BACKGROUND Serum amyloid A1(SAA1)is an acute-phase protein involved in acute or chronic hepatitis.Its function is still controversial.In addition,the effect of the expression of SAA1 and its molecular function on the ...BACKGROUND Serum amyloid A1(SAA1)is an acute-phase protein involved in acute or chronic hepatitis.Its function is still controversial.In addition,the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma(HCC)is still unclear.AIM To demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways.METHODS SAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)in GEPIA tool,and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal.The high or low expression group was then drawn based on the median level of SAA1 expression.The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC,including tumor grade,patient disease stage,and the TP53 mutation.The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal.The tumor purity score and the immune score were analyzed with CIBERSORT.The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions.GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy.Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC.The similar genes of SAA1 in HCC were identified in GEPIA,and the proteinprotein interaction of SAA1 was conducted in the Metascape tool.The expression of C-X-C motif chemokine ligand 2,C-C motif chemokine ligand 23,and complement C5a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal,respectively.RESULTS SAA1 expression was decreased in HCC,and lower SAA1 expression predicted poorer overall survival,progression-free survival,and disease-specific survival.Furthermore,SAA1 expression was further decreased with increased tumor grade and patient disease stage.Also,SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53.SAA1 expression was negatively correlated with the TP53 mutation.Lower SAA1 predicted poorer survival rate,especially in the patients with no hepatitis virus infection,other than those with hepatitis virus infection.Moreover,the SAA1 expression was negatively correlated with tumor purity.In contrast,SAA1 expression was positively correlated with the immune score in HCC,and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC.Decreased SAA1 was closely associated with the immune tolerance of HCC.C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1,which could also serve as favorable prognosis markers for HCC.CONCLUSION SAA1 is downregulated in the liver tumor,and it is closely involved in the progression of HCC.Lower SAA1 expression indicates lower survival rate,especially for those patients without hepatitis virus infection.Lower SAA1 expression also suggests lower immune infiltrating cells,especially for those with immune cells exerting anti-tumor immune function.SAA1 expression is closely associated with the anti-tumor immune pathways.展开更多
Banana(Musa spp.),being a globally significant fruit crop,faces a myriad of threats from various diseases,such as Fusarium wilt,Xanthomonas wilt,bunchy top disease,and weevils disease.This review provides an overview ...Banana(Musa spp.),being a globally significant fruit crop,faces a myriad of threats from various diseases,such as Fusarium wilt,Xanthomonas wilt,bunchy top disease,and weevils disease.This review provides an overview of recent advancements in molecular mechanisms and immune signaling pathways underlying disease resistance in banana.First,the review discusses the latest research advances on banana pests and diseases.Subsequently,this review explores the immune responses and signaling pathways,pattern recognition receptor-triggered immunity,effector-triggered immunity,cell death,reactive oxygen species,autophagy,hormonal pathways,and other players involved in bananaedisease interactions.Finally,the review discusses the current understanding of the genetic architecture of disease resistance in banana,focusing on the identification of defense-related genes and quantitative trait loci associated with resistance to major pathogens and offering recommendations for genetic research.The conclusion underscores the significance of research on banana immunity,specifically highlighting the crucial need to identify endogenous resistance genes and elucidate immune signaling pathways for future efforts aimed at breeding disease-resistant banana.This review offers a comprehensive perspective on the molecular mechanisms underlying disease resistance in banana and serves as a valuable reference for breeding efforts aimed at enhancing banana's resistance to pathogens.展开更多
BACKGROUND Colon adenocarcinoma(COAD)ranks second in terms of cancer-related deaths.We found that fatty acid-binding protein 4(FABP4),which is related to cell adhesion and immunity,affects the occurrence and developme...BACKGROUND Colon adenocarcinoma(COAD)ranks second in terms of cancer-related deaths.We found that fatty acid-binding protein 4(FABP4),which is related to cell adhesion and immunity,affects the occurrence and development of COAD.This study focused on the possibility of using FABP4 as a biomarker for COAD and constructed a nomogram for predicting the survival of COAD patients.AIM To verify the possibility of using FABP4 as a biomarker for COAD.METHODS A total of 453 COAD tissue samples,along with 41 normal tissue samples,were obtained from The Cancer Genome Atlas database.The difference in FABP4 expression between COAD tissues and normal tissues was analyzed,and the