The H4 subtype of avian influenza virus(AIV)is prevalent worldwide,but only receives little attention due to its low pathogenicity in poultry.Consequently,it remains largely unclear whether H4 AIVs pose a potential th...The H4 subtype of avian influenza virus(AIV)is prevalent worldwide,but only receives little attention due to its low pathogenicity in poultry.Consequently,it remains largely unclear whether H4 AIVs pose a potential threat to the poultry industry and public health.During the period from 2011 to 2022,we conducted an active surveillance programm.A total of 154,762 swab samples were collected across various provinces,and 427 H4 viruses were detected,resulting in a positivity rate of 0.28%.All H4 viruses were isolated from poultry,primarily from ducks in live poultry markets.We further investigated the genetic evolutionary characteristics and pathogenicity of 20 H4Nx viruses isolated in our program.Phylogenetic analysis revealed that the 20 H4Nx viruses belonged to the Eurasian lineage and exhibited significant genetic diversity,with 19 distinct genotypes identified.Molecular characterization indicated that these viruses were low-pathogenicity AIVs with limited binding affinity to human receptors,yet they contained mutations associated with enhanced viral replication and pathogenicity in mammals.Pathogenicity tests conducted in ducks demonstrated that H4 viruses were weakly pathogenic,exhibiting limited replication and transmission capabilities.However,some viruses were able to replicate effectively in mice and induce weight loss.For instance,DK/AH/AG61/11(H4N6)can replicate efficiently in MDCK cells,indicating a potential threat to mammals.These findings underscore the importance of ongoing surveillance of H4 AIVs to better understand their evolution and transmission dynamics and to prevent potential public health risks.展开更多
Background:Accumulating studies have shown the important role of circular RNAs(circRNAs)in the oncogenesis and metastasis of various cancers.We previously reported that circACTN4 could bind with FUBP1 to promote tumor...Background:Accumulating studies have shown the important role of circular RNAs(circRNAs)in the oncogenesis and metastasis of various cancers.We previously reported that circACTN4 could bind with FUBP1 to promote tumorigenesis and the development of breast cancer(BC)by increasing the expression of MYC.However,its exact molecular mechanism and biological function have not been fully elucidated.Methods:Here,Circular RNA microarray analysis was conducted in 3 pairs of BC and paracancerous tissues.The expression of circACTN4 in BC cells and tissues was detected via reverse transcription‒quantitative PCR(RT‒qPCR).Cell Counting Kit-8(CCK-8),5-ethynyl-2-deoxyuridine(EdU),transwell migration,and invasion assays were performed to further detect the biological functions of circACTN4 in BC cells.Xenograft models were used to investigate the in vivo role of circACTN4.Fluorescence in situ hybridization,Chromatin immunoprecipitation(ChIP)‒qPCR,coimmunoprecipitation,fluorometric,western blot,and rescue experiments were performed to explore the mechanism of circACTN4.Results:Our results revealed that circACTN4 was highly expressed in BC cells and tissues.The upregulated expression of circACTN4 was significantly related to the T stage and TNM stage and poor prognosis of patients with BC.circACTN4 was located primarily in the nucleus of BC cells.Upregulation of circACTN4 significantly increased the proliferation,invasion,and