Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-caten...A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing cli...Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.展开更多
Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbio-sis.However,it has been challenging to clarify which specific intestinal microbiota and their metabolites ...Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbio-sis.However,it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets.Results In this study,we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score,and elevated levels of lipopolysaccharide(LPS)and D-lactate(D-LA)compared to healthy piglets.Subsequently,we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets.Diarrheal piglets demonstrated intestinal microbiota dysbiosis,characterized pri-marily by a higher Firmicutes to Bacteroidota ratio,a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri,and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron.Functional pro-filing of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes(KEGG)data was performed,and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diar-rhea.Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets.Furthermore,we explored the effects of dietary indole-3-aldehyde(IAld),a key tryptophan metabolite,on intestinal development and gut barrier function in weaned piglets.Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell(ISC)expansion in piglets.The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids.Conclusions These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intesti-nal development by promoting ISC expansion in weaned piglets.展开更多
The role of small bowel capsule endoscopy (CE) in suspected small bowel bleedingis well established and current European and other international guidelinesposition it as the first line test after negative bidirectiona...The role of small bowel capsule endoscopy (CE) in suspected small bowel bleedingis well established and current European and other international guidelinesposition it as the first line test after negative bidirectional endoscopies. Insuspected mid-lower gastrointestinal bleeding (MLGIB) the diagnostic yield ofcolonoscopy is poor and may cause a delay in detecting small bowel disease. Acrucial aspect of small bowel capsule endoscope performance is the timing of theprocedure, the interval between the bleeding episode and capsule ingestion isinversely related to the diagnostic yield as confirmed by a recent meta-analysis.Currently the ongoing advances achieved by video CE in particular to evaluateboth small bowel and colon in a single test using double headed capsules, raisesquestions regarding the position of pan intestinal capsule in the current algorithmto investigate patients presenting with suspected MLGIB ahead of colonoscopy.Early evidence suggests pan intestinal capsule could fit well as a diagnostic“filter” test in this cohort of patients, thereby reserving invasive conventionalcolonoscopy or device assisted enteroscopy as therapeutics options only. The recentdevelopment of magnetically controlled CE and a blood sensing capsule pushthe boundaries of CE even further in patients presenting with suspected gastrointestinalbleeding. This review will discuss the current available evidence andfuture directions of CE in suspected MLGIB.展开更多
2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-...2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.展开更多
BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are ra...BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are rarely subjected to investig-ations for SIBO.AIM To estimate the frequency of SIBO in children having functional upper GI sym-ptoms(as cases)and to compare the result of the SIBO status to that of the con-trols.METHODS Children aged 6 to 18 who presented with upper GI symptoms were selected for the study.All children were subjected to upper GI endoscopy before being advised of any proton pump inhibitors(PPIs).Children with normal endoscopy were assigned as cases,and children having any endoscopic lesion were design-ated as controls.Both groups were subjected to a glucose-hydrogen breath test by Bedfont Gastrolyser.RESULTS A total of 129 consecutive children who were naive to PPIs and had normal ba-seline investigations were included in the study.Among them,67 patients had endoscopic lesions and served as the control group,with six cases being excluded due to the presence of Helicobacter pylori in gastric biopsies.Sixty-two children with normal endoscopy results formed the case group.In the case group,35 children(59%)tested positive for hydrogen breath tests,compared to 13 children(21%)in the control group.The calculated odds ratio was 5.38(95%confidence interval:2.41-12.0),which was statistically significant.Further analysis of symptoms revealed that nausea,halitosis,foul-smelling eructation,and epigastric fullness were positive predictors of SIBO.CONCLUSION It is worthwhile to investigate and treat SIBO in all children presenting with upper GI symptoms that are not explained by endoscopy findings.展开更多
