The weak adhesion between nanocarriers and the intestinal mucosa was one of the main reasons caused the failure in oral delivery.Inspired by the“antiskid tires”with complex chiral patterns,mesoporous silica nanopart...The weak adhesion between nanocarriers and the intestinal mucosa was one of the main reasons caused the failure in oral delivery.Inspired by the“antiskid tires”with complex chiral patterns,mesoporous silica nanoparticles AT-R@CMSN exhibiting geometrical chiral structure were designed to improve the surface/interface roughness in nanoscale,and employed as the hosting system for insoluble drugs nimesulide(NMS)and ibuprofen(IBU).Once performing the delivery tasks,AT-R@CMSN with rigid skeleton protected the loaded drug and reduced the irritation of drug on gastrointestinal tract(GIT),while their porous structure deprived drug crystal and improved drug release.More importantly,AT-R@CMSN functioned as“antiskid tire”to produce higher friction on intestinal mucosa and substantively influencedmultiple biological processes,including“contact”,“adhesion”,“retention”,“permeation”and“uptake”,compared to the achiral S@MSN,thereby improving the oral adsorption effectiveness of such drug delivery systems.By engineering AT-R@CMSN to overcome the stability,solubility and permeability bottlenecks of drugs,orally administered NMS or IBU loaded AT-R@CMSN could achieve higher relative bioavailability(705.95%and 444.42%,respectively)and stronger anti-inflammation effect.In addition,AT-R@CMSN displayed favorable biocompatibility and biodegradability.Undoubtedly,the present finding helped to understand the oral adsorption process of nanocarriers,and provided novel insights into the rational design of nanocarriers.展开更多
Background:The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development,oxidative stress,mitochondrial function and AMPK-mTOR signaling pathway.Methods:Seven...Background:The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development,oxidative stress,mitochondrial function and AMPK-mTOR signaling pathway.Methods:Seventy-two pigs were divided into two treatments and received either a basal diet or the same diet supplemented with 750 mg/kg tributyrin.Each treatment has six replicates of six pigs.After 14 days,6 pigs from each treatment were selected and the jejunal samples were collected.Results:Results showed that supplemental tributyrin increased(P<0.05)villus height and villus height:crypt depth of weaned pigs.Pigs fed tributyrin had greater(P<0.05)RNA/DNA and protein/DNA ratios than pigs on the control group.The mRNA levels of sodium glucose transport protein-1 and glucose transporter-2 in the jejunum were upregulated(P<0.05)in pigs fed the tributyrin diet.Dietary tributyrin supplementation lowered(P<0.05)the malondialdehyde and hydrogen peroxide(H2O2)content in jejunum,enhanced(P<0.05)the mitochondrial function,as demonstrated by decreased(P<0.05)reactive oxygen species level and increased(P<0.05)mitochondrial membrane potential.Furthermore,tributyrin increased(P<0.05)mitochondrial DNA content and the mRNA abundance of genes related to mitochondrial functions,including peroxisomal proliferator-activated receptor-γcoactivator-1α,mitochondrial transcription factor A,nuclear respiratory factor-1 in the jejunum.Supplementation with tributyrin elevated(P<0.05)the phosphorylation level of AMPK and inhibited(P<0.05)the phosphorylation level of mTOR in jejunum compared with the control group.Conclusions:These findings suggest that dietary supplementation with tributyrin promotes intestinal mucosa growth,extenuates oxidative stress,improves mitochondrial function and modulates the AMPK-mTOR signal pathway of weaned pigs.展开更多
BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC ...BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.展开更多
Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits we...Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits were made into hemorrhagic shock,then reperfused with different liquids.These rabbits were divided by random number table into three groups:sham operation group(Sham group),reperfusion with normal saline group(NS group),reperfusion with 1%GLP group(LS group).Bacterial translocation of blood and TNF-αcontent in serum were respectively observed at the time before shock,40 min after shock,40 min and 90 min after.TNF-αcontent in intestinal mucosa and the degree of intestinal mucosal injury were examined at 90 min post-resuscitation.Results 1 With the extension of reperfusion time,the positive rate of blood bacteria increased gradually in NS group,which was significantly higher than that of Sham group and LS group(P<0.05),meanwhile the degree of intestinal mucosal injury in NS group was more severe than that of Sham group and LS group too(P<0.05).2TNF-αcontent in serum of NS group and LS group were increased obviously compared with that before shock and in Sham group(P<0.05).TNF-αcontent in serum was further increased after reperfusion with NS,which was distinctly higher than that in LS group.TNF-αcontent in intestinal mucosa of NS group was significantly higher than that in LS group and Sham group too(P<0.05).Conclusion GLP can protect intestinal mucosa against HS-R injury,and its effects may relate with the change of TNF-αin hemorrhagic shock rabbits.展开更多
