AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Cr...AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Crohn’s disease(CD)were allocated into the herb-partitioned moxibustion combined with acupuncture(HMA)group(n=30)or the mesalazine(MESA)group(n=30)using a parallel control method.There were 2 sets of acupoints used alternately for HMA treatment.The following points were included in Set A:ST25(Tianshu),RN6(Qihai),and RN9(Shuifen)for herb-partitioned moxibustion and ST36(Zusanli),ST37(Shangjuxu),LI11(Quchi),and LI4(Hegu)for acupuncture.The points for Set B included BL23(Shenshu)and BL25(Dachangshu)for herb-partitioned moxibustion and EX-B2 of T6-T1(Jiajixue)fo r acupuncture.The patients received the same treatment6 times a week for 12 consecutive weeks.The MESA group received 1 g of mesalazine enteric coated tablets4 times daily for 12 consecutive weeks.Intestinaltissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session.Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1(ZO-1),occludin,and claudin-1.The m RNA levels were also evaluated.RESULTS:After the treatment,both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients;the patients treated with HMA showed better improvement.HMA significantly increased the expression of ZO-1(P=0.000),occludin(P=0.021),and claudin-1(P=0.016).MESA significantly increased the expression of ZO-1(P=0.016)and occludin(P=0.026).However,there was no significant increase in the expression of claudin-1(P=0.935).There was no statistically significant difference between the two groups for the expression of occludin and claudin-1(P>0.05).The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group(2333.34±35展开更多
The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important ...The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traff ic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identif ied in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.展开更多
AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.METHODS:In Caco-2 cell monolayer models,the disruption of barrier function by oxid...AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.METHODS:In Caco-2 cell monolayer models,the disruption of barrier function by oxidative stress is mediated by H2O2.The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance(TER)and permeability was estimated by measuring the paracellular transport of FITC-labeled4-kDa dextran(FD4).The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux.The expression of tight junction(TJ)proteins was assessed using reverse-transcription polymerase chain reaction(RT-PCR)and immunofluorescence staining.RESULTS:Without H2O2treatment,fucoidan significantly increased the TER compared to control(P<0.05),indicating a direct enhancement of intestinal epithelial barrier function.Next,H2O2disrupted the epithelial barrier function in a time-dependent manner.Fucoidan prevented the H2O2-induced destruction in a dosedependent manner.Fucoidan significantly decreased H2O2-induced FD4 flux(P<0.01),indicating the prevention of disruption in paracellular permeability.RTPCR showed that Caco-2 cells endogenously expressed claudin-1 and-2,and occludin and that H2O2reduced the mRNA expression of these TJ proteins.Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin.Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface.H2O2disrupted the integrity of claudin-1.Treatment with fucoidan dramatically attenuated the expression of claudin-1.CONCLUSION:Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1.Thus,fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.展开更多
The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving p...The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving polymorphonuclear leukocytes (PMNL),as a major actor in digestive carcinogenesis,the different cellular and molecular events occurring in this process are still not completely understood.The transepithelial migration of PMNL,which is the ultimate step of the afflux of PMNL into the digestive mucosa,is a complex phenomenon involving sequential interaction of molecules expressed both on PMNL and on digestive epithelial cells.Chronic inflammatory areas rich in PMNL [so-called (chronic active inflammation)] and iterative transepithelial migration of PMNL certainly evoke intracellular signals,which lead toward progressive transformation of epithelia.Among these different signals,the mutagenic effect of reactive oxygen species and nitrates,the activation of the nuclear factor-κB pathway,and the modulation of expression of certain microRNA are key actors.Following the initiation of carcinogenesis,PMNL are involved in the progression and invasion of digestive carcinomas,with which they interact.It is noteworthy that different subpopulations of PMNL,which can have some opposite effects on tumor growth,in association with different levels of transforming growth factor-β and with the number of CD8 positive T lymphocytes,could be present during the development of digestive carcinoma.Other factors that involve PMNL,such as massive elastase release,and the production of angiogenic factors,can participate in the progression of neoplastic cells through tissues.PMNL may play a major role in the onset of metastases,since they allow the tumor cells to cross the endothelial barrier and to migrate into the blood stream.Finally,PMNL play a role,alone or in association with other cell parameters,in the initiation,promotion,progression and dissemination of digestive carcinomas.This review focuses on the main currently acce展开更多
基金Research from the corresponding author’s laboratory was supported by grants from National Institutes of Health,USA(No.R01GM117628,R01GM122406,and R01DK123826)Merit Review Award(No.I01BX001690)from US Department of Veterans Affairs.
