Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying m...Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.展开更多
BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.Howeve...BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.展开更多
Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorou...Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorouracil(5-Fu).Methods:Forty male Sprague-Dawley rats were randomly divided into control,chemotherapy,moxibustion and probiotics groups.The IM rat model was established by intraperitoneal injection of 5-Fu.Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days.Tissue morphology,serum levels of inflammatory factors and the expression levels of tight junction proteins,caspase-1,gasdermin D and NLRP3 were evaluated in colon tissue,through hematoxylin and eosin staining,electron microscopy,enzyme-linked immunosorbent assay,Western blotting,quantitative realtime reverse transcription polymerase chain reaction and immunofluorescence.Gut microbiome profiling was conducted through 16 S rRNA amplicon sequencing.Results:Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins,reduced cell apoptosis and the expression levels of caspase-1,gasdermin D and NLRP3;they also decreased the serum levels of tumor necrosis factor-α,interleukin(IL)-6,IL-1βand IL-18,while increasing serum levels of IL-10.Moxibustion and probiotic treatments also corrected the reduction inα-diversity andβ-diversity in IM rats,greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapytreated rats to levels observed in healthy animals.We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors.Finally,moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.Conclusion:Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation.Moreover,moxibustion modulates the gut microbiota,likely via decreasing the expression levels of the NLRP3 inflammasome.展开更多
BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestina...BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.展开更多
Restoring the balance of gut microbiota has emerged as a critical strategy in treating intestinal disorders,with probiotics playing a pivotal role in maintaining bacterial equilibrium.Surgical preparations,trauma,and ...Restoring the balance of gut microbiota has emerged as a critical strategy in treating intestinal disorders,with probiotics playing a pivotal role in maintaining bacterial equilibrium.Surgical preparations,trauma,and digestive tract reconstruction associated with intestinal surgeries often disrupt the intestinal flora,prompting interest in the potential role of probiotics in postoperative recovery.Lan et al conducted a prospective randomized study on 60 patients with acute appendicitis,revealing that postoperative administration of Bacillus licheniformis capsules facilitated early resolution of inflammation and restoration of gastrointestinal motility,offering a novel therapeutic avenue for accelerated postoperative recovery.This editorial delves into the effects of perioperative probiotic supplementation on physical and intestinal recovery following surgery.Within the framework of enhanced recovery after surgery,the exploration of new probiotic supplementation strategies to mitigate surgical complications and reshape gut microbiota is particularly intriguing.展开更多
The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and ...The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and intestinal infections can cause damage to the intestinal mucosal barrier and dysfunction.The aim of this study was to investigate the improvement mechanism of malvidin-3-O-galactoside(M3G)on small intestinal mucosal barrier function.C57BL/6J male mice were given dextran sodium sulfate(DSS)for 7 days to induce enteritis,and then were fed normally with or without M3G supplementation for another 7 days.The results showed that M3G supplementation significantly improved the disease activity index(DAI)score and small intestinal tissue injury in mice with DSS induced enteritis.M3G ameliorated the small intestinal mucosal mechanical barrier function by modulating the expression of mucin 2(MUC2),zona occludens 1(ZO-1),Occludin,Claudin-1,intestinal fatty acid binding protein(iFABP),and trefoil factor 3(TFF3)in the small intestine mucosa,and the serum levels of D-lactic acid(D-LA),lipopolysaccharide(LPS),and diamine oxidase(DAO)were significantly decreased.Additionally,M3G also relieved the small intestinal immunologic barrier of mice by decreasing the immune protein levels of immunoglobulin A(IgA),immunoglobulin M(IgM),and immunoglobulin G(IgG)in serum,and secretory immunoglobulin A(SIgA)level in small intestine tissue.Furthermore,M3G inhibited the expression of Notch pathway-related proteins such as Notch1,Notch intracellular domain(NICD),delta-like ligand 4(DLL4),delta-like ligand 1(DLL1),and hairy/enhancer of split 1(Hes1).In conclusion,the results demonstrated that M3G can improve intestinal mucosal barrier function by inhibiting Notch pathway.展开更多
BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in se...BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in sepsis.Moreover,no consensus on goal enteral caloric intake has been reached in sepsis.AIM To investigate the effects of different goal caloric requirements of enteral nutrition on the gastrointestinal function and outcomes in the acute phase of sepsis.METHODS Patients were randomly assigned to receive 30%(defined as group A),60%(group B),or 100%(group C)of goal caloric requirements of enteral nutrition in this prospective pilot clinical trial.The acute gastrointestinal injury(AGI)grades,incidence of feeding intolerance(FI),daily caloric intake,nutritional and inflammatory markers,and biomarkers of mucosal barrier function were collected during the first 7 d of enteral feeding.The clinical severity and outcome variables were also recorded.RESULTS A total of 54 septic patients were enrolled.The days to goal calorie of group C(2.55±0.82)were significantly longer than those of group A(3.50±1.51;P=0.046)or B(4.85±1.68;P<0.001).The FI incidence of group C(16.5%)was higher than that of group A(5.0%)or B(8.7%)(P=0.009).No difference in the incidence of FI symptoms was found between groups A and B.The serum levels of barrier function biomarkers of group B were significantly lower than those of group A(P<0.05)on the 7th day of feeding.The prealbumin and IL-6 levels of group A were lower than those of group B(P<0.05)on the 7th day of feeding.No significant differences in the clinical outcome variables or 28-d mortality were found among the three groups.CONCLUSION Early moderate enteral underfeeding(60%of goal requirements)could improve the intestinal barrier function and nutritional and inflammatory status without increasing the incidence of FI symptoms in sepsis.However,further large-scale prospective clinical trials and animal studies are required to test our findings.Moreover,the effects of different protein intake on gastrointestinal function and outcomes should also be investigated in future work.展开更多
BACKGROUND： The gut is capable of inducing multiple organ dysfunction syndrome （MODS）. In the diagnosis and treatment of critical ill patients, doctors should pay particular attention to the protection or recovery ...BACKGROUND： The gut is capable of inducing multiple organ dysfunction syndrome （MODS）. In the diagnosis and treatment of critical ill patients, doctors should pay particular attention to the protection or recovery of intestinal barrier function. However, no reliable diagnostic criteria are available clinically. This study aimed to assess the changes of intestinal mucosal barrier function in surgically critical ill patients as well as their signi？ cance.METHODS： Thirty-eight surgically critical ill patients were enrolled as a study group （APACHE II〉8 scores）, and 15 non-critical ill patients without intestinal dysfunction were selected as a control group （APACHE II〈6）. General information, symptoms, physical signs, and APACHE II scores of the patients were recorded. The patients in the study group were subdivided into an intestinal dysfunction group （n=26） and a non-intestinal dysfunction group （n=12）. Three ml venous blood was collected from the control group on admission and the same volume of plasma was collected from the study group both on admission and in the period of recovery. The plasma concentrations of endotoxin, diamine oxidase （DAO）, D-lactate, and intestinal fatty-acid binding protein （iFABP） were detected respectively. The data collected were analyzed by the SPSS 17.0 software for Windows. RESULTS： The levels of variables were significantly higher in the study group than in the control group （P〈0.01）. They were higher in the intestinal dysfunction group than in the non-intestinal dysfunction group （DAO P〈0.05, endotoxin, D-lactate, iFABP P〈0.01）. In the non-intestinal dysfunction group compared with the control group, the level of endotoxin was not significant （P〉0.05）, but the levels of DAO, D-lactate and iFABP were statistically significant （P〈0.05）. The levels of variables in acute stage were higher than those in recovery stage （P〈0.01）.The death group showed higher levels of variables than the survival group （endotoxin and D-lactate P〈0.01, DAO and iFABP P〈0.05）.CONCLUSION： The plasma concentrations of endotoxin, DAO, D-lactate, and intestinal fatty-acid binding protein （iFABP） could re？ ect a better function of the intestinal mucosa barrier in surgically critical ill patients.展开更多
Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are inter...Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.展开更多
AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobari...AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.展开更多
BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfun...BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.展开更多
AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS...AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.展开更多
AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatit...AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP). METHODS:A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups:normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining. RESULTS:Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.CONCLUSION:Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.展开更多
AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A contr...AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.展开更多
AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.
