Plant peroxidase （POD） belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and bioch...Plant peroxidase （POD） belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and biochemical processes and plays a crucial role in the maintenance of plant growth and development. In this study, the structures and functions of proteins encoded by 73 gene of POD family in Arabidopsis were analyzed with bioinformatics method, including the number of amino acids, isoelectric point, transmemberane domains, signal peptides, secondary structures and phosphorylation sites, and the phylogenic trees with and without signal peptides were constructed by using Mega4.0 software, to investigate the structural characteristics. In addition, the structures of AtPER members were analyzed, to reveal the relationship between the structures and functions, thereby providing theoretical basis for the research of plant oxidative stress resistance.展开更多
Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were ava...Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database:GSE12606,GSE36895 and GSE66272.The differentially expressed genes were screened with GEO2R and J Venn online tools.Functional annotation including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was applied to identify the possible function of the hub genes involved in prognosis of ccRCC.In protein protein interaction network(PPI network),the STRING online tool was used to visualize the network of the differentially expressed genes,and the core gene was selected by MCODE App in Cytoscape software.Finally,GEPIA Survival Plot was performed to assess genes associated with worse survival.Results We totally found 648 diflerentially expressed genes,including 222 up-regulated genes and 426 down-regulated genes.PPI network showed that in 28 up-regulated genes 7(CCNE2,CDK1,CDC6,CCNB2,BUB1,TTK and PTTG1)enriched in cell cycle and 4 genes(CCNE2,CDK1,CCNB2 and RRM2)enriched in p53 signaling pathway.GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1,CCNB2,RRM2t BUB1,and PTTG1 had a worse survival.GEPIA Box Plot showed that BUB1,CCNB2,PTTG1,and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues(P<O.OS).Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1,and RRM2 might manifest a poor prognosis.展开更多
Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe n...Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.展开更多
Background:To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS)and explore the molecular mechanism of MTLE-HS.Methods:Micro...Background:To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS)and explore the molecular mechanism of MTLE-HS.Methods:Microarray data of MTLE-HS were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between MTLE-HS with and without febrile seizure history were screened by the GEO2R software.Pathway enrichment and gene ontology of the DEGs were analyzed using the DAVID online database and FunRich software.Protein–protein interaction(PPI)networks among DEGs were constructed using the STRING database and analyzed by Cytoscape.Results:A total of 515 DEGs were identified in MTLE-HS samples with a febrile seizure history compared to MTLEHS samples without febrile seizure,including 25 down-regulated and 490 up-regulated genes.These DEGs were expressed mostly in plasma membrane and synaptic vesicles.The major molecular functions of those genes were voltage-gated ion channel activity,extracellular ligand-gated ion channel activity and calcium ion binding.The DEGs were mainly involved in biological pathways of cell communication signal transduction and transport.Five genes(SNAP25,SLC32A1,SYN1,GRIN1,and GRIA1)were significantly expressed in the MTLE-HS with prolonged febrile seizures.Conclusion:The pathogenesis of MTLE-HS involves multiple genes,and prolonged febrile seizures could cause differential expression of genes.Thus,investigations of those genes may provide a new perspective into the mechanism of MTLE-HS.展开更多
Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,w...Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.展开更多
The purpose of this review is to explore the intersection of computational engineering and biomedical science,highlighting the transformative potential this convergence holds for innovation in healthcare and medical r...The purpose of this review is to explore the intersection of computational engineering and biomedical science,highlighting the transformative potential this convergence holds for innovation in healthcare and medical research.The review covers key topics such as computational modelling,bioinformatics,machine learning in medical diagnostics,and the integration of wearable technology for real-time health monitoring.Major findings indicate that computational models have significantly enhanced the understanding of complex biological systems,while machine learning algorithms have improved the accuracy of disease prediction and diagnosis.The synergy between bioinformatics and computational techniques has led to breakthroughs in personalized medicine,enabling more precise treatment strategies.Additionally,the integration of wearable devices with advanced computational methods has opened new avenues for continuous health monitoring and early disease detection.The review emphasizes the need for interdisciplinary collaboration to further advance this field.Future research should focus on developing more robust and scalable computational models,enhancing data integration techniques,and addressing ethical considerations related to data privacy and security.By fostering innovation at the intersection of these disciplines,the potential to revolutionize healthcare delivery and outcomes becomes increasingly attainable.展开更多
Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have groupe...Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.展开更多
BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alte...BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.展开更多
Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and hea...Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.展开更多
Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessi...Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessing therapeutic efficacy and monitoring acupuncture treatment.Methods miRNA microarray data(CEL and TXT formats)were acquired from human and murine RA models,with the latter undergoing acupuncture treatment.Data were normalized using the robust multi-array average(RMA)method and analyzed for differential expression.Differential expression analysis identified miRNAs through a comparative analysis of RA human tissues,acupuncture-treated murine RA models,and a bibliographic search for miRNAs implicated in RA pathogenesis and acupuncture treatment.Bioinformatics analysis was performed to identify potential target genes for each miRNA and signaling pathways via search tools for the Retrieval of Interacting Genes/Proteins(STRING)and ShinyGO.Gene-drug interaction analysis was performed through Drug-Gene Interaction Database(DGIdb)screening.Interaction networks were constructed with the Cytoscape v3.10.3 software.Results The hsa-miR-125a-5p and hsa-miR-125b-5p were identified as potential biomarkers associated with RA pathogenesis,presenting 468 and 455 target genes,respectively.These genes were enriched in 20 signaling pathways,including Janus kinasa-signal transducer and activator of transcription(JAK-STAT),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase-protein kinase B(PI3K-Akt),and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway,which have been associated with RA pathogenesis and progression.Drug-gene interaction networks revealed that 22 genes were significantly associated with 58 RA treatment drugs,among which 13 genes interacted with members of the hsa-miR-125 family.Conclusion The hsa-miR-125a-5p and hsa-miR-125b-5p demonstrate critical regulatory role in RA pathogenesis by modulating signaling pathways,including JAK-STAT,MAPK,PI3K-Akt,and NF-κB.Our findings show that the hsa-miR-125a-5p and hsa-miR-125b-5p exhibit differential expression patterns in response to pharmacological intervention in various diseases,including RA management.This suggests their potential roles as biomarkers for monitoring acupuncture treatment.Although existing evidence indicates that acupuncture can modify miRNA expression profiles,rigorous validation through biological models remains essential to confirm these results.展开更多
