The spinal origin of cholestatic itch in experimental obstructive jaundice mouse model remains poorly understood. In this study, the jaundice model was established by bile duct ligation （BDL） in mice, and differenti...The spinal origin of cholestatic itch in experimental obstructive jaundice mouse model remains poorly understood. In this study, the jaundice model was established by bile duct ligation （BDL） in mice, and differential gene expression patterns were analyzed in the lower thoracic spinal cord involved in cholestatic pruritus after BDL operation using high-throughput RNA sequencing. At 21st day after BDL, the expression levels of ENSRNOG00000060523, ENSRNOG00000058405 and ENSRNOG00000055193 mRNA were significantly up-regulated, and those of ENSRNOG00000042197, ENSRNOG00000008478, ENSRNOG00000019607, ENSRNOG00000020647, ENSRNOG00000046289, Gemin8, Serpina3n and Trim63 mRNA were significantly down-regulated in BDL group. The RNAseq data of selected mRNAs were validated by RT-qPCR. The expression levels of ENSRNOG00000042197, ENSRNOG00000008478, ENSRNOG00000019607, ENSRNOG00000020647, ENSRNOG00000046289 and Serpina3n mRNA were significantly down-regulated in BDL group. This study suggested that cholestatic pruritus in experimental obstructive jaundice mouse model is related with in the changes of gene expression profiles in spinal cord.展开更多
Objoctive To identify differential genes between normal ovarian epithelium tissue and ovarian epithelial cancer using representational difference analysis of cDNA （cDNA-RDA）. Methods cDNA-RDA was performed to ident...Objoctive To identify differential genes between normal ovarian epithelium tissue and ovarian epithelial cancer using representational difference analysis of cDNA （cDNA-RDA）. Methods cDNA-RDA was performed to identify the differentially expressed sequences between cDNAs from cancer tissue and cDNAs from normal ovarian tissue in the same patient who was in the early stage of ovarian serous cystadenocarcinoma. These differentially expressed fragments were cloned and analyzed, then sequenced and compared with known genes. Results Three differentially cxpressed cDNA fragments were isolated using cDNA from normal ovarian tissue as tester and cDNA from cancer tissue as driver amplicon by cDNA-RDA. DP Ⅲ- 1 and DP Ⅲ-2 cDNA clone showed significant homology to the cDNA of alpha actin gene; DPⅢ-3 cDNA clone showed significant homology to the cDNA oftransgelin gene. Conclusion cDNA-RDA can bc used to sensitively identify the differentially expressed genes in ovarian serous cystadenocarcinoma. Ovarian serous cystadenocarcinoma involves alteration of multiple genes.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 The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greate...BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unkn...BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.展开更多
Introduction:Verruca vulgaris is one of the most common low-risk HPV infections and is characterized by excessive proliferation of keratinocytes.Currently,very little genetic information is available regarding verruca...Introduction:Verruca vulgaris is one of the most common low-risk HPV infections and is characterized by excessive proliferation of keratinocytes.Currently,very little genetic information is available regarding verruca vulgaris in the Chinese population.This study aimed to obtain comprehensive transcript information of verruca vulgaris by RNA sequencing.Methods:High-throughput sequencing was performed on three fresh verruca vulgaris samples and adjacent normal skin on the Illumina sequencing platform.The transcriptomes were analyzed using bioinformatics and the differentially expressed genes(DEGs)were verified by immunohistochemistry.Verruca vulgaris exhibited a unique molecular signature.Results:In total,1,643 DEGs were identified in verruca vulgaris compared to normal skin.The functions of the DEGs were studies by Gene Ontology(GO)enrichment,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,DEGs Reactome analysis,disease annotation function,and STRING protein-protein interaction(PPI)network analysis.The results revealed 595 GO terms associated with the cell cycle,signal transduction,immune system,signaling molecules,and interaction.The Reactome analysis revealed enrichment in reversible hydration of carbon dioxide and BMP signaling,while the disease annotation function revealed that the enriched DEGs are involved in keratosis disorders.The STRING PPI network showed that the edges with the highest density mainly included the 2′-5′oligoadenylate synthase(OAS)family-related proteins.Furthermore,the M-code analysis found ISG15,IRF7,and OASL were scored as significant modules and their high expression compared to the control was verified by immunohistochemistry.Conclusion:These findings contribute to the genetic information of verruca vulgaris in the Chinese population,revealing that interferon-stimulated genes may play essential roles in verruca vulgaris.展开更多
