Chemotherapy-induced diarrhea(CID)is a major concern for cancer patients and is associated with significant morbidity and mortality.Currently,the clinical management of CID is limited.The utilization of antidiarrheal ...Chemotherapy-induced diarrhea(CID)is a major concern for cancer patients and is associated with significant morbidity and mortality.Currently,the clinical management of CID is limited.The utilization of antidiarrheal medications,such as loperamide and octreotide,is relatively limited because of their unsatisfactory efficacy and adverse effects.In recent years,traditional Chinese medicine(TCM)has attracted great interest because of its beneficial effect in treating CID,which has multitarget and low-toxicity therapeutic characteristics.TCM exhibits remarkable therapeutic potential in the prevention and treatment of CID.It can alleviate and treat CID by regulating chemical drug metabolism,improving the integrity of the intestinal barrier,stimulating proliferation while suppressing the apoptosis of intestinal epithelial cells,ameliorating oxidative stress and inflammation and regulating bile acids and aquaporins.However,large-scale,randomized,double-blind clinical trials of TCM for the treatment of CID are lacking,and most preclinical experiments have not been translated to clinical trials.Accordingly,this review highlights the clinical efficacy and molecular mechanisms of TCM against CID via PubMed,Web of Science and China National Knowledge Infrastructure and proposes that future research on TCM against CID should focus on strengthening the connection from bench to bed,which may help to comprehensively evaluate the therapeutic potential of TCM against CID.展开更多
Chronic diarrhea remains a frequent and debilitating complication among individuals living with HIV,particularly in the context of advanced immunosuppression.Its multifactorial nature often complicates both diagnosis ...Chronic diarrhea remains a frequent and debilitating complication among individuals living with HIV,particularly in the context of advanced immunosuppression.Its multifactorial nature often complicates both diagnosis and treatment.We present insights from our recent study investigating gut microbial alterations using 16S rRNA sequencing in HIV-positive patients with diarrheal syndrome of unclear etiology.展开更多
Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biologic...Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biological functions as nutritional interventions.Despite the interest in organic acids and monoglycerides,few studies have examined the effects of the combination of these acid-based additives in weaned pigs under disease challenge conditions.Therefore,this study aimed to investigate the effects of dietary supplementation with blend of organic acids and/or medium-chain fatty acid monoglycerides on intestinal health and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC)F18 at 4-week of age.Results Dietary supplementation of organic acids,monoglycerides,or both organic acids and monoglycerides(combination)reduced(P<0.05)the diarrhea frequency of ETEC F18-infected pigs throughout the experimental period(d−7 to 21 post-inoculation).This is consistent with the reduced(P<0.05)proportion ofβ-hemolytic coliforms in feces observed for the organic acid and combination treatments on d 10 post-inoculation.Supplementation of organic acids,monoglycerides,or combination also reduced(P<0.05)bacterial translocation in mesenteric lymph nodes on d 21 post-inoculation.Pigs fed with monoglycerides or combination had lower(P<0.05)white blood cells on d 5 post-inoculation,and pigs fed the combination also had lower(P<0.05)lymphocytes than pigs in control group.Monoglyceride supplementation increased(P<0.05)white blood cells and neutrophils compared with control group on d 14 post-inoculation.However,supplementation with organic acid blend,monoglyceride blend,or combination did not affect growth performance in this experiment.Conclusions Supplementation with monoglycerides or organic acids alone or in combination improves the detrimental effects of ETEC F18 infection in weaned pigs,as indicated by reduced diarrhea,fecal shedding ofβ-hemolytic coliforms,and bacterial translocation,and thus enhancing disease resistance.Monoglycerides reduced the inflammatory response during peak infection,but their immunomodulatory and possible synergistic effects with organic acids need to be further investigated.展开更多
Background:The forest musk deer,a rare fauna species found in China,is famous for its musk secretion which is used in selected Traditional Chinese medicines.However,over-hunting has led to musk deer becoming an endang...Background:The forest musk deer,a rare fauna species found in China,is famous for its musk secretion which is used in selected Traditional Chinese medicines.However,over-hunting has led to musk deer becoming an endangered species,and their survival is also greatly challenged by various high incidence and high mortality respiratory and intestinal diseases such as septic pneumonia and enteritis.Accumulating evidence has demonstrated that Akkermannia muciniphila(AKK)is a promising probiotic,and we wondered whether AKK could be used as a food additive in animal breeding pro-grammes to help prevent intestinal diseases.Methods:We isolated one AKK strain from musk deer feces(AKK-D)using an im-proved enrichment medium combined with real-time PCR.After confirmation by 16S rRNA gene sequencing,a series of in vitro tests was conducted to evaluate the probiotic effects of AKK-D by assessing its reproductive capability,simulated gas-trointestinal fluid tolerance,acid and bile salt resistance,self-aggregation ability,hy-drophobicity,antibiotic sensitivity,hemolysis,harmful metabolite production,biofilm formation ability,and bacterial adhesion to gastrointestinal mucosa.Results:The AKK-D strain has a probiotic function similar to that of the standard strain in humans(AKK-H).An in vivo study found that AKK-D significantly amelio-rated symptoms in the enterotoxigenic Escherichia coli(ETEC)-induced murine diar-rhea model.AKK-D improved organ damage,inhibited inflammatory responses,and improved intestinal barrier permeability.Additionally,AKK-D promoted the reconsti-tution and maintenance of the homeostasis of gut microflora,as indicated by the fact that AKK-D-treated mice showed a decrease in Bacteroidetes and an increase in the proportion of other beneficial bacteria like Muribaculaceae,Muribaculum,and unclas-sified f_Lachnospiaceae compared with the diarrhea model mice.Conclusion:Taken together,our data show that this novel AKK-D strain might be a potential probiotic for use in musk deer breeding,although further extensive system-atic research is still needed.展开更多
Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face in...Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.展开更多