Objective To investigate the effect of exogenous thyroid hormone on serum NO and iNOS activity of intestinal mucosa in septic rats. Methods Septic model was established by cecal ligation puncture (CLP) in male SD rats...Objective To investigate the effect of exogenous thyroid hormone on serum NO and iNOS activity of intestinal mucosa in septic rats. Methods Septic model was established by cecal ligation puncture (CLP) in male SD rats. Triiodothyronine ( T3 ) was administered intraperitoneally to correct the low T3 syndrome of septic rats. Blood was collected to examine serum NO and thyroid hormone concentration. Intestinal mucosa iNOS activity was assayed using immunochemical stain. Results Mortality rate in the prevention group was significantly lower than the septic group (Log rank = 3. 85, P 【 0.05). Serum NO concentration was significantly lower in the prevention group (F=19.6,F【0.01). The degree of inflammatory injury of intestinal mucosa was much milder in the prevention group than in the septic group (x2 = 5.303,P【0. 05). Mucosa iNOS activity was also significantly lower in the prevention group (x2 = 4. 876, P【0. 01). Conclusion Thyroid hormone protects the intestinal mucosa barrier inhibiting the expression of展开更多
[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural ...[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.展开更多
Inflammatory bowel diseases(IBDs) are chronic inflammatory disorders of the bowel,including ulcerative colitis and Crohn's disease.A single etiology has not been identified,but rather the pathogenesis of IBD is ve...Inflammatory bowel diseases(IBDs) are chronic inflammatory disorders of the bowel,including ulcerative colitis and Crohn's disease.A single etiology has not been identified,but rather the pathogenesis of IBD is very complex and involves several major and minor contributors,employing different inflammatory pathways which have different roles in different patients.Although new and powerful medical treatments are available,many are biological drugs or immunosuppressants,which are associated with significant side effects and elevated costs.As a result,the need for predicting disease course and response to therapy is essential.Major attempts have been made at identifying clinical characteristics,concurrent medical therapy,and serological and genetic markers as predictors of response to biological agents.Only few reports exist on how mucosal/tissue markers are able to predict clinical behavior of the disease or its response to therapy.The aim of this paper therefore is to review the little information available regarding tissue markers as predictors of response to therapy,and reevaluate the role of tissue factors associated with disease severity,which can eventually be ranked as "tissue factor predictors".Five main categories are assessed,including mucosal cytokines and chemokines,adhesion molecules and markers of activation,immune and non-immune cells,and other mucosal components.Improvement in the design and specificity of clinical studies are mandatory to be able to classify tissue markers as predictors of disease course and response to specific therapy,obtain the goal of achieving "personalized pathogenesisoriented therapy" in IBD.展开更多
An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that co...An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical treatment.By implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,however,is largely observational,requiring repeated invasive endoscopic examinations,sometimes with mucosal biopsies.Other indirect imaging methods may play a role in this assessment along with other surrogate markers,including intestinal permeability.These measurements may have significant limitations that prohibit precise correlation with symptom-based disease activity indices in clinical trials.This likely reflects the dynamic nature of this evolving and individualized inflammatory process that tends to be focused,but not limited,to the mucosa of the intestinal tract.展开更多
Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this stud...Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...展开更多
OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decrease...OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decreased weight loss,colon contracture,disease activity index(DAI),colon mucosa damage index(CMDI)and histopathological index(HI).HLJ2 also decreased myeloperoxidase(MPO)activity and reduced production of the inflammatory cytokines TNF-α,IL^(-1)β,and IL-6.HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate(DSS)and increased the expression of ZO-1 and claudin-1.Fecal 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2,including increased abundance of probiotics such as Lachnospiraceae,Prevotellaceae,and Lactobacillaceae.At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae,Porphyromonadaceae,Deferribacteraceae,and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice.CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation,regulates the intestinal flora,and protects the intestinal mucosa.It is thus a potential therapeutic agent for ulcerative colitis.展开更多
