scholarly journals Identifying hub genes and immune infiltration of osteoarthritis using comprehensive bioinformatics analysis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zheng-yuan Wu ◽  
Gang Du ◽  
Yi-cai Lin
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Cell Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Joint Space ◽  
Mast Cell Activation ◽  
Healthy Controls ◽  
Bioinformatics Analyses ◽  
Immune Infiltration

Abstract Background Osteoarthritis (OA) is the most common chronic degenerative joint disorder globally that is characterized by synovitis, cartilage degeneration, joint space stenosis, and sub-cartilage bone hyperplasia. However, the pathophysiologic mechanisms of OA have not been thoroughly investigated. Methods In this study, we conducted various bioinformatics analyses to identify hub biomarkers and immune infiltration in OA. The gene expression profiles of synovial tissues from 29 healthy controls and 36 OA samples were obtained from the gene expression omnibus database to identify differentially expressed genes (DEGs). The CIBERSORT algorithm was used to explore the association between immune infiltration and arthritis. Results Eighteen hub DEGs were identified as critical biomarkers for OA. Through gene ontology and pathway enrichment analyses, it was found that these DEGs were primarily involved in PI3K-Akt signaling pathway and Rap1 signaling pathway. Furthermore, immune infiltration analysis revealed differences in immune infiltration between patients with OA and healthy controls. The hub gene ZNF160 was closely related to immune cells, especially mast cell activation in OA. Conclusion Overall, this study presented a novel method to identify hub DEGs and their correlation with immune infiltration, which may provide novel insights into the diagnosis and treatment of patients with OA.

scholarly journals Exploring the Mechanism of Skeletal Muscle in a Tacrolimus-Induced Posttransplantation Diabetes Mellitus Model on Gene Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Chenlei Zheng ◽  
Cheng Wang ◽  
Tan Zhang ◽  
Ding Li ◽  
Xiao-feng Ni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Muscle Development ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Quadriceps Muscle ◽  
Control Group ◽  
Bioinformatics Analyses

Objective. Posttransplantation diabetes mellitus (PTDM) is a known complication of transplantation that affects the prognosis. Tacrolimus (Tac or FK506) is a widely used immunosuppressant that has been reported to be a risk factor for PTDM and to further induce complications in heart and skeletal muscles, but the mechanism is still largely unknown. In our preliminary experiments, we found that after Tac treatment, blood glucose increased, and the weight of skeletal muscle declined. Here, we hypothesize that tacrolimus can induce PTDM and influence the atrophy of skeletal muscle. Methods. We designed preliminary experiments to establish a tacrolimus-induced PTDM model. Gene expression profiles in quadriceps muscle from this rat model were characterized by oligonucleotide microarrays. Then, differences in gene expression profiles in muscle from PTDM rats that received tacrolimus and control subjects were analyzed by using GeneSpring GX 11.0 software (Agilent). Functional annotation and enrichment analysis of differentially expressed genes (DEGs) helped us identify clues for the side effects of tacrolimus. Results. Our experiments found that the quadriceps in tacrolimus-induced PTDM group were smaller than those in the control group. The study identified 275 DEGs that may be responsible for insulin resistance and the progression of PTDM, including 86 upregulated genes and 199 downregulated genes. GO and KEGG functional analysis of the DEGs showed a significant correlation between PTDM and muscle development. PPI network analysis screened eight hub genes and found that they were related to troponin and tropomyosin. Conclusions. This study explored the molecular mechanism of muscle atrophy in a tacrolimus-induced PTDM model by bioinformatics analyses. We identified 275 DEGs and identified significant biomarkers for predicting the development and progression of tacrolimus-induced PTDM.

Gene Expression Profiles During Hepatic Stellate Cell Activation in Culture and In Vivo

2007 ◽  
Vol 132 (5) ◽  
pp. 1937-1946 ◽  
Author(s):  
Samuele De Minicis ◽  
Ekihiro Seki ◽  
Hiroshi Uchinami ◽  
Johannes Kluwe ◽  
Yonghui Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Hepatic Stellate Cell Activation

scholarly journals Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 361
Author(s):  
Shuo-Yu Wang ◽  
Yin-Hwa Shih ◽  
Tzong-Ming Shieh ◽  
Yu-Hsin Tseng
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Proteasome Inhibitors ◽  
Gene Expression Profiles ◽  
Nuclear Factor Κb ◽  
High Dose ◽  
Hl60 Cells ◽  
Expression Arrays ◽  
Study Results

Over half of older patients with acute myeloid leukemia (AML) do not respond to cytotoxic chemotherapy, and most responders relapse because of drug resistance. Cytarabine is the main drug used for the treatment of AML. Intensive treatment with high-dose cytarabine can increase the overall survival rate and reduce the relapse rate, but it also increases the likelihood of drug-related side effects. To optimize cytarabine treatment, understanding the mechanism underlying cytarabine resistance in leukemia is necessary. In this study, the gene expression profiles of parental HL60 cells and cytarabine-resistant HL60 (R-HL60) cells were compared through gene expression arrays. Then, the differential gene expression between parental HL60 and R-HL60 cells was measured using KEGG software. The expression of numerous genes associated with the nuclear factor κB (NF-κB) signaling pathway changed during the development of cytarabine resistance. Proteasome inhibitors inhibited the activity of non-canonical NF-κB signaling pathway and induced the apoptosis of R-HL60 cells. The study results support the application and possible mechanism of proteasome inhibitors in patients with relapsed or refractory leukemia.

