Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. The aim of the study was to use this experimental model to elucidate if Thl 7 cells are involve...Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. The aim of the study was to use this experimental model to elucidate if Thl 7 cells are involved in the development of gastrointestinal hypermotility. Colonic smooth muscle contractility was investigated in response to acetylcholine. The levels of IL-17, IL-23 and TGF-β1 in colon were measured by Western blotting. Flow cytometric detection of intracellular IFN-7/IL-4/ IL- 17 cytokine production was used to analyze the proportions of CD4＋ T cells subsets in colon. Our results showed that colonic muscle contractility was increased 2 weeks post infection （PI） and stayed high 12 weeks PI when no discernible inflammation was present in the gut. The proportion of Th17 cells and the expression of IL-17 were up-regulated in colon 2 weeks PI and returned to normal 8 weeks PI. The content of IL-17 was correlated with the colonic smooth muscle hypercontracility 2 weeks PI. Meanwhile, TGF-β1 was increased 2 weeks PI, while IL-23 was normal. Our results suggest that Th17 cells affect the colonic muscle contractility in mice infected with Trichinella spiralis at intestine stage but not at muscle stage and the effect of Th17 cells on muscle contractility might be induced by TGF-β1. Other cytokines might be involved in the hypercontracility of colonic smooth muscle at muscle stage.展开更多
Ulcerative colitis(UC)is a type of chronic inflammatory recurrent disease.At present,the etiology and pathogenesis are still unclear,and immune factors are usually considered to be the final link in the pathogenesis o...Ulcerative colitis(UC)is a type of chronic inflammatory recurrent disease.At present,the etiology and pathogenesis are still unclear,and immune factors are usually considered to be the final link in the pathogenesis of UC.Due to the increasing incidence of this disease,longer course of disease,and difficult to heal,related research has gradually deepened,and related researches on intestinal flora,immunity,genetics,etc.have become hotspots.A large amount of evidence indicates that regulatory T cells(Treg),helper T cell 17(Th17),Th17/Treg immune axis and intestinal microbiota in UC patients play an important role in regulating the occurrence and development of diseases.In recent years,the intestine has been gradually discovered There is also a certain correlation between the tract microbiota and the Th17/Treg immune axis.Therefore,this article examines a large number of relevant Chinese and English materials at home and abroad in recent years to analyze the Th17/Treg cells,intestinal microbiota and the relationship between the two in UC patients.The existing relevance and other issues are briefly discussed and summarized in order to provide more practical basis for clinical targeted therapy.展开更多
Objective: To explore the effects of nutritional support and intervention on intestinal flora, Th cellular immune response and inflammatory response in patients with severe ulcerative colitis. Methods: A total of 90 U...Objective: To explore the effects of nutritional support and intervention on intestinal flora, Th cellular immune response and inflammatory response in patients with severe ulcerative colitis. Methods: A total of 90 UC patients who were diagnosed and treated in the hospital between August 2014 and January 2017 were divided into the control group (n=45) and the nutritional intervention group (n=45) by random number table. Control group received clinical routine therapy for UC, and nutritional intervention group received routine therapy as well as nutritional support and intervention. The differences in the intestinal flora distribution, Th1/Th2 cytokine contents and inflammatory mediator contents were compared between the two groups. Results: Before intervention, there was no statistically significant difference in the intestinal flora distribution, Th1/Th2 cytokine contents and inflammatory mediator contents between the two groups. After intervention, the number of enterobacter and enterococcus in nutritional intervention group were lower than those in control group whereas the number of lactobacilli, Bifidobacterium and clostridium butyricum were higher than those in control group;serum IL-2 and IFN-γ contents were lower than those of control group whereas IL-4 and IL-10 contents were higher than those of control group;serum MCP-1, MIP-1a and HMGB-1 contents were lower than those of control group. Conclusion: Nutritional support and intervention can further balance the intestinal flora distribution and Th1/Th2 immune response and suppress the systemic inflammatory response in patients with severe ulcerative colitis.展开更多
Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Meth...Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.展开更多
