Unrevealing of dysregulated hub genes linked with immune system and inflammatory signaling pathways in the pathogenesis of irritable bowel syndrome by system biology approaches

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain and altered bowel movements. This disorder affects up to 10–23% of people globally and can affect both children and adults. Therefore, it is important to uncover early and novel therapeutic biomarkers and also reveal the pathobiology mechanisms of IBS. The main goal of this study is to investigate the hub genes and putative molecular mechanisms in IBS. Firstly, we identified 73 mutual differentially expressed genes (DEGs) from three RNA-seq databases. Then, functional gene annotation and pathway analysis of these common DEGs were enriched with interferon signaling, interferon gamma signaling, antigen processing-cross presentation, adaptive immune system, cytokine signaling in immune system, type II interferon signaling (IFNG), notch signaling pathway, MAPK signaling pathway, and IL-4 signaling pathway. In addition, a total number of 9 hub genes discovered as candidates of potential therapeutic biomarkers of IBS pathogenesis. Furthermore, transcription factors and regulatory protein kinases were identified as key signature molecules linked with IBS pathobiology. Taken together, this current study provided a novel understanding of biological mechanisms of IBS and may provide promising therapeutic targets

Unraveling the Mechanism of Immunity and Inflammation Related to Molecular Signatures Crosstalk Among Obesity, T2D, and AD: Insights From Bioinformatics Approaches

Individuals with type 2 diabetes (T2D) and obesity have a higher risk of developing Alzheimer disease (AD), and increasing evidence indicates a link between impaired immune signaling pathways and the development of AD. However, the shared cellular mechanisms and molecular signatures among these 3 diseases remain unknown. The purpose of this study was to uncover similar molecular markers and pathways involved in obesity, T2D, and AD using bioinformatics and a network biology approach. First, we investigated the 3 RNA sequencing (RNA-seq) gene expression data sets and determined 224 commonly shared differentially expressed genes (DEGs) from obesity, T2D, and AD diseases. Gene ontology and pathway enrichment analyses revealed that mutual DEGs were mainly enriched with immune and inflammatory signaling pathways. In addition, we constructed a protein-protein interactions network for finding hub genes, which have not previously been identified as playing a critical role in these 3 diseases. Furthermore, the transcriptional factors and protein kinases regulating commonly shared DEGs among obesity, T2D, and AD were also identified. Finally, we suggested potential drug candidates as possible therapeutic interventions for 3 diseases. The results of this bioinformatics analysis provided a new understanding of the potential links between obesity, T2D, and AD pathologies

System biology approaches to identify hub genes linked with ECM organization and inflammatory signaling pathways in schizophrenia pathogenesis

Schizophrenia (SZ) is a chronic and devastating mental illness that affects around 20 million individuals worldwide. Cognitive deficits and structural and functional changes of the brain, abnormalities of brain ECM components, chronic neuroinflammation, and devastating clinical manifestation during SZ are likely etiological factors shown by affected individuals. However, the pathophysiological events associated with multiple regulatory pathways involved in the brain of this complex disorder are still unclear. This study aimed to develop a pipeline based on bioinformatics and systems biology approaches for identifying potential therapeutic targets involving possible biological mechanisms from SZ patients and healthy volunteers. About 420 overlapping differentially expressed genes (DEGs) from three RNA-seq datasets were identified. Gene ontology (GO), and pathways analysis showed several biological mechanisms enriched by the commonly shared DEGs, including extracellular matrix organization (ECM) organization, collagen fibril organization, integrin signaling pathway, inflammation mediated by chemokines and cytokines signaling pathway, and GABA-B receptor II and IL4 mediated signaling. Besides, 15 hub genes (FN1, COL1A1, COL3A1, COL1A2, COL5A1, COL2A1, COL6A2, COL6A3, MMP2, THBS1, DCN, LUM, HLA-A, HLA-C, and FBN1) were discovered by comprehensive analysis, which was mainly involved in the ECM organization and inflammatory signaling pathway. Furthermore, the miRNA target of the hub genes was analyzed with the random-forest-based approach software miRTarBase. In addition, the transcriptional factors and protein kinases regulating overlapping DEGs in SZ, namely, SUZ12, EZH2, TRIM28, TP53, EGR1, CSNK2A1, GSK3B, CDK1, and MAPK14, were also identified. The results point to a new understanding that the hub genes (fibronectin 1, collagen, matrix metalloproteinase-2, and lumican) in the ECM organization and inflammatory signaling pathways may be involved in the SZ occurrence and pathogenesis