growth of BC cells,whereas the downregulation of circACTN4 exerted the opposite effects and induced G1/S cell cycle arrest.Mechanistically,we showed that circACTN4 could upregulate the expression of MYC and that MYC might interact with TIP60 histone acetyltransferase to increase the recruitment of TIP60 to MYC target genes and histone H4 acetylation(AcH4),thus promoting the progression of the breast cancer cell cycle and tumorigenesis.Conclusion:Taken together,our findings reveal for the first time a new mechanism by which circACTN4 could promote oncogenesis and the development of BC by increasing the AcH4 of MYC target genes via TIP60.Therefore,circACTN4 could be a novel target for BC diagnosis and remedy.展开更多
目的观察参芪补肺汤对慢性阻塞性肺疾病(COPD)肺气虚证大鼠支气管平滑肌(ASM)中乙酰化组蛋白H4、组蛋白去乙酰化酶-2(HDAC2)和核因子-κB p65(NF-κB p65)表达的影响。方法取SD大鼠40只,随机分为正常组、模型组、参芪补肺汤组、氨茶碱组...目的观察参芪补肺汤对慢性阻塞性肺疾病(COPD)肺气虚证大鼠支气管平滑肌(ASM)中乙酰化组蛋白H4、组蛋白去乙酰化酶-2(HDAC2)和核因子-κB p65(NF-κB p65)表达的影响。方法取SD大鼠40只,随机分为正常组、模型组、参芪补肺汤组、氨茶碱组,每组10只。运用气管内注射脂多糖加烟熏28 d的方法建立COPD肺气虚证大鼠模型。光镜下观察肺组织的病理形态学变化,运用图像分析法测量小气道管壁和ASM的厚度,采用免疫组化和Western blot方法检测大鼠ASM中乙酰化组蛋白H4、HDAC2和NF-κB p65的蛋白表达,实时荧光定量PCR方法检测大鼠ASM组织中HDAC2 m RNA和NF-κB p65 m RNA的表达。结果与正常组比较,模型组大鼠气道管壁和ASM厚度明显增高(P<0.05);与模型组比较,参芪补肺汤组和氨茶碱组气道管壁和ASM厚度明显降低(P<0.05);参芪补肺汤组与氨茶碱组比较差异无统计学意义(P>0.05)。与正常组比较,模型组乙酰化组蛋白H4的蛋白表达、NF-κB p65 m RNA和蛋白的表达明显增高(P<0.05);HDAC2m RNA和蛋白的表达均明显降低(P<0.05);与模型组比较,参芪补肺汤组和氨茶碱组乙酰化组蛋白H4的蛋白表达、NF-κB p65 m RNA和蛋白的表达明显增高(P<0.05);HDAC2 m RNA和蛋白的表达明显降低(P<0.05)。参芪补肺汤组与氨茶碱组比较差异均无统计学意义(P>0.05)。结论参芪补肺汤可抑制COPD肺气虚证模型大鼠ASM增殖,其机制与其提高HDAC2的表达,使组蛋白H4去乙酰化,从而抑制NF-κB p65的表达有关。展开更多
基金funded by the National Key Research and Development Program of China(Grant No.2021YFD1800201).
文摘The H4 subtype of avian influenza virus(AIV)is prevalent worldwide,but only receives little attention due to its low pathogenicity in poultry.Consequently,it remains largely unclear whether H4 AIVs pose a potential threat to the poultry industry and public health.During the period from 2011 to 2022,we conducted an active surveillance programm.A total of 154,762 swab samples were collected across various provinces,and 427 H4 viruses were detected,resulting in a positivity rate of 0.28%.All H4 viruses were isolated from poultry,primarily from ducks in live poultry markets.We further investigated the genetic evolutionary characteristics and pathogenicity of 20 H4Nx viruses isolated in our program.Phylogenetic analysis revealed that the 20 H4Nx viruses belonged to the Eurasian lineage and exhibited significant genetic diversity,with 19 distinct genotypes identified.Molecular characterization indicated that these viruses were low-pathogenicity AIVs with limited binding affinity to human receptors,yet they contained mutations associated with enhanced viral replication and pathogenicity in mammals.Pathogenicity tests conducted in ducks demonstrated that H4 viruses were weakly pathogenic,exhibiting limited replication and transmission capabilities.However,some viruses were able to replicate effectively in mice and induce weight loss.For instance,DK/AH/AG61/11(H4N6)can replicate efficiently in MDCK cells,indicating a potential threat to mammals.These findings underscore the importance of ongoing surveillance of H4 AIVs to better understand their evolution and transmission dynamics and to prevent potential public health risks.
基金supported by National Natural Science Foundation of China(No.82173170,Junxia ChenNo.82103089,Lei Xing)Natural Science Foundation of Chongqing,China(No.CSTB2022BSXMJCX0057,Lei Xing).
