Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold an...Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.展开更多
Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal he...Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal health-promot-ing of the consumer.However,information is lacking regarding the application prospect of LAB fermented milk in the animal industry.This study investigated the effects of lactic acid bacteria-fermented formula milk(LFM)on the growth performance,intestinal immunity,microbiota composition,and transcriptomic responses in weaned piglets.A total of 24 male weaned piglets were randomly divided into the control(CON)and LFM groups.Each group consisted of 6 replicates(cages)with 2 piglets per cage.Each piglet in the LFM group were supplemented with 80 mL LFM three times a day,while the CON group was treated with the same amount of drinking water.Results:LFM significantly increased the average daily gain of piglets over the entire 14 d(P<0.01)and the average daily feed intake from 7 to 14 d(P<0.05).Compared to the CON group,ileal goblet cell count,villus-crypt ratio,sIgA,and lactate concentrations in the LFM group were significantly increased(P<0.05).Transcriptomic analysis of ileal mucosa identified 487 differentially expressed genes(DEGs)between two groups.Especially,DEGs involved in the intestinal immune network for IgA production pathways,such as polymeric immunoglobulin receptor(PIGR),were significantly up-regulated(P<0.01)by LFM supplementation.Moreover,trefoil factor 2(TFF2)in the LFM group,one of the DEGs involved in the secretory function of goblet cells,was also significantly up-regulated(P<0.01).Sequenc-ing of the 16S rRNA gene of microbiota demonstrated that LFM led to selective enrichment of lactate-producing and short-chain fatty acid(SCFA)-producing bacteria in the ileum,such as an increase in the relative abundance of Entero-coccus(P=0.09)and Acetitomaculum(P<0.05).Conclusions:LFM can improve intestinal health and immune tolerance,thus enhancing the growth performance of weaned piglets.The changes in microbiota and metabolites induced by LFM might mediate the regulation of the secretory function of goblet cells.展开更多
The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by ...The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.展开更多
The 778th Xiangshan Science Conference,themed“Regional Immunity in the Lung and Respiratory Tract:Challenges and Opportunities”,convened in Beijing on April 8–9,2025.Co-chaired by four leading scientists-ProfessorG...The 778th Xiangshan Science Conference,themed“Regional Immunity in the Lung and Respiratory Tract:Challenges and Opportunities”,convened in Beijing on April 8–9,2025.Co-chaired by four leading scientists-ProfessorGeorge FuGao(Institute of Microbiology,Chinese Academy of Sciences),Professor Chen Dong(Westlake University School of Medicine),Professor Zhigang Tian(University of Science and Technology of China).展开更多
Objective To explore the role of curcumin(Cur)in improving IgA nephropathy(IgAN)and its related mechanisms.Methods Fifty 7-month-old miR-23b knockout(miR-23b^(-/-))mice weighing(25±5)g were used to establish an I...Objective To explore the role of curcumin(Cur)in improving IgA nephropathy(IgAN)and its related mechanisms.Methods Fifty 7-month-old miR-23b knockout(miR-23b^(-/-))mice weighing(25±5)g were used to establish an IgAN disease model,and were randomly divided into IgAN group,IgAN+Cur(150 mg/kg)group and IgAN+Cur(300 mg/kg)group using simple randomisation.展开更多
The mucosal immune system serves as our front-line defense against pathogens. It also tightly maintains immune tolerance to self-symbiotic bacteria, which are usually called commensals. Sensing both types of microorga...The mucosal immune system serves as our front-line defense against pathogens. It also tightly maintains immune tolerance to self-symbiotic bacteria, which are usually called commensals. Sensing both types of microorganisms is modulated by signalling primarily through various pattern-recognition receptors （PRRs） on barrier epithelial cells or immune cells. After sensing, proinflammatory molecules such as cytokines are released by these cells to mediate either defensive or tolerant responses. The interleukin-17 （IL-17） family members belong to a newly characterized cytokine subset that is critical for the maintenance of mucosal homeostasis. In this review, we will summarize recent progress on the diverse functions and signals of this family of cytokines at different mucosal edges.展开更多
In recent years,many studies have shown that the intestinal microflora has various effects that are linked to the critical physiological functions and pathological systems of the host.The intestinal microbial communit...In recent years,many studies have shown that the intestinal microflora has various effects that are linked to the critical physiological functions and pathological systems of the host.The intestinal microbial community is widely involved in the metabolism of food components such as protein,which is one of the essential nutrients in diets.Additionally,dietary protein/amino acids have been shown to have had a profound impact on profile and operation of gut microbiota.This review summarizes the current liter-ature on the mutual interaction between intestinal microbiota and protein/amino acid metabolism for host mucosal immunity and health.展开更多