results were verified by immunohistochemistry.The WGCNA algorithm links FABP4 expression with an enrichment analysis and with immune cell infiltration pathways.The biological functions of FABP4 and its coexpressed genes were explored through enrichment analyses.The ESTIMATE,CIBERSORT and ssGSEA methods were used for the immune infiltration analysis.Finally,risk scores were calculated by a Cox analysis.A nomogram was constructed by combining risk scores with routine clinicopathological factors.We assessed the accuracy of survival predictions based on the C-index.The C-index ranges from 0.5 to 1.0,and in general,a C-index value greater than 0.65 indicates a reasonable estimate.The results were validated using the Gene Expression Omnibus(GEO)database.RESULTS FABP4 was significantly differentially expressed in COAD.It is a promising auxiliary biomarker for screening and diagnosis.Enrichment analyses suggested that FABP4 may influence the invasion and progression of COAD through cell adhesion.The immunological analysis revealed that FABP4 expression in COAD was significantly positively correlated with immune cell infiltration.Moreover,a nomogram to predict the survival of COAD patients was successfully constructed by integrating the calculated risk scores of 15 candidate genes and routine clinicopathological factors.This nomogram could effectively predict 1-year,3-year,and 5-year survival(C-index=0.786)and was verified(C-index=0.73).CONCLUSION This study established FABP4 as an effective biomarker for screening,assisting in the diagnosis and determining the prognosis.展开更多
Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanism...Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanisms.Methods:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in epilepsy.Through differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub genes.Results:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated genes.Enrichment analysis underscored significant alterations in immune pathways in epilepsy.Two central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and inflammation.Subsequent experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic target.Conclusion:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune system.These findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.展开更多
Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus ...Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.展开更多
Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regu...Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to S.uberis,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring S.uberis subclinical mastitis and healthy control cows(n=3/group)were studied.Results:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns.The DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide scale.In general,DNA methylation level was lower in S.uberis‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDR<0.05)were identified between SUG and CTG,including 132,237,7412 and 34,693 DMCs in the context of CpG,CHG and CHH(H=A or T or C),respectively.Besides,101,612 methylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in SUG.Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑value<0.001).Functional enrichment of genes harboring≥15 DMCs,DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response to S.uberis infection,especially cytokine activities.Furthermore,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discriminated between SUG and CTG.Conclusion:The integration of methylome and transcriptome of milk somatic cells suggests the possible involve‑ment of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S.uberis.The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.展开更多
Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated ...Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated to this exciting field, and focused on new progress in personalized drug development and antibody drug against checkpoint pathway. Tais meeting report summarizes the key developments presented and discussed at the meeting, with a focus on immunotherapy, especially on the CTLA-4 and PD-1/PD-L1 pathways. The monoclonal antibody drugs intervening these checkpoint pathways have the potential to play a larger role in personalize medicine within the near future. Here we intended to provide a comprehensive summary about ongoing trends and future perspectives on personalized medicine in cancer therapy.展开更多
Endometrial carcinoma(EC)is a prevalent gynecological cancer,and its interaction with the immune system is pivotal in cancer progression.This comprehensive review explores the molecular mechanisms involved in the regu...Endometrial carcinoma(EC)is a prevalent gynecological cancer,and its interaction with the immune system is pivotal in cancer progression.This comprehensive review explores the molecular mechanisms involved in the regulation of EC by tumor-infiltrating immune cells.This review discusses the composition and functions of various immune cell types within the tumor microenvironment,including T cells,B cells,macrophages,and natural killer cells,and elucidates their specific roles in cancer control.It also delves into the immune evasion strategies employed by EC cells,with a specific focus on immune checkpoint pathways and their influence on tumor development.Signaling pathways,cytokines,and chemokines mediating immune responses within the tumor microenvironment are also detailed.Furthermore,clinical implications and therapeutic strategies,such as immunotherapies,are also reviewed,and relevant clinical trials are discussed.Additionally,this review discusses the existing gaps in our knowledge,suggests potential avenues for future research,and emphasizes the significance of understanding these mechanisms for enhanced EC treatment.This review provides an exhaustive overview of the current knowledge,supporting the ongoing quest for more effective therapeutic interventions on EC.展开更多
