIMM0120152039)the SKLDR/SIMM Projects from Shanghai Institute of MateriaMedica,China(No.SIMM 1501ZZ-03)support of "Youth Innovation Promotion Association"(No.2016258) from Chinese Academy of Sciences"Young Talent Supporting Project" from China Association for Science and Technology(No.2016QNRC001)Shanghai "Pujiang Program"(No.16PJ1410600)
文摘Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15（1） and mycalenitrile-16（2）,along with five known related ones（3-7）,were isolated from the South China Sea sponge Mycale lissochela.The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those reported in the literature.In bioassay,compounds 1 and 7 exhibited significant PTPIB（Protein-tyrosine phosphatase 1B,a recognized target for diabetes and obesity） inhibitory activities with IC（50） values of 8.6 and 3.1 μmoI/L,respectively.A preliminary SAR analysis of the isolated compounds with their PTP1 B inhibitory effects was described.
基金supported by the National Natural Science Foundation of China (No. 31561143011)the IAEA-Coordinated Research Projects (D1.5016, RAS5083)。
文摘Nitrogen(N) losses in cropland resulting from the application of synthetic fertilizers decrease crop productivity and exacerbate environmental pollution.Mitigation measures, such as reduction in N fertilizer application rates, can have unintentional adverse effects on crop yield. We conducted a meta-analysis of soil N_(2)O emissions from agricultural fields across China under contrasting mitigation scenarios as a novel approach to identify the most effective strategy for the mitigation of emissions of N_(2)O derived from N fertilizer use in China. Current standard agricultural practice was used as a baseline scenario(BS), and 12 potential mitigation scenarios(S1–S12) were derived from the available literature and comprised single and combinations of management scenarios that accounted for crop yield. Mitigation scenarios S6(nitrification inhibitor 3,4-dimethylpyrazole phosphate) and S11(20% reduction in N application rate plus nitrification inhibitor dicyandiamide) in maize, rice, and wheat crops led to an average 56.0% reduction in N_(2)O emissions at the national level, whereas scenario S4(nitrification inhibitor dicyandiamide) led to yield optimization, with a 14.0% increase for maize and 8.0% increase for rice as compared to the BS. Implementation of these most effective mitigation scenarios(S4, S6, and S11) might help China, as a signatory to the 2015 United Nations Framework Convention on Climate Change(Paris Agreement), to achieve a 30% reduction in N_(2)O emissions by 2030.