Polymeric immunoglobulin(Ig)receptor-like(pIgRL)molecules have been identified in teleost fish.However,compared to functional studies of their related genes(e.g.,mammalian CD300 family)in eliminating pathogen invasion...Polymeric immunoglobulin(Ig)receptor-like(pIgRL)molecules have been identified in teleost fish.However,compared to functional studies of their related genes(e.g.,mammalian CD300 family)in eliminating pathogen invasion while preserving homeostasis,the roles of pIgRL in teleost fish remain unclear.In this study,we demonstrated that a pair of pIgRL molecules in zebrafish,pIgRL3.5 and pIgRL4.2,were highly expressed in the intestine and immune cells.Moreover,we constructed an Edwardsiella piscicida infection model,which induced strong inflammatory responses in the zebrafish intestine.Interestingly,pIgRL3.5 and pIgRL4.2 exhibited opposite inducible expression patterns in response to bacterial infection,suggesting that they perform different roles.More importantly,by conducting overexpression and knockdown experiments,our findings demonstrated that zebrafish pIgRL3.5 played a protective role in host defense against E.piscicida infection by inhibiting excessive inflammatory responses.In contrast,pIgRL4.2 facilitated pathogen growth and dissemination in zebrafish intestine.Collectively,our findings are the first to demonstrate that a pair of pIgRL molecules in teleost fish play opposite roles in mucosal immune response to bacterial infection.Therefore,our results provide crucial insights into the conserved role of pIgRL molecules in immune regulatory functions throughout vertebrate evolution.展开更多
Chinese herbal medicine(CHM),with a range of pharmacological and molecular targets,has unique advantages in the comprehensive treatment of colorectal cancer(CRC);however,its clinical application remains limited owing ...Chinese herbal medicine(CHM),with a range of pharmacological and molecular targets,has unique advantages in the comprehensive treatment of colorectal cancer(CRC);however,its clinical application remains limited owing to undetermined anti-CRC mechanisms.Recent studies have shown that gut microbes mediate the intestinal barrier,metabolism,and immunity,which,in turn,affect CRC initiation,progression,and CHM therapy.Here,we summarize the mechanisms and clinical applications of the gut microbiota involved in CRC,together with the latest studies of CHM in CRC therapy and its anti-tumor molecular basis from the gut microbiota perspective.This review highlights the gut microbiota as a“bridge”to clarify the scientific of CHM in treating CRC.More efforts should be focused on how the gut microbiome interacts with CHM to elucidate the mechanism of action of CHM and provide a more applicable basis for CHM-and microbiota-related therapies for the treatment of CRC.展开更多
The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the ...The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.展开更多
BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and fu...BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.展开更多
Based on mucosal immunization to promote both mucosal and systemic immune responses,next-generation coronavirus disease 2019(COVID-19)vaccines would be administered intranasally or orally.The goal of severe acute resp...Based on mucosal immunization to promote both mucosal and systemic immune responses,next-generation coronavirus disease 2019(COVID-19)vaccines would be administered intranasally or orally.The goal of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines is to provide adequate immune protection and avoid severe disease and death.Mucosal vaccine candidates for COVID-19 including vector vaccines,recombinant subunit vaccines and live attenuated vaccines are under development.Furthermore,subunit protein vaccines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings,resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines.Additional to their ability to trigger stable,protective immune responses at the sites of pathogenic infection,the development of‘specific’mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics.However,their efficacy and safety should be confirmed.展开更多
Porcine epidemic diarrhea virus(PEDV),an enteric coronavirus,is widely spread worldwide and causes huge economic losses.The effective measure to control the viral infection is to develop ideal vaccines.Here,the collag...Porcine epidemic diarrhea virus(PEDV),an enteric coronavirus,is widely spread worldwide and causes huge economic losses.The effective measure to control the viral infection is to develop ideal vaccines.Here,the collagenase equivalent domain(COE)of PEDV was displayed on the surface of nanoparticles(NPs)in order to develop a newer,safer and more effective subunit vaccine against PEDV.The monomeric COE was displayed on the mi3 protein,which self-assembles into nanoparticles composed of 60 subunits,using the SpyTag/SpyCatcher system.The size,zeta potential,microstructure of the COE-mi3 virus-like particles(VLPs)were investigated.The COE-mi3 VLPs that possessed good security,stability and better retention can be more efficiently taken up by antigen-presenting cells(APCs)and help promote dendritic cells(DCs)maturation.Moreover,COE-mi3 VLPs could prominently improve specifc antibody levels including neutralizing antibodies(NAbs),and serum IgG,mucosal IgA.Moreover,COE-mi3 VLPs elicited more activation of CD4^(+)and CD8^(+)T cells and production of IFN-γand IL-4 cytokines.In particular,COE-mi3 VLPs is an effectual antigen-delivery platform to enhance germinal center(GC)B cell responses.This structure-based self-assembly of NP gives great potential to be developed as a new subunit vaccines attractive platform,and may also provide new ideas for the development of other enteric coronavirus vaccines.展开更多
