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 du...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.展开更多
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 func...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
The dinoflagellate Prorocentrum minimum is known to affect the normal physiological function of Exopalaemon carinicauda by inducing oxidative stress,apoptosis,and cellular injury.To study the effects of P.minimum on t...The dinoflagellate Prorocentrum minimum is known to affect the normal physiological function of Exopalaemon carinicauda by inducing oxidative stress,apoptosis,and cellular injury.To study the effects of P.minimum on the immune defense system of shrimp,E.carinicauda were exposed to 5×10^(3)cells mL^(-1)and 5×10^(4)cells mL^(-1)of P.minimum for 336 h in treatment groups,while E.carinicauda cultured in filtered seawater was employed as control.The total hemocyte counts(THC),hemocyanin concentration(HEM),and the activity of alkaline phosphatase(AKP)in hemolymph serum,as well as expressions of six immunity-related genes in hemocytes,hepatopancreases and gills were determined.The exposure of P.minimum significantly reduced the THC,HEM concentration and AKP activity in hemolymph serum.Immunity-related genes expressed differently in hemocytes,hepatopancreases and gills.Compared with the control group,the expressions of Crustin and pro PO in hemocytes were significantly up-regulated in the treatment groups,while the up-regulated expressions of LGBP,Lysozyme and Serpin were only found in the group exposed to 5×10^(4)cells mL^(-1)of P.minimum.In the gills of E.carinicauda exposed to P.minimum,the down-regulation of ALF,proPO and Serpin,up-regulation of LGBP and Lysozyme,as well as unaffected Crustin were observed.In hepatopancreases,the up-regulated expressions of LGBP,Crustin,Lysozyme,Serpin and proPO(only in 5×10^(3)cells mL^(-1)of P.minimum group)were found in the treatment groups.After exposure to P.minimum for 336 h,shrimps were injected with Vibrio parahaemolyticus and WSSV.The results showed that the mortality rates of shrimp in the treatment groups were significantly increased with a dose-dependent effect,which suggests that exposure to P.minimum may reduce the immunity of E.carinicauda.The research indicates that hemocytes and hepatopancreases play important roles in protecting the shrimp immune response to harmful algae,while the protection effect of hemolymph serum and gills may be suppressed.Since the exposure to P.minimum depressed the immunity of E.carinicauda,further studies are needed to confirm whether the presence of the algae will affect the susceptibility of shrimp to pathogens.展开更多
The objective of this study was to determine the role of SLC15A4 in the muramyl dipeptide(MDP)-mediated inflammatory response of bovine rumen epithelial cells(BRECs).First,changes in the m RNA expression of proinflamm...The objective of this study was to determine the role of SLC15A4 in the muramyl dipeptide(MDP)-mediated inflammatory response of bovine rumen epithelial cells(BRECs).First,changes in the m RNA expression of proinflammatory factor genes in BRECs following 10μg m L^(–1)MDP treatments were examined.RT-q PCR results showed that the expression of pro-inflammatory factor(IL-1β,IL-6,and TNF-α)m RNAs were significantly increased under MDP stimulation(P<0.001).Moreover,SLC15A4-Knockout(SLC15A4-KO)cells were obtained through lentivirus packaging,transfection,screening,and cell monoclonal culture.In order to gain further insight into the potential function of SLC15A4,we utilized transcriptome data,which revealed a change in the genes between WT-BRECs and SLC15A4-KO.Five down-regulated pro-inflammatory genes and 13 down-regulated chemokine genes related to the inflammatory response were identified.Meanwhile,the down-regulated genes were mostly enriched in the nuclear factorκB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathways.The results of RT-q PCR also verified these detected changes.To further determine the mechanism of how WT and SLC15A4-KO BRECs are involved in inflammatory responses,we investigated the inflammatory responses of cells exposed to MDP.WT-BRECs and SLC15A4-KO were treated with a culture medium containing 10μg m L^(–1)MDP,in comparison to a control without MDP.Our results show that SLC15A4-KO BRECs had reduced the expression of genes(IL-6,TNF-α,CXCL2,CXCL3,CXCL9,and CCL2)and proteins(p-p65 and p-p44/42)from the MDP-mediated inflammatory response compared to WT-BRECs(P<0.05).In this experiment,CRISPR-Cas9 was used to KO the di/tripeptide transporter SLC15A4,and its role was confirmed via the MDP-induced inflammatory response in BRECs.This work will provide a theoretical basis for studying the pro-inflammatory mechanism of MDP and its application in the prevention and treatment of subacute rumen acidosis in dairy cows.展开更多
