Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A complet...Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.展开更多
BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome prolifer...BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.展开更多
Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.S...Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.展开更多
The trajectory tracking control performance of nonholonomic wheeled mobile robots(NWMRs)is subject to nonholonomic constraints,system uncertainties,and external disturbances.This paper proposes a barrier function-base...The trajectory tracking control performance of nonholonomic wheeled mobile robots(NWMRs)is subject to nonholonomic constraints,system uncertainties,and external disturbances.This paper proposes a barrier function-based adaptive sliding mode control(BFASMC)method to provide high-precision,fast-response performance and robustness for NWMRs.Compared with the conventional adaptive sliding mode control,the proposed control strategy can guarantee that the sliding mode variables converge to a predefined neighborhood of origin with a predefined reaching time independent of the prior knowledge of the uncertainties and disturbances bounds.Another advantage of the proposed algorithm is that the control gains can be adaptively adjusted to follow the disturbances amplitudes thanks to the barrier function.The benefit is that the overestimation of control gain can be eliminated,resulting in chattering reduction.Moreover,a modified barrier function-like control gain is employed to prevent the input saturation problem due to the physical limit of the actuator.The stability analysis and comparative experiments demonstrate that the proposed BFASMC can ensure the prespecified convergence performance of the NWMR system output variables and strong robustness against uncertainties/disturbances.展开更多
Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the ...Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the intestinal barrier function,microbial ecology,and performance of broilers under HS.A total of 144 yellow-feathered broilers(male,56 days old)with 682.59±7.38 g were randomly assigned to 3 groups:1)TN(thermal neutral zone,23.6±1.8℃),2)HS(heat stress,33.2±1.5℃ for 10 h/d),and 3)HSE(HS+0.1%EPS).Each group contained 6 replicates with 8 broilers per replicate.The study was conducted for 4 weeks;feed intake and body weights were measured at the end of weeks 2 and 4.At the end of the feeding trial,small intestine samples were collected for histomorphology,antioxidant,secretory immunoglobulin A(s Ig A)content,apoptosis,gene and protein expression analysis;cecal contents were also collected for microbiota analysis based on 16S r DNA sequencing.Results Dietary EPS promoted the average daily gain(ADG)of broilers during 3–4 weeks of HS(P<0.05).At the end of HS on broilers,the activity of total superoxide dismutase(T-SOD),glutathione S-transferase(GST),and the content of s Ig A in jejunum were improved by EPS supplementation(P<0.05).Besides,dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers(P<0.05).Addition of EPS in HS group broilers'diet upregulated the relative m RNA expression of Occludin,ZO-1,γ-GCLc and IL-10 of the jejunum(P<0.05),whereas downregulated the relative m RNA expression of NF-κB p65,TNF-αand IL-1βof the jejunum(P<0.05).Dietary EPS increased the protein expression of Occludin and ZO-1,whereas it reduced the protein expression of NF-κB p65 and MLCK(P<0.01)and tended to decrease the protein expression of TNF-α(P=0.094)in heat-stressed broilers.Furthermore,the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression(P<0.05)and negatively correlated with jejunal Occludin level(P<0.05).However,the proportions of Lactobacillus,Barnesiella,Subdoligranulum,Megasphaera,Collinsella,and Blautia among the three groups were positively related to ADG(P<0.05).Conclusions EPS can be used as a feed additive in yellow-feathered broilers.It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression.These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.展开更多
Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrati...Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.展开更多
We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of ac...We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of action of elafibranor(EFN),a dual agonist of peroxisome proliferator-activated receptorα(PPARα)and peroxisome PPARδ(PPARδ).EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis.ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis(ASH),with chronic ASH eventually leading to fibrosis,cirrhosis,and,in some cases,hepatocellular carcinoma.The pathogenesis of ALD is driven by hepatic steatosis,oxidative stress,and acetaldehyde toxicity.Alcohol consumption disrupts lipid metabolism by inactivating PPARα,exacerbating the progression of ALD.EFN primarily activates PPARα,promoting lipolysis andβ-oxidation in ethanol-stimulated HepG2 cells,which significantly reduces hepatic steatosis,apoptosis,and fibrosis in an ALD mouse model.Additionally,alcohol disrupts the gut-liver axis at several interconnected levels,contributing to a proinflammatory environment in the liver.EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy,inhibiting apoptosis and inflammatory responses,and enhancing intestinal barrier function through PPARδactivation.展开更多
●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were tre...●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.展开更多
Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long...Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function.The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.Results Dietary polysaccharide deprivation induced intestinal barrier dysfunction,decreased growth performance,altered microbial composition(Faecalibacterium,Dorea,and Coprobacillus),and reduced isobutyrate concentration.The results showed that APS fa cilitates intestinal barrier function in broiler chickens,including a thicker mucus layer,reduced crypt depth,and the growth of tight junction proteins.We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides,a commensal bacterium that plays a predominant role in enhancing intestinal barrier function.An in vitro g rowth assan further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis.Dietary APS supplementation increased the concentrations of isobutyrate and bile acid(mainly chenodeoxycholic acid and deoxycholate acid)and activated signaling pathways related to intestinal barrier function(such as protein processing in the endoplasmic reticulum,tight junctions,and adherens junction signaling pathways).Conclusions APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis,and increasing the concentrations of isobutyrate and bile acids(mainly CDCA and DCA).These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.展开更多
Although constraint satisfaction approaches have achieved fruitful results,system states may lose their smoothness and there may be undesired chattering of control inputs due to switching characteristics.Furthermore,i...Although constraint satisfaction approaches have achieved fruitful results,system states may lose their smoothness and there may be undesired chattering of control inputs due to switching characteristics.Furthermore,it remains a challenge when there are additional constraints on control torques of robotic systems.In this article,we propose a novel high-order control barrier function(HoCBF)-based safety control method for robotic systems subject to input-output constraints,which can maintain the desired smoothness of system states and reduce undesired chattering vibration in the control torque.In our design,augmented dynamics are introduced into the HoCBF by constructing its output as the control input of the robotic system,so that the constraint satisfaction is facilitated by HoCBFs and the smoothness of system states is maintained by the augmented dynamics.This proposed scheme leads to the quadratic program(QP),which is more user-friendly in implementation since the constraint satisfaction control design is implemented as an add-on to an existing tracking control law.The proposed closed-loop control system not only achieves the requirements of real-time capability,stability,safety and compliance,but also reduces undesired chattering of control inputs.Finally,the effectiveness of the proposed control scheme is verified by simulations and experiments on robotic manipulators.展开更多
Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs wer...Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs were divided into parenteral nutrition(PN) group(7 dogs)and early intrajejunal nutrition(EIN) group(8). EIN was delivered nutrients via a nee-dle jejunostomy catheter feeding at 48h after operation.SAP model was induced by injecting 1 ml/kg of com-bined solution of 5% sodium taurocholate and 8000-10000 BAEE units trypsin/ml into the pancreas via thepancreatic duct. Systemic blood samples were ob-tained before and 1, 3, 5, 7 d following SAP, and culturedby aerobic as well as anaerobic bacterial growth. Systemicplasma and portal vein endotoxin levels were quantifiedby the chromogenic limulus amebocyte lysate (LAL)technique. Portal vein blood and specimens of tissuefrom the mesenteriolum and mesocolon lymph nodes,lung, pulmonary portal lymph nodes, pancreatitis tissueand periopancreas tissue were adopted before the experi-ment was finished. Aliquots of the homogenata were cul-tured as blood mentioned above to determine the magnitudeof the bacteria DNA, protein and the villi, the thickness ofmucosa, and the whole bowel wall of the ileum and trans-verse colon were measured.Results: The study showed that the levels of systemicplasma endotoxin and the magnitude of bacterialtranslocation to the portal and systemic blood and dis-tant organ were reduced significantly in the EINgroup as compared with the TPN group. The contentsof protein and DNA, the height of villi, the thicknessof mucosa and whole bowel wall of the ileum andtransverse colon in the EIN group were higher thanthose in the PN group.Conclusion: Our results suggested that EIN is safe andeffective to be adopted by intrajejunal delivery of nu-trients in SAP, decreases the occurrence of gut bacterialtranslocation, and improves the gut barrier function.展开更多
BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD...BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.展开更多
BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the e...BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.展开更多
AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection...AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS： Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups： parenteral nutrition （PN group, n = 7）, PN＋enteral nutrition （EN group, n = 7） and PN ＋ EN ＋ probiotics （probiotics group, n = 7） via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d （1 x 10^8 cfu/mL）. The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins （occludin） and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electronmicroscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS： （1） The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DNA-proflles in EN group and probiotic group were similar to that of normal rats. The number of DNAprofiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. （2） The expression of occludin and IgA in the small and large intestine in EN group （2.309 ± 0.336, 15.440 ± 2.383） and probiotic group （2.938 ± 0.515, 16.230 ± 3.183） was improved as compared with PN group （1.207 ± 0.587, P 〈 0.05, 11.189 ± 2.108, P 〈 0.01）. The expression of occludin in probiotic group （intestine： 2.93 ± 0.515; cecum： 3.40 ± 0.617） was higher than that in EN group （intestine： 2.309 ± 0.336; cecum： 2.076 ± 0.670; P 〈 0.05）. The expression of IgA, especially in EN group （intestine： 15.440 ± 2.383） and probiotic EN group （large intestine： 12.516 ± 1.542） significantly increased as compared with PN group （intestine： 11.189 ± 2.108; cecum： 10.160 ± 1.643; P 〈 0.01）. The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. （3） The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic （0.082 ± 0.029） and EN （0.125 ± 0.040） groups as compared with PN group （0.403 ± 0.181, P 〈 0.05）. CONCLUSION： Application of EN combined with probiotics could improve the expression of transmembrane binding proteins （occludin） and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.展开更多
