scholarly journals Identification of the Resveratrol Potential Targets in the Treatment of Osteoarthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Meng Zhou ◽  
Dacheng Wang ◽  
Jing Tang
Keyword(s):  
Differentially Expressed Genes ◽  
Target Genes ◽  
The Elderly ◽  
Microarray Gene Expression Data ◽  
Differentially Expressed ◽  
Microarray Gene Expression ◽  
Natural Polyphenol ◽  
Important Health ◽  
Effective Drugs ◽  
Six Genes

Objectives. Osteoarthritis (OA) is a chronic joint degenerative disease and has become an important health problem for the elderly. However, there is still a lack of effective drugs for the treatment of OA. Our research combines bioinformatics and experimental strategies to determine the target of resveratrol for OA treatment. Methods. First, the differentially expressed genes (DEGs) of OA joint tissues were obtained from the related microarray gene expression data. Second, resveratrol, a natural polyphenol compound, was used to screen the drug treatment target genes. Third, the drug-disease network was established, and the resveratrol target genes for OA treatment were obtained and verified through experimental verification. Results. A total of 300 differentially expressed genes with 246 upregulated and 54 downregulated were found in OA joint tissues, and 310 resveratrol potential target genes were obtained. Finally, six genes, namely, CXCL1, HIF1A, IL-6, MMP3, NOX4, and PTGS2, were selected to validate the treatment effects of the resveratrol. The results showed that all six genes in human OA chondrocytes were significantly increased. In addition, in these chondrocytes, CXCL1, HIF1A, IL-6, MMP3, NOX4, and PTGS2 were reduced considerably, but HIF1A was significantly increased after resveratrol treatment. Conclusions. Our data indicates that CXCL1, HIF1A, IL-6, MMP3, NOX4, and PTGS2 are all targets of resveratrol therapy. Our findings may provide valuable information for the mechanism and therapeutic of OA.

scholarly journals Identification of the Resveratrol Potential Targets in the Treatment of Osteoarthritis

2021 ◽  
Author(s):  
Meng Zhou ◽  
Dacheng Wang ◽  
Jing Tang
Keyword(s):  
Differentially Expressed Genes ◽  
Target Genes ◽  
The Elderly ◽  
Microarray Gene Expression Data ◽  
Differentially Expressed ◽  
Microarray Gene Expression ◽  
Natural Polyphenol ◽  
Important Health ◽  
Effective Drugs ◽  
Six Genes

Abstract Objectives: Osteoarthritis (OA) is a chronic joint degenerative disease and has become an important health problem for the elderly. However, there is still a lack of effective drugs for the treatment of OA. Our research combines bioinformatics and experimental strategies to determine the target of resveratrol for OA treatment. Methods: First, the differentially expressed genes (DEGs) of OA joint tissues were obtained from the related microarray gene expression data. Second, resveratrol, a natural polyphenol compound, was used to screen the drug treatment target genes. Third, the drug-disease network was established, and the resveratrol target genes for OA treatment were obtained and verified through experimental verification. Results: A total of 300 differentially expressed genes with 246 up-regulated and 54 down-regulated were found in OA joint tissues, and 310 resveratrol potential target genes were obtained. Finally, six genes, including CXCL1, HIF1A, IL-6, MMP3, NOX4, and PTGS2, were selected to validate the treatment effects of the resveratrol. The results showed that all six genes in human OA chondrocytes were significantly increased. In addition, in these chondrocytes, CXCL1, HIF1A, IL-6, MMP3, NOX4, and PTGS2 were reduced considerably, but HIF1A was significantly increased after resveratrol treatment.Conclusions: Our data indicates that CXCL1, HIF1A, IL-6, MMP3, NOX4 and PTGS2 are all targets of resveratrol therapy. Our findings may provide valuable information for the mechanism and therapeutic of OA.

scholarly journals Identification of key immune regulatory genes in HIV–1 Progression

2020 ◽  
Author(s):  
Sk Md Mosaddek Hossain ◽  
Lutfunnesa Khatun ◽  
Sumanta Ray ◽  
Anirban Mukhopadhyay
Keyword(s):  
Differentially Expressed Genes ◽  
Permutation Test ◽  
Biological Significance ◽  
Microarray Gene Expression Data ◽  
Regulatory Genes ◽  
Differentially Expressed ◽  
Microarray Gene Expression ◽  
Module Preservation ◽  
The Difference ◽  
Hiv 1