[Objectives]To explore the pharmacodynamic effect of the Castanopsis sclerophylla(Lindl)Schottk fruit on diarrhea model mice.[Methods]The anti-diarrheal efficacy of the C.sclerophylla fruit was evaluated using a casto...[Objectives]To explore the pharmacodynamic effect of the Castanopsis sclerophylla(Lindl)Schottk fruit on diarrhea model mice.[Methods]The anti-diarrheal efficacy of the C.sclerophylla fruit was evaluated using a castor oil-induced acute diarrhea model in mice and the small intestinal charcoal propulsion test,with assessment of onset time of diarrhea,frequency of loose stools,and small intestinal propulsion rate.[Results]Compared with the model group,the C.sclerophylla frui-treated group demonstrated significantly delayed onset of diarrhea,reduced frequency of loose stools,and decreased small intestinal charcoal propulsion rate in a dose-dependent manner,with the high-dose group achieving efficacy comparable to the loperamide-treated group.[Conclusions]The C.sclerophylla fruit has certain anti-diarrhea effect,and its anti-diarrhea mechanism may be related to the inhibition of small intestinal peristalsis.展开更多
Background The composition and relative abundances of intestinal microbiota are closely related to animal growth,development and health.This study provides a comprehensive analysis of the spatial distribution and temp...Background The composition and relative abundances of intestinal microbiota are closely related to animal growth,development and health.This study provides a comprehensive analysis of the spatial distribution and temporal dynamics of intestinal fungi in pigs,with a focus on fungal alterations associated with diarrhea.Methods Intestinal digesta from duodenum,jejunum,ileum,cecum,colon and feces of 8 finishing pigs(180 days old)were collected.Fecal samples were also collected from 18 pigs across different growth stages,including lactation(3 d),nursery(26 d,35 d,49 d),growing(120 d)and finishing(180 d).Additionally,feces were collected from 32 diarrheal and 32 healthy piglets at 28 days old.Fungal community profiling in these samples was performed using internal transcribed spacer(ITS)sequencing.Results A total of 9,224 amplicon sequence variants(ASVs)were detected in all of 220 samples.Intestinal fungal diversity exhibited clear biogeographic patterns,with significantly lower richness and Shannon index in the ileum(P<0.05)and significantly higher richness in the large intestine and feces(P<0.05).The fungal community structure also varied significantly across intestinal segments,with Kazachstania dominating in the ileum and Geotrichum in the duodenum and jejunum.Across growth stages,fecal fungal diversity increased after weaning.PCoA results revealed that fungal structure exhibited significant temporal changes(R=0.7313,P=0.001),with the core fungal taxa dominated by Diutina catenulata,Aspergillus restrictus and Tahromyces munnarensis.In addition,by comparing the fungal community of piglets with and without diarrhea,the richness and Shannon index were significantly higher in the diarrheal piglets than those in healthy piglets(P<0.05)with Kazachstania,Diutina and Aspergillus enriched in diarrheal piglets and Geotrichum,Tahromyces and Piromyces in healthy piglets.Conclusions The intestinal fungal community in pigs shows distinct spatial variation,with greater diversity in the large intestine.Fungal composition shifts dynamically with age,particularly around the weaning transition.This study highlights specific fungal taxa associated with diarrhea caused by weaning stress,offering new insights into the interplay between gut fungi and pig health.展开更多
Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glut...Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.展开更多
This review examines the distinct mechanisms of Tuina massage and topical herbal medicine in pediatric diarrhea management,focusing on their independent regulation of gastrointestinal metabolism and barrier function.T...This review examines the distinct mechanisms of Tuina massage and topical herbal medicine in pediatric diarrhea management,focusing on their independent regulation of gastrointestinal metabolism and barrier function.Tuina therapy primarily enhances gastrointestinal motility through the stimulation of targeted acupoints such as Tianshu(ST25)and Shenque(CV8),activating vagal efferent pathways to normalize motility hormones including motilin while suppressing pro-inflammatory cytokines such interleukin-6 and tumor necrosis factor-alpha.It further reinforces mucosal defense by inhibiting mast cell degranulation and augmenting microcirculation via nitric oxide-mediated vasodilation.Herbal medicine containing bioactive compounds from Atractylodes macrocephala and Poria cocos directly restores intestinal barrier integrity by upregulating tight junction proteins occludin and zonula occludens-1,inhibiting epithelial apoptosis,and stimulating MUC2 production.These formulations additionally reprogram enterocyte metabolism by reactivating mitochondrial tricarboxylic acid cycle flux and modulating short-chain fatty acid profiles,with the independent prebiotic effects enhancing commensal butyrate production.Tuina primarily modulates neuroimmune pathways and motility,and herbal medicine directly targets epithelial repair and metabolism.These therapeutic pathways may address core diarrhea pathophysiology,providing holistic complementary therapies.Standardized protocols and interdisciplinary research are urgently needed for clinical translation.展开更多
BACKGROUND Collagenous sprue is a serious intestinal malabsorption disorder characterized by dull and flattened intestinal villi with subepithelial collagen deposition.At present,fewer than 100 cases have been reporte...BACKGROUND Collagenous sprue is a serious intestinal malabsorption disorder characterized by dull and flattened intestinal villi with subepithelial collagen deposition.At present,fewer than 100 cases have been reported in the literature.Owing to the rarity of this disease,clinicians and pathologists have insufficient understanding of it.CASE SUMMARY The authors present a case of a 34-year-old female patient who presented with severe watery diarrhea with significant weight loss.She also experienced blurred binocular vision.The intestinal lesions were located mainly in the small intestine,which presented flat and dull intestinal villi with subepithelial collagen deposition.Masson staining was positive.Glucocorticoids were effective for this patient,but there seemed to be glucocorticoid dependence.CONCLUSION Collagenous stomatitis diarrhea is a rare intestinal malabsorption disease that needs to be diagnosed in combination with special clinical manifestations and unique histological features.展开更多
