Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administratio...Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administration has the advantage of being needle free and self-administered,thereby improving compliance and coverage of large populations.In China,the experience of COVID-19 has promoted substantial efforts in the development of nasal vaccinations in the general health protection strategy.The hurdles we are facing in the development of mucosal vaccines,however,come from the still limited knowledge of the mechanisms controlling mucosal immunity in different anatomical locations and in response to different pathogens/vaccines.Identifying and filling the knowledge gaps in order to develop effective and safe mucosal immunization strategies requires global collaboration,not only at the scientific level but,most importantly,by engaging public and private health organizations,governments,and regulatory authorities.We have highlighted here some of the crucial issues in mucosal immunization and provided suggestions for the way forward toward a global preparedness effort to prevent infectious diseases and ensure vaccine equity.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 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 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
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
To investigate the immune responses to the attenuated Mycoplasma hyopneumoniae 168 strain vaccine,8-15 d old piglets were immunized with M.hyopneurnoniae 168 strain vaccine by intrapulmonic route.And the specific IgG ...To investigate the immune responses to the attenuated Mycoplasma hyopneumoniae 168 strain vaccine,8-15 d old piglets were immunized with M.hyopneurnoniae 168 strain vaccine by intrapulmonic route.And the specific IgG antibody in serum,lymphoproliferation,IFNT,and specific secretory IgA(SIgA)antibody in bronchoalveolar lavage fluid were detected on 30 and 60 d post-immunization(DPI),respectively.On 60 DPI,all the pigs except for those in health control group were challenged with a field M.hyopneumoniae strain JS.Necropsy was performed on 30 d post-challenge(DPC).The results showed that IFN7 and specific SIgA were stimulated on surface of respiratory tract after immunization.And peripheral blood mononuclear cells could also be proliferated about 1.81 and 2.12 fold on 30 and 60 DPI when stimulated by M.hyopneumoniae protein in vitro.However,no serum IgG antibody against M.hyopneumoniae was detected during the whole immune phage.After challenge,vaccinated pigs were observed with only very slight histological lesion in individual lobes.None of vaccinated pigs showed any clinical signs.While the unvaccinated pigs from challenge control group showed varying degrees of clinical sign and severe macroscopical lesion of mycoplasmal pneumonia of swine(MPS).The result suggested that the attenuated M.hyopneumoniae 168 strain vaccine inoculated by intrapulmonic route could activate the systemic cellular immunity,the local mucosal immunity and IFNγsecretion in respiratory tract to against M.hyopneumoniae infection in piglets.展开更多
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
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
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
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
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
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
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
[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
[Objective] This study aimed to investigate the distribution law of different goblet cells in the intestinal tracts of African ostrich chicks. [Method] Alcian blue/pe- riodic acid-schiff reaction （AB/PAS） was adopte...[Objective] This study aimed to investigate the distribution law of different goblet cells in the intestinal tracts of African ostrich chicks. [Method] Alcian blue/pe- riodic acid-schiff reaction （AB/PAS） was adopted to observe and analyze the types and distribution of goblet cells in the intestinal tracts of ostrich chicks. Acid mu- copolysaccharide could be stained blue with alcian blue （AB）, and neutral mu- copolysaccharide could be stained red with periodic acid-schiff reagent （PAS）. [Result] According to AB/PAS results, goblet cells in the intestinal tracts were divided in- to four types： TypeⅠ was pure red, with AB negative result and PAS positive result containing neutral mucoitin; type Ⅱ was pure blue, with AB positive result and PAS negative result containing acidic mucoitin; type Ⅲ was purple reddish, with PAS posi- tive result greater than AB; typeⅣ was purple blue, with AB positive result greater than PAS. Large quantities of goblet cells were found in the intestinal tracts of os- trich chicks, mostly type III and IV.The quantities of goblet cells were decreased gradually in the duodenum, jejunum and ileum, while the quantities were increased in the cecum, colon and rectum. The goblet cells in the large intestine are more than that in the small intestine. The most quantities of goblet cells were contained in rectum. [Conclusion] These results indicate that the distribution of goblet cells is closely related with the structure and function of intestinal tracts. The mucus secret- ed by the goblet Cells plays a series of important roles in the digestion and mucosal immunization.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