Background: The roll-out of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was certainly among the fastest in medical history. Vaccination campaigns around the world began a year after t...Background: The roll-out of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was certainly among the fastest in medical history. Vaccination campaigns around the world began a year after the outbreak in 2019. When Austria started vaccinating the population in 2020, we took the opportunity to collect data from the first sets of patients receiving the vaccine in our study region of East Tyrol. Purpose: Many studies have been conducted examining the immunogenicity of the new vaccines using classic serological test methods in combination with an IFN-γ ELISpot. Undeniable disadvantages of using IFN-γ to characterize the status of the cellular immunity are that 1) being an acute phase cytokine, IFN-γ loses signal strength in the long run and 2) IFN-γ does not provide information about the involvement of T helper 2 (Th2) cells in the immune process. This implies that it can affect false negative data about the cell-mediated immune status. Method: Therefore, in addition to a chemiluminescent immunoassay and the enzymatic IFN-γ ELISpot, this study included a fluorescent ELISpot assay using precoated human SARS-CoV-2-specific IFN-γ/IL-2/IL-5 ELISpot kits to show a more holistic overview on the involvement of T helper 1 (Th1) cells as signal senders of IL-2 and Th2 cells as senders of IL-5. Results and Conclusion: Our study confirms good immunogenicity of Pfizer/BioNTech BNT162b2 COVID-19 (Comirnaty) with strong Th1 and vanishingly small Th2 participation. The fluorescent three color iSpot can improve the diagnostic results’ significance for the individual, especially when the infection has been longer in the past and the IFN-γ signal diminishes.展开更多
BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor mi...BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor microenvironmental immune response and tumorigenesis,and serves as the potential target for cellular and antibody immunotherapy.However,the immunotherapeutic role of STEAP4 in gastric cancer(GC)remains unclear.AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells,and explore the potential value of STEAP4 as an immune prognostic indicator in GC.METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients.Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature.R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC(GSE62254)by the ESTIMATE algorithm,and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis.RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues,and STEAP4 expression was positively correlated with the clinical stage of GC.In GC,the expression of STEAP4 was positively correlated with the infiltration levels of B cells,CD4+T cells,macrophages,neutrophils,and dendritic cells.The expression level of STEAP4 was strongly correlated with most of the immune markers.In addition,STEAP4 expression was inversely correlated with tumor purity,but correlated with stromal score(r=0.43,P<0.001),immune score(r=0.29,P<0.001)and estimate score(r=0.39,P<0.001).Moreover,stromal,immune,and estimate scores were higher in the STEAP4 high expression group,whereas tumor purity was higher in the STEAP4 Low expression group.The relationship between STEAP4 expression and prognosis of patients with GC was further investigated,and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival.In addition,Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC.CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC,with significantly high levels being associated with poor prognosis.Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells,which may contribute to the regulation of the tumor microenvironment.In conclusion,STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration,as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.展开更多
Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence ...Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.展开更多
BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporalit...BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporality of reinfection,provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and consequently helps in global public health and vaccination strategy.Among the patients who became infected with SARS-CoV-2,the majority who did not progress to death were those who developed the mild COVID-19,so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G(IgG)in mild cases of COVID-19.METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction(RT-qPCR)-positive volunteers from the municipality of Toledo/Paraná/Brazil,underwent two distinct serological tests,enzyme-linked immunosorbent assay,and detection of anti-nucleocapsid IgG.Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021.All assays were performed in duplicate and the manufacturers'recommendations were strictly followed.The data were statistically analyzed using multiple logistic regression;the variables were selected by applying the P<0.05 criterion.RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo.The time periods when the highest number of participants with detectable IgG was observed were 1,2 and 3 mo.It was observed that 9.42%of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57%were also IgG negative at less than 1 mo.At 5 mo,3.14%of volunteers were IgG negative,and at 6 or 7 mo,1 volunteer(0.52%)had no detectable IgG.During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study,no statistical significance was observed for any association analyzed.Moreover,considering the age category between 31 and 59 years as the exposed group,the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older,showing that in both age categories there was no association between the pair of variables analyzed.Regarding chronic disease,the exposure group consisted of the participants without any comorbidity,so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.CONCLUSION A temporal pattern of IgG response was not observed,but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.展开更多
In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free viru...In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.展开更多