Objective:To evaluate the anti-shigellosis activity of the hydroethanol extract of Diospyros gilletii(D.gilletii)stem bark in Shigella flexneri(S.flexneri)-induced diarrheal mice.Methods:The hydroethanolic extract was...Objective:To evaluate the anti-shigellosis activity of the hydroethanol extract of Diospyros gilletii(D.gilletii)stem bark in Shigella flexneri(S.flexneri)-induced diarrheal mice.Methods:The hydroethanolic extract was obtained by maceration of D.gilletii stem bark in 70%hydroethanol(water꞉ethanol;30꞉70,v/v)solution.Then,mice pretreated with cyclophosphamide for immunosuppression were administered orally with an inoculum containing S.flexneri,and subsequently treated with 100,200,and 400 mg/kg of the hydroethanol extracts for 10 days.The bacterial colonies were enumerated and hematological and biochemical parameters were determined.Serum pro-inflammatory mediators including IL-1β,IL-18,and TNF-α,and nitric oxide levels were quantified by ELISA.Histological analyses of the kidney,liver,and colon were also conducted.Results:Treatment with 200 and 400 mg/kg of the hydroethanolic extracts markedly inhibited the growth of S.flexneri.Moreover,treatment with D.gilletii extract downregulated the levels of IL-1β,IL-18,and TNF-α,and restored hematological and biochemical parameters as well as histological architecture of the colon,liver,and kidneys.Additionally,the oral administration of 2000 mg/kg D.gilletii extract did not induce any sign of toxicity,with a median lethal dose greater than 2000 mg/kg.Conclusions:D.gilletii extract demonstrates the anti-shigellosis effects in S.flexneri-induced diarrheal mice,supporting the traditional use of this plant in treating diarrhea.展开更多
Tacrolimus (TAC) is increasingly used for immunosuppression in organ transplantation,dermatomyositis/polymyositis,and myasthenia gravis(MG) patients.^([1]) TAC has a narrow therapeutic window with overexposure leading...Tacrolimus (TAC) is increasingly used for immunosuppression in organ transplantation,dermatomyositis/polymyositis,and myasthenia gravis(MG) patients.^([1]) TAC has a narrow therapeutic window with overexposure leading to acute and chronic forms of adverse reactions (ADRs).After oral administration,TAC is predominantly absorbed in the duodenum and jejunum and has highly variable pharmacokinetics,particularly when diarrhea occurs.^([2,3]) Few data has been published on TAC overexposure following mild diarrhea.Mild diarrhea is relatively common and often unreported,which can easily be overlooked by physicians,especially in the emergency department.Here,we report the occurrence of serious ADRs to TAC after mild diarrhea in a MG patient with community-acquired pneumonia(CAP),including nephrotoxicity,metabolic abnormalities and severe immunosuppression.展开更多
The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porci...The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear.In this study,we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus(PEDV)infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms.The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics.Among the altered intestinal bacteria,the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group.A strain of C.perfringens type A,named DQ21,was successfully isolated from the intestines of healthy piglets.The metabolites of swine C.perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2(IPEC-J2)cells,and PEDV infection and pathogenicity in suckling piglets.Palmitic acid(PA)was identified as one of those metabolites with metabolomic technology,and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets.PA also increased the neutralizing antibody titer in the immune sera of mice.Furthermore,PA mediated the palmitoylation of the PEDV S protein,which improved virion stability and membrane fusion,thereby enhancing viral infection.Overall,our study demonstrates a novel mechanism of PEDV infection,with implications for PEDV pathogenicity.展开更多
The cross-species infection of coronaviruses has resulted in several major epidemics since 2003.Porcine epidemic diarrhea virus(PEDV)is a devastating swine enteric coronavirus,which targets pigs as the only natural re...The cross-species infection of coronaviruses has resulted in several major epidemics since 2003.Porcine epidemic diarrhea virus(PEDV)is a devastating swine enteric coronavirus,which targets pigs as the only natural reservoir.In this study,the nucleic acid of PEDV was detected in rat fecal samples collected from pig farms.Further animal tests showed that PEDV can cause systemic infections in neonatal mice and rats via intracranial inoculation.The brain,lung,intestine and spleen were all targets for PEDV in rodents in contrast to the intestine being targeted in pigs.Morbidity and mortality vary via different infection routes.PEDV was also detectable in feces after infection,suggesting that the infected rodents were potential infectious sources.Moreover,the cerebral tropism of PEDV was verified in piglets via orally inoculation,which had not been identified before.In conclusion,our findings demonstrate that PEDV could cross the species barrier to infect mice and rats through different routes in experimental settings.Although it is highly devastating to piglets,PEDV changes the target organs and turns to be milder when meeting with new hosts.Based on these findings,more attention should be paid to the potential cross-species infection of PEDV.展开更多
Clostridium difficile infection(CDI)is a major global public health concern,accounting for 15%-25%of antibiotic-associated diarrhea,50%-75%of antibiotic-associated colitis,and nearly all cases of pseudomembranous coli...Clostridium difficile infection(CDI)is a major global public health concern,accounting for 15%-25%of antibiotic-associated diarrhea,50%-75%of antibiotic-associated colitis,and nearly all cases of pseudomembranous colitis.Over the past decade,CDI outbreaks have become increasingly prevalent in North America and Europe,with rising incidence and mortality rates.In 2019,the Centers for Disease Control and Prevention(CDC)in the United States classified CDI as a“critical”public health threat in their report on antibiotic resistance threats[1].CDI incidence varies widely across countries,healthcare settings,and age groups,with cumulative incidence rates ranging from 1.12 to 631.80 per 100,000 people annually[2].As the epidemiology of CDI continues to evolve and our understanding of the disease advances,reassessing its burden remains essential.The Global Burden of Disease,Injury,and Risk Factors Study(GBD 2021)database offers new insights into this issue.展开更多
Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)signi...Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)significantly inhibits PEDV replication in a dose-dependent manner in vitro,with negligible cytotoxicity.Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle.Using a CoV-RdRp-Gluc reporter system,we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase(RdRp),and determined a low IC50 value of 0.1364μM.Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV.Transcriptome analysis of Vero E6 cells,with and without CFZ treatment,revealed a significant change in transcriptional activity at 8 h postinfection(hpi).Moreover,the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ in vitro.Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.展开更多
Swine acute diarrhea syndrome coronavirus(SADS-CoV),an emerging bat-origin Alphacoronavirus with demonstrated zoonotic potential,poses a significant threat to swine health and has considerable economic implications.Cu...Swine acute diarrhea syndrome coronavirus(SADS-CoV),an emerging bat-origin Alphacoronavirus with demonstrated zoonotic potential,poses a significant threat to swine health and has considerable economic implications.Currently,no licensed vaccines are available.We constructed a replication-deficient human adenovirus type 5(Ad5)vectored vaccine candidate,rAd5-SADS-S,which ex-presses the SADS-CoV spike(S)glycoprotein.The rAd5-SADS-S vaccine elicited robust SADS-CoV-specific humoral immunity and potent cellular responses in both mice and pigs.Notably,rAd5-SADS-S conferred passive protection to neonatal mice against lethal SADS-CoV challenge.These findings establish a preclinical foundation for the development of SADS-CoV vaccines.展开更多
Porcine epidemic diarrhea(PED),caused by porcine epidemic diarrhea virus(PEDV),can induce 80–100%mortality in newborn piglets;therefore,specific and rapid detection methods are important for the prevention of this vi...Porcine epidemic diarrhea(PED),caused by porcine epidemic diarrhea virus(PEDV),can induce 80–100%mortality in newborn piglets;therefore,specific and rapid detection methods are important for the prevention of this viral infection.In particular,methods for detecting neutralizing antibodies(nAbs)can be used to evaluate the immunization effect of PEDV vaccines.The spike protein of PEDV(PEDV-S)has been universally used as an antigen to develop immunoassays to detect nAbs.Nanobodies(Nbs)offer advantages such as ease of genetic engineering and low production costs,making them promising for diagnostic applications.In this study,PEDV-S was expressed via the baculovirus system and was used as an antigen to immunize Bactrian camels.A total of 10 Nbs against PEDV-S were first screened and expressed as fusion proteins with horseradish peroxidase(HRP)in HEK293T cells.A Nb-HRP fusion protein named PEDV-S-Nb13-HRP was subsequently selected and used as a probe for developing a competitive enzyme-linked immunosorbent assay(cELISA)to detect anti-PEDV nAbs.Optimization assays identified 80 ng/well of PEDV-S as the optimal coating antigen concentration.The optimal dilution of PEDV-S-Nb13-HRP was 1:200,and the optimal serum dilution was 1:10.The cutoff value of cELISA was determined as 28.1%,demonstrating high specificity,repeatability,stability,and good agreement rates with two commercial ELISA kits(93.6%)and a serum neutralization test(96.34%).Additionally,the results of the detection of IgA antibodies in oral and milk samples from sows were in good agreement with those of the IDEXX PEDV IgA kit.These results demonstrate that the cELISA is a reliable and cost-effective method for detecting anti-PEDV nAbs.展开更多
In this study,the effects of compound Chinese herbal medicine on growth performance and occurrence of diarrhea in weaned piglets were investigated.A compound Chinese herbal medicine that consisted of Astragalus membra...In this study,the effects of compound Chinese herbal medicine on growth performance and occurrence of diarrhea in weaned piglets were investigated.A compound Chinese herbal medicine that consisted of Astragalus membranaceus,Codonopsis pilosula,Epimedium sagittatum,massa medicata fermentata,Atractylodes macrocephala,malt,Glycyrrhiza uralensis,Angelica sinensis and Crataegus pinnatifida,was crushed and then passed through a 500-mesh sieve.The obtained powder was added to the basal diet of weaned piglets.A total of 100 healthy crossbred weaned piglets,aging 26±2 days,were selected.They were randomly divided into 5groups（20 piglets/group） in according to principles of similar parity（3-5）,similar body weight and half male and half female.The piglets in the control group were fed with basal diet.For the piglets in the I,II and III groups,0.4%,0.7% and 1.0%of Chinese herbal medicine additive were added to the basal diets,respectively.The basal diet of piglets in the IV group was added with 30 mg/kg of oxytetracycline.The results showed the incidences of diarrhea in I,II and III groups were4.85%,5.14% and 5.63% lower than that of control groups（P〈0.05）.There was no significant difference in incidence of diarrhea between the control and the IV groups.展开更多
Objective To observe the clinical effect of warm needling in the treatment of diarrhea irritable bowel syndrome. Methods One hundred and twenty patients with diarrhea irritable bowel syndrome were randomly divided int...Objective To observe the clinical effect of warm needling in the treatment of diarrhea irritable bowel syndrome. Methods One hundred and twenty patients with diarrhea irritable bowel syndrome were randomly divided into a warm needling group and a western medicine group by random digit table method, 60 patients were included in each group. Tiānshū （天枢 ST 25）, Zúsānl （足三里 ST 36） and Sānyīnjiāo （三阴交 SP 6） were selected as the main acupoints for the warm needling group, the needles were retained for 30 min, once a day, an interval of 1 day was set up after treatment for six days, and the treatment were carried out for continuous four weeks. The patients in the western medicine group were orally administered with 2 mg loperamide hydrochloride capsules, 3 times a day, and the treatment were carried out for continuous four weeks. The treatment effects were compared between the two groups, and the recurrence rates were counted after for six-month followup. Results The total effective rate in the warm needling group was 86.7% （52/60） and the total effective rate in the western medicine group was 71.7% （43/60）, and the difference between the two groups was statistically significant （P0.05）; after six-month follow-up, the recurrence rate in the warm needling group was 21.4% （6/28）, while the recurrence rate in the western medicine group was 54.5% （12/22）, and the difference between the two groups was statistically significant （P0.05）. Conclusion The warm needling therapy shows relatively satisfactory treatment effects in the treatment of diarrhea irritable bowel syndrome and the recurrence rate is relatively low.展开更多
基金supported by the Innovative Team Project of Ordinary Universities in Guangdong Province(No.2022KCXTD016).