Microarray-Based Gene Expression Analysis Identifies Potential Diagnostic and Prognostic Biomarkers for Waldenström Macroglobulinemia

2018 ◽  
Vol 140 (2) ◽  
pp. 87-96
Author(s):  
Haitao Xu ◽  
Fusheng Yao
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mitogen Activated Protein Kinase ◽  
Ppi Network ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia

Waldenström macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is rare but a clinicopathologically distinct B-cell malignancy. This study assessed differentially expressed genes (DEGs) to identify potential WM biomarkers and uncover the underlying the molecular mechanisms of WM progression using gene expression profiles from the Gene Expression Omnibus database. DEGs were identified using the LIMMA package and their potential functions were then analyzed by using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and the protein-protein interaction (PPI) network analysis by using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Data showed that among 1,756 DEGs, 926 were upregulated and 830 were downregulated by comparing WM BM CD19+ with normal PB CD19+ B cell samples, whereas 241 DEGs (95 upregulated and 146 downregulated) were identified by comparing WM BM CD138+ with normal BM CD138+ plasma cell samples. The DEGs were enriched in different GO terms and pathways, including the apoptotic process, cell cycle arrest, immune response, cell adhesion, mitogen-activated protein kinase signaling pathway, toll-like receptor signaling pathway, and the gonadotropin-releasing hormone signaling pathway. Hub nodes in the PPI network included CDK1, JUN, CREBBP, EP300, CAD, CDK2, and MAPK14. Bioinformatics analysis of the GSE9656 dataset identified 7 hub genes that might play an important role in WM development and progression. Some of the candidate genes and pathways may serve as promising therapeutic targets for WM.

scholarly journals Immune Condition of Colorectal Cancer Patients Featured by Serum Chemokines and Gene Expressions of CD4+ Cells in Blood

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Takuya Komura ◽  
Masaaki Yano ◽  
Akimitsu Miyake ◽  
Hisashi Takabatake ◽  
Masaki Miyazawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Blood Parameters ◽  
Healthy Controls ◽  
Cd4 Cells ◽  
Gene Expressions ◽  
Expression Levels ◽  
Cd8 Cells

Background. Colorectal cancer (CRC), the most common malignancy worldwide, causes inflammation. We explored the inflammatory pathophysiology of CRC by assessing the peripheral blood parameters. Methods. The differences in gene expression profiles of whole blood cells and cell subpopulations between CRC patients and healthy controls were analyzed using DNA microarray. Serum cytokine/chemokine concentrations in CRC patients and healthy controls were measured via multiplex detection immunoassays. In addition, we explored correlations between the expression levels of certain genes of peripheral CD4+ cells and serum chemokine concentrations. Results. The gene expression profiles of peripheral CD4+ cells of CRC patients differed from those of healthy controls, but this was not true of CD8+ cells, CD14+ cells, CD15+ cells, or CD19+ cells. Serum IL-8 and eotaxin-1 levels were significantly elevated in CRC patients, and the levels substantially correlated with the expression levels of certain genes of CD4+ cells. Interestingly, the relationships between gene expression levels in peripheral CD4+ cells and serum IL-8 and eotaxin-1 levels resembled those of monocytes/macrophages, not T cells. Conclusions. Serum IL-8 and eotaxin-1 concentrations increased and were associated with changes in the gene expression of peripheral CD4+ cells in CRC patients.

Identification of DMSA-Coated Fe3O4 Nanoparticles Induced-Apoptosis Response Genes in Human Monocytes by cDNA Microarrays

2013 ◽  
Vol 749 ◽  
pp. 377-383 ◽  
Author(s):  
Ying Xun Liu ◽  
Jian Yuan Huang ◽  
Dong Liang Wang ◽  
Jin Ke Wang
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Dependent Manner ◽  
Receptor Signaling ◽  
Apoptosis Pathway ◽  
Receptor Signaling Pathway

