Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementat...Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.展开更多
This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid acc...This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.展开更多
Thrombin blockers have been shown to be effective for various pathological conditions,but their use is limited due to the potential for serious bleeding adverse effects.This study introduced a novel bioactive peptide(...Thrombin blockers have been shown to be effective for various pathological conditions,but their use is limited due to the potential for serious bleeding adverse effects.This study introduced a novel bioactive peptide(P-2-CG) from oyster,that mitigated thrombin-mediated barrier dysfunction and prothrombotic phenotypes in human pulmonary microvascular endothelial cells(HPMECs).P-2-CG significantly attenuated the increase in endothelial monolayer permeability induced by thrombin through the possible attenuation of RhoA activation and it promoted barrier recovery by enhancing endothelial cell adhesion.Additionally,P-2-CG was found to decrease the pro-thrombotic phenotype induced by thrombin in HPMEC by reducing the extrinsic trigger tissue factor mRNA expression,which resulted in prolonged plasma clotting time,decreased Factor Xa activation,and reduced thrombin generation.Moreover,P-2-CG inhibited thrombosis efficiently by blocking intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression via tyrosine phosphorylation of nuclear factor-κB p65.P-2-CG inhibits thrombin mediated inflammation and provides a potential therapeutic option for treating endothelial dysfunction and thrombosis.展开更多
In this paper,an adaptive neural backstepping control method based on barrier Lyapunov function is proposed for hypersonic vehicle considering full state constraints.The longitudinal dynamic of hypersonic vehicle can ...In this paper,an adaptive neural backstepping control method based on barrier Lyapunov function is proposed for hypersonic vehicle considering full state constraints.The longitudinal dynamic of hypersonic vehicle can be divided into two subsystems,i.e.,altitude subsystem and velocity subsystem and the controllers are designed with backstepping method,respectively.In the designing process,the radial basis function neural networks are used to approximate the unknown nonlinear functions of longitudinal dynamic,therefore,the accuracy requirement of hypersonic vehicle model is largely reduced.In order to handle the explosion of complexity issues occurring in the backstepping method,a tracking differentiator is introduced to calculate the differential of virtual control law.The barrier Lyapunov function is constructed to overcome the full system dynamic state constraints and an auxiliary system is designed for overcome the input state saturation issue.The stability is carried out based on Lyapunov theory,and the signals of closed-loop system established are uniformly ultimately bounded.The simulation results show that the controller designed for hypersonic vehicle can guarantee the good tracking performance.展开更多
Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects ...Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects and underlying mechanisms on gut health.In this study,a mouse model together with fecal microbiota transplantation(FMT)was utilized to study the effects and mechanisms of fermented DFRB(FR)on gut barrier function.We found that FR improved the intestinal morphology,gut tight junction proteins,mucin,antimicrobial peptides,and interleukin 22(IL-22)and promoted the gut Clostridium butyricum and butyrate.Notably,correlation analysis indicated gut C.butyricum and butyrate were two FR-induced effectors that improved gut health.FMT results suggested that C.butyricum,butyrate,and fecal microbiota from the FR group all reduced prolyl hydroxylase 2(PHD2)expression by activating peroxisome proliferator-activated receptor gamma(PPARγ)in the mouse colon.This decrease in gut PHD2 subsequently upregulated the hypoxia-inducible factor-1 alpha(HIF-1α)expression,which in turn increased the expression of its targeted downstream tight junction proteins,mucin and antimicrobial peptides,and colonic IL-22 secretion.Overall,FR-derived C.butyricum and butyrate might improve gut barrier function through the HIF-1 signaling pathway,which provides a reference for the application of fermented DFRB as a potential functional food for improving of gut barrier function.展开更多
The objective of this paper is to present a robust safety-critical control system based on the active disturbance rejection control approach, designed to guarantee safety even in the presence of model inaccuracies, un...The objective of this paper is to present a robust safety-critical control system based on the active disturbance rejection control approach, designed to guarantee safety even in the presence of model inaccuracies, unknown dynamics, and external disturbances. The proposed method combines control barrier functions and control Lyapunov functions with a nonlinear extended state observer to produce a robust and safe control strategy for dynamic systems subject to uncertainties and disturbances. This control strategy employs an optimization-based control, supported by the disturbance estimation from a nonlinear extended state observer. Using a quadratic programming algorithm, the controller computes an optimal, stable, and safe control action at each sampling instant. The effectiveness of the proposed approach is demonstrated through numerical simulations of a safety-critical interconnected adaptive cruise control system.展开更多