Background:Edible vaccines produced in genetically modified plants represent a novel approach to immunization,to express antigens capable of eliciting immune responses at mucosal surfaces.This method provides a potent...Background:Edible vaccines produced in genetically modified plants represent a novel approach to immunization,to express antigens capable of eliciting immune responses at mucosal surfaces.This method provides a potential cost-effective solution for vaccine delivery,particularly beneficial in resource-limited settings.Aim:This review aims to assess the efficacy of edible vaccines derived from transgenic plants in eliciting immune responses in animal models against various infectious and parasitic diseases.Methods:A comprehensive search of PubMed,Embase,and Scopus up to June 2024 identified 138 references.Following Cochrane guidelines,PRISMA standards,and the CAMARADES risk of bias checklist,16 studies met the inclusion criteria and focused on edible vaccines for animal immunization.Results:The findings indicate that edible vaccines can effectively elicit both humoral and mucosal immune responses in animals.For instance,transgenic plants expressing antigens for hepatitis B and human papillomavirus demonstrated high efficacy,with significant increases in antigen-specific antibody levels post-immunization.Studies on bacterial diseases using LT-B antigens from Escherichia coli expressed in corn showed robust,sustained antibody responses.Additionally,for parasitic diseases,transgenic rice expressing Ascaris antigen reduced larval burden,indicating protective efficacy.However,variations in immune response depending on plant type and antigen stability highlight the need for further optimization to achieve consistent efficacy across different diseases.展开更多
Mucosal vaccines would be game-changing for blocking pathogenic transmission,prompting protection where microorganism first enters that those intramuscular ones could not be able to achieve.The exploration of the vacc...Mucosal vaccines would be game-changing for blocking pathogenic transmission,prompting protection where microorganism first enters that those intramuscular ones could not be able to achieve.The exploration of the vaccines at mucosal surfaces is gaining momentum due to the unique immune reservoir they offer in a minimally invasive manner.Nevertheless,the application of mucosal vaccines faces challenges,including barriers such as degrading enzymes,mucus interference,and clearance mechanisms.The field of mucosal vaccination is still in its early stages,and its advancement will significantly benefit from foundational inquiries into immune activation mechanisms and the innovation of delivery technologies for optimal efficacy.It is highly central to design efficient systems for mucosal vaccine development,herein,this article offers the insights towards the status,bottlenecks and solutions in this field,the intricacies of the immune response,fundamental mechanisms,applications of the delivery strategies for various forms of mucosal vaccines are explored.Collectively,this review conducts systematical analysis on biological and chemical strategies designed to augment vaccine uptake across mucosal tissues,antigen design and delivery methods strengthening vaccination efficacy,with emphasis on the emerging m RNA mucosal vaccines,offering new insights into recent advancements,trends and future scenarios,aiming to harness mucosal immunity(MI)for comprehensive protection against infections and other diseases.展开更多
In this study,we comparatively investigated the immunomodulatory effects of garlic oligosaccharides(GPs)with different molecular weights(GPs-U2,GPs-U1 and GPs-U0.3)on RAW264.7 macrophages in vitro and cyclophosphamide...In this study,we comparatively investigated the immunomodulatory effects of garlic oligosaccharides(GPs)with different molecular weights(GPs-U2,GPs-U1 and GPs-U0.3)on RAW264.7 macrophages in vitro and cyclophosphamide(CY)-induced immunosuppressed mice model(C57BL/6 male mice)in vivo.All three GPs displayed high immunomodulatory effects in enhancing cell viability and promoting the secretion of cytokines(i.e.tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-10)in RAW264.7 macrophages in vitro,especially GPs-U2 exhibited the highest immune activity.Furthermore,GPs-U2 showed good immune effects in CY-induced immunosuppressed mice model in vivo by regulating cytokine secretion,antioxidant levels,goblet cells numbers,expression of tight junction proteins(TJs)and short-chain fatty acids(SCFAs)content.In addition,GPs-U2 maintained mucosal immunity by increasing the abundance of Bacteroidota and Verrucomicrobiota and decreasing the abundance of Firmicutes.These findings support the immune-enhancing effects of GPs-U2 in vitro and in vivo,and provide a scientific basis for the rational use of GPs to alleviate immunosuppression and related diseases.展开更多
基金supported by the Gates Foundation(INV-059115)the Alliance of International Science Organizations(ANSO-CR-KP-2022-01)partly supported by the National Natural Science Foundation of China(92469301).
