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
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
[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
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
BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore th...BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore the biological processes and mechanisms of intestinal injury associated with AP,and to find potential targets for early prevention or treatment of intestinal barrier injury.METHODS This study utilized single-cell RNA sequencing of the small intestine,alongside in vitro and in vivo experiments,to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.RESULTS Seventeen major cell types and 33232 cells were identified across all samples,including normal,AP1(4x caerulein injections,animals sacrificed 2 h after the last injection),and AP2(8x caerulein injections,animals sacrificed 4 h after the last injection).An average of 980 genes per cell was found in the normal intestine,compared to 927 in the AP1 intestine and 1382 in the AP2 intestine.B cells,dendritic cells,mast cells(MCs),and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine.Enterocytes,brush cells,enteroendocrine cells,and goblet cells maintained numbers similar to the normal intestine,while cytotoxic T cells and natural killer(NK)cells increased.Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities.Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities.Activated MCs,secreted chemokine(C-C motif)ligand 5(CCL5),promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury,suggesting that CCL5 from MCs is a potential target for addressing dysfunction.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
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 Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In Chin...BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In China,5.6%-11.5%of the population has IBS,with diarrheal IBS(IBS-D)comprising about 31.5%of the total.AIM To investigate how human umbilical cord mesenchymal stem cells(hUC-MSCs)can alleviate the symptoms with the help of an IBS-D rat model.METHODS Sixty specific pathogen-free-grade male Sprague-Dawley rats were acquired and divided into five groups:Control group,model group,and three hUC-MSC groups with different doses.The model group was induced using a combination of acetic acid and binding stress.We determined the body weight of the mice;analyzed their fecal characteristics,inflammatory factors,and intestinal tissue damage;and conducted intestinal flora analyses.RESULTS The results showed that hUC-MSCs observably restored the dramatic weight loss in the rat model and also lowered the fecal water content to some extent.In addition,hUC-MSCs reduced the expression of inflammatory factors to alleviate the inflammatory response and increased the expression of intestinal barrier functional proteins to restore the colon injury by colonizing the colon tissue.In addition,hUC-MSCs were able to maintain the abundance and diversity of gut flora.CONCLUSION Thus,hUC-MSCs can reduce the expression of inflammatory factors,improve the expression of intestinal barrier functional proteins,and maintain the abundance and diversity of intestinal flora in IBS-D by colonizing the colon tissue.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
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
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 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
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: 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
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 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
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
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.
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.
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.
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 National Natural Science Foundation of China,No.82300739Hunan Provincial Natural Science Foundation,No.2023JJ40821Changsha Natural Science Foundation,No.kq2208308.
文摘BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore the biological processes and mechanisms of intestinal injury associated with AP,and to find potential targets for early prevention or treatment of intestinal barrier injury.METHODS This study utilized single-cell RNA sequencing of the small intestine,alongside in vitro and in vivo experiments,to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.RESULTS Seventeen major cell types and 33232 cells were identified across all samples,including normal,AP1(4x caerulein injections,animals sacrificed 2 h after the last injection),and AP2(8x caerulein injections,animals sacrificed 4 h after the last injection).An average of 980 genes per cell was found in the normal intestine,compared to 927 in the AP1 intestine and 1382 in the AP2 intestine.B cells,dendritic cells,mast cells(MCs),and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine.Enterocytes,brush cells,enteroendocrine cells,and goblet cells maintained numbers similar to the normal intestine,while cytotoxic T cells and natural killer(NK)cells increased.Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities.Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities.Activated MCs,secreted chemokine(C-C motif)ligand 5(CCL5),promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury,suggesting that CCL5 from MCs is a potential target for addressing dysfunction.
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.
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approved by the Institutional Animal Care and Use Committee of Cloud-Clone Corp Wuhan(protocol No.IACU23-1252,on November 29,2023).
文摘BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In China,5.6%-11.5%of the population has IBS,with diarrheal IBS(IBS-D)comprising about 31.5%of the total.AIM To investigate how human umbilical cord mesenchymal stem cells(hUC-MSCs)can alleviate the symptoms with the help of an IBS-D rat model.METHODS Sixty specific pathogen-free-grade male Sprague-Dawley rats were acquired and divided into five groups:Control group,model group,and three hUC-MSC groups with different doses.The model group was induced using a combination of acetic acid and binding stress.We determined the body weight of the mice;analyzed their fecal characteristics,inflammatory factors,and intestinal tissue damage;and conducted intestinal flora analyses.RESULTS The results showed that hUC-MSCs observably restored the dramatic weight loss in the rat model and also lowered the fecal water content to some extent.In addition,hUC-MSCs reduced the expression of inflammatory factors to alleviate the inflammatory response and increased the expression of intestinal barrier functional proteins to restore the colon injury by colonizing the colon tissue.In addition,hUC-MSCs were able to maintain the abundance and diversity of gut flora.CONCLUSION Thus,hUC-MSCs can reduce the expression of inflammatory factors,improve the expression of intestinal barrier functional proteins,and maintain the abundance and diversity of intestinal flora in IBS-D by colonizing the colon tissue.
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 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.
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.
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 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 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.
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.
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.
