BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.展开更多
Defects in intestinal barrier function characterized by an increase in intestinal permeability contribute to intestinal inflammation.Growing evidence has shown that an increase in intestinal permeability has a pathoge...Defects in intestinal barrier function characterized by an increase in intestinal permeability contribute to intestinal inflammation.Growing evidence has shown that an increase in intestinal permeability has a pathogenic role in diseases such as inflammatory bowel disease(IBD)and celiac disease,and functional bowel disorders such as irritable bowel syndrome.Therefore,clarification of the inflammatory responses,the defense pathway and the corresponding regulatory system is essential and may lead to the development of new therapies.MicroRNAs(miRNAs)are small(19-22nt)noncoding RNA molecules that regulate genes at the post-transcriptional level by base-pairing to specific messenger RNAs for degradation to repress translation.Recent studies suggested that miRNAs are important in the immune response and mediate a critical role in multiple immune response-related disorders.Based on these discoveries,attention has been focused on understanding the role of miRNAs in regulating intestinal barrier dysfunction,especially in IBD.Here,we provide a review of the most recent state-of-the-art research on miRNAs in intestinal barrier dysfunction.展开更多
BACKGROUND：Triggering receptor expressed on myeloid cells-1 （TREM-1） in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased...BACKGROUND：Triggering receptor expressed on myeloid cells-1 （TREM-1） in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis （SAP）, suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS： Sixty-four male Wistar rats were randomly divided into a sham operation group （SO group, n=32） and a SAP group （n=32）. A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase （DAO） and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β （IL-1β）, and tumor necrosis factor-α （TNF-α） mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction （RT-PCR）. Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group （P〈0.01, P〈0.05）. The expression levels of TREM-1, IL-1β and TNF-a mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group （P〈0.01, P〈0.05）. The expression level of TREM-lmRNA was positively correlated with IL-1βand TNF-α mRNA （r=0.956, P=0.044; r=0.986, P=0.015）, but the correlation was not found between IL-1β mRNA and TNF-a mRNA （P=0.133）. Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS： The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-I might play an important role in the development of intestinal barrier dysfunction in rats with SAP.展开更多
BACKGROUND Explore the risk factors of gastrointestinal dysfunction after gastrointestinal tumor surgery and to provide evidence for the prevention and intervention of gastrointestinal dysfunction in patients with gas...BACKGROUND Explore the risk factors of gastrointestinal dysfunction after gastrointestinal tumor surgery and to provide evidence for the prevention and intervention of gastrointestinal dysfunction in patients with gastrointestinal tumor surgery.AIM To investigate the potential risk factors for gastrointestinal dysfunction following gastrointestinal tumor surgery and to present information supporting the prevention and management of gastrointestinal dysfunction in surgery patients.METHODS Systematically searched the relevant literature from PubMed,Web of Science,Cochrane Library,Embase,CNKI,China Biomedical Database,Wanfang Database,and Weipu Chinese Journal Database self-established until October 1,2022.Review Manager 5.3 software was used for meta-analysis after two researchers independently screened literature,extracted data,and evaluated the risk of bias in the included studies.RESULTS A total of 23 pieces of literature were included,the quality of which was medium or above,and the total sample size was 43878.The results of meta-analysis showed that the patients were male(OR=1.58,95%CI:1.25-2.01,P=0.002)and≥60 years old(OR=2.60,95%CI:1.76-2.87,P<0.001),physical index≥25.3 kg/m2(OR=1.6,95%CI:1.00-1.12,P=0.040),smoking history(OR=1.89,95%CI:1.31-2.73,P<0.001),chronic obstructive pulmonary disease(OR=1.49,95%CI:1.22-1.83,P<0.001),enterostomy(OR=1.47,95%CI:1.26-1.70,P<0.001),history of abdominal surgery(OR=2.90,95%CI:1.67-5.03,P<0.001),surgical site(OR=1.2,95%CI:1.40-2.62,P<0.001),operation method(OR=1.68,95%CI:1.08-2.62,P=0.020),operation duration(OR=2.65,95%CI:1.92-3.67,P<0.001),abdominal adhesion grade(OR=2.52,95%CI:1.90-3.56,P<0.001),postoperative opioid history(OR=5.35,95%CI:3.29-8.71,P<0.001),tumor TNM staging(OR=2.58,95%CI:1.84-3.62,P<0.001),postoperative blood transfusion(OR=2.92,95%CI:0.88-9.73,P=0.010)is a risk factor for postoperative gastrointestinal dysfunction in patients with gastrointestinal tumors.CONCLUSION There are many factors affecting gastrointestinal dysfunction in gastrointestinal patients after surgery.Clinical staff should identify relevant risk factors early and implement targeted intervention measures on the basis of personalized assessment to improve the clinical prognosis of patients.展开更多
Objective:To analyze the effect of intestinal function-recovering decoction on multiple organ dysfunction syndrome in rats,and to investigate a novel solution to multiple organ dysfunction syndrome.Methods:Multiple or...Objective:To analyze the effect of intestinal function-recovering decoction on multiple organ dysfunction syndrome in rats,and to investigate a novel solution to multiple organ dysfunction syndrome.Methods:Multiple organ dysfunction syndrome was induced in 60 Sprague-Dawley rats by intestinal ischemia-reperfusion combined with cecal ligation and puncture.Then these rats were intragastrically administered physiological saline(group Ⅰ,n=20),ampicillin(group Ⅱ,n=20) or intestinal function-recovering decoction(group Ⅲ,n=20).After treatment, serum malondialdehyde and superoxide dismutase levels were compared among three groups. Simultaneously,bacterial culture of various organ tissues was performed and bacterial and endotoxin translocation were observed.Results:Compared with group 1,serum malondialdehyde, alanine aminotransferase and aspartate aminotransferase levels were significantly decreased(all P<0.05) and serum superoxide dismutase level was significantly increased(P<0.05) in the group Ⅲ. However,there were no significant differences in these indices between groups Ⅱ and Ⅲ(P>0.05). The rate of bacterial translocation in the groups Ⅱ and Ⅲ was significantly lower than in the group Ⅰ(P<0.05),and no significant difference was observed between groups Ⅱ and Ⅲ(P>0.05). Conclusions:Intestinal function-recovering decoction can significantly reduce endotoxin and bacterial translocation and stabilize enteral oxidative-antioxidative balance.展开更多
