Mast cells (MC) are pivotal elements in several physiological and immunological functions of the gastro- intestinal (GI) tract. MC translate the stress signals that has been transmitted through brain gut axis into rel...Mast cells (MC) are pivotal elements in several physiological and immunological functions of the gastro- intestinal (GI) tract. MC translate the stress signals that has been transmitted through brain gut axis into release of proinflammatory mediators that can cause stimulation of nerve endings that could affect afferent nerve terminals and change their perception, affect intestinal motility, increase intestinal hyperpermeability and, in susceptible individuals, modulate the inflammation. Thus, it is not surprising that MC are an important element in the pathogenesis of inflammatory bowel disease and non inflammatory GI disorders such as IBS and mast cell enterocolitis.展开更多
目的研究蛋白激酶C(PKC)的亚型PKCδ在大鼠肺微血管内皮细胞(RPMVEC)中的表达及其抑制剂Rottlerin对脂多糖(LPS)导致RPMVEC单层通透性增高的影响。方法取体外培养的RPMVEC进行PKCδ的W estern b lot和免疫组化检测,用针头式滤器检测LPS...目的研究蛋白激酶C(PKC)的亚型PKCδ在大鼠肺微血管内皮细胞(RPMVEC)中的表达及其抑制剂Rottlerin对脂多糖(LPS)导致RPMVEC单层通透性增高的影响。方法取体外培养的RPMVEC进行PKCδ的W estern b lot和免疫组化检测,用针头式滤器检测LPS及LPS+Rottlerin干预后RPMVEC单层滤过系数(K f)的变化。结果PKCδ在RPMVEC中有广泛的表达,其表达部位主要位于胞质。Rot-tlerin能减低LPS导致的RPMVEC单层通透性增高。结论LPS导致RPMVEC损伤的机制与PKC的激活有关,PKCδ亚型抑制剂可减轻LPS诱导的RPMVEC单层通透性增高。展开更多
Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors ...Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated.This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children.Data sources We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children.Databases including Medline,Scopus,and Web of Science were searched for studies published in any language with the terms"chil-dren","idiopathic nephrotic syndrome","immunopathogenesis","T cells","circulating permeability factors",and"B cells".Results Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome.Recently,some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome.Conclusions Both T-and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome,like two sides of one coin,but the role of B cell seems more important than T cells.展开更多
AIM: To test the hypothesis that hydrolysis of sphingomyelin to ceramide changes the composition of tight junctions (TJs) with increasing permeability of the intestinal epithelium. METHODS: Monolayers of Caco-2 cells ...AIM: To test the hypothesis that hydrolysis of sphingomyelin to ceramide changes the composition of tight junctions (TJs) with increasing permeability of the intestinal epithelium. METHODS: Monolayers of Caco-2 cells were used as an in vitro model for the intestinal barrier. Permeability was determined by quantifi cation of transepithelialflux and transepithelial resistance. Sphingolipid-rich membrane microdomains were isolated by a discontinuous sucrose gradient and characterized by Western-blot. Lipid content of microdomains was analysed by tandem mass spectrometry. Ceramide was subcellularly localized by immunofluorescent staining.RESULTS: Exogenous sphingomyelinase increased transepithelial permeability and decreased transepithelial resistance at concentrations as low as 0.01 U/mL. Lipid analysis showed rapid accumulation of ceramide in the membrane fractions containing occludin and claudin-4, representing TJs. In these fractions we observed a concomitant decrease of sphingomyelin and cholesterol with increasing concentrations of ceramide. Immunofluorescent staining confirmed clustering of ceramide at the sites of cell-cell contacts. Neutralization of surface ceramide prevented the permeability-increase induced by platelet activating factor. CONCLUSION: Our findings indicate that changes in lipid composition of TJs impair epithelial barrier functions. Generation of ceramide by sphingomyelinases might contribute to disturbed barrier function seen in diseases such as inflammatory, infectious, toxic or radiogenic bowel disease.展开更多
Angiopoietin-1 (Ang-1) is a newly-found endothelium-specific proangiogenic factor and it had been proved essential roles in both vasculogenesis and angiogensis. Among them, its anti-leakage ability may have great pote...Angiopoietin-1 (Ang-1) is a newly-found endothelium-specific proangiogenic factor and it had been proved essential roles in both vasculogenesis and angiogensis. Among them, its anti-leakage ability may have great potential applications in clinical treatment of vascular hyper-permeability in a variety of diseases such as cancer, diabetic retinopathy, rheumatoid arthritis, asthma. In this review, some research progresses focused on this aspect are discussed. [展开更多