The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastroi...The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system,focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.展开更多
At birth the piglet＇s immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet＇s mucosal immune system develops over the first few weeks but has not reached maturity at...At birth the piglet＇s immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet＇s mucosal immune system develops over the first few weeks but has not reached maturity at weaning ages which are common on commercial farms. At weaning piglets are presented with a vast and diverse range of microbial and dietary/environmental antigens. Their ability to distinguish between antigens and mount a protective response to potential pathogens and to develop tolerance to dietary antigens is critical to their survival and failure to do so is reflected in the high incidence of morbidity and mortality in the post-weaning period. A growing recognition that the widespread use of antibiotics to control infection during this critical period should be controlled has led to detailed studies of those factors which drive the development of the mucosal immune system, the role of gut microbiota in driving this process, the origin of the bacteria that colonise the young piglet＇s intestine and the impact of rearing environment. This review briefly describes how the mucosal immune system is equipped to respond ＂appropriately＂ to antigenic challenge and the programmed sequence by which it develops. The results of studies on the critical interplay between the host immune system and gut microbiota are discussed along with the effects of rearing environment. By comparing these with results from human studies on the development of allergies in children, an approach to promote an earlier maturation of the piglet immune system to resist the challenges of weaning are outlined.展开更多
AIM： To explore the effect of Gui Zhi decoction on enteric mucosal immune in type Ⅱ collagen-induced arthritis （CIA） in DBA mice. METHODS： Eighty DBA/1, weighing 18-22 g, were randomly divided into four groups wi...AIM： To explore the effect of Gui Zhi decoction on enteric mucosal immune in type Ⅱ collagen-induced arthritis （CIA） in DBA mice. METHODS： Eighty DBA/1, weighing 18-22 g, were randomly divided into four groups with 20 in each group： control group, CIA group, treatment groups at high dosage and low dosage （GZH and GZL）. CIA was induced by immunization with type Ⅱ collagen （CII） emulsified with equal complete adjuvant at 0.1 mg CII each mouse. Blood lymphocyte suspension was screened for CD4 and CD8 expression using a flow cytometry, the CD4 and CD8 and secretory IgA （sIgA）-positive cells in enteric lamina propria tested with immunohistochemical staining. Tumor necrosis factor-alpha （TNF-α）, interleukin-1 （IL-1）-β, and IL-6 concentrations in serum were assayed with RIA. RESULTS： Gui Zhi decoction can lower the arthritic scores and decrease the occurrence of arthritis. The CD4, CD8, and sIgA-positive cells in CIA mice are less than in control mice, and in Gui Zhi decoction at high dosage could restore the lowered CD4- and CD8-positive cells in lamina propria, and at both high and low dosages could increase the lowered sIgA-positive cells in lamina propria, even still lower than in normal mice. In periphery, the CD4 cells in periphery are higher in CIA mice than in control mice, and Gui Zhi decoction at high and low dosages could decrease the CD4 and CD8 cells. Also, Gui Zhi decoction at high dosage could decrease the IL-6 and TNF-α concentration in serum. CONCLUSION： Gui Zhi decoction can lower the arthritic scores and decrease the incidence of CIA in mice, and the mechanism is in part regulating enteric mucosal immune.展开更多
[Objectives]To explore the molecular mechanisms of Yinqiao anti-epidemic formula(YQAEF)in regulating mucosal immune system of respiratory tract.[Methods]The active components of YQAEF were obtained from the TCMSP data...[Objectives]To explore the molecular mechanisms of Yinqiao anti-epidemic formula(YQAEF)in regulating mucosal immune system of respiratory tract.[Methods]The active components of YQAEF were obtained from the TCMSP database,and RMIS targets were obtained from the GeneCards database.A"YQAEF components-RMIS targets-pathways"network was constructed by analyzing the above data to screen core targets for molecular docking verification.A mouse model of acute upper respiratory tract infection(AURI)was developed.Based on the experimental models,the key pathway target genes screened by network pharmacology were verified in vivo.