BACKGROUND Post-pancreaticoduodenectomy(PD)intestinal failure(IF)is rare and associated with poor outcomes.To our knowledge,the role of intestinal transplantation(ITx)as a rescue treatment for this complication has ne...BACKGROUND Post-pancreaticoduodenectomy(PD)intestinal failure(IF)is rare and associated with poor outcomes.To our knowledge,the role of intestinal transplantation(ITx)as a rescue treatment for this complication has never been reported.CASE SUMMARY A 42-year-old female with a benign neurilemmoma of the duodenum underwent PD.Her superior mesenteric vein(SMV)was injured during surgery and required reconstruction.She experienced SMV thrombosis and bowel gangrene requiring massive bowel resection.Consequently,she developed short gut syndrome and an enterocutaneous fistula,leading to prolonged hospitalization for wound care and total parenteral nutrition(TPN)support.She was referred to our hospital for ITx evaluation.Upon arrival,she had cholestasis due to IF-associated liver disease.After gastrointestinal(GI)reconstruction to restore GI continuity,she was eligible for multi-visceral transplantation(MVTx).The anticipated allograft included the stomach,small intestine,liver,pancreas,and duodenum.She found a suitable donor after two years of waiting.The MVTx procedure was straightforward with signs of immediate function.Enteral feeding was initiated on postoperative day(POD)7.TPN weaning was achieved on POD 28,and the patient was discharged on POD 69.Two years post-MVTx,she is healthy with excellent graft function.To our knowledge,this is the first case report on MVTx as the treatment for fatal post-PD complications and also the first reported case of ITx in Southeast Asia.CONCLUSION Post-PD IF is rare and lethal.Intestinal and MVTx might be a rescue treatment for IF after GI surgery in eligible patients.展开更多
BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing int...BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.展开更多
Utilizing transporter-mediated drug delivery to achieve effective oral absorption emerges as a promising strategy.Researchers have been concentrated on discovering solutions to the issues of low solubility and poor pe...Utilizing transporter-mediated drug delivery to achieve effective oral absorption emerges as a promising strategy.Researchers have been concentrated on discovering solutions to the issues of low solubility and poor permeability of insoluble drugs,whereas,current reports have revealed that drug transporter proteins are abundantly expressed in the mucosa of intestinal epithelial cells,and that their mediated drug absorption effectively improved the bioavailability of orally administered drugs.There are two main categories based on the transporter mechanism,which include the family of ATP-binding cassette(ABC)transporters with efflux effects that reduce drug bioavailability and the family of solute carriers(SLC)transporters with uptake effects that promote drug absorption,respectively.Thus,we review studies of intestinal transporter-mediated delivery of drugs to enhance oral absorption,including the types of intestinal transporters,distribution characteristics,and strategies for enhancing oral absorption using transporter-mediated drug delivery systems are summarized,with the aim of providing important theoretical references for the development of intestinal-targeted delivery system.展开更多
BACKGROUND Recently,intestinal stenting combined with laparoscopic surgery has received increasing attention as a treatment option for acute intestinal obstruction.However,its safety and efficacy have not yet been est...BACKGROUND Recently,intestinal stenting combined with laparoscopic surgery has received increasing attention as a treatment option for acute intestinal obstruction.However,its safety and efficacy have not yet been established.AIM To assess the efficacy and safety of combining intestinal stenting with laparoscopic surgery for the management of acute intestinal obstruction.METHODS Clinical data from 74 patients with colorectal cancer and acute intestinal obstruction,who were admitted to the emergency department of the authors’hospital between October 2023 and November 2024,were collected and analyzed.Patients were divided into two groups based on the surgical intervention:A control group(emergency open surgery,n=37)and a study group(intestinal stent implantation combined with laparoscopic surgery,n=37).Observation indicators included stent placement rate,obstruction relief rate,and stent-related complications.RESULTS Intestinal stent placement was 100%successful in the study group,all of whom experienced relief from obstruction while exhibiting a significantly lower rate of ostomy creation and a higher rate of primary anastomosis than in the control group,as well as less intraoperative blood loss,shorter time to flatus,and shorter hospital stay.The complication rate was 5.41%(2/37;bleeding and re-obstruction),with no statistically significant difference between the two groups in terms of operative duration or perioperative mortality.The overall complication rates were 5.41%(2/37)and 21.62%(8/37)in the intervention and control groups,respectively.Tumor recurrence and overall survival rates were 2.70%and 97.30%in the study group and 13.51%and 91.89%in the control group,respectively.CONCLUSION Intestinal stenting relieved acute obstructions,reduced the number of emergency surgeries,and supported laparoscopic procedures while improving primary anastomosis rates,minimizing ostomy occurrence,surgical trauma,and complications,and accelerating recovery.展开更多
Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary e...Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.展开更多
The intestinal barrier is crucial for homeostasis.This study aimed to investigate the protective effects of earthworm protein hydrolysates(EWPH)on the intestinal mucosal barrier and elucidate the underlying mechanisms...The intestinal barrier is crucial for homeostasis.This study aimed to investigate the protective effects of earthworm protein hydrolysates(EWPH)on the intestinal mucosal barrier and elucidate the underlying mechanisms.We first hydrolyzed earthworm protein using alcalase and identified the primary peptide components of EWPH through Nano LC-MS/MS analysis.Network pharmacology and bioinformatics approaches were employed to predict potential targets associated with the intestinal mucosal barrier.Experimentally,we demonstrated that EWPH effectively protects against dextran sulfate sodium(DSS)-induced intestinal barrier damage in mice.The protective mechanisms involve not only the inhibition of the Toll-like receptor 4(TLR4)-nuclear factor-kB(NF-kB)/mitogen-activated protein kinases(MAPK)signaling pathway in the intestinal epithelium but also the suppression of other key molecules implicated in intestinal mucosal barrier damage,including phosphorylated-SRC proto-oncogene(p-SRC),phosphorylated-signal transducer and activator of transcription 3(p-STAT3),Caspase-3,and matrix metalloproteinase-9(MMP9),thereby mitigating intestinal inflammation and mucosal barrier injury.This study provides evidence that EWPH have the potential to safeguard the intestinal barrier hemostasis.展开更多
BACKGROUND Colonoscopy quality relies heavily on adequate bowel preparation,yet traditional methods often result in suboptimal compliance.Emerging network-based monitoring systems offer promise for improving both prep...BACKGROUND Colonoscopy quality relies heavily on adequate bowel preparation,yet traditional methods often result in suboptimal compliance.Emerging network-based monitoring systems offer promise for improving both preparation quality and patient cooperation,potentially enhancing clinical outcomes.AIM To evaluate the effectiveness of an intestinal network monitoring system in enhancing the quality of bowel preparation for colonoscopy and its impact on patient psychological and physiological responses,compliance,and adverse event rates.METHODS Between July 2019 and July 2020,800 enteroscopy patients who met the inclusion criteria in the outpatient clinic of the gastroenterology department of our hospital were randomly divided into 400 cases each in the experimental group(network monitoring group)and the control group(verbal+written preaching group),and the psychological and physiological stress response situation,colon Boston Bowel Preparation Scale,enteroscopy to blindness,arrival time to blindness,and polyp detection rate of the patients were compared before and after the intervention,compliance and adverse reactions were compared.RESULTS There was no difference in anxiety and depression scores,heart rate and systolic blood pressure between the groups before the intervention(P>0.05),and after the intervention,the patients’anxiety and depression scores were lower and lower in the study group(P<0.05);heart rate and systolic blood pressure were elevated,but lower in the test group(P<0.05).The left hemicolon,right hemicolon,transverse colon and total Boston Bowel Preparation Scale scores were lower in the test group than in the control group(P<0.05),the colonoscopy arrival rate and polyp detection rate were higher than those in the control group,and the time to arrival and time to exit the scope were shorter than those in the control group(P<0.05),and the dietary preparations,the preparations for taking medications and the total adherence scores were higher than those in the control group(P<0.05).The incidence of adverse reactions in the experimental group was 11.00%,which was lower than that in the control group(P<0.05).CONCLUSION The Bowel Network Monitoring System has potential clinical promotion value in improving the quality of colonoscopic bowel preparation,which can effectively alleviate patient anxiety and depression,improve the quality of colonoscopic bowel preparation and patient compliance,and has a high degree of safety.展开更多
