BACKGROUND Idiopathic mesenteric phlebosclerosis(IMP)is a rare condition that causes ischaemic colitis,has various clinical manifestations,and may even be asymptomatic,often resulting in clinical misdiagnosis.CASE SUM...BACKGROUND Idiopathic mesenteric phlebosclerosis(IMP)is a rare condition that causes ischaemic colitis,has various clinical manifestations,and may even be asymptomatic,often resulting in clinical misdiagnosis.CASE SUMMARY We report the case of a 44-year-old woman with chief complaints of abdominal pain,vomiting and decreased defecation.One year prior,the patient was asymptomatic and therefore misdiagnosed with inflammatory bowel disease based on incidental findings on an abdominal computed tomography(CT)scan.The present abdominal CT scan revealed an intestinal obstruction,diffuse thickening of the entire colon wall and calcification of the mesenteric and colonic veins.Colonoscopy revealed multiple ulcerations and extensive dark purple discolouration of the oedematous mucosa.Colonic transit studies suggested a decrease in colonic motility.IMP was considered the underlying cause of her pseudoileus,which was potentially linked to her consumption of Chinese medicinal teas for more than 30 years.The patient underwent conservative medical treatment,and her symptoms gradually improved.She exhibited no signs of ileus or other significant discomfort at the outpatient follow-up one year after the discontinuation of Chinese herbal tea consumption.CONCLUSION IMP can present with symptoms of pseudoileus as initial complication.Clinicians can use CT and colonoscopy for differential diagnoses.展开更多
BACKGROUND Chronic intestinal pseudo-obstruction(CIPO)is a rare and debilitating disorder,characterized by severe impairments in gastrointestinal motility.The affected sites include the enteric/intrinsic autonomic ner...BACKGROUND Chronic intestinal pseudo-obstruction(CIPO)is a rare and debilitating disorder,characterized by severe impairments in gastrointestinal motility.The affected sites include the enteric/intrinsic autonomic nerves(neuropathy),intestinal smooth muscle cells(myopathy),and interstitial cells of Cajal(mesenchymopathy).The etiology can be genetic,idiopathic,or acquired.Owing to its nonspecific clinical presentation and lack of definitive diagnostic methods,misdiagnosis of CIPO is common.CASE SUMMARY This case involved an older male with insidious onset in adolescence who presented with postprandial bloating,intermittent diarrhea,and weight loss.During the disease course,the patient experienced two episodes of intestinal obstruction.Imaging revealed multisegmental digestive tract abnormalities(gastric emptying disorder,significant duodenal dilatation,and segmental jejunal dilatation).Whole-exome sequencing revealed a rare MYH11 mutation[NM_0010-40113.2:C.5819del(p.Pro1940HisfsTer91)],confirming hereditary myopathic CIPO.CONCLUSION This report adds to our current understanding of CIPO etiology by reinforcing the role of MYH11 variants in the pathogenesis of the CIPO phenotype.展开更多
Chronic intestinal pseudo-obstruction (CIPO) is a se- vere digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. ...Chronic intestinal pseudo-obstruction (CIPO) is a se- vere digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features in- testinal pseudo-obstruction can be classified into three main categories:neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseu- do-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases.展开更多
Intestinal pseudo-obstruction secondary to systemic lupus erythematosus(SLE) is a rare syndrome described in recent decades. There are slightly over 30 published cases in the English language literature, primarily ass...Intestinal pseudo-obstruction secondary to systemic lupus erythematosus(SLE) is a rare syndrome described in recent decades. There are slightly over 30 published cases in the English language literature, primarily associated with renal and hematological disease activity. Its presentation and evolution are a diagnostic challenge for the clinician. We present four cases of intestinal pseudo-obstruction due to lupus in young Mexican females. One patient had a previous diagnosis of SLE and all presented with a urinary tract infection of varying degrees of severity during their evolution. We consider that recognition of the disease is of vital importance because it allows for establishing appropriate management, leading to a better prognosis and avoiding unnecessary surgery and complications.展开更多
Chronic intestinal pseudo-obstruction(CIPO)is a type of intestinal dysfunction presenting as symptoms of intestinal obstruction but without actual mechanical obstruction.An extremely low incidence,non-specific clinica...Chronic intestinal pseudo-obstruction(CIPO)is a type of intestinal dysfunction presenting as symptoms of intestinal obstruction but without actual mechanical obstruction.An extremely low incidence,non-specific clinical symptoms,strong heterogeneity,and no definitive cause in some patients make CIPO very difficult to diagnose correctly.Imaging and gastrointestinal manometry are commonly used.Most patients have progressive worsening of their symptoms and require intervention,and nutritional assessment and treatment are very important to determine the prognosis.With improvements in surgical techniques,small bowel transplantation is a feasible treatment option for patients with advanced CIPO;however,the long-term prognosis for CIPO patients remains unsatisfactory.Generally,the disease is rare and difficult to diagnose,which leads to clinicians’lack of understanding of the disease and results in a high rate of misdiagnosis.This review describes the characteristics of CIPO and the latest developments in diagnosis and treatment,in detail.The goal of our review is to improve clinicians'understanding of CIPO so that the disease is identified quickly and accurately,and treated as early as possible to improve patients’quality of life.展开更多
