scholarly journals Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shan-Shan Huang ◽  
Dong-Yang Guo ◽  
Bing-Bing Jia ◽  
Guo-Long Cai ◽  
Jing Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quantitative Polymerase Chain Reaction ◽  
Enrichment Analysis ◽  
Go Enrichment ◽  
Polymerase Chain ◽  
Stress Related Genes ◽  
Go Enrichment Analysis ◽  
Necrosis Factor ◽  
Differential Genes ◽  
Dimethyl Itaconate

AbstractMacrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS + Adenosine Triphosphate, ATP). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1β expression. Then, real-time quantitative polymerase chain reaction (RT-qPCR) was used to confirm the result of RNA-sequencing of the upregulated oxidative stress-related genes (Gclc and Gss) and downregulated inflammation-related genes (IL-12β and IL-1β). In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that signaling pathways, such as tumor necrosis factor (TNF), Jak, Toll-like receptor and IL-17, were altered after DI treatment. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS + ATP-induced macrophage pyroptosis and upregulated the IL-1β expression. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress.

scholarly journals Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 530 ◽  
Author(s):  
Eugenie Mussard ◽  
Sundy Jousselin ◽  
Annabelle Cesaro ◽  
Brigitte Legrain ◽  
Eric Lespessailles ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quantitative Polymerase Chain Reaction ◽  
Andrographis Paniculata ◽  
Ros Production ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Dichlorofluorescein Diacetate ◽  
Polymerase Chain ◽  
Factor Α ◽  
Necrosis Factor

Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.

scholarly journals Exploring the Oxidative Stress Mechanism of Buyang Huanwu Decoction in Intervention of Vascular Dementia Based on Systems Biology Strategy

2021 ◽  
Vol 2021 ◽  
pp. 1-29
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yaqiao Yi ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Systems Biology ◽  
Vascular Dementia ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Buyang Huanwu Decoction ◽  
Pathway Enrichment ◽  
Go Enrichment ◽  
Go Enrichment Analysis

Objective. To explore the oxidative stress mechanism of modified Buyang Huanwu decoction (MBHD) in intervention of vascular dementia (VD) based on systems biology strategy. Methods. In this study, through the reverse virtual target prediction technology and transcriptomics integration strategy, the active ingredients and potential targets of MBHD treatment of VD were analyzed, and the drug-disease protein-protein interaction (PPI) network was constructed. Then, bioinformatics analysis methods are used for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis, and finally find the core biological process. After that, in animal models, low-throughput technology is used to detect gene expression and protein expression of key molecular targets in oxidative stress-mediated inflammation and apoptosis signaling pathways to verify the mechanism of MBHD treatment of VD rats. Finally, the potential interaction relationship between MBHD and VD-related molecules is further explored through molecular docking technology. Results. There are a total of 54 MBHD components, 252 potential targets, and 360 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate neuronal apoptosis, nitric oxide synthesis and metabolism, platelet activation, NF-κB signaling pathway-mediated inflammation, oxidative stress, angiogenesis, etc. Among them, SIRT1, NF-κB, BAX, BCL-2, CASP3, and APP may be important targets for MBHD to treat VD. Low-throughput technology (qRT-PCR/WB/immunohistochemical technology) detects oxidative stress-mediated inflammation and apoptosis-related signaling pathway molecules. The molecular docking results showed that 64474-51-7, cycloartenol, ferulic acid, formononetin, kaempferol, liquiritigenin, senkyunone, wallichilide, xanthinin, and other molecules can directly interact with NF-κB p65, BAX, BCL-2, and CASP3. Conclusion. The active compounds of MBHD interact with multiple targets and multiple pathways in a synergistic manner, and have important therapeutic effects on VD mainly by balancing oxidative stress/anti-inflammatory and antiapoptotic, enhancing metabolism, and enhancing the immune system.

scholarly journals The Arabidopsis HY2 Gene Acts as a Positive Regulator of NaCl Signaling during Seed Germination

2021 ◽  
Vol 22 (16) ◽  
pp. 9009
Author(s):  
Mingxin Piao ◽  
Jinpeng Zou ◽  
Zhifang Li ◽  
Junchuan Zhang ◽  
Liang Yang ◽  
...  
Keyword(s):  
Salt Stress ◽  
Stress Response ◽  
Seed Germination ◽  
Plant Stress ◽  
Ion Homeostasis ◽  
Enrichment Analysis ◽  
Salt Stress Response ◽  
Go Enrichment ◽  
Stress Related Genes ◽  
Go Enrichment Analysis