Inflammatory bowel disease(IBD),a chronic disorder characterized by intestinal inflammation and mucosal damage,includes mainly Crohn’s disease and ulcerative colitis.However,the cause of its onset remains unclear.The...Inflammatory bowel disease(IBD),a chronic disorder characterized by intestinal inflammation and mucosal damage,includes mainly Crohn’s disease and ulcerative colitis.However,the cause of its onset remains unclear.The pathogenesis of IBD is closely related to host genetic susceptibility,disorders of the intestinal flora,damage to the intestinal mucosal barrier,and abnormal intestinal mucosal immunity.On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD,the influence of genetics on the intestinal barrier and intestinal microbiota;the metagenomics,metatranscriptomics,and metabolomics of the intestinal microbiota involved in IBD;and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.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
Diet and nutrition significantly influence health, largely by regulating intestinalnutrient absorption. The intestinal epithelium, as the primary site for nutrientuptake, undergoes continuous renewal driven by precise...Diet and nutrition significantly influence health, largely by regulating intestinalnutrient absorption. The intestinal epithelium, as the primary site for nutrientuptake, undergoes continuous renewal driven by precise regulation of intestinalstem cells (ISCs). Nutrient sensing and metabolism are key determinants of ISCfate, making ISCs a central link between nutrient metabolism and the regulationof intestinal tissue renewal and homeostasis. Understanding how ISCs respond ormake adaptations to nutritional signals is therefore vital for maintaining intestinalhomeostasis. Recent studies have spotlighted the origin and identity of ISCs andbroadened our insight into the plasticity and function of ISCs under differentconditions. Mitochondria, the central hubs of energy production and metabolicsignals provided by dietary components and metabolic substrates, such as glucose,amino acids, and lipids, govern the intricate balance between self-renewal anddifferentiation of ISCs. This review highlights the importance of nutrient sensing,metabolic regulation, and mitochondrial function in the specification of ISC fate.A thorough understanding of these mechanisms paves the way for the developmentof stem cell-based therapy for the mucosal healing of gastrointestinaldiseases and diet intervention to foster body health.展开更多
BACKGROUND Postoperative recurrence is common in Crohn’s disease(CD),with endoscopic lesions in a majority of patients by 12 months after surgery.Ileocolonoscopy is the reference standard but is invasive and poorly s...BACKGROUND Postoperative recurrence is common in Crohn’s disease(CD),with endoscopic lesions in a majority of patients by 12 months after surgery.Ileocolonoscopy is the reference standard but is invasive and poorly suited to frequent surveillance.Intestinal ultrasound(IUS)-including small intestine contrast ultrasound and contrast enhanced ultrasound-is a repeatable,noninvasive alternative.AIM To summarize the evidence on the diagnostic accuracy and prognostic value of IUS for detecting postoperative recurrence in CD.METHODS We systematically searched PubMed and EMBASE through June 2025 for original English-language studies evaluating IUS against clinical or endoscopic outcomes in postoperative CD.This scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline.After screening 259 unique records,41 full texts were assessed and 20 studies were included.RESULTS Bowel wall thickness thresholds of≥5 mm at the neo-terminal ileum predict endoscopic recurrence with sensitivities 81%-94%and specificities 86%-100%;lower cutoffs at the anastomosis(≥3-3.5 mm)also carry risk(data from singlecenter cohorts).Dualsite assessment(neo-terminal ileum+ileocolonic anastomosis)improves performance.Adding Doppler hyperemia or mesenteric lymphadenopathy increases accuracy;combining bowel wall thickness≥3 mm with fecal calprotectin≥50μg/g yields high specificity(approximately 93%-100%)with a negative predictive value of nearly 95%when both are negative.Contrast enhanced ultrasound-based composite scores reach approximately 98%diagnostic accuracy in prospective cohorts.Small intestine contrast ultrasound shows similarly strong early diagnostic performance-for example,an area under the receiver operating characteristic curve up to 0.95 when using ileocolonic anastomosis wall thickness≥3 mm to 3.5 mm plus lesion length,with 82%-94%sensitivity and>90%specificity reported even within 7 days postresection.Overall,IUS shows moderate agreement with endoscopy(κapproximately 0.5-0.8)and stronger prognostic value when performed within 12 months post-surgery.CONCLUSION IUS can be integrated into postoperative surveillance algorithms-particularly within the first year-and can reduce routine endoscopy in selected patients.Research priorities include standardized thresholds and composite scoring,consensus training/competency,and multicenter validation including artificial intelligenceassisted interpretation.展开更多
BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche ...BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.展开更多
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
文摘A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
基金Supported by Guangdong Provincial Medical Research Fund General Program,No.B2025209Guangzhou Science and Technology Program Project,No.2025A03J3269.