The safty, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the cl...The safty, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the clinical implication studied. Seventy six adult patients whose hepatic function were in Child B or C grade were randomly assigned in EN group (30 cases), total parenteral nutrition (TPN) group (26 cases) and control group (CON, 20 cases). The patients received different nutritional sopport. The signs of nutritional condition and hepatic function were massured at 1 day before, 5 days and 10 days after the surgical operation respectively. The changes in the urine lactulose (L) and mannitol (M) contents and L/M ratio were observed by using pulsed electrochemical detection (HPLC PED) to acquire the defferent effects among the different nutritional support performence. The results showed that the patients in the EN group and TPN group had no worse hepatic function damage after operation. The patients in the EN group reached the positive nitrogen balance earlier, had a less weight loss than in the TPN group with the difference being significant ( P <0 05). There was no obvious change in L/M ratio in the postoperative patients in the EN group ( P >0.05), but there was significant difference in L/M between TPN group and CON group ( P <0.05). It was concluded that EN was a rational, safe, effective and practical nutrition support mathod in the patients with damaged hepatic function patients after surgical operation and EN can effectively protect the structure and function of gut barrier from sever infection.展开更多
Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approach...Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.展开更多
Two common chronic childhood diseases-celiac disease(CD)and type 1 diabetes(T1D)-result from complex pathological mechanisms where genetic susceptibility,environmental exposure,alterations in intestinal permeability a...Two common chronic childhood diseases-celiac disease(CD)and type 1 diabetes(T1D)-result from complex pathological mechanisms where genetic susceptibility,environmental exposure,alterations in intestinal permeability and immune responses play central roles.In this study,we investigated whether these characteristics were universal for CD independently of T1D association.For this purpose,we studied 36 children with normal small-bowel mucosa and 26 children with active CD,including 12 patients with T1D.In samples from the small-bowel mucosa,we detected the lowest expression of tight junction protein 1(TJP1)mRNA in CD patients with T1D,indicating an increase in intestinal permeability.Furthermore,these samples displayed the highest expression of forkhead box P3(FoxP3)mRNA,a marker for regulatory T cells,as compared with other patient groups.At the same time,serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase(tTG)were the highest in CD patients with T1D.In contrast,no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins.There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals.Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability,strong local immune activation and increased immunoregulatory mechanisms in the small bowel.Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors(virus infections),unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions.展开更多
文摘The weak adhesion between nanocarriers and the intestinal mucosa was one of the main reasons caused the failure in oral delivery.Inspired by the“antiskid tires”with complex chiral patterns,mesoporous silica nanoparticles AT-R@CMSN exhibiting geometrical chiral structure were designed to improve the surface/interface roughness in nanoscale,and employed as the hosting system for insoluble drugs nimesulide(NMS)and ibuprofen(IBU).Once performing the delivery tasks,AT-R@CMSN with rigid skeleton protected the loaded drug and reduced the irritation of drug on gastrointestinal tract(GIT),while their porous structure deprived drug crystal and improved drug release.More importantly,AT-R@CMSN functioned as“antiskid tire”to produce higher friction on intestinal mucosa and substantively influencedmultiple biological processes,including“contact”,“adhesion”,“retention”,“permeation”and“uptake”,compared to the achiral S@MSN,thereby improving the oral adsorption effectiveness of such drug delivery systems.By engineering AT-R@CMSN to overcome the stability,solubility and permeability bottlenecks of drugs,orally administered NMS or IBU loaded AT-R@CMSN could achieve higher relative bioavailability(705.95%and 444.42%,respectively)and stronger anti-inflammation effect.In addition,AT-R@CMSN displayed favorable biocompatibility and biodegradability.Undoubtedly,the present finding helped to understand the oral adsorption process of nanocarriers,and provided novel insights into the rational design of nanocarriers.