Ultra-processed foods(UPFs)are believed to contribute to the development of multiple chronic inflammatory diseases,including inflammatory bowel diseases and metabolic syndrome,based on epidemiological studies and emer...Ultra-processed foods(UPFs)are believed to contribute to the development of multiple chronic inflammatory diseases,including inflammatory bowel diseases and metabolic syndrome,based on epidemiological studies and emerging preclinical and clinical research.Several aspects of food processing and for-mulation in the development of chronic inflammatory diseases are currently being studied.Ongoing research emphasizes epidemiological evidence and mechanistic insights regarding UPFs and their interaction with the intestinal microbiota.In this review,we explore UPFs,their interaction with the intestinal microbiota,and the implications for gastrointestinal health.展开更多
BACKGROUND Ferroptosis is a newly recognized form of regulated cell death characterized by iron-dependent accumulation of lipid reactive oxygen species.It has been extensively studied in various diseases,including can...BACKGROUND Ferroptosis is a newly recognized form of regulated cell death characterized by iron-dependent accumulation of lipid reactive oxygen species.It has been extensively studied in various diseases,including cancer,Parkinson’s disease,and stroke.However,its precise role and underlying mechanisms in ischemia/reperfusion injury,particularly in the intestinal ischemia-reperfusion(IIR),remain unclear.In current work,we aimed to investigate the participation of histone lactylation during IIR progression.AIM To investigate the role of mitochondrial alanyl-tRNA synthetase 2(AARS2)in ferroptosis and its epigenetic regulation of acyl-CoA synthetase long-chain family member 4(ACSL4)through histone lactylation during IIR injury.METHODS We established a mouse model to mimic IIR and conducted AARS2 knockdown as treatment.The expression of AARS2 in intestinal tissues was measured by western blot.The integrity of intestinal tissues was detected by hematoxylin and eosin staining,serum fatty acid-binding protein,protein levels of ZO-1 and occluding.An in vitro hypoxia-reperfusion(H/R)cell model was established,and cell viability was measured by CCK-8.The in vitro and in vivo ferroptosis was determined by the accumulation of Fe2+and malondialdehyde(MDA).The epigenetic regulation of ACSL4 by AARS2 was detected by chromatin immunoprecipitation(ChIP)assay and luciferase reporter assay.RESULTS We observed a notable elevated AARS2 level in intestinal tissue of mice in IIR model group,which was reversed by shAARS2 treatment.Knockdown of AARS2 repressed alleviated intestinal barrier disruption and repressed the accumulation of ferroptosis biomarker Fe2+and MDA during IIR.The in vitro results showed that shAARS2 alleviated impaired cell viability caused by H/R,as well as repressed ferroptosis.Knockdown of AARS2 notably downregulated the RNA and protein expression of ACSL4.Mechanistically,knockdown of AARS2 downregulated the enrichment of H3K18 La modification on AARS2,as well as suppressed its promoter activity.Overexpression of AARS2 could abolish the protective effects of shACSL4 in vitro.CONCLUSION The elevation of AARS2 during IIR led to cell ferroptosis via epigenetically upregulating the expression of ACSL4.Our findings presented AARS2 as a promising therapeutic target for IIR.展开更多
Anthocyanin,as a typical food bioactive molecule,is capable of reversing inflammatory,oxidative and allergic condition thus contributes to intestinal health.We were wondering whether anthocyanin has influence on the i...Anthocyanin,as a typical food bioactive molecule,is capable of reversing inflammatory,oxidative and allergic condition thus contributes to intestinal health.We were wondering whether anthocyanin has influence on the infiltration of inflammatory cells into the intestinal mucosa and thus help enhancing intestinal barrier which could be damaged in some metabolic diseases.In this study,the influence of anthocyanin(administered orally)on the alterations(including structure and permeability)of the intestinal mucosa in mice in response to a high fat-high cholesterol(HFHC)diet was investigated.Primary T helper 17(Th17)cells were isolated from mouse intestine tissues to observe the modulatory role of anthocyanin through the transcription phosphorylated STAT 3(p-STAT3).The results indicated that anthocyanin significantly alleviated HFHC-induced impairment in the intestinal structures and permeability in a dose-dependent manner;moreover,anthocyanin appeared to inhibit HFHC induced the expression of p-STAT3,thereby disturbing Th17 cell differentiation.In high-fat diet(HFD,cholesterol level non-modified)-challenged mice selective p-STAT3 inhibitor significantly reversed the effects of anthocyanin,which were decreased amount of interleukin(IL)-17A(produced and released from Th17 cells)and the protected intestinal structure/function.In summary,the results of this study suggest that anthocyanin may attenuate the damage of intestinal barrier in HFHC mice through regulating intestinal STAT3-Th17-IL-17A signal transduction pathway.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to ...AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.展开更多