文摘Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.
基金National Natural Science Foundation of China(32372830 and 31972528).
文摘Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbio-sis.However,it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets.Results In this study,we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score,and elevated levels of lipopolysaccharide(LPS)and D-lactate(D-LA)compared to healthy piglets.Subsequently,we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets.Diarrheal piglets demonstrated intestinal microbiota dysbiosis,characterized pri-marily by a higher Firmicutes to Bacteroidota ratio,a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri,and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron.Functional pro-filing of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes(KEGG)data was performed,and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diar-rhea.Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets.Furthermore,we explored the effects of dietary indole-3-aldehyde(IAld),a key tryptophan metabolite,on intestinal development and gut barrier function in weaned piglets.Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell(ISC)expansion in piglets.The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids.Conclusions These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intesti-nal development by promoting ISC expansion in weaned piglets.
文摘The role of small bowel capsule endoscopy (CE) in suspected small bowel bleedingis well established and current European and other international guidelinesposition it as the first line test after negative bidirectional endoscopies. Insuspected mid-lower gastrointestinal bleeding (MLGIB) the diagnostic yield ofcolonoscopy is poor and may cause a delay in detecting small bowel disease. Acrucial aspect of small bowel capsule endoscope performance is the timing of theprocedure, the interval between the bleeding episode and capsule ingestion isinversely related to the diagnostic yield as confirmed by a recent meta-analysis.Currently the ongoing advances achieved by video CE in particular to evaluateboth small bowel and colon in a single test using double headed capsules, raisesquestions regarding the position of pan intestinal capsule in the current algorithmto investigate patients presenting with suspected MLGIB ahead of colonoscopy.Early evidence suggests pan intestinal capsule could fit well as a diagnostic“filter” test in this cohort of patients, thereby reserving invasive conventionalcolonoscopy or device assisted enteroscopy as therapeutics options only. The recentdevelopment of magnetically controlled CE and a blood sensing capsule pushthe boundaries of CE even further in patients presenting with suspected gastrointestinalbleeding. This review will discuss the current available evidence andfuture directions of CE in suspected MLGIB.
基金financially supported by the National Key Research and Development Program of China(2022YFF1100402)National Center of Technology Innovation for Dairy(2022-Open subject-11)+1 种基金Young Elite Scientist Sponsorship Program by CAST(YESS20200271)the National Natural Science Foundation of China(32101919)。
文摘2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.
文摘BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are rarely subjected to investig-ations for SIBO.AIM To estimate the frequency of SIBO in children having functional upper GI sym-ptoms(as cases)and to compare the result of the SIBO status to that of the con-trols.METHODS Children aged 6 to 18 who presented with upper GI symptoms were selected for the study.All children were subjected to upper GI endoscopy before being advised of any proton pump inhibitors(PPIs).Children with normal endoscopy were assigned as cases,and children having any endoscopic lesion were design-ated as controls.Both groups were subjected to a glucose-hydrogen breath test by Bedfont Gastrolyser.RESULTS A total of 129 consecutive children who were naive to PPIs and had normal ba-seline investigations were included in the study.Among them,67 patients had endoscopic lesions and served as the control group,with six cases being excluded due to the presence of Helicobacter pylori in gastric biopsies.Sixty-two children with normal endoscopy results formed the case group.In the case group,35 children(59%)tested positive for hydrogen breath tests,compared to 13 children(21%)in the control group.The calculated odds ratio was 5.38(95%confidence interval:2.41-12.0),which was statistically significant.Further analysis of symptoms revealed that nausea,halitosis,foul-smelling eructation,and epigastric fullness were positive predictors of SIBO.CONCLUSION It is worthwhile to investigate and treat SIBO in all children presenting with upper GI symptoms that are not explained by endoscopy findings.
