Cysteine-rich polycomb-like(CPP)is a small gene family in plants,which plays key role in plant development and stress response.Although CPP transcription factors have been characterized in several other plant species,...Cysteine-rich polycomb-like(CPP)is a small gene family in plants,which plays key role in plant development and stress response.Although CPP transcription factors have been characterized in several other plant species,a genome-wide characterization of the CPP gene family has been absent in Camellia sinensis.In this study,we totally identified 7,8,and 8 non-redundant CsCPP genes in three published genomes,including Camellia sinensis var.assamica cv.Yunkang-10(CSA-YK10),Camellia sinensis var.sinensis cv.Biyun(CSS-BY)and Camellia sinensis var.sinensis cv.Shuchazao(CSS-SCZ).CPP proteins from tea tree and other plant species were classified into three groups,which were further divided into four subgroups based on phylogenetic relationships.Most CPP genes in the same subgroup had similar gene structures and conserved motifs.The cis-acting elements analysis indicated that CPP genes might be involved in plant growth,development and stress responses.Analysis of gene expression using qRT-PCR experiments validated that CPP genes exhibited different expression patterns across the examined tissues.All the genes were expressed differentially in a range of tissues,indicating that CPPs were involved in a range of developmental and physiological processes.This study has obtained new insights into the evolution and function of the CPP gene family in the growth and development of tea plants,and also provide candidate genes for further functional characterization in tea tree.展开更多
BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greate...BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.展开更多
Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emo...Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.展开更多
Rice is one of the most important stable food as well as a monocotyledonous model organism for the plant research community.Here,we present RED（Rice Expression Database;http：//expression.ic4r.org）,an integrated dat...Rice is one of the most important stable food as well as a monocotyledonous model organism for the plant research community.Here,we present RED（Rice Expression Database;http：//expression.ic4r.org）,an integrated database of rice gene expression profiles derived entirely from RNA-Seq data.RED features a comprehensive collection of 284 high-quality RNA-Seq experiments,integrates a large number of gene expression profiles and covers a wide range of rice growth stages as well as various treatments.Based on massive expression profiles,RED provides a list of housekeeping and tissue-specific genes and dynamically constructs co-expression networks for gene（s） of interest.Besides,it provides user-friendly web interfaces for querying,browsing and visualizing expression profiles of concerned genes.Together,as a core resource in BIG Data Center,RED bears great utility for characterizing the function of rice genes and better understanding important biological processes and mechanisms underlying complex agronomic traits in rice.展开更多
Background： RING H2 finger E3 ligase （RH2FE3） genes encode cysteine rich proteins that mediate E3 ubiquitin ligase activity and degrade target substrates. The roles of these genes in plant responses to phytohormone...Background： RING H2 finger E3 ligase （RH2FE3） genes encode cysteine rich proteins that mediate E3 ubiquitin ligase activity and degrade target substrates. The roles of these genes in plant responses to phytohormones and abiotic stresses are well documented in various species, but their roles in cotton fiber development are poorly understood. To date, genome wide identification and expression analyses of Gossypium hirsutum RH2FE3 genes have not been reported. Methods： We performed computational identification, structural and phylogenetic analyses, chromosomal distribution analysis and estimated KJKs values of G hirsutum RH2FE3 genes. Orthologous and paralogous gene pairs were identified by all versus all BLASTP searches. We predicted cis regulatory elements and analyzed microarray data sets to generate heatmaps at different development stages. Tissue specific expression in cotton fiber, and hormonal and abiotic stress responses were determined by quantitative real time polymerase chain reaction （qRT PCR） analysis. Results： We investigated 140 G hirsutum, 80 G. orboreum, and evolutionary mechanisms and compared them with orthologs 89 G. roimondii putative RH2FB genes and their in Arobidopsis and rice. A domain based analysis of the G hirsutum RH2FE3 genes predicted conserved signature motifs and gene structures. Chromosomal localization showed the genes were distributed across all G hirsutum chromosomes, and 60 duplication events （4 tandem and 56 segmental duplications） and 98 orthologs were detected, cis elements were detected in the promoter regions of G hirsutum RH2FE3 genes. Microarray data and qRT PCR analyses showed that G hirsutum RH2FE3 genes were strongly correlated with cotton fiber development. Additionally, almost all the （brassinolide, gibberellic acid （GA）, indole 3-acetic acid drought, and salt）. dentified genes were up regulated in response to phytohormones （IAA）, and salicylic acid （SA）） and abiotic stresses （cold, heat, Conclusions： The genome wide identification, comprehensive analysis, and characterization of conserved domains and gene structures, as well as phylogenetic analysis, cis element prediction, and expression profile analysis of G hirsutum RH2FE3 genes and their roles in cotton fiber development and responses to plant hormones and abiotic stresses are reported here for the first time. Our findings will contribute to the genome wide analysis of putative RH2FE3 genes in other species and lay a foundation for future physiological and functional research on G hirsutum RH2FE3 genes.展开更多
Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray dat...Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray data packages were downloaded from the Gene Expression Omnibus for planning,testing,and review of data.We identified KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV from a key module for validation.Results We found that the five genes were related to a poor prognosis,and the expression levels of these genes were associated with tumor stage.Furthermore,Kaplan-Meier plotter showed that the five hub genes had better prognostic values.The mean levels of methylation in lung adenocarcinoma(LUAD)were significantly lower than those in healthy lung tissues for the hub genes.However,gene set enrichment analysis(GSEA)for single hub genes showed that all of them were immune-related.Conclusion Our findings demonstrated that KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV are all candidate diagnostic and prognostic biomarkers for LUAD.They may have clinical implications in LUAD patients not only for the improvement of risk stratification but also for therapeutic decisions and prognosis prediction.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
BEL1-like homeodomain(BLH)family proteins are homeodomain transcription factors,which are found ubiquitously in plants and play important roles in regulating meristem and flower development.Although BLH proteins have ...BEL1-like homeodomain(BLH)family proteins are homeodomain transcription factors,which are found ubiquitously in plants and play important roles in regulating meristem and flower development.Although BLH proteins have been reported in some plant species,there is very little information available for plants in the Malus genus(e.g.,apple tree:Malus domestica).In the present study,we identified 19 apple MdBLH genes.Phylogenetic analysis revealed that the MdBLH genes could be divided into five groups.Analysis of gene structure showed that MdBLH gene has four exons,and the third exon was 61 bp in length.Chromosomal location analysis suggested that the MdBLH genes are not distributed uniformly on 12 chromosomes.Eleven MdBLH genes were cloned by RT-PCR,and their expression patterns were also determined.Among them,the expression levels of MdBLH4.1 and MdBLH9.1 could be induced by sodium chloride stress,while the expression levels of MdATH1.1,MdBLH8.1,MdBLH8.3,and MdBLH11.1 were down-regulated by such stress.Transcriptional levels of MdATH1.1 and MdBLH7.2 were down-regulated by mannitol stress.The result of yeast two-hybrid experiment showed that MdBEL1.1 interacted with apple ovate family proteins 6(MdOFP6),and MdBLH3.1 interacted with the MdOFP4,MdOFP6,MdOFP13,and MdOFP16 proteins.Our results provide a strong theoretical basis and a valuable reference for analyzing of the biological functions of MdBLH proteins as transcription factors in apple growth,development,and stress and also for the construction of regulatory networks.展开更多
Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of protein...Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of proteins in lung(A549)and colon(HT29)cancer cell lines was examined by using proteomics analysis.The protein-protein interaction study of differentially expressed proteins was done by using the Search Tool for the Retrieval of Interacting Genes(STRING),and the results showed that the proteins interacting with each other belong to different pathways.展开更多
Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new op...Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new opportunity for investigating diagnosis,treatment,and prognosis of spinal cord injury.However,differentially expressed genes are not consistent among studies,and many key genes and signaling pathways have not yet been accurately studied.GSE5296 was retrieved from the Gene Expression Omnibus DataSet.Differentially expressed genes were obtained using R/Bioconductor software(expression changed at least two-fold;P < 0.05).Database for Annotation,Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors.The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease.In total,this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5,4,and 24 hours,and 3,7,and 28 days after spinal cord injury.The number of downregulated genes was smaller than the number of upregulated genes at each time point.Database for Annotation,Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord.Additionally,expression levels of these inflammation-related genes were maintained for at least 28 days.Moreover,399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes.Among the 10 upregulated differentially expressed genes with the highest degrees of distribution,six genes were transcription factors.Among these transcription factors,ATF3 showed the greatest change.ATF3 was upregulated within 30 minutes,and its expression levels remained high at28 days after spinal cord injury.These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.展开更多