A systems biology approach was employed to gain insight into tick biology and interactions between vectors and pathogens.Haemaphysalis longicornis serves as one of the primary vectors of Babesia microti,significantly ...A systems biology approach was employed to gain insight into tick biology and interactions between vectors and pathogens.Haemaphysalis longicornis serves as one of the primary vectors of Babesia microti,significantly impacting human and animal health.Obtaining more information about their relationship is crucial for a comprehensive un-derstanding of tick and pathogen biology,pathogen transmission dynamics,and potential control strategies.RNA sequencing of uninfected and B.microti-infected ticks resulted in the identification of 15056 unigenes.Among these,1051 were found to be differentially expressed,with 796 being upregulated and 255 downregulated(P<0.05).Integrated tran-scriptomics datasets revealed the pivotal role of immune-related pathways,including the Toll,Janus kinase/signal transducer and activator of transcription(JAK-STAT),immunod-eficiency,and RNA interference(RNAi)pathways,in response to infection.Consequently,3 genes encoding critical transcriptional factor Dorsal,Relish,and STAT were selected for RNAi experiments.The knockdown of Dorsal,Relish,and STAT resulted in a substantial increase in Babesia infection levels compared to the respective controls.These findings significantly advanced our understanding of tick–Babesia molecular interactions and pro-posed novel tick antigens as potential vaccine targets against tick infestations and pathogen transmission.展开更多
Plants are constantly exposed to invasions by various pathogens due to their sessile lifestyle.Therefore,plants have evolved sophisticated immune systems to defend against pathogen infections.Rice,as a staple food cro...Plants are constantly exposed to invasions by various pathogens due to their sessile lifestyle.Therefore,plants have evolved sophisticated immune systems to defend against pathogen infections.Rice,as a staple food crop in the world,is persistently threatened by pathogenic attacks,leading to significant yield losses.For example,diseases such as rice blast and bacterial leaf blight severely impact rice production.展开更多
Monochamus alternatus, the main vector beetles of invasive pinewood nematode, has established a symbiotic relationship with a native ectotrophic fungal symbiont, Sporothrix sp. 1, in China. The immune response ofM. al...Monochamus alternatus, the main vector beetles of invasive pinewood nematode, has established a symbiotic relationship with a native ectotrophic fungal symbiont, Sporothrix sp. 1, in China. The immune response ofM. alternatus to S. sp. 1 in the coexistence of beetles and fungi is, however, unknown. Here, we report that immune responses ofM. alternatus pupae to infection caused by ectotrophic symbiotic fungus S. sp. 1 and entomopathogenic fungus Beauveria bassiana differ significantly. The S. sp. 1 did not kill the beetles while B. bassiana killed all upon injection. The transcriptome results showed that the numbers of differentially expressed genes in M. aIternatus infected with S. sp. 1 were 2-fold less than those infected with B. bassiana at 48 hours post infection. It was noticed that Toll and IMD pathways played a leading role in the beetle＇s immune system when infected by symbiotic fungus, but upon infection by entomopathogenic fimgus, only the Toll pathway gets triggered actively. Furthermore, the beetles could tolerate the infection of symbiotic fungi by retracing their Toll and IMD pathways at 48 h. This study provided a comprehensive sequence resource ofM. alternatus transcriptome for further study of the immune interactions between host and associated fungi.展开更多
The innate immune signaling network follows a canonical format for signal transmission.The innate immune pathway is crucial for defense against pathogens,yet its mechanistic crosstalk with aging processes remains larg...The innate immune signaling network follows a canonical format for signal transmission.The innate immune pathway is crucial for defense against pathogens,yet its mechanistic crosstalk with aging processes remains largely unexplored.Retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ),a key mediator of antiviral immunity within this pathway,has an enigmatic role in stem cell senescence.Our study reveals that RIG-Ⅰlevels increase in human genetic and physiological cellular aging models,and its accumulation drives cellular senescence.Conversely,CRISPR/Cas9-mediated RIG-Ⅰdeletion or pharmacological inhibition in human mesenchymal stem cells(h MSCs)confers resistance to senescence.Mechanistically,RIG-Ⅰbinds to endogenous m RNAs,with CDKN1A m RNA being a prominent target.Specifically,RIG-Ⅰstabilizes CDKN1A m RNA,resulting in elevated CDKN1A transcript levels and increased p21 Cip1 protein expression,which precipitates senescence.Collectively,our findings establish RIG-Ⅰas a post-transcriptional regulator of senescence and suggest potential targets for the mitigation of aging-related diseases.展开更多
Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the r...Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after BBR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13B(Tumor necrosis factor superfamily 13b,encoding B lymphocyte stimulator[BLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased BLyS levels,while BBR reversed this effect.Conclusion:BBR might inhibit V.parvula and further weaken the immunomodulatory effect of B cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.展开更多
Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function ...Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function are maintained through multidimensional mechanisms that can proficiently remove foreign pathogenic microorganisms while effectively maintaining local symbiotic microbial homeostasis.The basic immune mechanisms of the insect gut,such as the dual oxidase-reactive oxygen species(Duox-ROS)system and the immune deficiency(Imd)-signaling pathway,are involved in the maintenance of microbial homeostasis.This paper reviews the role of physical defenses,the Duox-ROS and Imd signaling pathways,the Janus kinase/signal transducers and activators of transcription signaling pathway,and intestinal symbiotic flora in the homeostatic maintenance of the insect gut microbiome.展开更多
Due to the absence of acquired immunity,insects primarily rely on their innate immune system to resist pathogenic microorganisms and parasitoids in natural habitats.This innate immune system can be classified into cel...Due to the absence of acquired immunity,insects primarily rely on their innate immune system to resist pathogenic microorganisms and parasitoids in natural habitats.This innate immune system can be classified into cellular immunity and humoral immunity.Cellular immunity is mediated by hemocytes,which perform phagocytosis,aggregation,and encapsulation to fight against invaders,whereas the humoral immunity primarily activates the immune signaling pathways and induces the generation of immune effectors.Existing studies have revealed that the hemipteran aphids lack some crucial immune genes compared to other insect species,indicating the different immune mechanisms in aphids.The current review summarizes the adverse impacts of pathogenic microorganisms and parasitoids on aphids,introduces the cellular and humoral immune systems in insects,and analyzes the differences between aphids and other insect species.Furthermore,our review also discussed the existing prospects and challenges in aphid immunity research,and proposed the potential application of immune genes in green pest management.展开更多
文摘BACKGROUND Serum amyloid A1(SAA1)is an acute-phase protein involved in acute or chronic hepatitis.Its function is still controversial.In addition,the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma(HCC)is still unclear.AIM To demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways.METHODS SAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)in GEPIA tool,and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal.The high or low expression group was then drawn based on the median level of SAA1 expression.The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC,including tumor grade,patient disease stage,and the TP53 mutation.The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal.The tumor purity score and the immune score were analyzed with CIBERSORT.The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions.GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy.Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC.The similar genes of SAA1 in HCC were identified in GEPIA,and the proteinprotein interaction of SAA1 was conducted in the Metascape tool.The expression of C-X-C motif chemokine ligand 2,C-C motif chemokine ligand 23,and complement C5a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal,respectively.RESULTS SAA1 expression was decreased in HCC,and lower SAA1 expression predicted poorer overall survival,progression-free survival,and disease-specific survival.Furthermore,SAA1 expression was further decreased with increased tumor grade and patient disease stage.Also,SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53.SAA1 expression was negatively correlated with the TP53 mutation.Lower SAA1 predicted poorer survival rate,especially in the patients with no hepatitis virus infection,other than those with hepatitis virus infection.Moreover,the SAA1 expression was negatively correlated with tumor purity.In contrast,SAA1 expression was positively correlated with the immune score in HCC,and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC.Decreased SAA1 was closely associated with the immune tolerance of HCC.C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1,which could also serve as favorable prognosis markers for HCC.CONCLUSION SAA1 is downregulated in the liver tumor,and it is closely involved in the progression of HCC.Lower SAA1 expression indicates lower survival rate,especially for those patients without hepatitis virus infection.Lower SAA1 expression also suggests lower immune infiltrating cells,especially for those with immune cells exerting anti-tumor immune function.SAA1 expression is closely associated with the anti-tumor immune pathways.
