scholarly journals Exploration of the Role of Serine Proteinase Inhibitor A3 in Alcohol Dependence Using Gene Expression Omnibus Database

2022 ◽  
Vol 12 ◽  
Author(s):  
Bo Zhang ◽  
Gang Wang ◽  
Cheng Bing Huang ◽  
Jian Nan Zhu ◽  
Yong Xue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Dependence ◽  
Proteinase Inhibitor ◽  
Serine Proteinase ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Healthy Controls ◽  
Serine Proteinase Inhibitor ◽  
Ppi Networks

Background: Alcohol dependence is an overall health-related challenge; however, the specific mechanisms underlying alcohol dependence remain unclear. Serine proteinase inhibitor A3 (SERPINA3) plays crucial roles in multiple human diseases; however, its role in alcohol dependence clinical practice has not been confirmed.Methods: We screened Gene Expression Omnibus (GEO) expression profiles, and identified differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were generated using STRING and Cytoscape, and the key clustering module was identified using the MCODE plugin. SERPINA3-based target microRNA prediction was performed using online databases. Functional enrichment analysis was performed. Fifty-eight patients with alcohol dependence and 20 healthy controls were recruited. Clinical variables were collected and follow-up was conducted for 8 months for relapse.Results:SERPINA3 was identified as a DEG. ELANE and miR-137 were identified after PPI analysis. The enriched functions and pathways included acute inflammatory response, response to stress, immune response, and terpenoid backbone biosynthesis. SERPINA3 concentrations were significantly elevated in the alcohol dependence group than in healthy controls (P < 0.001). According to the median value of SERPINA3 expression level in alcohol dependence group, patients were divided into high SERPINA3 (≥2677.33 pg/ml, n = 29) and low SERPINA3 groups (<2677.33 pg/ml, n = 29). Binary logistic analysis indicated that IL-6 was statistically significant (P = 0.015) Kaplan-Meier survival analysis did not indicate any difference in event-free survival between patients with low and high SERPINA3 levels (P = 0.489) after 8 months of follow-up. Receiver characteristic curve analysis revealed that SERPINA3 had an area under the curve of 0.921 (P < 0.0001), with a sensitivity and specificity of 93.1 and 80.0%, respectively. Cox regression analysis revealed that aspartate transaminase level was a negative predictor of relapse (β = 0.003; hazard ratio = 1.003; P = 0.03).Conclusions:SERPINA3 level was remarkably elevated in patients with alcohol dependence than healthy controls, indicating that SERPINA3 is correlated with alcohol dependence. However, SERPINA3 may not be a potential predictive marker of relapse with patients in alcohol dependence.

scholarly journals 975. Why Sex Make a Difference in HIV Clinical Course? Bioinformatics Analysis of Differential Expressed Gene in Females and Males with HIV Disease

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S516-S517
Author(s):  
Kulachanya Suwanwongse ◽  
Nehad Shabarek
Keyword(s):  
Gene Expression ◽  
Bioinformatics Analysis ◽  
Underlying Mechanism ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Gender Inequalities ◽  
Hiv Disease ◽  
Go Analysis ◽  
Hiv Progression ◽  
Pathway Analyses