BACKGROUND Esophageal replacement(ER)with gastric pull-up(GPU)or jejunal interposition(JI)used to be the standard treatment for long-gap esophageal atresia(LGEA).Changes of the ER grafts on a macro-and microscopic lev...BACKGROUND Esophageal replacement(ER)with gastric pull-up(GPU)or jejunal interposition(JI)used to be the standard treatment for long-gap esophageal atresia(LGEA).Changes of the ER grafts on a macro-and microscopic level however,are unknown.AIM To evaluate long-term clinical symptoms and anatomical and mucosal changes in adolescents and adults after ER for LGEA.METHODS A cohort study was conducted including all LGEA patients≥16 years who had undergone GPU or JI between 1985-2003 at two tertiary referral centers in the Netherlands.Patients underwent clinical assessment,contrast study and endoscopy with biopsy.Data was collected prospectively.Group differences between JI and GPU patients,and associations between different outcome measures were assessed using the Fisher’s exact test for bivariate variables and the Mann-Whitney U-test for continuous variables.Differences with a P-value<0.05 were considered statistically significant.RESULTS Nine GPU patients and eleven JI patients were included.Median age at follow-up was 21.5 years and 24.4 years,respectively.Reflux was reported in six GPU patients(67%)vs four JI patients(36%)(P=0.37).Dysphagia symptoms were reported in 64%of JI patients,compared to 22%of GPU patients(P=0.09).Contrast studies showed dilatation of the jejunal graft in six patients(55%)and graft lengthening in four of these six patients.Endoscopy revealed columnar-lined esophagus in three GPU patients(33%)and intestinal metaplasia was histologically confirmed in two patients(22%).No association was found between reflux symptoms and macroscopic anomalies or intestinal metaplasia.Three GPU patients(33%)experienced severe feeding problems vs none in the JI group.The median body mass index of JI patients was 20.9 kg/m^(2) vs 19.5 kg/m^(2) in GPU patients(P=0.08).CONCLUSION The majority of GPU patients had reflux and intestinal metaplasia in 22%.The majority of JI patients had dysphagia and a dilated graft.Follow-up after ER for LGEA is essential.展开更多
Objective To observe the effect of Modified Xijiao Dihuang Decoction(加味犀角地黄汤,MXDD)on rats with radiation enteritis,and explore its action mechanism.Methods Thirty female Sprague Dawley rats were divided into th...Objective To observe the effect of Modified Xijiao Dihuang Decoction(加味犀角地黄汤,MXDD)on rats with radiation enteritis,and explore its action mechanism.Methods Thirty female Sprague Dawley rats were divided into the control,model,dexamethasone(DXM),golden bifid(GB)and MXDD groups using random number table,6 rats in each group.Except the control group,the other rats were developed into radiation enteritis model by exposing to a single 60Co-γray at a dose of 11 Gy.The rats in the DXM,GB and MXDD groups were treated with DXM(1.425 mg/kg),GB(0.8 g/kg)and MXDD(36.0 g/kg)for 3 days,respectively.Body weight and diarrhea condition of rats were evaluated daily.On day 3,the feces of rats were collected for intestinal flora detection and the small intestinal tissues were also collected.Bacterial species annotation,alpha and beta diversities as well as composition of intestinal flora were detected and compared.The protein and mRNA expressions of interleukin 17(IL-17),retinoid-related orphan nuclear receptor gamma t(ROR-γt)and forkhead/winged helix transcription factor p3(FoxP3)were determined by Western blot and polymerase chain reaction,respectively.The abundance and diversity of intestinal flora as well as the proportion at the phylum and genus levels were assayed by 16S rRNA metagenome sequencing.Correlation between intestinal flora and Th17/Treg was analyzed by heatmap method.Results On day 1 to 3 after radiation,compared with the control group,the body weight in model group was decreased(P<0.05 or P<0.01).Compared with the model group,MXDD could alleviate weight loss and diarrhea caused by irradiation.At the phylum level,MXDD cause a significant increase in Firmicutes,and a decrease in Proteobacteria(P<0.05 or P<0.01).At the genus level,MXDD reduced the proportion of Escherichia Shigella(P<0.01).In addition,IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment(P<0.05).Besides,Firmicutes and Lactobacillus were positively correlated with FoxP3(r=0.73,0.79,respectively;P<0.01),negatively correlated with IL-17(r=0.66,0.64,respectively;P<0.01 or P<0.05)and ROR-γt(r0.73,0.81,respectively;P<0.01).Proteobacteria and Escherichia Shigella both had positive correlation with IL-17(r 0.77,0.57,respectively;P<0.01 or P<0.05)and ROR-γt(r=0.94,0.79,respectively;P<0.01)and negative correlation with FoxP3(r0.74,0.65;P<0.01).Conclusion MXDD could improve the survival status of irradiated rats by regulating the richness,diversity and composition of intestinal flora,and restoring the balance of Th17/Treg.展开更多