基金Supported by National Natural Science Foundation of China,No.30772831,No.81473757the National Basic Research Program of China,973 Program,No.2009CB522900
文摘AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Crohn’s disease(CD)were allocated into the herb-partitioned moxibustion combined with acupuncture(HMA)group(n=30)or the mesalazine(MESA)group(n=30)using a parallel control method.There were 2 sets of acupoints used alternately for HMA treatment.The following points were included in Set A:ST25(Tianshu),RN6(Qihai),and RN9(Shuifen)for herb-partitioned moxibustion and ST36(Zusanli),ST37(Shangjuxu),LI11(Quchi),and LI4(Hegu)for acupuncture.The points for Set B included BL23(Shenshu)and BL25(Dachangshu)for herb-partitioned moxibustion and EX-B2 of T6-T1(Jiajixue)fo r acupuncture.The patients received the same treatment6 times a week for 12 consecutive weeks.The MESA group received 1 g of mesalazine enteric coated tablets4 times daily for 12 consecutive weeks.Intestinaltissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session.Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1(ZO-1),occludin,and claudin-1.The m RNA levels were also evaluated.RESULTS:After the treatment,both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients;the patients treated with HMA showed better improvement.HMA significantly increased the expression of ZO-1(P=0.000),occludin(P=0.021),and claudin-1(P=0.016).MESA significantly increased the expression of ZO-1(P=0.016)and occludin(P=0.026).However,there was no significant increase in the expression of claudin-1(P=0.935).There was no statistically significant difference between the two groups for the expression of occludin and claudin-1(P>0.05).The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group(2333.34±35
文摘The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traff ic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identif ied in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.
文摘AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.METHODS:In Caco-2 cell monolayer models,the disruption of barrier function by oxidative stress is mediated by H2O2.The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance(TER)and permeability was estimated by measuring the paracellular transport of FITC-labeled4-kDa dextran(FD4).The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux.The expression of tight junction(TJ)proteins was assessed using reverse-transcription polymerase chain reaction(RT-PCR)and immunofluorescence staining.RESULTS:Without H2O2treatment,fucoidan significantly increased the TER compared to control(P<0.05),indicating a direct enhancement of intestinal epithelial barrier function.Next,H2O2disrupted the epithelial barrier function in a time-dependent manner.Fucoidan prevented the H2O2-induced destruction in a dosedependent manner.Fucoidan significantly decreased H2O2-induced FD4 flux(P<0.01),indicating the prevention of disruption in paracellular permeability.RTPCR showed that Caco-2 cells endogenously expressed claudin-1 and-2,and occludin and that H2O2reduced the mRNA expression of these TJ proteins.Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin.Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface.H2O2disrupted the integrity of claudin-1.Treatment with fucoidan dramatically attenuated the expression of claudin-1.CONCLUSION:Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1.Thus,fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.
文摘The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving polymorphonuclear leukocytes (PMNL),as a major actor in digestive carcinogenesis,the different cellular and molecular events occurring in this process are still not completely understood.The transepithelial migration of PMNL,which is the ultimate step of the afflux of PMNL into the digestive mucosa,is a complex phenomenon involving sequential interaction of molecules expressed both on PMNL and on digestive epithelial cells.Chronic inflammatory areas rich in PMNL [so-called (chronic active inflammation)] and iterative transepithelial migration of PMNL certainly evoke intracellular signals,which lead toward progressive transformation of epithelia.Among these different signals,the mutagenic effect of reactive oxygen species and nitrates,the activation of the nuclear factor-κB pathway,and the modulation of expression of certain microRNA are key actors.Following the initiation of carcinogenesis,PMNL are involved in the progression and invasion of digestive carcinomas,with which they interact.It is noteworthy that different subpopulations of PMNL,which can have some opposite effects on tumor growth,in association with different levels of transforming growth factor-β and with the number of CD8 positive T lymphocytes,could be present during the development of digestive carcinoma.Other factors that involve PMNL,such as massive elastase release,and the production of angiogenic factors,can participate in the progression of neoplastic cells through tissues.PMNL may play a major role in the onset of metastases,since they allow the tumor cells to cross the endothelial barrier and to migrate into the blood stream.Finally,PMNL play a role,alone or in association with other cell parameters,in the initiation,promotion,progression and dissemination of digestive carcinomas.This review focuses on the main currently acce