The term “microgravity” is used to describe the “weightlessness” or “zero-g” circumstances that can only be found in space beyond earth’s atmosphere. Rhodobacter sphaeroides is a gram-negative purple phototroph...The term “microgravity” is used to describe the “weightlessness” or “zero-g” circumstances that can only be found in space beyond earth’s atmosphere. Rhodobacter sphaeroides is a gram-negative purple phototroph, used as a model organism for this study due to its genomic complexity and metabolic versatility. Its genome has been completely sequenced, and profiles of the differential gene expression under aerobic, semi-aerobic, and photosynthetic conditions were examined. In this study, we hypothesized that R. sphaeroides will show altered growth characteristics, morphological properties, and gene expression patterns when grown under simulated microgravity. To test that, we measured the optical density and colony-forming units of cell cultures grown under both microgravity and normal gravity conditions. Differences in the cell morphology were observed using scanning electron microscopy (SEM) images by measuring the length and the surface area of the cells under both conditions. Furthermore, we also identified homologous genes of R. spheroides using the differential gene expression study of Acidovorax under microgravity in our laboratory. Growth kinetics results showed that R. sphaeroides cells grown under microgravity experience a shorter log phase and early stationary phase compared to the cells growing under normal gravity conditions. The length and surface area of the cells under microgravity were significantly higher confirming that bacterial cells experience altered morphological features when grown under microgravity conditions. Differentially expressed homologous gene analysis indicated that genes coding for several COG and GO functions, such as metabolism, signal-transduction, transcription, translation, chemotaxis, and cell motility are differentially expressed to adapt and survive microgravity.展开更多
Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture ...Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture industry.To understand the immune response of the turbot against V.anguillarum infection and to explore novel immune-related genes,the transcriptome analysis of turbot spleen and gills were conducted after V.anguillarum infection.Differentially expressed genes(DEGs)were identified in spleen and gill of the turbot amounted to 17261 and 16436,respectively.A large number of immunerelated DEGs were enriched in cytokine-cytokine receptor interaction signaling pathway,and the others by the kyoto encyclopedia of genes and genomes(KEGG)enrichment.The gene ontology(GO)classification analysis revealed that V.anguillarum infection had the greatest effect on biological processes and cellular components.Twelve immune-related DEGs were identified in the spleen(cstl.1,egfl6,lamb21,v2rx4,calcr,and gpr78a)and gills(ghra,sh3gl2a,cst12,inhbaa,cxcl8,and il-1b)by heat map.The proteinprotein interaction(PPI)networks were constructed to analyze the immune mechanism.The results demonstrate that the maturation and antigen processing of major histocompatibility complex(MHC)class II molecule,and calcitonin-or adrenomedullin-regulated physiological activity were important events in the immunity of turbot against V.anguillarum infection.In the gills,the protein interactions in TGF-βsignaling pathway,production of inflammatory factors,and endocytosis regulation were most significant.Our research laid a foundation for discovering novel immune-related genes and enriching the knowledge of immune mechanisms of turbot against V.anguillarum infection.展开更多
Objective The prognosis of glioblastoma is poor,and therapy-resistance is largely attributed to intratumor hypoxia.Hyperbaric oxygen(HBO)effectively alleviates hypoxia.However,the sole role of HBO in glioblastoma rema...Objective The prognosis of glioblastoma is poor,and therapy-resistance is largely attributed to intratumor hypoxia.Hyperbaric oxygen(HBO)effectively alleviates hypoxia.However,the sole role of HBO in glioblastoma remains controversial.We previously reported that HBO can promote apoptosis,shorten protrusions,and delay growth of glioblastoma,but the molecular mechanism is unclear.We aimed to test candidate genes in HBO-exposed glioblastoma cells and to analyze their correlation with the survival of glioblastoma patients.Methods Glioblastoma cell lines exposed to repetitive HBO or normobaric air(NBA)were collected for RNA isolation and microarray data analysis.GO analysis,KEGG pathway analysis and survival analysis of the differentially expressed genes(DEGs)were performed.Results HBO not only inhibited hypoxia-inducing genes including CA9,FGF11,PPFIA4,TCAF2 and SLC2A12,but also regulated vascularization by downregulating the