[Results]The main active components of YQAEF involved in the regulation of the RMIS included quercetin,acetic acid,and raffinose.Key targets,such as angiotensin-converting enzyme(ACE),galactosidase alpha(GLA),matrix metalloproteinase 2(MMP2),Serpin Family E Member 1(SERPINE1),and myeloperoxidase(MPO)and important viral infection and endocrine resistance signaling pathways were included in the regulation of the RMIS with YQAEF.Molecular docking assays showed that the key targets had good binding activities with the components of YQAEF.Based on the results of network pharmacology,key target proteins in ACE,GLA,MMP2,SERPINE1,and MPO were selected for experimental verification.The results showed that ACE/ACE2 and MPO expressions were increased in the oral and throat mucosa of the AURI mice.Under YQAEF treatment,the expression levels of ACE/ACE2 and MPO were decreased.[Conclusions]This study revealed the mechanism of YQAEF in the regulation of RMIS,which is associated with multiple components,targets,and pathways.Further experiments confirmed that YQAEF interfered with MPO and ACE/ACE2 signaling pathways to regulate the RMIS in the oral and throat mucosa tissue of mice with AURI,and provide a new direction for exploring the potential antiviral mechanism of YQAEF.展开更多
IM To undergo apoptosis during negative and positive selection processes in rat mucosal immune system which are implicated in the pathogenesis of various mucosal diseases. METHODS Female SpragueDawley rats were g...IM To undergo apoptosis during negative and positive selection processes in rat mucosal immune system which are implicated in the pathogenesis of various mucosal diseases. METHODS Female SpragueDawley rats were given protein synthesis inhibitor, cycloheximide, intravenously or intraperitoneally, an apoptosis was recognized by morphological hallmark under light and electronmicroscopy, and the expression of proliferating cell nuclear antigen was visualized immunohistochemically. RESULTS The apoptosis of mucosal lymphocytes in the digestive tract, as well as in trachea, uterus and lacrimal gland was induced by cycloheximide (>10mg·kg-1 body weight), which were located mainly in lamina propria and germinal centers of lymphoid nodules. At the same time, a portion of crypt epithelial cells of proliferating zone in small and large intestine, and the epithelial cells in genital tract were also found to undergo apoptosis. Immunostainings showed that apoptotic cells expressed proliferating cell nuclear antigen. CONCLUSION Apoptosis of lymphocytes in mucosal immune system can be induced by cycloheximide. This model will facilitate the understanding of normal mucosal immune system and its role in the pathogenesis of related diseases such as inflammatory bowel diseases.展开更多
This study explored the impact of astaxanthin(AST)supplementation on growth performance,serum lipid profile,gut morphology,and antioxidant and immune function in the intestinal mucosa of Pekin ducks subjected to overf...This study explored the impact of astaxanthin(AST)supplementation on growth performance,serum lipid profile,gut morphology,and antioxidant and immune function in the intestinal mucosa of Pekin ducks subjected to overfeeding.A total of 150 male Pekin ducks at one day of age were randomly allotted into five treatment groups with five replicates of six ducks each.The control group and ad libitum group(ALG)received a basal diet while others received basal diets supplemented with AST at 40 mg/kg(Lowdose group[LDG]),80 mg/kg(medium-dose group[MDG]),and 120 mg/kg(high-dose group[HDG]).After 1 to 14 d on basal diets(brooding phase),the ducks were assigned to the dietary treatment groups for 15 to 38 d(Grower phase)and 39 to 42 d(overfeeding period).Results indicated that AST supplementation improved final body weight and weight gain at both the grower and overfeeding phases(P<0.05).Overfeeding increased the serum lipid level,altered intestinal morphology,and led to higher expression of pro-inflammatory factors and oxidative stress biomarkers while reducing antioxidant enzyme activity,associated gene expression,and anti-inflammatory factors in the duodenal and jejunal mucosa(P<0.05).Additionally,overfeeding caused increased apoptotic cell counts in the duodenal and jejunal mucosa of the control group(P<0.05),culminating in intestinal tissue damage and dysfunction.Dietary supplementation of AST mitigated these adverse effects,alleviated intestinal damage and promoted gut health.It exerted a hypolipidemic effect,improved villi morphometrics in the duodenum,jejunum,and ileum,and enhanced the levels of interleukin-4(IL-4),soluble tumor necrosis factor-alpha receptor(sTNFaR),and transforming growth factor-beta(TGF-b)(P<0.05).It also increased the activities of antioxidant enzymes and the mRNA expression of key antioxidant-related genes,including nuclear factor erythroid 2-related factor 2(Nrf2),glutathione S-transferases(GSTs),and glutamate-cysteine ligase catalytic subunit(GCLC)(P<0.05).Moreover,it reduced the expression of pro-inflammatory factors,oxidative stress biomarkers such as reactive oxygen species(ROS)and malondialdehyde(MDA),and the number of apoptotic cells in the duodenal and jejunal mucosa(P<0.05).Immunoglobulin secretion and mucosal immunity were also significantly improved with AST supplementation(P<0.05).Variations among the AST dietary groups suggest that a medium dosage of 80 mg/kg could effectively mitigate intestinal damage from overfeeding while enhancing growth performance,antioxidant defences,and immune responses.Our results would provide a theoretical reference for using AST as a nutritional strategy to enhance gut health in ducks exposed to overfeeding.展开更多
基金supported by the National Key R&D Program of China(2021YFD1300403)the Major Program of Heilongjiang Province of China(2021ZX12B08-02).