BACKGROUND:Severe acute pancreatitis(SAP)can result in intestinal mucosal injury.This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP.M...BACKGROUND:Severe acute pancreatitis(SAP)can result in intestinal mucosal injury.This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP.METHODS:Liposomes containing clodronate or phosphate buffered saline(PBS)were prepared by the thin-film method SAP models were prepared by a uniform injection of sodium taurocholate(2 mL/kg body weight)into the subcapsular space of the pancreas.Sprague-Dawley rats were randomly divided into a control group(C group),a SAP plus PBS-containing liposomes group(P group)and a SAP plus clodronate-containing liposomes group(T group).At 2 and 6 hours after the establishment of SAP models,2 mL blood samples were taken from the superior mesenteric vein to measure the contents of serum TNF-αand IL-12.Pathological changes in the intestine and pancreas were observed using hematoxylin and eosin staining,while apoptosis was detected using TUNEL staining.In addition,the macrophage markers cluster of differentiation 68(CD68)in the intestinal tissue was assessed with immunohistochemistry.RESULTS:At the two time points,the levels of TNF-αand IL-12 in the P group were higher than those in the C group(P<0.05)Compared with the P group,the levels of TNF-αand IL-12 decreased in the T group(P<0.05).The pathological scores of the intestinal mucosa and pancreas in the T group were lower than those of the P group.In the T group,large numbers of TUNEL-positive cells were observed,but none or few in the C and P groups.The number of CD68-positive macrophages decreased in the T group.CONCLUSIONS:Clodronate-containing liposomes have prote-ctive effects against intestinal mucosal injury in rats with SAP.The blockade of macrophages may provide a novel therapeutic strategy in SAP.展开更多
Objective:This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn’s disease(CD)regulated by moxibustion through bile acid(BA)enterohepatic circulation and intestinal f...Objective:This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn’s disease(CD)regulated by moxibustion through bile acid(BA)enterohepatic circulation and intestinal farnesoid X receptor(FXR).Methods:Sprague-Dawley rats were randomly divided into control group,CD model group,mild moxibustion group and herb-partitioned moxibustion group.CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu(ST25)and Qihai(CV6).The changes in CD symptoms were rated according to the disease activity index score,the serum and colon tissues of rats were collected,and the pathological changes in colon tissues were observed via histopathology.Western blot,immunohistochemistry(IHC)and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.Results:Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD,inhibited inflammation and repaired mucosal damage to the colon in CD rats.Meanwhile,moxibustion could improve the abnormal expression of BA in the colon,liver and serum,downregulate the expression of interferon-γand upregulate the expression of FXR mRNA,and inhibit Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)mRNA.The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression.Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR.Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65.In particular,herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.Conclusion:Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA,activating colonic FXR,regulating the TLR4/MyD88 pathway,inhibiting intestinal inflammation and repairing the intestinal mucosal barrier.Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation.Please cite this article as:Shen JC,Qi Q,Han D,Lu Y,Huang R,Zhu Y,Zhang LS,Qin XD,Zhang F,Wu HG,Liu HR.Moxibustion improves experimental colitis in rats with Crohn’s disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor.J Integr Med.2023;21(2):194–204.展开更多
Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemen...Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemented AC on Salmonella-infected chickens.Methods A total of 240 hatchling chickens were randomly allocated to 4 treatments,each with 6 replicates.Birds were fed a basal diet supplemented with 0(CON,and ST),100(ACL)and 400(ACH)mg/kg of AC for d 60,and orally challenged with PBS(CON)or 10^(9) CFU/bird(ST,ACL,ACH)Salmonella Typhimurium at d 14 and 16.Results(1)Compared with birds in ST,AC supplementation increased the body weight(BW)at d 18 and the average daily gain(ADG)from d 1 to 18 of the Salmonella-infected chickens(P<0.05);(2)AC decreased the number of Salmonella cells in the liver and spleen,the contents of NO in plasma and inflammatory cytokines in ileal mucosa of Salmonella-infected chickens(P<0.05);(3)Salmonella infection decreased the ileal villi height,villi height to crypt depth(V/C),and the expression of zonulaoccludins-1(ZO-1),claudin-1,occludin,and mucin 2(MUC2)in ileal mucosa.AC supplementation relieved these adverse effects,and decreased ileal crypt depth(P<0.05);(4)In cecal microbiota of Salmonella-infected chickens,AC increased(P<0.05)the alpha-diversity(Chao1,Pd,Shannon and Sobs indexes)and the relative abundance of Firmicutes,and decreased(P<0.05)the relative abundance of Proteobacteria and Bacteroidota and the enrichment of drug antimicrobial resistance,infectious bacterial disease,and immune disease pathways.Conclusions Dietary AC protected chicken against Salmonella infection via inhibiting the Salmonella colonization in liver and spleen,suppressing secretion of inflammatory cytokines,up-regulating the expression of ileal barrier-related genes,and ameliorating the composition and function of cecal microbes.Under conditions here used,100 mg/kg bilberry anthocyanin was recommended.展开更多
Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade ma...Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.展开更多
BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factor...BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.展开更多
文摘Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2021B1515140043,No.2022A1515140124 and No.2023A1515140115.