Abstract Background Human immunodeficiency virus (HIV) disease progression are different among genders, in which women usually progress to acquired immunodeficiency syndrome (AIDS) faster than men. The mechanisms resulting in the gender biases of HIV progression are unclear. We conducted a bioinformatics analysis of differentially expressed genes (DEGs) in women and men with HIV disease to understand the sex-based differences in HIV pathogenesis. Methods We obtained microarray data from the Gene Expression Omnibus (GEO) database using our pre-defined search strategy and analyzed data using the GEO2R platform. The t-test was done to compare DEGs between females and males with HIV diseases. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was implemented to systematically extract biological features and processes of retrieving DEGs via gene ontology (GO) analysis. A Systemic search was performed to evaluate each DEG function and its possible association with HIV. Results One gene expression profiling data were retrieved: GSE 140713, composed of 40 males and 10 females with HIV1 infected samples. A GEO2R analysis yielded 19 DEGs (Table 1). The GO analysis result was demonstrated in Tables 2 and 3. Following a systemic search, we found two DEGs, which have previous studies reported an association with HIV: DDX3X (20 studies) and PDS5 (1 study). We proposed DDX3X (t 5.3, p 0.0037) is responsible for gender inequalities of HIV progression because of: 1. DDX3X is needed in the HIV1 life cycle. 2. Several studies confirmed a positive correlation between DDX3X expression and HIV1 replication. 3. Our study found an up-regulated DDX3X expression in women corresponded to the fact that women progress to AIDS faster than men. 4. Our GO analysis showed female up-regulated genes were enriched in positive regulation of the gene expression pathway, which can be explained by DDX3X and its underlying mechanism. Table 1: DEGs in women and men with HIV1 disease Table 2: GO functional enrichment pathway analyses of overall retrieving DEGs Table 3: GO functional enrichment pathway analyses of down- and up-regulated clusters of DEGs Conclusion Aberrant DDX3X expression may contribute to sex-based differences in HIV disease. Drugs modifying DDX3X gene expression will be beneficial in the treatment of HIV especially resolving the HIV drug resistance problem because current anti-HIV drugs target viral components posed the risk of viral mutation. Disclosures All Authors: No reported disclosures

scholarly journals The Serine Proteinase Inhibitor (Serpin) Plasminogen Activation Inhibitor Type 2 Protects against Viral Cytopathic Effects by Constitutive Interferon α/β Priming

1998 ◽  
Vol 187 (11) ◽  
pp. 1799-1811 ◽  
Author(s):  
Toni M. Antalis ◽  
May La Linn ◽  
Karen Donnan ◽  
Luis Mateo ◽  
Joy Gardner ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Proteinase Inhibitor ◽  
Rapid Development ◽  
Serine Proteinase ◽  
Productive Infection ◽  
Interferon Α ◽  
Serine Proteinase Inhibitor ◽  
Cytopathic Effects ◽  
Inhibitor Type

The serine proteinase inhibitor (serpin) plasminogen activator inhibitor type 2 (PAI-2) is well characterized as an inhibitor of extracellular urokinase-type plasminogen activator. Here we show that intracellular, but not extracellular, PAI-2 protected cells from the rapid cytopathic effects of alphavirus infection. This protection did not appear to be related to an effect on apoptosis but was associated with a PAI-2–mediated induction of constitutive low-level interferon (IFN)-α/β production and IFN-stimulated gene factor 3 (ISGF3) activation, which primed the cells for rapid induction of antiviral genes. This primed phenotype was associated with a rapid development of resistance to infection by the PAI-2 transfected cells and the establishment of a persistent productive infection. PAI-2 was also induced in macrophages in response to viral RNA suggesting that PAI-2 is a virus response gene. These observations, together with the recently demonstrated PAI-2–mediated inhibition of tumor necrosis factor-α induced apoptosis, (a) illustrate that PAI-2 has an additional and distinct function as an intracellular regulator of signal transduction pathway(s) and (b) demonstrate a novel activity for a eukaryotic serpin.

scholarly journals The Axonally Secreted Serine Proteinase Inhibitor, Neuroserpin, Inhibits Plasminogen Activators and Plasmin but Not Thrombin

1998 ◽  
Vol 273 (4) ◽  
pp. 2312-2321 ◽  
Author(s):  
Thomas Osterwalder ◽  
Paolo Cinelli ◽  
Antonio Baici ◽  
Amedea Pennella ◽  
Stefan Robert Krueger ◽  
...  
Keyword(s):  
Proteinase Inhibitor ◽  
Serine Proteinase ◽  
Plasminogen Activators ◽  
Serine Proteinase Inhibitor
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