Human tongue cancer （TC） is an aggressive malignancy with a very poor prognosis. There is an urgent need to elucidate the underlying molecular mechanisms involved in TC progression, mRNA expression profiles play a v...Human tongue cancer （TC） is an aggressive malignancy with a very poor prognosis. There is an urgent need to elucidate the underlying molecular mechanisms involved in TC progression, mRNA expression profiles play a vital role in the exploration of cancer-related genes. Therefore, the purpose of our study was to identify the progression associated candidate genes of TC by bioinformatics analysis. Five microarray datasets of TC samples were downloaded from the Gene Expression Onmibus （GEO） database and the data of 133 TC patients were screened from The Cancer Genome Atlas （TCGA） head and neck squamous cell carcinoma （HNSC） database. The integrated analysis of five microarray datasets and the RNA sequencing data of TC samples in TCGA-HNSC was performed to obtain 1023 overlapping differentially expressed genes （DEGs） in TC and adjacent normal tissue （ANT） samples. Next, Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis was conducted to enrich the significant pathways of the 1023 DEGs and PI3K- Akt signaling pathway （P=0.011） was selected to be the candidate pathway. A total of 23 DEGs with ｜log2 fold change （FC）｜ ≥1.0 in phosphatidylinositol 3-kinase-serine/threonine kinase （PI3K-Akt） signaling pathway were subjected to survival analysis of 125 eligible TC samples in TCGA database, indicating increased integrin-α3 gene （ITGA3） expression was significantly associated with poorer prognosis. Taken together, our study suggested ITGA3 may facilitate the development of TC via activating PI3K-Akt signaling pathway.展开更多
Renal ischemia-reperfusion injury(IRI)is a major cause of acute kidney injury(AKI),which could induce the poor prognosis.The purpose of this study was to characterize the molecular mechanism of the functional changes ...Renal ischemia-reperfusion injury(IRI)is a major cause of acute kidney injury(AKI),which could induce the poor prognosis.The purpose of this study was to characterize the molecular mechanism of the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.The gene expression profiles of CD11 b^(+)/Ly6 C^(intermediate)macrophages of the sham surgery mice,and the mice 4 h,24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database.Analysis of m RNA expression profiles was conducted to identify differentially expressed genes(DEGs),biological processes and pathways by the series test of cluster.Protein-protein interaction network was constructed and analysed to discover the key genes.A total of 6738 DEGs were identified and assigned to 20 model profiles.DEGs in profile 13 were one of the predominant expression profiles,which are involved in immune cell chemotaxis and proliferation.Signet analysis showed that Atp5 a1,Atp5 o,Cox4 i,Cdc42,Rac2 and Nhp2 were the key genes involved in oxidation-reduction,apoptosis,migration,M1-M2 differentiation,and proliferation of macrophages.RPS18 may be an appreciate reference gene as it was stable in macrophages.The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.Moreover,the vital gene Nhp2 may involve the polarization of macrophages,which may be a new target to affect the process of AKI.展开更多
METHODS:In the present study,female SpragueDawley rats were randomly divided into four groups with 6 of each,including normal control group(NC),jumpinginduced muscle injury model group(JI),JI with electroacupuncture s...METHODS:In the present study,female SpragueDawley rats were randomly divided into four groups with 6 of each,including normal control group(NC),jumpinginduced muscle injury model group(JI),JI with electroacupuncture stimulation treatment group(EA),and JI with non-electroacupuncture stimulation group(NEA).Transmission electron microscopy,transcriptome sequencing and analysis,prediction of protein interaction networks,real-time polymerase chain reaction verification,and Western blotting were performed on the gastrocnemius muscle of ipsilateral lower limbs.RESULTS:The structural repair of injured gastrocnemius myofibers following jumping training in EA rats was better than that of NEA rats.A total of 136 genes were differentially expressed in EA rats relative to JI rats,with 55 genes upregulated and 81 genes downregulated.According to results of transcriptome analysis,and prediction of protein mutual interaction by the online STRING database,Heat shock protein beta-7(Hspb7)and myozenin2(Myoz2)genes were targeted.Expressions of Hspb7 and Myoz2 mRNAs were increased in EA rats relative to JI rats(P<0.05).The expression of Hspb7 protein was upregulated in EA rats relative to that in NC,JI,and NEA rats(P<0.01,<0.05,and<0.05,respectively).The expression of Myoz2 protein was upregulated in EA rats relative to that in NC and JI rats(both P<0.01,respectively).CONCLUSIONS:The present results suggest that electroacupuncture stimulation at Zusanli(ST36)could improve muscle healing following jumping-induced muscle injury,owing to the upregulation of Hspb7 and Myoz2 proteins.展开更多