Irritable bowel syndrome (IBS) is an intestinal functional disorder with the highest prevalence in the industrialized world. The intestinal microbiota (IM) plays a role in the pathogenesis of IBS and is not merely a c...Irritable bowel syndrome (IBS) is an intestinal functional disorder with the highest prevalence in the industrialized world. The intestinal microbiota (IM) plays a role in the pathogenesis of IBS and is not merely a consequence of this disorder. Previous research efforts have not revealed unequivocal microbiological signatures of IBS, and the experimental results are contradictory. The experimental methodologies adopted to investigate the complex intestinal ecosystem drastically impact the quality and significance of the results. Therefore, to consider the methodological aspects of the research on IM in IBS, we reviewed 29 relevant original research articles identified through a PubMed search using three combinations of keywords: “irritable bowel syndrome + microflora”, “irritable bowel syndrome + microbiota” and “irritable bowel syndrome + microbiome”. For each study, we reviewed the quality and significance of the scientific evidence obtained with respect to the experimental method adopted. The data obtained from each study were compared with all considered publications to identify potential inconsistencies and explain contradictory results. The analytical revision of the studies referenced in the present review has contributed to the identification of microbial groups whose relative abundance significantly alters IBS, suggesting that these microbial groups could be IM signatures for this syndrome. The identification of microbial biomarkers in the IM can be advantageous for the development of new diagnostic tools and novel therapeutic strategies for the treatment of different subtypes of IBS.展开更多
AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive v...AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.展开更多
AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal g...AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal group (n = 12): normal BN rats without any drug or operation; (2) SGT group (syngeneic transplant of BN-BN, n = 12): both donors and recipients were BN rats; and (3) AGT group (allogeneic transplant of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one d after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (aP < 0.01, bP < 0.001, respectively). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both aP < 0.01, bP < 0.05, respectively). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87± 0.13) were remarkably reduced (both aP < 0.01, bP < 0.05, respectively). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.展开更多
The intestinal mucosa is a highly compartmentalized structure that forms a directbarrier between the host intestine and the environment, and its dysfunction couldresult in a serious disease. As T cells, which are impo...The intestinal mucosa is a highly compartmentalized structure that forms a directbarrier between the host intestine and the environment, and its dysfunction couldresult in a serious disease. As T cells, which are important components of themucosal immune system, interact with gut microbiota and maintain intestinalhomeostasis, they may be involved in the process of intestinal barrier dysfunction.P2X7 receptor (P2X7R), a member of the P2X receptors family, mediates the effectsof extracellular adenosine triphosphate and is expressed by most innate or adaptiveimmune cells, including T cells. Current evidence has demonstrated thatP2X7R is involved in inflammation and mediates the survival and differentiationof T lymphocytes, indicating its potential role in the regulation of T cell function.In this review, we summarize the available research about the regulatory role andmechanism of P2X7R on the intestinal mucosa-derived T cells in the setting ofintestinal barrier dysfunction.展开更多
AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in pa...AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome criteria(depending on the year of diagnosis)for IBS.2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings.We assessed other functional symptoms(epigastric pain,nausea,vomiting,belching,constipation and diarrhea)in patients suffering from GERD,IBS or both.RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4±10.3 years) also hadGERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) =3.2, 95% confidence interval (CI): 2.9-3.7, P<0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR=3.6, 95% CI: 3.1-4.3, P<0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P<0.05).CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.展开更多
Objective:To study the correlation of intestinal flora disturbance with immune response and inflammatory response in patients with MODS.Methods: 60 patients with MODS who were treated in our hospital between August 20...Objective:To study the correlation of intestinal flora disturbance with immune response and inflammatory response in patients with MODS.Methods: 60 patients with MODS who were treated in our hospital between August 2013 and January 2017 were collected as the observation group, and 50 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. The differences in intestinal flora distribution in the feces samples, peripheral blood contents of T lymphocyte subsets and serum levels of immunoglobulin and inflammatory factors were compared between two groups of subjects. The relationship of intestinal flora distribution with immune response and inflammatory response was assessed by Pearson test.Results: Bifidobacterium and lactobacillus count as well as B/E value in feces of observation group were lower than those of normal control group while escherichia coli and enterococcus count were higher than those of normal control group;peripheral blood CD4+T lymphocyte proportion and CD4+/CD8+ratio were lower than those of normal control group while CD8+T lymphocyte proportion was higher than that of normal control group;serum immunoglobulin IgA, IgM and IgG levels were lower than those of normal control group;serum inflammatory factors PCT, IL-1, IL-6, IL-8 and TNF-α levels were higher than those of normal control group. Pearson test showed that the intestinal flora disturbance in patients with MODS is directly correlated with the immune response function and inflammatory response.Conclusion:There is obvious intestinal flora disturbance in patients with MODS, and it is one of the important causes of immune function injury and systemic inflammatory response in patients.展开更多
