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: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
Maize (Zea raays L.) is one of the most important crops because of the remarkable properties of its hybrid, which is responsible for the high commercial value of hybrid maize. The genetic basis of heterosis (hybrid...Maize (Zea raays L.) is one of the most important crops because of the remarkable properties of its hybrid, which is responsible for the high commercial value of hybrid maize. The genetic basis of heterosis (hybrid vigor) is not well understood. A differential display technique was performed to identify genes with differential expression across twelve maize inbred lines and thirty-three hybrids during ear development. An incomplete diallel design was used to investigate the relationship between the global framework of differential gene expression and heterosis. It was found that the genes belonging to MONO pattern (i.e., genes expressed in both parental lines and in hybrid) was the highest in percentage among the total five patterns and illustrated that the properties of differentially expressed genes are not entirely responsible for heterosis. Furthermore,a larger number of differentially expressed genes in hybrid, which serves as a major reservoir for generating novel phenotypes that exhibit heterosis of certain agronomic traits during early development and differentiation of maize ear. Moreover, there were some silent genesin hybrids that are responsible for the arrest or abortion of spikelets and for the increase in kernels weight.展开更多
Background A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait,and expression quantitative trait loci(eQTL)studies provide important information to help close that gap...Background A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait,and expression quantitative trait loci(eQTL)studies provide important information to help close that gap.However,two concerns that arise with eQTL analyses using RNA-sequencing data are normalization of data across samples and the data not following a normal distribution.Multiple pipelines have been suggested to address this.For instance,the most recent analysis of the human and farm Genotype-Tissue Expression(GTEx)project proposes using trimmed means of M-values(TMM)to normalize the data followed by an inverse normal transformation.Results In this study,we reasoned that eQTL analysis could be carried out using the same framework used for dif-ferential gene expression(DGE),which uses a negative binomial model,a statistical test feasible for count data.Using the GTEx framework,we identified 35 significant eQTLs(P<5×10^(–8))following the ANOVA model and 39 significant eQTLs(P<5×10^(–8))following the additive model.Using a differential gene expression framework,we identified 930 and six significant eQTLs(P<5×10^(–8))following an analytical framework equivalent to the ANOVA and additive model,respectively.When we compared the two approaches,there was no overlap of significant eQTLs between the two frameworks.Because we defined specific contrasts,we identified trans eQTLs that more closely resembled what we expect from genetic variants showing complete dominance between alleles.Yet,these were not identified by the GTEx framework.Conclusions Our results show that transforming RNA-sequencing data to fit a normal distribution prior to eQTL analysis is not required when the DGE framework is employed.Our proposed approach detected biologically relevant variants that otherwise would not have been identified due to data transformation to fit a normal distribution.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
BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has graduall...BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.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
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
BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-posi...BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown.The epigenetic modification of DNA hydroxymethylation is critical in tumor development.Further,5-hydroxymethylcytosine(5hmC)is an important base for DNA demethylation and epigenetic regulation.It is also involved in the assembly of chromosomes and the regulation of gene expression.However,the mechanism of action of 5hmC in HBsAgpositive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated.AIM To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma(HCC)progression from cirrhosis.METHODS Forty HBsAg-positive carriers,forty patients with liver cirrhosis,and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants.Free DNA was extracted using a cf-DNA kit.cfDNA was extracted by 5hmC DNA sequencing for principal component analysis,the expression profiles of the three groups of samples were detected,and the differentially expressed genes(DEGs)modified by hydroxymethylation were screened.Bioinformatic analysis was used to enrich DEGs,such as in biological pathways.RESULTS A total of 16455 hydroxymethylated genes were identified.Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients,of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers.Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes,of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis.These genes may have potential loci that are undiscovered or unelucidated,which contribute to the development and progression of liver cancer.Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion.The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2.CONCLUSION The occurrence and development of liver cancer involves multiple genes and pathways,which may be potential targets for preventing hepatitis B carriers from developing liver cancer.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
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
Heat shock transcription factor(HSF)are essential regulators of heat shock protein(HSP)gene expression in plants and algae,contributing to their resilience against biotic and abiotic stresses.However,the localization,...Heat shock transcription factor(HSF)are essential regulators of heat shock protein(HSP)gene expression in plants and algae,contributing to their resilience against biotic and abiotic stresses.However,the localization,structure,phylogenetic relationship,and characteristics of PtHSF genes in microalgae,especially in diatom Phaeodactylum tricornutum,remain largely unexplored.This study presents a comprehensive analysis of the PtHSF gene family in P.tricornutum.A genome-wide analysis identified 68 PtHSF genes,which were classified into two distinct subfamilies:traditional and untraditional.Motif and structure analyses revealed evidence of multiple duplication events within the PtHSF gene family.Expression profiling revealed diurnal patterns,with 34 genes being downregulated during the light period and upregulated during the dark period,while 19 genes exhibited the opposite pattern.These findings suggest that PtHSF genes may have specialized functions during the diurnal cycle and play a crucial role in maintaining cellular homeostasis in response to various stresses.Notably,PtHSF16,30,and 43 genes exhibited higher expression levels,suggesting their potential importance.This study provides a valuable foundation for future investigations into the specific functions of HSFs under different stress conditions and their regulatory mechanisms in P.tricornutum and other microalgae.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: 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