文摘Chemotherapy-induced diarrhea(CID)is a major concern for cancer patients and is associated with significant morbidity and mortality.Currently,the clinical management of CID is limited.The utilization of antidiarrheal medications,such as loperamide and octreotide,is relatively limited because of their unsatisfactory efficacy and adverse effects.In recent years,traditional Chinese medicine(TCM)has attracted great interest because of its beneficial effect in treating CID,which has multitarget and low-toxicity therapeutic characteristics.TCM exhibits remarkable therapeutic potential in the prevention and treatment of CID.It can alleviate and treat CID by regulating chemical drug metabolism,improving the integrity of the intestinal barrier,stimulating proliferation while suppressing the apoptosis of intestinal epithelial cells,ameliorating oxidative stress and inflammation and regulating bile acids and aquaporins.However,large-scale,randomized,double-blind clinical trials of TCM for the treatment of CID are lacking,and most preclinical experiments have not been translated to clinical trials.Accordingly,this review highlights the clinical efficacy and molecular mechanisms of TCM against CID via PubMed,Web of Science and China National Knowledge Infrastructure and proposes that future research on TCM against CID should focus on strengthening the connection from bench to bed,which may help to comprehensively evaluate the therapeutic potential of TCM against CID.
文摘Chronic diarrhea remains a frequent and debilitating complication among individuals living with HIV,particularly in the context of advanced immunosuppression.Its multifactorial nature often complicates both diagnosis and treatment.We present insights from our recent study investigating gut microbial alterations using 16S rRNA sequencing in HIV-positive patients with diarrheal syndrome of unclear etiology.
基金supported by Animal Nutrition,Eastman Chemical Company,Kingsport,TN,USA.
文摘Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biological functions as nutritional interventions.Despite the interest in organic acids and monoglycerides,few studies have examined the effects of the combination of these acid-based additives in weaned pigs under disease challenge conditions.Therefore,this study aimed to investigate the effects of dietary supplementation with blend of organic acids and/or medium-chain fatty acid monoglycerides on intestinal health and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC)F18 at 4-week of age.Results Dietary supplementation of organic acids,monoglycerides,or both organic acids and monoglycerides(combination)reduced(P<0.05)the diarrhea frequency of ETEC F18-infected pigs throughout the experimental period(d−7 to 21 post-inoculation).This is consistent with the reduced(P<0.05)proportion ofβ-hemolytic coliforms in feces observed for the organic acid and combination treatments on d 10 post-inoculation.Supplementation of organic acids,monoglycerides,or combination also reduced(P<0.05)bacterial translocation in mesenteric lymph nodes on d 21 post-inoculation.Pigs fed with monoglycerides or combination had lower(P<0.05)white blood cells on d 5 post-inoculation,and pigs fed the combination also had lower(P<0.05)lymphocytes than pigs in control group.Monoglyceride supplementation increased(P<0.05)white blood cells and neutrophils compared with control group on d 14 post-inoculation.However,supplementation with organic acid blend,monoglyceride blend,or combination did not affect growth performance in this experiment.Conclusions Supplementation with monoglycerides or organic acids alone or in combination improves the detrimental effects of ETEC F18 infection in weaned pigs,as indicated by reduced diarrhea,fecal shedding ofβ-hemolytic coliforms,and bacterial translocation,and thus enhancing disease resistance.Monoglycerides reduced the inflammatory response during peak infection,but their immunomodulatory and possible synergistic effects with organic acids need to be further investigated.
基金This research was funded by Shaanxi Administration of Traditional Chinese Medicine Projects(2021-QYZL-01,2021-QYPT-001)Key R&D Project in Shaanxi Province(2023-YBSF-463)+1 种基金the Foundation of Science and Technology in Shaanxi Province(2020TD-050)the Fundamental Research Funds for the Central Universities(GK202205010).
文摘Background:The forest musk deer,a rare fauna species found in China,is famous for its musk secretion which is used in selected Traditional Chinese medicines.However,over-hunting has led to musk deer becoming an endangered species,and their survival is also greatly challenged by various high incidence and high mortality respiratory and intestinal diseases such as septic pneumonia and enteritis.Accumulating evidence has demonstrated that Akkermannia muciniphila(AKK)is a promising probiotic,and we wondered whether AKK could be used as a food additive in animal breeding pro-grammes to help prevent intestinal diseases.Methods:We isolated one AKK strain from musk deer feces(AKK-D)using an im-proved enrichment medium combined with real-time PCR.After confirmation by 16S rRNA gene sequencing,a series of in vitro tests was conducted to evaluate the probiotic effects of AKK-D by assessing its reproductive capability,simulated gas-trointestinal fluid tolerance,acid and bile salt resistance,self-aggregation ability,hy-drophobicity,antibiotic sensitivity,hemolysis,harmful metabolite production,biofilm formation ability,and bacterial adhesion to gastrointestinal mucosa.Results:The AKK-D strain has a probiotic function similar to that of the standard strain in humans(AKK-H).An in vivo study found that AKK-D significantly amelio-rated symptoms in the enterotoxigenic Escherichia coli(ETEC)-induced murine diar-rhea model.AKK-D improved organ damage,inhibited inflammatory responses,and improved intestinal barrier permeability.Additionally,AKK-D promoted the reconsti-tution and maintenance of the homeostasis of gut microflora,as indicated by the fact that AKK-D-treated mice showed a decrease in Bacteroidetes and an increase in the proportion of other beneficial bacteria like Muribaculaceae,Muribaculum,and unclas-sified f_Lachnospiaceae compared with the diarrhea model mice.Conclusion:Taken together,our data show that this novel AKK-D strain might be a potential probiotic for use in musk deer breeding,although further extensive system-atic research is still needed.
基金financially supported by the Green Development and Demonstration Programme(GUDP)(case number 34009-19-1585)。
文摘Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.
基金Supported by Zhongshan City Medical Research Project(2023A020437).