Visceral myopathy is one of the causes of chronic intestinal pseudo-obstruction. Most cases pathologically reveal degenerative changes of myocytes or muscularis propia atrophy and fibrosis. Abnormal layering of muscul...Visceral myopathy is one of the causes of chronic intestinal pseudo-obstruction. Most cases pathologically reveal degenerative changes of myocytes or muscularis propia atrophy and fibrosis. Abnormal layering of muscularis propria is extremely rare. We report a case of a 9-mo-old Thai male baby who presented with chronic intestinal pseudo-obstruction. Histologic findings showed abnormal layering of small intestinal muscularis propria with an additional oblique layer and aberrant muscularization in serosa. The patient also had a short small bowel without malrotation, brachydactyly,and absence of the 2nd to 4th middle phalanges of both hands. The patient was treated with cisapride and combined parenteral and enteral nutritional support.He had gradual clinical improvement and gained body weight. Subsequently, the parenteral nutrition was discontinued. The previously reported cases are reviewed and discussed.展开更多
Intestinal pseudo-obstruction (IPO) either acute or chronic is a condition including features of intestinal ileus in absence of mechanical obstruction. Our paper presents such a rare case of idiopathic IPO in a 53-yea...Intestinal pseudo-obstruction (IPO) either acute or chronic is a condition including features of intestinal ileus in absence of mechanical obstruction. Our paper presents such a rare case of idiopathic IPO in a 53-year-old male patient with recurrent episodes of pseudo-obstruction, which were successfully resolved by anticholinesterase agents, motilin agonists or colonic decompression. However, the patient finally underwent total colectomy. Huge colonic dilatation was identified intraoperatorily, while histology showed a neuropathic variant of chronic intestinal pseudo-obstruction. Etiologic mechanisms and current therapeutic methods are reviewed in this paper, which concludes that IPO is a condition in which conservative treatment usually fails. Total colectomy with ileoanal pouch may be the only solution in these situations.展开更多
AIM: To reveal the frequency, characteristics and prognosis of chronic intestinal pseudo-obstruction (CIP) in mitochondrial disease patients. METHODS: Between January 2000 and December 2010, 31 patients (13 males and ...AIM: To reveal the frequency, characteristics and prognosis of chronic intestinal pseudo-obstruction (CIP) in mitochondrial disease patients. METHODS: Between January 2000 and December 2010, 31 patients (13 males and 18 females) were di-agnosed with mitochondrial diseases at our hospital. We conducted a retrospective review of the patients' sex, subclass of mitochondrial disease, age at onset of mitochondrial disease, frequency of CIP and the age at its onset, and the duration of survival. The age at onset or at the first diagnosis of the disorder that led to the clinical suspicion of mitochondrial disease was also examined. RESULTS: Twenty patients were sub-classified with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), 8 with chronic progressive external ophthalmoplegia (CPEO), and 3 with myoclonus epilepsy associated with ragged-red fibers (MERRF). Nine patients were diagnosed with CIP, 8 of the 20 (40.0%) patients with MELAS, 0 of the 8 (0.0%) patients with CPEO, and 1 of the 3 (33.3%) patients with MERRF. The median age (range) at the diagnosis and the median age at onset of mitochondrial disease were 40 (17-69) and 25 (12-63) years in patients with CIP, and 49 (17-81) and 40 (11-71) years in patients without CIP. During the survey period, 5 patients (4 patients with MELAS and 1 with CPEO) died. The cause of death was cardiomyopathy in 2 patients with MELAS, cerebral infarction in 1 patient with MELAS, epilepsy and aspiration pneumonia in 1 patient with MELAS, and multiple metastases from gastric cancer and aspiration pneumonia in 1 patient with CPEO. CONCLUSION: Patients with CIP tend to have disorders that are suspected to be related to mitochondrial diseases at younger ages than are patients without CIP.展开更多