文摘Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.
基金supported by the National Natural Science Foundation of China(31872362 and 32072688)the Agricultural Science and Technology Independent Innovation Fund Project of Jiangsu Province[CX(19)1006].
文摘Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal health-promot-ing of the consumer.However,information is lacking regarding the application prospect of LAB fermented milk in the animal industry.This study investigated the effects of lactic acid bacteria-fermented formula milk(LFM)on the growth performance,intestinal immunity,microbiota composition,and transcriptomic responses in weaned piglets.A total of 24 male weaned piglets were randomly divided into the control(CON)and LFM groups.Each group consisted of 6 replicates(cages)with 2 piglets per cage.Each piglet in the LFM group were supplemented with 80 mL LFM three times a day,while the CON group was treated with the same amount of drinking water.Results:LFM significantly increased the average daily gain of piglets over the entire 14 d(P<0.01)and the average daily feed intake from 7 to 14 d(P<0.05).Compared to the CON group,ileal goblet cell count,villus-crypt ratio,sIgA,and lactate concentrations in the LFM group were significantly increased(P<0.05).Transcriptomic analysis of ileal mucosa identified 487 differentially expressed genes(DEGs)between two groups.Especially,DEGs involved in the intestinal immune network for IgA production pathways,such as polymeric immunoglobulin receptor(PIGR),were significantly up-regulated(P<0.01)by LFM supplementation.Moreover,trefoil factor 2(TFF2)in the LFM group,one of the DEGs involved in the secretory function of goblet cells,was also significantly up-regulated(P<0.01).Sequenc-ing of the 16S rRNA gene of microbiota demonstrated that LFM led to selective enrichment of lactate-producing and short-chain fatty acid(SCFA)-producing bacteria in the ileum,such as an increase in the relative abundance of Entero-coccus(P=0.09)and Acetitomaculum(P<0.05).Conclusions:LFM can improve intestinal health and immune tolerance,thus enhancing the growth performance of weaned piglets.The changes in microbiota and metabolites induced by LFM might mediate the regulation of the secretory function of goblet cells.
基金supported by National Key Research and Development Program of China(2019YFC1605003-3)the Science and Technology Projects of Xiamen Science and Technology Bureau(3502Z20183034)。
文摘The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.
文摘The 778th Xiangshan Science Conference,themed“Regional Immunity in the Lung and Respiratory Tract:Challenges and Opportunities”,convened in Beijing on April 8–9,2025.Co-chaired by four leading scientists-ProfessorGeorge FuGao(Institute of Microbiology,Chinese Academy of Sciences),Professor Chen Dong(Westlake University School of Medicine),Professor Zhigang Tian(University of Science and Technology of China).
文摘Objective To explore the role of curcumin(Cur)in improving IgA nephropathy(IgAN)and its related mechanisms.Methods Fifty 7-month-old miR-23b knockout(miR-23b^(-/-))mice weighing(25±5)g were used to establish an IgAN disease model,and were randomly divided into IgAN group,IgAN+Cur(150 mg/kg)group and IgAN+Cur(300 mg/kg)group using simple randomisation.
基金This work was supported by grants from the National Natural Science Foundation of China （81430036, 81230075, 91429307, 31329002, 91329301 and 91542119）, the 973 Program （2013CB944904）, and the Science and Technology Commission of Shanghai Municipality （131C1408900）.
文摘The mucosal immune system serves as our front-line defense against pathogens. It also tightly maintains immune tolerance to self-symbiotic bacteria, which are usually called commensals. Sensing both types of microorganisms is modulated by signalling primarily through various pattern-recognition receptors （PRRs） on barrier epithelial cells or immune cells. After sensing, proinflammatory molecules such as cytokines are released by these cells to mediate either defensive or tolerant responses. The interleukin-17 （IL-17） family members belong to a newly characterized cytokine subset that is critical for the maintenance of mucosal homeostasis. In this review, we will summarize recent progress on the diverse functions and signals of this family of cytokines at different mucosal edges.
基金grants from the National Natural Science Foundation,China(31872370)Fundamental Research Funds for the Central Universities,China(XDJK2019B014)Natural Science Foundation Project of CQ CSTC(cstc2018jcyjAX0025).
文摘In recent years,many studies have shown that the intestinal microflora has various effects that are linked to the critical physiological functions and pathological systems of the host.The intestinal microbial community is widely involved in the metabolism of food components such as protein,which is one of the essential nutrients in diets.Additionally,dietary protein/amino acids have been shown to have had a profound impact on profile and operation of gut microbiota.This review summarizes the current liter-ature on the mutual interaction between intestinal microbiota and protein/amino acid metabolism for host mucosal immunity and health.
基金supported by grants from the National Natural Science Foundation of China(32225050,32073001)to Z.X.the National Natural Science Foundation of China(3210210315)to Y.Y.Y.
文摘Polymeric immunoglobulin(Ig)receptor-like(pIgRL)molecules have been identified in teleost fish.However,compared to functional studies of their related genes(e.g.,mammalian CD300 family)in eliminating pathogen invasion while preserving homeostasis,the roles of pIgRL in teleost fish remain unclear.In this study,we demonstrated that a pair of pIgRL molecules in zebrafish,pIgRL3.5 and pIgRL4.2,were highly expressed in the intestine and immune cells.Moreover,we constructed an Edwardsiella piscicida infection model,which induced strong inflammatory responses in the zebrafish intestine.Interestingly,pIgRL3.5 and pIgRL4.2 exhibited opposite inducible expression patterns in response to bacterial infection,suggesting that they perform different roles.More importantly,by conducting overexpression and knockdown experiments,our findings demonstrated that zebrafish pIgRL3.5 played a protective role in host defense against E.piscicida infection by inhibiting excessive inflammatory responses.In contrast,pIgRL4.2 facilitated pathogen growth and dissemination in zebrafish intestine.Collectively,our findings are the first to demonstrate that a pair of pIgRL molecules in teleost fish play opposite roles in mucosal immune response to bacterial infection.Therefore,our results provide crucial insights into the conserved role of pIgRL molecules in immune regulatory functions throughout vertebrate evolution.
基金supported by the National Natural Science Foundation of China(82104955,82205223)the Shanghai Rising-Star Program(22QA1408700,21YF1444500)the China Postdoctoral Science Foundation(2022M712154)。
文摘Chinese herbal medicine(CHM),with a range of pharmacological and molecular targets,has unique advantages in the comprehensive treatment of colorectal cancer(CRC);however,its clinical application remains limited owing to undetermined anti-CRC mechanisms.Recent studies have shown that gut microbes mediate the intestinal barrier,metabolism,and immunity,which,in turn,affect CRC initiation,progression,and CHM therapy.Here,we summarize the mechanisms and clinical applications of the gut microbiota involved in CRC,together with the latest studies of CHM in CRC therapy and its anti-tumor molecular basis from the gut microbiota perspective.This review highlights the gut microbiota as a“bridge”to clarify the scientific of CHM in treating CRC.More efforts should be focused on how the gut microbiome interacts with CHM to elucidate the mechanism of action of CHM and provide a more applicable basis for CHM-and microbiota-related therapies for the treatment of CRC.
基金The Deutsche Forschungsgemeinschaft, No. Ni575/4-1
文摘The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.
基金the National Key Technology Support Program during“12th Five-Year Plan”Period of China,No.2014BAI08B00the Project“The role of the gut microbiota and metabolites in the pathogenesis of diarrheapredominant irritable bowel syndrome”of China-Japan Friendship Hospital,No.2019-64-K44.
文摘BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.
文摘Based on mucosal immunization to promote both mucosal and systemic immune responses,next-generation coronavirus disease 2019(COVID-19)vaccines would be administered intranasally or orally.The goal of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines is to provide adequate immune protection and avoid severe disease and death.Mucosal vaccine candidates for COVID-19 including vector vaccines,recombinant subunit vaccines and live attenuated vaccines are under development.Furthermore,subunit protein vaccines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings,resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines.Additional to their ability to trigger stable,protective immune responses at the sites of pathogenic infection,the development of‘specific’mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics.However,their efficacy and safety should be confirmed.
基金supported by the Major Scientific and Technological Project of the Henan Province,China(221100110600)the Beijing Life Science Academy,China(2024500CA0010)+1 种基金the Major Program of National Natural Science Foundation of China(32192452)the Chinese Postdoctoral Science Foundation(2023M743209)。
文摘Porcine epidemic diarrhea virus(PEDV),an enteric coronavirus,is widely spread worldwide and causes huge economic losses.The effective measure to control the viral infection is to develop ideal vaccines.Here,the collagenase equivalent domain(COE)of PEDV was displayed on the surface of nanoparticles(NPs)in order to develop a newer,safer and more effective subunit vaccine against PEDV.The monomeric COE was displayed on the mi3 protein,which self-assembles into nanoparticles composed of 60 subunits,using the SpyTag/SpyCatcher system.The size,zeta potential,microstructure of the COE-mi3 virus-like particles(VLPs)were investigated.The COE-mi3 VLPs that possessed good security,stability and better retention can be more efficiently taken up by antigen-presenting cells(APCs)and help promote dendritic cells(DCs)maturation.Moreover,COE-mi3 VLPs could prominently improve specifc antibody levels including neutralizing antibodies(NAbs),and serum IgG,mucosal IgA.Moreover,COE-mi3 VLPs elicited more activation of CD4^(+)and CD8^(+)T cells and production of IFN-γand IL-4 cytokines.In particular,COE-mi3 VLPs is an effectual antigen-delivery platform to enhance germinal center(GC)B cell responses.This structure-based self-assembly of NP gives great potential to be developed as a new subunit vaccines attractive platform,and may also provide new ideas for the development of other enteric coronavirus vaccines.