AbstractIn the last few decades, application of DNA microarray technology has sprung up as a powerful technique for discovering stage specific changes in expression pattern of a disease progression. Human Immunodeficiency Virus (HIV) infection causes Acquired Immunodeficiency Syndrome (AIDS) which is one of the most devastating diseases affecting humankind. Here, we have proposed a framework to examine the difference among microarray gene expression data of uninfected and three different HIV–1 infection stages using module preservation statistics. Initially, we detected differentially expressed genes among all the stages and identified coexpression modules by using topological overlap as a dissimilarity measure. To examine relationship among co-expression modules, we have compiled a module eigenegene network for each sample category which models similarity among all coexpression modules. To further examine the network, we have found clusters in it which are termed as ‘meta-modules’. Different module preservation statistics with two composite statistics: “Zsummary” and “MedianRank” are utilized to examine changes in structure of coexpression modules. We have applied our proposed methodology to discover modular changes between uninfected and acute samples, acute and chronic samples, chronic and AIDS samples. We have found several interesting results on preservation characteristics of gene modules across different stages. Some genes are identified to be preserved in a pair of stages while alter their characteristics across other stages. We further validated the obtained results using permutation test and classification techniques. Biological significance of the obtained modules have been examined using gene ontology and pathway based analysis. Additionally, we have detected key immune regulatory hub genes in the associated protein-protein interaction networks (PPINs) of the differentially expressed genes (DEGs) using twelve topological and centrality analysis methods. Moreover, we have analyzed the key immune regulatory genes which interacts with HIV-1 proteins inside the preserved and perturbed meta-modules across different HIV-1 stages and thus likely to act as potential biomarkers in HIV–1 progression.

Potential genes and pathways along with immune cells infiltration in the progression of atherosclerosis identified via microarray gene expression dataset re-analysis

Vascular ◽  
2020 ◽  
Vol 28 (5) ◽  
pp. 643-654 ◽  
Author(s):  
Jing Xu ◽  
Yuejin Yang
Keyword(s):  
Differentially Expressed Genes ◽  
Immune Cells ◽  
Interaction Network ◽  
Wilcoxon Test ◽  
Differentially Expressed ◽  
P Value ◽  
The Novel ◽  
Microarray Gene Expression ◽  
Progression Of Atherosclerosis ◽  
Geo Database

Objective Atherosclerosis is a chronic inflammatory process characterized by the accumulation and formation of lipid-rich plaques within the layers of the arterial wall. Although numerous studies have reported the underlying pathogenesis, no data-based studies have been conducted to analyze the potential genes and immune cells infiltration in the different stages of atherosclerosis via bioinformatics analysis. Methods In this study, we downloaded GSE100927 and GSE28829 from NCBI-GEO database. Gene ontology and pathway enrichment were performed via the DAVID database. The protein interaction network was constructed via STRING. Enriched hub genes were analyzed by the Cytoscape software. The evaluation of the infiltrating immune cells in the dataset samples was performed by the CIBERSORT algorithm. Results We identified 114 common upregulated differentially expressed genes and 22 common downregulated differentially expressed genes. (adjust p value < 0.01 and log FC ≥ 1). A cluster of 10 genes including CYBA, SLC11A1, FCER1G, ITGAM, ITGB2, CD53, ITGAX, VAMP8, CLEC5A, and CD300A were found to be significant. Through the deconvolution algorithm CIBERSORT, we analyzed the significant alteration of immune cells infiltration in the progression of atherosclerosis with the threshold of the Wilcoxon test at p value <0.05. Conclusions These results may reveal the underlying correlations between genes and immune cells in atherosclerosis, which enable us to investigate the novel insights for the development of treatments and drugs.

scholarly journals Bayesian Mixture Model Analysis for Detecting Differentially Expressed Genes

2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Zhenyu Jia ◽  
Shizhong Xu
Keyword(s):  
Mixture Model ◽  
Differentially Expressed Genes ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Control Treatment ◽  
Microarray Gene Expression ◽  
Bayesian Mixture Model ◽  
Bayesian Mixture ◽  
Truncated Normal ◽  
Upregulated Genes