Chronic intestinal pseudo-obstruction(CIPO) is a rare disease due to a severe gastrointestinal motility disorder which may mimic,on both clinical and radiological grounds,mechanical obstruction.We report a case of a 2...Chronic intestinal pseudo-obstruction(CIPO) is a rare disease due to a severe gastrointestinal motility disorder which may mimic,on both clinical and radiological grounds,mechanical obstruction.We report a case of a 26-year-old woman who presented to our institution for plain abdominal radiography for referred long-lasting constipation with recurrent episodes of abdominal pain and distension.At X-ray,performed both in the upright and supine position,an isolated air-fluid level was depicted in the left flank,together with a number of radiological signs suggestive of pneumoperitoneum.First,subphrenic radiolucency could be observed in the upright film.Second,the intestinal wall of some jejunal loops appeared to be outlined in the right flank.Third,the inferior cardiac border was clearly depicted in the upright film.The patient however had no evidence ofperitoneal signs but only hypoactive bowel movements.Unenhanced multi-detector computed tomography(MDCT) of the abdomen and pelvis was therefore performed.MDCT revealed abnormal air-driven distension of the small and large bowel,without evidence of extraluminal air.All radiological signs of pneumoperitoneum turned out to be false-positive results.The patient was submitted to pan-colonoscopy and to anorectal manometry to rule out Hirshprung's disease,and was finally discharged with a diagnosis of CIPO.展开更多
Herpes zoster(HZ) infection occurs in approximately 10% to 30% of individuals. Visceral neuropathies secondary to HZ can cause cystitis and urinary retention. But colonic pseudo-obstruction can also occur. Peripheral ...Herpes zoster(HZ) infection occurs in approximately 10% to 30% of individuals. Visceral neuropathies secondary to HZ can cause cystitis and urinary retention. But colonic pseudo-obstruction can also occur. Peripheral neuropathy may reveal segmental motor paresis of either upper or lower limbs, the abdominal muscles or the diaphragm. We report the case of a 62-year-old male patient who presented with abdominal distention and cutaneous vesicular eruption on the left side of the abdominal wall. Plain X-rays and computed tomography scan showed distended small bowel. A diagnosis of intestinal pseudo-obstruction was made secondary to segmental paresis of the small intestine and visceral neuropathy. Conservative management was successful and the patient was discharged uneventfully. Intestinal pseudo-obstruction ought to be consideredwhen dealing with non-obstructive(adynamic) conditions of the digestive tract associated with HZ infection; since early recognition may help to avoid unnecessary surgery.展开更多
Chronic intestinal pseudo-obstruction (CIP) is an infre-quent complication of an active systemic lupus erythema-tosus (SLE). We illustrate a case of SLE inactive-related CIP. A 51-year old female with inactive SLE (EC...Chronic intestinal pseudo-obstruction (CIP) is an infre-quent complication of an active systemic lupus erythema-tosus (SLE). We illustrate a case of SLE inactive-related CIP. A 51-year old female with inactive SLE (ECLAM score 2) was hospitalized with postprandial fullness, vomiting, abdominal bloating and abdominal pain. She had had no bowel movements for five days. Plain abdominal X-ray revealed multiple fluid levels and dilated small and large bowel loops with air-fluid levels. Intestinal contrast radiology detected dilated loops. CIP was diagnosed. The patient was treated with prokinetics, octreotide, claritromycin, rifaximin, azathioprine and tegaserod without any clinical improvement. Then methylprednisolone (500 mg iv daily) was started. After the first administration, the patient showed peristaltic movements. A bowel movement was reported after the second administration. A plain abdominal X-ray revealed no air-fluid levels. Steroid therapy was slowly reduced with complete resolution of the symptoms. The patient is still in a good clinical condition. SLE-related CIP is generally reported as a complication of an active disease. In our case, CIP was the only clinical demonstration of the SLE.展开更多
Percutaneous endoscopic colostomy （PEC） is increasingly proposed as an alternative to surgery to treat various disorders, including acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction and relapsi...Percutaneous endoscopic colostomy （PEC） is increasingly proposed as an alternative to surgery to treat various disorders, including acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction and relapsing sigmoid volvulus. We report on a severe complication that occurred two months after PEC placement. A 74-year-old man with a history of chronic intestinal pseudo-obstruction evolving since 8 years was readmitted to our hospital and received PEC to provide long-standing relief. The procedure was uneventful and greatly improved the patient＇s quality of life. Two months later, the patient developed acute stercoral peritonitis. At laparotomy, the colostomy flange was embedded in the abdominal wall but no pressure necrosis was found at the level of the colonic wall. This complication was likely related to inadvertent traction of the colostomy tube. Subtotal colectomy with terminal ileostomy was performed. We review the major features of 60 cases of PEC reported to date, including indications and complications.展开更多
Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mecha...Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood.Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs.Methods Firstly,two groups of weaning pigs were fed a basal diet,or basal diet supplemented with 4 mg DON/kg for 3 weeks.Additionally,another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline.In addition,the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line(IPEC-1)by overexpressed plasmids of dynamin related protein 1(Drp1)and mitofusin 2(Mfn2)which were determined by animal studies.Finally,a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage.Results Dietary DON caused jejunal damage and inflammation,reduced intestinal Drp1,mitofusin 1(Mfn1)and Mfn2,and induced cell apoptosis.DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2,and increased cell apoptosis.Moreover,DON challenge also resulted in cell damage and mitochondrial dysfunction,accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells.Subsequently,Mfn2,but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression,suppressed cell apoptosis,mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge.Finally,M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis,rescued mitochondrial dysfunction,barrier function impairment and cell damage.Conclusions Overall,our study demonstrates that DON exposure triggers Mfn2 protein dysregulation,which in turn mediates DON-induced intestinal epithelial damage in piglets.展开更多
The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a se...The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.展开更多
The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
The intestine is a key component of the barrier,absorption,and immune systems,contributing significantly to maintaining internal homeostasis and influencing disease progression.Its distinctive physiological functions ...The intestine is a key component of the barrier,absorption,and immune systems,contributing significantly to maintaining internal homeostasis and influencing disease progression.Its distinctive physiological functions arise from a complex interplay between its structure and microenvironment.Recent advancements in bioengineering technologies now enable the construction of in vitro intestinal models that faithfully recapitulate the organizational and functional characteristics of native tissue.This review examines the interface between in vitro models and native intestinal biology,offering insights into the replication of organ functions from a manufacturing perspective.We explore bioengineering strategies that enable the mapping of cross-scale structures and the creation of biomimetic environments essential for physiological performance.Furthermore,we discuss pragmatic optimization strategies for applying these models to both physiological and pathological studies,thereby enhancing their translational potential for drug development,disease modeling,and personalized medicine.In contrast to previous reviews,this work proposes an engineering-centered framework for linking structural fabrication strategies to functional performance across intestinal model types.展开更多
Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minima...Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.展开更多
Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compo...Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.展开更多
Background Selective breeding for disease resistance is an effective strategy to control duck hepatitis A virus type 3(DHAV-3)in waterfowl.However,the mechanism underlying resistance remains poorly understood,particul...Background Selective breeding for disease resistance is an effective strategy to control duck hepatitis A virus type 3(DHAV-3)in waterfowl.However,the mechanism underlying resistance remains poorly understood,particularly those associated with antioxidant defense,intestinal development and host-microbiota interactions.Method A total of 1001-day-old Pekin ducklings were used in this study with 50 DHAV-3 susceptible and resistant ducks,respectively.Samples were collected at 7 days post-hatching(D7),D21 and D42,10 birds per group.We compared DHAV-3 resistant and susceptible ducks during early development with respect to immune organ indices,antioxidant capacity,intestinal morphology,barrier-related gene expression and cecal microbiota.Result Resistant ducks exhibited higher spleen indices and stronger antioxidant capacity,characterized by increased superoxide dismutase,reduced glutathione,and total antioxidant capacity,along with lower malondialdehyde levels at D7 and D21.In contrast,susceptible ducks showed compensatory thymus hypertrophy and delayed development of antioxidant defense and intestinal maturation.Ileal morphology revealed greater villus height and width with more regular arrangement in resistant ducks at D7,whereas these differences diminished at D21 and D42.Gene expression analysis demonstrated higher early expression of the tight junction proteins CLDN1 and CLDN3 in resistant ducks,while susceptible ducks displayed elevated MUC2 and OCLN,suggesting stress induced compensatory responses.Cecal microbiota analysis revealed distinct colonization patterns in early development.Resistant ducks were enriched with Firmicutes and beneficial genera such as Enterococcus and Lactobacillus,whereas susceptible ducks harbored higher abundances of Bacteroidota and potentially opportunistic taxa.Microbial diversity increased with age in both groups,but resistant ducks displayed more orderly succession and enrichment of SCFA producing genera,including Subdoligranulum and Phascolarctobacterium,which positively correlated with plasma antioxidant indices.Conclusion DHAV-3 resistant ducks exhibit early advantages in antioxidant defense,intestinal barrier development and colonization by beneficial microbiota,which collectively contribute to enhanced disease resistance.These findings highlight the synergistic roles of host physiology and gut microbiota in shaping resistance.In the future,integrating genomic selection with microbiota modulation and antioxidant interventions may accelerate the breeding of highly resistant duck lines and provide scientific evidence and practical strategies for controlling duck viral hepatitis.展开更多
Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors ...Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.展开更多
文摘BACKGROUND Idiopathic mesenteric phlebosclerosis(IMP)is a rare condition that causes ischaemic colitis,has various clinical manifestations,and may even be asymptomatic,often resulting in clinical misdiagnosis.CASE SUMMARY We report the case of a 44-year-old woman with chief complaints of abdominal pain,vomiting and decreased defecation.One year prior,the patient was asymptomatic and therefore misdiagnosed with inflammatory bowel disease based on incidental findings on an abdominal computed tomography(CT)scan.The present abdominal CT scan revealed an intestinal obstruction,diffuse thickening of the entire colon wall and calcification of the mesenteric and colonic veins.Colonoscopy revealed multiple ulcerations and extensive dark purple discolouration of the oedematous mucosa.Colonic transit studies suggested a decrease in colonic motility.IMP was considered the underlying cause of her pseudoileus,which was potentially linked to her consumption of Chinese medicinal teas for more than 30 years.The patient underwent conservative medical treatment,and her symptoms gradually improved.She exhibited no signs of ileus or other significant discomfort at the outpatient follow-up one year after the discontinuation of Chinese herbal tea consumption.CONCLUSION IMP can present with symptoms of pseudoileus as initial complication.Clinicians can use CT and colonoscopy for differential diagnoses.
基金Supported by The National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-129.
文摘BACKGROUND Chronic intestinal pseudo-obstruction(CIPO)is a rare and debilitating disorder,characterized by severe impairments in gastrointestinal motility.The affected sites include the enteric/intrinsic autonomic nerves(neuropathy),intestinal smooth muscle cells(myopathy),and interstitial cells of Cajal(mesenchymopathy).The etiology can be genetic,idiopathic,or acquired.Owing to its nonspecific clinical presentation and lack of definitive diagnostic methods,misdiagnosis of CIPO is common.CASE SUMMARY This case involved an older male with insidious onset in adolescence who presented with postprandial bloating,intermittent diarrhea,and weight loss.During the disease course,the patient experienced two episodes of intestinal obstruction.Imaging revealed multisegmental digestive tract abnormalities(gastric emptying disorder,significant duodenal dilatation,and segmental jejunal dilatation).Whole-exome sequencing revealed a rare MYH11 mutation[NM_0010-40113.2:C.5819del(p.Pro1940HisfsTer91)],confirming hereditary myopathic CIPO.CONCLUSION This report adds to our current understanding of CIPO etiology by reinforcing the role of MYH11 variants in the pathogenesis of the CIPO phenotype.
文摘Chronic intestinal pseudo-obstruction (CIPO) is a se- vere digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features in- testinal pseudo-obstruction can be classified into three main categories:neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseu- do-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases.
文摘Intestinal pseudo-obstruction secondary to systemic lupus erythematosus(SLE) is a rare syndrome described in recent decades. There are slightly over 30 published cases in the English language literature, primarily associated with renal and hematological disease activity. Its presentation and evolution are a diagnostic challenge for the clinician. We present four cases of intestinal pseudo-obstruction due to lupus in young Mexican females. One patient had a previous diagnosis of SLE and all presented with a urinary tract infection of varying degrees of severity during their evolution. We consider that recognition of the disease is of vital importance because it allows for establishing appropriate management, leading to a better prognosis and avoiding unnecessary surgery and complications.
基金Supported by the Initial Scientific Research Fund of Young of Beijing Tsinghua Changgung Hospital,No.12020C1003.
文摘Chronic intestinal pseudo-obstruction(CIPO)is a type of intestinal dysfunction presenting as symptoms of intestinal obstruction but without actual mechanical obstruction.An extremely low incidence,non-specific clinical symptoms,strong heterogeneity,and no definitive cause in some patients make CIPO very difficult to diagnose correctly.Imaging and gastrointestinal manometry are commonly used.Most patients have progressive worsening of their symptoms and require intervention,and nutritional assessment and treatment are very important to determine the prognosis.With improvements in surgical techniques,small bowel transplantation is a feasible treatment option for patients with advanced CIPO;however,the long-term prognosis for CIPO patients remains unsatisfactory.Generally,the disease is rare and difficult to diagnose,which leads to clinicians’lack of understanding of the disease and results in a high rate of misdiagnosis.This review describes the characteristics of CIPO and the latest developments in diagnosis and treatment,in detail.The goal of our review is to improve clinicians'understanding of CIPO so that the disease is identified quickly and accurately,and treated as early as possible to improve patients’quality of life.