基金supported by the Intramural Research Program of the National Institutes of HealthNational Institute of Dental and Craniofacial Research, USA+1 种基金supported by grant 2012DFA31370 from the International S&T Cooperation Program of Chinathe National Nature Science Foundation of China (81321002)
文摘The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system,focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.
文摘At birth the piglet＇s immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet＇s mucosal immune system develops over the first few weeks but has not reached maturity at weaning ages which are common on commercial farms. At weaning piglets are presented with a vast and diverse range of microbial and dietary/environmental antigens. Their ability to distinguish between antigens and mount a protective response to potential pathogens and to develop tolerance to dietary antigens is critical to their survival and failure to do so is reflected in the high incidence of morbidity and mortality in the post-weaning period. A growing recognition that the widespread use of antibiotics to control infection during this critical period should be controlled has led to detailed studies of those factors which drive the development of the mucosal immune system, the role of gut microbiota in driving this process, the origin of the bacteria that colonise the young piglet＇s intestine and the impact of rearing environment. This review briefly describes how the mucosal immune system is equipped to respond ＂appropriately＂ to antigenic challenge and the programmed sequence by which it develops. The results of studies on the critical interplay between the host immune system and gut microbiota are discussed along with the effects of rearing environment. By comparing these with results from human studies on the development of allergies in children, an approach to promote an earlier maturation of the piglet immune system to resist the challenges of weaning are outlined.
基金Supported by the project of National Natural Science Foundation of China, No. 30171133 and 39870952
文摘AIM： To explore the effect of Gui Zhi decoction on enteric mucosal immune in type Ⅱ collagen-induced arthritis （CIA） in DBA mice. METHODS： Eighty DBA/1, weighing 18-22 g, were randomly divided into four groups with 20 in each group： control group, CIA group, treatment groups at high dosage and low dosage （GZH and GZL）. CIA was induced by immunization with type Ⅱ collagen （CII） emulsified with equal complete adjuvant at 0.1 mg CII each mouse. Blood lymphocyte suspension was screened for CD4 and CD8 expression using a flow cytometry, the CD4 and CD8 and secretory IgA （sIgA）-positive cells in enteric lamina propria tested with immunohistochemical staining. Tumor necrosis factor-alpha （TNF-α）, interleukin-1 （IL-1）-β, and IL-6 concentrations in serum were assayed with RIA. RESULTS： Gui Zhi decoction can lower the arthritic scores and decrease the occurrence of arthritis. The CD4, CD8, and sIgA-positive cells in CIA mice are less than in control mice, and in Gui Zhi decoction at high dosage could restore the lowered CD4- and CD8-positive cells in lamina propria, and at both high and low dosages could increase the lowered sIgA-positive cells in lamina propria, even still lower than in normal mice. In periphery, the CD4 cells in periphery are higher in CIA mice than in control mice, and Gui Zhi decoction at high and low dosages could decrease the CD4 and CD8 cells. Also, Gui Zhi decoction at high dosage could decrease the IL-6 and TNF-α concentration in serum. CONCLUSION： Gui Zhi decoction can lower the arthritic scores and decrease the incidence of CIA in mice, and the mechanism is in part regulating enteric mucosal immune.
基金Supported by Suzhou Science and Technology Development Plan project (SKY2022206)The Ninth Batch of Suzhou Gusu Health Key Talents Project (GSWS2022107).
文摘[Objectives]To explore the molecular mechanisms of Yinqiao anti-epidemic formula(YQAEF)in regulating mucosal immune system of respiratory tract.[Methods]The active components of YQAEF were obtained from the TCMSP database,and RMIS targets were obtained from the GeneCards database.A"YQAEF components-RMIS targets-pathways"network was constructed by analyzing the above data to screen core targets for molecular docking verification.A mouse model of acute upper respiratory tract infection(AURI)was developed.Based on the experimental models,the key pathway target genes screened by network pharmacology were verified in vivo.[Results]The main active components of YQAEF involved in the regulation of the RMIS included quercetin,acetic acid,and raffinose.Key targets,such as angiotensin-converting enzyme(ACE),galactosidase alpha(GLA),matrix metalloproteinase 2(MMP2),Serpin Family E Member 1(SERPINE1),and myeloperoxidase(MPO)and important viral infection and endocrine resistance signaling pathways were included in the regulation of the RMIS with YQAEF.Molecular docking assays showed that the key targets had good binding activities with the components of YQAEF.Based on the results of network pharmacology,key target proteins in ACE,GLA,MMP2,SERPINE1,and MPO were selected for experimental verification.The results showed that ACE/ACE2 and MPO expressions were increased in the oral and throat mucosa of the AURI mice.Under YQAEF treatment,the expression levels of ACE/ACE2 and MPO were decreased.[Conclusions]This study revealed the mechanism of YQAEF in the regulation of RMIS,which is associated with multiple components,targets,and pathways.Further experiments confirmed that YQAEF interfered with MPO and ACE/ACE2 signaling pathways to regulate the RMIS in the oral and throat mucosa tissue of mice with AURI,and provide a new direction for exploring the potential antiviral mechanism of YQAEF.