[Objectives]To observe the effects of chloramphenicol prednisone liniment on anti-inflammatory and anti-pruritic responses and skin barrier function in an acute eczema mouse model and explore its potential underlying ...[Objectives]To observe the effects of chloramphenicol prednisone liniment on anti-inflammatory and anti-pruritic responses and skin barrier function in an acute eczema mouse model and explore its potential underlying mechanism.[Methods]Twenty-four female SPF-grade ICR mice were randomly and equally assigned to three groups:the blank control group,the acute eczema group,and the chloramphenicol prednisone liniment group according to the random number table method,with 8 mice per group.Except for the blank control group,the acute eczema model was established by applying 2,4-dinitrochlorobenzene(DNCB)to the right dorsal area.On day 10(d10),0.1 mL of normal saline was administered to the modeling site in both the blank control group and the acute eczema group,whereas chloramphenicol prednisone liniment was applied to the positive drug group.Medication was applied twice daily in all three groups for a total duration of 14 d.Sixty minutes following the final administration of the drug,the development of eczema in mice was visually assessed,and the severity of skin lesions was scored.Trans-epidermal water loss(TEWL)was measured using a multifunctional skin tester.Experiments inducing and alleviating pruritus were performed to compare the frequency of mice licking their bodies,the latency period before pruritus onset,and the duration of pruritus episodes.Levels of histamine and substance P(SP)in the lesion tissues were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]Compared to the acute eczema group,the chloramphenicol prednisone liniment group exhibited a prolonged latency period of pruritus,an increased inhibition rate,and a shortened duration of pruritus.Additionally,there was a significant reduction in the frequency of mice licking their bodies,as well as in six eczema severity indicators:redness and swelling,scratch marks,papules,blisters,exudation or erosion at the lesion site,and the degree of skin swelling.Furthermore,levels of TEWL,histamine,and SP were also significantly decreased(P<0.05).[Conclusions]Chloramphenicol prednisone liniment exhibits anti-inflammatory and anti-pruritic properties.Its mechanism of action may involve the inhibition of mast cell activation within the lesion tissues of eczema model mice,thereby reducing the release of histamine and other active substances.This process alleviates inflammatory damage associated with eczema and contributes to the restoration of skin barrier function.展开更多
This paper introduces a novel chattering-free terminal sliding mode control(SMC)strategy to address chaotic behavior in permanent magnet synchronous generators(PMSG)for offshore wind turbine systems.By integrating an ...This paper introduces a novel chattering-free terminal sliding mode control(SMC)strategy to address chaotic behavior in permanent magnet synchronous generators(PMSG)for offshore wind turbine systems.By integrating an adaptive exponential reaching law with a continuous barrier function,the proposed approach eliminates chattering and ensures robust performance under model uncertainties.The methodology combines adaptive SMC with dynamic switching to estimate and compensates for unknown uncertainties,providing smooth and stable control.Finally,the performance and effectiveness of the proposed approach are compared with those of a previous study.展开更多
This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier...This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.展开更多
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: 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
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
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.
This article considers a Markov-dependent risk model with a constant dividend barrier. A system of integro-differential equations with boundary conditions satisfied by the expected discounted penalty function, with gi...This article considers a Markov-dependent risk model with a constant dividend barrier. A system of integro-differential equations with boundary conditions satisfied by the expected discounted penalty function, with given initial environment state, is derived and solved. Explicit formulas for the discounted penalty function are obtained when the initial surplus is zero or when all the claim amount distributions are from rational family. In two state model, numerical illustrations with exponential claim amounts are given.展开更多
This paper presents a copula technique to develop time-variant seismic fragility curves for corroded bridges at the system level and considers the realistic time-varying dependence among component seismic demands. Bas...This paper presents a copula technique to develop time-variant seismic fragility curves for corroded bridges at the system level and considers the realistic time-varying dependence among component seismic demands. Based on material deterioration mechanisms and incremental dynamic analysis, the time-evolving seismic demands of components were obtained in the form of marginal probability distributions. The time-varying dependences among bridge components were then captured with the best fitting copula function, which was selected from the commonly used copula classes by the empirical distribution based analysis method. The system time-variant fragility curves at different damage states were developed and the effects of time-varying dependences among components on the bridge system fragility were investigated. The results indicate the time-varying dependence among components significantly affects the time-variant fragility of the bridge system. The copula technique captures the nonlinear dependence among component seismic demands accurately and easily by separating the marginal distributions and the dependence among them.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
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
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
AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and ...AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.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 effe...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-αas 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+andγδTCR+lymphocytes.In contrast,compared to the control group,supplementation with probiotics reduced the levels of serum endotoxin,TNF-αand 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
基金The National Natural Science Foundation of China(32302759,32372924)the CAST Youth Talent Support Project-Special Program for Doctoral Students(156-O-230-0000375-5)。
文摘Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.