Double sex and mab-3-related transcription factor 1(Dmrt1),which is expressed in goat male germline stem cells(mGSCs)and Sertoli cells,is one of the most conserved transcription factors involved in sex determination.I...Double sex and mab-3-related transcription factor 1(Dmrt1),which is expressed in goat male germline stem cells(mGSCs)and Sertoli cells,is one of the most conserved transcription factors involved in sex determination.In this study,we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs.Dmrt1 recruited promyelocytic leukemia zinc finger(Plzf),also known as zinc finger and BTB domain-containing protein 16(Zbtb16),to repress the Toll-like receptor 4(TLR4)-dependent inflammatory signaling pathway and nuclear factor(NF)-κB.Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells,while the expression of proinflammatory factors were significantly enhanced.We also demonstrated that Dmrt1 stimulated proliferation of mGSCs,but repressed apoptosis caused by the immune response.Thus,Dmrt1 is sufficient to reduce inflammation in the testes,thereby establishing the stability of spermatogenesis and the testicular microenvironment.展开更多
Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated...Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.展开更多
Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17...Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.展开更多
Receptor-like cytoplasmic kinases(RLCKs)represent a large family of proteins in plants.In Arabidopsis and rice,several RLCKs in subfamily VII(RLCKs-VII)have been implicated in pathogen-associated molecular pattern-tri...Receptor-like cytoplasmic kinases(RLCKs)represent a large family of proteins in plants.In Arabidopsis and rice,several RLCKs in subfamily VII(RLCKs-VII)have been implicated in pathogen-associated molecular pattern-triggered immunity and basal resistance against bacterial and fungal pathogens.However,little is known about roles of RLCKs-VII of the important crop common wheat(Triticum aestivum)in immune responses.Here,we isolated a RLCK-VII-encoding gene from wheat,designated as TaRLCK1B,and investigated its role in host immune response to infection of a necrotrophic fungus Rhizoctonia cerealis that is a major pathogen of sharp eyespot,a destructive disease of wheat.RNA-sequencing and RT-qPCR analyses showed that transcriptional level of TaRLCK1B was significantly higher in sharp eyespot-resistant wheat cultivars than in susceptible wheat cultivars.The gene transcription was rapidly and markedly elevated in the resistant wheat cultivars by R.cerealis infection.The TaRLCK1B protein was closely related to OsRLCK176,a rice resistance-related RLCKs-VII,with 84.03%identity.Virus-induced gene silencing plus wheat response to R.cerealis assay results indicated that silencing of TaRLCK1 impaired resistance to R.cerealis.Meantime,silencing of TaRLCK1 significantly elevated both the content of H2 O2(a major kind of reactive oxygen species,ROS)and the transcriptional level of the ROS-generating enzyme-encoding gene RBOH,but repressed the expression of the ROS-scavenging enzyme-encoding gene CAT1 at 18 hours after inoculation(hai)with R.cerealis.Taken together,these data suggested that TaRLCK1B was required for the early immune response of wheat to R.cerealis through modulating ROS signaling in wheat.展开更多
Background:Previous studies had shown that short-term acute heat stress(HS)affected the host’s metabolism and intestinal microbiota independent of feed intake(FI)reduction,and long-term calorie restriction caused int...Background:Previous studies had shown that short-term acute heat stress(HS)affected the host’s metabolism and intestinal microbiota independent of feed intake(FI)reduction,and long-term calorie restriction caused intestinal morphological injuries and gut microbial alterations.However,research on the effects of constant chronic HS on intestinal microbial composition and the roles of FI reduction played in is limited.This study aimed to investigate the effects of 7-day constant chronic HS on the composition of intestinal microbes in growing-finishing pigs,and its relationship with pigs’performance,intestinal morphology,and ileal immune response.Twenty-four growingfinishing pigs(Duroc×Large White×Landrace,30±1 kg body weight)were randomly assigned to three treatments(n=8),1)thermal neutral(TN)conditions(25±1℃)with ad libitum FI,2)HS conditions(35±1℃)with ad libitum FI,3)pair-fed(PF)with HS under TN conditions to discriminate the confounding effects of dissimilar FI,and the FI was the previous day’s average FI of HS.The small intestinal segments(duodenum,jejunum,and ileum)and feces were collected on d 8.Results:Results indicated that HS drastically declined(P<0.05)average daily gain(ADG)and average daily feed intake(ADFI)(about 61%)in comparison with TN,and caused hyperpyrexia,meanwhile PF caused hypothermia.Morphological observation by light and electron microscopes showed that both HS and PF treatment decreased(P<0.05)the villus and microvillus height compared with TN.Additionally,HS increased(P<0.05)protein expression of heat shock protein 70 in the duodenum,jejunum,and ileum.Furthermore,the expression of tight junction protein zonula occluden-1(ZO-1)in the duodenum and ileum,and Occludin in the ileum were enhanced(P<0.05)compared with TN and PF.Moreover,HS significantly enhanced(P<0.05)the mRNA relative expression of inflammatory cytokines(TLR-2,TLR-4,and tumor necrosis factor-α(TNF-α),IL-6,IL-8,PG1–5,β-defensin 2(pBD-2)),mucins(mucin-1 