Objective:To explore the key molecules regulated by norcantharidin(NCTD)in colon cancer treatment.Methods:We used cell counting kit-8 and 5-ethnyl-20-deoxyuridine/Hoechst staining assays to study the effects of NCTD o...Objective:To explore the key molecules regulated by norcantharidin(NCTD)in colon cancer treatment.Methods:We used cell counting kit-8 and 5-ethnyl-20-deoxyuridine/Hoechst staining assays to study the effects of NCTD on cell proliferation in colon cancer.Annexin V-fluorescein isothiocyanate/propidium iodide staining was used to evaluate apoptosis,whereas Transwell assays were conducted to evaluate migration and invasion.We performed RNA sequencing to analyze the changes in gene expression after treatment.Differential analysis was performed using differential expression sequencing 2(Deseq2)in R.Cytoscape was used to construct a competing endogenous RNA(ceRNA)network and Gene Expression Omnibus(GEO)datasets were used to validate sine oculis homeobox homolog 4(SIX4)expression in colon cancer tissues.Furthermore,the prognostic potential of SIX4 was evaluated using receiver-oper-ating characteristic curves.We conducted an immune infiltration analysis to explore the SIX4 relation-ship with the immune microenvironment in colon cancer.Finally,SIX4 expression,pan-cancer prognosis,tumor mutation burden(TMB)correlations,microsatellite instability(MSI),and mismatch repair(MMR)were analyzed.Results:NCTD inhibited colon cancer cell proliferation(P<0.0001),induced apoptosis(P=0.0007),and suppressed the migration and invasion of colon cancer cells.The H19/miR-193b-3p/SIX4 axis was identified as the key ceRNA network involved in the anticancer activity of NCTD.SIX4 is highly expressed in colon cancer tissues,shortening patient survival and affecting immune infiltration.A pan-cancer analysis showed that SIX4 overexpression affects the survival of various cancers.Finally,we correlated SIX4 expression with TMB,MSI,and MMR expression.Conclusion:NCTD inhibits the malignant behaviour of colon cancer cells.SIX4 is abnormally expressed in multiple tumor types,significantly affecting the overall survival of patients with cancer,and is a core regulatory target of NCTD in the treatment of colon cancer.展开更多
Background:Kidney renal clear cell carcinoma(KIRC),a prevalent urological malignancy,represents about 3%of all adult malignancies.KIRC,accounting for~75%of renal malignancies,has poor prognosis in metastatic stages.Id...Background:Kidney renal clear cell carcinoma(KIRC),a prevalent urological malignancy,represents about 3%of all adult malignancies.KIRC,accounting for~75%of renal malignancies,has poor prognosis in metastatic stages.Identifying robust prognostic markers remains urgent.Block of proliferation 1(BOP1),a WD40-repeat protein,is implicated in cancer pathogenesis,but its role in KIRC is unclear.This study aimed to characterize BOP1 expression in KIRC and evaluate its prognostic value.Methods:BOP1 transcriptional levels were assessed through TCGA-KIRC RNA sequencing datasets.ROC curve construction was implemented via R statistical packages for diagnostic evaluation.Patient survival outcomes were visualized through Kaplan-Meier plotting with log-rank testing.Multivariate logistic regression models quantified associations between BOP1 expression and clinicopathological parameters.TIMER algorithm analyzed immune microenvironment composition.Genomic alterations and epigenetic modifications were investigated using cBioPortal and MethSurv platforms respectively.BOP1 protein levels in 786-O clear cell renal cell carcinoma(ccRCC)versus HK-2(normal renal)cell lines were validated by immunoblotting.Results:Evaluation of the TCGA database demonstrated that BOP1 mRNA abundance was higher in tumor specimens than in corresponding adjacent tissues.Patients with KIRC who had high BOP1 expression had differential overall survival(OS),disease-specific survival(DSS),and disease-free interval(DFI).BOP1 expression accurately recognised tumour tissues versus normal tissues(AUC=0.858),and the area under the ROCs for survival at 1,3,and 5 years were all greater than 0.6.The BOP1 gene variant rate was<1%.Out of the 15 DNA methylation CpG sites examined,7 exhibited prognostic significance in KIRC.BOP1 displayed a distinct relationship with immune cell infiltration in KIRC.The 786-O experimental group exhibited substantially higher BOP1 expression,as confirmed by Western blot detection.Conclusion:This study indicates that heightened BOP1 expression is linked to an adverse prognosis in KIRC,establishing it as an independent risk factor for this disease.These findings establish BOP1 as a novel and independent prognostic biomarker for KIRC,offering potential clinical utility for risk stratification and personalized therapeutic strategies.展开更多
As a high-value eudicot family,many famous horticultural crop genomes have been deciphered in Oleaceae.However,there are currently no bioinformatics platforms focused on empowering genome research in Oleaceae.Herein,w...As a high-value eudicot family,many famous horticultural crop genomes have been deciphered in Oleaceae.However,there are currently no bioinformatics platforms focused on empowering genome research in Oleaceae.Herein,we developed the first comprehensive Oleaceae Genome Research Platform(OGRP,https://oleaceae.cgrpoee.top/).In OGRP,70 genomes of 10 Oleaceae species and 46 eudicots and 366 transcriptomes involving 18 Oleaceae plant tissues can be obtained.We built 34 window-operated bioinformatics tools,collected 38 professional practical software programs,and proposed 3 new pipelines,namely ancient polyploidization identification,ancestral karyotype reconstruction,and gene family evolution.Employing these pipelines to reanalyze the Oleaceae genomes,we clarified the polyploidization,reconstructed the ancestral karyotypes,and explored the effects of paleogenome evolution on genes with specific biological regulatory roles.Significantly,we generated a series of comparative genomic resources focusing on the Oleaceae,comprising 108 genomic synteny dot plots,1952225 collinear gene pairs,multiple genome alignments,and imprints of paleochromosome rearrangements.Moreover,in Oleaceae genomes,researchers can efficiently search for 1785987 functional annotations,22584 orthogroups,29582 important trait genes from 74 gene families,12664 transcription factor-related genes,9178872 transposable elements,and all involved regulatory pathways.In addition,we provided downloads and usage instructions for the tools,a species encyclopedia,ecological resources,relevant literatures,and external database links.In short,ORGP integrates rich data resources and powerful analytical tools with the characteristic of continuous updating,which can efficiently empower genome research and agricultural breeding in Oleaceae and other plants.展开更多
