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
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
Objective:To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase(G6PD)and the clinicopathological characteristics,prognosis and immune cell infiltration of hepatocellular carcinoma(...Objective:To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase(G6PD)and the clinicopathological characteristics,prognosis and immune cell infiltration of hepatocellular carcinoma(HCC).Methods:The expression of G6PD in liver cancer tissues and normal tissues is extracted from TCGA and GEO databases,validated by immunohistochemistry,and the correlation between G6PD expression and clinical features is analyzed.The clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier,Cox regression,and prognostic line graph models.Functional enrichment analysis is performed by protein-protein interaction(PPI)network,GO/KEGG,GSEA and for G6PD-associated differentially expressed genes(DEGs).TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results:Analysis of TCGA and GEO datasets revealed that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues(P<0.001).G6PD expression is associated with histological grade,pathological stage,T-stage,vascular infiltration,and AFP level(P<0.05);HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group(P<0.05).The level of G6PD expression affects the levels of macrophages,dendritic cells,B cells,and follicular helper T cells in the tumor microenvironment.Conclusion:High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma,and G6PD may be a target for immunotherapy of HCC.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underp...Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.展开更多
AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyse...AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.展开更多
To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was struct...To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study...Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.展开更多
The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for...The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for data mining and detected the biological behavior of endothelial cells(ECs)under hypoxia conditions and high dose dexamethasone to reveal the mechanisms above.Six differential expression mi RNAs(DE-miRNAs)were filtered from Gene Expression Omnibus(GEO)database GSE60093 which contained ECs treated with high dose glucocorticoid and control samples.Enrichment and PPI network analyses of the DE-miRNAs target genes showed the most remarkable pathway was HIF-1 signaling pathway and high dose glucocorticoid as a negative regulator of cell differentiation,energy metabolism,migration and cytokines secretion.Glucocorticoids also reduced the activity of autocrine/paracrine via limiting ion channels and transmembrane transporter process.In cytological experiment,HUVECs were divided into four groups:hypoxia group(H),hypoxia+dexamethasone group(HD),dexamethasone group(D),the normal group(N).Cell activity detection and Live/Dead dyeing showed cell activity and the number of live cells in Group H was higher than the other three groups at 24 h after intervention,while cell activity,number and proportion of live cells in HD group were worst.Cytoskeleton staining showed HD group met cytoskeleton form disorders.The scratch assay showed cell migration ability of Group H was strongest while cell migration ability of the HD group was worst.MIF expression in HD group showed a trend of bimodal,the peak of VEGF-A secretion lagged behind the MIF’s.Expression of MIF and VEGF-A in the HD group were low.High dose dexamethasone suppressed the active response of ECs to hypoxia stimulation via directly inhibiting the expression of MIF and interdicting autocrine/paracrine mechanism.We infered that the treatment with high dose glucocorticoid would inhibit neo-angiogenesis under hypoxia followed by aggravating hypoxia/ischemia and osteonecrosis.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
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
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
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
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.
文摘Objective:To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase(G6PD)and the clinicopathological characteristics,prognosis and immune cell infiltration of hepatocellular carcinoma(HCC).Methods:The expression of G6PD in liver cancer tissues and normal tissues is extracted from TCGA and GEO databases,validated by immunohistochemistry,and the correlation between G6PD expression and clinical features is analyzed.The clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier,Cox regression,and prognostic line graph models.Functional enrichment analysis is performed by protein-protein interaction(PPI)network,GO/KEGG,GSEA and for G6PD-associated differentially expressed genes(DEGs).TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results:Analysis of TCGA and GEO datasets revealed that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues(P<0.001).G6PD expression is associated with histological grade,pathological stage,T-stage,vascular infiltration,and AFP level(P<0.05);HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group(P<0.05).The level of G6PD expression affects the levels of macrophages,dendritic cells,B cells,and follicular helper T cells in the tumor microenvironment.Conclusion:High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma,and G6PD may be a target for immunotherapy of HCC.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
基金National Natural Science Foundation of China,Grant/Award Number:No.82560858Beijing Science and Technology New Star Program Cross-cooperation Project,Grant/Award Number:No.20240484711Jiangxi Provincial Natural Science Foundation,Grant/Award Number:20252BAC200586。
文摘Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.
文摘AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.
基金Supported by Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9,Yuejiao Gao Han[2024]No.30)Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)+1 种基金Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)Quality Engineering and Teaching Reform Projects of Zhaoqing University(zlgc202239,zlgc202207,zlgc2024005,zlgc2024038).
文摘To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81972073(to HZ)a grant from the Taishan Scholars Program ofShandong Province-Young Taishan Scholars,No.tsqn201909197(to HZ)+1 种基金a grant from Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)a grant from Academic Expert International Innovation Summit,No.22JRRCRC00010(to SF).
文摘Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.
基金the National Natural Science Foundation of Chinagrant number:81301562 and 81572147。
文摘The exact molecular and cytological mechanism of how glucocorticoids induce vascular repair disorders in glucocorticoid-induced avascular necrosis of the femoral head is still unclear.We used bioinformatical tools for data mining and detected the biological behavior of endothelial cells(ECs)under hypoxia conditions and high dose dexamethasone to reveal the mechanisms above.Six differential expression mi RNAs(DE-miRNAs)were filtered from Gene Expression Omnibus(GEO)database GSE60093 which contained ECs treated with high dose glucocorticoid and control samples.Enrichment and PPI network analyses of the DE-miRNAs target genes showed the most remarkable pathway was HIF-1 signaling pathway and high dose glucocorticoid as a negative regulator of cell differentiation,energy metabolism,migration and cytokines secretion.Glucocorticoids also reduced the activity of autocrine/paracrine via limiting ion channels and transmembrane transporter process.In cytological experiment,HUVECs were divided into four groups:hypoxia group(H),hypoxia+dexamethasone group(HD),dexamethasone group(D),the normal group(N).Cell activity detection and Live/Dead dyeing showed cell activity and the number of live cells in Group H was higher than the other three groups at 24 h after intervention,while cell activity,number and proportion of live cells in HD group were worst.Cytoskeleton staining showed HD group met cytoskeleton form disorders.The scratch assay showed cell migration ability of Group H was strongest while cell migration ability of the HD group was worst.MIF expression in HD group showed a trend of bimodal,the peak of VEGF-A secretion lagged behind the MIF’s.Expression of MIF and VEGF-A in the HD group were low.High dose dexamethasone suppressed the active response of ECs to hypoxia stimulation via directly inhibiting the expression of MIF and interdicting autocrine/paracrine mechanism.We infered that the treatment with high dose glucocorticoid would inhibit neo-angiogenesis under hypoxia followed by aggravating hypoxia/ischemia and osteonecrosis.
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.
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.
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.