基金Supported by Faculty of Medicine,Ramathibodi Hospital,Mahidol University,Thailand
文摘Visceral myopathy is one of the causes of chronic intestinal pseudo-obstruction. Most cases pathologically reveal degenerative changes of myocytes or muscularis propia atrophy and fibrosis. Abnormal layering of muscularis propria is extremely rare. We report a case of a 9-mo-old Thai male baby who presented with chronic intestinal pseudo-obstruction. Histologic findings showed abnormal layering of small intestinal muscularis propria with an additional oblique layer and aberrant muscularization in serosa. The patient also had a short small bowel without malrotation, brachydactyly,and absence of the 2nd to 4th middle phalanges of both hands. The patient was treated with cisapride and combined parenteral and enteral nutritional support.He had gradual clinical improvement and gained body weight. Subsequently, the parenteral nutrition was discontinued. The previously reported cases are reviewed and discussed.
文摘Intestinal pseudo-obstruction (IPO) either acute or chronic is a condition including features of intestinal ileus in absence of mechanical obstruction. Our paper presents such a rare case of idiopathic IPO in a 53-year-old male patient with recurrent episodes of pseudo-obstruction, which were successfully resolved by anticholinesterase agents, motilin agonists or colonic decompression. However, the patient finally underwent total colectomy. Huge colonic dilatation was identified intraoperatorily, while histology showed a neuropathic variant of chronic intestinal pseudo-obstruction. Etiologic mechanisms and current therapeutic methods are reviewed in this paper, which concludes that IPO is a condition in which conservative treatment usually fails. Total colectomy with ileoanal pouch may be the only solution in these situations.
基金Health and Labour Sciences Research Grants for Research on Intractable Diseases, awarded to Nakajima A, from the Ministry of Health, Labour and Welfare of Japan
文摘AIM: To reveal the frequency, characteristics and prognosis of chronic intestinal pseudo-obstruction (CIP) in mitochondrial disease patients. METHODS: Between January 2000 and December 2010, 31 patients (13 males and 18 females) were di-agnosed with mitochondrial diseases at our hospital. We conducted a retrospective review of the patients' sex, subclass of mitochondrial disease, age at onset of mitochondrial disease, frequency of CIP and the age at its onset, and the duration of survival. The age at onset or at the first diagnosis of the disorder that led to the clinical suspicion of mitochondrial disease was also examined. RESULTS: Twenty patients were sub-classified with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), 8 with chronic progressive external ophthalmoplegia (CPEO), and 3 with myoclonus epilepsy associated with ragged-red fibers (MERRF). Nine patients were diagnosed with CIP, 8 of the 20 (40.0%) patients with MELAS, 0 of the 8 (0.0%) patients with CPEO, and 1 of the 3 (33.3%) patients with MERRF. The median age (range) at the diagnosis and the median age at onset of mitochondrial disease were 40 (17-69) and 25 (12-63) years in patients with CIP, and 49 (17-81) and 40 (11-71) years in patients without CIP. During the survey period, 5 patients (4 patients with MELAS and 1 with CPEO) died. The cause of death was cardiomyopathy in 2 patients with MELAS, cerebral infarction in 1 patient with MELAS, epilepsy and aspiration pneumonia in 1 patient with MELAS, and multiple metastases from gastric cancer and aspiration pneumonia in 1 patient with CPEO. CONCLUSION: Patients with CIP tend to have disorders that are suspected to be related to mitochondrial diseases at younger ages than are patients without CIP.
文摘Chronic intestinal pseudo-obstruction(CIPO) is a rare disease due to a severe gastrointestinal motility disorder which may mimic,on both clinical and radiological grounds,mechanical obstruction.We report a case of a 26-year-old woman who presented to our institution for plain abdominal radiography for referred long-lasting constipation with recurrent episodes of abdominal pain and distension.At X-ray,performed both in the upright and supine position,an isolated air-fluid level was depicted in the left flank,together with a number of radiological signs suggestive of pneumoperitoneum.First,subphrenic radiolucency could be observed in the upright film.Second,the intestinal wall of some jejunal loops appeared to be outlined in the right flank.Third,the inferior cardiac border was clearly depicted in the upright film.The patient however had no evidence ofperitoneal signs but only hypoactive bowel movements.Unenhanced multi-detector computed tomography(MDCT) of the abdomen and pelvis was therefore performed.MDCT revealed abnormal air-driven distension of the small and large bowel,without evidence of extraluminal air.All radiological signs of pneumoperitoneum turned out to be false-positive results.The patient was submitted to pan-colonoscopy and to anorectal manometry to rule out Hirshprung's disease,and was finally discharged with a diagnosis of CIPO.