and mucin-2)and P65 protein level in the ileal mucosa tissue.Intestinal microbiota analysis by 16S rRNA sequencing showed lower(P<0.10)αdiversity in both HS and PF,and a separated cluster ofβdiversity among groups.Compared with TN,HS but not PF mainly reduced(FDR<0.05)Bacteroidetes(phylum),Bacteroidia(class)and elevated the proportions of Proteobacteria(phylum,FDR<0.05),Bacillales(order,FDR<0.05),Planococcaceae(family,FDR<0.05),Kurthia(genus,FDR<0.05),Streptococcaceae(family,FDR<0.10)and Streptococcus(genus,FDR<0.10).Notably,Lactobacillales(order)was decreased(FDR<0.05)by PF alone.Furthermore,the Spearman correlation analysis indicated that the microbes prevalent in HS were positively(P<0.05)associated with intestinal morphological injuries indicators and ileal immune response parameters,and the microbes reduced in HS were negatively(P<0.05)with the performance data.Conclusions:Intestinal morphological injuries and ileal immune response caused by constant chronic HS independent of FI showed close connections with alterations in intestinal microbiota in growing-finishing pigs.展开更多
In this study,juvenile turbot Scophthalmus maximus were vaccinated with attenuated Edwardsiella tarda(EIBAV1)and reared at two different densities,low density(LD),(5.25±0.02)kg m−2,as control group and high densi...In this study,juvenile turbot Scophthalmus maximus were vaccinated with attenuated Edwardsiella tarda(EIBAV1)and reared at two different densities,low density(LD),(5.25±0.02)kg m−2,as control group and high density(HD),(20.53±0.05)kg m−2,as experimental group.Only density was considered as the variable.Five weeks after vaccination,the transcriptomes of spleen and head kidney from the turbot in two groups were analyzed with RNA-Seq technology.A total of 447 million reads were assembled into 41136 genes with an average length of 1274 bp and a N50 size of 2295 bp.A comparison of gene expression between HD and LD groups revealed 1155 differentially expressed genes(DEGs).Enrichment and pathway analysis of the 10 immune-related DEGs showed the centrality of toll-like receptor signaling pathway,cytosolic DNA-sensing pathway and platelet activation in the host immune responses.The 5 overexpressed inflammatory cytokines and 5 downregulated signal-regulated cytokines genes are covered by these immune-related DEGs.It was inferred that cells suffer damage and the immune response is restrained in turbot under crowding stress.展开更多
After more than four decades of hepatitis B virus(HBV)vaccine implementation,its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved.Most countries have included ...After more than four decades of hepatitis B virus(HBV)vaccine implementation,its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved.Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth.All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications.However,there are still many drawbacks to overcome.The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization.Additionally,the current most widely used second-generation vaccines do not induce protective immunity in 5%to 10%of the population,particularly in people over 40-years-old,obese(body mass index>25 kg/m2),heavy smokers,and patients undergoing dialysis or infection with human immunodeficiency virus.Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance,particularly in difficult settings.These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.展开更多
Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great ...Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.展开更多
基金Supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY23D060002)the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties(No.2021C02069-5)+1 种基金the Pingyang County Science and Technology Strengthening Agriculture Industry Upgrading Project(No.2023PY003)the National Natural Science Foundation of China(No.41906107)。
文摘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.
基金The financial supports from the Key Program of the National Natural Science Foundation of China(32130082)Jiangxi High Level Talent Cultivation Project(20204BCJ24006)+1 种基金Project of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201911)Central Government Guide Local Special Fund Project for Scientific and Technological Development of Jiangxi Province(20212ZDD02008)。
文摘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.
基金funded by the National Natural Science Foundation of China(32060637 and 32260708)the Highlevel Talent Innovation and Entrepreneurship Funding Project in Guizhou Province,China((2021)01)+3 种基金the Guizhou Provincial Science and Technology Innovation Talent Team Project,China(Qian Ke He Pingtai RencaiCXTD(2021)004)the Systematic and Applied Acarology Society International Joint Project,England(2022(01))the Growth Project of Youth Talent in Ordinary Universities in Guizhou Province,China((2021)079)the Natural Science Special Project in Guizhou University,China((2020)02)。
文摘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.
基金supported by grants from the Natural Science Foundation of Hunan Province(2022JJ80044)the Youth Science Foundation of Xiangya Hospital(2019Q13).
文摘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.
基金the financial support received from the Natural Science Foundation of China(32202202 and 31871735)the Zhejiang Provincial Natural Science Foundation of China(LGN22C200027)the Open Fund of the Key Laboratory of Biosafety Detection for Zhejiang Market Regulation(2022BS004)。
文摘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.