This study aimed to investigate the role of autophagy-related genes in osteoarthritis(OA)and evaluate the therapeutic potential of Eucommin A,a key lignan component derived from Eucommia ulmoides.Gene expression profi...This study aimed to investigate the role of autophagy-related genes in osteoarthritis(OA)and evaluate the therapeutic potential of Eucommin A,a key lignan component derived from Eucommia ulmoides.Gene expression profiles from OA patients and healthy controls were retrieved from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified and intersected with autophagy-related genes from the Human Autophagy Database to pinpoint OA-specific autophagy candidates.Functional enrichment analyses via GO and KEGG highlighted involvement in nutrient response,apoptosis,and PI3K-Akt/FoxO signaling pathways.Core genes were prioritized using machine learning algorithms combined with protein-protein interaction(PPI)network analysis,followed by diagnostic validation in an independent cohort.Molecular docking and 100-ns molecular dynamics simulations were conducted to assess the binding stability between Eucommin A and the core targets.Interaction mechanisms were characterized using root mean square deviation(RMSD),root mean square fluctuation(RMSF),radius of gyration(Rg),and MM/GBSA binding free energy calculations.Among 2436 DEGs,56 were autophagy-related and significantly enriched in key biological processes.Machine learning identified EGFR,MAPK3,and MAPK8 as hub genes,with EGFR and MAPK8 exhibiting significant diagnostic value(AUC>0.5).Eucommin A demonstrated strong binding affinity to EGFR and MAPK8 via hydrogen bonding and hydrophobic interactions.Molecular dynamics simulations confirmed stable ligand-target complexes and favorable binding free energy profiles.These findings suggested EGFR and MAPK8 as diagnostic biomarkers for OA-related autophagy.Moreover,Eucommin A exerted multi-target therapeutic effects by stabilizing these autophagy-related proteins,proposing a novel strategy for OA treatment through modulation of autophagy.展开更多
Bioinformatics,an interdisciplinary field that integrates computer science,biology,information technology,and statistics,plays a pivotal role in analyzing and interpreting biological data.It has become an indispensabl...Bioinformatics,an interdisciplinary field that integrates computer science,biology,information technology,and statistics,plays a pivotal role in analyzing and interpreting biological data.It has become an indispensable tool in the design and discovery of novel drugs by facilitating the analysis of biological datasets and aiding in the identification of potential therapeutic targets.With the rise of antibiotic resistance among bacterial species,the demand for new drug development has intensified.However,the process of drug discovery remains labor-intensive,costly,and time-consuming.The identification of new drugs involves multiple critical stages,including target identification,structural analysis of the target protein,selection of potential drug candidates,safety and efficacy assessments,drug optimization,and ultimately,validation.Bioinformatics contributes significantly to each of these phases.For instance,through the analysis of protein sequences and genetic data,researchers can pinpoint potential drug targets.Once a target protein is identified,bioinformatics tools enable detailed structural analysis of the protein.Upon locating the potential ligand-binding site,large compound databases can be screened to discover viable drug candidates.Simulations further aid in examining the interaction between the target protein and biomolecules,providing valuable insights into the drug’s safety and efficacy.Moreover,bioinformatics-driven drug optimization helps improve both safety and effectiveness.Recent advances,such as pharmacophore modeling and molecular docking techniques,have accelerated the screening process,narrowing thousands of candidate molecules down to a select few with promising therapeutic potential.In this study,bioinformatics was leveraged within the framework of network pharmacology to design and discover new drugs.展开更多
Objective:Employing bioinformatics methodologies to identify core genes intricately associated with the pathogenesis and progression of gastric cancer,and to evaluate their clinical significance.Method:Gene expression...Objective:Employing bioinformatics methodologies to identify core genes intricately associated with the pathogenesis and progression of gastric cancer,and to evaluate their clinical significance.Method:Gene expression datasets GSE19826 and GSE13911 were acquired from the Gene Expression Omnibus(GEO).Differential gene expression analysis was conducted using GEO2R.Common differentially expressed genes(DEGs)were discerned via Venn diagram analysis on a bioinformatics platform.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),were performed on these overlapping DEGs.A protein-protein interaction(PPI)network was constructed with the STRING database,and central hub genes were identified using Cytoscape software.The expression profiles,prognostic value,and immune infiltration correlations of these key genes were further examined utilizing the GEPIA,Kaplan-Meier plotter,Human Protein Atlas(HPA),and TIMER databases.Results:Analysis revealed 120 commonly differentially expressed genes.These genes were significantly enriched in biological pathways concerning muscle cell cytoskeleton regulation,nutrient absorption,and extracellular matrix receptor interactions.PPI network analysis highlighted 10 core genes,including COL1A1,COL1A2,BGN,THBS2,COL5A2,and TIMP1.These genes exhibited marked upregulation in GC tissues.Statistical evaluation confirmed a significant link between their elevated expression and unfavorable patient outcomes(P<0.01).Furthermore,immune infiltration assessment indicated a positive correlation between the expression of these genes and macrophage infiltration within the tumor microenvironment,implying their involvement in modulating the immune response in GC,which could affect tumor behavior and clinical progression.Conclusion:The six genes identified may function as diagnostic biomarkers and represent promising therapeutic targets for gastric cancer.展开更多
BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mech...BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mechanism remains unclear.Circular RNAs(circRNAs),which are formed from protein-coding genes,can sequester microRNAs or proteins,modulate transcription and interfere with splicing.Authoritative studies suggest that circRNAs may play an important role in myocardial I/R injury.AIM To explore the role and mechanism of circRNAs in myocardial I/R injury.METHODS We constructed a myocardial I/R injury model using ligation of the left anterior descending coronary artery,and evaluated the success of the validated model using triphenyltetrazolium chloride and hematoxylin-eosin staining.Then,left ventricular samples from different groups were selected for mRNA-sequence,and differential gene screening was performed on the obtained results.The differentially obtained mRNAs were divided into up-regulated and down-regulated according to their expression levels,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis were performed,respectively.Then,the obtained circRNA and microRNA(miRNA)were paired for analysis,and the binding sites of miRNA and mRNA were virtual screened.Finally,the obtained circRNA,miRNA and mRNA were constructed by ceRNA mutual most useful network.RESULTS We used an RNA sequencing array to investigate the expression signatures of circRNAs in myocardial I/R injury using three samples from the I/R group and three samples from the sham group.A total of 142 upregulated and 121 downregulated circRNAs were found to be differentially expressed(fold change≥2,P<0.05).GO and KEGG functional analyses of these circRNAs were performed.GO analysis revealed that these circRNAs were involved mainly in cellular and intracellular processes.KEGG analysis demonstrated that 6 of the top 20 pathways were correlated with cell apoptosis.Furthermore,a circRNA-miRNA coexpression network and ceRNA network based on these genes were constructed,revealing that mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 might be key regulators of myocardial I/R injury.CONCLUSION This research provides new insights into the mechanism of myocardial I/R,which mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 are expected to be new therapeutic targets for myocardial I/R injury.展开更多
Background:A thorough examination of the physicochemical properties,higher-order structure,subcellular localization,and selective pressure of the cytochrome c oxidase subunit I(COX1)protein of the endemic species Eoth...Background:A thorough examination of the physicochemical properties,higher-order structure,subcellular localization,and selective pressure of the cytochrome c oxidase subunit I(COX1)protein of the endemic species Eothenomys miletus(E.miletus)in the Hengduan Mountains provides further insights into molecular characteristics and function of the COX1 gene in E.miletus.Method:The physicochemical properties and higher-order structure of the COX1 protein of E.miletus were analyzed using bioinformatics software.Subsequently,a phylogenetic tree was constructed using Mega 7.0 software based on the COX1 gene from 19 species of the Arvicolinae subfamily and 3 species of the Muridae.Selection pressure analysis was performed using the PAML 4.7 software and the Datamonkey online website.Results:The COX1 protein of E.miletus comprises/consists of 514 amino acids,with leucine(Leu/L)being the most prevalent amino acid(11.5%).This hydrophilic protein contains 42 phosphorylation sites and 4 N-glycosylation sites.It possesses a transmembrane domain and lacks signal peptide distribution,thus classifying it as a non-GPI-anchored protein.The secondary structure of the COX1 protein consists ofα-helices(36.77%),random coils(33.85%),and extended chains,a composition consistent with/findings that align with its tertiary structure.Significant genetic differentiation exists among species within the Arvicolinae subfamily,a finding consistent with morphological identification results.The COX1 gene in Arvicolinae species exhibits purifying selection.Conclusion:This study analyzed the physicochemical properties of the COX1 protein in E.miletus.Phylogenetic and selection pressure analyses reveal significant genetic divergence among Arvicolinae species,and demonstrate that the COX1 gene is evolutionarily conserved within the Arvicolinae subfamily.展开更多
Ericaceae is a diverse family of flowering plants distributed nearly worldwide,and it includes 126 genera and more than 4,000 species.In the present study,we developed The Ericaceae Genome Resource(TEGR,http://www.teg...Ericaceae is a diverse family of flowering plants distributed nearly worldwide,and it includes 126 genera and more than 4,000 species.In the present study,we developed The Ericaceae Genome Resource(TEGR,http://www.tegr.com.cn)as a comprehensive,user-friendly,web-based functional genomic database that is based on 16 published genomes from 16 Ericaceae species.The TEGR database contains information on many important functional genes,including 763 auxin genes,2,407 flowering genes,20,432 resistance genes,617 anthocyanin-related genes,and 470 N^(6)-methyladenosine(m^(6)A)modification genes.We identified a total of 599,174 specific guide sequences for CRISPR in the TEGR database.The gene duplication events,synteny analysis,and orthologous analysis of the16 Ericaceae species were performed using the TEGR database.The TEGR database contains 614,821 functional genes annotated through the GO,Nr,Pfam,TrEMBL,and Swiss-Prot databases.The TEGR database provides the Primer Design,Hmmsearch,Synteny,BLAST,and JBrowse tools for helping users perform comprehensive comparative genome analyses.All the high-quality reference genome sequences,genomic features,gene annotations,and bioinformatics results can be downloaded from the TEGR database.In the future,we will continue to improve the TEGR database with the latest data sets when they become available and to provide a useful resource that facilitates comparative genomic studies.展开更多
Kinesins are a superfamily of proteins widely present in eukaryotes,playing crucial roles in plant cell wall assembly,cell elongation regulation,gravity sensing,and fertility control.In this study,bioinformatics analy...Kinesins are a superfamily of proteins widely present in eukaryotes,playing crucial roles in plant cell wall assembly,cell elongation regulation,gravity sensing,and fertility control.In this study,bioinformatics analysis of the OsKMP2 gene(LOC_Os02g28850)was performed using online tools such as ExPASy-ProtParam,ProtScale,CD-search,and DNAMAN software.Additionally,qRT-PCR was employed to analyze the tissue expression pattern of OsKMP2.The results showed that the molecular weight of the OsKMP2 is 118.39728 kDa,and it is a hydrophilic and unstable acidic protein.Secondary structure prediction revealed that it primarily consists ofα-helices(69.45%),random coils(25.19%),and extended strands(5.36%).The gene was expressed in various rice tissues,with the highest expression level observed in leaves.These results indicate that the OsKMP2 gene exhibits high evolutionary conservation and functional diversity in rice.展开更多
基金Supported by National Natural Science Foundation of China(31070361)the Fundamental Research Funds for the Central Universities(0910KYZY43,1112KYQN31)+1 种基金"985 Project"from Minzu University of China(MUC98504-14)Scientific Research Project from State Ethnic Affairs Commission(10ZY01)~~
文摘Plant peroxidase （POD） belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and biochemical processes and plays a crucial role in the maintenance of plant growth and development. In this study, the structures and functions of proteins encoded by 73 gene of POD family in Arabidopsis were analyzed with bioinformatics method, including the number of amino acids, isoelectric point, transmemberane domains, signal peptides, secondary structures and phosphorylation sites, and the phylogenic trees with and without signal peptides were constructed by using Mega4.0 software, to investigate the structural characteristics. In addition, the structures of AtPER members were analyzed, to reveal the relationship between the structures and functions, thereby providing theoretical basis for the research of plant oxidative stress resistance.