文摘Herpes zoster(HZ) infection occurs in approximately 10% to 30% of individuals. Visceral neuropathies secondary to HZ can cause cystitis and urinary retention. But colonic pseudo-obstruction can also occur. Peripheral neuropathy may reveal segmental motor paresis of either upper or lower limbs, the abdominal muscles or the diaphragm. We report the case of a 62-year-old male patient who presented with abdominal distention and cutaneous vesicular eruption on the left side of the abdominal wall. Plain X-rays and computed tomography scan showed distended small bowel. A diagnosis of intestinal pseudo-obstruction was made secondary to segmental paresis of the small intestine and visceral neuropathy. Conservative management was successful and the patient was discharged uneventfully. Intestinal pseudo-obstruction ought to be consideredwhen dealing with non-obstructive(adynamic) conditions of the digestive tract associated with HZ infection; since early recognition may help to avoid unnecessary surgery.
文摘Chronic intestinal pseudo-obstruction (CIP) is an infre-quent complication of an active systemic lupus erythema-tosus (SLE). We illustrate a case of SLE inactive-related CIP. A 51-year old female with inactive SLE (ECLAM score 2) was hospitalized with postprandial fullness, vomiting, abdominal bloating and abdominal pain. She had had no bowel movements for five days. Plain abdominal X-ray revealed multiple fluid levels and dilated small and large bowel loops with air-fluid levels. Intestinal contrast radiology detected dilated loops. CIP was diagnosed. The patient was treated with prokinetics, octreotide, claritromycin, rifaximin, azathioprine and tegaserod without any clinical improvement. Then methylprednisolone (500 mg iv daily) was started. After the first administration, the patient showed peristaltic movements. A bowel movement was reported after the second administration. A plain abdominal X-ray revealed no air-fluid levels. Steroid therapy was slowly reduced with complete resolution of the symptoms. The patient is still in a good clinical condition. SLE-related CIP is generally reported as a complication of an active disease. In our case, CIP was the only clinical demonstration of the SLE.
文摘Percutaneous endoscopic colostomy （PEC） is increasingly proposed as an alternative to surgery to treat various disorders, including acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction and relapsing sigmoid volvulus. We report on a severe complication that occurred two months after PEC placement. A 74-year-old man with a history of chronic intestinal pseudo-obstruction evolving since 8 years was readmitted to our hospital and received PEC to provide long-standing relief. The procedure was uneventful and greatly improved the patient＇s quality of life. Two months later, the patient developed acute stercoral peritonitis. At laparotomy, the colostomy flange was embedded in the abdominal wall but no pressure necrosis was found at the level of the colonic wall. This complication was likely related to inadvertent traction of the colostomy tube. Subtotal colectomy with terminal ileostomy was performed. We review the major features of 60 cases of PEC reported to date, including indications and complications.
基金financially supported by the Project of National Key R&D Program of China(2022YFD1300403)the Natural Science Foundation of Hubei Province Project(2024AFB926)Hubei Provincial Science and Technology Program(2025CSA037)。
文摘Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood.Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs.Methods Firstly,two groups of weaning pigs were fed a basal diet,or basal diet supplemented with 4 mg DON/kg for 3 weeks.Additionally,another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline.In addition,the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line(IPEC-1)by overexpressed plasmids of dynamin related protein 1(Drp1)and mitofusin 2(Mfn2)which were determined by animal studies.Finally,a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage.Results Dietary DON caused jejunal damage and inflammation,reduced intestinal Drp1,mitofusin 1(Mfn1)and Mfn2,and induced cell apoptosis.DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2,and increased cell apoptosis.Moreover,DON challenge also resulted in cell damage and mitochondrial dysfunction,accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells.Subsequently,Mfn2,but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression,suppressed cell apoptosis,mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge.Finally,M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis,rescued mitochondrial dysfunction,barrier function impairment and cell damage.Conclusions Overall,our study demonstrates that DON exposure triggers Mfn2 protein dysregulation,which in turn mediates DON-induced intestinal epithelial damage in piglets.
基金Financial support from the National Natural Science Foundation of China(32502106)One health Interdisciplinary Research Project,Institute of One Health Science,Ningbo University(NBUOH202502)the Ningbo Top Talent Project(215-432094250).