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). In addition, Arabidopsis long hypocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in the plant stress response signal network remains unknown. Here, we described the function of HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2, which positively mediated the expression of downstream stress-related genes of RD29A, RD29B, and DREB2A. Further quantitative proteomics showed the patterns of 7391 proteins under salt stress. HY2 was then found to specifically mediate 215 differentially regulated proteins (DRPs), which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic and metabolic pathways, hormone response (SA, JA, ABA, ethylene), the reactive oxygen species (ROS) metabolic pathway, photosynthesis, and detoxification pathways to respond to salt stress. More importantly, ANNAT1–ANNAT2–ANNAT3–ANNAT4 and GSTU19–GSTF10–RPL5A–RPL5B–AT2G32060, two protein interaction networks specifically regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to resist salt stress.

scholarly journals Network Pharmacology Reveals the Multiple Mechanisms of Xiaochaihu Decoction in the Treatment of Non-alcoholic Fatty Liver Disease

2020 ◽  
Author(s):  
Qichao Hu ◽  
Shizhang Wei ◽  
Jianxia Wen ◽  
Wenwen Zhang ◽  
Yinxiao Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Enrichment Analysis ◽  
Active Ingredients ◽  
Alcoholic Fatty Liver ◽  
Stress Regulation ◽  
Metabolism Regulation ◽  
Go Enrichment ◽  
Go Enrichment Analysis ◽  
And Oxidative Stress

Abstract Background Non-alcoholic fatty liver (NAFLD) is a chronic disease worldwide, which poses a huge threat to human health. Xiaochaihu decoction is a well-known traditional Chinese medicine prescription. It has been proven effective in treating NAFLD but its mechanism is still unclear.Objective Multiple mechanisms of Xiaochaihu decoction are explored by identifying and connecting potential targets and active ingredients in the treatment of NAFLD.Methods Active ingredients and related targets of seven herbs were collected from TCMSP database. The related targets of NAFLD were obtained from Genes cards database, TDD and OMIM database. The intersected targets of disease targets and drug targets were input into STRING database to construct protein-protein interaction network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis.Results After screening and removal of duplicates, a total of 145 active ingredients and 105 potential targets were obtained. PPI network manifested that AKT1, IL6 and JUNwere the key target proteins. The results of GO enrichment analysis mainly involved cytokine receptor binding, cytokine activity, and heme binding. The results of KEGG analysis suggested that the mechanism mainly involved in AGE-RAGE signaling pathway in diabetic complications, Hepatitis C, fluid shear stress and atherosclerosis. The signaling pathways were further integrated as network manner. The network contained immunity regulation, metabolism regulation and oxidative stress regulation.Conclusion Xiaochaihu decoction plays a key role in the treatment of NAFLD with multiple targets and pathways. Immunity regulation, metabolism regulation and oxidative stress regulation consist of the crucial regulation cores in mechanism.

scholarly journals Selection of Cashmere Fineness Functional Genes by Translatomics

2022 ◽  
Vol 12 ◽  
Author(s):  
Yu Zhang ◽  
Dongyun Zhang ◽  
Yanan Xu ◽  
Yuting Qin ◽  
Ming Gu ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Enrichment Analysis ◽  
Phenotypic Traits ◽  
Functional Region ◽  
Papillomavirus Infection ◽  
Extracellular Region ◽  
Genome Wide ◽  
Go Enrichment ◽  
Go Enrichment Analysis ◽  
Differential Genes

Cashmere fineness is an important index to evaluate cashmere quality. Liaoning Cashmere Goat (LCG) has a large cashmere production and long cashmere fiber, but its fineness is not ideal. Therefore, it is important to find genes involved in cashmere fineness that can be used in future endeavors aiming to improve this phenotype. With the continuous advancement of research, the regulation of cashmere fineness has made new developments through high-throughput sequencing and genome-wide association analysis. It has been found that translatomics can identify genes associated with phenotypic traits. Through translatomic analysis, the skin tissue of LCG sample groups differing in cashmere fineness was sequenced by Ribo-seq. With these data, we identified 529 differentially expressed genes between the sample groups among the 27197 expressed genes. From these, 343 genes were upregulated in the fine LCG group in relation to the coarse LCG group, and 186 were downregulated in the same relationship. Through GO enrichment analysis and KEGG enrichment analysis of differential genes, the biological functions and pathways of differential genes can be found. In the GO enrichment analysis, 491 genes were significantly enriched, and the functional region was mainly in the extracellular region. In the KEGG enrichment analysis, the enrichment of the human papillomavirus infection pathway was seen the most. We found that the COL6A5 gene may affect cashmere fineness.

