Potential Key Genes Research Articles

Screening of core genes and prediction of ceRNA regulation mechanism of circRNAs in nasopharyngeal carcinoma by bioinformatics analysis.

Background: Nasopharyngeal carcinoma (NPC) represents a highly aggressive malignant tumor. Competing endogenous RNAs (ceRNA) regulation is a common regulatory mechanism in tumors. The ceRNA network links the functions between mRNAs and ncRNAs, thus playing an important regulatory role in diseases. This study screened the potential key genes in NPC and predicted regulatory mechanisms using bioinformatics analysis. Methods: The merged microarray data of three NPC-related mRNA expression microarrays from the Gene Expression Omnibus (GEO) database and the expression data of tumor samples or normal samples from the nasopharynx and tonsil in The Cancer Genome Atlas (TCGA) database were both subjected to differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA). The results from two different databases were intersected with WGCNA results to obtain potential regulatory genes in NPC, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The hub-gene in candidate genes was discerned through Protein-Protein Interaction (PPI) analysis and its upstream regulatory mechanism was predicted by miRwalk and circbank databases. Results: Totally 68 upregulated genes and 96 downregulated genes in NPC were screened through GEO and TCGA. According to WGCNA, the NPC-related modules were screened from GEO and TCGA analysis results, and the genes in the modules were obtained. After the results of differential analysis and WGCNA were intersected, 74 differentially expressed candidate genes associated with NPC were discerned. Finally, fibronectin 1 (FN1) was identified as a hub-gene in NPC. Prediction of upstream regulatory mechanisms of FN1 suggested that FN1 may be regulated by ceRNA mechanisms involving multiple circRNAs, thereby influencing NPC progression through ceRNA regulation. Conclusion: FN1 is identified as a key regulator in NPC development and is likely to be regulated by numerous circRNA-mediated ceRNA mechanisms.

Prevalence of Anemia Among Chronic Obstructive Pulmonary Disease Patients and Identification of Diagnostic Markers Associated with the Disease

Background: A co-morbidity of chronic obstructive pulmonary disease (COPD) has been identified as ane-mia. Chronic obstructive pulmonary disease is now known to have systemic inflammation, making it a po-tential cause of chronic anemia (ACD). According to preliminary findings, anemia may be more common than predicted in COPD patients, occurring in 10% to 15% of cases. This study aims to investigate the prevalence of anemia in COPD patients and look for biomarkers linked to the disease. Methods: In a retrospective study conducted at a university hospital in Kwara state, Nigeria, 280 patients (166 men and 114 women) with spirometry-confirmed COPD were assessed for the incidence of anemia. The gene expression profiles of microarray data, including GSE148004, were acquired from the Gene Expression Omnibus (GEO) database to discover potential candidate key genes linked to the onset and prognosis of COPD. DAVID was used to examine the pathway enrichment analysis of the differentially expressed genes (DEGs) from the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: Anemia was found in 104 people (88 men and 16 women), providing a frequency of 37.1%. Addi-tionally, 57.1% of the patients developed acute exacerbations. There were 9458 DEGs overall, of which 3772 were up-regulated, and 5686 were down-regulated. In the current study, DEGs revealed that the NEDD9 gene was over-expressed in COPD patients. Conclusion: Patients with COPD typically experience anemia, which is linked to higher morbidity in hospi-tal admissions and exacerbations. These patients’ clinical outcomes may be improved by treating their ane-mia. A potential biological relationship between anemia and COPD is IL1R1..