Control-treatment design is widely used in microarray gene expression experiments. The purpose of such a design is to detect genes that express differentially between the control and the treatment. Many statistical procedures have been developed to detect differentially expressed genes, but all have pros and cons and room is still open for improvement. In this study, we propose a Bayesian mixture model approach to classifying genes into one of three clusters, corresponding to clusters of downregulated, neutral, and upregulated genes, respectively. The Bayesian method is implemented via the Markov chain Monte Carlo (MCMC) algorithm. The cluster means of down- and upregulated genes are sampled from truncated normal distributions whereas the cluster mean of the neutral genes is set to zero. Using simulated data as well as data from a real microarray experiment, we demonstrate that the new method outperforms all methods commonly used in differential expression analysis.

scholarly journals Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells

2015 ◽  
Vol 112 (25) ◽  
pp. 7743-7748 ◽  
Author(s):  
Muhammad Akhtar Ali ◽  
Shady Younis ◽  
Ola Wallerman ◽  
Rajesh Gupta ◽  
Leif Andersson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Target Genes ◽  
Egf Receptor ◽  
Differentially Expressed ◽  
Striking Difference ◽  
Human Colorectal Cancer ◽  
Chip Sequencing

The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle–related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.

scholarly journals Inferring the genetic responses to acute drought stress across an ecological gradient

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Jessica K. Devitt ◽  
Albert Chung ◽  
John J. Schenk
Keyword(s):  
Drought Stress ◽  
Differentially Expressed Genes ◽  
Target Genes ◽  
De Novo ◽  
Water Movement ◽  
Model Systems ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Ecological Gradient ◽  
Genetic Responses

Abstract Background How do xerophytic species thrive in environments that experience extreme annual drought? Although critical to the survival of many species, the genetic responses to drought stress in many non-model organisms has yet to be explored. We investigated this question in Mentzelia section Bartonia (Loasaceae), which occurs throughout western North America, including arid lands. To better understand the genetic responses to drought stress among species that occur in different habitats, the gene expression levels of three species from Mentzelia were compared across a precipitation gradient. Two de novo reference transcriptomes were generated and annotated. Leaf and root tissues were collected from control and drought shocked plants and compared to one another for differential expression. A target-gene approach was also implemented to better understand how drought-related genes from model and crop species function in non-model systems. Results When comparing the drought-shock treatment plants to their respective control plants, we identified 165 differentially expressed clusters across all three species. Differentially expressed genes including those associated with water movement, photosynthesis, and delayed senescence. The transcriptome profiling approach was coupled with a target genes approach that measured expression of 90 genes associated with drought tolerance in model organisms. Comparing differentially expressed genes with a ≥ 2 log-fold value between species and tissue types showed significant differences in drought response. In pairwise comparisons, species that occurred in drier environments differentially expressed greater genes in leaves when drought shocked than those from wetter environments, but expression in the roots mostly produced opposite results. Conclusions Arid-adapted species mount greater genetic responses compared to the mesophytic species, which has likely evolved in response to consistent annual drought exposure across generations. Drought responses also depended on organ type. Xerophytes, for example, mounted a larger response in leaves to downregulate photosynthesis and senescence, while mobilizing carbon and regulating water in the roots. The complexity of drought responses in Mentzelia suggest that whole organism responses need to be considered when studying drought and, in particular, the physiological mechanisms in which plants regulate water, carbon, cell death, metabolism, and secondary metabolites.

scholarly journals Comparing Genomic Profiles of Women With and Without Fibromyalgia

2015 ◽  
Vol 17 (4) ◽  
pp. 373-383 ◽  
Author(s):  
Nada Lukkahatai ◽  
Brian Walitt ◽  
Alexandra Espina ◽  
Dan Wang ◽  
Leorey N. Saligan
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Functional Disability ◽  
Differentially Expressed ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microarray Gene Expression ◽  
Expression Arrays ◽  
Rate Analysis ◽  
American College Of Rheumatology ◽  
Gene And Protein Expression

Background: Fibromyalgia syndrome (FMS), a chronic musculoskeletal condition characterized by diffuse pain, fatigue, sleep impairment, and cognitive dysfunction, is associated with significant functional disability. Its underlying biological mechanisms are unknown. This study investigated differentially expressed genes between women with FMS and healthy volunteers. Methods: Women who met the 1990 or 2010 American College of Rheumatology fibromyalgia criteria were compared to age- and race-matched pain-free healthy women. Peripheral blood samples were collected, and a full genome microarray gene expression analysis was performed. One-way analysis of variance was used to identify differentially expressed genes using the filtering criterion of 1% false discovery rate. Analysis of canonical pathways associated with these genes was performed. Confirmatory quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay verified microarray results. Independent t-tests compared gene and protein expression between groups. Result: Participants were 54 women with FMS and 25 controls. Expression arrays from a subset of women with FMS ( n = 29) and controls ( n = 20) showed upregulation of 12 genes (>1.8-fold change, p < .05) in the FMS sample. Differentially expressed genes were related to B-cell development, primary immunodeficiency signaling, and mitotic roles of polo-like kinase. CENPK and HSP90AA1 were the most differentially expressed genes ( p < .01). Conclusion: Activity of interrelated pathways related to immune response, and homeostasis appears to be relevant to the experience of FMS. Replication and exploration of the relationship between gene expression and symptom severity will help determine clinical relevance of these findings.