文摘[Objectives]To explore the pharmacodynamic effect of the Castanopsis sclerophylla(Lindl)Schottk fruit on diarrhea model mice.[Methods]The anti-diarrheal efficacy of the C.sclerophylla fruit was evaluated using a castor oil-induced acute diarrhea model in mice and the small intestinal charcoal propulsion test,with assessment of onset time of diarrhea,frequency of loose stools,and small intestinal propulsion rate.[Results]Compared with the model group,the C.sclerophylla frui-treated group demonstrated significantly delayed onset of diarrhea,reduced frequency of loose stools,and decreased small intestinal charcoal propulsion rate in a dose-dependent manner,with the high-dose group achieving efficacy comparable to the loperamide-treated group.[Conclusions]The C.sclerophylla fruit has certain anti-diarrhea effect,and its anti-diarrhea mechanism may be related to the inhibition of small intestinal peristalsis.
基金funded by the National Natural Science Foundation of China(32372907)State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products(No.10417000023 CE0601G/004/002)。
文摘Background The composition and relative abundances of intestinal microbiota are closely related to animal growth,development and health.This study provides a comprehensive analysis of the spatial distribution and temporal dynamics of intestinal fungi in pigs,with a focus on fungal alterations associated with diarrhea.Methods Intestinal digesta from duodenum,jejunum,ileum,cecum,colon and feces of 8 finishing pigs(180 days old)were collected.Fecal samples were also collected from 18 pigs across different growth stages,including lactation(3 d),nursery(26 d,35 d,49 d),growing(120 d)and finishing(180 d).Additionally,feces were collected from 32 diarrheal and 32 healthy piglets at 28 days old.Fungal community profiling in these samples was performed using internal transcribed spacer(ITS)sequencing.Results A total of 9,224 amplicon sequence variants(ASVs)were detected in all of 220 samples.Intestinal fungal diversity exhibited clear biogeographic patterns,with significantly lower richness and Shannon index in the ileum(P<0.05)and significantly higher richness in the large intestine and feces(P<0.05).The fungal community structure also varied significantly across intestinal segments,with Kazachstania dominating in the ileum and Geotrichum in the duodenum and jejunum.Across growth stages,fecal fungal diversity increased after weaning.PCoA results revealed that fungal structure exhibited significant temporal changes(R=0.7313,P=0.001),with the core fungal taxa dominated by Diutina catenulata,Aspergillus restrictus and Tahromyces munnarensis.In addition,by comparing the fungal community of piglets with and without diarrhea,the richness and Shannon index were significantly higher in the diarrheal piglets than those in healthy piglets(P<0.05)with Kazachstania,Diutina and Aspergillus enriched in diarrheal piglets and Geotrichum,Tahromyces and Piromyces in healthy piglets.Conclusions The intestinal fungal community in pigs shows distinct spatial variation,with greater diversity in the large intestine.Fungal composition shifts dynamically with age,particularly around the weaning transition.This study highlights specific fungal taxa associated with diarrhea caused by weaning stress,offering new insights into the interplay between gut fungi and pig health.
基金Funding support was from the Novo Nordisk Foundation with the project's grant number NNFSA210073688.
文摘Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.
基金Supported by the Key Research and Development Program of Zhejiang Province,No.2024C03211the Traditional Chinese Medicine Science and Technology Plan Project of Zhejiang Province,No.2023ZL498.
文摘This review examines the distinct mechanisms of Tuina massage and topical herbal medicine in pediatric diarrhea management,focusing on their independent regulation of gastrointestinal metabolism and barrier function.Tuina therapy primarily enhances gastrointestinal motility through the stimulation of targeted acupoints such as Tianshu(ST25)and Shenque(CV8),activating vagal efferent pathways to normalize motility hormones including motilin while suppressing pro-inflammatory cytokines such interleukin-6 and tumor necrosis factor-alpha.It further reinforces mucosal defense by inhibiting mast cell degranulation and augmenting microcirculation via nitric oxide-mediated vasodilation.Herbal medicine containing bioactive compounds from Atractylodes macrocephala and Poria cocos directly restores intestinal barrier integrity by upregulating tight junction proteins occludin and zonula occludens-1,inhibiting epithelial apoptosis,and stimulating MUC2 production.These formulations additionally reprogram enterocyte metabolism by reactivating mitochondrial tricarboxylic acid cycle flux and modulating short-chain fatty acid profiles,with the independent prebiotic effects enhancing commensal butyrate production.Tuina primarily modulates neuroimmune pathways and motility,and herbal medicine directly targets epithelial repair and metabolism.These therapeutic pathways may address core diarrhea pathophysiology,providing holistic complementary therapies.Standardized protocols and interdisciplinary research are urgently needed for clinical translation.
文摘BACKGROUND Collagenous sprue is a serious intestinal malabsorption disorder characterized by dull and flattened intestinal villi with subepithelial collagen deposition.At present,fewer than 100 cases have been reported in the literature.Owing to the rarity of this disease,clinicians and pathologists have insufficient understanding of it.CASE SUMMARY The authors present a case of a 34-year-old female patient who presented with severe watery diarrhea with significant weight loss.She also experienced blurred binocular vision.The intestinal lesions were located mainly in the small intestine,which presented flat and dull intestinal villi with subepithelial collagen deposition.Masson staining was positive.Glucocorticoids were effective for this patient,but there seemed to be glucocorticoid dependence.CONCLUSION Collagenous stomatitis diarrhea is a rare intestinal malabsorption disease that needs to be diagnosed in combination with special clinical manifestations and unique histological features.
基金funded by the Yaounde-Bielefeld Bilateral Graduate School for Natural Products with Anti-parasite and Antibacterial Activity(YaBiNaPA)(grant number:57316173).