文摘IM To undergo apoptosis during negative and positive selection processes in rat mucosal immune system which are implicated in the pathogenesis of various mucosal diseases. METHODS Female SpragueDawley rats were given protein synthesis inhibitor, cycloheximide, intravenously or intraperitoneally, an apoptosis was recognized by morphological hallmark under light and electronmicroscopy, and the expression of proliferating cell nuclear antigen was visualized immunohistochemically. RESULTS The apoptosis of mucosal lymphocytes in the digestive tract, as well as in trachea, uterus and lacrimal gland was induced by cycloheximide (>10mg·kg-1 body weight), which were located mainly in lamina propria and germinal centers of lymphoid nodules. At the same time, a portion of crypt epithelial cells of proliferating zone in small and large intestine, and the epithelial cells in genital tract were also found to undergo apoptosis. Immunostainings showed that apoptotic cells expressed proliferating cell nuclear antigen. CONCLUSION Apoptosis of lymphocytes in mucosal immune system can be induced by cycloheximide. This model will facilitate the understanding of normal mucosal immune system and its role in the pathogenesis of related diseases such as inflammatory bowel diseases.
基金supported by a subtheme of the National Key Research and Development Program of China(2021YFD1300300)Construction of Peking Duck Industry Chain Standard Technical System for Geographical Indication of Beijing(11000024T 000002810090)+1 种基金the Beijing Innovation Consortium of Agriculture Research System(BAIC 06-2025)the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciences.
文摘This study explored the impact of astaxanthin(AST)supplementation on growth performance,serum lipid profile,gut morphology,and antioxidant and immune function in the intestinal mucosa of Pekin ducks subjected to overfeeding.A total of 150 male Pekin ducks at one day of age were randomly allotted into five treatment groups with five replicates of six ducks each.The control group and ad libitum group(ALG)received a basal diet while others received basal diets supplemented with AST at 40 mg/kg(Lowdose group[LDG]),80 mg/kg(medium-dose group[MDG]),and 120 mg/kg(high-dose group[HDG]).After 1 to 14 d on basal diets(brooding phase),the ducks were assigned to the dietary treatment groups for 15 to 38 d(Grower phase)and 39 to 42 d(overfeeding period).Results indicated that AST supplementation improved final body weight and weight gain at both the grower and overfeeding phases(P<0.05).Overfeeding increased the serum lipid level,altered intestinal morphology,and led to higher expression of pro-inflammatory factors and oxidative stress biomarkers while reducing antioxidant enzyme activity,associated gene expression,and anti-inflammatory factors in the duodenal and jejunal mucosa(P<0.05).Additionally,overfeeding caused increased apoptotic cell counts in the duodenal and jejunal mucosa of the control group(P<0.05),culminating in intestinal tissue damage and dysfunction.Dietary supplementation of AST mitigated these adverse effects,alleviated intestinal damage and promoted gut health.It exerted a hypolipidemic effect,improved villi morphometrics in the duodenum,jejunum,and ileum,and enhanced the levels of interleukin-4(IL-4),soluble tumor necrosis factor-alpha receptor(sTNFaR),and transforming growth factor-beta(TGF-b)(P<0.05).It also increased the activities of antioxidant enzymes and the mRNA expression of key antioxidant-related genes,including nuclear factor erythroid 2-related factor 2(Nrf2),glutathione S-transferases(GSTs),and glutamate-cysteine ligase catalytic subunit(GCLC)(P<0.05).Moreover,it reduced the expression of pro-inflammatory factors,oxidative stress biomarkers such as reactive oxygen species(ROS)and malondialdehyde(MDA),and the number of apoptotic cells in the duodenal and jejunal mucosa(P<0.05).Immunoglobulin secretion and mucosal immunity were also significantly improved with AST supplementation(P<0.05).Variations among the AST dietary groups suggest that a medium dosage of 80 mg/kg could effectively mitigate intestinal damage from overfeeding while enhancing growth performance,antioxidant defences,and immune responses.Our results would provide a theoretical reference for using AST as a nutritional strategy to enhance gut health in ducks exposed to overfeeding.