基金supported by the Natural Science Foundation of Guangdong Province(Grant Nos.2022A15151104922023A1515012955)Guangzhou Science and Technology Plan Project(Grant No.2023A04J0795).
文摘Banana(Musa spp.),being a globally significant fruit crop,faces a myriad of threats from various diseases,such as Fusarium wilt,Xanthomonas wilt,bunchy top disease,and weevils disease.This review provides an overview of recent advancements in molecular mechanisms and immune signaling pathways underlying disease resistance in banana.First,the review discusses the latest research advances on banana pests and diseases.Subsequently,this review explores the immune responses and signaling pathways,pattern recognition receptor-triggered immunity,effector-triggered immunity,cell death,reactive oxygen species,autophagy,hormonal pathways,and other players involved in bananaedisease interactions.Finally,the review discusses the current understanding of the genetic architecture of disease resistance in banana,focusing on the identification of defense-related genes and quantitative trait loci associated with resistance to major pathogens and offering recommendations for genetic research.The conclusion underscores the significance of research on banana immunity,specifically highlighting the crucial need to identify endogenous resistance genes and elucidate immune signaling pathways for future efforts aimed at breeding disease-resistant banana.This review offers a comprehensive perspective on the molecular mechanisms underlying disease resistance in banana and serves as a valuable reference for breeding efforts aimed at enhancing banana's resistance to pathogens.
基金Supported by the University Scientific Research Project of Anhui Province,No.2024AH051916the Quality Engineering Project of Anhui Province,No.2022sx159 and No.2022sdxx031the Key Research and Development Project of Anhui Province,No.2022e07020036.
文摘BACKGROUND Colon adenocarcinoma(COAD)ranks second in terms of cancer-related deaths.We found that fatty acid-binding protein 4(FABP4),which is related to cell adhesion and immunity,affects the occurrence and development of COAD.This study focused on the possibility of using FABP4 as a biomarker for COAD and constructed a nomogram for predicting the survival of COAD patients.AIM To verify the possibility of using FABP4 as a biomarker for COAD.METHODS A total of 453 COAD tissue samples,along with 41 normal tissue samples,were obtained from The Cancer Genome Atlas database.The difference in FABP4 expression between COAD tissues and normal tissues was analyzed,and the results were verified by immunohistochemistry.The WGCNA algorithm links FABP4 expression with an enrichment analysis and with immune cell infiltration pathways.The biological functions of FABP4 and its coexpressed genes were explored through enrichment analyses.The ESTIMATE,CIBERSORT and ssGSEA methods were used for the immune infiltration analysis.Finally,risk scores were calculated by a Cox analysis.A nomogram was constructed by combining risk scores with routine clinicopathological factors.We assessed the accuracy of survival predictions based on the C-index.The C-index ranges from 0.5 to 1.0,and in general,a C-index value greater than 0.65 indicates a reasonable estimate.The results were validated using the Gene Expression Omnibus(GEO)database.RESULTS FABP4 was significantly differentially expressed in COAD.It is a promising auxiliary biomarker for screening and diagnosis.Enrichment analyses suggested that FABP4 may influence the invasion and progression of COAD through cell adhesion.The immunological analysis revealed that FABP4 expression in COAD was significantly positively correlated with immune cell infiltration.Moreover,a nomogram to predict the survival of COAD patients was successfully constructed by integrating the calculated risk scores of 15 candidate genes and routine clinicopathological factors.This nomogram could effectively predict 1-year,3-year,and 5-year survival(C-index=0.786)and was verified(C-index=0.73).CONCLUSION This study established FABP4 as an effective biomarker for screening,assisting in the diagnosis and determining the prognosis.