The external environment plays a decisive role in the changes of the intestinal microecology.The low oxygen environment of the plateau disturbs the barrier function of the intestinal mucosa,altered flora structure exa...The external environment plays a decisive role in the changes of the intestinal microecology.The low oxygen environment of the plateau disturbs the barrier function of the intestinal mucosa,altered flora structure exacerbates intestinal mucosal barrier damage.It is possible that the mechanism of intestinal mucosal injury is the upregulation of the expression of hypoxia-inducible factor HIF-1αin the intestine under hypoxic environment,along with the sustained expression of inducible nitric oxide synthase(iNOS),which triggers intestinal mucosal injury.展开更多
Since the 1918 influenza pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced the largest pandemic throughout the globe. SARS-CoV and the Middle East respiratory syndrome (MERS-CoV) ...Since the 1918 influenza pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced the largest pandemic throughout the globe. SARS-CoV and the Middle East respiratory syndrome (MERS-CoV) are both members of the Beta CoV. The coronavirus disease of 2019 (COVID-19) has terrible implications and is currently a serious health concern throughout the world. SARS-CoV-2 affects the respiratory system first since it is the major site of entrance into the patient, but it can also damage other systems. Aside from the typical respiratory problems, several COVID-19 patients develop gastrointestinal (GI) symptoms such as weight loss, vomiting, nausea, and diarrhea. SARS-CoV-2 may infect the GI system via the angiotensin-converting enzyme 2 (ACE2) receptor, and indications of a fecal-oral transmission pathway are growing. Globally, GI disorders (GIDs) are becoming a major source of morbidity in youth. The condition has a significant financial impact on healthcare systems and hurts people's lives;nonetheless, very little is documented about the condition's worldwide prevalence and incidence. Alterations in gut sensitivity, motility, microbiota, immunological function, and central nervous system processing are all factors that contribute to GIDs. GI malfunction results in changes in changes in gut bacteria as well as an elevation in inflammatory cytokines. As a result, recognizing GI symptoms that precede COVID-19 respiratory issues may be crucial for better early identification and treatment. In GI epithelial cells of the intestinal mucosa, ACE2 and transmembrane protease serine-type 2 were also discovered to be substantially expressed. SARS-CoV-2 may also infect and multiply in both GI and liver cells in a dynamic manner. These findings suggest that SARS-CoV-2 might be a viable target for the GI tract. This review focuses on the GI complications that arise due to COVID-19 and how the CoVs give rise to GI symptoms.展开更多
BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorptio...BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorption,regulate metabolic pathways associated with childhood growth and inflammation,and may be affected by EED.AIM To investigate bile acid metabolism in Bangladeshi children with EED and its association with growth impairment.METHODS We conducted a cross-sectional study of 100 Bangladeshi infants(aged 6-9 months)and quantified serum and fecal bile acids using LC-MS/MS.We compared profiles to a control group of 6 American children(6-12 months)and 80 older Bangladeshi children(aged 2 years).RESULTS Bangladeshi infants had higher levels of plasma unconjugated primary(65.23%vs 44.25%,P=0.003)and sulfated primary bile acids(12.98%vs<0.001%,P=0.01),with lower primary conjugated bile acids(0.69%vs 2.74%,P≤0.001)compared to American children.Stool unconjugated primary bile acids were inversely associated with weight-for-age[regression coefficient(β)=-0.01,P=0.01]and height-for-age Z scores(β=-0.01,P=0.03).Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth(β=-1096.68,P=0.05).Fecal myeloperoxidase was associated with sulfated secondary bile acids(β=-0.40,P=0.04).Compared to 2-year-old children,the Bangladeshi infant’s serum had higher levels of unconjugated primary bile acids(65.23%vs 9.20%,P≤0.001)and lower levels of primary conjugated bile acids(0.69%vs 80.38%,P≤0.001).CONCLUSION Our data suggests an age-dependent defect in conjugation of primary bile acids in Bangladeshi children with compensatory hydrophilic shunting.Additionally,bile acid profiles are associated with intestinal overgrowth.展开更多
The relationship between gut microbiota and host health and disease is intricate,with microbiota-derived metabolites playing a crucial role in the gut-organ axis.In this study,we observe significantly decreased levels...The relationship between gut microbiota and host health and disease is intricate,with microbiota-derived metabolites playing a crucial role in the gut-organ axis.In this study,we observe significantly decreased levels of microbial metabolites,particularly tryptophan derivatives in osteoporosis mice.Loss of tryptophan induced intestinal epithelial barrier dysfunction which compromised intestinal barrier integrity,leading to bone inflammatory responses and pathological osteoporosis.Through supplementation of tryptophan-producing bacteria,we effectively repair damaged intestinal barriers in colitis mice and mitigate bone loss,indicating the link between chronic colitis and osteoporosis.This approach offers a promising synthetic biology-based strategy to improve osteoporosis therapy by targeting gut tryptophan.This intervention also alleviates age-related osteoporosis in an aged mouse model,providing a potential therapeutic avenue for combating osteoporosis,a disease of growing concern in aging populations.展开更多
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.