文摘Objective:To evaluate the anti-shigellosis activity of the hydroethanol extract of Diospyros gilletii(D.gilletii)stem bark in Shigella flexneri(S.flexneri)-induced diarrheal mice.Methods:The hydroethanolic extract was obtained by maceration of D.gilletii stem bark in 70%hydroethanol(water꞉ethanol;30꞉70,v/v)solution.Then,mice pretreated with cyclophosphamide for immunosuppression were administered orally with an inoculum containing S.flexneri,and subsequently treated with 100,200,and 400 mg/kg of the hydroethanol extracts for 10 days.The bacterial colonies were enumerated and hematological and biochemical parameters were determined.Serum pro-inflammatory mediators including IL-1β,IL-18,and TNF-α,and nitric oxide levels were quantified by ELISA.Histological analyses of the kidney,liver,and colon were also conducted.Results:Treatment with 200 and 400 mg/kg of the hydroethanolic extracts markedly inhibited the growth of S.flexneri.Moreover,treatment with D.gilletii extract downregulated the levels of IL-1β,IL-18,and TNF-α,and restored hematological and biochemical parameters as well as histological architecture of the colon,liver,and kidneys.Additionally,the oral administration of 2000 mg/kg D.gilletii extract did not induce any sign of toxicity,with a median lethal dose greater than 2000 mg/kg.Conclusions:D.gilletii extract demonstrates the anti-shigellosis effects in S.flexneri-induced diarrheal mice,supporting the traditional use of this plant in treating diarrhea.
基金supported by the Clinical Research Foundation of Zhejiang Provincial Medical Association (2020ZYC-A113)。
文摘Tacrolimus (TAC) is increasingly used for immunosuppression in organ transplantation,dermatomyositis/polymyositis,and myasthenia gravis(MG) patients.^([1]) TAC has a narrow therapeutic window with overexposure leading to acute and chronic forms of adverse reactions (ADRs).After oral administration,TAC is predominantly absorbed in the duodenum and jejunum and has highly variable pharmacokinetics,particularly when diarrhea occurs.^([2,3]) Few data has been published on TAC overexposure following mild diarrhea.Mild diarrhea is relatively common and often unreported,which can easily be overlooked by physicians,especially in the emergency department.Here,we report the occurrence of serious ADRs to TAC after mild diarrhea in a MG patient with community-acquired pneumonia(CAP),including nephrotoxicity,metabolic abnormalities and severe immunosuppression.
基金supported by the National Natural Science Foundation of China(U23A20236)the Key Research and Development Program,Guidance Projects of Heilongjiang Province,China(GZ20220029)。
文摘The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear.In this study,we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus(PEDV)infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms.The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics.Among the altered intestinal bacteria,the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group.A strain of C.perfringens type A,named DQ21,was successfully isolated from the intestines of healthy piglets.The metabolites of swine C.perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2(IPEC-J2)cells,and PEDV infection and pathogenicity in suckling piglets.Palmitic acid(PA)was identified as one of those metabolites with metabolomic technology,and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets.PA also increased the neutralizing antibody titer in the immune sera of mice.Furthermore,PA mediated the palmitoylation of the PEDV S protein,which improved virion stability and membrane fusion,thereby enhancing viral infection.Overall,our study demonstrates a novel mechanism of PEDV infection,with implications for PEDV pathogenicity.
基金supported by the Basic Research Innovation Group Project of Gansu Province(No.25JRRA434)the National Natural Science Foundation of China(U22A20522).
文摘The cross-species infection of coronaviruses has resulted in several major epidemics since 2003.Porcine epidemic diarrhea virus(PEDV)is a devastating swine enteric coronavirus,which targets pigs as the only natural reservoir.In this study,the nucleic acid of PEDV was detected in rat fecal samples collected from pig farms.Further animal tests showed that PEDV can cause systemic infections in neonatal mice and rats via intracranial inoculation.The brain,lung,intestine and spleen were all targets for PEDV in rodents in contrast to the intestine being targeted in pigs.Morbidity and mortality vary via different infection routes.PEDV was also detectable in feces after infection,suggesting that the infected rodents were potential infectious sources.Moreover,the cerebral tropism of PEDV was verified in piglets via orally inoculation,which had not been identified before.In conclusion,our findings demonstrate that PEDV could cross the species barrier to infect mice and rats through different routes in experimental settings.Although it is highly devastating to piglets,PEDV changes the target organs and turns to be milder when meeting with new hosts.Based on these findings,more attention should be paid to the potential cross-species infection of PEDV.
基金supported by the Beijing Natural Science Foundation(No.L202008)the Chinese Center for Disease Control and Prevention Foundation(No.201833).
文摘Clostridium difficile infection(CDI)is a major global public health concern,accounting for 15%-25%of antibiotic-associated diarrhea,50%-75%of antibiotic-associated colitis,and nearly all cases of pseudomembranous colitis.Over the past decade,CDI outbreaks have become increasingly prevalent in North America and Europe,with rising incidence and mortality rates.In 2019,the Centers for Disease Control and Prevention(CDC)in the United States classified CDI as a“critical”public health threat in their report on antibiotic resistance threats[1].CDI incidence varies widely across countries,healthcare settings,and age groups,with cumulative incidence rates ranging from 1.12 to 631.80 per 100,000 people annually[2].As the epidemiology of CDI continues to evolve and our understanding of the disease advances,reassessing its burden remains essential.The Global Burden of Disease,Injury,and Risk Factors Study(GBD 2021)database offers new insights into this issue.
基金supported by a grant from the National Key Research and Development Plans of China(No.2021YFD1800401)to Zhe Wangthe National Natural Science Foundation of China(No.32070128)to Zhe Wang+5 种基金the Shanghai Biomedical Science and Technology Support Special Project(No.21S11900200)to Zhe Wangthe National Natural Science Foundation of China(No.31472211)to ZhiBiao Yangthe Natural Science Foundation of Shanghai(No.21ZR1433900)to Zhibiao Yangthe National Key Research and Development Program of China(No.2022YFD1800805)to Yanjun Zhouthe Pinduoduo-China Agricultural University Research Fund(PC2024A01003)to Xiangfeng Wangthe Biomedicine and Technology Supporting Project of the Shanghai Science and Technology Innovation Plan(Grant No.22S11902200,China)to Tao Sun.
文摘Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)significantly inhibits PEDV replication in a dose-dependent manner in vitro,with negligible cytotoxicity.Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle.Using a CoV-RdRp-Gluc reporter system,we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase(RdRp),and determined a low IC50 value of 0.1364μM.Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV.Transcriptome analysis of Vero E6 cells,with and without CFZ treatment,revealed a significant change in transcriptional activity at 8 h postinfection(hpi).Moreover,the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ in vitro.Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.