文摘Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administration has the advantage of being needle free and self-administered,thereby improving compliance and coverage of large populations.In China,the experience of COVID-19 has promoted substantial efforts in the development of nasal vaccinations in the general health protection strategy.The hurdles we are facing in the development of mucosal vaccines,however,come from the still limited knowledge of the mechanisms controlling mucosal immunity in different anatomical locations and in response to different pathogens/vaccines.Identifying and filling the knowledge gaps in order to develop effective and safe mucosal immunization strategies requires global collaboration,not only at the scientific level but,most importantly,by engaging public and private health organizations,governments,and regulatory authorities.We have highlighted here some of the crucial issues in mucosal immunization and provided suggestions for the way forward toward a global preparedness effort to prevent infectious diseases and ensure vaccine equity.
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 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.
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.
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supported by the Natural Science Foundation of Jiangsu Province,China(BK2007711)the China Postdoctoral Fundation(20070421022)the Three Agricultural Projects Fundation of Jiangsu Province,China(SX2007082)
文摘To investigate the immune responses to the attenuated Mycoplasma hyopneumoniae 168 strain vaccine,8-15 d old piglets were immunized with M.hyopneurnoniae 168 strain vaccine by intrapulmonic route.And the specific IgG antibody in serum,lymphoproliferation,IFNT,and specific secretory IgA(SIgA)antibody in bronchoalveolar lavage fluid were detected on 30 and 60 d post-immunization(DPI),respectively.On 60 DPI,all the pigs except for those in health control group were challenged with a field M.hyopneumoniae strain JS.Necropsy was performed on 30 d post-challenge(DPC).The results showed that IFN7 and specific SIgA were stimulated on surface of respiratory tract after immunization.And peripheral blood mononuclear cells could also be proliferated about 1.81 and 2.12 fold on 30 and 60 DPI when stimulated by M.hyopneumoniae protein in vitro.However,no serum IgG antibody against M.hyopneumoniae was detected during the whole immune phage.After challenge,vaccinated pigs were observed with only very slight histological lesion in individual lobes.None of vaccinated pigs showed any clinical signs.While the unvaccinated pigs from challenge control group showed varying degrees of clinical sign and severe macroscopical lesion of mycoplasmal pneumonia of swine(MPS).The result suggested that the attenuated M.hyopneumoniae 168 strain vaccine inoculated by intrapulmonic route could activate the systemic cellular immunity,the local mucosal immunity and IFNγsecretion in respiratory tract to against M.hyopneumoniae infection in piglets.
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.
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.
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.
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 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.
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 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.
基金Supported by National Natural Science Foundation of China (30972152)Specialized Research Fund for the Doctoral Program of Higher Education of China (200805040023)~~
文摘[Objective] This study aimed to investigate the distribution law of different goblet cells in the intestinal tracts of African ostrich chicks. [Method] Alcian blue/pe- riodic acid-schiff reaction （AB/PAS） was adopted to observe and analyze the types and distribution of goblet cells in the intestinal tracts of ostrich chicks. Acid mu- copolysaccharide could be stained blue with alcian blue （AB）, and neutral mu- copolysaccharide could be stained red with periodic acid-schiff reagent （PAS）. [Result] According to AB/PAS results, goblet cells in the intestinal tracts were divided in- to four types： TypeⅠ was pure red, with AB negative result and PAS positive result containing neutral mucoitin; type Ⅱ was pure blue, with AB positive result and PAS negative result containing acidic mucoitin; type Ⅲ was purple reddish, with PAS posi- tive result greater than AB; typeⅣ was purple blue, with AB positive result greater than PAS. Large quantities of goblet cells were found in the intestinal tracts of os- trich chicks, mostly type III and IV.The quantities of goblet cells were decreased gradually in the duodenum, jejunum and ileum, while the quantities were increased in the cecum, colon and rectum. The goblet cells in the large intestine are more than that in the small intestine. The most quantities of goblet cells were contained in rectum. [Conclusion] These results indicate that the distribution of goblet cells is closely related with the structure and function of intestinal tracts. The mucus secret- ed by the goblet Cells plays a series of important roles in the digestion and mucosal immunization.
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.