基金Supported by Grant for Key Clinical Discipline Construction of Shanghai Municipality,China,No.ZK2012B20Phase Ⅱ Outstanding Young Medical Personnel Training Fund of Jinshan District Health Systems,Shanghai,China,No.JWKJ-RCYQ-201207
文摘Defects in intestinal barrier function characterized by an increase in intestinal permeability contribute to intestinal inflammation.Growing evidence has shown that an increase in intestinal permeability has a pathogenic role in diseases such as inflammatory bowel disease(IBD)and celiac disease,and functional bowel disorders such as irritable bowel syndrome.Therefore,clarification of the inflammatory responses,the defense pathway and the corresponding regulatory system is essential and may lead to the development of new therapies.MicroRNAs(miRNAs)are small(19-22nt)noncoding RNA molecules that regulate genes at the post-transcriptional level by base-pairing to specific messenger RNAs for degradation to repress translation.Recent studies suggested that miRNAs are important in the immune response and mediate a critical role in multiple immune response-related disorders.Based on these discoveries,attention has been focused on understanding the role of miRNAs in regulating intestinal barrier dysfunction,especially in IBD.Here,we provide a review of the most recent state-of-the-art research on miRNAs in intestinal barrier dysfunction.
基金The study was supported by a grant from the National Natural Science Foundation of China （81070287）.
文摘BACKGROUND：Triggering receptor expressed on myeloid cells-1 （TREM-1） in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis （SAP）, suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS： Sixty-four male Wistar rats were randomly divided into a sham operation group （SO group, n=32） and a SAP group （n=32）. A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase （DAO） and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β （IL-1β）, and tumor necrosis factor-α （TNF-α） mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction （RT-PCR）. Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group （P〈0.01, P〈0.05）. The expression levels of TREM-1, IL-1β and TNF-a mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group （P〈0.01, P〈0.05）. The expression level of TREM-lmRNA was positively correlated with IL-1βand TNF-α mRNA （r=0.956, P=0.044; r=0.986, P=0.015）, but the correlation was not found between IL-1β mRNA and TNF-a mRNA （P=0.133）. Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS： The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-I might play an important role in the development of intestinal barrier dysfunction in rats with SAP.
文摘BACKGROUND Explore the risk factors of gastrointestinal dysfunction after gastrointestinal tumor surgery and to provide evidence for the prevention and intervention of gastrointestinal dysfunction in patients with gastrointestinal tumor surgery.AIM To investigate the potential risk factors for gastrointestinal dysfunction following gastrointestinal tumor surgery and to present information supporting the prevention and management of gastrointestinal dysfunction in surgery patients.METHODS Systematically searched the relevant literature from PubMed,Web of Science,Cochrane Library,Embase,CNKI,China Biomedical Database,Wanfang Database,and Weipu Chinese Journal Database self-established until October 1,2022.Review Manager 5.3 software was used for meta-analysis after two researchers independently screened literature,extracted data,and evaluated the risk of bias in the included studies.RESULTS A total of 23 pieces of literature were included,the quality of which was medium or above,and the total sample size was 43878.The results of meta-analysis showed that the patients were male(OR=1.58,95%CI:1.25-2.01,P=0.002)and≥60 years old(OR=2.60,95%CI:1.76-2.87,P<0.001),physical index≥25.3 kg/m2(OR=1.6,95%CI:1.00-1.12,P=0.040),smoking history(OR=1.89,95%CI:1.31-2.73,P<0.001),chronic obstructive pulmonary disease(OR=1.49,95%CI:1.22-1.83,P<0.001),enterostomy(OR=1.47,95%CI:1.26-1.70,P<0.001),history of abdominal surgery(OR=2.90,95%CI:1.67-5.03,P<0.001),surgical site(OR=1.2,95%CI:1.40-2.62,P<0.001),operation method(OR=1.68,95%CI:1.08-2.62,P=0.020),operation duration(OR=2.65,95%CI:1.92-3.67,P<0.001),abdominal adhesion grade(OR=2.52,95%CI:1.90-3.56,P<0.001),postoperative opioid history(OR=5.35,95%CI:3.29-8.71,P<0.001),tumor TNM staging(OR=2.58,95%CI:1.84-3.62,P<0.001),postoperative blood transfusion(OR=2.92,95%CI:0.88-9.73,P=0.010)is a risk factor for postoperative gastrointestinal dysfunction in patients with gastrointestinal tumors.CONCLUSION There are many factors affecting gastrointestinal dysfunction in gastrointestinal patients after surgery.Clinical staff should identify relevant risk factors early and implement targeted intervention measures on the basis of personalized assessment to improve the clinical prognosis of patients.