GRAP2: A Novel Immune-Related Prognosis Biomarker in Cervical Cancer

Background: Immune infiltration of the tumor microenvironment offers unlimited possibilities for therapeutic strategies in cervical cancer, where GRAP2 is an adaptor protein engaged in diverse signal activations. However, uncertainty exists regarding GRAP2’s prognostic significance and its relationship to immune infiltration. Methods: The data on cervical cancer cases were downloaded from The Cancer Genome Atlas (TCGA) database. The ESTIMATE computational technique was utilized to calculate the amount of immunological and stromal components, which helped us to identify the differential expression genes (DEGs). Among them, GRAP2 was considered to be related to overall survival based on a protein-protein interaction network and a univariate Cox regression analysis. Thus, based on the Gene Expression Omnibus (GEO) and TCGA databases, we evaluated GRAP2’s influence on clinical prognosis. Furthermore, GRAP2 expression was analyzed by Gene Set Enrichment Analysis (GSEA). Finally, we used CIBERSORTx analysis to assess the proportion of tumor-infiltrating immune cells (TICs) and the connection between GRAP2 and the tumor immune microenvironment. Results: ESTIMATEScore was associated with cervical cancer patient’s prognosis. There are 791 DEGs and 11 potential key genes were identified including GRAP2. In survival analyses with clinical information, We found that the GRAP2 high expression group exhibited a significantly longer overall survival (OS) than the low expression group and that the gene expression gradually declined as the Federation of International of Gynecologists and Obstetricians (FIGO) stage and M classification increased. GRAP2 was strongly linked with immunity and metabolism, according to GSEA. Finally, we discovered that 11 different TIC types and GRAP2 expressions were linked. Conclusions: GRAP2 may be a novel immune-related prognosis biomarker in cervical cancer.

Potential key genes are expected to become biomarker for early diagnosis of colorectal cancer through bioinformatics analysis

ABSTRACT Colorectal cancer (CRC) is the leading cause of cancer-related deaths in the world. The aim of this study was to identify the potential key genes, and associated pathways for early-onset CRC through bioinformatics methods. We integrated the gene expression patterns of CRC from three RNAseq datasets (GSE8671, GSE20916, GSE39582) from GEO database to identify DEGs between CRC and normal samples. We established a gene co-expression network through WGCNA. Through the WGCNA calculation, the genes were divided into six modules. The WGCNA analysis screened 242 genes associated with pathological stage and colorectal adenocarcinoma, 31 of which had the ability to predict OS with an AUC >0.7. The GSE39582 dataset identified 2040 DEGs between the CRC and normal samples. The two were intersected to obtain two genes: NPM1 and PANK3. The two genes were used as a threshold to divide the samples into high group and low group for survival analysis. Survival analysis showed that increased expression of both genes was significantly associated with a poorer prognosis. These two genes (NPM1 and PANK3) could be possible marker genes for early diagnosis of CRC, providing ideas for other experimental studies in the future.

Genome-wide DNA methylation and transcription analysis reveal the potential epigenetic mechanism of heat stress response in the sea cucumber Apostichopus japonicus

DNA methylation is an important epigenetic modification that regulates many biological processes. The sea cucumber Apostichopus japonicus often suffers from heat stress that affects its growth and leads to significant economic losses. In this study, the mRNA expression patterns and DNA methylation characteristics in the body wall of A. japonicus under heat stress were analyzed by whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing (RNA-seq). We found that CpG was the main DNA methylation type, and heat stress caused a significant increase in the overall methylation level and methylation rate, especially in the intergenic region of the A. japonicus genome. In total, 1,409 differentially expressed genes (DEGs) and 17,927 differentially methylated genes (DMGs) were obtained by RNA-seq and WGBS, respectively. Association analysis between DNA methylation and transcription identified 569 negatively correlated genes in both DMGs and DEGs, which indicated that DNA methylation affects on transcriptional regulation in response to heat stress. These negatively correlated genes were significantly enriched in pathways related to energy metabolism and immunoregulation, such as the thyroid hormone signaling pathway, renin secretion, notch signaling pathway and microRNAs in cancer. In addition, potential key genes, including heat shock protein (hsp70), calcium-activated chloride channel regulator 1(clca1), and tenascin R (tnr), were obtained and their expression and methylation were preliminarily verified. The results provide a new perspective for epigenetic and transcriptomic studies of A. japonicus response to heat stress, and provide a reference for breeding sea cucumbers resistant to high temperatures.

Identification of Immune Infiltration and Prognostic Biomarkers in Small Cell Lung Cancer Based on Bioinformatic Methods from 3 Studies.

This study aimed to investigate the correlation between gene expression and immune cell infiltration and the overall survival rate in tumor tissues, which may contribute to the therapy and prognosis of small cell lung cancer (SCLC) patients. SCLC is the most aggressive type of lung neoplasm. There is no proper marker for the treatment and prediction of prognosis in SCLC. Three gene expression profiles of SCLC patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified between normal lung samples and SCLC lung samples. Functional enrichment analysis of all DEGs was performed to explore the linkage among DEGs, the tumor immune microenvironment, and SCLC tumorigenesis. The common genes among the 3 groups in the Venn diagram and hub genes in protein-protein interaction (PPI) networks were considered potential key genes in SCLC patients. The TIMER (tumor immune estimation resource) database calculation and Kaplan-Meier survival curves were used to investigate the association between potential key genes and immune infiltrate prognosis of SCLC patients. A total of 750 (top 250 from each study) differentially expressed genes (DEGs) were identified. CLDN18 and BRIP1 were significantly related to immune infiltration in the tumor microenvironment. SHCBP1 and KIF23 were related mostly to prognosis in SCLC patients. The present study may provide some potential biomarkers for the therapy and prognosis of SCLC.

Identification MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 as the potential immune-related key genes involved in ischaemic cardiomyopathy by random forest and nomogram.

The immune molecular mechanisms involved in ischaemic cardiomyopathy (ICM) have not been fully elucidated. The current study aimed to elucidate the immune cell infiltration pattern of the ICM and identify key immune-related genes that participate in the pathologic process of the ICM. The differentially expressed genes (DEGs) were identified from two datasets (GSE42955 combined with GSE57338) and the top 8 key DEGs related to ICM were screened using random forest and used to construct the nomogram model. Moreover, the "CIBERSORT" software package was used to determine the proportion of infiltrating immune cells in the ICM. A total of 39 DEGs (18 upregulated and 21 downregulated) were identified in the current study. Four upregulated DEGs, including MNS1, FRZB, OGN, and LUM, and four downregulated DEGs, SERP1NA3, RNASE2, FCN3 and SLCO4A1, were identified by the random forest model. The nomogram constructed based on the above 8 key genes suggested a diagnostic value of up to 99% to distinguish the ICM from healthy participants. Meanwhile, most of the key DEGs presented prominent interactions with immune cell infiltrates. The RT-qPCR results suggested that the expression levels of MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 between the ICM and control groups were consistent with the bioinformatic analysis results. These results suggested that immune cell infiltration plays a critical role in the occurrence and progression of ICM. Several key immune-related genes, including the MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 genes, are expected to be reliable serum markers for the diagnosis of ICM and potential molecular targets for ICM immunotherapy.

GID2 Interacts With CDKN3 and Regulates Pancreatic Cancer Growth and Apoptosis

Dysregulation of deubiquitinase or ubiquitinase-mediated protein expression contributes to various diseases, including cancer. In the present study, we identified GID2, a subunit of the glucose-induced degradation-deficient (GID) complex that functions as an E3 ubiquitin ligase, as a potential key candidate gene in pancreatic cancer (PC) progression. The functional role and potential mechanism of GID2 in PC progression were investigated. Integrated bioinformatics analysis was performed to identify differentially expressed genes in PC based on the Gene Expression Profiling Interactive Analysis data sets. We found that GID2 was upregulated in PC tissues and that a high level of GID2 expression in clinical PC samples was positively associated with tumor stage and poor survival. Functional assays elucidated that GID2 expression promoted cell growth in vitro and accelerated tumor growth in vivo. GID2 knockdown effectively attenuated the malignant behaviors of PC cells and tumor formation. Furthermore, the protein network that interacted with the GID2 protein was constructed based on the GeneMANIA website. Cyclin-dependent kinase inhibitor 3 (CDKN3), a cell cycle regulator, was identified as a potential target of the GID2 protein. We revealed that GID2 positively regulated CDKN3 expression and inhibited CDKN3 ubiquitination. Furthermore, CDKN3 downregulation reversed the promoting effects of GID2 on PC progression. Therefore, the present study demonstrated that GID2 might regulate PC progression by maintaining the stability of the CDKN3 protein. These findings highlight the potential roles of the GID2/CDKN3 axis as a potential therapeutic target in PC.

Cocultivation of pigeon pea hairy root cultures and Aspergillus for the enhanced production of cajaninstilbene acid.

Pigeon pea hairy root cultures (PPHRCs) have been proven to be a promising alternative for the production of health-beneficial phenolic compounds, such as the most important health-promoting compound, i.e., cajaninstilbene acid (CSA). In this study, PPHRCs were cocultured with live Aspergillus fungi for further improving phenolic productivity via biological elicitation. Aspergillus oryzae CGMCC 3.951 (AO 3.951) was found to be the optimal fungus that could achieve the maximum increment of CSA (10.73-fold increase) in 42-day-old PPHRCs under the inoculum size of mycelia 0.50% and cocultivation time 36h. More precisely, the contents of CSA in hairy roots and culture media after fungal elicitation increased by 9.87- and 62.18-fold over control, respectively. Meanwhile, the contents of flavonoid glycosides decreased, while aglycone yields increased upon AO 3.951 elicitation. Moreover, AO 3.951 could trigger the oxidative stress and pathogen defense response thus activating the expression of biosynthesis- and ABC transporter-related genes, which contributed to the intracellular accumulation and extracellular secretion of phenolic compounds (especially CSA) in PPHRCs. And PAL2, 4CL2, STS1, and I3'H were likely to be the potential key enzyme genes regulating the biosynthesis of CSA, and ABCB11X1-1, ABCB11, and ABCG24X2 were closely related to the transmembrane transport of CSA. Overall, the cocultivation approach could make PPHRCs more commercially attractive for the production of high-value phenolic compounds such as CSA and flavonoid aglycones in nutraceutical/medicinal fields. And the elucidation of crucial biosynthesis and transport genes was important for systematic metabolic engineering aimed at increasing CSA productivity. KEY POINTS: • Cocultivation of PPHRCs and live fungi was to enhance CSA production and secretion. • PPHRCs augmented CSA productivity 10.73-fold when cocultured with AO 3.951 mycelia. • Several biosynthesis and transport genes related to CSA production were clarified.

Identification of key genes and active components of Astragalus membranaceus in the treatment of colorectal cancer based on bioinformatics analysis

Purpose: To investigate the bio-active components and key targets of Astragalus membranaceus (AM) in the treatment of colorectal cancer (CRC) through bioinformatics analysis.Methods: An AM action network was constructed after taking intersection of the target genes in AM and CRC-related genes. After that, Protein-Protein Interaction analysis, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the intersected genes. Then, the differential genes in GSE70772 and GSE113513 datasets were screened separately and intersected with genes from the PPI analysis to obtain the key targets.Results: After intersection with potential targets of AM and CRC-related genes, 105 genes were screened by PPI analysis. Then, 20 genes were identified as potential target genes of AM in GSE70772 and GSE113513 datasets. These genes were intersected with the 105 genes. Finally, a key gene called MET was identified as the key target of action of AM in the treatment of CRC, and methylnissolin (MOL000380) was the active component of AM.Conclusion: MET a potential key target gene of AM, whose active component is methylnissolin, in the treatment of CRC. Thus, the findings of this study may provide a scientific basis for the further development of AM for the treatment of CRC.

Combined transcriptomics and in-silico approach uncovers the role of prognostic biomarkers in hepatocellular carcinoma

Liver cancer is among the top five death-causing malignancies. High mortality rate, poor prognosis, and minimal drug options for hepatocellular carcinoma (HCC) patients led to the necessity to find potential key genes. Identifying key regulatory genes modulating the pathogenesis of HCC will lead to identifying new drug targets that help lessen the gap between incidence, diagnosis, and effective treatment of this malignancy. In this work, we constructed a protein-protein interaction (PPI) network (weighted) by considering the survival information and gene expression data from publicly available HCC patient datasets. A module comprising 83 genes was significantly associated with HCC and its survival rate. Interestingly, fourteen genes including, AURKA, AURKB, CCNB1, CCNB2, CDK1, CDC6, BIRC5, BUB1B, KIF2C, CENPE, KIF20A, KIF23, PLK1, and PRC1 were the top differential genes among all 83-module genes. Based on survival and prognosis significance, CCNB1 was identified as the most prominent target, therefore, we performed a virtual screening of natural compounds to predict small molecule inhibitors against Cyclin B1 (CCNB1). The analysis of binding affinities and the residues of active site interacted with the top hit ligands identify hypericin (highest binding affinity, −14.2 kcal/mol) as the best possible inhibitor for anticancer therapy development compared to the other ligands. Our study provided a rationale to evaluate hypericin as a promising anticancer agent against CCNB1-mediated HCC.

Identification of Key Genes Involved in Glioblastoma by Integrated Bioinformatics Analysis

Glioblastoma (GBM) is the most frequently identified malignancy of the brain. Due to the special tumor location, it is extremely urgent to explore key genes involved in the pathogenesis of GBM. In this study, we tried to identify vital genes that participate in the GBM progression by analyzing TCGA-sourced transcriptome data and identified 3183 differentially expressed genes (DEGs). Meanwhile, we also observed that CRYGN, MICAL2, BICDL1, PLK2, MTHFD2, OSMR, COL22A1, MSTN, and G0S2 expressions were significantly associated with patients’ survival. Immune infiltration analysis indicated that eight genes enhanced the immune infiltration in GBM, while BICDL1 had no significant effect. In conclusion, our study demonstrates that the eight genes are potential key genes involved in GBM and significantly connected to patients’ prognosis.

Distinctive clinicopathological features and differential gene expression of cerebral venous thrombosis mimicking brain tumors

Cerebral venous thrombosis (CVT), a rare type of cerebrovascular disease, can mimic a brain tumor (CVT mimicking brain tumor [CVTMBT]), due to its space-occupying imaging features. We aimed to describe the clinicopathological features and identify the thrombophilia-related gene expression changes in the brain following CVT. We conducted a retrospective qualitative study of CVT patients who were misdiagnosed with brain tumors before surgery at our hospital from 2016 to 2021. We analyzed the clinicopathological characteristics of the cases from our hospital and previously published cases. Five subjects were retrospectively studied, but one refused to provide biological specimens. We performed messenger ribonucleic acid (mRNA) sequencing from eight specimens (four CVTMBT and four non-CVTMBT samples). Differentially expressed genes (DEGs) were screened using the “edge” package in R 3.6.1 software. Thrombophilia-related genes were obtained from the MalaCards human disease database and were cross-checked with DEGs. The intersection was considered to be the potential genes in the pathogenesis of CVTMBT. The medical histories of the five patients with CVTMBT included oral non-steroidal anti-inflammatory drug use, oral contraceptive use, cesarean section, and anemia. All patients underwent craniotomy and were pathologically diagnosed with CVT. The follow-up results revealed that all patients had favorable outcomes without any recurrence. DEG analysis revealed 813 upregulated and 253 downregulated DEGs between patients with CVTMBT and controls. Nine DEGs were associated with thrombophilia, including SERPINE1, SELP, THBD, ITGB3, TFPI, F13A1, PROS1, PPBP, and PROCR, which were considered potential key genes in CVTMBT. CVTMBT presents with enhancement and mass effect on magnetic resonance imaging, accompanied by various predisposing factors, shorter disease duration, and coagulation dysfunction. The nine key genes identified as potential key genes in the pathogenesis of CVTMBT may be potential biomarkers for accurate screening and appropriate treatment.

QTL mapping and candidate gene analysis for yield and grain weight/size in Tartary buckwheat

BackgroundGrain weight/size influences not only grain yield (GY) but also nutritional and appearance quality and consumer preference in Tartary buckwheat. The identification of quantitative trait loci (QTLs)/genes for grain weight/size is an important objective of Tartary buckwheat genetic research and breeding programs.ResultsHerein, we mapped the QTLs for GY, 1000-grain weight (TGW), grain length (GL), grain width (GW) and grain length–width ratio (L/W) in four environments using 221 recombinant inbred lines (XJ-RILs) derived from a cross of 'Xiaomiqiao × Jinqiaomai 2'. In total, 32 QTLs, including 7 for GY, 5 for TGW, 6 for GL, 11 for GW and 3 for L/W, were detected and distributed in 24 genomic regions. Two QTL clusters, qClu-1-3 and qClu-1-5, located on chromosome Ft1, were revealed to harbour 7 stable major QTLs for GY (qGY1.2), TGW (qTGW1.2), GL (qGL1.1 and qGL1.4), GW (qGW1.7 and qGW1.10) and L/W (qL/W1.2) repeatedly detected in three and above environments. A total of 59 homologues of 27 known plant grain weight/size genes were found within the physical intervals of qClu-1-3 and qClu-1-5. Six homologues, FtBRI1, FtAGB1, FtTGW6, FtMADS1, FtMKK4 and FtANT, were identified with both non-synonymous SNP/InDel variations and significantly differential expression levels between the two parents, which may play important roles in Tatary buckwheat grain weight/size control and were chosen as core candidate genes for further investigation.ConclusionsTwo stable major QTL clusters related to grain weight/size and six potential key candidate genes were identified by homology comparison, SNP/InDel variations and qRT‒qPCR analysis between the two parents. Our research provides valuable information for improving grain weight/size and yield in Tartary buckwheat breeding.

Lineage-specific regulatory changes in hypertrophic cardiomyopathy unraveled by single-nucleus RNA-seq and spatial transcriptomics

Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder characterized by cardiomyocyte hypertrophy and cardiac fibrosis. Pathological cardiac remodeling in the myocardium of HCM patients may progress to heart failure. An in-depth elucidation of the lineage-specific changes in pathological cardiac remodeling of HCM is pivotal for the development of therapies to mitigate the progression. Here, we performed single-nucleus RNA-seq of the cardiac tissues from HCM patients or healthy donors and conducted spatial transcriptomic assays on tissue sections from patients. Unbiased clustering of 55,122 nuclei from HCM and healthy conditions revealed 9 cell lineages and 28 clusters. Lineage-specific changes in gene expression, subpopulation composition, and intercellular communication in HCM were discovered through comparative analyses. According to the results of pseudotime ordering, differential expression analysis, and differential regulatory network analysis, potential key genes during the transition towards a failing state of cardiomyocytes such as FGF12, IL31RA, and CREB5 were identified. Transcriptomic dynamics underlying cardiac fibroblast activation were also uncovered, and potential key genes involved in cardiac fibrosis were obtained such as AEBP1, RUNX1, MEOX1, LEF1, and NRXN3. Using the spatial transcriptomic data, spatial activity patterns of the candidate genes, pathways, and subpopulations were confirmed on patient tissue sections. Moreover, we showed experimental evidence that in vitro knockdown of AEBP1 could promote the activation of human cardiac fibroblasts, and overexpression of AEBP1 could attenuate the TGFβ-induced activation. Our study provided a comprehensive analysis of the lineage-specific regulatory changes in HCM, which laid the foundation for targeted drug development in HCM.

Comprehensive bioinformatics analysis revealed potential key genes and pathways underlying abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a permanent, asymptomatic segmental dilatation of the abdominal aorta, with a high mortality risk upon rupture. Identification of potential key genes and pathways may help to develop curative drugs for AAA. We conducted RNA-seq on abdominal aortic tissues from both AAA patients and normal individuals as a control group. Integrated bioinformatic analysis was subsequently performed to comprehensively reveal potential key genes and pathways. A total of 1148 differential expressed genes (DEGs) (631 up-regulated and 517 down-regulated) were identified in our study. Gene Ontology (GO) analysis revealed enrichment in terms related to extracellular matrix organization, while KEGG analysis indicated enrichment in hematopoietic cell lineage and ECM-receptor interaction. Protein-protein interaction (PPI) network analysis revealed several candidate key genes, and differential expression of 6 key genes (CXCL8, CCL2, PTGS2, SELL, CCR7, and CXCL1) was validated by Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic curve (ROC) analysis demonstrated these genes’ high discriminatory ability between AAA and normal tissues. Immunohistochemistry indicated that several key genes were highly expressed in AAA tissues. Single-cell RNA sequencing revealed differential distribution patterns of these identified key genes among various cell types. 26 potential drugs linked to our key genes were found through DGIdb. Overall, our study provides a comprehensive evaluation of potential key genes and pathways in AAA, which could pave the way for the development of curative pharmacological therapies.

Plasminogen Activator Inhibitor-1 Potentiates Neutrophil Infiltration and Tissue Injury in Colitis.

The mechanism underlying inflammatory bowel disease (IBD) remains unclear. We aimed to identify early diagnostic biomarkers and understand their roles in the pathogenesis of IBD. Methods: We identified plasminogen activator inhibitor-1 (PAI-1) as a potential key gene that is upregulated in IBD based on published transcriptomic datasets. To further determine the role of PAI-1 in disease pathogenesis, we induced colitis in wild-type (WT) and PAI-1 knockout (KO) mice by administering dextran sulfate sodium (DSS). We used an RNA array of genes and 16S rRNA sequencing of the microbiome to analyze PAI-1 function. The colon and serum PAI-1 levels in humans were further evaluated for their diagnostic value. Results: PAI-1 expression was significantly increased in patients and DSS-induced WT mice but reduced in PAI-1 KO mice. These changes were associated with significantly decreased neutrophil infiltration in colonic tissues. The RNA array revealed that the CXC chemokines CXCL1 and CXCL5 and their common receptor CXCR2 were among the most significantly different genes between the PAI-1 KO mice with DSS-induced colitis and the WT mice. Mechanistically, PAI-1 deficiency led to blunted activation of the NF-κB pathway in the colon epithelium. The gut microbiome was altered in the PAI-1 KO mice, which showed enriched abundances of short-chain fatty acid-producing genera and diminished abundances of pathogenic genera. Receiver operating characteristic (ROC) curve analysis revealed the diagnostic value of PAI-1. Conclusions: Our data suggest a previously unknown function of PAI-1 inducing neutrophil-mediated chemokine expression by activating the NF-κB pathway and affecting the function of the gut microbiome. PAI-1 could be a potential diagnostic biomarker and a therapeutic target in IBD.