The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the princ...The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.展开更多
基金supported by a grant from the National Natural Sciences Foundation of China(No.30770986)
文摘Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. The aim of the study was to use this experimental model to elucidate if Thl 7 cells are involved in the development of gastrointestinal hypermotility. Colonic smooth muscle contractility was investigated in response to acetylcholine. The levels of IL-17, IL-23 and TGF-β1 in colon were measured by Western blotting. Flow cytometric detection of intracellular IFN-7/IL-4/ IL- 17 cytokine production was used to analyze the proportions of CD4＋ T cells subsets in colon. Our results showed that colonic muscle contractility was increased 2 weeks post infection （PI） and stayed high 12 weeks PI when no discernible inflammation was present in the gut. The proportion of Th17 cells and the expression of IL-17 were up-regulated in colon 2 weeks PI and returned to normal 8 weeks PI. The content of IL-17 was correlated with the colonic smooth muscle hypercontracility 2 weeks PI. Meanwhile, TGF-β1 was increased 2 weeks PI, while IL-23 was normal. Our results suggest that Th17 cells affect the colonic muscle contractility in mice infected with Trichinella spiralis at intestine stage but not at muscle stage and the effect of Th17 cells on muscle contractility might be induced by TGF-β1. Other cytokines might be involved in the hypercontracility of colonic smooth muscle at muscle stage.
基金National natural science foundation of China(No.81803951)。
文摘Ulcerative colitis(UC)is a type of chronic inflammatory recurrent disease.At present,the etiology and pathogenesis are still unclear,and immune factors are usually considered to be the final link in the pathogenesis of UC.Due to the increasing incidence of this disease,longer course of disease,and difficult to heal,related research has gradually deepened,and related researches on intestinal flora,immunity,genetics,etc.have become hotspots.A large amount of evidence indicates that regulatory T cells(Treg),helper T cell 17(Th17),Th17/Treg immune axis and intestinal microbiota in UC patients play an important role in regulating the occurrence and development of diseases.In recent years,the intestine has been gradually discovered There is also a certain correlation between the tract microbiota and the Th17/Treg immune axis.Therefore,this article examines a large number of relevant Chinese and English materials at home and abroad in recent years to analyze the Th17/Treg cells,intestinal microbiota and the relationship between the two in UC patients.The existing relevance and other issues are briefly discussed and summarized in order to provide more practical basis for clinical targeted therapy.
文摘Objective: To explore the effects of nutritional support and intervention on intestinal flora, Th cellular immune response and inflammatory response in patients with severe ulcerative colitis. Methods: A total of 90 UC patients who were diagnosed and treated in the hospital between August 2014 and January 2017 were divided into the control group (n=45) and the nutritional intervention group (n=45) by random number table. Control group received clinical routine therapy for UC, and nutritional intervention group received routine therapy as well as nutritional support and intervention. The differences in the intestinal flora distribution, Th1/Th2 cytokine contents and inflammatory mediator contents were compared between the two groups. Results: Before intervention, there was no statistically significant difference in the intestinal flora distribution, Th1/Th2 cytokine contents and inflammatory mediator contents between the two groups. After intervention, the number of enterobacter and enterococcus in nutritional intervention group were lower than those in control group whereas the number of lactobacilli, Bifidobacterium and clostridium butyricum were higher than those in control group;serum IL-2 and IFN-γ contents were lower than those of control group whereas IL-4 and IL-10 contents were higher than those of control group;serum MCP-1, MIP-1a and HMGB-1 contents were lower than those of control group. Conclusion: Nutritional support and intervention can further balance the intestinal flora distribution and Th1/Th2 immune response and suppress the systemic inflammatory response in patients with severe ulcerative colitis.
基金funding support from the Guangdong Provincial Key Construction Unit Project of Traditional Chinese Medicine Pediatrics (Guangdong Traditional Chinese Medicine Office Letter [2018] No. 202)。
文摘Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.