expression of COL1A1,COL8A1,COL12A1,RHOJ and FILIP1L,ultimately attenuated hypoxic microenvironment of glioblastoma.HBO attenuated inflammatory microenvironment by reducing the expression of NLRP2,CARD8,MYD88 and CD180.HBO prevented metastasis by downregulating the expression of NTM,CXCL12,CXCL13,CXCR4,CXCR5,CDC42,IGFBP3,IGFBP5,GPC6,MMP19,ADAMTS1,EFEMP1,PTBP3,NF1 and PDCD1.HBO upregulated the expression of BAK1,PPIF,DDIT3,TP53I11 and FAS,whereas downregulated the expression of MDM4 and SIVA1,thus promoting apoptosis.HBO upregulated the expression of CDC25A,MCM2,PCNA,RFC33,DSCC1 and CDC14A,whereas downregulated the expression of ASNS,CDK6,CDKN1B,PTBP3 and MAD2L1,thus inhibiting cell cycle progression.Among these DEGs,17 indicator-genes of HBO prolonging survival were detected.Conclusions HBO is beneficial for glioblastoma.Glioblastoma patients with these predictive indicators may prolong survival with HBO therapy.These potential therapeutic targets especially COL1A1,ADAMTS1 and PTBP3 deserve further validation.展开更多
BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candi...BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.展开更多
BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the preval...BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.展开更多
Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of ...Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.展开更多
Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study lever...Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study leverages computational tools to dissect the differential gene expression profiles in retinoblastoma. Methods: Employing an in silico approach, we analyzed gene expression data from public repositories by applying rigorous statistical models, including limma and de seq 2, for identifying differentially expressed genes DEGs. Our findings were validated through cross-referencing with independent datasets and existing literature. We further employed functional annotation and pathway analysis to elucidate the biological significance of these DEGs. Results: Our computational analysis confirmed the dysregulation of key retinoblastoma-associated genes. In comparison to normal retinal tissue, RB1 exhibited a 2.5-fold increase in expression (adjusted p Conclusions: Our analysis reinforces the critical genetic alterations known in retinoblastoma and unveils new avenues for research into the disease’s molecular basis. The discovery of chemoresistance markers and immune-related genes opens potential pathways for personalized treatment strategies. The study’s outcomes emphasize the power of in silico analyses in unraveling complex cancer genomics.展开更多
Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of nov...Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.展开更多
[Objectives]To investigate the molecular mechanism of gene differential expression in A.tuberosum under Botrytis cinerea stress.[Methods]The leaf of A.tuberosum was inoculated with B.cinerea to induce resistance,then ...[Objectives]To investigate the molecular mechanism of gene differential expression in A.tuberosum under Botrytis cinerea stress.[Methods]The leaf of A.tuberosum was inoculated with B.cinerea to induce resistance,then leaf samples were taken at 2,4,8,12 and 24 h,respectively,after inoculation,and used for cDNA-SCoT analysis to detect the gene differential expressions.[Results]More than 800 bands with length of 100-1800 bp were obtained using 60 SCoT primers.A total of 40 differentially expressed EST sequences were screened out,and 18 non-redundant ESTs with high quality were obtained by cluster analyses of the ESTs sequencing.The results of BlastN showed that the differential genes of A.tuberosum mainly related to disease defense,signal transduction,and protein metabolism.[Conclusions]Further analysis of gene function indicated that brassinosteroid biosynthesis-like proteins,NBS-LRR type disease resistance protein,jasmonic acid induced protein,abscisic stress ripening protein may be involved in the process of the incompatible interaction between the A.tuberosum and B.cinerea.展开更多
Background:Tuberculosis is a leading cause of death worldwide.BCG is an effective vaccine,but not widely used in many parts of the world due to a variety of issues.Mycobacterium vaccae(M.vaccae)is another vaccine used...Background:Tuberculosis is a leading cause of death worldwide.BCG is an effective vaccine,but not widely used in many parts of the world due to a variety of issues.Mycobacterium vaccae(M.vaccae)is another vaccine used in human subjects to prevent tuberculosis.In the current study,we investigated the potential mechanisms of M.vaccae vaccination by determining differentially expressed genes in mice infected with M.tuberculosis before and after M.vaccae vaccination.Methods:Three days after exposure to M.tuberculosis H37 Rv strain(5×10~5 CFU),adult BALB/c mice randomly received either M.vaccae vaccine(22.5μg)or vehicle via intramuscular injection(n=8).Booster immunization was conducted 14 and 28 days after the primary immunization.Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis.Results:M.vaccae vaccination provided protection against M.tuberculosis infection(most prominent in the lungs).We identified 2,326 upregulated and 2,221 downregulated genes in vaccinated mice.These changes could be mapped to a total of 123 signaling pathways(68 upregulated and 55 downregulated).Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3 K-Akt signaling pathway as most likely to be functional.Conclusions:M.vaccae vaccine provided good protection in mice against M.tuberculosis infection,via a highly complex set of molecular changes.Our findings may provide clue to guide development of more effective vaccine against tuberculosis.展开更多
One of the impediments in the genetic improvement of cotton fiber is the paucity of information about genes associated with fiber development.Availability of chromosome arm substitution line CS-
AIM: To investigate the impact of hepatitis B virus (HBV) infection on cellular gene expression, by conducting both in vitro and in vivo studies. METHODS: Knockdown of HBV was targeted by stable expression of short ha...AIM: To investigate the impact of hepatitis B virus (HBV) infection on cellular gene expression, by conducting both in vitro and in vivo studies. METHODS: Knockdown of HBV was targeted by stable expression of short hairpin RNA (shRNA) in huH-1 cells. Cellular gene expression was compared using a human 30K cDNA microarray in the cells and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR) (qRT-PCR) in the cells, hepatocellular carcinoma (HCC) and surrounding non-cancerous liver tissues (SL). RESULTS: The expressions of HBsAg and HBx protein were markedly suppressed in the cells and in HBx transgenic mouse liver, respectively, after introduction of shRNA. Of the 30K genes studied, 135 and 103 genes were identified as being down- and up-regulated, respectively, by at least twofold in the knockdown cells. Functional annotation revealed that 85 and 62 genes were classified into four up-regulated and five down-regulated functional categories, respectively. When gene expression levels were compared between HCC and SL, eight candidate genes that were confirmed to be up- or down-regulated in the knockdown cells by both microarray and qRT-PCR analyses were not expressed as expected from HBV reduction in HCC, but had similar expression patterns in HBV- and hepatitis C virus-associated cases. In contrast, among the eight genes, only APM2 was constantly repressed in HBV non-associated tissues irrespective of HCC or SL. CONCLUSION: The signature of cellular gene expression should provide new information regarding the pathophysiological mechanisms of persistent hepatitis and hepatocarcinogenesis that are associated with HBV infection.展开更多
AIM： To identify tumor associated genes of rectal cancer and to probe the application possibility of gene expression profiles for the classification of tumors.METHODS： Rectal cancer tissues and their paired normal m...AIM： To identify tumor associated genes of rectal cancer and to probe the application possibility of gene expression profiles for the classification of tumors.METHODS： Rectal cancer tissues and their paired normal mucosa were obtained from patients undergoing surgical resection of rectal cancer. Total RNA was extracted using Trizol reagents. First strand cDNA synthesis was indirectly labeled with aminoallyl-dUTP and coupled with Cy3 or Cy5 dye NHS mono-functional ester. After normalization to total spots, the genes which background subtracted intensity did not exceed 2 SD above the mean blank were excluded. The data were then sorted to obtain genes differentially expressed by ≥ 2 fold up or down in at least 5 of the 21 patients.RESULTS： In the 21 rectal cancer patients, 23 genes were up-regulated in at least 5 samples and 15 genes were down-regulated in at least 5 patients. Hierachical cluster analysis classified the patients into two groups according to the clinicopathological stage, with one group being all above stage Ⅱ and one group all below stage Ⅱ.CONCLUSION： The up-regulated genes and downregulated genes may be molecular markers of rectal cancer. The expression profiles can be used for classification of rectal cancer.展开更多
The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and cells.It is crucial to explore the molecular an...The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and cells.It is crucial to explore the molecular and biological process alterations that occur after SCI for therapy development.The differences between the rostral and caudal regions around an SCI lesion have received little attention.Here,we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after SCI.We identified a set of differentially expressed genes,including Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1,between rostral and caudal regions at different time points following SCI.Functional enrichment analysis indicated that these genes were involved in response to mechanical stimulus,blood vessel development,and brain development.We then chose Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining validation.Our results indicate alterations in different biological events enriched in the rostral and caudal lesion areas,providing new insights into the pathology of SCI.展开更多