基金supported by the Ningxia Natural Science Foundation(Grant No.2022AAC03741)the Ningxia Medical University Scientific Research Fund(Grant No.XZ2021025).
文摘Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanisms.Methods:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in epilepsy.Through differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub genes.Results:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated genes.Enrichment analysis underscored significant alterations in immune pathways in epilepsy.Two central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and inflammation.Subsequent experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic target.Conclusion:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune system.These findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.
基金supported by the Science and Technology Beneficiary Program of Ningxia Hui Autonomous Region(No.2023CMG03027)the Ningxia Key Research and Development Program(No.2022BEG03167)the National Natural Science Foundation of China(No.82060275).
文摘Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.
文摘Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to S.uberis,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring S.uberis subclinical mastitis and healthy control cows(n=3/group)were studied.Results:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns.The DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide scale.In general,DNA methylation level was lower in S.uberis‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDR<0.05)were identified between SUG and CTG,including 132,237,7412 and 34,693 DMCs in the context of CpG,CHG and CHH(H=A or T or C),respectively.Besides,101,612 methylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in SUG.Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑value<0.001).Functional enrichment of genes harboring≥15 DMCs,DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response to S.uberis infection,especially cytokine activities.Furthermore,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discriminated between SUG and CTG.Conclusion:The integration of methylome and transcriptome of milk somatic cells suggests the possible involve‑ment of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S.uberis.The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.
文摘Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated to this exciting field, and focused on new progress in personalized drug development and antibody drug against checkpoint pathway. Tais meeting report summarizes the key developments presented and discussed at the meeting, with a focus on immunotherapy, especially on the CTLA-4 and PD-1/PD-L1 pathways. The monoclonal antibody drugs intervening these checkpoint pathways have the potential to play a larger role in personalize medicine within the near future. Here we intended to provide a comprehensive summary about ongoing trends and future perspectives on personalized medicine in cancer therapy.
文摘Endometrial carcinoma(EC)is a prevalent gynecological cancer,and its interaction with the immune system is pivotal in cancer progression.This comprehensive review explores the molecular mechanisms involved in the regulation of EC by tumor-infiltrating immune cells.This review discusses the composition and functions of various immune cell types within the tumor microenvironment,including T cells,B cells,macrophages,and natural killer cells,and elucidates their specific roles in cancer control.It also delves into the immune evasion strategies employed by EC cells,with a specific focus on immune checkpoint pathways and their influence on tumor development.Signaling pathways,cytokines,and chemokines mediating immune responses within the tumor microenvironment are also detailed.Furthermore,clinical implications and therapeutic strategies,such as immunotherapies,are also reviewed,and relevant clinical trials are discussed.Additionally,this review discusses the existing gaps in our knowledge,suggests potential avenues for future research,and emphasizes the significance of understanding these mechanisms for enhanced EC treatment.This review provides an exhaustive overview of the current knowledge,supporting the ongoing quest for more effective therapeutic interventions on EC.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions,National Natural Science Foundation of China(32170142,81971917,81271792,81471571)Jiangsu Natural Science Foundation(BK20211310),and funding from Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases.