基金financially supported by the earmarked fund for National Key R&D Program of China(No.2019YFD0900403)the Modern Agro-Industry Technology Research System(No.CARS-48)+2 种基金the Program of Shandong Leading Talent(No.LNJY2015002)the Central Public-Interest Scientific Institution Basal Research Fund of CAFS(No.2020TD46)the Scientific Research Start-Up Funding of Shandong Agricultural University(No.72188)。
文摘The dinoflagellate Prorocentrum minimum is known to affect the normal physiological function of Exopalaemon carinicauda by inducing oxidative stress,apoptosis,and cellular injury.To study the effects of P.minimum on the immune defense system of shrimp,E.carinicauda were exposed to 5×10^(3)cells mL^(-1)and 5×10^(4)cells mL^(-1)of P.minimum for 336 h in treatment groups,while E.carinicauda cultured in filtered seawater was employed as control.The total hemocyte counts(THC),hemocyanin concentration(HEM),and the activity of alkaline phosphatase(AKP)in hemolymph serum,as well as expressions of six immunity-related genes in hemocytes,hepatopancreases and gills were determined.The exposure of P.minimum significantly reduced the THC,HEM concentration and AKP activity in hemolymph serum.Immunity-related genes expressed differently in hemocytes,hepatopancreases and gills.Compared with the control group,the expressions of Crustin and pro PO in hemocytes were significantly up-regulated in the treatment groups,while the up-regulated expressions of LGBP,Lysozyme and Serpin were only found in the group exposed to 5×10^(4)cells mL^(-1)of P.minimum.In the gills of E.carinicauda exposed to P.minimum,the down-regulation of ALF,proPO and Serpin,up-regulation of LGBP and Lysozyme,as well as unaffected Crustin were observed.In hepatopancreases,the up-regulated expressions of LGBP,Crustin,Lysozyme,Serpin and proPO(only in 5×10^(3)cells mL^(-1)of P.minimum group)were found in the treatment groups.After exposure to P.minimum for 336 h,shrimps were injected with Vibrio parahaemolyticus and WSSV.The results showed that the mortality rates of shrimp in the treatment groups were significantly increased with a dose-dependent effect,which suggests that exposure to P.minimum may reduce the immunity of E.carinicauda.The research indicates that hemocytes and hepatopancreases play important roles in protecting the shrimp immune response to harmful algae,while the protection effect of hemolymph serum and gills may be suppressed.Since the exposure to P.minimum depressed the immunity of E.carinicauda,further studies are needed to confirm whether the presence of the algae will affect the susceptibility of shrimp to pathogens.
基金the National Natural Science Foundation of China(31972589)the earmarked fund for China Agriculture Research System(CARS-36)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX21-3283)。
文摘The objective of this study was to determine the role of SLC15A4 in the muramyl dipeptide(MDP)-mediated inflammatory response of bovine rumen epithelial cells(BRECs).First,changes in the m RNA expression of proinflammatory factor genes in BRECs following 10μg m L^(–1)MDP treatments were examined.RT-q PCR results showed that the expression of pro-inflammatory factor(IL-1β,IL-6,and TNF-α)m RNAs were significantly increased under MDP stimulation(P<0.001).Moreover,SLC15A4-Knockout(SLC15A4-KO)cells were obtained through lentivirus packaging,transfection,screening,and cell monoclonal culture.In order to gain further insight into the potential function of SLC15A4,we utilized transcriptome data,which revealed a change in the genes between WT-BRECs and SLC15A4-KO.Five down-regulated pro-inflammatory genes and 13 down-regulated chemokine genes related to the inflammatory response were identified.Meanwhile,the down-regulated genes were mostly enriched in the nuclear factorκB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathways.The results of RT-q PCR also verified these detected changes.To further determine the mechanism of how WT and SLC15A4-KO BRECs are involved in inflammatory responses,we investigated the inflammatory responses of cells exposed to MDP.WT-BRECs and SLC15A4-KO were treated with a culture medium containing 10μg m L^(–1)MDP,in comparison to a control without MDP.Our results show that SLC15A4-KO BRECs had reduced the expression of genes(IL-6,TNF-α,CXCL2,CXCL3,CXCL9,and CCL2)and proteins(p-p65 and p-p44/42)from the MDP-mediated inflammatory response compared to WT-BRECs(P<0.05).In this experiment,CRISPR-Cas9 was used to KO the di/tripeptide transporter SLC15A4,and its role was confirmed via the MDP-induced inflammatory response in BRECs.This work will provide a theoretical basis for studying the pro-inflammatory mechanism of MDP and its application in the prevention and treatment of subacute rumen acidosis in dairy cows.