文摘Background:Accumulating studies have shown the important role of circular RNAs(circRNAs)in the oncogenesis and metastasis of various cancers.We previously reported that circACTN4 could bind with FUBP1 to promote tumorigenesis and the development of breast cancer(BC)by increasing the expression of MYC.However,its exact molecular mechanism and biological function have not been fully elucidated.Methods:Here,Circular RNA microarray analysis was conducted in 3 pairs of BC and paracancerous tissues.The expression of circACTN4 in BC cells and tissues was detected via reverse transcription‒quantitative PCR(RT‒qPCR).Cell Counting Kit-8(CCK-8),5-ethynyl-2-deoxyuridine(EdU),transwell migration,and invasion assays were performed to further detect the biological functions of circACTN4 in BC cells.Xenograft models were used to investigate the in vivo role of circACTN4.Fluorescence in situ hybridization,Chromatin immunoprecipitation(ChIP)‒qPCR,coimmunoprecipitation,fluorometric,western blot,and rescue experiments were performed to explore the mechanism of circACTN4.Results:Our results revealed that circACTN4 was highly expressed in BC cells and tissues.The upregulated expression of circACTN4 was significantly related to the T stage and TNM stage and poor prognosis of patients with BC.circACTN4 was located primarily in the nucleus of BC cells.Upregulation of circACTN4 significantly increased the proliferation,invasion,and growth of BC cells,whereas the downregulation of circACTN4 exerted the opposite effects and induced G1/S cell cycle arrest.Mechanistically,we showed that circACTN4 could upregulate the expression of MYC and that MYC might interact with TIP60 histone acetyltransferase to increase the recruitment of TIP60 to MYC target genes and histone H4 acetylation(AcH4),thus promoting the progression of the breast cancer cell cycle and tumorigenesis.Conclusion:Taken together,our findings reveal for the first time a new mechanism by which circACTN4 could promote oncogenesis and the development of BC by increasing the AcH4 of MYC target genes via TIP60.Therefore,circACTN4 could be a novel target for BC diagnosis and remedy.
文摘目的观察参芪补肺汤对慢性阻塞性肺疾病(COPD)肺气虚证大鼠支气管平滑肌(ASM)中乙酰化组蛋白H4、组蛋白去乙酰化酶-2(HDAC2)和核因子-κB p65(NF-κB p65)表达的影响。方法取SD大鼠40只,随机分为正常组、模型组、参芪补肺汤组、氨茶碱组,每组10只。运用气管内注射脂多糖加烟熏28 d的方法建立COPD肺气虚证大鼠模型。光镜下观察肺组织的病理形态学变化,运用图像分析法测量小气道管壁和ASM的厚度,采用免疫组化和Western blot方法检测大鼠ASM中乙酰化组蛋白H4、HDAC2和NF-κB p65的蛋白表达,实时荧光定量PCR方法检测大鼠ASM组织中HDAC2 m RNA和NF-κB p65 m RNA的表达。结果与正常组比较,模型组大鼠气道管壁和ASM厚度明显增高(P<0.05);与模型组比较,参芪补肺汤组和氨茶碱组气道管壁和ASM厚度明显降低(P<0.05);参芪补肺汤组与氨茶碱组比较差异无统计学意义(P>0.05)。与正常组比较,模型组乙酰化组蛋白H4的蛋白表达、NF-κB p65 m RNA和蛋白的表达明显增高(P<0.05);HDAC2m RNA和蛋白的表达均明显降低(P<0.05);与模型组比较,参芪补肺汤组和氨茶碱组乙酰化组蛋白H4的蛋白表达、NF-κB p65 m RNA和蛋白的表达明显增高(P<0.05);HDAC2 m RNA和蛋白的表达明显降低(P<0.05)。参芪补肺汤组与氨茶碱组比较差异均无统计学意义(P>0.05)。结论参芪补肺汤可抑制COPD肺气虚证模型大鼠ASM增殖,其机制与其提高HDAC2的表达,使组蛋白H4去乙酰化,从而抑制NF-κB p65的表达有关。