Background:The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus ...Background:The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus infections in human and animal models.Methods:We collected a large amount of transcriptome research data related to influenza virus-i nfected human and animal models in public databases(GEO and ArrayExpress),and extracted and integrated array and metadata.The gene expression matrix was generated through strictly quality control,balance,standardization,batch correction,and gene annotation.We then analyzed gene expression in different species,virus,cells/tissues or after antibody/vaccine treatment and imported sample metadata and gene expression datasets into the database.Results:Overall,maintaining careful processing and quality control,we collected 8064 samples from 103 independent datasets,and constructed a comparative transcriptomics database of influenza virus named the Flu-CED database(Influenza comparative expression database,https://flu.com-med.org.cn/).Using integrated and processed transcriptomic data,we established a user-friendly website for realizing the integration,online retrieval,visualization,and exploration of gene expression of influenza virus infection in different species and the biological functions involved in differential genes.Flu-CED can quickly query single and multi-gene expression profiles,combining different experimental conditions for comparative transcriptome analysis,identifying differentially expressed genes(DEGs)between comparison groups,and conveniently finding DEGs.Conclusion:Flu-CED provides data resources and tools for analyzing gene expression in human and animal models infected with influenza virus that can deepen our understanding of the mechanisms underlying disease occurrence and development,and enable prediction of key genes or therapeutic targets that can be used for medical research.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common cancers and has a poor prognosis.Treatment of GC has remained unchanged over the past few years.AIM To investigate the potential therapeutic targets and related r...BACKGROUND Gastric cancer(GC)is one of the most common cancers and has a poor prognosis.Treatment of GC has remained unchanged over the past few years.AIM To investigate the potential therapeutic targets and related regulatory biomarkers of GC.METHODS We obtained the public GC transcriptome sequencing dataset from the Gene Expression Omnibus database.The datasets contained 348 GC tissues and 141 healthy tissues.In total,251 differentially expressed genes(DEGs)were identified,including 187 down-regulated genes and 64 up-regulated genes.The DEGs’enriched functions and pathways include Progesterone-mediated oocyte maturation,cell cycle,and oocyte meiosis,Hepatitis B,and the Hippo signaling pathway.Survival analysis showed that BUB1,MAD2L1,CCNA2,CCNB1,and BIRC5 may be associated with regulation of the cell cycle phase mitotic spindle checkpoint pathway.We selected 26 regulated genes with the aid of the protein-protein interaction network analyzed by Molecular Complex Detection.RESULTS We focused on three critical genes,which were highly expressed in GC,but negatively related to patient survival.Furthermore,we found that knockdown of Yu K et al.Biochemical analysis in GC WJCC https://www.wjgnet.com 5024 July 26,2023 Volume 11 Issue 21 BIRC5,TRIP13 or UBE2C significantly inhibited cell proliferation and induced cell apoptosis.In addition,knockdown of BIRC5,TRIP13 or UBE2C increased cellular sensitivity to cisplatin.CONCLUSION Our study identified significantly upregulated genes in GC with a poor prognosis using integrated bioinformatics methods.展开更多
BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.Th...BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.展开更多
[目的]Heavy metal ATPase(HMA)蛋白参与了植物对多种金属离子的吸收和转运。本研究通过对谷子HMA进行全基因组表征、表达及同源分析以解析其功能。[方法]通过蛋白同源比对和保守结构域筛选谷子HMA基因家族成员;采用生物信息学手段系统...[目的]Heavy metal ATPase(HMA)蛋白参与了植物对多种金属离子的吸收和转运。本研究通过对谷子HMA进行全基因组表征、表达及同源分析以解析其功能。[方法]通过蛋白同源比对和保守结构域筛选谷子HMA基因家族成员;采用生物信息学手段系统分析了谷子HMA的理化性质、家族扩张、保守基序、系统发育关系及蛋白质分子对接;基于不同浓度Cd、Fe胁迫下的转录组和荧光定量PCR分析了其对不同金属离子的响应;基于模式物种水稻的同源比对预测了部分SiHMA的功能。[结果]在谷子基因组中共鉴定到12个HMA基因,并将其分为2个亚组,有6个HMA基因参与到2次串联重复(4个基因,占比33.3%)和1次片段复制事件(2个基因,占比16.7%)中。SiHMA基因在不同组织中对Cd、Fe胁迫表现出不同的响应模式。预测了SiHMA可能的功能,SiHMA5参与细胞中Zn、Cu、Pb和Cd等金属离子的外排过程,SiHMA10可能参与植物体内Cu的装载和运输。[结论]重复事件和片段复制在谷子HMA基因家族扩张和SiHMA功能进化中发挥作用。植物激素、应激胁迫等多种顺式作用元件参与到SiHMA响应非生物胁迫途径中,我们根据同源比较、组织表达特征和前人研究,预测了SiHMA1、SiHMA5、SiHMA6和SiHMA10等基因可能的功能,以上结果可为进一步研究HMA基因家族及其在谷子中的生物学功能提供理论基础。展开更多
文摘Cysteine-rich polycomb-like(CPP)is a small gene family in plants,which plays key role in plant development and stress response.Although CPP transcription factors have been characterized in several other plant species,a genome-wide characterization of the CPP gene family has been absent in Camellia sinensis.In this study,we totally identified 7,8,and 8 non-redundant CsCPP genes in three published genomes,including Camellia sinensis var.assamica cv.Yunkang-10(CSA-YK10),Camellia sinensis var.sinensis cv.Biyun(CSS-BY)and Camellia sinensis var.sinensis cv.Shuchazao(CSS-SCZ).CPP proteins from tea tree and other plant species were classified into three groups,which were further divided into four subgroups based on phylogenetic relationships.Most CPP genes in the same subgroup had similar gene structures and conserved motifs.The cis-acting elements analysis indicated that CPP genes might be involved in plant growth,development and stress responses.Analysis of gene expression using qRT-PCR experiments validated that CPP genes exhibited different expression patterns across the examined tissues.All the genes were expressed differentially in a range of tissues,indicating that CPPs were involved in a range of developmental and physiological processes.This study has obtained new insights into the evolution and function of the CPP gene family in the growth and development of tea plants,and also provide candidate genes for further functional characterization in tea tree.