文摘The spinal origin of cholestatic itch in experimental obstructive jaundice mouse model remains poorly understood. In this study, the jaundice model was established by bile duct ligation （BDL） in mice, and differential gene expression patterns were analyzed in the lower thoracic spinal cord involved in cholestatic pruritus after BDL operation using high-throughput RNA sequencing. At 21st day after BDL, the expression levels of ENSRNOG00000060523, ENSRNOG00000058405 and ENSRNOG00000055193 mRNA were significantly up-regulated, and those of ENSRNOG00000042197, ENSRNOG00000008478, ENSRNOG00000019607, ENSRNOG00000020647, ENSRNOG00000046289, Gemin8, Serpina3n and Trim63 mRNA were significantly down-regulated in BDL group. The RNAseq data of selected mRNAs were validated by RT-qPCR. The expression levels of ENSRNOG00000042197, ENSRNOG00000008478, ENSRNOG00000019607, ENSRNOG00000020647, ENSRNOG00000046289 and Serpina3n mRNA were significantly down-regulated in BDL group. This study suggested that cholestatic pruritus in experimental obstructive jaundice mouse model is related with in the changes of gene expression profiles in spinal cord.
文摘Objoctive To identify differential genes between normal ovarian epithelium tissue and ovarian epithelial cancer using representational difference analysis of cDNA （cDNA-RDA）. Methods cDNA-RDA was performed to identify the differentially expressed sequences between cDNAs from cancer tissue and cDNAs from normal ovarian tissue in the same patient who was in the early stage of ovarian serous cystadenocarcinoma. These differentially expressed fragments were cloned and analyzed, then sequenced and compared with known genes. Results Three differentially cxpressed cDNA fragments were isolated using cDNA from normal ovarian tissue as tester and cDNA from cancer tissue as driver amplicon by cDNA-RDA. DP Ⅲ- 1 and DP Ⅲ-2 cDNA clone showed significant homology to the cDNA of alpha actin gene; DPⅢ-3 cDNA clone showed significant homology to the cDNA oftransgelin gene. Conclusion cDNA-RDA can bc used to sensitively identify the differentially expressed genes in ovarian serous cystadenocarcinoma. Ovarian serous cystadenocarcinoma involves alteration of multiple genes.
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 The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.
基金Supported by National Natural Science Foundation of China,No.82100594.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.
基金The National Natural Science Foundation of China(Grant No.81903227)supported our study.
文摘Introduction:Verruca vulgaris is one of the most common low-risk HPV infections and is characterized by excessive proliferation of keratinocytes.Currently,very little genetic information is available regarding verruca vulgaris in the Chinese population.This study aimed to obtain comprehensive transcript information of verruca vulgaris by RNA sequencing.Methods:High-throughput sequencing was performed on three fresh verruca vulgaris samples and adjacent normal skin on the Illumina sequencing platform.The transcriptomes were analyzed using bioinformatics and the differentially expressed genes(DEGs)were verified by immunohistochemistry.Verruca vulgaris exhibited a unique molecular signature.Results:In total,1,643 DEGs were identified in verruca vulgaris compared to normal skin.The functions of the DEGs were studies by Gene Ontology(GO)enrichment,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,DEGs Reactome analysis,disease annotation function,and STRING protein-protein interaction(PPI)network analysis.The results revealed 595 GO terms associated with the cell cycle,signal transduction,immune system,signaling molecules,and interaction.The Reactome analysis revealed enrichment in reversible hydration of carbon dioxide and BMP signaling,while the disease annotation function revealed that the enriched DEGs are involved in keratosis disorders.The STRING PPI network showed that the edges with the highest density mainly included the 2′-5′oligoadenylate synthase(OAS)family-related proteins.Furthermore,the M-code analysis found ISG15,IRF7,and OASL were scored as significant modules and their high expression compared to the control was verified by immunohistochemistry.Conclusion:These findings contribute to the genetic information of verruca vulgaris in the Chinese population,revealing that interferon-stimulated genes may play essential roles in verruca vulgaris.