文摘BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
基金supported by the National Natural Science Foundation of China(No.82030118,82074232,81830120,81774095and 8170388)the Project of Shanghai Science and Technology Committee(No.19401972200)Shanghai Training Project for Leading Talents of Traditional Chinese Medicine(No.ZY[2018-2020]-RCPY-1024)。
文摘Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorouracil(5-Fu).Methods:Forty male Sprague-Dawley rats were randomly divided into control,chemotherapy,moxibustion and probiotics groups.The IM rat model was established by intraperitoneal injection of 5-Fu.Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days.Tissue morphology,serum levels of inflammatory factors and the expression levels of tight junction proteins,caspase-1,gasdermin D and NLRP3 were evaluated in colon tissue,through hematoxylin and eosin staining,electron microscopy,enzyme-linked immunosorbent assay,Western blotting,quantitative realtime reverse transcription polymerase chain reaction and immunofluorescence.Gut microbiome profiling was conducted through 16 S rRNA amplicon sequencing.Results:Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins,reduced cell apoptosis and the expression levels of caspase-1,gasdermin D and NLRP3;they also decreased the serum levels of tumor necrosis factor-α,interleukin(IL)-6,IL-1βand IL-18,while increasing serum levels of IL-10.Moxibustion and probiotic treatments also corrected the reduction inα-diversity andβ-diversity in IM rats,greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapytreated rats to levels observed in healthy animals.We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors.Finally,moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.Conclusion:Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation.Moreover,moxibustion modulates the gut microbiota,likely via decreasing the expression levels of the NLRP3 inflammasome.
基金Supported by the National Natural Science Foundation of China,No.81673795.
文摘BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.
文摘Restoring the balance of gut microbiota has emerged as a critical strategy in treating intestinal disorders,with probiotics playing a pivotal role in maintaining bacterial equilibrium.Surgical preparations,trauma,and digestive tract reconstruction associated with intestinal surgeries often disrupt the intestinal flora,prompting interest in the potential role of probiotics in postoperative recovery.Lan et al conducted a prospective randomized study on 60 patients with acute appendicitis,revealing that postoperative administration of Bacillus licheniformis capsules facilitated early resolution of inflammation and restoration of gastrointestinal motility,offering a novel therapeutic avenue for accelerated postoperative recovery.This editorial delves into the effects of perioperative probiotic supplementation on physical and intestinal recovery following surgery.Within the framework of enhanced recovery after surgery,the exploration of new probiotic supplementation strategies to mitigate surgical complications and reshape gut microbiota is particularly intriguing.
基金Liaoning Provincial Department of Education Project-General Project(LJKMZ20221060)National Key R&D Program of China(2022YFD1600505).