文摘Background:Edible vaccines produced in genetically modified plants represent a novel approach to immunization,to express antigens capable of eliciting immune responses at mucosal surfaces.This method provides a potential cost-effective solution for vaccine delivery,particularly beneficial in resource-limited settings.Aim:This review aims to assess the efficacy of edible vaccines derived from transgenic plants in eliciting immune responses in animal models against various infectious and parasitic diseases.Methods:A comprehensive search of PubMed,Embase,and Scopus up to June 2024 identified 138 references.Following Cochrane guidelines,PRISMA standards,and the CAMARADES risk of bias checklist,16 studies met the inclusion criteria and focused on edible vaccines for animal immunization.Results:The findings indicate that edible vaccines can effectively elicit both humoral and mucosal immune responses in animals.For instance,transgenic plants expressing antigens for hepatitis B and human papillomavirus demonstrated high efficacy,with significant increases in antigen-specific antibody levels post-immunization.Studies on bacterial diseases using LT-B antigens from Escherichia coli expressed in corn showed robust,sustained antibody responses.Additionally,for parasitic diseases,transgenic rice expressing Ascaris antigen reduced larval burden,indicating protective efficacy.However,variations in immune response depending on plant type and antigen stability highlight the need for further optimization to achieve consistent efficacy across different diseases.
基金supported by the National Natural Science Foundation of China(No.82400017)the Guangdong Provincial Basic Science Fund(No.2023A1515110028)+4 种基金the High-level University Construction Fund(No.06–445–1122)the Open Project of State Key Laboratory of Respiratory Disease(No.SKLRD-OP-202409)the grant from State Key Laboratory of Respiratory Diseases(No.SKLRD-Z-202311 to Dr.Li)the GMU postdoc start-up fundingthe Pearl River Rising Scholar Fellowship。
文摘Mucosal vaccines would be game-changing for blocking pathogenic transmission,prompting protection where microorganism first enters that those intramuscular ones could not be able to achieve.The exploration of the vaccines at mucosal surfaces is gaining momentum due to the unique immune reservoir they offer in a minimally invasive manner.Nevertheless,the application of mucosal vaccines faces challenges,including barriers such as degrading enzymes,mucus interference,and clearance mechanisms.The field of mucosal vaccination is still in its early stages,and its advancement will significantly benefit from foundational inquiries into immune activation mechanisms and the innovation of delivery technologies for optimal efficacy.It is highly central to design efficient systems for mucosal vaccine development,herein,this article offers the insights towards the status,bottlenecks and solutions in this field,the intricacies of the immune response,fundamental mechanisms,applications of the delivery strategies for various forms of mucosal vaccines are explored.Collectively,this review conducts systematical analysis on biological and chemical strategies designed to augment vaccine uptake across mucosal tissues,antigen design and delivery methods strengthening vaccination efficacy,with emphasis on the emerging m RNA mucosal vaccines,offering new insights into recent advancements,trends and future scenarios,aiming to harness mucosal immunity(MI)for comprehensive protection against infections and other diseases.
基金supported by the Key R&D Program(Science and Technology Innovation Boosting Action Plan for Rural Revitalization)of Shandong Provincial(2022TZXD0020).
文摘In this study,we comparatively investigated the immunomodulatory effects of garlic oligosaccharides(GPs)with different molecular weights(GPs-U2,GPs-U1 and GPs-U0.3)on RAW264.7 macrophages in vitro and cyclophosphamide(CY)-induced immunosuppressed mice model(C57BL/6 male mice)in vivo.All three GPs displayed high immunomodulatory effects in enhancing cell viability and promoting the secretion of cytokines(i.e.tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-10)in RAW264.7 macrophages in vitro,especially GPs-U2 exhibited the highest immune activity.Furthermore,GPs-U2 showed good immune effects in CY-induced immunosuppressed mice model in vivo by regulating cytokine secretion,antioxidant levels,goblet cells numbers,expression of tight junction proteins(TJs)and short-chain fatty acids(SCFAs)content.In addition,GPs-U2 maintained mucosal immunity by increasing the abundance of Bacteroidota and Verrucomicrobiota and decreasing the abundance of Firmicutes.These findings support the immune-enhancing effects of GPs-U2 in vitro and in vivo,and provide a scientific basis for the rational use of GPs to alleviate immunosuppression and related diseases.