Background: Alginate oligosaccharide(AOS), produced from alginate by alginate lyase-mediated depolymerisation, is a potential substitute for antibiotics and possesses growth-enhancing effects. Nevertheless, the mechan...Background: Alginate oligosaccharide(AOS), produced from alginate by alginate lyase-mediated depolymerisation, is a potential substitute for antibiotics and possesses growth-enhancing effects. Nevertheless, the mechanisms by which AOS regulates porcine growth remain to be elucidated. Therefore, we investigated the AOS-mediated changes in the growth performance of weaned pigs by determining the intestinal morphology, barrier function,as well as epithelium apoptosis.Methods: Twenty-four weaned pigs were distributed into two groups(n = 12) and received either a basal diet(control group) or the same diet supplemented with 100 mg/kg AOS. On d 15, D-xylose(0.1 g/kg body weight)was orally administrated to eight randomly selected pigs per treatment, and their serum and intestinal mucosa samples were collected 1 h later.Results: Our results showed that inclusion of AOS in the diet for 2 wk increased(P < 0.05) the average daily body weight gain in weaned pigs. Notably, AOS supplementation ameliorated the intestinal morphology and barrier function, as suggested by the enhanced(P < 0.05) intestinal villus height, secretory immunoglobulin A content and goblet cell counts. Compared to the control group, AOS ingestion both decreased(P < 0.05) the total apoptotic percentage and increased(P < 0.05) the proportion of S phase in the intestinal epithelial cells. Furthermore, AOS not only up-regulated(P < 0.05) the B-cell lymphoma-2(BCL2) transcriptional level but also down-regulated(P < 0.05) the B-cell lymphoma-2-associated X protein(BAX), cysteinyl aspartate-specific proteinase-3(caspase-3) and caspase-9 transcriptional levels in the small intestine.Conclusions: In summary, this study provides evidence that supplemental AOS beneficially affects the growth performance of weaned pigs, which may result from the improved intestinal morphology and barrier function,as well as the inhibited enterocyte death, through reducing apoptosis via mitochondria-dependent apoptosis.展开更多
BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestina...BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestinal barrier function in intestinal injury.This study aimed to investigate the effect of GlyGln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive therapy.METHODS:Twelve inbred Lewis rats were selected randomly as donors,and 24 inbred Brown Norway (BN) rats as recipients of allogenetic LT.The recipients were divided into a control group (Ala,n=12) and an experimental group (Gly-Gln,n=12).In each group,6 normal BN rats were sampled for normal parameters on preoperative day 3.The 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days,and the 6 recipients in the experimental group were given Gly-Gln in the same manner.The 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 days.They were harvested for sampling on postoperative day 8.The following parameters were assessed:intestinal mucosal protein content,mucosal ultrastructure,ileocecal sIgA content,portal plasma levels of endotoxin and TNF-α,and bacterial translocation.RESULTS:All recipients were alive after LT.On preoperative day 3,all parameters were similar in the two groups.On postoperative day 8,all parameters in the two groups were remarkably changed from those on preoperative day 3.However,compared to the Ala group,supplementation withGly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA,improved mucosal microvilli,and decreased portal plasma levels of endotoxin and TNF-α as well as bacterial translocation.CONCLUSION:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.展开更多
AIM： To evaluate the effects of combined treatment of glutamine （Gln） and recombinant human growth hormone（rhGH） on intestinal barrier function following portal hypertension surgery. METHODS： This study was desi...AIM： To evaluate the effects of combined treatment of glutamine （Gln） and recombinant human growth hormone（rhGH） on intestinal barrier function following portal hypertension surgery. METHODS： This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups： control group （n = 20） and supplemental group （adding Gin and rhGH, n = 22）. Every patient received isocaloric and isonitrogenous standard total parenteral nutrition （TPN） starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein （CRP） levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively. RESULTS： On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group （33.7±5.5 vs 31.0 ± 5.4, P 〈 0.05, （1.17±0.32 vs 1.05 ± 0.15, P 〈 0.05, 13.94±1.09 vs 12.33±1.33, P 〈 0.05, and 368.12 ± 59.25 vs 318.12 ± 45.65, P 〈 0.05, respectively）, whereas the increase in serum TNF-α concentration was significantly reduced （41.02 ± 27.56 vs 160.09 ± 35.17, P 〈 0.05）. The increase in L/M ratio was significantly lower in the supplemental group than in the control group （0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P 〈 0.05）. Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION： Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.展开更多
AIM: To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.