文摘A systems biology approach was employed to gain insight into tick biology and interactions between vectors and pathogens.Haemaphysalis longicornis serves as one of the primary vectors of Babesia microti,significantly impacting human and animal health.Obtaining more information about their relationship is crucial for a comprehensive un-derstanding of tick and pathogen biology,pathogen transmission dynamics,and potential control strategies.RNA sequencing of uninfected and B.microti-infected ticks resulted in the identification of 15056 unigenes.Among these,1051 were found to be differentially expressed,with 796 being upregulated and 255 downregulated(P<0.05).Integrated tran-scriptomics datasets revealed the pivotal role of immune-related pathways,including the Toll,Janus kinase/signal transducer and activator of transcription(JAK-STAT),immunod-eficiency,and RNA interference(RNAi)pathways,in response to infection.Consequently,3 genes encoding critical transcriptional factor Dorsal,Relish,and STAT were selected for RNAi experiments.The knockdown of Dorsal,Relish,and STAT resulted in a substantial increase in Babesia infection levels compared to the respective controls.These findings significantly advanced our understanding of tick–Babesia molecular interactions and pro-posed novel tick antigens as potential vaccine targets against tick infestations and pathogen transmission.
基金supported by the Beijing Life Science Academy(202400CC0050)the National Natural Science Foundation of China(32320103003)+2 种基金Chinese Universities Scientific Fund(2025TC023)Pinduoduo-China Agricultural University Research Fund(PC2023B02012)2115 Talent Development Program of China Agricultural University.
文摘Plants are constantly exposed to invasions by various pathogens due to their sessile lifestyle.Therefore,plants have evolved sophisticated immune systems to defend against pathogen infections.Rice,as a staple food crop in the world,is persistently threatened by pathogenic attacks,leading to significant yield losses.For example,diseases such as rice blast and bacterial leaf blight severely impact rice production.
基金supported by the Forestry Industry Research Special Funds for Public Welfare Project(201204501)National Key Plan for Scientific Research and Development of China(2016YFC1200604,2016YFD0500300)+2 种基金the High Technology Research and Development Program(HTRDP)of China(2014AA020529)National Natural Science Foundation of China(31572272,31370650,31402013,31221091,31672291,L1524009)the CAS Key Research Projects of the Frontier Science(QYZDBSSW-SMC014),and CAS(2015-SM-C-02)
文摘Monochamus alternatus, the main vector beetles of invasive pinewood nematode, has established a symbiotic relationship with a native ectotrophic fungal symbiont, Sporothrix sp. 1, in China. The immune response ofM. alternatus to S. sp. 1 in the coexistence of beetles and fungi is, however, unknown. Here, we report that immune responses ofM. alternatus pupae to infection caused by ectotrophic symbiotic fungus S. sp. 1 and entomopathogenic fungus Beauveria bassiana differ significantly. The S. sp. 1 did not kill the beetles while B. bassiana killed all upon injection. The transcriptome results showed that the numbers of differentially expressed genes in M. aIternatus infected with S. sp. 1 were 2-fold less than those infected with B. bassiana at 48 hours post infection. It was noticed that Toll and IMD pathways played a leading role in the beetle＇s immune system when infected by symbiotic fungus, but upon infection by entomopathogenic fimgus, only the Toll pathway gets triggered actively. Furthermore, the beetles could tolerate the infection of symbiotic fungi by retracing their Toll and IMD pathways at 48 h. This study provided a comprehensive sequence resource ofM. alternatus transcriptome for further study of the immune interactions between host and associated fungi.