Drugs for the treatment and prevention of nervous system diseases must permeate the bloodbrain barrier to take effect.In vitro models of the blood-brain barrier are therefore important in the investigation of drug per...Drugs for the treatment and prevention of nervous system diseases must permeate the bloodbrain barrier to take effect.In vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation mechanisms.However,to date,no unified method has been described for establishing a blood-brain barrier model.Here,we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyester Transwell cell culture membrane with 0.4-μm pores,and conducted transepithelial electrical resistance measurements,leakage tests and assays for specific bloodbrain barrier enzymes.We show that the permeability of our model is as low as that of the bloodbrain barrier in vivo.Our model will be a valuable tool in the study of the mechanisms of action of neuroprotective drugs.展开更多
OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine(TCM) on the intestinal mucosal permeability in rats with ulcerative coli...OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine(TCM) on the intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium(DSS).METHODS: Totally 55 male Wistar rats(body weight of 170-190 g) were randomly divided into the blank group(n = 10) and the model duplication group(n = 45). The blank group was not intervened, while the other was modeled with 5% dextran sulfate sodium by gavaging in a dosage of4 m L per day to induce ulcerative colitis, a total of7 days. Then, the model rats were divided into model blank group, mesalazine group and TCM group,and each group was consisted of 15 rats. They were given retention enema 10 min with normal saline,mesalazine enema(0.036 g/m L), and Yang-activating and stasis-eliminating decoction [0.54 g/m L of a decoction boiled by Puhuang(Pollen Typhae), Xiebai(Bulbus Allii Macrostemonis) and Wulingzhi(Faeces Trogopteri)] for 10 days respectively. Afterwards,all of the rats were evaluated by disease activity index(DAI), histological changes of distal colon, expression of occludin protein and ultrastructure of intestinal epithelial cells. Furthermore, ratio of lactulose to mannitol(L/M) discharged in urine was evaluated.RESULTS: Comparing the results between TCM and model control groups, scores of DAI and histological lesions decreased significantly(P = 0.000 <0.01), ultrastructures of intestinal epithelial cells and tight junctions were more complete. The expression of occludin protein(P = 0.001 < 0.01) increased while the L/M value decreased significantly(P = 0.000 < 0.01) in TCM group. There was no statistical difference between the TCM and mesalazine groups in results of each item(P > 0.05).CONCLUSION: The decoction prepared with Yang-activating and stasis-eliminating TCM medicianls can restore intestinal mucosal epithelial cells and tight junctions the model rats with ulcerative colitis; it can reduce histological lesions and protect the permeabi展开更多
文摘Mast cells (MC) are pivotal elements in several physiological and immunological functions of the gastro- intestinal (GI) tract. MC translate the stress signals that has been transmitted through brain gut axis into release of proinflammatory mediators that can cause stimulation of nerve endings that could affect afferent nerve terminals and change their perception, affect intestinal motility, increase intestinal hyperpermeability and, in susceptible individuals, modulate the inflammation. Thus, it is not surprising that MC are an important element in the pathogenesis of inflammatory bowel disease and non inflammatory GI disorders such as IBS and mast cell enterocolitis.
文摘目的研究蛋白激酶C(PKC)的亚型PKCδ在大鼠肺微血管内皮细胞(RPMVEC)中的表达及其抑制剂Rottlerin对脂多糖(LPS)导致RPMVEC单层通透性增高的影响。方法取体外培养的RPMVEC进行PKCδ的W estern b lot和免疫组化检测,用针头式滤器检测LPS及LPS+Rottlerin干预后RPMVEC单层滤过系数(K f)的变化。结果PKCδ在RPMVEC中有广泛的表达,其表达部位主要位于胞质。Rot-tlerin能减低LPS导致的RPMVEC单层通透性增高。结论LPS导致RPMVEC损伤的机制与PKC的激活有关,PKCδ亚型抑制剂可减轻LPS诱导的RPMVEC单层通透性增高。
基金This study was supported by the National Natural Foundation of China(81770710)Key Research and Development Plan of Zhejiang Province(2019C03028)the Major projects jointly constructed by the Zhejiang Province,and National Health Commission(WKJ-ZJ-1908).
文摘Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated.This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children.Data sources We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children.Databases including Medline,Scopus,and Web of Science were searched for studies published in any language with the terms"chil-dren","idiopathic nephrotic syndrome","immunopathogenesis","T cells","circulating permeability factors",and"B cells".Results Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome.Recently,some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome.Conclusions Both T-and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome,like two sides of one coin,but the role of B cell seems more important than T cells.