基金It is supported by a grant from Special Scientific Research Project of Health Care funded by Ministry of Health(No.201202011)
文摘Objective:To analyze the effect of intestinal function-recovering decoction on multiple organ dysfunction syndrome in rats,and to investigate a novel solution to multiple organ dysfunction syndrome.Methods:Multiple organ dysfunction syndrome was induced in 60 Sprague-Dawley rats by intestinal ischemia-reperfusion combined with cecal ligation and puncture.Then these rats were intragastrically administered physiological saline(group Ⅰ,n=20),ampicillin(group Ⅱ,n=20) or intestinal function-recovering decoction(group Ⅲ,n=20).After treatment, serum malondialdehyde and superoxide dismutase levels were compared among three groups. Simultaneously,bacterial culture of various organ tissues was performed and bacterial and endotoxin translocation were observed.Results:Compared with group 1,serum malondialdehyde, alanine aminotransferase and aspartate aminotransferase levels were significantly decreased(all P<0.05) and serum superoxide dismutase level was significantly increased(P<0.05) in the group Ⅲ. However,there were no significant differences in these indices between groups Ⅱ and Ⅲ(P>0.05). The rate of bacterial translocation in the groups Ⅱ and Ⅲ was significantly lower than in the group Ⅰ(P<0.05),and no significant difference was observed between groups Ⅱ and Ⅲ(P>0.05). Conclusions:Intestinal function-recovering decoction can significantly reduce endotoxin and bacterial translocation and stabilize enteral oxidative-antioxidative balance.
文摘Ultra-processed foods(UPFs)are believed to contribute to the development of multiple chronic inflammatory diseases,including inflammatory bowel diseases and metabolic syndrome,based on epidemiological studies and emerging preclinical and clinical research.Several aspects of food processing and for-mulation in the development of chronic inflammatory diseases are currently being studied.Ongoing research emphasizes epidemiological evidence and mechanistic insights regarding UPFs and their interaction with the intestinal microbiota.In this review,we explore UPFs,their interaction with the intestinal microbiota,and the implications for gastrointestinal health.
文摘BACKGROUND Ferroptosis is a newly recognized form of regulated cell death characterized by iron-dependent accumulation of lipid reactive oxygen species.It has been extensively studied in various diseases,including cancer,Parkinson’s disease,and stroke.However,its precise role and underlying mechanisms in ischemia/reperfusion injury,particularly in the intestinal ischemia-reperfusion(IIR),remain unclear.In current work,we aimed to investigate the participation of histone lactylation during IIR progression.AIM To investigate the role of mitochondrial alanyl-tRNA synthetase 2(AARS2)in ferroptosis and its epigenetic regulation of acyl-CoA synthetase long-chain family member 4(ACSL4)through histone lactylation during IIR injury.METHODS We established a mouse model to mimic IIR and conducted AARS2 knockdown as treatment.The expression of AARS2 in intestinal tissues was measured by western blot.The integrity of intestinal tissues was detected by hematoxylin and eosin staining,serum fatty acid-binding protein,protein levels of ZO-1 and occluding.An in vitro hypoxia-reperfusion(H/R)cell model was established,and cell viability was measured by CCK-8.The in vitro and in vivo ferroptosis was determined by the accumulation of Fe2+and malondialdehyde(MDA).The epigenetic regulation of ACSL4 by AARS2 was detected by chromatin immunoprecipitation(ChIP)assay and luciferase reporter assay.RESULTS We observed a notable elevated AARS2 level in intestinal tissue of mice in IIR model group,which was reversed by shAARS2 treatment.Knockdown of AARS2 repressed alleviated intestinal barrier disruption and repressed the accumulation of ferroptosis biomarker Fe2+and MDA during IIR.The in vitro results showed that shAARS2 alleviated impaired cell viability caused by H/R,as well as repressed ferroptosis.Knockdown of AARS2 notably downregulated the RNA and protein expression of ACSL4.Mechanistically,knockdown of AARS2 downregulated the enrichment of H3K18 La modification on AARS2,as well as suppressed its promoter activity.Overexpression of AARS2 could abolish the protective effects of shACSL4 in vitro.CONCLUSION The elevation of AARS2 during IIR led to cell ferroptosis via epigenetically upregulating the expression of ACSL4.Our findings presented AARS2 as a promising therapeutic target for IIR.
基金supported by the National Natural Science Foundation of China(81973022 and 81730090)。
文摘Anthocyanin,as a typical food bioactive molecule,is capable of reversing inflammatory,oxidative and allergic condition thus contributes to intestinal health.We were wondering whether anthocyanin has influence on the infiltration of inflammatory cells into the intestinal mucosa and thus help enhancing intestinal barrier which could be damaged in some metabolic diseases.In this study,the influence of anthocyanin(administered orally)on the alterations(including structure and permeability)of the intestinal mucosa in mice in response to a high fat-high cholesterol(HFHC)diet was investigated.Primary T helper 17(Th17)cells were isolated from mouse intestine tissues to observe the modulatory role of anthocyanin through the transcription phosphorylated STAT 3(p-STAT3).The results indicated that anthocyanin significantly alleviated HFHC-induced impairment in the intestinal structures and permeability in a dose-dependent manner;moreover,anthocyanin appeared to inhibit HFHC induced the expression of p-STAT3,thereby disturbing Th17 cell differentiation.In high-fat diet(HFD,cholesterol level non-modified)-challenged mice selective p-STAT3 inhibitor significantly reversed the effects of anthocyanin,which were decreased amount of interleukin(IL)-17A(produced and released from Th17 cells)and the protected intestinal structure/function.In summary,the results of this study suggest that anthocyanin may attenuate the damage of intestinal barrier in HFHC mice through regulating intestinal STAT3-Th17-IL-17A signal transduction pathway.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
基金Supported by The research grants from Shanghai Municipal Science and Technology CommissionNo.114119b2900+1 种基金Shanghai Municipal Key Laboratory of Pancreatic DiseaseNo.P2012006
文摘AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.