文摘BACKGROUND Esophageal replacement(ER)with gastric pull-up(GPU)or jejunal interposition(JI)used to be the standard treatment for long-gap esophageal atresia(LGEA).Changes of the ER grafts on a macro-and microscopic level however,are unknown.AIM To evaluate long-term clinical symptoms and anatomical and mucosal changes in adolescents and adults after ER for LGEA.METHODS A cohort study was conducted including all LGEA patients≥16 years who had undergone GPU or JI between 1985-2003 at two tertiary referral centers in the Netherlands.Patients underwent clinical assessment,contrast study and endoscopy with biopsy.Data was collected prospectively.Group differences between JI and GPU patients,and associations between different outcome measures were assessed using the Fisher’s exact test for bivariate variables and the Mann-Whitney U-test for continuous variables.Differences with a P-value<0.05 were considered statistically significant.RESULTS Nine GPU patients and eleven JI patients were included.Median age at follow-up was 21.5 years and 24.4 years,respectively.Reflux was reported in six GPU patients(67%)vs four JI patients(36%)(P=0.37).Dysphagia symptoms were reported in 64%of JI patients,compared to 22%of GPU patients(P=0.09).Contrast studies showed dilatation of the jejunal graft in six patients(55%)and graft lengthening in four of these six patients.Endoscopy revealed columnar-lined esophagus in three GPU patients(33%)and intestinal metaplasia was histologically confirmed in two patients(22%).No association was found between reflux symptoms and macroscopic anomalies or intestinal metaplasia.Three GPU patients(33%)experienced severe feeding problems vs none in the JI group.The median body mass index of JI patients was 20.9 kg/m^(2) vs 19.5 kg/m^(2) in GPU patients(P=0.08).CONCLUSION The majority of GPU patients had reflux and intestinal metaplasia in 22%.The majority of JI patients had dysphagia and a dilated graft.Follow-up after ER for LGEA is essential.
文摘Objective To observe the effect of Modified Xijiao Dihuang Decoction(加味犀角地黄汤,MXDD)on rats with radiation enteritis,and explore its action mechanism.Methods Thirty female Sprague Dawley rats were divided into the control,model,dexamethasone(DXM),golden bifid(GB)and MXDD groups using random number table,6 rats in each group.Except the control group,the other rats were developed into radiation enteritis model by exposing to a single 60Co-γray at a dose of 11 Gy.The rats in the DXM,GB and MXDD groups were treated with DXM(1.425 mg/kg),GB(0.8 g/kg)and MXDD(36.0 g/kg)for 3 days,respectively.Body weight and diarrhea condition of rats were evaluated daily.On day 3,the feces of rats were collected for intestinal flora detection and the small intestinal tissues were also collected.Bacterial species annotation,alpha and beta diversities as well as composition of intestinal flora were detected and compared.The protein and mRNA expressions of interleukin 17(IL-17),retinoid-related orphan nuclear receptor gamma t(ROR-γt)and forkhead/winged helix transcription factor p3(FoxP3)were determined by Western blot and polymerase chain reaction,respectively.The abundance and diversity of intestinal flora as well as the proportion at the phylum and genus levels were assayed by 16S rRNA metagenome sequencing.Correlation between intestinal flora and Th17/Treg was analyzed by heatmap method.Results On day 1 to 3 after radiation,compared with the control group,the body weight in model group was decreased(P<0.05 or P<0.01).Compared with the model group,MXDD could alleviate weight loss and diarrhea caused by irradiation.At the phylum level,MXDD cause a significant increase in Firmicutes,and a decrease in Proteobacteria(P<0.05 or P<0.01).At the genus level,MXDD reduced the proportion of Escherichia Shigella(P<0.01).In addition,IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment(P<0.05).Besides,Firmicutes and Lactobacillus were positively correlated with FoxP3(r=0.73,0.79,respectively;P<0.01),negatively correlated with IL-17(r=0.66,0.64,respectively;P<0.01 or P<0.05)and ROR-γt(r0.73,0.81,respectively;P<0.01).Proteobacteria and Escherichia Shigella both had positive correlation with IL-17(r 0.77,0.57,respectively;P<0.01 or P<0.05)and ROR-γt(r=0.94,0.79,respectively;P<0.01)and negative correlation with FoxP3(r0.74,0.65;P<0.01).Conclusion MXDD could improve the survival status of irradiated rats by regulating the richness,diversity and composition of intestinal flora,and restoring the balance of Th17/Treg.
基金supported by“Jiaotong University Star”Program,China(Grant No.:YG2022QN082)the National Natural Science Foundation of China(Grant No.:82204887)+1 种基金the Science Foundation for Shanghai Committee of Science Project,China(Grant Nos.:21S21901400,23S21901200)the Natural Science Research Foundation of Jiading District,China(Grant No.:JDKW-2021-0023).
文摘The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.