文摘The term “microgravity” is used to describe the “weightlessness” or “zero-g” circumstances that can only be found in space beyond earth’s atmosphere. Rhodobacter sphaeroides is a gram-negative purple phototroph, used as a model organism for this study due to its genomic complexity and metabolic versatility. Its genome has been completely sequenced, and profiles of the differential gene expression under aerobic, semi-aerobic, and photosynthetic conditions were examined. In this study, we hypothesized that R. sphaeroides will show altered growth characteristics, morphological properties, and gene expression patterns when grown under simulated microgravity. To test that, we measured the optical density and colony-forming units of cell cultures grown under both microgravity and normal gravity conditions. Differences in the cell morphology were observed using scanning electron microscopy (SEM) images by measuring the length and the surface area of the cells under both conditions. Furthermore, we also identified homologous genes of R. spheroides using the differential gene expression study of Acidovorax under microgravity in our laboratory. Growth kinetics results showed that R. sphaeroides cells grown under microgravity experience a shorter log phase and early stationary phase compared to the cells growing under normal gravity conditions. The length and surface area of the cells under microgravity were significantly higher confirming that bacterial cells experience altered morphological features when grown under microgravity conditions. Differentially expressed homologous gene analysis indicated that genes coding for several COG and GO functions, such as metabolism, signal-transduction, transcription, translation, chemotaxis, and cell motility are differentially expressed to adapt and survive microgravity.
基金the National Key Research and Development Program of the Ministry of Science and Technology(CN)(No.2022YFD2400401)the Key Research and Development Plan of Shandong Province(CN)(for Academician Team in Shandong)(No.2023ZLYS02)+1 种基金the Fundamental Research Funds for the Central Universities(No.202261029)the Enterprise Authorized Project(No.20200025)。
文摘Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture industry.To understand the immune response of the turbot against V.anguillarum infection and to explore novel immune-related genes,the transcriptome analysis of turbot spleen and gills were conducted after V.anguillarum infection.Differentially expressed genes(DEGs)were identified in spleen and gill of the turbot amounted to 17261 and 16436,respectively.A large number of immunerelated DEGs were enriched in cytokine-cytokine receptor interaction signaling pathway,and the others by the kyoto encyclopedia of genes and genomes(KEGG)enrichment.The gene ontology(GO)classification analysis revealed that V.anguillarum infection had the greatest effect on biological processes and cellular components.Twelve immune-related DEGs were identified in the spleen(cstl.1,egfl6,lamb21,v2rx4,calcr,and gpr78a)and gills(ghra,sh3gl2a,cst12,inhbaa,cxcl8,and il-1b)by heat map.The proteinprotein interaction(PPI)networks were constructed to analyze the immune mechanism.The results demonstrate that the maturation and antigen processing of major histocompatibility complex(MHC)class II molecule,and calcitonin-or adrenomedullin-regulated physiological activity were important events in the immunity of turbot against V.anguillarum infection.In the gills,the protein interactions in TGF-βsignaling pathway,production of inflammatory factors,and endocytosis regulation were most significant.Our research laid a foundation for discovering novel immune-related genes and enriching the knowledge of immune mechanisms of turbot against V.anguillarum infection.
基金supported by Fundamental-Clinical Research Cooperation Fund of Capital Medical University[No.17JL(TTZX)]Capital’s Funds for Health Improvement and Research(No.2022-2-1072).