文摘BACKGROUND Post-pancreaticoduodenectomy(PD)intestinal failure(IF)is rare and associated with poor outcomes.To our knowledge,the role of intestinal transplantation(ITx)as a rescue treatment for this complication has never been reported.CASE SUMMARY A 42-year-old female with a benign neurilemmoma of the duodenum underwent PD.Her superior mesenteric vein(SMV)was injured during surgery and required reconstruction.She experienced SMV thrombosis and bowel gangrene requiring massive bowel resection.Consequently,she developed short gut syndrome and an enterocutaneous fistula,leading to prolonged hospitalization for wound care and total parenteral nutrition(TPN)support.She was referred to our hospital for ITx evaluation.Upon arrival,she had cholestasis due to IF-associated liver disease.After gastrointestinal(GI)reconstruction to restore GI continuity,she was eligible for multi-visceral transplantation(MVTx).The anticipated allograft included the stomach,small intestine,liver,pancreas,and duodenum.She found a suitable donor after two years of waiting.The MVTx procedure was straightforward with signs of immediate function.Enteral feeding was initiated on postoperative day(POD)7.TPN weaning was achieved on POD 28,and the patient was discharged on POD 69.Two years post-MVTx,she is healthy with excellent graft function.To our knowledge,this is the first case report on MVTx as the treatment for fatal post-PD complications and also the first reported case of ITx in Southeast Asia.CONCLUSION Post-PD IF is rare and lethal.Intestinal and MVTx might be a rescue treatment for IF after GI surgery in eligible patients.
基金Supported by the National Natural Science Foundation of China,No.81971814Pudong New Area Health Talent Training Program,No.2025PDWSYCBJ-04Shanghai’s 2023“Technology Innovation Action Plan”Medical Innovation Research Project,No.23Y11908300。
文摘BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.
基金funded by the National Natural Science Foundation of China(No.82304730)the Project of Academic and Technical Leaders in Major Disciplines in Jiangxi Province(No.20212BCJL23060)+3 种基金the Natural Science Foundation of Jiangxi Province(No.20232BAB216128)the Project of Jiangxi Provincial Department of Education(No.GJJ2200977)the Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(Nos.CXTD-22004,CXTD-22008)the PhD Startup Foundation of Affiliated Hospital of Jiangxi University of Chinese Medicine(No.23KYQDZJ02).
文摘Utilizing transporter-mediated drug delivery to achieve effective oral absorption emerges as a promising strategy.Researchers have been concentrated on discovering solutions to the issues of low solubility and poor permeability of insoluble drugs,whereas,current reports have revealed that drug transporter proteins are abundantly expressed in the mucosa of intestinal epithelial cells,and that their mediated drug absorption effectively improved the bioavailability of orally administered drugs.There are two main categories based on the transporter mechanism,which include the family of ATP-binding cassette(ABC)transporters with efflux effects that reduce drug bioavailability and the family of solute carriers(SLC)transporters with uptake effects that promote drug absorption,respectively.Thus,we review studies of intestinal transporter-mediated delivery of drugs to enhance oral absorption,including the types of intestinal transporters,distribution characteristics,and strategies for enhancing oral absorption using transporter-mediated drug delivery systems are summarized,with the aim of providing important theoretical references for the development of intestinal-targeted delivery system.
文摘BACKGROUND Recently,intestinal stenting combined with laparoscopic surgery has received increasing attention as a treatment option for acute intestinal obstruction.However,its safety and efficacy have not yet been established.AIM To assess the efficacy and safety of combining intestinal stenting with laparoscopic surgery for the management of acute intestinal obstruction.METHODS Clinical data from 74 patients with colorectal cancer and acute intestinal obstruction,who were admitted to the emergency department of the authors’hospital between October 2023 and November 2024,were collected and analyzed.Patients were divided into two groups based on the surgical intervention:A control group(emergency open surgery,n=37)and a study group(intestinal stent implantation combined with laparoscopic surgery,n=37).Observation indicators included stent placement rate,obstruction relief rate,and stent-related complications.RESULTS Intestinal stent placement was 100%successful in the study group,all of whom experienced relief from obstruction while exhibiting a significantly lower rate of ostomy creation and a higher rate of primary anastomosis than in the control group,as well as less intraoperative blood loss,shorter time to flatus,and shorter hospital stay.The complication rate was 5.41%(2/37;bleeding and re-obstruction),with no statistically significant difference between the two groups in terms of operative duration or perioperative mortality.The overall complication rates were 5.41%(2/37)and 21.62%(8/37)in the intervention and control groups,respectively.Tumor recurrence and overall survival rates were 2.70%and 97.30%in the study group and 13.51%and 91.89%in the control group,respectively.CONCLUSION Intestinal stenting relieved acute obstructions,reduced the number of emergency surgeries,and supported laparoscopic procedures while improving primary anastomosis rates,minimizing ostomy occurrence,surgical trauma,and complications,and accelerating recovery.
