Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune res...Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.展开更多
Background:Chronic obstructive pulmonary disease(COPD)is a progressive chronic inflammatory disease characterized by irreversible airflow limitation.Fritillaria thunbergii Miq.Zhebeimu(ZBM)has a long history in treati...Background:Chronic obstructive pulmonary disease(COPD)is a progressive chronic inflammatory disease characterized by irreversible airflow limitation.Fritillaria thunbergii Miq.Zhebeimu(ZBM)has a long history in treating COPD,but the underlying mechanism is still unclear.Methods:This study explored the pathological mechanism of COPD through RNA-Seq analysis and single-cell sequencing data analysis.And the mechanism of ZBM and blood entering sRNAs for COPD was verified with network pharmacology analysis and in vitro experiments.Results:The results showed that inflammation and oxidative stress exacerbated the progression of COPD,and the expression of HSP90AA1,PTGS2,and AGRN genes significantly increased in the lung tissue of patients.Network pharmacology analysis suggests that the natural products contained in ZBM may directly target HSP90AA1,PTGS2,and AGRN for the treatment of COPD.Analysis of the blood entering sRNA contained in the decoction of ZBM revealed its excellent antioxidant and anti-macrophage polarization effects.Meanwhile,ZBM decoction,sRNA2,and sRNA5 reduce oxidative stress and inflammation by acting on prostaglandin-endoperoxide synthase 2(PTGS2),nitric oxide synthase 2(NOS2),ATP-binding cassette,subfamily C member 1(ABCC1),and xeroderma pigmentosum complementation group C(XPC)genes.Conclusion:Our study demonstrated that ZBM extract and ZBM derived sRNA2 and sRNA5 can relieve COPD by regulating PTGS2-NOS2-XPC-ABCC1 axis.展开更多
基金supported by the National Natural Science Foundation of China (32373181)National Key Research and Development Program (2023YFD2400700)+2 种基金Science and Technology Plan Project of Fujian Province (2022L3059)High-quality Development of Marine and Fishery Industry Special Fund Project of Fujian Province (FJHYF-L-2023-5)Open Fund of Fujian Province Key Laboratory of Special Aquatic Formula Feed (TMKJZ2302)。
文摘Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.
文摘Background:Chronic obstructive pulmonary disease(COPD)is a progressive chronic inflammatory disease characterized by irreversible airflow limitation.Fritillaria thunbergii Miq.Zhebeimu(ZBM)has a long history in treating COPD,but the underlying mechanism is still unclear.Methods:This study explored the pathological mechanism of COPD through RNA-Seq analysis and single-cell sequencing data analysis.And the mechanism of ZBM and blood entering sRNAs for COPD was verified with network pharmacology analysis and in vitro experiments.Results:The results showed that inflammation and oxidative stress exacerbated the progression of COPD,and the expression of HSP90AA1,PTGS2,and AGRN genes significantly increased in the lung tissue of patients.Network pharmacology analysis suggests that the natural products contained in ZBM may directly target HSP90AA1,PTGS2,and AGRN for the treatment of COPD.Analysis of the blood entering sRNA contained in the decoction of ZBM revealed its excellent antioxidant and anti-macrophage polarization effects.Meanwhile,ZBM decoction,sRNA2,and sRNA5 reduce oxidative stress and inflammation by acting on prostaglandin-endoperoxide synthase 2(PTGS2),nitric oxide synthase 2(NOS2),ATP-binding cassette,subfamily C member 1(ABCC1),and xeroderma pigmentosum complementation group C(XPC)genes.Conclusion:Our study demonstrated that ZBM extract and ZBM derived sRNA2 and sRNA5 can relieve COPD by regulating PTGS2-NOS2-XPC-ABCC1 axis.
基金supported by grants from National High Technology Development Program of China (2006AA02Z323)National Sciences Foundation of China (90608004,30470411)~~