文摘This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.
基金supported by The National Natural Science Foundation of China (32130085 and 32202021)。
文摘Thrombin blockers have been shown to be effective for various pathological conditions,but their use is limited due to the potential for serious bleeding adverse effects.This study introduced a novel bioactive peptide(P-2-CG) from oyster,that mitigated thrombin-mediated barrier dysfunction and prothrombotic phenotypes in human pulmonary microvascular endothelial cells(HPMECs).P-2-CG significantly attenuated the increase in endothelial monolayer permeability induced by thrombin through the possible attenuation of RhoA activation and it promoted barrier recovery by enhancing endothelial cell adhesion.Additionally,P-2-CG was found to decrease the pro-thrombotic phenotype induced by thrombin in HPMEC by reducing the extrinsic trigger tissue factor mRNA expression,which resulted in prolonged plasma clotting time,decreased Factor Xa activation,and reduced thrombin generation.Moreover,P-2-CG inhibited thrombosis efficiently by blocking intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression via tyrosine phosphorylation of nuclear factor-κB p65.P-2-CG inhibits thrombin mediated inflammation and provides a potential therapeutic option for treating endothelial dysfunction and thrombosis.
基金supported by the National Natural Science Foundation of China(No.61903374).
文摘In this paper,an adaptive neural backstepping control method based on barrier Lyapunov function is proposed for hypersonic vehicle considering full state constraints.The longitudinal dynamic of hypersonic vehicle can be divided into two subsystems,i.e.,altitude subsystem and velocity subsystem and the controllers are designed with backstepping method,respectively.In the designing process,the radial basis function neural networks are used to approximate the unknown nonlinear functions of longitudinal dynamic,therefore,the accuracy requirement of hypersonic vehicle model is largely reduced.In order to handle the explosion of complexity issues occurring in the backstepping method,a tracking differentiator is introduced to calculate the differential of virtual control law.The barrier Lyapunov function is constructed to overcome the full system dynamic state constraints and an auxiliary system is designed for overcome the input state saturation issue.The stability is carried out based on Lyapunov theory,and the signals of closed-loop system established are uniformly ultimately bounded.The simulation results show that the controller designed for hypersonic vehicle can guarantee the good tracking performance.
基金supported by grants from the National Key R&D Program(2023YFD1301303)National Natural Science Foundation of China(32472950,U21A20249)+1 种基金China Agriculture Research System of MOF and MARA(CARS-35)National Center of Technology Innovation for Pigs,Zhejiang Agricultural Talents,Taishan Industrial Leading Talents Project.
文摘Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects and underlying mechanisms on gut health.In this study,a mouse model together with fecal microbiota transplantation(FMT)was utilized to study the effects and mechanisms of fermented DFRB(FR)on gut barrier function.We found that FR improved the intestinal morphology,gut tight junction proteins,mucin,antimicrobial peptides,and interleukin 22(IL-22)and promoted the gut Clostridium butyricum and butyrate.Notably,correlation analysis indicated gut C.butyricum and butyrate were two FR-induced effectors that improved gut health.FMT results suggested that C.butyricum,butyrate,and fecal microbiota from the FR group all reduced prolyl hydroxylase 2(PHD2)expression by activating peroxisome proliferator-activated receptor gamma(PPARγ)in the mouse colon.This decrease in gut PHD2 subsequently upregulated the hypoxia-inducible factor-1 alpha(HIF-1α)expression,which in turn increased the expression of its targeted downstream tight junction proteins,mucin and antimicrobial peptides,and colonic IL-22 secretion.Overall,FR-derived C.butyricum and butyrate might improve gut barrier function through the HIF-1 signaling pathway,which provides a reference for the application of fermented DFRB as a potential functional food for improving of gut barrier function.
基金supported by the Fondo para el Primer Proyecto of the Comitépara el Desarrollo de la Investigación(CODI)at the Universidad de Antioquia(Grant Number PRV2024-78509)。
文摘The objective of this paper is to present a robust safety-critical control system based on the active disturbance rejection control approach, designed to guarantee safety even in the presence of model inaccuracies, unknown dynamics, and external disturbances. The proposed method combines control barrier functions and control Lyapunov functions with a nonlinear extended state observer to produce a robust and safe control strategy for dynamic systems subject to uncertainties and disturbances. This control strategy employs an optimization-based control, supported by the disturbance estimation from a nonlinear extended state observer. Using a quadratic programming algorithm, the controller computes an optimal, stable, and safe control action at each sampling instant. The effectiveness of the proposed approach is demonstrated through numerical simulations of a safety-critical interconnected adaptive cruise control system.