基金supported by the National Key R&D Program of China(2023YFA1800100and 2024YFF1206600)the National Natural Science Foundation of China(32100664)the Basic and Applied Basic Research Foundation of Guangdong Province(2024B1515040019 and 2022A1515012042).
文摘Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.
文摘The intestinal barrier is crucial for homeostasis.This study aimed to investigate the protective effects of earthworm protein hydrolysates(EWPH)on the intestinal mucosal barrier and elucidate the underlying mechanisms.We first hydrolyzed earthworm protein using alcalase and identified the primary peptide components of EWPH through Nano LC-MS/MS analysis.Network pharmacology and bioinformatics approaches were employed to predict potential targets associated with the intestinal mucosal barrier.Experimentally,we demonstrated that EWPH effectively protects against dextran sulfate sodium(DSS)-induced intestinal barrier damage in mice.The protective mechanisms involve not only the inhibition of the Toll-like receptor 4(TLR4)-nuclear factor-kB(NF-kB)/mitogen-activated protein kinases(MAPK)signaling pathway in the intestinal epithelium but also the suppression of other key molecules implicated in intestinal mucosal barrier damage,including phosphorylated-SRC proto-oncogene(p-SRC),phosphorylated-signal transducer and activator of transcription 3(p-STAT3),Caspase-3,and matrix metalloproteinase-9(MMP9),thereby mitigating intestinal inflammation and mucosal barrier injury.This study provides evidence that EWPH have the potential to safeguard the intestinal barrier hemostasis.
基金Supported by the Changshu Municipal Health Commission Science and Technology Program,No.csws201902。
文摘BACKGROUND Colonoscopy quality relies heavily on adequate bowel preparation,yet traditional methods often result in suboptimal compliance.Emerging network-based monitoring systems offer promise for improving both preparation quality and patient cooperation,potentially enhancing clinical outcomes.AIM To evaluate the effectiveness of an intestinal network monitoring system in enhancing the quality of bowel preparation for colonoscopy and its impact on patient psychological and physiological responses,compliance,and adverse event rates.METHODS Between July 2019 and July 2020,800 enteroscopy patients who met the inclusion criteria in the outpatient clinic of the gastroenterology department of our hospital were randomly divided into 400 cases each in the experimental group(network monitoring group)and the control group(verbal+written preaching group),and the psychological and physiological stress response situation,colon Boston Bowel Preparation Scale,enteroscopy to blindness,arrival time to blindness,and polyp detection rate of the patients were compared before and after the intervention,compliance and adverse reactions were compared.RESULTS There was no difference in anxiety and depression scores,heart rate and systolic blood pressure between the groups before the intervention(P>0.05),and after the intervention,the patients’anxiety and depression scores were lower and lower in the study group(P<0.05);heart rate and systolic blood pressure were elevated,but lower in the test group(P<0.05).The left hemicolon,right hemicolon,transverse colon and total Boston Bowel Preparation Scale scores were lower in the test group than in the control group(P<0.05),the colonoscopy arrival rate and polyp detection rate were higher than those in the control group,and the time to arrival and time to exit the scope were shorter than those in the control group(P<0.05),and the dietary preparations,the preparations for taking medications and the total adherence scores were higher than those in the control group(P<0.05).The incidence of adverse reactions in the experimental group was 11.00%,which was lower than that in the control group(P<0.05).CONCLUSION The Bowel Network Monitoring System has potential clinical promotion value in improving the quality of colonoscopic bowel preparation,which can effectively alleviate patient anxiety and depression,improve the quality of colonoscopic bowel preparation and patient compliance,and has a high degree of safety.
基金Supported by the National Natural Science Foundation of China,No.82574996Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+3 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.2025SF-YBXM-498the“Nursery Cultivation Plan”Project of Shaanxi Provincial Academy of Chinese Medicine and Shaanxi Provincial Hospital of Traditional Chinese Medicine,No.2025-04the Fifth Batch of Outstanding Clinical Talents in Traditional Chinese Medicine Project of Shaanxi Province.