基金supported by grants from the National Natural Science Foundation of China(32473022)awarded to Q.W.the Major Science and Technology Project of Gansu Province(23ZDNA007)awarded to Q.W.+3 种基金the State Key Laboratory for Animal Disease Control and Prevention(SKLADCPKFKT202410)awarded to Y.Z.the Distinguished Young Scholars of Chinese Academy of Agricultural Sciences(CAAS)awarded to Q.WBasic Research Center,the Innovation Program of Chinese Academy of Agricultural Sciences(CAAS BRC-LPDC-2025-01)awarded to Q.Wthe Central Public-interest Scientific Institution Basal Research Fund(S2023002)awarded to Y.Z.
文摘Swine acute diarrhea syndrome coronavirus(SADS-CoV),an emerging bat-origin Alphacoronavirus with demonstrated zoonotic potential,poses a significant threat to swine health and has considerable economic implications.Currently,no licensed vaccines are available.We constructed a replication-deficient human adenovirus type 5(Ad5)vectored vaccine candidate,rAd5-SADS-S,which ex-presses the SADS-CoV spike(S)glycoprotein.The rAd5-SADS-S vaccine elicited robust SADS-CoV-specific humoral immunity and potent cellular responses in both mice and pigs.Notably,rAd5-SADS-S conferred passive protection to neonatal mice against lethal SADS-CoV challenge.These findings establish a preclinical foundation for the development of SADS-CoV vaccines.
基金funded by grants from the National Key R&D Program of China(2023YFD1800304)the National Natural Science Foundation of China to QZ(32273041)+1 种基金the Natural Science Foundation of Shaanxi Province of China(2022JC-12)the Central Public interest Scientific Institution Basal Research Fund,National Data Center of Animal Health.
文摘Porcine epidemic diarrhea(PED),caused by porcine epidemic diarrhea virus(PEDV),can induce 80–100%mortality in newborn piglets;therefore,specific and rapid detection methods are important for the prevention of this viral infection.In particular,methods for detecting neutralizing antibodies(nAbs)can be used to evaluate the immunization effect of PEDV vaccines.The spike protein of PEDV(PEDV-S)has been universally used as an antigen to develop immunoassays to detect nAbs.Nanobodies(Nbs)offer advantages such as ease of genetic engineering and low production costs,making them promising for diagnostic applications.In this study,PEDV-S was expressed via the baculovirus system and was used as an antigen to immunize Bactrian camels.A total of 10 Nbs against PEDV-S were first screened and expressed as fusion proteins with horseradish peroxidase(HRP)in HEK293T cells.A Nb-HRP fusion protein named PEDV-S-Nb13-HRP was subsequently selected and used as a probe for developing a competitive enzyme-linked immunosorbent assay(cELISA)to detect anti-PEDV nAbs.Optimization assays identified 80 ng/well of PEDV-S as the optimal coating antigen concentration.The optimal dilution of PEDV-S-Nb13-HRP was 1:200,and the optimal serum dilution was 1:10.The cutoff value of cELISA was determined as 28.1%,demonstrating high specificity,repeatability,stability,and good agreement rates with two commercial ELISA kits(93.6%)and a serum neutralization test(96.34%).Additionally,the results of the detection of IgA antibodies in oral and milk samples from sows were in good agreement with those of the IDEXX PEDV IgA kit.These results demonstrate that the cELISA is a reliable and cost-effective method for detecting anti-PEDV nAbs.
基金Supported by Natural Science Foundation of Fujian Provincial Department of Education(JA14406)~~
文摘In this study,the effects of compound Chinese herbal medicine on growth performance and occurrence of diarrhea in weaned piglets were investigated.A compound Chinese herbal medicine that consisted of Astragalus membranaceus,Codonopsis pilosula,Epimedium sagittatum,massa medicata fermentata,Atractylodes macrocephala,malt,Glycyrrhiza uralensis,Angelica sinensis and Crataegus pinnatifida,was crushed and then passed through a 500-mesh sieve.The obtained powder was added to the basal diet of weaned piglets.A total of 100 healthy crossbred weaned piglets,aging 26±2 days,were selected.They were randomly divided into 5groups（20 piglets/group） in according to principles of similar parity（3-5）,similar body weight and half male and half female.The piglets in the control group were fed with basal diet.For the piglets in the I,II and III groups,0.4%,0.7% and 1.0%of Chinese herbal medicine additive were added to the basal diets,respectively.The basal diet of piglets in the IV group was added with 30 mg/kg of oxytetracycline.The results showed the incidences of diarrhea in I,II and III groups were4.85%,5.14% and 5.63% lower than that of control groups（P〈0.05）.There was no significant difference in incidence of diarrhea between the control and the IV groups.
文摘Objective To observe the clinical effect of warm needling in the treatment of diarrhea irritable bowel syndrome. Methods One hundred and twenty patients with diarrhea irritable bowel syndrome were randomly divided into a warm needling group and a western medicine group by random digit table method, 60 patients were included in each group. Tiānshū （天枢 ST 25）, Zúsānl （足三里 ST 36） and Sānyīnjiāo （三阴交 SP 6） were selected as the main acupoints for the warm needling group, the needles were retained for 30 min, once a day, an interval of 1 day was set up after treatment for six days, and the treatment were carried out for continuous four weeks. The patients in the western medicine group were orally administered with 2 mg loperamide hydrochloride capsules, 3 times a day, and the treatment were carried out for continuous four weeks. The treatment effects were compared between the two groups, and the recurrence rates were counted after for six-month followup. Results The total effective rate in the warm needling group was 86.7% （52/60） and the total effective rate in the western medicine group was 71.7% （43/60）, and the difference between the two groups was statistically significant （P0.05）; after six-month follow-up, the recurrence rate in the warm needling group was 21.4% （6/28）, while the recurrence rate in the western medicine group was 54.5% （12/22）, and the difference between the two groups was statistically significant （P0.05）. Conclusion The warm needling therapy shows relatively satisfactory treatment effects in the treatment of diarrhea irritable bowel syndrome and the recurrence rate is relatively low.