基金National Natural Science Foundation of China(31872387)Zhejiang Provincial Natural Science Foundation(Sodium butyrate promotes restoration of intestinal barrier induced by oxidative stress in piglets through AMPK mediated mitophagy)and Zhejiang Provincal Key R&D Project(2019C02051).
文摘Background:The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development,oxidative stress,mitochondrial function and AMPK-mTOR signaling pathway.Methods:Seventy-two pigs were divided into two treatments and received either a basal diet or the same diet supplemented with 750 mg/kg tributyrin.Each treatment has six replicates of six pigs.After 14 days,6 pigs from each treatment were selected and the jejunal samples were collected.Results:Results showed that supplemental tributyrin increased(P<0.05)villus height and villus height:crypt depth of weaned pigs.Pigs fed tributyrin had greater(P<0.05)RNA/DNA and protein/DNA ratios than pigs on the control group.The mRNA levels of sodium glucose transport protein-1 and glucose transporter-2 in the jejunum were upregulated(P<0.05)in pigs fed the tributyrin diet.Dietary tributyrin supplementation lowered(P<0.05)the malondialdehyde and hydrogen peroxide(H2O2)content in jejunum,enhanced(P<0.05)the mitochondrial function,as demonstrated by decreased(P<0.05)reactive oxygen species level and increased(P<0.05)mitochondrial membrane potential.Furthermore,tributyrin increased(P<0.05)mitochondrial DNA content and the mRNA abundance of genes related to mitochondrial functions,including peroxisomal proliferator-activated receptor-γcoactivator-1α,mitochondrial transcription factor A,nuclear respiratory factor-1 in the jejunum.Supplementation with tributyrin elevated(P<0.05)the phosphorylation level of AMPK and inhibited(P<0.05)the phosphorylation level of mTOR in jejunum compared with the control group.Conclusions:These findings suggest that dietary supplementation with tributyrin promotes intestinal mucosa growth,extenuates oxidative stress,improves mitochondrial function and modulates the AMPK-mTOR signal pathway of weaned pigs.
基金Suzhou Science and Technology Program,No.SLT202005Suzhou Municipal Commission of Health and Family Planning,No.LCZX202031+1 种基金Suzhou New District Science and Technology Plan,No.2019Z009Independent Innovation Project of National High Tech Development Zone Hospital,No.SGY2018C03.
文摘BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.