Salinity resistance and differential gene expression associated with salinity in cotton germplasm were studied,because of the large scale area of salinity in China,and its significant negative effects
The mRNA differential display (DDRT-PCR) technique was adopted to find out the genes related tosettlement metamorphosis development process of Ruditapes philippinarum larvae.In this study,we haveobtained three hundred...The mRNA differential display (DDRT-PCR) technique was adopted to find out the genes related tosettlement metamorphosis development process of Ruditapes philippinarum larvae.In this study,we haveobtained three hundred and forty-six amplification bands in total from pediveliger larvae,veliger larvae,eye spot larvae and post-larvae.Sixty-five out of three hundred and forty-six bands are distinctly differen-tial display from band pattern,which can be put into four groups,standing for different expression char-acters.Sixteen differential display bands were cloned,sequenced and analyzed and nine different se-quences are obtained in the study.Three sequences have higher similarity to the cDNAs deposited indatabase and three are very similar to the rDNA of other species,considered as the rDNA of Ruditapesphilippinarum.The rest three sequences are found to be novel sequences after analyzed.Their accessionnumbers are AY916799,AY916798,and AY916797 respectively.We thought the novel sequences arepossibly relevant to the early embryo development of Ruditapes philippinarum larvae and can provide somefundamental understandings that are helpful for the improvement of scallop seed raising industry.展开更多
<strong>Objective:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">DNA copy number alterati...<strong>Objective:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">DNA copy number alterations and difference expression are frequently observed in ovarian cancer. The purpose of this way was to pinpoint gene expression change that w</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">as</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> associated with alterations in DNA copy number and could therefore enlighten some potential oncogenes and stability genes with functional roles in cancers, and investigated the bioinformatics significance for those correlated genes</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">. </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Method: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">We obtained the DNA copy </span><span style="font-family:Verdana;">number and mRNA expression data from the Cancer Genomic Atlas and</span><span style="font-family:Verdana;"> identified the most statistically significant copy number alteration regions using the GISTIC. Then identified the significance genes between the tumor samples within the copy number alteration regions and analyzed the correlation using a binary matrix. The selected genes were subjected to bio</span><span><span style="font-family:Verdana;">informatics analysis using GSEA tool. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> GISTIC analysis results</span></span><span style="font-family:Verdana;"> showed there were 45 significance copy number amplification regions in the ovarian cancer, SAM and Fisher’s exact test found there have 40 genes can affect the expression level, which located in the amplification regions. That means we obtained 40 genes which have a correlation between copy number amplification and drastic up- and down-expression, which p-value < 0.05 (Fisher’s exact test) and an FDR < 0.05. GSEA enrichment analysis found these genes w</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ere</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> overlapped with the several published studies which were focused on the gene study of tumorigenesis. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The use of statistics and bioinformatics to analyze the microarray data can found an interaction network involved.</span></span></span></span><span style="font-family:""> <a name="OLE_LINK16"></a><a name="OLE_LINK10"></a><span><span style="font-family:Verdana;">The combination of the copy number data and expression has pro</span><span style="font-family:Verdana;">vided a short list of candidate genes that are consistent with tumor</span><span style="font-family:Verdana;"> driving roles. These would offer new ideas for early diagnosis and treat target of ovarian cancer.</span></span></span>展开更多
Menopause is one of the key physiological events in the female life and can increase the risk for a number of complex autoimmune, neurodegenerative, metabolic, and cardiovascular disorders. Circulating monocytes can d...Menopause is one of the key physiological events in the female life and can increase the risk for a number of complex autoimmune, neurodegenerative, metabolic, and cardiovascular disorders. Circulating monocytes can differentiate into various cell types and play an important role in tissue morphogenesis and immune response. We studied gene expression profiles of peripheral blood monocytes in healthy pre- and postmenopausal women using Affymetrix Human U133A GeneChip array that contains probes for -14,500 genes. Comparative analyses between the samples showed that 20 genes were up- and 20 were down-regulated. Of these genes, 28 were classified into six major GO categories relevant to such biological processes as the cell proliferation, immune response, cellular metabolism, and the others. The remaining 12 genes have yet unidentified biological functions. Our results support the hypothesis that functional state of circulating monocytes is indeed affected by menopause, and resulting changes may be determined through the genomewide gene expression profiling. Several differentially expressed genes identified in this study may be candidates for further studies of menopause-associated systemic autoimmune, neurodegenerative, and cardiovascular disorders. Our study is only the first attempt in this direction, but it lays a basis for further research.展开更多
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.