文摘Inflammatory bowel disease(IBD),a chronic disorder characterized by intestinal inflammation and mucosal damage,includes mainly Crohn’s disease and ulcerative colitis.However,the cause of its onset remains unclear.The pathogenesis of IBD is closely related to host genetic susceptibility,disorders of the intestinal flora,damage to the intestinal mucosal barrier,and abnormal intestinal mucosal immunity.On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD,the influence of genetics on the intestinal barrier and intestinal microbiota;the metagenomics,metatranscriptomics,and metabolomics of the intestinal microbiota involved in IBD;and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.
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 Ministry of Science and Technology of China,No.2022YFF1203300National Key Research and Development Program,No.2023YFC2307001China Postdoctoral Science Foundation,No.2023TQ0125 and No.2024M751031.
文摘Diet and nutrition significantly influence health, largely by regulating intestinalnutrient absorption. The intestinal epithelium, as the primary site for nutrientuptake, undergoes continuous renewal driven by precise regulation of intestinalstem cells (ISCs). Nutrient sensing and metabolism are key determinants of ISCfate, making ISCs a central link between nutrient metabolism and the regulationof intestinal tissue renewal and homeostasis. Understanding how ISCs respond ormake adaptations to nutritional signals is therefore vital for maintaining intestinalhomeostasis. Recent studies have spotlighted the origin and identity of ISCs andbroadened our insight into the plasticity and function of ISCs under differentconditions. Mitochondria, the central hubs of energy production and metabolicsignals provided by dietary components and metabolic substrates, such as glucose,amino acids, and lipids, govern the intricate balance between self-renewal anddifferentiation of ISCs. This review highlights the importance of nutrient sensing,metabolic regulation, and mitochondrial function in the specification of ISC fate.A thorough understanding of these mechanisms paves the way for the developmentof stem cell-based therapy for the mucosal healing of gastrointestinaldiseases and diet intervention to foster body health.
文摘BACKGROUND Postoperative recurrence is common in Crohn’s disease(CD),with endoscopic lesions in a majority of patients by 12 months after surgery.Ileocolonoscopy is the reference standard but is invasive and poorly suited to frequent surveillance.Intestinal ultrasound(IUS)-including small intestine contrast ultrasound and contrast enhanced ultrasound-is a repeatable,noninvasive alternative.AIM To summarize the evidence on the diagnostic accuracy and prognostic value of IUS for detecting postoperative recurrence in CD.METHODS We systematically searched PubMed and EMBASE through June 2025 for original English-language studies evaluating IUS against clinical or endoscopic outcomes in postoperative CD.This scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline.After screening 259 unique records,41 full texts were assessed and 20 studies were included.RESULTS Bowel wall thickness thresholds of≥5 mm at the neo-terminal ileum predict endoscopic recurrence with sensitivities 81%-94%and specificities 86%-100%;lower cutoffs at the anastomosis(≥3-3.5 mm)also carry risk(data from singlecenter cohorts).Dualsite assessment(neo-terminal ileum+ileocolonic anastomosis)improves performance.Adding Doppler hyperemia or mesenteric lymphadenopathy increases accuracy;combining bowel wall thickness≥3 mm with fecal calprotectin≥50μg/g yields high specificity(approximately 93%-100%)with a negative predictive value of nearly 95%when both are negative.Contrast enhanced ultrasound-based composite scores reach approximately 98%diagnostic accuracy in prospective cohorts.Small intestine contrast ultrasound shows similarly strong early diagnostic performance-for example,an area under the receiver operating characteristic curve up to 0.95 when using ileocolonic anastomosis wall thickness≥3 mm to 3.5 mm plus lesion length,with 82%-94%sensitivity and>90%specificity reported even within 7 days postresection.Overall,IUS shows moderate agreement with endoscopy(κapproximately 0.5-0.8)and stronger prognostic value when performed within 12 months post-surgery.CONCLUSION IUS can be integrated into postoperative surveillance algorithms-particularly within the first year-and can reduce routine endoscopy in selected patients.Research priorities include standardized thresholds and composite scoring,consensus training/competency,and multicenter validation including artificial intelligenceassisted interpretation.
文摘BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.