scholarly journals Analysis of Soybean Somatic Embryogenesis Using Chromosome Segment Substitution Lines and Transcriptome Sequencing

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 943
Author(s):  
Li ◽  
Cheng ◽  
Bai ◽  
Shi ◽  
Yu ◽  
...  
Keyword(s):  
Somatic Embryogenesis ◽  
Differentially Expressed Genes ◽  
Transcriptome Sequencing ◽  
Target Genes ◽  
Differentially Expressed ◽  
Chromosome Segment ◽  
Substitution Lines ◽  
Chromosome Segment Substitution Lines ◽  
Segment Substitution ◽  
Extreme Materials

Soybean is an important cash crop that is widely used as a source of vegetable protein and edible oil. The regeneration ability of soybean directly affects the application of biotechnology. In this study, we used the exogenous hormone 2,4-D to treat immature embryos. Different levels of somatic incidence were selected from the chromosome segment substitution lines (CSSLs) constructed by SN14 and ZYD00006. Transcriptome sequencing of extreme materials was performed, and 2666 differentially expressed genes were obtained. At the same time, a difference table was generated by combining the data on CSSL rearrangement. In the extreme materials, a total of 93 differentially expressed genes were predicted and were then analyzed by cluster analysis and Gene Ontology (GO) annotation. After screening and annotating the target genes, three differentially expressed genes with hormone pathways were identified. The expression patterns of the target genes were verified by real-time quantitative PCR (qRT-PCR). Haplotype polymorphism detection and linkage disequilibrium analysis were performed on the candidate gene Glyma.09g248200. This study provided more information on the regulation network of soybean somatic embryogenesis and regeneration processes, and further identified important genes in the soybean regeneration process and provided a theoretical basis for accelerating the application of biotechnology to soybean for improving its breeding efficiency.

scholarly journals Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Eduardo Pérez-Palma ◽  
Víctor Andrade ◽  
Mario O. Caracci ◽  
Bernabé I. Bustos ◽  
Camilo Villaman ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Hippocampal Neurons ◽  
Target Genes ◽  
Primary Cultures ◽  
Stem Cell Differentiation ◽  
Differentially Expressed ◽  
Molecular Networks ◽  
Biological Processes ◽  
Neuronal Structure ◽  
Transcriptional Changes

Wnt/β-catenin signaling modulates brain development and function and its deregulation underlies pathological changes occurring in neurodegenerative and neurodevelopmental disorders. Since one of the main effects of Wnt/β-catenin signaling is the modulation of target genes, in the present work we examined global transcriptional changes induced by short-term Wnt3a treatment (4 h) in primary cultures of rat hippocampal neurons. RNAseq experiments allowed the identification of 170 differentially expressed genes, including known Wnt/β-catenin target genes such as Notum, Axin2, and Lef1, as well as novel potential candidates Fam84a, Stk32a, and Itga9. Main biological processes enriched with differentially expressed genes included neural precursor (GO:0061364,p-adjusted = 2.5 × 10−7), forebrain development (GO:0030900,p-adjusted = 7.3 × 10−7), and stem cell differentiation (GO:0048863p-adjusted = 7.3 × 10−7). Likewise, following activation of the signaling cascade, the expression of a significant number of genes with transcription factor activity (GO:0043565,p-adjusted = 4.1 × 10−6) was induced. We also studied molecular networks enriched upon Wnt3a activation and detected three highly significant expression modules involved in glycerolipid metabolic process (GO:0046486,p-adjusted = 4.5 × 10−19), learning or memory (GO:0007611,p-adjusted = 4.0 × 10−5), and neurotransmitter secretion (GO:0007269,p-adjusted = 5.3 × 10−12). Our results indicate that Wnt/β-catenin mediated transcription controls multiple biological processes related to neuronal structure and activity that are affected in synaptic dysfunction disorders.

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