文摘Background: The roll-out of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was certainly among the fastest in medical history. Vaccination campaigns around the world began a year after the outbreak in 2019. When Austria started vaccinating the population in 2020, we took the opportunity to collect data from the first sets of patients receiving the vaccine in our study region of East Tyrol. Purpose: Many studies have been conducted examining the immunogenicity of the new vaccines using classic serological test methods in combination with an IFN-γ ELISpot. Undeniable disadvantages of using IFN-γ to characterize the status of the cellular immunity are that 1) being an acute phase cytokine, IFN-γ loses signal strength in the long run and 2) IFN-γ does not provide information about the involvement of T helper 2 (Th2) cells in the immune process. This implies that it can affect false negative data about the cell-mediated immune status. Method: Therefore, in addition to a chemiluminescent immunoassay and the enzymatic IFN-γ ELISpot, this study included a fluorescent ELISpot assay using precoated human SARS-CoV-2-specific IFN-γ/IL-2/IL-5 ELISpot kits to show a more holistic overview on the involvement of T helper 1 (Th1) cells as signal senders of IL-2 and Th2 cells as senders of IL-5. Results and Conclusion: Our study confirms good immunogenicity of Pfizer/BioNTech BNT162b2 COVID-19 (Comirnaty) with strong Th1 and vanishingly small Th2 participation. The fluorescent three color iSpot can improve the diagnostic results’ significance for the individual, especially when the infection has been longer in the past and the IFN-γ signal diminishes.
基金the National Natural Science Foundation of China,No.82273457 and No.81501539Guangdong Basic and Applied Basic Research Foundation,No.2023A1515012762 and No.2021A1515012180+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor microenvironmental immune response and tumorigenesis,and serves as the potential target for cellular and antibody immunotherapy.However,the immunotherapeutic role of STEAP4 in gastric cancer(GC)remains unclear.AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells,and explore the potential value of STEAP4 as an immune prognostic indicator in GC.METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients.Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature.R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC(GSE62254)by the ESTIMATE algorithm,and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis.RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues,and STEAP4 expression was positively correlated with the clinical stage of GC.In GC,the expression of STEAP4 was positively correlated with the infiltration levels of B cells,CD4+T cells,macrophages,neutrophils,and dendritic cells.The expression level of STEAP4 was strongly correlated with most of the immune markers.In addition,STEAP4 expression was inversely correlated with tumor purity,but correlated with stromal score(r=0.43,P<0.001),immune score(r=0.29,P<0.001)and estimate score(r=0.39,P<0.001).Moreover,stromal,immune,and estimate scores were higher in the STEAP4 high expression group,whereas tumor purity was higher in the STEAP4 Low expression group.The relationship between STEAP4 expression and prognosis of patients with GC was further investigated,and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival.In addition,Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC.CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC,with significantly high levels being associated with poor prognosis.Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells,which may contribute to the regulation of the tumor microenvironment.In conclusion,STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration,as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.
基金supported in part by the grant from National Natural Science Foundation of China(82171818,81703048,82041019,and 82101919)the grant from Defense Industrial Technology Development Program of China(JCKY2020802B001)Beijing Municipal Science and Technology Commission(Z201100005420024)。
文摘Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.
文摘BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporality of reinfection,provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and consequently helps in global public health and vaccination strategy.Among the patients who became infected with SARS-CoV-2,the majority who did not progress to death were those who developed the mild COVID-19,so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G(IgG)in mild cases of COVID-19.METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction(RT-qPCR)-positive volunteers from the municipality of Toledo/Paraná/Brazil,underwent two distinct serological tests,enzyme-linked immunosorbent assay,and detection of anti-nucleocapsid IgG.Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021.All assays were performed in duplicate and the manufacturers'recommendations were strictly followed.The data were statistically analyzed using multiple logistic regression;the variables were selected by applying the P<0.05 criterion.RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo.The time periods when the highest number of participants with detectable IgG was observed were 1,2 and 3 mo.It was observed that 9.42%of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57%were also IgG negative at less than 1 mo.At 5 mo,3.14%of volunteers were IgG negative,and at 6 or 7 mo,1 volunteer(0.52%)had no detectable IgG.During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study,no statistical significance was observed for any association analyzed.Moreover,considering the age category between 31 and 59 years as the exposed group,the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older,showing that in both age categories there was no association between the pair of variables analyzed.Regarding chronic disease,the exposure group consisted of the participants without any comorbidity,so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.CONCLUSION A temporal pattern of IgG response was not observed,but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.
基金The work was supported by NSF of China(11201002)Natural Science Foundation of Universities in Anhui Province(KJ2017A815).
文摘In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.
基金This work was supported by the China National Basic Research Program(2016YFA0100203)National Natural Science Foundation of China(31572399Detail,32072806,32072815,32002246)+3 种基金State Key Lab of Reproductive Regulation&Breeding of Grassland Livestock(SKL-OT-201801)Science and Technology Major Project of Inner Mongolia Autonomous Region of China(ZDZX2018065)and Shaanxi Province Science and Technology Innovation Team(2019TD-036)The authors thank Dr.John Clotaire Daguia Zambe for helpful comments about this paper,Jia Fang for the PGL3-NF-κB luciferase reporter plasmid,and Dong-Xue Che for bioinformatics analysis.