基金supported by the National Natural Science Foundation of China(82192863,82361148131,82125011,81921006,92149301,92168201,82122024,82322025,82330044,32341001,92049304,92049116,32121001,82071588,82361148130,8231101626,82201714,82271600)the National Key Research and Development Program of China(2020YFA0804000,2022YFA1103700,2020YFA0112200+13 种基金the STI2030-Major Projects-2021ZD0202400,2021YFF1201000,2021YFA1101000)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation(Z230011,Z240018,JQ24044)the Informatization Plan of Chinese Academy of Sciences(CASWX2022SDC-XK14)New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY2023-13)CAS Youth Interdisciplinary Team,Key Laboratory of Alzheimer’s Disease of Zhejiang Province(ZJAD-2024001)Excellent Young Talents Program of Capital Medical University(12300927)The Project for Technology Development of Beijingaffiliated Medical Research Institutes(11000023T000002036310)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)Youth Innovation Promotion Association of CAS(2022083)The Fellowship of China Postdoctoral Science Foundation(2022M712216)Initiative Scientific Research Program,Institute of Zoology,Chinese Academy of Sciences(2023IOZ0102)。
文摘The innate immune signaling network follows a canonical format for signal transmission.The innate immune pathway is crucial for defense against pathogens,yet its mechanistic crosstalk with aging processes remains largely unexplored.Retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ),a key mediator of antiviral immunity within this pathway,has an enigmatic role in stem cell senescence.Our study reveals that RIG-Ⅰlevels increase in human genetic and physiological cellular aging models,and its accumulation drives cellular senescence.Conversely,CRISPR/Cas9-mediated RIG-Ⅰdeletion or pharmacological inhibition in human mesenchymal stem cells(h MSCs)confers resistance to senescence.Mechanistically,RIG-Ⅰbinds to endogenous m RNAs,with CDKN1A m RNA being a prominent target.Specifically,RIG-Ⅰstabilizes CDKN1A m RNA,resulting in elevated CDKN1A transcript levels and increased p21 Cip1 protein expression,which precipitates senescence.Collectively,our findings establish RIG-Ⅰas a post-transcriptional regulator of senescence and suggest potential targets for the mitigation of aging-related diseases.
基金supported by the grants from the National Key R&D Program of China(No.2020YFA0509200)the National Natural Science Foundation of China(Nos.82002622,81830081,31970718,and 81972203)+1 种基金the Shanghai Municipal Health Commission,Collaborative Innovation Cluster Project(No.2019CXJQ02)the Youth Project of Shanghai Municipal Health Commission(No.20194Y0096)
文摘Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after BBR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13B(Tumor necrosis factor superfamily 13b,encoding B lymphocyte stimulator[BLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased BLyS levels,while BBR reversed this effect.Conclusion:BBR might inhibit V.parvula and further weaken the immunomodulatory effect of B cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.
文摘Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function are maintained through multidimensional mechanisms that can proficiently remove foreign pathogenic microorganisms while effectively maintaining local symbiotic microbial homeostasis.The basic immune mechanisms of the insect gut,such as the dual oxidase-reactive oxygen species(Duox-ROS)system and the immune deficiency(Imd)-signaling pathway,are involved in the maintenance of microbial homeostasis.This paper reviews the role of physical defenses,the Duox-ROS and Imd signaling pathways,the Janus kinase/signal transducers and activators of transcription signaling pathway,and intestinal symbiotic flora in the homeostatic maintenance of the insect gut microbiome.
基金supported by the Major Project of China National Tobacco Corporation(110202201020(LS-04))National Key Research and Development Program of China(2022YFD1401800 and 2023YFD1700304).
文摘Due to the absence of acquired immunity,insects primarily rely on their innate immune system to resist pathogenic microorganisms and parasitoids in natural habitats.This innate immune system can be classified into cellular immunity and humoral immunity.Cellular immunity is mediated by hemocytes,which perform phagocytosis,aggregation,and encapsulation to fight against invaders,whereas the humoral immunity primarily activates the immune signaling pathways and induces the generation of immune effectors.Existing studies have revealed that the hemipteran aphids lack some crucial immune genes compared to other insect species,indicating the different immune mechanisms in aphids.The current review summarizes the adverse impacts of pathogenic microorganisms and parasitoids on aphids,introduces the cellular and humoral immune systems in insects,and analyzes the differences between aphids and other insect species.Furthermore,our review also discussed the existing prospects and challenges in aphid immunity research,and proposed the potential application of immune genes in green pest management.
