Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

Effect of dietary supplement of inactivated Lactobacillus plantarum Ep-M 17 on growth performance,immune response,disease resistance,and intestinal microbiota in Penaeus vannamei

Our previous study found that feeding with Lactobacillus plantarum Ep-M17 could effectively affect the growth performance,immune response,and gut microbiota of Penaeus vannamei.However,high temperature and pressure during feed pelletizing is the main problem that can lead to a decrease in the activity of probiotics or cause their inactivation.Further investigation needs to investigate whether inactivated Ep-M17 can exert similar effects as live Ep-M17.Therefore,we evaluated the effects of inactivated L.plantarum Ep-M17 on growth performance,immune response,disease resistance,and gut microbiota in P.vannamei.Results show that adding inactivated Ep-M17 to the feed also promoted body weight gain and increased relative immune protection in shrimp.Also,histological examination revealed that the administration of inactivated Ep-M17 led to improvements in the density and distribution of microvilli in the intestines and enhancements in the abundance of B and R cells in the hepatopancreas.Additionally,the inactivated Ep-M17 supplementation resulted in increased activity levels of nutrient immune-related enzymes in both the shrimp hepatopancreas and intestines.Moreover,it stimulated the expression of Lvlec,PEN-3a,Crustin,LGBP,Lysozyme,and proPo genes in both the hepatopancreas and intestines.Furthermore,the inactivated Ep-M17 also increased bacterial diversity in the gut of shrimp and promoted the abundance of specific flora,facilitating the host organism’s metabolism and immunity to improve the disease resistance of shrimp.Therefore,supplementation of inactivated L.plantarum Ep-M17 in shrimp diets can exert similar effects as live L.plantarum Ep-M17 effectively improving growth performance,gut microbiota,immune response,and disease resistance in P.vannamei.

Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

Immune response to inactivated bacterial vector carrying the recombinant K39 antigen of Leishmania infantum in mice

Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.

Acupoint catgut-embedding therapy ameliorates DNCB-induced atopic dermatitis in BALB/c mice by regulating Th2 type immune response and reducing infiltration of CD4^(+)and CD8^(+)cells

Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.

Impact of minimally invasive surgery on immune function and stress response in gastric cancer patients

BACKGROUND Gastric cancer remains a leading cause of cancer-related mortality globally.Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery.AIM To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer,focusing on its potential to reduce trauma,accelerate recovery,and achieve comparable oncological out-comes.METHODS This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December 2023.The patients were divided into two groups:Minimally invasive surgery group(n=102),who underwent laparoscopic gastrectomy,and open surgery group(n=101),who underwent traditional open gastrectomy.We compared surgical indicators(surgical incision size,intraop-erative blood loss,surgical duration,and number of lymph nodes dissected),recovery parameters(time to first flatus,time to start eating,time to ambulation,and length of hospital stay),immune function(levels of IgA,IgG,and IgM),intestinal barrier function(levels of D-lactic acid and diamine oxidase),and stress response(levels of C-reactive protein,interleukin-6,and procalcitonin).RESULTS The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators,including smaller incisions,less blood loss,shorter surgery time,and more lymph nodes dissected(P<0.05 for all).Recovery was also faster in the minimally invasive surgery group,with earlier return of bowel function,earlier initiation of diet,quicker mobilization,and shorter hospital stays(P<0.05 for all).Furthermore,patients in the minimally invasive surgery group had better preserved immune function,superior intestinal barrier function,and a less pronounced stress response postoperatively(P<0.05 for all).CONCLUSION Laparoscopic minimally invasive surgery for gastric cancer not only provides superior surgical indicators and faster recovery but also offers advantages in preserving immune function,protecting intestinal barrier function,and mitigating the stress response compared to traditional open surgery.These findings support the broader adoption of laparoscopic techniques in the management of gastric cancer.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

A glycine-rich nuclear effector VdCE51 of Verticillium dahliae suppresses plant immune responses by inhibiting the accumulation of GhTRXH2

Verticillium dahliae is an important soil-borne fungal pathogen that causes great yield losses in many cash crops.Effectors of this fungus are known to regulate plant immunity but the mechanism much remains unclear.A glycine-rich nuclear effector,VdCE51,was able to suppress immune responses in tobacco against Botrytis cinerea and Sclerotinia sclerotiorum.This effector was a required factor for full virulence of V.dahliae,and its nuclear localization was a requisite for suppressing plant immunity.The thioredoxin GhTRXH2,identified as a positive regulator of plant immunity,was a host target of VdCE51.Our findings show a virulence regulating mechanism whereby the secreted nuclear effector VdCE51 interferes with the transcription of PR genes,and the SA signaling pathway by inhibiting the accumulation of GhTRXH2,thus suppressing plant immunity.

Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing E.coli challenged weaned piglets

Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

A novel secreted protein FgHrip1 from Fusarium graminearum triggers immune responses in plants

Fusarium graminearum,the primary pathogenic fungus responsible for Fusarium head blight(FHB)in wheat,secretes abundant chemical compounds that interact with host plants.In this study,a secreted protein FgHrip1,isolated from the culture filtrate of F.graminearum,was found to induce typical cell death in tobacco.The FgHrip1 gene was then cloned and expressed in Escherichia coli.Further bioassay analysis showed that the recombinant FgHrip1 induced early defense induction events,such as reactive oxygen species(ROS)production,callose deposition,and up-regulation of defense-related genes in tobacco.Furthermore,FgHrip1 significantly enhanced immunity in tobacco seedlings against Pseudomonas syringae pv.tabaci 6605(Pst.6605)and tobacco mosaic virus(TMV).FgHrip1-treated wheat spikes also exhibited defense-related transcript accumulation and developed immunity against FHB infection.Whereas the expression of FgHrip1 was induced during the infection process,the deletion of the gene impaired the virulence of F.graminearum.Our results suggest that FgHrip1triggers immunity and induces disease resistance in tobacco and wheat,thereby providing new insight into strategy for biocontrol of FHB.

A mite parasitoid,Pyemotes zhonghuajia,negatively impacts the fitness traits and immune response of the fall armyworm,Spodoptera frugiperda

Parasitoids are key regulators in ecological communities and widely used as agents in biocontrol programmes.The fall armyworm,Spodoptera frugiperda,recently invaded multiple continents and caused substantial economic losses in agriculture.Pyemotes zhonghuajia,a newly identified mite parasitoid,has shown potential for controlling various agricultural insect pests.Therefore,this study tested the performance of P.zhonghuajia in parasitising S.frugiperda.We also investigated the sublethal effects of parasitism by P.zhonghuajia on host fitness traits,transgenerational impacts,and cellular and humoral immunity.Our result showed that the fifth-instar larvae of S.frugiperda parasitised by 40 P.zhonghuajia were all dead(i.e.,a lethal effect),while parasitism by 5 or 10 P.zhonghuajia was considered sublethal since many S.frugiperda survived to adulthood and produced offspring after mating.The sublethal influences from parasitism by P.zhonghuajia resulted in reduced pupal weight,adult emergence rate and fecundity,but increased developmental time and longevity.Parasitism at both lethal(40 mites)and sublethal(10 mites)levels impaired the cellular and humoral immunity of S.frugiperda.This study presents the first empirical evidence that mite parasitoids can negatively influence host immunity.Moreover,it provides insights into the biocontrol potential of mite parasitoids and their interactions with hosts.

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

Comparison of immune responses and intestinal flora in epicutaneously sensitized BALB/c or C57BL/6 mouse models of food allergy

Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.

DDHD2 is involved in the malignant progression of early luminal A breast cancer by changing cell membrane proteins and immune responses functionality

Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

Effects of Mycotoxin from Maize on Immune Response of Vaccine for Piglets

[Objective] The aim of this study was to investigate the effects of mycotoxin from moldy maize on immune response of piglets.[Method] ELISA method was used to determine the content of Aflatoxin B1 and ochratoxin A in maize; after the piglets were fed with the moldy maize,the corresponding antibody titers in the serums of piglets were measured.[Result] Antibody levels of tested group were obvious lower than that of the control,while the histological section of immune organs also suggested that mycotoxin could significantly inhibit the immune response of piglets.[Conclusion] Mycotoxin in maize had important effects on the internal organs and immune response of piglets.