文摘Objective The prognosis of glioblastoma is poor,and therapy-resistance is largely attributed to intratumor hypoxia.Hyperbaric oxygen(HBO)effectively alleviates hypoxia.However,the sole role of HBO in glioblastoma remains controversial.We previously reported that HBO can promote apoptosis,shorten protrusions,and delay growth of glioblastoma,but the molecular mechanism is unclear.We aimed to test candidate genes in HBO-exposed glioblastoma cells and to analyze their correlation with the survival of glioblastoma patients.Methods Glioblastoma cell lines exposed to repetitive HBO or normobaric air(NBA)were collected for RNA isolation and microarray data analysis.GO analysis,KEGG pathway analysis and survival analysis of the differentially expressed genes(DEGs)were performed.Results HBO not only inhibited hypoxia-inducing genes including CA9,FGF11,PPFIA4,TCAF2 and SLC2A12,but also regulated vascularization by downregulating the expression of COL1A1,COL8A1,COL12A1,RHOJ and FILIP1L,ultimately attenuated hypoxic microenvironment of glioblastoma.HBO attenuated inflammatory microenvironment by reducing the expression of NLRP2,CARD8,MYD88 and CD180.HBO prevented metastasis by downregulating the expression of NTM,CXCL12,CXCL13,CXCR4,CXCR5,CDC42,IGFBP3,IGFBP5,GPC6,MMP19,ADAMTS1,EFEMP1,PTBP3,NF1 and PDCD1.HBO upregulated the expression of BAK1,PPIF,DDIT3,TP53I11 and FAS,whereas downregulated the expression of MDM4 and SIVA1,thus promoting apoptosis.HBO upregulated the expression of CDC25A,MCM2,PCNA,RFC33,DSCC1 and CDC14A,whereas downregulated the expression of ASNS,CDK6,CDKN1B,PTBP3 and MAD2L1,thus inhibiting cell cycle progression.Among these DEGs,17 indicator-genes of HBO prolonging survival were detected.Conclusions HBO is beneficial for glioblastoma.Glioblastoma patients with these predictive indicators may prolong survival with HBO therapy.These potential therapeutic targets especially COL1A1,ADAMTS1 and PTBP3 deserve further validation.
文摘BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.
文摘BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.
基金National Natural Science Foundation of China(81960877).
文摘Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.
文摘Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study leverages computational tools to dissect the differential gene expression profiles in retinoblastoma. Methods: Employing an in silico approach, we analyzed gene expression data from public repositories by applying rigorous statistical models, including limma and de seq 2, for identifying differentially expressed genes DEGs. Our findings were validated through cross-referencing with independent datasets and existing literature. We further employed functional annotation and pathway analysis to elucidate the biological significance of these DEGs. Results: Our computational analysis confirmed the dysregulation of key retinoblastoma-associated genes. In comparison to normal retinal tissue, RB1 exhibited a 2.5-fold increase in expression (adjusted p Conclusions: Our analysis reinforces the critical genetic alterations known in retinoblastoma and unveils new avenues for research into the disease’s molecular basis. The discovery of chemoresistance markers and immune-related genes opens potential pathways for personalized treatment strategies. The study’s outcomes emphasize the power of in silico analyses in unraveling complex cancer genomics.
文摘Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.
基金Supported by Key Scientific Research Projects of Colleges and Universities in Henan Province(21B210007).
文摘[Objectives]To investigate the molecular mechanism of gene differential expression in A.tuberosum under Botrytis cinerea stress.[Methods]The leaf of A.tuberosum was inoculated with B.cinerea to induce resistance,then leaf samples were taken at 2,4,8,12 and 24 h,respectively,after inoculation,and used for cDNA-SCoT analysis to detect the gene differential expressions.[Results]More than 800 bands with length of 100-1800 bp were obtained using 60 SCoT primers.A total of 40 differentially expressed EST sequences were screened out,and 18 non-redundant ESTs with high quality were obtained by cluster analyses of the ESTs sequencing.The results of BlastN showed that the differential genes of A.tuberosum mainly related to disease defense,signal transduction,and protein metabolism.[Conclusions]Further analysis of gene function indicated that brassinosteroid biosynthesis-like proteins,NBS-LRR type disease resistance protein,jasmonic acid induced protein,abscisic stress ripening protein may be involved in the process of the incompatible interaction between the A.tuberosum and B.cinerea.