AIM:To investigate the effect of probiotics supplemented by gut on the tight junctions of epithelial cells, barrier function and the microflora of rats with abdominal infection. METHODS: After the model of cecal ligat...AIM:To investigate the effect of probiotics supplemented by gut on the tight junctions of epithelial cells, barrier function and the microflora of rats with abdominal infection. METHODS: After the model of cecal ligation and perforation established, SD rats were divided into two groups: parenteral nutrition (PN) group and PIM+probiotics (probiotics) group, PN solution was supplemented by neck vein and probiotics was delivered via the jejunostomy tube for five days. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocation rate (BTR). The ultra-structure of epithelial tight junctions and microvilli of the gut were observed by electron microscopy; occluding expression was measured by indirect-immune fluorescence method; anaerobic bacterial growth by anaerobic culture and DNA fingerprint of bacterial colonies of the feces by PCR. RESULTS: The quantity of lactobacteria and bifydobacteria in probiotics group was higher than that of PN group. The profiles of DNA fingerprint expression in probiotics group were similar to that in the normal group, a new 16S rDNA sequence appeared in the profile in PN group. The occludin expression, the integrality of the gut epithelial tight junction and microvilli in probiotics group were improved as compared with PN group. The BTR and endotoxin in blood were reduced more significantly in probiotics group as compared with PN group. CONCLUSION: The probiotics could improve the gut microflora disturbance, increase occludin expression, maintain the gut epithelial tight junction and decrease the bacterial translocations rate.展开更多
AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS S...AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS Six experimental groups were established-normal control, EPEC, Bifidobacteria infantis(B. infantis), B. longum, B. bifidum, and B. youth groups. Optimal EPEC endotoxin concentration, bifidobacteria fold dilution, and treatment duration were determined. Quantitative real-time polymerase chain reaction and western blot, respectively, were conducted to detect TLR2 and TLR4 m RNA and protein expression in IEC-18 cells. Transepithelial electrical resistance(TEER) was measured by the EVOM chopstick voltohmmeter in each group. All experiments were conducted in triplicate and data were analyzed on SPSS 16.RESULTS TLR2 and TLR4 m RNA and protein expression in the EPEC group were significantly higher than in the control group(P < 0.05). TLR2 m RNA and protein expression in the B. infantis, B. longum and B. youth groups were significantly lower than in the normal control group(P < 0.05). TLR4 m RNA and protein expression in the B. bifidum and B. youth groups were significantly lower than in normal controls(P < 0.05). In addition, the TEER in B. infantis, B. longum, B. bifidum, and B. youth groups were decreased by 19%, 18%, 23% and 23%, respectively, after 120 min of intervention, as compared to the control group. However, the TEER in the EPEC group was significantly decreased by 67% in comparison to the normal control group(P < 0.05).CONCLUSION Bifidobacteria protect IEC-18 cells against injury by down-regulating TLR2 and TLR4 expression and enhance intestinal barrier function to protect the intestinal epithelial cells from pathogenic invasion.展开更多
基金Key International Cooperation Program of the National Natural Science Foundation of China(32120103011)Jiangsu Shuang Chuang Tuan Dui program(JSSCTD202147)+1 种基金Jiangsu Shuang Chuang Ren Cai program(JSSCRC2021541)Initiation Funds of Yangzhou University for Distinguished Scientists.
文摘Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.
文摘BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.
基金This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2022R1I1A3070740).
文摘Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.