文摘The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and intestinal infections can cause damage to the intestinal mucosal barrier and dysfunction.The aim of this study was to investigate the improvement mechanism of malvidin-3-O-galactoside(M3G)on small intestinal mucosal barrier function.C57BL/6J male mice were given dextran sodium sulfate(DSS)for 7 days to induce enteritis,and then were fed normally with or without M3G supplementation for another 7 days.The results showed that M3G supplementation significantly improved the disease activity index(DAI)score and small intestinal tissue injury in mice with DSS induced enteritis.M3G ameliorated the small intestinal mucosal mechanical barrier function by modulating the expression of mucin 2(MUC2),zona occludens 1(ZO-1),Occludin,Claudin-1,intestinal fatty acid binding protein(iFABP),and trefoil factor 3(TFF3)in the small intestine mucosa,and the serum levels of D-lactic acid(D-LA),lipopolysaccharide(LPS),and diamine oxidase(DAO)were significantly decreased.Additionally,M3G also relieved the small intestinal immunologic barrier of mice by decreasing the immune protein levels of immunoglobulin A(IgA),immunoglobulin M(IgM),and immunoglobulin G(IgG)in serum,and secretory immunoglobulin A(SIgA)level in small intestine tissue.Furthermore,M3G inhibited the expression of Notch pathway-related proteins such as Notch1,Notch intracellular domain(NICD),delta-like ligand 4(DLL4),delta-like ligand 1(DLL1),and hairy/enhancer of split 1(Hes1).In conclusion,the results demonstrated that M3G can improve intestinal mucosal barrier function by inhibiting Notch pathway.
基金Supported by National Natural Science Foundation of China,No.81701881Nanjing Medical Science and Technology Development Foundation,No.YKK17102.
文摘BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in sepsis.Moreover,no consensus on goal enteral caloric intake has been reached in sepsis.AIM To investigate the effects of different goal caloric requirements of enteral nutrition on the gastrointestinal function and outcomes in the acute phase of sepsis.METHODS Patients were randomly assigned to receive 30%(defined as group A),60%(group B),or 100%(group C)of goal caloric requirements of enteral nutrition in this prospective pilot clinical trial.The acute gastrointestinal injury(AGI)grades,incidence of feeding intolerance(FI),daily caloric intake,nutritional and inflammatory markers,and biomarkers of mucosal barrier function were collected during the first 7 d of enteral feeding.The clinical severity and outcome variables were also recorded.RESULTS A total of 54 septic patients were enrolled.The days to goal calorie of group C(2.55±0.82)were significantly longer than those of group A(3.50±1.51;P=0.046)or B(4.85±1.68;P<0.001).The FI incidence of group C(16.5%)was higher than that of group A(5.0%)or B(8.7%)(P=0.009).No difference in the incidence of FI symptoms was found between groups A and B.The serum levels of barrier function biomarkers of group B were significantly lower than those of group A(P<0.05)on the 7th day of feeding.The prealbumin and IL-6 levels of group A were lower than those of group B(P<0.05)on the 7th day of feeding.No significant differences in the clinical outcome variables or 28-d mortality were found among the three groups.CONCLUSION Early moderate enteral underfeeding(60%of goal requirements)could improve the intestinal barrier function and nutritional and inflammatory status without increasing the incidence of FI symptoms in sepsis.However,further large-scale prospective clinical trials and animal studies are required to test our findings.Moreover,the effects of different protein intake on gastrointestinal function and outcomes should also be investigated in future work.
文摘BACKGROUND： The gut is capable of inducing multiple organ dysfunction syndrome （MODS）. In the diagnosis and treatment of critical ill patients, doctors should pay particular attention to the protection or recovery of intestinal barrier function. However, no reliable diagnostic criteria are available clinically. This study aimed to assess the changes of intestinal mucosal barrier function in surgically critical ill patients as well as their signi？ cance.METHODS： Thirty-eight surgically critical ill patients were enrolled as a study group （APACHE II〉8 scores）, and 15 non-critical ill patients without intestinal dysfunction were selected as a control group （APACHE II〈6）. General information, symptoms, physical signs, and APACHE II scores of the patients were recorded. The patients in the study group were subdivided into an intestinal dysfunction group （n=26） and a non-intestinal dysfunction group （n=12）. Three ml venous blood was collected from the control group on admission and the same volume of plasma was collected from the study group both on admission and in the period of recovery. The plasma concentrations of endotoxin, diamine oxidase （DAO）, D-lactate, and intestinal fatty-acid binding protein （iFABP） were detected respectively. The data collected were analyzed by the SPSS 17.0 software for Windows. RESULTS： The levels of variables were significantly higher in the study group than in the control group （P〈0.01）. They were higher in the intestinal dysfunction group than in the non-intestinal dysfunction group （DAO P〈0.05, endotoxin, D-lactate, iFABP P〈0.01）. In the non-intestinal dysfunction group compared with the control group, the level of endotoxin was not significant （P〉0.05）, but the levels of DAO, D-lactate and iFABP were statistically significant （P〈0.05）. The levels of variables in acute stage were higher than those in recovery stage （P〈0.01）.The death group showed higher levels of variables than the survival group （endotoxin and D-lactate P〈0.01, DAO and iFABP P〈0.05）.CONCLUSION： The plasma concentrations of endotoxin, DAO, D-lactate, and intestinal fatty-acid binding protein （iFABP） could re？ ect a better function of the intestinal mucosa barrier in surgically critical ill patients.