文摘The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
基金the support from the National Key Research and Development Program of China(Nos.2024YFB4607700 and 2018YFA0703000)the Natural Science Foundation of Zhejiang Province(Nos.LDQ23E050001 and LQ24H260006)+2 种基金the National Natural Science Foundation of China(Nos.62303290,52305325,and 52405305)Shanghai Magnolia Talent Program Pujiang Project(No.23PJD036)The project was also supported by the State Key Laboratory of Materials Processing and Die&Mould Technology,Huazhong University of Science and Technology(No.P2025-002).
文摘The intestine is a key component of the barrier,absorption,and immune systems,contributing significantly to maintaining internal homeostasis and influencing disease progression.Its distinctive physiological functions arise from a complex interplay between its structure and microenvironment.Recent advancements in bioengineering technologies now enable the construction of in vitro intestinal models that faithfully recapitulate the organizational and functional characteristics of native tissue.This review examines the interface between in vitro models and native intestinal biology,offering insights into the replication of organ functions from a manufacturing perspective.We explore bioengineering strategies that enable the mapping of cross-scale structures and the creation of biomimetic environments essential for physiological performance.Furthermore,we discuss pragmatic optimization strategies for applying these models to both physiological and pathological studies,thereby enhancing their translational potential for drug development,disease modeling,and personalized medicine.In contrast to previous reviews,this work proposes an engineering-centered framework for linking structural fabrication strategies to functional performance across intestinal model types.
基金National Natural Science Foundation of China,Grant/Award Number:82172140。
文摘Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.
基金funded by the National Natural Science Foundation of China(32101915)Natural Science Foundation of Jiangxi Province(20224BAB205005)+1 种基金Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province(20232BCJ23090)Natural Science Foundation of Chongqing(CSTB2023NSCQMSX0497).
文摘Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.
基金supported by the National Key R&D Program of China(2022YFD1301800)grants from the National Natural Science Foundation of China(grant number 32502899)+1 种基金China Agriculture Research System of MOF and MARA(CARS-42-10)the Agricultural Science and Technology Innovation Program of CAAS(CAAS-ASTIP-2023-IFR-13)。
文摘Background Selective breeding for disease resistance is an effective strategy to control duck hepatitis A virus type 3(DHAV-3)in waterfowl.However,the mechanism underlying resistance remains poorly understood,particularly those associated with antioxidant defense,intestinal development and host-microbiota interactions.Method A total of 1001-day-old Pekin ducklings were used in this study with 50 DHAV-3 susceptible and resistant ducks,respectively.Samples were collected at 7 days post-hatching(D7),D21 and D42,10 birds per group.We compared DHAV-3 resistant and susceptible ducks during early development with respect to immune organ indices,antioxidant capacity,intestinal morphology,barrier-related gene expression and cecal microbiota.Result Resistant ducks exhibited higher spleen indices and stronger antioxidant capacity,characterized by increased superoxide dismutase,reduced glutathione,and total antioxidant capacity,along with lower malondialdehyde levels at D7 and D21.In contrast,susceptible ducks showed compensatory thymus hypertrophy and delayed development of antioxidant defense and intestinal maturation.Ileal morphology revealed greater villus height and width with more regular arrangement in resistant ducks at D7,whereas these differences diminished at D21 and D42.Gene expression analysis demonstrated higher early expression of the tight junction proteins CLDN1 and CLDN3 in resistant ducks,while susceptible ducks displayed elevated MUC2 and OCLN,suggesting stress induced compensatory responses.Cecal microbiota analysis revealed distinct colonization patterns in early development.Resistant ducks were enriched with Firmicutes and beneficial genera such as Enterococcus and Lactobacillus,whereas susceptible ducks harbored higher abundances of Bacteroidota and potentially opportunistic taxa.Microbial diversity increased with age in both groups,but resistant ducks displayed more orderly succession and enrichment of SCFA producing genera,including Subdoligranulum and Phascolarctobacterium,which positively correlated with plasma antioxidant indices.Conclusion DHAV-3 resistant ducks exhibit early advantages in antioxidant defense,intestinal barrier development and colonization by beneficial microbiota,which collectively contribute to enhanced disease resistance.These findings highlight the synergistic roles of host physiology and gut microbiota in shaping resistance.In the future,integrating genomic selection with microbiota modulation and antioxidant interventions may accelerate the breeding of highly resistant duck lines and provide scientific evidence and practical strategies for controlling duck viral hepatitis.
基金supported by the National Natural Science Foundation of China to L.H.(32470754 and 32070750)to X.M.(32170824 and 32322027)HRHl program of Westlake Laboratory of Life Sciences and Biomedicine to X.M.(1011103360222B1).
文摘Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.