基金the China Scholarship Council(202106690037)the Natural Science Foundation of Anhui Province(19080885QE194)。
文摘The trajectory tracking control performance of nonholonomic wheeled mobile robots(NWMRs)is subject to nonholonomic constraints,system uncertainties,and external disturbances.This paper proposes a barrier function-based adaptive sliding mode control(BFASMC)method to provide high-precision,fast-response performance and robustness for NWMRs.Compared with the conventional adaptive sliding mode control,the proposed control strategy can guarantee that the sliding mode variables converge to a predefined neighborhood of origin with a predefined reaching time independent of the prior knowledge of the uncertainties and disturbances bounds.Another advantage of the proposed algorithm is that the control gains can be adaptively adjusted to follow the disturbances amplitudes thanks to the barrier function.The benefit is that the overestimation of control gain can be eliminated,resulting in chattering reduction.Moreover,a modified barrier function-like control gain is employed to prevent the input saturation problem due to the physical limit of the actuator.The stability analysis and comparative experiments demonstrate that the proposed BFASMC can ensure the prespecified convergence performance of the NWMR system output variables and strong robustness against uncertainties/disturbances.
基金funded by the National Nature Science Foundation of China(32002196)。
文摘Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the intestinal barrier function,microbial ecology,and performance of broilers under HS.A total of 144 yellow-feathered broilers(male,56 days old)with 682.59±7.38 g were randomly assigned to 3 groups:1)TN(thermal neutral zone,23.6±1.8℃),2)HS(heat stress,33.2±1.5℃ for 10 h/d),and 3)HSE(HS+0.1%EPS).Each group contained 6 replicates with 8 broilers per replicate.The study was conducted for 4 weeks;feed intake and body weights were measured at the end of weeks 2 and 4.At the end of the feeding trial,small intestine samples were collected for histomorphology,antioxidant,secretory immunoglobulin A(s Ig A)content,apoptosis,gene and protein expression analysis;cecal contents were also collected for microbiota analysis based on 16S r DNA sequencing.Results Dietary EPS promoted the average daily gain(ADG)of broilers during 3–4 weeks of HS(P<0.05).At the end of HS on broilers,the activity of total superoxide dismutase(T-SOD),glutathione S-transferase(GST),and the content of s Ig A in jejunum were improved by EPS supplementation(P<0.05).Besides,dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers(P<0.05).Addition of EPS in HS group broilers'diet upregulated the relative m RNA expression of Occludin,ZO-1,γ-GCLc and IL-10 of the jejunum(P<0.05),whereas downregulated the relative m RNA expression of NF-κB p65,TNF-αand IL-1βof the jejunum(P<0.05).Dietary EPS increased the protein expression of Occludin and ZO-1,whereas it reduced the protein expression of NF-κB p65 and MLCK(P<0.01)and tended to decrease the protein expression of TNF-α(P=0.094)in heat-stressed broilers.Furthermore,the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression(P<0.05)and negatively correlated with jejunal Occludin level(P<0.05).However,the proportions of Lactobacillus,Barnesiella,Subdoligranulum,Megasphaera,Collinsella,and Blautia among the three groups were positively related to ADG(P<0.05).Conclusions EPS can be used as a feed additive in yellow-feathered broilers.It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression.These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.
基金funded by the National Natural Science Foundation of China(32273074,31972746,31872538 and 31772809)the Basic Scientific Research Project of Liaoning Provincial Department of Education,China(LJKZ0632)。
文摘Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.
基金Supported by the National Natural Science Foundation of China,No.82474164,No.82305046,and No.82000572Natural Science Foundation of Jiangsu Province,No.BK20220467+1 种基金Major Project of the Natural Science Research of Jiangsu Higher Education Institutions,No.22KJB310013Science and Technology Project of Jiangsu Province,No.BK20200840.
文摘We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of action of elafibranor(EFN),a dual agonist of peroxisome proliferator-activated receptorα(PPARα)and peroxisome PPARδ(PPARδ).EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis.ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis(ASH),with chronic ASH eventually leading to fibrosis,cirrhosis,and,in some cases,hepatocellular carcinoma.The pathogenesis of ALD is driven by hepatic steatosis,oxidative stress,and acetaldehyde toxicity.Alcohol consumption disrupts lipid metabolism by inactivating PPARα,exacerbating the progression of ALD.EFN primarily activates PPARα,promoting lipolysis andβ-oxidation in ethanol-stimulated HepG2 cells,which significantly reduces hepatic steatosis,apoptosis,and fibrosis in an ALD mouse model.Additionally,alcohol disrupts the gut-liver axis at several interconnected levels,contributing to a proinflammatory environment in the liver.EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy,inhibiting apoptosis and inflammatory responses,and enhancing intestinal barrier function through PPARδactivation.
基金Supported by the National Natural Science Foundation of China(No.81770889)Zhuhai Science and Technology Program(No.ZH22036201210134PWC).
文摘●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.