基金the National Technical system of Chinese Medicinal Materials Industry(No.CARS-21)the Key Natural Science Projects of West Anhui University in China(No.WXZR201932)+4 种基金the Training Program of Innovate and Entrepreneurship of National College students in China(No.201810376058,201810376061)Anhui Provincial Natural Science Foundation in China(No.2017A030311022)Anhui Provincial University Natural Science Project in China(No.KJ2018A0413,KJ2017a407)Anhui Provincial Quality of Undergraduate project in China(No.2018zygc075,2018jyxm1153,2018jyxm1155)the Teaching and Research Projects of West Anhui University in China(No.wxxy2018026).
文摘Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database:GSE12606,GSE36895 and GSE66272.The differentially expressed genes were screened with GEO2R and J Venn online tools.Functional annotation including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was applied to identify the possible function of the hub genes involved in prognosis of ccRCC.In protein protein interaction network(PPI network),the STRING online tool was used to visualize the network of the differentially expressed genes,and the core gene was selected by MCODE App in Cytoscape software.Finally,GEPIA Survival Plot was performed to assess genes associated with worse survival.Results We totally found 648 diflerentially expressed genes,including 222 up-regulated genes and 426 down-regulated genes.PPI network showed that in 28 up-regulated genes 7(CCNE2,CDK1,CDC6,CCNB2,BUB1,TTK and PTTG1)enriched in cell cycle and 4 genes(CCNE2,CDK1,CCNB2 and RRM2)enriched in p53 signaling pathway.GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1,CCNB2,RRM2t BUB1,and PTTG1 had a worse survival.GEPIA Box Plot showed that BUB1,CCNB2,PTTG1,and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues(P<O.OS).Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1,and RRM2 might manifest a poor prognosis.
基金supported by the National Natural Science Foundation of China,Nos.82071307(to HL),82271362(to HL),82171294(to JW),82371303(to JW),and 82301460(to PX)the Natural Science Foundation of Jiangsu Province,No.BK20211552(to HL)+1 种基金Suzhou Medical Technology Innovation Project-Clinical Frontier,No.SKY2022002(to ZY)the Science and Education Foundation for Health of Suzhou for Youth,No.KJXW2023001(to XL)。
文摘Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.
基金the Sanming Project of Medicine in Shenzhen(No.SZSM201911003)National Natural Science Foundation of China(No.81571266,81771405).
文摘Background:To investigate the effect of long-term febrile convulsions on gene expression in mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS)and explore the molecular mechanism of MTLE-HS.Methods:Microarray data of MTLE-HS were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between MTLE-HS with and without febrile seizure history were screened by the GEO2R software.Pathway enrichment and gene ontology of the DEGs were analyzed using the DAVID online database and FunRich software.Protein–protein interaction(PPI)networks among DEGs were constructed using the STRING database and analyzed by Cytoscape.Results:A total of 515 DEGs were identified in MTLE-HS samples with a febrile seizure history compared to MTLEHS samples without febrile seizure,including 25 down-regulated and 490 up-regulated genes.These DEGs were expressed mostly in plasma membrane and synaptic vesicles.The major molecular functions of those genes were voltage-gated ion channel activity,extracellular ligand-gated ion channel activity and calcium ion binding.The DEGs were mainly involved in biological pathways of cell communication signal transduction and transport.Five genes(SNAP25,SLC32A1,SYN1,GRIN1,and GRIA1)were significantly expressed in the MTLE-HS with prolonged febrile seizures.Conclusion:The pathogenesis of MTLE-HS involves multiple genes,and prolonged febrile seizures could cause differential expression of genes.Thus,investigations of those genes may provide a new perspective into the mechanism of MTLE-HS.
基金supported by the Key-Area Research and Development Program of Guangdong Province(Grant No.2020B020220003)National Natural Science Foundation of China(32202504)+2 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515030049)Guangdong Rural Revitalization Strategy Special Project(Grant No.2023-NJS-00-003)Special fund for scientific and technological talents introduction of Guangdong Academy of Agricultural Sciences(Grant No.R2021YJ-YB2004)。
文摘Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.
文摘The purpose of this review is to explore the intersection of computational engineering and biomedical science,highlighting the transformative potential this convergence holds for innovation in healthcare and medical research.The review covers key topics such as computational modelling,bioinformatics,machine learning in medical diagnostics,and the integration of wearable technology for real-time health monitoring.Major findings indicate that computational models have significantly enhanced the understanding of complex biological systems,while machine learning algorithms have improved the accuracy of disease prediction and diagnosis.The synergy between bioinformatics and computational techniques has led to breakthroughs in personalized medicine,enabling more precise treatment strategies.Additionally,the integration of wearable devices with advanced computational methods has opened new avenues for continuous health monitoring and early disease detection.The review emphasizes the need for interdisciplinary collaboration to further advance this field.Future research should focus on developing more robust and scalable computational models,enhancing data integration techniques,and addressing ethical considerations related to data privacy and security.By fostering innovation at the intersection of these disciplines,the potential to revolutionize healthcare delivery and outcomes becomes increasingly attainable.
文摘Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.
基金Supported by School-Level Key Projects at Bengbu Medical College,No.2021byzd109.
文摘BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.
基金supported by the Natural Science Foundation of Hunan Province,China(2022JJ30886).
文摘Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.
基金Programa de Investigadores e Investigadoras of the Consejo Mexiquense de Ciencia y Tecnología(COMECYT)(EESP2024-0038)。
文摘Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessing therapeutic efficacy and monitoring acupuncture treatment.Methods miRNA microarray data(CEL and TXT formats)were acquired from human and murine RA models,with the latter undergoing acupuncture treatment.Data were normalized using the robust multi-array average(RMA)method and analyzed for differential expression.Differential expression analysis identified miRNAs through a comparative analysis of RA human tissues,acupuncture-treated murine RA models,and a bibliographic search for miRNAs implicated in RA pathogenesis and acupuncture treatment.Bioinformatics analysis was performed to identify potential target genes for each miRNA and signaling pathways via search tools for the Retrieval of Interacting Genes/Proteins(STRING)and ShinyGO.Gene-drug interaction analysis was performed through Drug-Gene Interaction Database(DGIdb)screening.Interaction networks were constructed with the Cytoscape v3.10.3 software.Results The hsa-miR-125a-5p and hsa-miR-125b-5p were identified as potential biomarkers associated with RA pathogenesis,presenting 468 and 455 target genes,respectively.These genes were enriched in 20 signaling pathways,including Janus kinasa-signal transducer and activator of transcription(JAK-STAT),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase-protein kinase B(PI3K-Akt),and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway,which have been associated with RA pathogenesis and progression.Drug-gene interaction networks revealed that 22 genes were significantly associated with 58 RA treatment drugs,among which 13 genes interacted with members of the hsa-miR-125 family.Conclusion The hsa-miR-125a-5p and hsa-miR-125b-5p demonstrate critical regulatory role in RA pathogenesis by modulating signaling pathways,including JAK-STAT,MAPK,PI3K-Akt,and NF-κB.Our findings show that the hsa-miR-125a-5p and hsa-miR-125b-5p exhibit differential expression patterns in response to pharmacological intervention in various diseases,including RA management.This suggests their potential roles as biomarkers for monitoring acupuncture treatment.Although existing evidence indicates that acupuncture can modify miRNA expression profiles,rigorous validation through biological models remains essential to confirm these results.