文摘BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.
基金supported by the National Natural Science Foundation of China(81371213,81070987,and30971531)the grants from the Ministry of Science and Technology of China(2010CB945600 and 2010CB945601)
文摘Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.
基金supported by grants from Strategic Priority Research Program of the Chinese Academy of Sciences(No. XDA08020102 to Z.Z.and S.H.)International Partnership Program of the Chinese Academy of Sciences(No.153F11KYSB20160008)+3 种基金National Programs for High Technology Research and Development (863 ProgramNo.2015AA020108 to Z.Z.)National Natural Science Foundation of China(No.31100915 to LH.)the 100-Talent Program of Chinese Academy of Sciences(awarded to Z.Z.)
文摘Rice is one of the most important stable food as well as a monocotyledonous model organism for the plant research community.Here,we present RED（Rice Expression Database;http：//expression.ic4r.org）,an integrated database of rice gene expression profiles derived entirely from RNA-Seq data.RED features a comprehensive collection of 284 high-quality RNA-Seq experiments,integrates a large number of gene expression profiles and covers a wide range of rice growth stages as well as various treatments.Based on massive expression profiles,RED provides a list of housekeeping and tissue-specific genes and dynamically constructs co-expression networks for gene（s） of interest.Besides,it provides user-friendly web interfaces for querying,browsing and visualizing expression profiles of concerned genes.Together,as a core resource in BIG Data Center,RED bears great utility for characterizing the function of rice genes and better understanding important biological processes and mechanisms underlying complex agronomic traits in rice.
基金supported by the Major Research Plan of National Natural Science Foundation of China(NO.31690093)Young Elite Scientist Sponsorship Program by CAST(China Association for Science and Technology)
文摘Background： RING H2 finger E3 ligase （RH2FE3） genes encode cysteine rich proteins that mediate E3 ubiquitin ligase activity and degrade target substrates. The roles of these genes in plant responses to phytohormones and abiotic stresses are well documented in various species, but their roles in cotton fiber development are poorly understood. To date, genome wide identification and expression analyses of Gossypium hirsutum RH2FE3 genes have not been reported. Methods： We performed computational identification, structural and phylogenetic analyses, chromosomal distribution analysis and estimated KJKs values of G hirsutum RH2FE3 genes. Orthologous and paralogous gene pairs were identified by all versus all BLASTP searches. We predicted cis regulatory elements and analyzed microarray data sets to generate heatmaps at different development stages. Tissue specific expression in cotton fiber, and hormonal and abiotic stress responses were determined by quantitative real time polymerase chain reaction （qRT PCR） analysis. Results： We investigated 140 G hirsutum, 80 G. orboreum, and evolutionary mechanisms and compared them with orthologs 89 G. roimondii putative RH2FB genes and their in Arobidopsis and rice. A domain based analysis of the G hirsutum RH2FE3 genes predicted conserved signature motifs and gene structures. Chromosomal localization showed the genes were distributed across all G hirsutum chromosomes, and 60 duplication events （4 tandem and 56 segmental duplications） and 98 orthologs were detected, cis elements were detected in the promoter regions of G hirsutum RH2FE3 genes. Microarray data and qRT PCR analyses showed that G hirsutum RH2FE3 genes were strongly correlated with cotton fiber development. Additionally, almost all the （brassinolide, gibberellic acid （GA）, indole 3-acetic acid drought, and salt）. dentified genes were up regulated in response to phytohormones （IAA）, and salicylic acid （SA）） and abiotic stresses （cold, heat, Conclusions： The genome wide identification, comprehensive analysis, and characterization of conserved domains and gene structures, as well as phylogenetic analysis, cis element prediction, and expression profile analysis of G hirsutum RH2FE3 genes and their roles in cotton fiber development and responses to plant hormones and abiotic stresses are reported here for the first time. Our findings will contribute to the genome wide analysis of putative RH2FE3 genes in other species and lay a foundation for future physiological and functional research on G hirsutum RH2FE3 genes.
