目的 分析血清果蝇母性DPP同源物(serum small mother against decapentaplegic,Smad)2、Smad3与冠状动脉粥样硬化性心脏病(冠心病)患者心脏猝死的相关性。方法 选取2018年3月至2020年6月无锡市人民医院收治的住院接受治疗的冠心病患者...目的 分析血清果蝇母性DPP同源物(serum small mother against decapentaplegic,Smad)2、Smad3与冠状动脉粥样硬化性心脏病(冠心病)患者心脏猝死的相关性。方法 选取2018年3月至2020年6月无锡市人民医院收治的住院接受治疗的冠心病患者134例为研究对象,随访1年,根据冠心病患者有无发生心脏猝死分为猝死组(21例)和未猝死组(113例)。采用酶联免疫吸附试验(ELISA)法检测患者血清中Smad2、Smad3浓度。采用动态心电图仪详细记录患者QT间期、PR间期、QRS波持续时间。采用受试者工作特征曲线(receiver operating characteristic curve,ROC)评价QRS波持续时间联合Smad2、Smad3对冠心病患者心脏猝死的诊断价值。应用二元Logistic回归分析对影响冠心病患者心脏猝死的危险因素进行分析。结果 与未猝死组相比,猝死组患者QRS波持续时间[(116.74±14.58)ms vs.(88.42±10.67)ms]、血清Smad2[(286.42±38.71)μg/L vs.(164.93±22.28)μg/L]、Smad3[(335.18±50.06)μg/L vs.(190.25±29.72)μg/L]浓度较高,差异有统计学意义(P<0.05)。ROC分析显示,QRS波持续时间、血清Smad2和Smad3浓度诊断冠心病患者心脏猝死的曲线下面积(area under the curve,AUC)分别为0.742、0.825、0.842;QRS波持续时间联合Smad2、Smad3诊断冠心病患者心脏猝死的AUC为0.893,其敏感度、特异度分别为81.00%、93.80%。QRS波持续时间、Smad2、Smad3是冠心病患者心脏猝死危险因素(P<0.05)。结论 动态心电图联合血清Smad2、Smad3浓度检测对预测冠心病患者心脏猝死有一定价值。展开更多
This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed ...This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.展开更多
report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-relatedcoronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropos...report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-relatedcoronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). Thisvirus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by afurin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity forhDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic inhuman airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoirhosts of coronaviruses poised for human disease emergence.展开更多
A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk.We developed an enzyme activity-screening platform to investigate how gut microbiot...A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk.We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology.We discovered that dipeptidyl peptidase 4(DPP4)is expressed by specific bacterial taxa of the microbiota.Microbial DPP4 was able to decrease the active glucagon like peptide-1(GLP-1)and disrupt glucose metabolism in mice with a leaky gut.Furthermore,the current drugs targeting human DPP4,including sitagliptin,had little effect on microbial DPP4.Using high-throughput screening,we identified daurisoline-d4(Dau-d4)as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.展开更多
文摘目的 分析血清果蝇母性DPP同源物(serum small mother against decapentaplegic,Smad)2、Smad3与冠状动脉粥样硬化性心脏病(冠心病)患者心脏猝死的相关性。方法 选取2018年3月至2020年6月无锡市人民医院收治的住院接受治疗的冠心病患者134例为研究对象,随访1年,根据冠心病患者有无发生心脏猝死分为猝死组(21例)和未猝死组(113例)。采用酶联免疫吸附试验(ELISA)法检测患者血清中Smad2、Smad3浓度。采用动态心电图仪详细记录患者QT间期、PR间期、QRS波持续时间。采用受试者工作特征曲线(receiver operating characteristic curve,ROC)评价QRS波持续时间联合Smad2、Smad3对冠心病患者心脏猝死的诊断价值。应用二元Logistic回归分析对影响冠心病患者心脏猝死的危险因素进行分析。结果 与未猝死组相比,猝死组患者QRS波持续时间[(116.74±14.58)ms vs.(88.42±10.67)ms]、血清Smad2[(286.42±38.71)μg/L vs.(164.93±22.28)μg/L]、Smad3[(335.18±50.06)μg/L vs.(190.25±29.72)μg/L]浓度较高,差异有统计学意义(P<0.05)。ROC分析显示,QRS波持续时间、血清Smad2和Smad3浓度诊断冠心病患者心脏猝死的曲线下面积(area under the curve,AUC)分别为0.742、0.825、0.842;QRS波持续时间联合Smad2、Smad3诊断冠心病患者心脏猝死的AUC为0.893,其敏感度、特异度分别为81.00%、93.80%。QRS波持续时间、Smad2、Smad3是冠心病患者心脏猝死危险因素(P<0.05)。结论 动态心电图联合血清Smad2、Smad3浓度检测对预测冠心病患者心脏猝死有一定价值。
基金supported through the Natural Science Foundation of Jiangsu Province(No.BK20201172)the Key Project of the Jiangsu Health Commission(No.ZDB2020016)the Jiangsu Province Key Research and Development Program:Social Development Project(No.BE2021653).
文摘This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.
文摘report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-relatedcoronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). Thisvirus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by afurin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity forhDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic inhuman airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoirhosts of coronaviruses poised for human disease emergence.
文摘A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk.We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology.We discovered that dipeptidyl peptidase 4(DPP4)is expressed by specific bacterial taxa of the microbiota.Microbial DPP4 was able to decrease the active glucagon like peptide-1(GLP-1)and disrupt glucose metabolism in mice with a leaky gut.Furthermore,the current drugs targeting human DPP4,including sitagliptin,had little effect on microbial DPP4.Using high-throughput screening,we identified daurisoline-d4(Dau-d4)as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.