scholarly journals Comprehensive biological information analysis of PTEN gene in pan-cancer

2021 ◽  
Author(s):  
Hang Zhang ◽  
Wenhan Zhou ◽  
Xiaoyi Yang ◽  
Shuzhan Wen ◽  
Baicheng Zhao ◽  
...  
Keyword(s):  
3D Structure ◽  
Enrichment Analysis ◽  
Biological Information ◽  
Pten Gene ◽  
Clinical Prognosis ◽  
Regulatory Pathways ◽  
Go Enrichment ◽  
Go Enrichment Analysis ◽  
Pan Cancer ◽  
Low Expression

Abstract Background PTEN is a multifunctional tumor suppressor gene mutating at high frequency in a variety of cancers. However, its expression in pan-cancer, correlated genes, survival prognosis, and regulatory pathways are not completely described. Here, we aimed to conduct a comprehensive analysis from the above perspectives in order to provide reference for clinical application. Methods we studied the expression levels in cancers by using data from TCGA and GTEx database. Obtain expression box plot from UALCAN database. Perform mutation analysis on the cBioportal website. Obtain correlation genes on the GEPIA website. Construct protein network and perform KEGG and GO enrichment analysis on the STRING database. Perform prognostic analysis on the Kaplan-Meier Plotter website. We also performed transcription factor prediction on the PROMO database and performed RNA-RNA association and RNA-protein interaction on the RNAup Web server and RPISEq. The gene 3D structure, protein sequence and conserved domain were obtained in NCBI respectively. Results PTEN was underexpressed in all cancers we studied. It was closely related to the clinical stage of tumors, suggesting PTEN may involved in cancer development and progression. The mutations of PTEN were present in a variety of cancers, most of which were truncation mutations and missense mutations. Among cancers (KIRC, LUAD, THYM, UCEC, Gastric Cancer, Liver Cancer, Lung Cancer, Breast Cancer), patients with low expression of PTEN had a shorter OS time and poorer OS prognosis. The low expression of PTEN can cause the deterioration of RFS in certain cancers (TGCT, UCEC, LIHC, LUAD, THCA), suggesting that the expression of PTEN was related to the clinical prognosis. Our study identified genes correlated with PTEN and performed GO enrichment analysis on 100 PTEN-related genes obtained from the GEPIA website. Conclusions The understanding of PTEN gene and the in-depth exploration of its related regulatory pathways may provide insight for the discovery of tumor-specific biomarkers and clinical potential therapeutic targets.

Transcriptome Signatures Reveal Candidate Key Genes in the Peripheral Blood Mononuclear Cells of Patients With Coronary Artery Disease

2020 ◽  
Author(s):  
Vijayakrishna Kolur ◽  
Basavaraj Vastrad ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti ◽  
Anandkumar Tengli
Keyword(s):  
Coronary Artery Disease ◽  
Gene Ontology ◽  
Coronary Artery ◽  
Regulatory Network ◽  
Target Gene ◽  
Enrichment Analysis ◽  
Hub Genes ◽  
Go Enrichment ◽  
Artery Disease ◽  
Go Enrichment Analysis

Abstract BackgroundCoronary artery disease (CAD) is one of the most common disorders in the cardiovascular system. This study aims to explore potential signaling pathways and important biomarkers that drive CAD development. MethodsThe CAD GEO Dataset GSE113079 was featured to screen differentially expressed genes (DEGs). The pathway and Gene Ontology (GO) enrichment analysis of DEGs were analyzed using the ToppGene. We screened hub and target genes from protein-protein interaction (PPI) networks, target gene - miRNA regulatory network and target gene - TF regulatory network, and Cytoscape software. Validations of hub genes were performed to evaluate their potential prognostic and diagnostic value for CAD. Results1,036 DEGs were captured according to screening criteria (525upregulated genes and 511downregulated genes). Pathway and Gene Ontology (GO) enrichment analysis of DEGs revealed that these up and down regulated genes are mainly enriched in thyronamine and iodothyronamine metabolism, cytokine-cytokine receptor interaction, nervous system process, cell cycle and nuclear membrane. Hub genes were validated to find out potential prognostic biomarkers, diagnostic biomarkers and novel therapeutic target for CAD. ConclusionsIn summary, our findings discovered pivotal gene expression signatures and signaling pathways in the progression of CAD. CAPN13, ACTBL2, ERBB3, GATA4, GNB4, NOTCH2, EXOSC10, RNF2, PSMA1 and PRKAA1 might contribute to the progression of CAD, which could have potential as biomarkers or therapeutic targets for CAD.