基金Natural Science Research Project of Henan Province Education Department(NO.2006310021)
文摘Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits were made into hemorrhagic shock,then reperfused with different liquids.These rabbits were divided by random number table into three groups:sham operation group(Sham group),reperfusion with normal saline group(NS group),reperfusion with 1%GLP group(LS group).Bacterial translocation of blood and TNF-αcontent in serum were respectively observed at the time before shock,40 min after shock,40 min and 90 min after.TNF-αcontent in intestinal mucosa and the degree of intestinal mucosal injury were examined at 90 min post-resuscitation.Results 1 With the extension of reperfusion time,the positive rate of blood bacteria increased gradually in NS group,which was significantly higher than that of Sham group and LS group(P<0.05),meanwhile the degree of intestinal mucosal injury in NS group was more severe than that of Sham group and LS group too(P<0.05).2TNF-αcontent in serum of NS group and LS group were increased obviously compared with that before shock and in Sham group(P<0.05).TNF-αcontent in serum was further increased after reperfusion with NS,which was distinctly higher than that in LS group.TNF-αcontent in intestinal mucosa of NS group was significantly higher than that in LS group and Sham group too(P<0.05).Conclusion GLP can protect intestinal mucosa against HS-R injury,and its effects may relate with the change of TNF-αin hemorrhagic shock rabbits.
文摘Objective To investigate the effect of exogenous thyroid hormone on serum NO and iNOS activity of intestinal mucosa in septic rats. Methods Septic model was established by cecal ligation puncture (CLP) in male SD rats. Triiodothyronine ( T3 ) was administered intraperitoneally to correct the low T3 syndrome of septic rats. Blood was collected to examine serum NO and thyroid hormone concentration. Intestinal mucosa iNOS activity was assayed using immunochemical stain. Results Mortality rate in the prevention group was significantly lower than the septic group (Log rank = 3. 85, P 【 0.05). Serum NO concentration was significantly lower in the prevention group (F=19.6,F【0.01). The degree of inflammatory injury of intestinal mucosa was much milder in the prevention group than in the septic group (x2 = 5.303,P【0. 05). Mucosa iNOS activity was also significantly lower in the prevention group (x2 = 4. 876, P【0. 01). Conclusion Thyroid hormone protects the intestinal mucosa barrier inhibiting the expression of
基金National Natural Science Foundation of China(31602099)Key Laboratory of Prevention and Control Agents for Animal Bacteriosis(Ministry of Agriculture)(KLPCAAB-2018-06)the Engineering Research Center of Ecology and Agricultural Use of Wetland,Ministry of Education(KF201913)。
文摘[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.
文摘Inflammatory bowel diseases(IBDs) are chronic inflammatory disorders of the bowel,including ulcerative colitis and Crohn's disease.A single etiology has not been identified,but rather the pathogenesis of IBD is very complex and involves several major and minor contributors,employing different inflammatory pathways which have different roles in different patients.Although new and powerful medical treatments are available,many are biological drugs or immunosuppressants,which are associated with significant side effects and elevated costs.As a result,the need for predicting disease course and response to therapy is essential.Major attempts have been made at identifying clinical characteristics,concurrent medical therapy,and serological and genetic markers as predictors of response to biological agents.Only few reports exist on how mucosal/tissue markers are able to predict clinical behavior of the disease or its response to therapy.The aim of this paper therefore is to review the little information available regarding tissue markers as predictors of response to therapy,and reevaluate the role of tissue factors associated with disease severity,which can eventually be ranked as "tissue factor predictors".Five main categories are assessed,including mucosal cytokines and chemokines,adhesion molecules and markers of activation,immune and non-immune cells,and other mucosal components.Improvement in the design and specificity of clinical studies are mandatory to be able to classify tissue markers as predictors of disease course and response to specific therapy,obtain the goal of achieving "personalized pathogenesisoriented therapy" in IBD.
文摘An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical treatment.By implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,however,is largely observational,requiring repeated invasive endoscopic examinations,sometimes with mucosal biopsies.Other indirect imaging methods may play a role in this assessment along with other surrogate markers,including intestinal permeability.These measurements may have significant limitations that prohibit precise correlation with symptom-based disease activity indices in clinical trials.This likely reflects the dynamic nature of this evolving and individualized inflammatory process that tends to be focused,but not limited,to the mucosa of the intestinal tract.
基金This work was supported in part by grants from the National Key Program for Fundamental Research and Development(Grant No.G1999054203)the National Natural Science Outstanding Youth Foundation of China(Grant No.30125020).