基金supported by Grants from the National Natural Science Foundation of China(81801643)the National Key Program for Infectious Disease of China(2018ZX10731301–005)+1 种基金Beijing Municipal Science&Technology Commission(Z181100001718005)the Medical Science and Technology Youth Cultivation Program of PLA(16QNP075)。
文摘Background:Tuberculosis is a leading cause of death worldwide.BCG is an effective vaccine,but not widely used in many parts of the world due to a variety of issues.Mycobacterium vaccae(M.vaccae)is another vaccine used in human subjects to prevent tuberculosis.In the current study,we investigated the potential mechanisms of M.vaccae vaccination by determining differentially expressed genes in mice infected with M.tuberculosis before and after M.vaccae vaccination.Methods:Three days after exposure to M.tuberculosis H37 Rv strain(5×10~5 CFU),adult BALB/c mice randomly received either M.vaccae vaccine(22.5μg)or vehicle via intramuscular injection(n=8).Booster immunization was conducted 14 and 28 days after the primary immunization.Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis.Results:M.vaccae vaccination provided protection against M.tuberculosis infection(most prominent in the lungs).We identified 2,326 upregulated and 2,221 downregulated genes in vaccinated mice.These changes could be mapped to a total of 123 signaling pathways(68 upregulated and 55 downregulated).Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3 K-Akt signaling pathway as most likely to be functional.Conclusions:M.vaccae vaccine provided good protection in mice against M.tuberculosis infection,via a highly complex set of molecular changes.Our findings may provide clue to guide development of more effective vaccine against tuberculosis.
文摘One of the impediments in the genetic improvement of cotton fiber is the paucity of information about genes associated with fiber development.Availability of chromosome arm substitution line CS-
文摘AIM: To investigate the impact of hepatitis B virus (HBV) infection on cellular gene expression, by conducting both in vitro and in vivo studies. METHODS: Knockdown of HBV was targeted by stable expression of short hairpin RNA (shRNA) in huH-1 cells. Cellular gene expression was compared using a human 30K cDNA microarray in the cells and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR) (qRT-PCR) in the cells, hepatocellular carcinoma (HCC) and surrounding non-cancerous liver tissues (SL). RESULTS: The expressions of HBsAg and HBx protein were markedly suppressed in the cells and in HBx transgenic mouse liver, respectively, after introduction of shRNA. Of the 30K genes studied, 135 and 103 genes were identified as being down- and up-regulated, respectively, by at least twofold in the knockdown cells. Functional annotation revealed that 85 and 62 genes were classified into four up-regulated and five down-regulated functional categories, respectively. When gene expression levels were compared between HCC and SL, eight candidate genes that were confirmed to be up- or down-regulated in the knockdown cells by both microarray and qRT-PCR analyses were not expressed as expected from HBV reduction in HCC, but had similar expression patterns in HBV- and hepatitis C virus-associated cases. In contrast, among the eight genes, only APM2 was constantly repressed in HBV non-associated tissues irrespective of HCC or SL. CONCLUSION: The signature of cellular gene expression should provide new information regarding the pathophysiological mechanisms of persistent hepatitis and hepatocarcinogenesis that are associated with HBV infection.
基金Supported by Major Project of Shandong Provincial Scienceand Technology, No.011100105Shandong Natural SciencesFunding Committee, No. Y2003C03
文摘AIM： To identify tumor associated genes of rectal cancer and to probe the application possibility of gene expression profiles for the classification of tumors.METHODS： Rectal cancer tissues and their paired normal mucosa were obtained from patients undergoing surgical resection of rectal cancer. Total RNA was extracted using Trizol reagents. First strand cDNA synthesis was indirectly labeled with aminoallyl-dUTP and coupled with Cy3 or Cy5 dye NHS mono-functional ester. After normalization to total spots, the genes which background subtracted intensity did not exceed 2 SD above the mean blank were excluded. The data were then sorted to obtain genes differentially expressed by ≥ 2 fold up or down in at least 5 of the 21 patients.RESULTS： In the 21 rectal cancer patients, 23 genes were up-regulated in at least 5 samples and 15 genes were down-regulated in at least 5 patients. Hierachical cluster analysis classified the patients into two groups according to the clinicopathological stage, with one group being all above stage Ⅱ and one group all below stage Ⅱ.CONCLUSION： The up-regulated genes and downregulated genes may be molecular markers of rectal cancer. The expression profiles can be used for classification of rectal cancer.
基金supported by Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX-2065(to XMC).
文摘The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and cells.It is crucial to explore the molecular and biological process alterations that occur after SCI for therapy development.The differences between the rostral and caudal regions around an SCI lesion have received little attention.Here,we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after SCI.We identified a set of differentially expressed genes,including Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1,between rostral and caudal regions at different time points following SCI.Functional enrichment analysis indicated that these genes were involved in response to mechanical stimulus,blood vessel development,and brain development.We then chose Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining validation.Our results indicate alterations in different biological events enriched in the rostral and caudal lesion areas,providing new insights into the pathology of SCI.