scholarly journals Mining Featured Biomarkers Linked with Epithelial Ovarian Cancer Based on Bioinformatics

Diagnostics ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 39
Author(s):  
◽  
Chanabasayya Vastrad ◽  
◽  
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Target Gene ◽  
Enrichment Analysis ◽  
Microrna Target ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Go Enrichment ◽  
Gene Regulatory ◽  
Go Enrichment Analysis

: Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information for further research. The gene expression profiles of E-MTAB-3706 which contained four high-grade ovarian epithelial cancer samples, four normal fallopian tube samples and four normal ovarian epithelium samples were downloaded from the ArrayExpress database. Pathway enrichment and Gene Ontology (GO) enrichment analysis of differentially expressed genes (DEGs) were performed, and protein-protein interaction (PPI) network, microRNA-target gene regulatory network and TFs (transcription factors ) -target gene regulatory network for up- and down-regulated were analyzed using Cytoscape. In total, 552 DEGs were found, including 276 up-regulated and 276 down-regulated DEGs. Pathway enrichment analysis demonstrated that most DEGs were significantly enriched in chemical carcinogenesis, urea cycle, cell adhesion molecules and creatine biosynthesis. GO enrichment analysis showed that most DEGs were significantly enriched in translation, nucleosome, extracellular matrix organization and extracellular matrix. From protein-protein interaction network (PPI) analysis, modules, microRNA-target gene regulatory network and TFs-target gene regulatory network for up- and down-regulated, and the top hub genes such as E2F4, SRPK2, A2M, CDH1, MAP1LC3A, UCHL1, HLA-C (major histocompatibility complex, class I, C) , VAT1, ECM1 and SNRPN (small nuclear ribonucleoprotein polypeptide N) were associated in pathogenesis of EOC. The high expression levels of the hub genes such as CEBPD (CCAAT enhancer binding protein delta) and MID2 in stages 3 and 4 were validated in the TCGA (The Cancer Genome Atlas) database. CEBPD andMID2 were associated with the worst overall survival rates in EOC. In conclusion, the current study diagnosed DEGs between normal and EOC samples, which could improve our understanding of the molecular mechanisms in the progression of EOC. These new key biomarkers might be used as therapeutic targets for EOC.

scholarly journals A Network Pharmacology Approach to Explore the Pharmacological Mechanism of Xiaoyao Powder on Anovulatory Infertility

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Huiping Liu ◽  
Liuting Zeng ◽  
Kailin Yang ◽  
Guomin Zhang
Keyword(s):  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Active Compounds ◽  
Pharmacological Mechanism ◽  
Go Enrichment ◽  
Human Proteins ◽  
Network Pictures ◽  
Go Enrichment Analysis ◽  
Anovulatory Infertility

Aim.To explore the pharmacological mechanism of Xiaoyao powder (XYP) on anovulatory infertility by a network pharmacology approach.Method.Collect XYP’s active compounds by traditional Chinese medicine (TCM) databases, and input them into PharmMapper to get their targets. Then note these targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and filter out targets that can be noted by human signal pathway. Get the information of modern pharmacology of active compounds and recipe’s traditional effects through databases. Acquire infertility targets by Therapeutic Target Database (TTD). Collect the interactions of all the targets and other human proteins via String and INACT. Put all the targets into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to do GO enrichment analysis. Finally, draw the network by Cytoscape by the information above.Result.Six network pictures and two GO enrichment analysis pictures are visualized.Conclusion.According to this network pharmacology approach some signal pathways of XYP acting on infertility are found for the first time. Some biological processes can also be identified as XYP’s effects on anovulatory infertility. We believe that evaluating the efficacy of TCM recipes and uncovering the pharmacological mechanism on a systematic level will be a significant method for future studies.

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