基金funded by the National Natural Science Foundation of China(82074284)China National Traditional Chinese Medicine Inheritance and Innovation Team Sub-project(ZYYCXTD-C-202005-10)+1 种基金China Medical Association of Minorities Research Project(2020MZ298-110101)Open Fund Project,Associated Key Laboratory of Traditional Mongolia Medicine Research and Development,National Ethnic Affairs Commission and Ministry of Education of China(MDK2020013).
文摘Objective:To explore the key molecules regulated by norcantharidin(NCTD)in colon cancer treatment.Methods:We used cell counting kit-8 and 5-ethnyl-20-deoxyuridine/Hoechst staining assays to study the effects of NCTD on cell proliferation in colon cancer.Annexin V-fluorescein isothiocyanate/propidium iodide staining was used to evaluate apoptosis,whereas Transwell assays were conducted to evaluate migration and invasion.We performed RNA sequencing to analyze the changes in gene expression after treatment.Differential analysis was performed using differential expression sequencing 2(Deseq2)in R.Cytoscape was used to construct a competing endogenous RNA(ceRNA)network and Gene Expression Omnibus(GEO)datasets were used to validate sine oculis homeobox homolog 4(SIX4)expression in colon cancer tissues.Furthermore,the prognostic potential of SIX4 was evaluated using receiver-oper-ating characteristic curves.We conducted an immune infiltration analysis to explore the SIX4 relation-ship with the immune microenvironment in colon cancer.Finally,SIX4 expression,pan-cancer prognosis,tumor mutation burden(TMB)correlations,microsatellite instability(MSI),and mismatch repair(MMR)were analyzed.Results:NCTD inhibited colon cancer cell proliferation(P<0.0001),induced apoptosis(P=0.0007),and suppressed the migration and invasion of colon cancer cells.The H19/miR-193b-3p/SIX4 axis was identified as the key ceRNA network involved in the anticancer activity of NCTD.SIX4 is highly expressed in colon cancer tissues,shortening patient survival and affecting immune infiltration.A pan-cancer analysis showed that SIX4 overexpression affects the survival of various cancers.Finally,we correlated SIX4 expression with TMB,MSI,and MMR expression.Conclusion:NCTD inhibits the malignant behaviour of colon cancer cells.SIX4 is abnormally expressed in multiple tumor types,significantly affecting the overall survival of patients with cancer,and is a core regulatory target of NCTD in the treatment of colon cancer.
基金supported by Young Talents Cultivation Program of Xianning City,the Natural Science Foundation of Hubei Province,China(No.2024AFB502)Ph.D.Start-up Funding(No.BK202413)Medical Fund(No.2023YKY04)of Hubei University of Science and Technology.
文摘Background:Kidney renal clear cell carcinoma(KIRC),a prevalent urological malignancy,represents about 3%of all adult malignancies.KIRC,accounting for~75%of renal malignancies,has poor prognosis in metastatic stages.Identifying robust prognostic markers remains urgent.Block of proliferation 1(BOP1),a WD40-repeat protein,is implicated in cancer pathogenesis,but its role in KIRC is unclear.This study aimed to characterize BOP1 expression in KIRC and evaluate its prognostic value.Methods:BOP1 transcriptional levels were assessed through TCGA-KIRC RNA sequencing datasets.ROC curve construction was implemented via R statistical packages for diagnostic evaluation.Patient survival outcomes were visualized through Kaplan-Meier plotting with log-rank testing.Multivariate logistic regression models quantified associations between BOP1 expression and clinicopathological parameters.TIMER algorithm analyzed immune microenvironment composition.Genomic alterations and epigenetic modifications were investigated using cBioPortal and MethSurv platforms respectively.BOP1 protein levels in 786-O clear cell renal cell carcinoma(ccRCC)versus HK-2(normal renal)cell lines were validated by immunoblotting.Results:Evaluation of the TCGA database demonstrated that BOP1 mRNA abundance was higher in tumor specimens than in corresponding adjacent tissues.Patients with KIRC who had high BOP1 expression had differential overall survival(OS),disease-specific survival(DSS),and disease-free interval(DFI).BOP1 expression accurately recognised tumour tissues versus normal tissues(AUC=0.858),and the area under the ROCs for survival at 1,3,and 5 years were all greater than 0.6.The BOP1 gene variant rate was<1%.Out of the 15 DNA methylation CpG sites examined,7 exhibited prognostic significance in KIRC.BOP1 displayed a distinct relationship with immune cell infiltration in KIRC.The 786-O experimental group exhibited substantially higher BOP1 expression,as confirmed by Western blot detection.Conclusion:This study indicates that heightened BOP1 expression is linked to an adverse prognosis in KIRC,establishing it as an independent risk factor for this disease.These findings establish BOP1 as a novel and independent prognostic biomarker for KIRC,offering potential clinical utility for risk stratification and personalized therapeutic strategies.
基金supported by the National Natural Science Foundation of China(32470676 and 32170236)Central Guidance on Local Science and Technology Development Fund of Hebei Province(246Z2508G)+2 种基金Hebei Natural Science Foundation(C2020209064)Tangshan Science and Technology Program Project(21130217C)Key research project of North China University of Science and Technology(ZD-YG-202313-23).