基金Supported by a grant from the Chinese Society of Clinical Oncology(No.Y-HR2018-293 and Y-HR2018-294).
文摘Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray data packages were downloaded from the Gene Expression Omnibus for planning,testing,and review of data.We identified KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV from a key module for validation.Results We found that the five genes were related to a poor prognosis,and the expression levels of these genes were associated with tumor stage.Furthermore,Kaplan-Meier plotter showed that the five hub genes had better prognostic values.The mean levels of methylation in lung adenocarcinoma(LUAD)were significantly lower than those in healthy lung tissues for the hub genes.However,gene set enrichment analysis(GSEA)for single hub genes showed that all of them were immune-related.Conclusion Our findings demonstrated that KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV are all candidate diagnostic and prognostic biomarkers for LUAD.They may have clinical implications in LUAD patients not only for the improvement of risk stratification but also for therapeutic decisions and prognosis prediction.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
基金This study was supported by Shandong Provincial Natural Science Foundation,China(Grant No.ZR2019MC071).
文摘BEL1-like homeodomain(BLH)family proteins are homeodomain transcription factors,which are found ubiquitously in plants and play important roles in regulating meristem and flower development.Although BLH proteins have been reported in some plant species,there is very little information available for plants in the Malus genus(e.g.,apple tree:Malus domestica).In the present study,we identified 19 apple MdBLH genes.Phylogenetic analysis revealed that the MdBLH genes could be divided into five groups.Analysis of gene structure showed that MdBLH gene has four exons,and the third exon was 61 bp in length.Chromosomal location analysis suggested that the MdBLH genes are not distributed uniformly on 12 chromosomes.Eleven MdBLH genes were cloned by RT-PCR,and their expression patterns were also determined.Among them,the expression levels of MdBLH4.1 and MdBLH9.1 could be induced by sodium chloride stress,while the expression levels of MdATH1.1,MdBLH8.1,MdBLH8.3,and MdBLH11.1 were down-regulated by such stress.Transcriptional levels of MdATH1.1 and MdBLH7.2 were down-regulated by mannitol stress.The result of yeast two-hybrid experiment showed that MdBEL1.1 interacted with apple ovate family proteins 6(MdOFP6),and MdBLH3.1 interacted with the MdOFP4,MdOFP6,MdOFP13,and MdOFP16 proteins.Our results provide a strong theoretical basis and a valuable reference for analyzing of the biological functions of MdBLH proteins as transcription factors in apple growth,development,and stress and also for the construction of regulatory networks.
基金This work was supported by the National Natural Science Foundation of China (No 30370904and No 30671258)the National High Technology Research and Development Program(863 project)of China (No 2006AA10Z121)the Program for New Century Excellent Talents in University(No NCET-07-0712)
文摘Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
文摘Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of proteins in lung(A549)and colon(HT29)cancer cell lines was examined by using proteomics analysis.The protein-protein interaction study of differentially expressed proteins was done by using the Search Tool for the Retrieval of Interacting Genes(STRING),and the results showed that the proteins interacting with each other belong to different pathways.
基金supported by the Natural Science Foundation of Shaanxi Province of China,No.2018JQ8029(to LG)
文摘Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new opportunity for investigating diagnosis,treatment,and prognosis of spinal cord injury.However,differentially expressed genes are not consistent among studies,and many key genes and signaling pathways have not yet been accurately studied.GSE5296 was retrieved from the Gene Expression Omnibus DataSet.Differentially expressed genes were obtained using R/Bioconductor software(expression changed at least two-fold;P < 0.05).Database for Annotation,Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors.The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease.In total,this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5,4,and 24 hours,and 3,7,and 28 days after spinal cord injury.The number of downregulated genes was smaller than the number of upregulated genes at each time point.Database for Annotation,Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord.Additionally,expression levels of these inflammation-related genes were maintained for at least 28 days.Moreover,399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes.Among the 10 upregulated differentially expressed genes with the highest degrees of distribution,six genes were transcription factors.Among these transcription factors,ATF3 showed the greatest change.ATF3 was upregulated within 30 minutes,and its expression levels remained high at28 days after spinal cord injury.These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.