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Maize (Zea raays L.) is one of the most important crops because of the remarkable properties of its hybrid, which is responsible for the high commercial value of hybrid maize. The genetic basis of heterosis (hybrid vigor) is not well understood. A differential display technique was performed to identify genes with differential expression across twelve maize inbred lines and thirty-three hybrids during ear development. An incomplete diallel design was used to investigate the relationship between the global framework of differential gene expression and heterosis. It was found that the genes belonging to MONO pattern (i.e., genes expressed in both parental lines and in hybrid) was the highest in percentage among the total five patterns and illustrated that the properties of differentially expressed genes are not entirely responsible for heterosis. Furthermore,a larger number of differentially expressed genes in hybrid, which serves as a major reservoir for generating novel phenotypes that exhibit heterosis of certain agronomic traits during early development and differentiation of maize ear. Moreover, there were some silent genesin hybrids that are responsible for the arrest or abortion of spikelets and for the increase in kernels weight.
基金partially funded by the Virginia Cattle Industry Board and the Virginia Agriculture CouncilVT Open Access Subvention Fund for the partial support of the publication fees
文摘Background A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait,and expression quantitative trait loci(eQTL)studies provide important information to help close that gap.However,two concerns that arise with eQTL analyses using RNA-sequencing data are normalization of data across samples and the data not following a normal distribution.Multiple pipelines have been suggested to address this.For instance,the most recent analysis of the human and farm Genotype-Tissue Expression(GTEx)project proposes using trimmed means of M-values(TMM)to normalize the data followed by an inverse normal transformation.Results In this study,we reasoned that eQTL analysis could be carried out using the same framework used for dif-ferential gene expression(DGE),which uses a negative binomial model,a statistical test feasible for count data.Using the GTEx framework,we identified 35 significant eQTLs(P<5×10^(–8))following the ANOVA model and 39 significant eQTLs(P<5×10^(–8))following the additive model.Using a differential gene expression framework,we identified 930 and six significant eQTLs(P<5×10^(–8))following an analytical framework equivalent to the ANOVA and additive model,respectively.When we compared the two approaches,there was no overlap of significant eQTLs between the two frameworks.Because we defined specific contrasts,we identified trans eQTLs that more closely resembled what we expect from genetic variants showing complete dominance between alleles.Yet,these were not identified by the GTEx framework.Conclusions Our results show that transforming RNA-sequencing data to fit a normal distribution prior to eQTL analysis is not required when the DGE framework is employed.Our proposed approach detected biologically relevant variants that otherwise would not have been identified due to data transformation to fit a normal distribution.
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.
基金Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0308.
文摘BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.
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.
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 Science and Technology Planning Project of Zhejiang Province,No.LGF20H160001.
文摘BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown.The epigenetic modification of DNA hydroxymethylation is critical in tumor development.Further,5-hydroxymethylcytosine(5hmC)is an important base for DNA demethylation and epigenetic regulation.It is also involved in the assembly of chromosomes and the regulation of gene expression.However,the mechanism of action of 5hmC in HBsAgpositive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated.AIM To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma(HCC)progression from cirrhosis.METHODS Forty HBsAg-positive carriers,forty patients with liver cirrhosis,and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants.Free DNA was extracted using a cf-DNA kit.cfDNA was extracted by 5hmC DNA sequencing for principal component analysis,the expression profiles of the three groups of samples were detected,and the differentially expressed genes(DEGs)modified by hydroxymethylation were screened.Bioinformatic analysis was used to enrich DEGs,such as in biological pathways.RESULTS A total of 16455 hydroxymethylated genes were identified.Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients,of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers.Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes,of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis.These genes may have potential loci that are undiscovered or unelucidated,which contribute to the development and progression of liver cancer.Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion.The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2.CONCLUSION The occurrence and development of liver cancer involves multiple genes and pathways,which may be potential targets for preventing hepatitis B carriers from developing liver cancer.
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.
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fundings of educational and scientific research projects for young and middle-aged teachers in Fujian Province(Grant number:2022JAT220693)Natural Science Foundation of Guangdong Province(Grant numbers:2024A1515013029 and 2022A1515012141).