文摘As a high-value eudicot family,many famous horticultural crop genomes have been deciphered in Oleaceae.However,there are currently no bioinformatics platforms focused on empowering genome research in Oleaceae.Herein,we developed the first comprehensive Oleaceae Genome Research Platform(OGRP,https://oleaceae.cgrpoee.top/).In OGRP,70 genomes of 10 Oleaceae species and 46 eudicots and 366 transcriptomes involving 18 Oleaceae plant tissues can be obtained.We built 34 window-operated bioinformatics tools,collected 38 professional practical software programs,and proposed 3 new pipelines,namely ancient polyploidization identification,ancestral karyotype reconstruction,and gene family evolution.Employing these pipelines to reanalyze the Oleaceae genomes,we clarified the polyploidization,reconstructed the ancestral karyotypes,and explored the effects of paleogenome evolution on genes with specific biological regulatory roles.Significantly,we generated a series of comparative genomic resources focusing on the Oleaceae,comprising 108 genomic synteny dot plots,1952225 collinear gene pairs,multiple genome alignments,and imprints of paleochromosome rearrangements.Moreover,in Oleaceae genomes,researchers can efficiently search for 1785987 functional annotations,22584 orthogroups,29582 important trait genes from 74 gene families,12664 transcription factor-related genes,9178872 transposable elements,and all involved regulatory pathways.In addition,we provided downloads and usage instructions for the tools,a species encyclopedia,ecological resources,relevant literatures,and external database links.In short,ORGP integrates rich data resources and powerful analytical tools with the characteristic of continuous updating,which can efficiently empower genome research and agricultural breeding in Oleaceae and other plants.
基金Guangzhou University of Chinese Medicine Shenzhen Hospital(Futian)Postdoctoral Foundation。
文摘This study aimed to investigate the role of autophagy-related genes in osteoarthritis(OA)and evaluate the therapeutic potential of Eucommin A,a key lignan component derived from Eucommia ulmoides.Gene expression profiles from OA patients and healthy controls were retrieved from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified and intersected with autophagy-related genes from the Human Autophagy Database to pinpoint OA-specific autophagy candidates.Functional enrichment analyses via GO and KEGG highlighted involvement in nutrient response,apoptosis,and PI3K-Akt/FoxO signaling pathways.Core genes were prioritized using machine learning algorithms combined with protein-protein interaction(PPI)network analysis,followed by diagnostic validation in an independent cohort.Molecular docking and 100-ns molecular dynamics simulations were conducted to assess the binding stability between Eucommin A and the core targets.Interaction mechanisms were characterized using root mean square deviation(RMSD),root mean square fluctuation(RMSF),radius of gyration(Rg),and MM/GBSA binding free energy calculations.Among 2436 DEGs,56 were autophagy-related and significantly enriched in key biological processes.Machine learning identified EGFR,MAPK3,and MAPK8 as hub genes,with EGFR and MAPK8 exhibiting significant diagnostic value(AUC>0.5).Eucommin A demonstrated strong binding affinity to EGFR and MAPK8 via hydrogen bonding and hydrophobic interactions.Molecular dynamics simulations confirmed stable ligand-target complexes and favorable binding free energy profiles.These findings suggested EGFR and MAPK8 as diagnostic biomarkers for OA-related autophagy.Moreover,Eucommin A exerted multi-target therapeutic effects by stabilizing these autophagy-related proteins,proposing a novel strategy for OA treatment through modulation of autophagy.
文摘Bioinformatics,an interdisciplinary field that integrates computer science,biology,information technology,and statistics,plays a pivotal role in analyzing and interpreting biological data.It has become an indispensable tool in the design and discovery of novel drugs by facilitating the analysis of biological datasets and aiding in the identification of potential therapeutic targets.With the rise of antibiotic resistance among bacterial species,the demand for new drug development has intensified.However,the process of drug discovery remains labor-intensive,costly,and time-consuming.The identification of new drugs involves multiple critical stages,including target identification,structural analysis of the target protein,selection of potential drug candidates,safety and efficacy assessments,drug optimization,and ultimately,validation.Bioinformatics contributes significantly to each of these phases.For instance,through the analysis of protein sequences and genetic data,researchers can pinpoint potential drug targets.Once a target protein is identified,bioinformatics tools enable detailed structural analysis of the protein.Upon locating the potential ligand-binding site,large compound databases can be screened to discover viable drug candidates.Simulations further aid in examining the interaction between the target protein and biomolecules,providing valuable insights into the drug’s safety and efficacy.Moreover,bioinformatics-driven drug optimization helps improve both safety and effectiveness.Recent advances,such as pharmacophore modeling and molecular docking techniques,have accelerated the screening process,narrowing thousands of candidate molecules down to a select few with promising therapeutic potential.In this study,bioinformatics was leveraged within the framework of network pharmacology to design and discover new drugs.
文摘Objective:Employing bioinformatics methodologies to identify core genes intricately associated with the pathogenesis and progression of gastric cancer,and to evaluate their clinical significance.Method:Gene expression datasets GSE19826 and GSE13911 were acquired from the Gene Expression Omnibus(GEO).Differential gene expression analysis was conducted using GEO2R.Common differentially expressed genes(DEGs)were discerned via Venn diagram analysis on a bioinformatics platform.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),were performed on these overlapping DEGs.A protein-protein interaction(PPI)network was constructed with the STRING database,and central hub genes were identified using Cytoscape software.The expression profiles,prognostic value,and immune infiltration correlations of these key genes were further examined utilizing the GEPIA,Kaplan-Meier plotter,Human Protein Atlas(HPA),and TIMER databases.Results:Analysis revealed 120 commonly differentially expressed genes.These genes were significantly enriched in biological pathways concerning muscle cell cytoskeleton regulation,nutrient absorption,and extracellular matrix receptor interactions.PPI network analysis highlighted 10 core genes,including COL1A1,COL1A2,BGN,THBS2,COL5A2,and TIMP1.These genes exhibited marked upregulation in GC tissues.Statistical evaluation confirmed a significant link between their elevated expression and unfavorable patient outcomes(P<0.01).Furthermore,immune infiltration assessment indicated a positive correlation between the expression of these genes and macrophage infiltration within the tumor microenvironment,implying their involvement in modulating the immune response in GC,which could affect tumor behavior and clinical progression.Conclusion:The six genes identified may function as diagnostic biomarkers and represent promising therapeutic targets for gastric cancer.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LQ23H020004The Medical and Health Research Project of Zhejiang province,No.2024KY983Basic Medical Health Technology Project of Wenzhou Science and Technology Bureau,No.Y20210818 and No.Y20210140.