文摘Human tongue cancer （TC） is an aggressive malignancy with a very poor prognosis. There is an urgent need to elucidate the underlying molecular mechanisms involved in TC progression, mRNA expression profiles play a vital role in the exploration of cancer-related genes. Therefore, the purpose of our study was to identify the progression associated candidate genes of TC by bioinformatics analysis. Five microarray datasets of TC samples were downloaded from the Gene Expression Onmibus （GEO） database and the data of 133 TC patients were screened from The Cancer Genome Atlas （TCGA） head and neck squamous cell carcinoma （HNSC） database. The integrated analysis of five microarray datasets and the RNA sequencing data of TC samples in TCGA-HNSC was performed to obtain 1023 overlapping differentially expressed genes （DEGs） in TC and adjacent normal tissue （ANT） samples. Next, Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis was conducted to enrich the significant pathways of the 1023 DEGs and PI3K- Akt signaling pathway （P=0.011） was selected to be the candidate pathway. A total of 23 DEGs with ｜log2 fold change （FC）｜ ≥1.0 in phosphatidylinositol 3-kinase-serine/threonine kinase （PI3K-Akt） signaling pathway were subjected to survival analysis of 125 eligible TC samples in TCGA database, indicating increased integrin-α3 gene （ITGA3） expression was significantly associated with poorer prognosis. Taken together, our study suggested ITGA3 may facilitate the development of TC via activating PI3K-Akt signaling pathway.
基金supported by grants from the National Natural Science Foundation of China(No.81670634)Graduate student scientific research innovation projects in Jiangsu province(No.KYLX15_0981)Nanjing Medical University Science and Technology Development Fund(No.2016NJMU065)
文摘Renal ischemia-reperfusion injury(IRI)is a major cause of acute kidney injury(AKI),which could induce the poor prognosis.The purpose of this study was to characterize the molecular mechanism of the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.The gene expression profiles of CD11 b^(+)/Ly6 C^(intermediate)macrophages of the sham surgery mice,and the mice 4 h,24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database.Analysis of m RNA expression profiles was conducted to identify differentially expressed genes(DEGs),biological processes and pathways by the series test of cluster.Protein-protein interaction network was constructed and analysed to discover the key genes.A total of 6738 DEGs were identified and assigned to 20 model profiles.DEGs in profile 13 were one of the predominant expression profiles,which are involved in immune cell chemotaxis and proliferation.Signet analysis showed that Atp5 a1,Atp5 o,Cox4 i,Cdc42,Rac2 and Nhp2 were the key genes involved in oxidation-reduction,apoptosis,migration,M1-M2 differentiation,and proliferation of macrophages.RPS18 may be an appreciate reference gene as it was stable in macrophages.The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.Moreover,the vital gene Nhp2 may involve the polarization of macrophages,which may be a new target to affect the process of AKI.
基金Supported by Science and Technology Department of Henan Province Effect Mechanisms of Acupuncture to Promote the Repair of Injured Skeletal Muscle(No.212102310260)Study on the Relationship between Hspb7 Protein and JAK/STAT Pathway and Electroacupuncture Intervention in Muscle Injury based on mRNA-Seq Analysis(No.222102320072)Science and Technology Bureau o Kaifeng:the Effect of Platelet Plasma Injection on Patellar Tendon Fibrosis(No.2003006)。
文摘METHODS:In the present study,female SpragueDawley rats were randomly divided into four groups with 6 of each,including normal control group(NC),jumpinginduced muscle injury model group(JI),JI with electroacupuncture stimulation treatment group(EA),and JI with non-electroacupuncture stimulation group(NEA).Transmission electron microscopy,transcriptome sequencing and analysis,prediction of protein interaction networks,real-time polymerase chain reaction verification,and Western blotting were performed on the gastrocnemius muscle of ipsilateral lower limbs.RESULTS:The structural repair of injured gastrocnemius myofibers following jumping training in EA rats was better than that of NEA rats.A total of 136 genes were differentially expressed in EA rats relative to JI rats,with 55 genes upregulated and 81 genes downregulated.According to results of transcriptome analysis,and prediction of protein mutual interaction by the online STRING database,Heat shock protein beta-7(Hspb7)and myozenin2(Myoz2)genes were targeted.Expressions of Hspb7 and Myoz2 mRNAs were increased in EA rats relative to JI rats(P<0.05).The expression of Hspb7 protein was upregulated in EA rats relative to that in NC,JI,and NEA rats(P<0.01,<0.05,and<0.05,respectively).The expression of Myoz2 protein was upregulated in EA rats relative to that in NC and JI rats(both P<0.01,respectively).CONCLUSIONS:The present results suggest that electroacupuncture stimulation at Zusanli(ST36)could improve muscle healing following jumping-induced muscle injury,owing to the upregulation of Hspb7 and Myoz2 proteins.