文摘Irritable bowel syndrome (IBS) is an intestinal functional disorder with the highest prevalence in the industrialized world. The intestinal microbiota (IM) plays a role in the pathogenesis of IBS and is not merely a consequence of this disorder. Previous research efforts have not revealed unequivocal microbiological signatures of IBS, and the experimental results are contradictory. The experimental methodologies adopted to investigate the complex intestinal ecosystem drastically impact the quality and significance of the results. Therefore, to consider the methodological aspects of the research on IM in IBS, we reviewed 29 relevant original research articles identified through a PubMed search using three combinations of keywords: “irritable bowel syndrome + microflora”, “irritable bowel syndrome + microbiota” and “irritable bowel syndrome + microbiome”. For each study, we reviewed the quality and significance of the scientific evidence obtained with respect to the experimental method adopted. The data obtained from each study were compared with all considered publications to identify potential inconsistencies and explain contradictory results. The analytical revision of the studies referenced in the present review has contributed to the identification of microbial groups whose relative abundance significantly alters IBS, suggesting that these microbial groups could be IM signatures for this syndrome. The identification of microbial biomarkers in the IM can be advantageous for the development of new diagnostic tools and novel therapeutic strategies for the treatment of different subtypes of IBS.
文摘AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.
基金Supported by National Basic Research Program (973) of China, No. 2007CB513005, No. 2009CB522401 and No. 2009CB522406
文摘AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal group (n = 12): normal BN rats without any drug or operation; (2) SGT group (syngeneic transplant of BN-BN, n = 12): both donors and recipients were BN rats; and (3) AGT group (allogeneic transplant of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one d after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (aP < 0.01, bP < 0.001, respectively). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both aP < 0.01, bP < 0.05, respectively). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87± 0.13) were remarkably reduced (both aP < 0.01, bP < 0.05, respectively). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.
基金Supported by The National Natural Science Foundation of China,No. 81801943Shanghai Pujiang Program,No. 21PJD009The Research Grant for Public Health Key Discipline of Shanghai Municipality,China,No. GWV-10.1-XK26
文摘The intestinal mucosa is a highly compartmentalized structure that forms a directbarrier between the host intestine and the environment, and its dysfunction couldresult in a serious disease. As T cells, which are important components of themucosal immune system, interact with gut microbiota and maintain intestinalhomeostasis, they may be involved in the process of intestinal barrier dysfunction.P2X7 receptor (P2X7R), a member of the P2X receptors family, mediates the effectsof extracellular adenosine triphosphate and is expressed by most innate or adaptiveimmune cells, including T cells. Current evidence has demonstrated thatP2X7R is involved in inflammation and mediates the survival and differentiationof T lymphocytes, indicating its potential role in the regulation of T cell function.In this review, we summarize the available research about the regulatory role andmechanism of P2X7R on the intestinal mucosa-derived T cells in the setting ofintestinal barrier dysfunction.
基金Supported by Digestive disease research center,Tehran University of Medical Sciences
文摘AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome criteria(depending on the year of diagnosis)for IBS.2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings.We assessed other functional symptoms(epigastric pain,nausea,vomiting,belching,constipation and diarrhea)in patients suffering from GERD,IBS or both.RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4±10.3 years) also hadGERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) =3.2, 95% confidence interval (CI): 2.9-3.7, P<0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR=3.6, 95% CI: 3.1-4.3, P<0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P<0.05).CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.
文摘Objective:To study the correlation of intestinal flora disturbance with immune response and inflammatory response in patients with MODS.Methods: 60 patients with MODS who were treated in our hospital between August 2013 and January 2017 were collected as the observation group, and 50 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. The differences in intestinal flora distribution in the feces samples, peripheral blood contents of T lymphocyte subsets and serum levels of immunoglobulin and inflammatory factors were compared between two groups of subjects. The relationship of intestinal flora distribution with immune response and inflammatory response was assessed by Pearson test.Results: Bifidobacterium and lactobacillus count as well as B/E value in feces of observation group were lower than those of normal control group while escherichia coli and enterococcus count were higher than those of normal control group;peripheral blood CD4+T lymphocyte proportion and CD4+/CD8+ratio were lower than those of normal control group while CD8+T lymphocyte proportion was higher than that of normal control group;serum immunoglobulin IgA, IgM and IgG levels were lower than those of normal control group;serum inflammatory factors PCT, IL-1, IL-6, IL-8 and TNF-α levels were higher than those of normal control group. Pearson test showed that the intestinal flora disturbance in patients with MODS is directly correlated with the immune response function and inflammatory response.Conclusion:There is obvious intestinal flora disturbance in patients with MODS, and it is one of the important causes of immune function injury and systemic inflammatory response in patients.
基金Tibet University Student Innovation Training Program(2020XCX023)。
文摘The external environment plays a decisive role in the changes of the intestinal microecology.The low oxygen environment of the plateau disturbs the barrier function of the intestinal mucosa,altered flora structure exacerbates intestinal mucosal barrier damage.It is possible that the mechanism of intestinal mucosal injury is the upregulation of the expression of hypoxia-inducible factor HIF-1αin the intestine under hypoxic environment,along with the sustained expression of inducible nitric oxide synthase(iNOS),which triggers intestinal mucosal injury.