基金supported by the National Natural Science Foundation of China(32272916)National key Research&Development Program of China(2023YFD1301400)+1 种基金the Program for Shaanxi Science&Technology from Shaanxi Provincial Science and Technology Department(2022GDTSLD-46-0302,2023KXJ-243,2023GXJS-02-01,K3031223075,L2022-QCYZXNY-004,2021TD-30,019HBGC-16,2019ZDXM3-02)the Yongjiang Innovative Research Team。
文摘Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function.The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.Results Dietary polysaccharide deprivation induced intestinal barrier dysfunction,decreased growth performance,altered microbial composition(Faecalibacterium,Dorea,and Coprobacillus),and reduced isobutyrate concentration.The results showed that APS fa cilitates intestinal barrier function in broiler chickens,including a thicker mucus layer,reduced crypt depth,and the growth of tight junction proteins.We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides,a commensal bacterium that plays a predominant role in enhancing intestinal barrier function.An in vitro g rowth assan further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis.Dietary APS supplementation increased the concentrations of isobutyrate and bile acid(mainly chenodeoxycholic acid and deoxycholate acid)and activated signaling pathways related to intestinal barrier function(such as protein processing in the endoplasmic reticulum,tight junctions,and adherens junction signaling pathways).Conclusions APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis,and increasing the concentrations of isobutyrate and bile acids(mainly CDCA and DCA).These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.
基金supported in part by the National Natural Science Foundation of China(62273311,61773351)Henan Provincial Science Foundation for Distinguished Young Scholars(242300421051)。
文摘Although constraint satisfaction approaches have achieved fruitful results,system states may lose their smoothness and there may be undesired chattering of control inputs due to switching characteristics.Furthermore,it remains a challenge when there are additional constraints on control torques of robotic systems.In this article,we propose a novel high-order control barrier function(HoCBF)-based safety control method for robotic systems subject to input-output constraints,which can maintain the desired smoothness of system states and reduce undesired chattering vibration in the control torque.In our design,augmented dynamics are introduced into the HoCBF by constructing its output as the control input of the robotic system,so that the constraint satisfaction is facilitated by HoCBFs and the smoothness of system states is maintained by the augmented dynamics.This proposed scheme leads to the quadratic program(QP),which is more user-friendly in implementation since the constraint satisfaction control design is implemented as an add-on to an existing tracking control law.The proposed closed-loop control system not only achieves the requirements of real-time capability,stability,safety and compliance,but also reduces undesired chattering of control inputs.Finally,the effectiveness of the proposed control scheme is verified by simulations and experiments on robotic manipulators.
文摘Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs were divided into parenteral nutrition(PN) group(7 dogs)and early intrajejunal nutrition(EIN) group(8). EIN was delivered nutrients via a nee-dle jejunostomy catheter feeding at 48h after operation.SAP model was induced by injecting 1 ml/kg of com-bined solution of 5% sodium taurocholate and 8000-10000 BAEE units trypsin/ml into the pancreas via thepancreatic duct. Systemic blood samples were ob-tained before and 1, 3, 5, 7 d following SAP, and culturedby aerobic as well as anaerobic bacterial growth. Systemicplasma and portal vein endotoxin levels were quantifiedby the chromogenic limulus amebocyte lysate (LAL)technique. Portal vein blood and specimens of tissuefrom the mesenteriolum and mesocolon lymph nodes,lung, pulmonary portal lymph nodes, pancreatitis tissueand periopancreas tissue were adopted before the experi-ment was finished. Aliquots of the homogenata were cul-tured as blood mentioned above to determine the magnitudeof the bacteria DNA, protein and the villi, the thickness ofmucosa, and the whole bowel wall of the ileum and trans-verse colon were measured.Results: The study showed that the levels of systemicplasma endotoxin and the magnitude of bacterialtranslocation to the portal and systemic blood and dis-tant organ were reduced significantly in the EINgroup as compared with the TPN group. The contentsof protein and DNA, the height of villi, the thicknessof mucosa and whole bowel wall of the ileum andtransverse colon in the EIN group were higher thanthose in the PN group.Conclusion: Our results suggested that EIN is safe andeffective to be adopted by intrajejunal delivery of nu-trients in SAP, decreases the occurrence of gut bacterialtranslocation, and improves the gut barrier function.
基金The study was reviewed and approved by the Fourth Hospital of Hebei Medical University Institutional Review Board(Approval No.2019082).
文摘BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.
基金supported by grants from the National Basic Research Program (973) of China (2007CB513005, 2009CB522406)a Research Grant awarded by the Health Bureau Fund ofZhejiang Province (2007QN006, 2008A050)
文摘BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.