文摘Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...
文摘OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decreased weight loss,colon contracture,disease activity index(DAI),colon mucosa damage index(CMDI)and histopathological index(HI).HLJ2 also decreased myeloperoxidase(MPO)activity and reduced production of the inflammatory cytokines TNF-α,IL^(-1)β,and IL-6.HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate(DSS)and increased the expression of ZO-1 and claudin-1.Fecal 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2,including increased abundance of probiotics such as Lachnospiraceae,Prevotellaceae,and Lactobacillaceae.At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae,Porphyromonadaceae,Deferribacteraceae,and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice.CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation,regulates the intestinal flora,and protects the intestinal mucosa.It is thus a potential therapeutic agent for ulcerative colitis.
基金This study was supported by the National Natural Science Foundation(No.30973871 and No.31071497)and National basic research program of China(No.2010CB530605).
文摘The safty, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the clinical implication studied. Seventy six adult patients whose hepatic function were in Child B or C grade were randomly assigned in EN group (30 cases), total parenteral nutrition (TPN) group (26 cases) and control group (CON, 20 cases). The patients received different nutritional sopport. The signs of nutritional condition and hepatic function were massured at 1 day before, 5 days and 10 days after the surgical operation respectively. The changes in the urine lactulose (L) and mannitol (M) contents and L/M ratio were observed by using pulsed electrochemical detection (HPLC PED) to acquire the defferent effects among the different nutritional support performence. The results showed that the patients in the EN group and TPN group had no worse hepatic function damage after operation. The patients in the EN group reached the positive nitrogen balance earlier, had a less weight loss than in the TPN group with the difference being significant ( P <0 05). There was no obvious change in L/M ratio in the postoperative patients in the EN group ( P >0.05), but there was significant difference in L/M between TPN group and CON group ( P <0.05). It was concluded that EN was a rational, safe, effective and practical nutrition support mathod in the patients with damaged hepatic function patients after surgical operation and EN can effectively protect the structure and function of gut barrier from sever infection.
基金supported by the National Natural Science Foundation of China(NO.81570675,NO.31872742)Clinical Innovation Foundation of Southwest Hospital(SWH2017JCZD-06)Top Talent Training Programme Foundation of Southwest Hospital(SWH2018BJKJ-04).
文摘Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.
基金grants 7749 and 8334 from the Estonian Science Foundation and by the European Union through the European Regional Development Fund and FP.The help of Mrs Tiina Ra¨go,MD,Mrs Anu Kaldmaa,Ms Kadri Eoma¨e,and Mrs Anu Ko˜iveer in the preparation of clinical material,cell culture and the performance of antibody assays is greatly appreciated.We also thank our colleagues from Finland,Professor Jorma Ilonen from Turku University,Professor Outi Vaarala from the National Institute for Health and Welfare and Professor Erkki Savilahti from the Children’s Hospital,University of Helsinki,for their support.
文摘Two common chronic childhood diseases-celiac disease(CD)and type 1 diabetes(T1D)-result from complex pathological mechanisms where genetic susceptibility,environmental exposure,alterations in intestinal permeability and immune responses play central roles.In this study,we investigated whether these characteristics were universal for CD independently of T1D association.For this purpose,we studied 36 children with normal small-bowel mucosa and 26 children with active CD,including 12 patients with T1D.In samples from the small-bowel mucosa,we detected the lowest expression of tight junction protein 1(TJP1)mRNA in CD patients with T1D,indicating an increase in intestinal permeability.Furthermore,these samples displayed the highest expression of forkhead box P3(FoxP3)mRNA,a marker for regulatory T cells,as compared with other patient groups.At the same time,serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase(tTG)were the highest in CD patients with T1D.In contrast,no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins.There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals.Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability,strong local immune activation and increased immunoregulatory mechanisms in the small bowel.Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors(virus infections),unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions.