Expressed Sequence Tags-1-Targeted MiRNA-326 in Gastric Cancer Induces Local Immune Inflammatory Microenvironment by Inducing T Helper Cell 17 Cell Differentiation

This study intends to assess miRNA-326’s effect on the immune-inflammatory microenvironment and its mechanism in gastric cancer (GC). GC adjacent tissues and tumor tissues were collected to analyze inflammatory factors by immunohistochemistry and ELISA, Est-1 and miRNA-326 level by Western blot or PCR, Th17 cells by flow cytometry. CD4+ T cells were transfected with Est-1 inhibitor, Est-1 mimics, or miR-326 mimics followed by measurement of Th17 differentiation-related genes via gene chips and inflammatory factor release. Inflammatory factors in serum of GC patients were significantly increased and miR-326 was upregulated with decreased Est-1 and unbalanced Th17/Treg cell ratio. miR-326 targeted Est-1 to inhibit its expression. After transfection with Est-1 inhibitor, Th17 differentiation-related genes were upregulated. After transfection with miR-326 mimics, Est-1 level was reduced and inflammation was enhanced with maturation of Th17 cells. In conclusion, miRNA-326 induces Th17 cell differentiation by targeting Est-1, thereby promoting the release of inflammatory factors and inducing immune inflammatory microenvironment.

Genomic and RNA-Seq Profiling of Patients with Heart Failure Identified Alterations in Phosphorylation and Immune Signaling Pathways

Background: Heart failure (HF) is a complex pathophysiological state in which the delivery of blood and nutrients to the tissues is inadequate. It is rarely curable and often associated with poor prognosis. The current study aimed to analyze the exomic and RNA-Seq data of patients with HF to identify the key altered pathways. Methods: Heart failure participants were recruited, and whole blood samples were collected. The samples were used for whole exome sequencing and RNA-Seq analysis. Gene expression and RNA-Seq results were verified by Gene chips and RT-PCRResults: We report a dysregulation of phosphorylation and immune signaling in patients with HF both by exomic and RNA-Seq data. We identified mutations in TITIN,OBSCURIN, NOD2, CDH2, MAP3K5, and SLC17A4 to be associated with HF by exomic analysis. And certain genes, S100A12, S100A8, S100A9, PFDN5, and TMCC2, were found upregulated in patients with HF by RNA-Seq. Conlcusion: Our results demonstrated the overall disruption of key phosphorylation and immune signaling pathways in patients with HF.

Research on Potential Pathogenesis of Advanced Diabetic Nephropathy based on Bioinformatic Analysis

Objective: Through the bioinformatic analysis of gene chips related to advanced diabetic nephropathy in the GEO database, the key genes of advanced diabetic nephropathy are screened, whose biological functions and signal pathways are predicted as well. Methods: The gene chips related to advanced diabetic nephropathy from the GEO expression profile database was downloaded, and the differentially expressed genes in patients with advanced diabetic nephropathy and normal people were analyzed through R. For the screened differentially expressed genes, the biological function of GO and the enrichment analysis of KEGG signal pathway were used to predict their biological functions and related signal pathways. In addition, a protein-protein interaction network was constructed, so as to screen core pathogenic genes utilizing STRING database and Cytoscape. Results: By analyzing the chip GSE142025, 301 differential genes were obtained, including 197 up-regulated genes and 104 down-regulated genes. Both GO annotation and enrichment analysis suggested that differential genes were mainly involved in immune-inflammatory response and cytokine action. Furthermore, KEGG pathway analysis suggested that the most important pathway related to advanced diabetic nephropathy was MAPK signaling pathway. Through protein-protein interaction network and module analysis, C3, CCR2, CCL19, and SAA1 were selected as the core sites of the interaction. Conclusions: Differential genes participate in the pathogenesis of advanced diabetic nephropathy through the KEGG pathway, the immune inflammatory response and cytokine action, which provides new ways for the diagnosis and treatment of advanced diabetic nephropathy.

Mechanism of E Lian Granule Reversing Chronic Atrophic Gastritis With Intestinal Metaplasia Based on Integrated Pharmacology and GEO Gene Chip