基金Supported by the National Natural Science Foundation of China, No.30471687
文摘AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS： Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups： parenteral nutrition （PN group, n = 7）, PN＋enteral nutrition （EN group, n = 7） and PN ＋ EN ＋ probiotics （probiotics group, n = 7） via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d （1 x 10^8 cfu/mL）. The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins （occludin） and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electronmicroscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS： （1） The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DNA-proflles in EN group and probiotic group were similar to that of normal rats. The number of DNAprofiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. （2） The expression of occludin and IgA in the small and large intestine in EN group （2.309 ± 0.336, 15.440 ± 2.383） and probiotic group （2.938 ± 0.515, 16.230 ± 3.183） was improved as compared with PN group （1.207 ± 0.587, P 〈 0.05, 11.189 ± 2.108, P 〈 0.01）. The expression of occludin in probiotic group （intestine： 2.93 ± 0.515; cecum： 3.40 ± 0.617） was higher than that in EN group （intestine： 2.309 ± 0.336; cecum： 2.076 ± 0.670; P 〈 0.05）. The expression of IgA, especially in EN group （intestine： 15.440 ± 2.383） and probiotic EN group （large intestine： 12.516 ± 1.542） significantly increased as compared with PN group （intestine： 11.189 ± 2.108; cecum： 10.160 ± 1.643; P 〈 0.01）. The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. （3） The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic （0.082 ± 0.029） and EN （0.125 ± 0.040） groups as compared with PN group （0.403 ± 0.181, P 〈 0.05）. CONCLUSION： Application of EN combined with probiotics could improve the expression of transmembrane binding proteins （occludin） and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.
基金supported by the Special Fund for Agro-scientific Research in the Public Interest(201403047)
文摘Background: Alginate oligosaccharide(AOS), produced from alginate by alginate lyase-mediated depolymerisation, is a potential substitute for antibiotics and possesses growth-enhancing effects. Nevertheless, the mechanisms by which AOS regulates porcine growth remain to be elucidated. Therefore, we investigated the AOS-mediated changes in the growth performance of weaned pigs by determining the intestinal morphology, barrier function,as well as epithelium apoptosis.Methods: Twenty-four weaned pigs were distributed into two groups(n = 12) and received either a basal diet(control group) or the same diet supplemented with 100 mg/kg AOS. On d 15, D-xylose(0.1 g/kg body weight)was orally administrated to eight randomly selected pigs per treatment, and their serum and intestinal mucosa samples were collected 1 h later.Results: Our results showed that inclusion of AOS in the diet for 2 wk increased(P < 0.05) the average daily body weight gain in weaned pigs. Notably, AOS supplementation ameliorated the intestinal morphology and barrier function, as suggested by the enhanced(P < 0.05) intestinal villus height, secretory immunoglobulin A content and goblet cell counts. Compared to the control group, AOS ingestion both decreased(P < 0.05) the total apoptotic percentage and increased(P < 0.05) the proportion of S phase in the intestinal epithelial cells. Furthermore, AOS not only up-regulated(P < 0.05) the B-cell lymphoma-2(BCL2) transcriptional level but also down-regulated(P < 0.05) the B-cell lymphoma-2-associated X protein(BAX), cysteinyl aspartate-specific proteinase-3(caspase-3) and caspase-9 transcriptional levels in the small intestine.Conclusions: In summary, this study provides evidence that supplemental AOS beneficially affects the growth performance of weaned pigs, which may result from the improved intestinal morphology and barrier function,as well as the inhibited enterocyte death, through reducing apoptosis via mitochondria-dependent apoptosis.
基金supported by grants from the National Basic Research Program(973)of China(2007CB513005 and 2009CB522406)the Health Bureau Fund of Zhejiang Province(2008A050)
文摘BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestinal barrier function in intestinal injury.This study aimed to investigate the effect of GlyGln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive therapy.METHODS:Twelve inbred Lewis rats were selected randomly as donors,and 24 inbred Brown Norway (BN) rats as recipients of allogenetic LT.The recipients were divided into a control group (Ala,n=12) and an experimental group (Gly-Gln,n=12).In each group,6 normal BN rats were sampled for normal parameters on preoperative day 3.The 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days,and the 6 recipients in the experimental group were given Gly-Gln in the same manner.The 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 days.They were harvested for sampling on postoperative day 8.The following parameters were assessed:intestinal mucosal protein content,mucosal ultrastructure,ileocecal sIgA content,portal plasma levels of endotoxin and TNF-α,and bacterial translocation.RESULTS:All recipients were alive after LT.On preoperative day 3,all parameters were similar in the two groups.On postoperative day 8,all parameters in the two groups were remarkably changed from those on preoperative day 3.However,compared to the Ala group,supplementation withGly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA,improved mucosal microvilli,and decreased portal plasma levels of endotoxin and TNF-α as well as bacterial translocation.CONCLUSION:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.