文摘Since the 1918 influenza pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced the largest pandemic throughout the globe. SARS-CoV and the Middle East respiratory syndrome (MERS-CoV) are both members of the Beta CoV. The coronavirus disease of 2019 (COVID-19) has terrible implications and is currently a serious health concern throughout the world. SARS-CoV-2 affects the respiratory system first since it is the major site of entrance into the patient, but it can also damage other systems. Aside from the typical respiratory problems, several COVID-19 patients develop gastrointestinal (GI) symptoms such as weight loss, vomiting, nausea, and diarrhea. SARS-CoV-2 may infect the GI system via the angiotensin-converting enzyme 2 (ACE2) receptor, and indications of a fecal-oral transmission pathway are growing. Globally, GI disorders (GIDs) are becoming a major source of morbidity in youth. The condition has a significant financial impact on healthcare systems and hurts people's lives;nonetheless, very little is documented about the condition's worldwide prevalence and incidence. Alterations in gut sensitivity, motility, microbiota, immunological function, and central nervous system processing are all factors that contribute to GIDs. GI malfunction results in changes in changes in gut bacteria as well as an elevation in inflammatory cytokines. As a result, recognizing GI symptoms that precede COVID-19 respiratory issues may be crucial for better early identification and treatment. In GI epithelial cells of the intestinal mucosa, ACE2 and transmembrane protease serine-type 2 were also discovered to be substantially expressed. SARS-CoV-2 may also infect and multiply in both GI and liver cells in a dynamic manner. These findings suggest that SARS-CoV-2 might be a viable target for the GI tract. This review focuses on the GI complications that arise due to COVID-19 and how the CoVs give rise to GI symptoms.
基金Supported by Children’s Hospital Foundation at VCU,No.1K23HD097282(to Donowitz JR)National Institutes of Health,No.5R01AI043596(to Donowitz JR)+6 种基金Bill and Melinda Gates Foundation,No.OPP1017093VA Merit Award,No.1I01BX005730VA ShEEP Grants,No.1 IS1 BX004777-01National Institutes of Health Grant,No.2R56DK115377-05A1PIDS Summer Research Scholars AwardVCU SOM Dean’s Summer Research Fellowshipand Research Career Scientist Award from the Department of Veterans Affairs,No.IK6BX004477.
文摘BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorption,regulate metabolic pathways associated with childhood growth and inflammation,and may be affected by EED.AIM To investigate bile acid metabolism in Bangladeshi children with EED and its association with growth impairment.METHODS We conducted a cross-sectional study of 100 Bangladeshi infants(aged 6-9 months)and quantified serum and fecal bile acids using LC-MS/MS.We compared profiles to a control group of 6 American children(6-12 months)and 80 older Bangladeshi children(aged 2 years).RESULTS Bangladeshi infants had higher levels of plasma unconjugated primary(65.23%vs 44.25%,P=0.003)and sulfated primary bile acids(12.98%vs<0.001%,P=0.01),with lower primary conjugated bile acids(0.69%vs 2.74%,P≤0.001)compared to American children.Stool unconjugated primary bile acids were inversely associated with weight-for-age[regression coefficient(β)=-0.01,P=0.01]and height-for-age Z scores(β=-0.01,P=0.03).Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth(β=-1096.68,P=0.05).Fecal myeloperoxidase was associated with sulfated secondary bile acids(β=-0.40,P=0.04).Compared to 2-year-old children,the Bangladeshi infant’s serum had higher levels of unconjugated primary bile acids(65.23%vs 9.20%,P≤0.001)and lower levels of primary conjugated bile acids(0.69%vs 80.38%,P≤0.001).CONCLUSION Our data suggests an age-dependent defect in conjugation of primary bile acids in Bangladeshi children with compensatory hydrophilic shunting.Additionally,bile acid profiles are associated with intestinal overgrowth.
基金the National Natural Science Foundation of China for their grants(No.32371476,82172425,T2321005,82102611,82472515)Jiangsu Provincial Medical Key Discipline(Laboratory)project(JSDW202223)+4 种基金Gusu Health Talent Project(GSWS2021015,2021(021))Natural Science Foundation of Jiangsu Province(No.BK20210089)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_3271,KYCX22_3222)supported by the Collaborative Innovation Center of Suzhou Nano Science&Technology,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the 111 Project.
文摘The relationship between gut microbiota and host health and disease is intricate,with microbiota-derived metabolites playing a crucial role in the gut-organ axis.In this study,we observe significantly decreased levels of microbial metabolites,particularly tryptophan derivatives in osteoporosis mice.Loss of tryptophan induced intestinal epithelial barrier dysfunction which compromised intestinal barrier integrity,leading to bone inflammatory responses and pathological osteoporosis.Through supplementation of tryptophan-producing bacteria,we effectively repair damaged intestinal barriers in colitis mice and mitigate bone loss,indicating the link between chronic colitis and osteoporosis.This approach offers a promising synthetic biology-based strategy to improve osteoporosis therapy by targeting gut tryptophan.This intervention also alleviates age-related osteoporosis in an aged mouse model,providing a potential therapeutic avenue for combating osteoporosis,a disease of growing concern in aging populations.
