BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative co...BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative colitis(UC).However,their correlation to endoscopic scores,disease severity and affected intestinal surface has not been extensively investigated.AIM To correlate FL,and for comparison white blood cell(WBC)and C-reactive protein(CRP),with endoscopic scores,disease extent and location in CD and UC.METHODS Retrospective analysis in 188 patients who had FL,CRP and WBC determined within 30 d of endoscopy.Disease location,disease extent(number of intestinal segments involved),disease severity(determined by endoscopic scores),timing of FL testing in relation to colonoscopy,as well as the use of effective fast acting medications(steroids and biologics)between colonoscopy and FL measurement,were recorded.RESULTS In 131 CD and 57 UC patients,both CRP and FL-but not WBC-distinguished disease severity(inactive,mild,moderate,severe).In patients receiving fastacting(steroids or biologics)treatment in between FL and colonoscopy,FL showed a higher correlation to endoscopic scores when tested before vs after the procedure(r=0.596,P<0.001,vs r=0.285,P=0.15 for the Simple Endoscopic Score for CD;and r=0.402,P=0.01 vs r=0.054 P=0.84 for Disease Activity Index).Finally,FL was significantly correlated with the diseased mucosal surface(colon-ileocolon>small bowel)and the number of inflamed colon segments.CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values.FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure–this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels.FL can accurately and timely characterize intestinal inflammation in IBD.展开更多
Addressing mucosal inflammatory disorders in the ocular surface or respiratory system remains a formidable challenge owing to the limited penetration of biological therapeutics across epithelial barriers.In this study...Addressing mucosal inflammatory disorders in the ocular surface or respiratory system remains a formidable challenge owing to the limited penetration of biological therapeutics across epithelial barriers.In this study,we explored the potential of human single-domain antibodies(UdAbs)as topical therapeutics for the targeted modulation of interleukin-33(IL-33)in two mucosal-associated inflammatory disorders.The anti-IL-33 UdAb A12 demonstrated potent inhibition of the IL-33-mediated signaling pathway,despite not potently blocking the IL-33 receptor interaction.Compared with the anti-IL-33 control IgG itepekimab,the topical delivery of A12 resulted in significantly elevated corneal concentrations in vivo,which resulted in negligible ocular penetration.Moreover,A12 considerably ameliorated dry eye disease severity by exerting anti-inflammatory effects.Furthermore,in another murine model of allergic asthma,inhaled A12 substantially reduced overall lung inflammation.Our findings revealed the capacity of UdAbs to penetrate mucosal barriers following noninvasive localized delivery,highlighting their potential as an innovative therapeutic strategy for modulating mucosal inflammation.展开更多
The recent study published in the World Journal of Gastroenterology examines the interplay among the neuroendocrine axis,gut microbiota,inflammatory markers,and gastrointestinal symptoms in irritable bowel syndrome(IB...The recent study published in the World Journal of Gastroenterology examines the interplay among the neuroendocrine axis,gut microbiota,inflammatory markers,and gastrointestinal symptoms in irritable bowel syndrome(IBS).By integrating all these factors into a single study,this approach reflects the modern concept of functional gastrointestinal disorders as disorders of the gut-brain interaction to be approached in a multiparametric manner,also incorporating non-gastroentero-logical elements and extending evaluations to parameters related to the neuroen-docrine axis.This invited letter to the editor summarizes the main results of the aforementioned study and highlights its multiparametric approach,including variables not strictly gastroenterological,in the study of IBS,and discusses its strengths and limitations.展开更多
BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestina...BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.展开更多
Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Metho...Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.展开更多
Inflammatory transcriptomic signatures and cell type compositions in inflamed and non-inflamed colonic mucosa of ulcerative colitis Ulcerative colitis(UC),a subtype of inflammatory bowel disease,arises from disrupted ...Inflammatory transcriptomic signatures and cell type compositions in inflamed and non-inflamed colonic mucosa of ulcerative colitis Ulcerative colitis(UC),a subtype of inflammatory bowel disease,arises from disrupted gut homeostasis,primarily due to an aberrant innate immune response to intestinal microbiota and an underlying genetic background.1 Recently,complete healing of mucosal inflammation has been suggested as a new therapeutic goal in UC treatment.2 However,this goal remains challenging,as approximately 20%of individuals in clinical remission still exhibit active mucosal inflammation.3 Understanding the molecular alterations underlying this persistent mucosal inflammation is crucial for advancing UC pathogenesis insights and treatment strategies.展开更多
Inflammatory bowel diseases(IBD),with an increasing incidence,pose a significant health burden.Although there have been significant advances in the treatment of IBD,more progress is still needed.Hyperbaric oxygen ther...Inflammatory bowel diseases(IBD),with an increasing incidence,pose a significant health burden.Although there have been significant advances in the treatment of IBD,more progress is still needed.Hyperbaric oxygen therapy(HBOT)has been shown to treat a host of conditions such as carbon monoxide poisoning,decompression sickness,and gas gangrene.In the last few years,there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for IBD.Related research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress,inhibiting mucosal inflammation,promoting ulcer healing,influencing gut microbes,and reducing the incidence of IBD complications.This paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.展开更多
基金Supported by an unrestricted research grant from Tech Lab,Blacksburg,VA,United States
文摘BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative colitis(UC).However,their correlation to endoscopic scores,disease severity and affected intestinal surface has not been extensively investigated.AIM To correlate FL,and for comparison white blood cell(WBC)and C-reactive protein(CRP),with endoscopic scores,disease extent and location in CD and UC.METHODS Retrospective analysis in 188 patients who had FL,CRP and WBC determined within 30 d of endoscopy.Disease location,disease extent(number of intestinal segments involved),disease severity(determined by endoscopic scores),timing of FL testing in relation to colonoscopy,as well as the use of effective fast acting medications(steroids and biologics)between colonoscopy and FL measurement,were recorded.RESULTS In 131 CD and 57 UC patients,both CRP and FL-but not WBC-distinguished disease severity(inactive,mild,moderate,severe).In patients receiving fastacting(steroids or biologics)treatment in between FL and colonoscopy,FL showed a higher correlation to endoscopic scores when tested before vs after the procedure(r=0.596,P<0.001,vs r=0.285,P=0.15 for the Simple Endoscopic Score for CD;and r=0.402,P=0.01 vs r=0.054 P=0.84 for Disease Activity Index).Finally,FL was significantly correlated with the diseased mucosal surface(colon-ileocolon>small bowel)and the number of inflamed colon segments.CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values.FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure–this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels.FL can accurately and timely characterize intestinal inflammation in IBD.