基金Chinese Academy of Medical Sciences Initiative for Innovative MedicineGrant/Award Number:2021-I2M-1-035+3 种基金Beijing Municipal Natural Science FoundationGrant/Award Number:M21027National Key Research and Development Program of ChinaGrant/Award Number:2021YFF0702800。
文摘Background:The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus infections in human and animal models.Methods:We collected a large amount of transcriptome research data related to influenza virus-i nfected human and animal models in public databases(GEO and ArrayExpress),and extracted and integrated array and metadata.The gene expression matrix was generated through strictly quality control,balance,standardization,batch correction,and gene annotation.We then analyzed gene expression in different species,virus,cells/tissues or after antibody/vaccine treatment and imported sample metadata and gene expression datasets into the database.Results:Overall,maintaining careful processing and quality control,we collected 8064 samples from 103 independent datasets,and constructed a comparative transcriptomics database of influenza virus named the Flu-CED database(Influenza comparative expression database,https://flu.com-med.org.cn/).Using integrated and processed transcriptomic data,we established a user-friendly website for realizing the integration,online retrieval,visualization,and exploration of gene expression of influenza virus infection in different species and the biological functions involved in differential genes.Flu-CED can quickly query single and multi-gene expression profiles,combining different experimental conditions for comparative transcriptome analysis,identifying differentially expressed genes(DEGs)between comparison groups,and conveniently finding DEGs.Conclusion:Flu-CED provides data resources and tools for analyzing gene expression in human and animal models infected with influenza virus that can deepen our understanding of the mechanisms underlying disease occurrence and development,and enable prediction of key genes or therapeutic targets that can be used for medical research.
文摘BACKGROUND Gastric cancer(GC)is one of the most common cancers and has a poor prognosis.Treatment of GC has remained unchanged over the past few years.AIM To investigate the potential therapeutic targets and related regulatory biomarkers of GC.METHODS We obtained the public GC transcriptome sequencing dataset from the Gene Expression Omnibus database.The datasets contained 348 GC tissues and 141 healthy tissues.In total,251 differentially expressed genes(DEGs)were identified,including 187 down-regulated genes and 64 up-regulated genes.The DEGs’enriched functions and pathways include Progesterone-mediated oocyte maturation,cell cycle,and oocyte meiosis,Hepatitis B,and the Hippo signaling pathway.Survival analysis showed that BUB1,MAD2L1,CCNA2,CCNB1,and BIRC5 may be associated with regulation of the cell cycle phase mitotic spindle checkpoint pathway.We selected 26 regulated genes with the aid of the protein-protein interaction network analyzed by Molecular Complex Detection.RESULTS We focused on three critical genes,which were highly expressed in GC,but negatively related to patient survival.Furthermore,we found that knockdown of Yu K et al.Biochemical analysis in GC WJCC https://www.wjgnet.com 5024 July 26,2023 Volume 11 Issue 21 BIRC5,TRIP13 or UBE2C significantly inhibited cell proliferation and induced cell apoptosis.In addition,knockdown of BIRC5,TRIP13 or UBE2C increased cellular sensitivity to cisplatin.CONCLUSION Our study identified significantly upregulated genes in GC with a poor prognosis using integrated bioinformatics methods.
基金National Key Research and Development Program of China,No.2021YFC2701704the National Clinical Medical Research Center for Geriatric Diseases,"Multicenter RCT"Research Project,No.NCRCG-PLAGH-20230010the Military Logistics Independent Research Project,No.2022HQZZ06.
文摘BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.
文摘[目的]Heavy metal ATPase(HMA)蛋白参与了植物对多种金属离子的吸收和转运。本研究通过对谷子HMA进行全基因组表征、表达及同源分析以解析其功能。[方法]通过蛋白同源比对和保守结构域筛选谷子HMA基因家族成员;采用生物信息学手段系统分析了谷子HMA的理化性质、家族扩张、保守基序、系统发育关系及蛋白质分子对接;基于不同浓度Cd、Fe胁迫下的转录组和荧光定量PCR分析了其对不同金属离子的响应;基于模式物种水稻的同源比对预测了部分SiHMA的功能。[结果]在谷子基因组中共鉴定到12个HMA基因,并将其分为2个亚组,有6个HMA基因参与到2次串联重复(4个基因,占比33.3%)和1次片段复制事件(2个基因,占比16.7%)中。SiHMA基因在不同组织中对Cd、Fe胁迫表现出不同的响应模式。预测了SiHMA可能的功能,SiHMA5参与细胞中Zn、Cu、Pb和Cd等金属离子的外排过程,SiHMA10可能参与植物体内Cu的装载和运输。[结论]重复事件和片段复制在谷子HMA基因家族扩张和SiHMA功能进化中发挥作用。植物激素、应激胁迫等多种顺式作用元件参与到SiHMA响应非生物胁迫途径中,我们根据同源比较、组织表达特征和前人研究,预测了SiHMA1、SiHMA5、SiHMA6和SiHMA10等基因可能的功能,以上结果可为进一步研究HMA基因家族及其在谷子中的生物学功能提供理论基础。