文摘BACKGROUND Myocardial ischemia/reperfusion(I/R)injury,which is associated with high morbidity and mortality,is a main cause of unexpected myocardial injury after acute myocardial infarction.However,the underlying mechanism remains unclear.Circular RNAs(circRNAs),which are formed from protein-coding genes,can sequester microRNAs or proteins,modulate transcription and interfere with splicing.Authoritative studies suggest that circRNAs may play an important role in myocardial I/R injury.AIM To explore the role and mechanism of circRNAs in myocardial I/R injury.METHODS We constructed a myocardial I/R injury model using ligation of the left anterior descending coronary artery,and evaluated the success of the validated model using triphenyltetrazolium chloride and hematoxylin-eosin staining.Then,left ventricular samples from different groups were selected for mRNA-sequence,and differential gene screening was performed on the obtained results.The differentially obtained mRNAs were divided into up-regulated and down-regulated according to their expression levels,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis were performed,respectively.Then,the obtained circRNA and microRNA(miRNA)were paired for analysis,and the binding sites of miRNA and mRNA were virtual screened.Finally,the obtained circRNA,miRNA and mRNA were constructed by ceRNA mutual most useful network.RESULTS We used an RNA sequencing array to investigate the expression signatures of circRNAs in myocardial I/R injury using three samples from the I/R group and three samples from the sham group.A total of 142 upregulated and 121 downregulated circRNAs were found to be differentially expressed(fold change≥2,P<0.05).GO and KEGG functional analyses of these circRNAs were performed.GO analysis revealed that these circRNAs were involved mainly in cellular and intracellular processes.KEGG analysis demonstrated that 6 of the top 20 pathways were correlated with cell apoptosis.Furthermore,a circRNA-miRNA coexpression network and ceRNA network based on these genes were constructed,revealing that mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 might be key regulators of myocardial I/R injury.CONCLUSION This research provides new insights into the mechanism of myocardial I/R,which mmu-circ-0001452,mmu-circ-0001637,and mmu-circ-0000870 are expected to be new therapeutic targets for myocardial I/R injury.
基金supported by the National Natural Science Foundation of China(32160254)Yunnan Fundamental Research Projects(202401AS070039).
文摘Background:A thorough examination of the physicochemical properties,higher-order structure,subcellular localization,and selective pressure of the cytochrome c oxidase subunit I(COX1)protein of the endemic species Eothenomys miletus(E.miletus)in the Hengduan Mountains provides further insights into molecular characteristics and function of the COX1 gene in E.miletus.Method:The physicochemical properties and higher-order structure of the COX1 protein of E.miletus were analyzed using bioinformatics software.Subsequently,a phylogenetic tree was constructed using Mega 7.0 software based on the COX1 gene from 19 species of the Arvicolinae subfamily and 3 species of the Muridae.Selection pressure analysis was performed using the PAML 4.7 software and the Datamonkey online website.Results:The COX1 protein of E.miletus comprises/consists of 514 amino acids,with leucine(Leu/L)being the most prevalent amino acid(11.5%).This hydrophilic protein contains 42 phosphorylation sites and 4 N-glycosylation sites.It possesses a transmembrane domain and lacks signal peptide distribution,thus classifying it as a non-GPI-anchored protein.The secondary structure of the COX1 protein consists ofα-helices(36.77%),random coils(33.85%),and extended chains,a composition consistent with/findings that align with its tertiary structure.Significant genetic differentiation exists among species within the Arvicolinae subfamily,a finding consistent with morphological identification results.The COX1 gene in Arvicolinae species exhibits purifying selection.Conclusion:This study analyzed the physicochemical properties of the COX1 protein in E.miletus.Phylogenetic and selection pressure analyses reveal significant genetic divergence among Arvicolinae species,and demonstrate that the COX1 gene is evolutionarily conserved within the Arvicolinae subfamily.
基金supported by the National Natural Science Foundation of China(32260097)the National Guidance of Local Science and Technology Development Fund of China([2023]009)。
文摘Ericaceae is a diverse family of flowering plants distributed nearly worldwide,and it includes 126 genera and more than 4,000 species.In the present study,we developed The Ericaceae Genome Resource(TEGR,http://www.tegr.com.cn)as a comprehensive,user-friendly,web-based functional genomic database that is based on 16 published genomes from 16 Ericaceae species.The TEGR database contains information on many important functional genes,including 763 auxin genes,2,407 flowering genes,20,432 resistance genes,617 anthocyanin-related genes,and 470 N^(6)-methyladenosine(m^(6)A)modification genes.We identified a total of 599,174 specific guide sequences for CRISPR in the TEGR database.The gene duplication events,synteny analysis,and orthologous analysis of the16 Ericaceae species were performed using the TEGR database.The TEGR database contains 614,821 functional genes annotated through the GO,Nr,Pfam,TrEMBL,and Swiss-Prot databases.The TEGR database provides the Primer Design,Hmmsearch,Synteny,BLAST,and JBrowse tools for helping users perform comprehensive comparative genome analyses.All the high-quality reference genome sequences,genomic features,gene annotations,and bioinformatics results can be downloaded from the TEGR database.In the future,we will continue to improve the TEGR database with the latest data sets when they become available and to provide a useful resource that facilitates comparative genomic studies.
基金Supported by College Student Innovation and Entrepreneurship Training Program(S202210553003)Hunan Provincial Education Department Outstanding Youth Research Project(23B0820).
文摘Kinesins are a superfamily of proteins widely present in eukaryotes,playing crucial roles in plant cell wall assembly,cell elongation regulation,gravity sensing,and fertility control.In this study,bioinformatics analysis of the OsKMP2 gene(LOC_Os02g28850)was performed using online tools such as ExPASy-ProtParam,ProtScale,CD-search,and DNAMAN software.Additionally,qRT-PCR was employed to analyze the tissue expression pattern of OsKMP2.The results showed that the molecular weight of the OsKMP2 is 118.39728 kDa,and it is a hydrophilic and unstable acidic protein.Secondary structure prediction revealed that it primarily consists ofα-helices(69.45%),random coils(25.19%),and extended strands(5.36%).The gene was expressed in various rice tissues,with the highest expression level observed in leaves.These results indicate that the OsKMP2 gene exhibits high evolutionary conservation and functional diversity in rice.