文摘Heat shock transcription factor(HSF)are essential regulators of heat shock protein(HSP)gene expression in plants and algae,contributing to their resilience against biotic and abiotic stresses.However,the localization,structure,phylogenetic relationship,and characteristics of PtHSF genes in microalgae,especially in diatom Phaeodactylum tricornutum,remain largely unexplored.This study presents a comprehensive analysis of the PtHSF gene family in P.tricornutum.A genome-wide analysis identified 68 PtHSF genes,which were classified into two distinct subfamilies:traditional and untraditional.Motif and structure analyses revealed evidence of multiple duplication events within the PtHSF gene family.Expression profiling revealed diurnal patterns,with 34 genes being downregulated during the light period and upregulated during the dark period,while 19 genes exhibited the opposite pattern.These findings suggest that PtHSF genes may have specialized functions during the diurnal cycle and play a crucial role in maintaining cellular homeostasis in response to various stresses.Notably,PtHSF16,30,and 43 genes exhibited higher expression levels,suggesting their potential importance.This study provides a valuable foundation for future investigations into the specific functions of HSFs under different stress conditions and their regulatory mechanisms in P.tricornutum and other microalgae.
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: 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.
文摘Salinity resistance and differential gene expression associated with salinity in cotton germplasm were studied,because of the large scale area of salinity in China,and its significant negative effects
基金the National High Technology Research and Development Programme of China(No.2002AA603015)
文摘The mRNA differential display (DDRT-PCR) technique was adopted to find out the genes related tosettlement metamorphosis development process of Ruditapes philippinarum larvae.In this study,we haveobtained three hundred and forty-six amplification bands in total from pediveliger larvae,veliger larvae,eye spot larvae and post-larvae.Sixty-five out of three hundred and forty-six bands are distinctly differen-tial display from band pattern,which can be put into four groups,standing for different expression char-acters.Sixteen differential display bands were cloned,sequenced and analyzed and nine different se-quences are obtained in the study.Three sequences have higher similarity to the cDNAs deposited indatabase and three are very similar to the rDNA of other species,considered as the rDNA of Ruditapesphilippinarum.The rest three sequences are found to be novel sequences after analyzed.Their accessionnumbers are AY916799,AY916798,and AY916797 respectively.We thought the novel sequences arepossibly relevant to the early embryo development of Ruditapes philippinarum larvae and can provide somefundamental understandings that are helpful for the improvement of scallop seed raising industry.
文摘<strong>Objective:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">DNA copy number alterations and difference expression are frequently observed in ovarian cancer. The purpose of this way was to pinpoint gene expression change that w</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">as</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> associated with alterations in DNA copy number and could therefore enlighten some potential oncogenes and stability genes with functional roles in cancers, and investigated the bioinformatics significance for those correlated genes</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">. </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Method: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">We obtained the DNA copy </span><span style="font-family:Verdana;">number and mRNA expression data from the Cancer Genomic Atlas and</span><span style="font-family:Verdana;"> identified the most statistically significant copy number alteration regions using the GISTIC. Then identified the significance genes between the tumor samples within the copy number alteration regions and analyzed the correlation using a binary matrix. The selected genes were subjected to bio</span><span><span style="font-family:Verdana;">informatics analysis using GSEA tool. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> GISTIC analysis results</span></span><span style="font-family:Verdana;"> showed there were 45 significance copy number amplification regions in the ovarian cancer, SAM and Fisher’s exact test found there have 40 genes can affect the expression level, which located in the amplification regions. That means we obtained 40 genes which have a correlation between copy number amplification and drastic up- and down-expression, which p-value < 0.05 (Fisher’s exact test) and an FDR < 0.05. GSEA enrichment analysis found these genes w</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ere</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> overlapped with the several published studies which were focused on the gene study of tumorigenesis. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The use of statistics and bioinformatics to analyze the microarray data can found an interaction network involved.</span></span></span></span><span style="font-family:""> <a name="OLE_LINK16"></a><a name="OLE_LINK10"></a><span><span style="font-family:Verdana;">The combination of the copy number data and expression has pro</span><span style="font-family:Verdana;">vided a short list of candidate genes that are consistent with tumor</span><span style="font-family:Verdana;"> driving roles. These would offer new ideas for early diagnosis and treat target of ovarian cancer.</span></span></span>
文摘Menopause is one of the key physiological events in the female life and can increase the risk for a number of complex autoimmune, neurodegenerative, metabolic, and cardiovascular disorders. Circulating monocytes can differentiate into various cell types and play an important role in tissue morphogenesis and immune response. We studied gene expression profiles of peripheral blood monocytes in healthy pre- and postmenopausal women using Affymetrix Human U133A GeneChip array that contains probes for -14,500 genes. Comparative analyses between the samples showed that 20 genes were up- and 20 were down-regulated. Of these genes, 28 were classified into six major GO categories relevant to such biological processes as the cell proliferation, immune response, cellular metabolism, and the others. The remaining 12 genes have yet unidentified biological functions. Our results support the hypothesis that functional state of circulating monocytes is indeed affected by menopause, and resulting changes may be determined through the genomewide gene expression profiling. Several differentially expressed genes identified in this study may be candidates for further studies of menopause-associated systemic autoimmune, neurodegenerative, and cardiovascular disorders. Our study is only the first attempt in this direction, but it lays a basis for further research.