基金grants from the University of Regensburg, as part of the ReForM-program, and from the German Research Foundation DFG (BO 2529/2-1) to JB
文摘AIM: To test the hypothesis that hydrolysis of sphingomyelin to ceramide changes the composition of tight junctions (TJs) with increasing permeability of the intestinal epithelium. METHODS: Monolayers of Caco-2 cells were used as an in vitro model for the intestinal barrier. Permeability was determined by quantifi cation of transepithelialflux and transepithelial resistance. Sphingolipid-rich membrane microdomains were isolated by a discontinuous sucrose gradient and characterized by Western-blot. Lipid content of microdomains was analysed by tandem mass spectrometry. Ceramide was subcellularly localized by immunofluorescent staining.RESULTS: Exogenous sphingomyelinase increased transepithelial permeability and decreased transepithelial resistance at concentrations as low as 0.01 U/mL. Lipid analysis showed rapid accumulation of ceramide in the membrane fractions containing occludin and claudin-4, representing TJs. In these fractions we observed a concomitant decrease of sphingomyelin and cholesterol with increasing concentrations of ceramide. Immunofluorescent staining confirmed clustering of ceramide at the sites of cell-cell contacts. Neutralization of surface ceramide prevented the permeability-increase induced by platelet activating factor. CONCLUSION: Our findings indicate that changes in lipid composition of TJs impair epithelial barrier functions. Generation of ceramide by sphingomyelinases might contribute to disturbed barrier function seen in diseases such as inflammatory, infectious, toxic or radiogenic bowel disease.
文摘Angiopoietin-1 (Ang-1) is a newly-found endothelium-specific proangiogenic factor and it had been proved essential roles in both vasculogenesis and angiogensis. Among them, its anti-leakage ability may have great potential applications in clinical treatment of vascular hyper-permeability in a variety of diseases such as cancer, diabetic retinopathy, rheumatoid arthritis, asthma. In this review, some research progresses focused on this aspect are discussed. [
基金supported by the National Natural Science Foundation of China,No.81374005,30973979grant from the National Science and Technology Support Program during the Twelfth"Five-Year"Plan Period of China,No.2012BAI26B03
文摘Drugs for the treatment and prevention of nervous system diseases must permeate the bloodbrain barrier to take effect.In vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation mechanisms.However,to date,no unified method has been described for establishing a blood-brain barrier model.Here,we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyester Transwell cell culture membrane with 0.4-μm pores,and conducted transepithelial electrical resistance measurements,leakage tests and assays for specific bloodbrain barrier enzymes.We show that the permeability of our model is as low as that of the bloodbrain barrier in vivo.Our model will be a valuable tool in the study of the mechanisms of action of neuroprotective drugs.
基金Supported by National Natural Science Foundation of China Project:the Effect and Mechanism of Ulcerative Colitis Rats in the Intestinal Barrier Permeability by Huayutongyang Formula(No.81373848)
文摘OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine(TCM) on the intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium(DSS).METHODS: Totally 55 male Wistar rats(body weight of 170-190 g) were randomly divided into the blank group(n = 10) and the model duplication group(n = 45). The blank group was not intervened, while the other was modeled with 5% dextran sulfate sodium by gavaging in a dosage of4 m L per day to induce ulcerative colitis, a total of7 days. Then, the model rats were divided into model blank group, mesalazine group and TCM group,and each group was consisted of 15 rats. They were given retention enema 10 min with normal saline,mesalazine enema(0.036 g/m L), and Yang-activating and stasis-eliminating decoction [0.54 g/m L of a decoction boiled by Puhuang(Pollen Typhae), Xiebai(Bulbus Allii Macrostemonis) and Wulingzhi(Faeces Trogopteri)] for 10 days respectively. Afterwards,all of the rats were evaluated by disease activity index(DAI), histological changes of distal colon, expression of occludin protein and ultrastructure of intestinal epithelial cells. Furthermore, ratio of lactulose to mannitol(L/M) discharged in urine was evaluated.RESULTS: Comparing the results between TCM and model control groups, scores of DAI and histological lesions decreased significantly(P = 0.000 <0.01), ultrastructures of intestinal epithelial cells and tight junctions were more complete. The expression of occludin protein(P = 0.001 < 0.01) increased while the L/M value decreased significantly(P = 0.000 < 0.01) in TCM group. There was no statistical difference between the TCM and mesalazine groups in results of each item(P > 0.05).CONCLUSION: The decoction prepared with Yang-activating and stasis-eliminating TCM medicianls can restore intestinal mucosal epithelial cells and tight junctions the model rats with ulcerative colitis; it can reduce histological lesions and protect the permeabi