基金supported by the National Natural Science Foundation of China(grant no.81774449).
文摘Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.
基金Supported by Scientific and Technical Research Funds from Chinese PLA during the Eleventh Five-Year Plan Period,No. 2008G093National Natural Science Foundation of China,No. 30900715National Science and Technology Ministry,No. 2009BAI85B03
文摘AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.
基金Supported by the National Natural Science Foundation of China,No.81600414Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2018255969Zhejiang TCM Science and Technology Project,No.2016ZA123 and No.2018ZA013.
文摘BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.
基金Supported by Zhenjiang Science and Technology Committee, No. SH2002015
文摘AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.
基金Zhenjiang Science and Technology Committee, No. SH2005044
文摘AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP). METHODS:A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups:normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining. RESULTS:Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.CONCLUSION:Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.
文摘AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.
基金Supported by The Natural Science Foundation of China,No.81270528the Natural Science Foundation of Tianjin,China,No.08JCYBJC08400,No.11JCZDJC27800 and No.12JCZDJC25200the Technology Foundation of Health Bureau of Tianjin,China,No.2011KY11
文摘AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.
基金supported by grants from the National Natural Science Foundation of China(81070287 and 30772117)the Graduate Research and Innovation Program of Jiangsu University(CX10B_010X)
文摘BACKGROUND:Severe acute pancreatitis(SAP)can result in intestinal mucosal injury.This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP.METHODS:Liposomes containing clodronate or phosphate buffered saline(PBS)were prepared by the thin-film method SAP models were prepared by a uniform injection of sodium taurocholate(2 mL/kg body weight)into the subcapsular space of the pancreas.Sprague-Dawley rats were randomly divided into a control group(C group),a SAP plus PBS-containing liposomes group(P group)and a SAP plus clodronate-containing liposomes group(T group).At 2 and 6 hours after the establishment of SAP models,2 mL blood samples were taken from the superior mesenteric vein to measure the contents of serum TNF-αand IL-12.Pathological changes in the intestine and pancreas were observed using hematoxylin and eosin staining,while apoptosis was detected using TUNEL staining.In addition,the macrophage markers cluster of differentiation 68(CD68)in the intestinal tissue was assessed with immunohistochemistry.RESULTS:At the two time points,the levels of TNF-αand IL-12 in the P group were higher than those in the C group(P<0.05)Compared with the P group,the levels of TNF-αand IL-12 decreased in the T group(P<0.05).The pathological scores of the intestinal mucosa and pancreas in the T group were lower than those of the P group.In the T group,large numbers of TUNEL-positive cells were observed,but none or few in the C and P groups.The number of CD68-positive macrophages decreased in the T group.CONCLUSIONS:Clodronate-containing liposomes have prote-ctive effects against intestinal mucosal injury in rats with SAP.The blockade of macrophages may provide a novel therapeutic strategy in SAP.
