AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and tre...AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic(P < 0.02) and histological scores(P < 0.01) and restored the densities of collagen fibers in tissue(P = 0.015;P = 0.001),the number of goblet cells(P = 0.021;P = 0.029),and the rate of apoptosis within the epithelium(P = 0.043;P = 0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.展开更多
Short-chain dehydrogenases/reductases(SDRs)are ubiquitously distributed across diverse organisms and play pivotal roles in the growth,as well as endogenous and exogenous metabolism of various substances,including drug...Short-chain dehydrogenases/reductases(SDRs)are ubiquitously distributed across diverse organisms and play pivotal roles in the growth,as well as endogenous and exogenous metabolism of various substances,including drugs.The expression levels of SDR genes are reportedly upregulated in the fenpropathrin(FEN)-resistant(FeR)strain of Tetranychus cinnabarinus.However,the functions of these SDR genes in acaricide tolerance remain elusive.In this study,the activity of SDRs was found to be significantly higher(2.26-fold)in the FeR strain compared to the susceptible strain(SS)of T.cinnabarinus.A specific upregulated SDR gene,named SDR112C1,exhibited significant overexpression(3.13-fold)in the FeR population compared with that in the SS population.Furthermore,the expression of SDR112C1 showed a significant increase in the response to FEN induction.Additionally,knockdown of the SDR112C1 gene resulted in decreased SDR activity and reduced mite viability against FEN.Importantly,heterologous expression and in vitro incubation assays confirmed that recombinant SDR112C1 could effectively deplete FEN.Moreover,the overexpression of the SDR112C1 gene in Drosophila melanogaster significantly decreased the toxicity of FEN to transgenic fruit flies.These findings suggest that the overexpression of SDR SDR112C1 is a crucial factor contributing to FEN tolerance in T.cinnabarinus.This discovery not only enhances our understanding of SDR-mediated acaricide tolerance but also introduces a new family of detoxification enzymes to consider in practice,beyond cytochrome P450s,carboxyl/choline esterases and glutathione S-transferases.展开更多
Background and Aims:End-stage liver disease is associated with disruptions in gut microbiota composition and function,which may facilitate gut-to-liver bacterial translocation,impacting liver graft integrity and clini...Background and Aims:End-stage liver disease is associated with disruptions in gut microbiota composition and function,which may facilitate gut-to-liver bacterial translocation,impacting liver graft integrity and clinical outcomes following liver transplantation.This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.Methods:This single-center,non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion(NMP).Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3,6,and 12.Stool microbiota was profiled via 16S rRNA gene sequencing,stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry,and breath volatile organic compounds(VOCs)were analyzed with selected-ion flow-tube mass spectrometry.Results:Both cohorts experienced a loss of microbiota diversity and dominance by single taxa.The NMP cohort demonstrated enrichment of several beneficial gut taxa,while the static cold storage cohort showed depletion of such taxa.Various gut bacteria were found to correlate with stool short-chain fatty acids(e.g.,lactic acid,butyric acid)and several VOCs.Conclusions:Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation.However,notable differences in microbiota composition and function were observed between liver graft preservation methods.Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.展开更多
基金Supported by Grants from the Brazilian Research CouncilFundao de Amparo à Pesquisa do Estado do Rio de Janeiro
文摘AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic(P < 0.02) and histological scores(P < 0.01) and restored the densities of collagen fibers in tissue(P = 0.015;P = 0.001),the number of goblet cells(P = 0.021;P = 0.029),and the rate of apoptosis within the epithelium(P = 0.043;P = 0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.
基金funded by the National Natural Science Foundation of China(U2202202)the National Key Research,Development Program of China(2023YFD1400000)Chongqing China Three Gorges Museum independent project(3GM2022-KTZ06).
文摘Short-chain dehydrogenases/reductases(SDRs)are ubiquitously distributed across diverse organisms and play pivotal roles in the growth,as well as endogenous and exogenous metabolism of various substances,including drugs.The expression levels of SDR genes are reportedly upregulated in the fenpropathrin(FEN)-resistant(FeR)strain of Tetranychus cinnabarinus.However,the functions of these SDR genes in acaricide tolerance remain elusive.In this study,the activity of SDRs was found to be significantly higher(2.26-fold)in the FeR strain compared to the susceptible strain(SS)of T.cinnabarinus.A specific upregulated SDR gene,named SDR112C1,exhibited significant overexpression(3.13-fold)in the FeR population compared with that in the SS population.Furthermore,the expression of SDR112C1 showed a significant increase in the response to FEN induction.Additionally,knockdown of the SDR112C1 gene resulted in decreased SDR activity and reduced mite viability against FEN.Importantly,heterologous expression and in vitro incubation assays confirmed that recombinant SDR112C1 could effectively deplete FEN.Moreover,the overexpression of the SDR112C1 gene in Drosophila melanogaster significantly decreased the toxicity of FEN to transgenic fruit flies.These findings suggest that the overexpression of SDR SDR112C1 is a crucial factor contributing to FEN tolerance in T.cinnabarinus.This discovery not only enhances our understanding of SDR-mediated acaricide tolerance but also introduces a new family of detoxification enzymes to consider in practice,beyond cytochrome P450s,carboxyl/choline esterases and glutathione S-transferases.
基金supported in part by a grant from the Lerner Research Institute,Cleveland Clinic to GAMC and CQ.
文摘Background and Aims:End-stage liver disease is associated with disruptions in gut microbiota composition and function,which may facilitate gut-to-liver bacterial translocation,impacting liver graft integrity and clinical outcomes following liver transplantation.This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.Methods:This single-center,non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion(NMP).Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3,6,and 12.Stool microbiota was profiled via 16S rRNA gene sequencing,stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry,and breath volatile organic compounds(VOCs)were analyzed with selected-ion flow-tube mass spectrometry.Results:Both cohorts experienced a loss of microbiota diversity and dominance by single taxa.The NMP cohort demonstrated enrichment of several beneficial gut taxa,while the static cold storage cohort showed depletion of such taxa.Various gut bacteria were found to correlate with stool short-chain fatty acids(e.g.,lactic acid,butyric acid)and several VOCs.Conclusions:Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation.However,notable differences in microbiota composition and function were observed between liver graft preservation methods.Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.