This study investigated the cell apoptosis and gene expression profiles of human THP-1 monocytes in order to identify the molecular mechanism of cell apoptosis induced by meso-2,-3-dimercaptosuccinnic acid-coated Fe3O4magnetic nanoparticles. Cell apoptosis was visualized with flow cytometry after treated by 50 and 100 μg/ml Fe3O4nanoparticles, and the gene expression profiles were detected with Affymetrix Human Genome U133 Plus 2.0 GeneChips® microarrays. The transmission electron microscopy obserbation revealed that THP-1 cells were effectively labeled by the Fe3O4nanoparticles. The internalized Fe3O4nanoparticles increased cell apoptosis in a dose-dependent manner, but not decreased cell viability significantly. The cDNA microarray results showed that hundreds of genes were significantly regulated at the concentration of 50 and 100 μg/ml, and the level of these genes exhibited a dose response, includingCD14,CD86,CFLAR,IL-1,NFKBIA,NLRC4,NAIPandAIP3. The Fe3O4nanoparticles treatments resulted in significantly altered in Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and Cell apoptosis signaling pathway. Gene ontology analysis of these differentially expressed genes demonstrated that mainly up-regulated genes were related to cytokine production and cell apoptosis. These results showed that the Fe3O4nanoparticles induced THP-1 cells apoptosis and the level of lots of genes involved in extrinsic apoptosis pathway differentially expressed, which further revealed demonstrated the relation between Fe3O4MNPs treatment and cell apoptosis.

scholarly journals Genetic and pharmacological inactivation of adenosine A2A receptor reveals an Egr-2-mediated transcriptional regulatory network in the mouse striatum

2005 ◽  
Vol 23 (1) ◽  
pp. 89-102 ◽  
Author(s):  
Liqun Yu ◽  
Peter M. Haverty ◽  
Juliana Mariani ◽  
Yumei Wang ◽  
Hai-Ying Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Transcriptional Regulatory Network ◽  
Expression Profiles ◽  
Mrna Level ◽  
Gene Expression Profiles ◽  
Bioinformatics Analyses ◽  
Mouse Striatum ◽  
Transcriptional Regulatory

The adenosine A2A receptor (A2AR) is highly expressed in the striatum, where it modulates motor and emotional behaviors. We used both microarray and bioinformatics analyses to compare gene expression profiles by genetic and pharmacological inactivation of A2AR and inferred an A2AR-controlled transcription network in the mouse striatum. A comparison between vehicle (VEH)-treated A2AR knockout (KO) mice (A2AR KO-VEH) and wild-type (WT) mice (WT-VEH) revealed 36 upregulated genes that were partially mimicked by treatment with SCH-58261 (SCH; an A2AR antagonist) and 54 downregulated genes that were not mimicked by SCH treatment. We validated the A2AR as a specific drug target for SCH by comparing A2AR KO-SCH and A2AR KO-VEH groups. The unique downregulation effect of A2AR KO was confirmed by comparing A2AR KO-SCH with WT-SCH gene groups. The distinct striatal gene expression profiles induced by A2AR KO and SCH should provide clues to the molecular mechanisms underlying the different phenotypes observed after genetic and pharmacological inactivation of A2AR. Furthermore, bioinformatics analysis discovered that Egr-2 binding sites were statistically overrepresented in the proximal promoters of A2AR KO-affected genes relative to the unaffected genes. This finding was further substantiated by the demonstration that the Egr-2 mRNA level increased in the striatum of both A2AR KO and SCH-treated mice and that striatal Egr-2 binding activity in the promoters of two A2AR KO-affected genes was enhanced in A2AR KO mice as assayed by chromatin immunoprecipitation. Taken together, these results strongly support the existence of an Egr-2-directed transcriptional regulatory network controlled by striatal A2ARs.

scholarly journals Potential genes and pathways associated with heterotopic ossification derived from analyses of gene expression profiles

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhanyu Yang ◽  
Delong Liu ◽  
Rui Guan ◽  
Xin Li ◽  
Yiwei Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Heterotopic Ossification ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Heterotopic Bone ◽  
Hub Genes ◽  
Ppi Networks

Abstract Background Heterotopic ossification (HO) represents pathological lesions that refer to the development of heterotopic bone in extraskeletal tissues around joints. This study investigates the genetic characteristics of bone marrow mesenchymal stem cells (BMSCs) from HO tissues and explores the potential pathways involved in this ailment. Methods Gene expression profiles (GSE94683) were obtained from the Gene Expression Omnibus (GEO), including 9 normal specimens and 7 HO specimens, and differentially expressed genes (DEGs) were identified. Then, protein–protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for further analysis. Results In total, 275 DEGs were differentially expressed, of which 153 were upregulated and 122 were downregulated. In the biological process (BP) category, the majority of DEGs, including EFNB3, UNC5C, TMEFF2, PTH2, KIT, FGF13, and WISP3, were intensively enriched in aspects of cell signal transmission, including axon guidance, negative regulation of cell migration, peptidyl-tyrosine phosphorylation, and cell-cell signaling. Moreover, KEGG analysis indicated that the majority of DEGs, including EFNB3, UNC5C, FGF13, MAPK10, DDIT3, KIT, COL4A4, and DKK2, were primarily involved in the mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and Wnt signaling pathway. Ten hub genes were identified, including CX3CL1, CXCL1, ADAMTS3, ADAMTS16, ADAMTSL2, ADAMTSL3, ADAMTSL5, PENK, GPR18, and CALB2. Conclusions This study presented novel insight into the pathogenesis of HO. Ten hub genes and most of the DEGs intensively involved in enrichment analyses may be new candidate targets for the prevention and treatment of HO in the future.

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