基金supported by the National Natural Sciences Foundation of China(No.81873374 and 81904303)the Health Industry Clinical Research Project of Shanghai Municipal Health Commission(No.20214Y0114)the Science and Technology Commission of Shanghai(No.21ZR1460000)。
文摘Objective:This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn’s disease(CD)regulated by moxibustion through bile acid(BA)enterohepatic circulation and intestinal farnesoid X receptor(FXR).Methods:Sprague-Dawley rats were randomly divided into control group,CD model group,mild moxibustion group and herb-partitioned moxibustion group.CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu(ST25)and Qihai(CV6).The changes in CD symptoms were rated according to the disease activity index score,the serum and colon tissues of rats were collected,and the pathological changes in colon tissues were observed via histopathology.Western blot,immunohistochemistry(IHC)and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.Results:Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD,inhibited inflammation and repaired mucosal damage to the colon in CD rats.Meanwhile,moxibustion could improve the abnormal expression of BA in the colon,liver and serum,downregulate the expression of interferon-γand upregulate the expression of FXR mRNA,and inhibit Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)mRNA.The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression.Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR.Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65.In particular,herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.Conclusion:Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA,activating colonic FXR,regulating the TLR4/MyD88 pathway,inhibiting intestinal inflammation and repairing the intestinal mucosal barrier.Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation.Please cite this article as:Shen JC,Qi Q,Han D,Lu Y,Huang R,Zhu Y,Zhang LS,Qin XD,Zhang F,Wu HG,Liu HR.Moxibustion improves experimental colitis in rats with Crohn’s disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor.J Integr Med.2023;21(2):194–204.
基金financially supported by Natural Science Foundation from Guangdong Province (2021A1515010830,2021A1515012412)National Key R&D Project (2018YFD0500600,2021YFD300404)+3 种基金China Agriculture Research System of MOF and MARA (CARS-41)the Key Realm R&D Program of Guangdong Province (2020B0202090004)National Natural Science Foundation of China (31802104)the Science and Technology Program of Guangdong Academy of Agricultural Sciences (202106TD,R2019PY-QF008),P.R.China。
文摘Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemented AC on Salmonella-infected chickens.Methods A total of 240 hatchling chickens were randomly allocated to 4 treatments,each with 6 replicates.Birds were fed a basal diet supplemented with 0(CON,and ST),100(ACL)and 400(ACH)mg/kg of AC for d 60,and orally challenged with PBS(CON)or 10^(9) CFU/bird(ST,ACL,ACH)Salmonella Typhimurium at d 14 and 16.Results(1)Compared with birds in ST,AC supplementation increased the body weight(BW)at d 18 and the average daily gain(ADG)from d 1 to 18 of the Salmonella-infected chickens(P<0.05);(2)AC decreased the number of Salmonella cells in the liver and spleen,the contents of NO in plasma and inflammatory cytokines in ileal mucosa of Salmonella-infected chickens(P<0.05);(3)Salmonella infection decreased the ileal villi height,villi height to crypt depth(V/C),and the expression of zonulaoccludins-1(ZO-1),claudin-1,occludin,and mucin 2(MUC2)in ileal mucosa.AC supplementation relieved these adverse effects,and decreased ileal crypt depth(P<0.05);(4)In cecal microbiota of Salmonella-infected chickens,AC increased(P<0.05)the alpha-diversity(Chao1,Pd,Shannon and Sobs indexes)and the relative abundance of Firmicutes,and decreased(P<0.05)the relative abundance of Proteobacteria and Bacteroidota and the enrichment of drug antimicrobial resistance,infectious bacterial disease,and immune disease pathways.Conclusions Dietary AC protected chicken against Salmonella infection via inhibiting the Salmonella colonization in liver and spleen,suppressing secretion of inflammatory cytokines,up-regulating the expression of ileal barrier-related genes,and ameliorating the composition and function of cecal microbes.Under conditions here used,100 mg/kg bilberry anthocyanin was recommended.
基金This work was supported by Chinese Natural Science Foundation Grants(81630080)the Fundamental Research Funds for the Central Universities of China(NO:2017-JYB-JS-101,2018-JYBZZ-JS075,2019-JYB-JSPYGD-011).
文摘Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.
基金Supported by National Natural Science Foundation of China,No.81501539the Natural Science Foundation of Guangdong Province,China,No.2016A030312008+2 种基金Science and Technology Planning Project of Shantou,China,No.200617105260368Medical Scientific Research Foundation of Guangdong,China,No.A2020627“Dengfeng Project”for the Construction of High-level Hospital in Guangdong Province-The First Affiliated Hospital of Shantou University College Supporting Funding,No.202003-10.
文摘BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.