文摘AIM： To evaluate the effects of combined treatment of glutamine （Gln） and recombinant human growth hormone（rhGH） on intestinal barrier function following portal hypertension surgery. METHODS： This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups： control group （n = 20） and supplemental group （adding Gin and rhGH, n = 22）. Every patient received isocaloric and isonitrogenous standard total parenteral nutrition （TPN） starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein （CRP） levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively. RESULTS： On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group （33.7±5.5 vs 31.0 ± 5.4, P 〈 0.05, （1.17±0.32 vs 1.05 ± 0.15, P 〈 0.05, 13.94±1.09 vs 12.33±1.33, P 〈 0.05, and 368.12 ± 59.25 vs 318.12 ± 45.65, P 〈 0.05, respectively）, whereas the increase in serum TNF-α concentration was significantly reduced （41.02 ± 27.56 vs 160.09 ± 35.17, P 〈 0.05）. The increase in L/M ratio was significantly lower in the supplemental group than in the control group （0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P 〈 0.05）. Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION： Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.
基金Supported by The National Natural Science Foundation Key Projects of China,No.81230057National Natural Science Foundation of China,No.81172325The Major Basic Research Program of Shanghai,No.12DZ1930502
文摘AIM: To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.
基金Supported by the National Natural Science Foundation of China,No. 30471687
文摘AIM:To investigate the effect of probiotics supplemented by gut on the tight junctions of epithelial cells, barrier function and the microflora of rats with abdominal infection. METHODS: After the model of cecal ligation and perforation established, SD rats were divided into two groups: parenteral nutrition (PN) group and PIM+probiotics (probiotics) group, PN solution was supplemented by neck vein and probiotics was delivered via the jejunostomy tube for five days. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocation rate (BTR). The ultra-structure of epithelial tight junctions and microvilli of the gut were observed by electron microscopy; occluding expression was measured by indirect-immune fluorescence method; anaerobic bacterial growth by anaerobic culture and DNA fingerprint of bacterial colonies of the feces by PCR. RESULTS: The quantity of lactobacteria and bifydobacteria in probiotics group was higher than that of PN group. The profiles of DNA fingerprint expression in probiotics group were similar to that in the normal group, a new 16S rDNA sequence appeared in the profile in PN group. The occludin expression, the integrality of the gut epithelial tight junction and microvilli in probiotics group were improved as compared with PN group. The BTR and endotoxin in blood were reduced more significantly in probiotics group as compared with PN group. CONCLUSION: The probiotics could improve the gut microflora disturbance, increase occludin expression, maintain the gut epithelial tight junction and decrease the bacterial translocations rate.
基金Supported by Medjaden Academy and Research Foundation for Young Scientists,No.MJA20170410
文摘AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS Six experimental groups were established-normal control, EPEC, Bifidobacteria infantis(B. infantis), B. longum, B. bifidum, and B. youth groups. Optimal EPEC endotoxin concentration, bifidobacteria fold dilution, and treatment duration were determined. Quantitative real-time polymerase chain reaction and western blot, respectively, were conducted to detect TLR2 and TLR4 m RNA and protein expression in IEC-18 cells. Transepithelial electrical resistance(TEER) was measured by the EVOM chopstick voltohmmeter in each group. All experiments were conducted in triplicate and data were analyzed on SPSS 16.RESULTS TLR2 and TLR4 m RNA and protein expression in the EPEC group were significantly higher than in the control group(P < 0.05). TLR2 m RNA and protein expression in the B. infantis, B. longum and B. youth groups were significantly lower than in the normal control group(P < 0.05). TLR4 m RNA and protein expression in the B. bifidum and B. youth groups were significantly lower than in normal controls(P < 0.05). In addition, the TEER in B. infantis, B. longum, B. bifidum, and B. youth groups were decreased by 19%, 18%, 23% and 23%, respectively, after 120 min of intervention, as compared to the control group. However, the TEER in the EPEC group was significantly decreased by 67% in comparison to the normal control group(P < 0.05).CONCLUSION Bifidobacteria protect IEC-18 cells against injury by down-regulating TLR2 and TLR4 expression and enhance intestinal barrier function to protect the intestinal epithelial cells from pathogenic invasion.