文摘[Objectives]To observe the effects of chloramphenicol prednisone liniment on anti-inflammatory and anti-pruritic responses and skin barrier function in an acute eczema mouse model and explore its potential underlying mechanism.[Methods]Twenty-four female SPF-grade ICR mice were randomly and equally assigned to three groups:the blank control group,the acute eczema group,and the chloramphenicol prednisone liniment group according to the random number table method,with 8 mice per group.Except for the blank control group,the acute eczema model was established by applying 2,4-dinitrochlorobenzene(DNCB)to the right dorsal area.On day 10(d10),0.1 mL of normal saline was administered to the modeling site in both the blank control group and the acute eczema group,whereas chloramphenicol prednisone liniment was applied to the positive drug group.Medication was applied twice daily in all three groups for a total duration of 14 d.Sixty minutes following the final administration of the drug,the development of eczema in mice was visually assessed,and the severity of skin lesions was scored.Trans-epidermal water loss(TEWL)was measured using a multifunctional skin tester.Experiments inducing and alleviating pruritus were performed to compare the frequency of mice licking their bodies,the latency period before pruritus onset,and the duration of pruritus episodes.Levels of histamine and substance P(SP)in the lesion tissues were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]Compared to the acute eczema group,the chloramphenicol prednisone liniment group exhibited a prolonged latency period of pruritus,an increased inhibition rate,and a shortened duration of pruritus.Additionally,there was a significant reduction in the frequency of mice licking their bodies,as well as in six eczema severity indicators:redness and swelling,scratch marks,papules,blisters,exudation or erosion at the lesion site,and the degree of skin swelling.Furthermore,levels of TEWL,histamine,and SP were also significantly decreased(P<0.05).[Conclusions]Chloramphenicol prednisone liniment exhibits anti-inflammatory and anti-pruritic properties.Its mechanism of action may involve the inhibition of mast cell activation within the lesion tissues of eczema model mice,thereby reducing the release of histamine and other active substances.This process alleviates inflammatory damage associated with eczema and contributes to the restoration of skin barrier function.
文摘This paper introduces a novel chattering-free terminal sliding mode control(SMC)strategy to address chaotic behavior in permanent magnet synchronous generators(PMSG)for offshore wind turbine systems.By integrating an adaptive exponential reaching law with a continuous barrier function,the proposed approach eliminates chattering and ensures robust performance under model uncertainties.The methodology combines adaptive SMC with dynamic switching to estimate and compensates for unknown uncertainties,providing smooth and stable control.Finally,the performance and effectiveness of the proposed approach are compared with those of a previous study.
基金Supported by Major Project of Zhongshan Science and Technology Bureau(2021B3009).
文摘This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.
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.
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.
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 in part by Hubei Normal University Post-graduate Foundation(2007D59 and 2007D60)the Science and Technology foundation of Hubei(D20092207)the National Natural Science Foundation of China(10671149)
文摘This article considers a Markov-dependent risk model with a constant dividend barrier. A system of integro-differential equations with boundary conditions satisfied by the expected discounted penalty function, with given initial environment state, is derived and solved. Explicit formulas for the discounted penalty function are obtained when the initial surplus is zero or when all the claim amount distributions are from rational family. In two state model, numerical illustrations with exponential claim amounts are given.
基金Natural Science Foundation of China under Grant No.51808376
文摘This paper presents a copula technique to develop time-variant seismic fragility curves for corroded bridges at the system level and considers the realistic time-varying dependence among component seismic demands. Based on material deterioration mechanisms and incremental dynamic analysis, the time-evolving seismic demands of components were obtained in the form of marginal probability distributions. The time-varying dependences among bridge components were then captured with the best fitting copula function, which was selected from the commonly used copula classes by the empirical distribution based analysis method. The system time-variant fragility curves at different damage states were developed and the effects of time-varying dependences among components on the bridge system fragility were investigated. The results indicate the time-varying dependence among components significantly affects the time-variant fragility of the bridge system. The copula technique captures the nonlinear dependence among component seismic demands accurately and easily by separating the marginal distributions and the dependence among them.
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.
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 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 Dutch Digestive Foundation(MLDS grant WO10-57 to Dejong CHC and Lenaerts K)and MLDS Career development grant CDG13-14 to Derikx JPM)the Netherlands Organisation for Scientific Research(Rubicon grant 2013/07161/ALW to Grootjans J)
文摘AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.
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 of Zhejiang 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-αas 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+andγδTCR+lymphocytes.In contrast,compared to the control group,supplementation with probiotics reduced the levels of serum endotoxin,TNF-αand 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.