基金supported by grants from the National Natural Science Foundation of China(82394450,92459301,32270984)the Science and Technology Commission of Shanghai Municipality(23XD1400800)+10 种基金the Shanghai Municipal Health Commission(GWVI-11.2-YQ46)the Fund of Fudan University and Cao’ejiang Basic Research(24FCB09)supported by the National Science Fund for Distinguished Young Scholars(82425015)the National Natural Science Foundation of China(82171102)the National Key Research and Development Program of China(2023YFA0915003)the Shanghai Medical Innovation Research Program(22Y21900900)the“Dawn”Program of the Shanghai Municipal Education Commission(24SG11)the Shanghai Science and Technology Innovation Action Plan for Cell and Gene Therapy(24J22800500)the Shanghai Science and Technology Innovation Action Plan for Advanced Materials(24CL2900802)the Shanghai Municipal Commission of Health(20254Z0019)the Shanghai Medicine and Health Development Foundation.
文摘Addressing mucosal inflammatory disorders in the ocular surface or respiratory system remains a formidable challenge owing to the limited penetration of biological therapeutics across epithelial barriers.In this study,we explored the potential of human single-domain antibodies(UdAbs)as topical therapeutics for the targeted modulation of interleukin-33(IL-33)in two mucosal-associated inflammatory disorders.The anti-IL-33 UdAb A12 demonstrated potent inhibition of the IL-33-mediated signaling pathway,despite not potently blocking the IL-33 receptor interaction.Compared with the anti-IL-33 control IgG itepekimab,the topical delivery of A12 resulted in significantly elevated corneal concentrations in vivo,which resulted in negligible ocular penetration.Moreover,A12 considerably ameliorated dry eye disease severity by exerting anti-inflammatory effects.Furthermore,in another murine model of allergic asthma,inhaled A12 substantially reduced overall lung inflammation.Our findings revealed the capacity of UdAbs to penetrate mucosal barriers following noninvasive localized delivery,highlighting their potential as an innovative therapeutic strategy for modulating mucosal inflammation.
文摘The recent study published in the World Journal of Gastroenterology examines the interplay among the neuroendocrine axis,gut microbiota,inflammatory markers,and gastrointestinal symptoms in irritable bowel syndrome(IBS).By integrating all these factors into a single study,this approach reflects the modern concept of functional gastrointestinal disorders as disorders of the gut-brain interaction to be approached in a multiparametric manner,also incorporating non-gastroentero-logical elements and extending evaluations to parameters related to the neuroen-docrine axis.This invited letter to the editor summarizes the main results of the aforementioned study and highlights its multiparametric approach,including variables not strictly gastroenterological,in the study of IBS,and discusses its strengths and limitations.
基金Supported by the National Natural Science Foundation of China,No.81673795.
文摘BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.
基金supported by the National Natural Science Foundation of China(No.81573737 and 82074213)the science foundation of Tianjin Municipal Health Bureau(No.2023169 and 2021045)the Tianjin Municipal Health Commission Science and Technology Project(No.TJWJ2022QN057).
文摘Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education of the Republic of Korea(No.2020R1I1A1A01073545 to E.M.S.,2020R1A2C1010786 to C.M.M.,2021R1A6A1A10044154 to J.K).
文摘Inflammatory transcriptomic signatures and cell type compositions in inflamed and non-inflamed colonic mucosa of ulcerative colitis Ulcerative colitis(UC),a subtype of inflammatory bowel disease,arises from disrupted gut homeostasis,primarily due to an aberrant innate immune response to intestinal microbiota and an underlying genetic background.1 Recently,complete healing of mucosal inflammation has been suggested as a new therapeutic goal in UC treatment.2 However,this goal remains challenging,as approximately 20%of individuals in clinical remission still exhibit active mucosal inflammation.3 Understanding the molecular alterations underlying this persistent mucosal inflammation is crucial for advancing UC pathogenesis insights and treatment strategies.
基金grants from Tai Shan Young Scholar Foundation of Shandong Province(Grant No.tsqn202103190)the National Natural Science Foundation of China(Grants No.82270562and 82200591).
文摘Inflammatory bowel diseases(IBD),with an increasing incidence,pose a significant health burden.Although there have been significant advances in the treatment of IBD,more progress is still needed.Hyperbaric oxygen therapy(HBOT)has been shown to treat a host of conditions such as carbon monoxide poisoning,decompression sickness,and gas gangrene.In the last few years,there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for IBD.Related research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress,inhibiting mucosal inflammation,promoting ulcer healing,influencing gut microbes,and reducing the incidence of IBD complications.This paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.
