Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins ...Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.展开更多
Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its ...Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells.In the brains of Alzheimer's disease(AD)patients,decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and A0 generation.In this review,we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD.The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed.It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.展开更多
The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was or...The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was originally published electronically on the publisher's internet portal on 13 March 2020 without open access.With the author(s)'decision to opt for Open Choice the copyright of the article changed to O The Author(s)2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/),which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.展开更多
The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into c...The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein,and the phosphorylation levels of PP2A Y307 and tau at different sites,as well as PP2A activity were detected at different time points after siRNA transfection.Twelve hours after siRNA transfec-tion,the protein level of Src was dramatically decreased,with decreased PP2A Y307 phosphorylation.However,the total PP2A protein level was also decreased,together with a decreased PP2A activity.Tau was hyperpho-sphorylated at the Ser198/199/202 sites.Multiple factors may be involved in the cellular regulation of PP2A activ-ity.Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.展开更多
Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission...Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.展开更多
基金supported by the National Natural Science Foundation of China(No.31771189)the Wuhan Health Commission(No.WX18C17 and No.WX19Q31)the Natural Science Foundation of Hubei Province,China(No.2017CFA065 and No.WJ2019H378).
文摘Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.
基金grants from National Natural Science Foundation of China(No.31970964 and No.31771189)Natural Science Foundation of Hubei Province,China(No.2017CFA065)Wuhan Health and Family Planning Commission(No.WX18C17).
文摘Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells.In the brains of Alzheimer's disease(AD)patients,decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and A0 generation.In this review,we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD.The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed.It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.
文摘The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was originally published electronically on the publisher's internet portal on 13 March 2020 without open access.With the author(s)'decision to opt for Open Choice the copyright of the article changed to O The Author(s)2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/),which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.
基金supported by the National Natural Science Foundation of China(Grant Nos.30500188,30471922 and 30731160621)Gamla Tja¨narinnor Foundation and Gun och Bertil Stohnes Stiftelse.
文摘The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein,and the phosphorylation levels of PP2A Y307 and tau at different sites,as well as PP2A activity were detected at different time points after siRNA transfection.Twelve hours after siRNA transfec-tion,the protein level of Src was dramatically decreased,with decreased PP2A Y307 phosphorylation.However,the total PP2A protein level was also decreased,together with a decreased PP2A activity.Tau was hyperpho-sphorylated at the Ser198/199/202 sites.Multiple factors may be involved in the cellular regulation of PP2A activ-ity.Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.
文摘Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.