文摘Double sex and mab-3-related transcription factor 1(Dmrt1),which is expressed in goat male germline stem cells(mGSCs)and Sertoli cells,is one of the most conserved transcription factors involved in sex determination.In this study,we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs.Dmrt1 recruited promyelocytic leukemia zinc finger(Plzf),also known as zinc finger and BTB domain-containing protein 16(Zbtb16),to repress the Toll-like receptor 4(TLR4)-dependent inflammatory signaling pathway and nuclear factor(NF)-κB.Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells,while the expression of proinflammatory factors were significantly enhanced.We also demonstrated that Dmrt1 stimulated proliferation of mGSCs,but repressed apoptosis caused by the immune response.Thus,Dmrt1 is sufficient to reduce inflammation in the testes,thereby establishing the stability of spermatogenesis and the testicular microenvironment.
基金the National Natural Science Foundation of China,Nos.81571213(to BW),81800583(to YYX),81601539(to DM)and 81601084(to YC)+3 种基金the National Key Research and Development Program of China,No.2017YFA0104304(to BW)the Nanjing Medical Science and Technique Development Foundation of China,Nos.QRX17006(to BW),QRX17057(to DM)the Key Project Medical Science and Technology Development Foundation,Nanjing Department of Health and the Nanjing Medical Science of China,No.201803024(to TYG)Innovation Platform,No.ZDX16005(to BW)。
文摘Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.
文摘Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.
基金This study was funded by the Natural Science Foundation of China(31771789)the National Key Project for Research on Transgenic Biology,China(2016ZX08002-001-004)+1 种基金Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2018QNRC001)The authors are very grateful to Prof.Jia Jizeng(ICS,CAAS)for providing the RIL population and Prof.Yu Jinfeng(Shandong Agricultural University,Shandong)for providing R.cerealis strain WK207.
文摘Receptor-like cytoplasmic kinases(RLCKs)represent a large family of proteins in plants.In Arabidopsis and rice,several RLCKs in subfamily VII(RLCKs-VII)have been implicated in pathogen-associated molecular pattern-triggered immunity and basal resistance against bacterial and fungal pathogens.However,little is known about roles of RLCKs-VII of the important crop common wheat(Triticum aestivum)in immune responses.Here,we isolated a RLCK-VII-encoding gene from wheat,designated as TaRLCK1B,and investigated its role in host immune response to infection of a necrotrophic fungus Rhizoctonia cerealis that is a major pathogen of sharp eyespot,a destructive disease of wheat.RNA-sequencing and RT-qPCR analyses showed that transcriptional level of TaRLCK1B was significantly higher in sharp eyespot-resistant wheat cultivars than in susceptible wheat cultivars.The gene transcription was rapidly and markedly elevated in the resistant wheat cultivars by R.cerealis infection.The TaRLCK1B protein was closely related to OsRLCK176,a rice resistance-related RLCKs-VII,with 84.03%identity.Virus-induced gene silencing plus wheat response to R.cerealis assay results indicated that silencing of TaRLCK1 impaired resistance to R.cerealis.Meantime,silencing of TaRLCK1 significantly elevated both the content of H2 O2(a major kind of reactive oxygen species,ROS)and the transcriptional level of the ROS-generating enzyme-encoding gene RBOH,but repressed the expression of the ROS-scavenging enzyme-encoding gene CAT1 at 18 hours after inoculation(hai)with R.cerealis.Taken together,these data suggested that TaRLCK1B was required for the early immune response of wheat to R.cerealis through modulating ROS signaling in wheat.