Retracted: Potential Progression Mechanism and Key Genes in Early Stage of mTBI.

[This retracts the article DOI: 10.1155/2022/3151090.].

MiR26-5p inhibits pathological pulmonary microvascular angiogenesis via down-regulating WNT5A.

Pathological micro angiogenesis is a key pathogenic factor in pulmonary diseases such as pulmonary hypertension and hepatopulmonary syndrome. More and more pieces of evidence show that excessive proliferation of pulmonary microvascular endothelial cells is the key event of pathological micro angiogenesis. The purpose of this research is to reveal the mechanism of miR26-5p regulating pulmonary microvascular hyperproliferation. Hepatopulmonary syndrome rat model was made by common bile duct ligation. HE and IHC staining were used for analysis of the pathology of the rat. CCK8, transwell, and wound healing assay were used to assess miR26-5p or target gene WNT5A functioned toward PMVECs. microRNA specific mimics and inhibitors were used for up/down-regulated miR26-5p expression in PMVECs. Recombinant lentivirus was used for overexpression/knockdown WNT5A expression in PMVECs. And the regulation relationship of miR26-5p and WNT5A was analyzed by dual-luciferase reporter assay. qPCR showed that miR26-5p was significantly down-regulated in the course of HPS disease. Bioinformatics data showed that WNT5A was one of the potential key target genes of miR26-5p. Immunohistochemistry and qPCR analysis showed that WNT5A was largely expressed in pulmonary microvascular endothelial cells, in addition, this molecule was significantly up-regulated with the progression of the disease. Furthermore, dual luciferase reporter assay showed that miR26-5p could bind to WNT5A 3 'UTR region to inhibit WNT5A synthesis. The results suggested MiR26-5p negatively regulated PMVECs proliferation and migration by WNT5A expression. Overexpression of miR26-5p may be a potentially beneficial strategy for HPS therapy.

ADAM19 and TUBB1 correlates with tumor infiltrating immune cells and predicts prognosis in osteosarcoma.

Osteosarcoma is the most common type of primary malignant bone tumor. This study aimed to explore potential key prognostic genes and their roles in osteosarcoma. Three microarray datasets for osteosarcoma were downloaded from GEO database. Differentially expressed genes (DEGs) were screened by Limma package. Functional enrichment analysis was performed based on DAVID, GeneMANIA, and Metascape databases. Prognostic value of DEGs was elevated by survival analysis. CIBERSORT was used to assess the infiltrating abundance of 22 immune cells, followed by the Pearson correlation analysis between immune cells and prognosis-related genes. Gene set enrichment analysis and drug-gene interactions prediction were performed for prognosis-related genes. A total of 8 common up-regulated DEGs and 13 common down-regulated DEGs were screened in GSE36001 and GSE56001 datasets. Enrichment analysis showed these DEGs were implicated in platelet activation, SMAD protein phosphorylation, lymphocyte/leukocyte/T cells activation, and cell migration. Survival analysis indicated that elevated expression of ADAM19 and TUBB1 were associated with favorable prognosis. CIBERSORT algorithm revealed higher infiltrating level of CD8 T cells, macrophages M0, and M2 in osteosarcoma. ADAM19 expression positively correlated with naïve B cells and negatively correlated with activated dendritic cells infiltrating abundance. TUBB1 expression positively correlated with gamma delta T cells while negatively correlated with helper follicular T cells infiltrating abundance. Total of 56 drugs were found to target TUBB1. ADAM19 and TUBB1 could be prognostic biomarkers in osteosarcoma. Both their expression correlates with tumor infiltrating immune cells. TUBB1 was a multi-drug target that might be a therapeutic target in osteosarcoma.