基金supported by National Key Research and Development Program of China(2016YFD0500501)the China Agriculture Research System of MOF and MARA+1 种基金the Science and Technology Program of Guangdong Academy of Agricultural Sciences(R2020PY-JG009,202106TD)the Project of Swine Innovation Team in Guangdong Modern Agricultural Research System(2021KJ126)。
文摘Background:Previous studies had shown that short-term acute heat stress(HS)affected the host’s metabolism and intestinal microbiota independent of feed intake(FI)reduction,and long-term calorie restriction caused intestinal morphological injuries and gut microbial alterations.However,research on the effects of constant chronic HS on intestinal microbial composition and the roles of FI reduction played in is limited.This study aimed to investigate the effects of 7-day constant chronic HS on the composition of intestinal microbes in growing-finishing pigs,and its relationship with pigs’performance,intestinal morphology,and ileal immune response.Twenty-four growingfinishing pigs(Duroc×Large White×Landrace,30±1 kg body weight)were randomly assigned to three treatments(n=8),1)thermal neutral(TN)conditions(25±1℃)with ad libitum FI,2)HS conditions(35±1℃)with ad libitum FI,3)pair-fed(PF)with HS under TN conditions to discriminate the confounding effects of dissimilar FI,and the FI was the previous day’s average FI of HS.The small intestinal segments(duodenum,jejunum,and ileum)and feces were collected on d 8.Results:Results indicated that HS drastically declined(P<0.05)average daily gain(ADG)and average daily feed intake(ADFI)(about 61%)in comparison with TN,and caused hyperpyrexia,meanwhile PF caused hypothermia.Morphological observation by light and electron microscopes showed that both HS and PF treatment decreased(P<0.05)the villus and microvillus height compared with TN.Additionally,HS increased(P<0.05)protein expression of heat shock protein 70 in the duodenum,jejunum,and ileum.Furthermore,the expression of tight junction protein zonula occluden-1(ZO-1)in the duodenum and ileum,and Occludin in the ileum were enhanced(P<0.05)compared with TN and PF.Moreover,HS significantly enhanced(P<0.05)the mRNA relative expression of inflammatory cytokines(TLR-2,TLR-4,and tumor necrosis factor-α(TNF-α),IL-6,IL-8,PG1–5,β-defensin 2(pBD-2)),mucins(mucin-1 and mucin-2)and P65 protein level in the ileal mucosa tissue.Intestinal microbiota analysis by 16S rRNA sequencing showed lower(P<0.10)αdiversity in both HS and PF,and a separated cluster ofβdiversity among groups.Compared with TN,HS but not PF mainly reduced(FDR<0.05)Bacteroidetes(phylum),Bacteroidia(class)and elevated the proportions of Proteobacteria(phylum,FDR<0.05),Bacillales(order,FDR<0.05),Planococcaceae(family,FDR<0.05),Kurthia(genus,FDR<0.05),Streptococcaceae(family,FDR<0.10)and Streptococcus(genus,FDR<0.10).Notably,Lactobacillales(order)was decreased(FDR<0.05)by PF alone.Furthermore,the Spearman correlation analysis indicated that the microbes prevalent in HS were positively(P<0.05)associated with intestinal morphological injuries indicators and ileal immune response parameters,and the microbes reduced in HS were negatively(P<0.05)with the performance data.Conclusions:Intestinal morphological injuries and ileal immune response caused by constant chronic HS independent of FI showed close connections with alterations in intestinal microbiota in growing-finishing pigs.
基金the National Key R&D Program of China(No.2017YFB0404001)the Central Public-Interest Scientific Institution Basal Research Fund,CAFS(No.2017HYZD04)+1 种基金the Qingdao Shinan District Science and Technology Bureau(No.2016-3-006)the Modern Agriculture Industry System Construction Special Funds(No.CARS-47-G24).
文摘In this study,juvenile turbot Scophthalmus maximus were vaccinated with attenuated Edwardsiella tarda(EIBAV1)and reared at two different densities,low density(LD),(5.25±0.02)kg m−2,as control group and high density(HD),(20.53±0.05)kg m−2,as experimental group.Only density was considered as the variable.Five weeks after vaccination,the transcriptomes of spleen and head kidney from the turbot in two groups were analyzed with RNA-Seq technology.A total of 447 million reads were assembled into 41136 genes with an average length of 1274 bp and a N50 size of 2295 bp.A comparison of gene expression between HD and LD groups revealed 1155 differentially expressed genes(DEGs).Enrichment and pathway analysis of the 10 immune-related DEGs showed the centrality of toll-like receptor signaling pathway,cytosolic DNA-sensing pathway and platelet activation in the host immune responses.The 5 overexpressed inflammatory cytokines and 5 downregulated signal-regulated cytokines genes are covered by these immune-related DEGs.It was inferred that cells suffer damage and the immune response is restrained in turbot under crowding stress.
文摘After more than four decades of hepatitis B virus(HBV)vaccine implementation,its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved.Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth.All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications.However,there are still many drawbacks to overcome.The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization.Additionally,the current most widely used second-generation vaccines do not induce protective immunity in 5%to 10%of the population,particularly in people over 40-years-old,obese(body mass index>25 kg/m2),heavy smokers,and patients undergoing dialysis or infection with human immunodeficiency virus.Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance,particularly in difficult settings.These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.
基金Grants from"Instituto de Salud Carlos Ⅲ",Spain and"European Regional Development Fund(ERDF),a way of making Europe",E.U.,No.PI12/00130"Fundacion de In-vestigacion Medica Mutua Madrilena",Spain,No.8922/2011Lokhande MU was funded by a research grant from"Asoci-acion de Hepatologia Translacional"No.AHT-2010/01,Spain
文摘Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.