Background: This study aimed to explore the main components and targets of E-Lian granule through which it reversed chronic atrophic gastritis with intestinal metaplasia, based on the traditional Chinese Medicine Integrated Pharmacology Network Computing Research Platform V2.0 (TCMIP V2.0) combined with GEO gene chips. It also aimed to construct various networks to predict and analyze the mechanism of E-Lian granule in treating gastric precancerous lesions. Methods: The effective traditional Chinese medicine components and targets of E-Lian granule prescription were obtained using TCMIP V2.0. The disease targets were collected using the TCMIP V2.0 platform and the verified gene chips in the GEO database, and the “drug components–targets” network, “compound–targets protein interaction network,” and “core compound targets–pathways network” were constructed using Cytoscape 3.6.1. The reliability of the predicted components and targets was verified using Pymol 1.7.2.1 and Autodock Vina 1.1.2 reverse molecular docking. Results: A total of 262 unique active components and 680 potential active targets of E-Lian granule were obtained. Moreover, 2247 unique disease targets of chronic atrophic gastritis with intestinal metaplasia were obtained by searching the “Disease/Symptom Target Database” combined with the GEO chip (GSE78523) and GeneCard database. Further, 178 complex targets and 38 complex core targets were obtained using Venn and Filter, respectively, such as ALB, TNF, PTGS2, RHOA, ESR1, HRAS, JUN, FOS, CASP3 and so forth. The GO and KEGG nrichment analyses showed that E-Lian granule reversed gastric precancerous lesions not only through the direct intervention of the cancer pathway, gastric cancer pathway, and epithelial signal transduction in Helicobacter pylori infection but also through PI3K/AKT, VEGF, MAPK, cAMP, cGMP, Th1/Th2,and other pathways. It also had a significant correlation with cholinergic, 5-hydroxytryptamine, dopaminergic, and other gastrointestinal hormone-related signals. Finally, the core target verified in the GSE78523 chip was successfully used to dock with the active components of E-Lian granules. The reliability of the prediction was also verified. Conclusions: The components and molecular mechanism of E-Lian granule in reversing chronic atrophic gastritis with intestinal metaplasia were predicted by integrated pharmacology, GEO chip, and reverse molecular docking, providing an important theoretical basis for further study of the effective substances and mechanism of E-Lian granule in treating chronic atrophic gastritis.

LncRNA DNAJC3-AS1 Regulates Fatty Acid Synthase via the EGFR Pathway to Promote the Progression of Colorectal Cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide. Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in tumorigenesis and the development of CRC. By constructing a differential lncRNA expression profile, we screened gene chips and found that DNAJC3-AS1 was highly expressed in CRC tissues and was associated with poor prognosis in patients with CRC. Further, we proved through assays such as wound healing, colony formation, and Cell Counting Kit-8 (CCK8) that interfering with DNAJC3-AS1 could reduce the proliferation, migration, and invasion of CRC cells. Mechanically, we found that DNAJC3-AS1 regulates fatty acid synthase to promote the progression of CRC via the epidermal growth factor receptor/phosphatidylinositol 3-kinase/protein kinase B/nuclear factor κB signaling pathway. Therefore, DNAJC3-AS1 may be a new target for the diagnosis and therapy of CRC.

Mechanisms of indigo naturalis on treating ulcerative colitis explored by GEO gene chips combined with network pharmacology and molecular docking

Oral administration of indigo naturalis (IN) can induce remission in ulcerative colitis (UC); however, the underlying mechanism remains unknown. The main active components and targets of IN were obtained by searching three traditional Chinese medicine network databases such as TCMSP and five Targets fishing databases such as PharmMapper. UC disease targets were obtained from three disease databases such as DrugBank,combined with four GEO gene chips. IN-UC targets were identified by matching the two. A protein–protein interaction network was constructed, and the core targets were screened according to the topological structure. GO and KEGG enrichment analysis and bioGPS localization were performed,and an Herbs-Components-Targets network, a Compound Targets-Organs location network, and a Core Targets-Signal Pathways network were established. Molecular docking technology was used to verify the main compounds-targets. Ten core active components and 184 compound targets of IN-UC, of which 43 were core targets, were enriched and analyzed by bioGPS, GO, and KEGG. The therapeutic effect of IN on UC may involve activation of systemic immunity, which is involved in the regulation of nuclear transcription, protein phosphorylation, cytokine activity, reactive oxygen metabolism, epithelial cell proliferation, and cell apoptosis through Th17 cell differentiation, the Jak-STAT and IL-17 signaling pathways, toll-like and NOD-like receptors, and other cellular and innate immune signaling pathways. The molecular mechanism underlying the effect of IN on inducing UC remission was predicted using a network pharmacology method, thereby providing a theoretical basis for further study of the effective components and mechanism of IN in the treatment of UC.

Research on Complex Classification Algorithm of Breast Cancer Chip Based on SVM-RFE Gene Feature Screening

Screening and classification of characteristic genes is a complex classification problem, and the characteristic sequences of gene expression show high-dimensional characteristics. How to select an effective gene screening algorithm is the main problem to be solved by analyzing gene chips. The combination of KNN, SVM, and SVM-RFE is selected to screen complex classification problems, and a new method to solve complex classification problems is provided. In the process of gene chip pretreatment, LogFC and P value equivalents in the gene expression matrix are screened, and different gene features are screened, and then SVM-RFE algorithm is used to sort and screen genes. Firstly, the characteristics of gene chips are analyzed and the number between probes and genes is counted. Clustering analysis among each sample and PCA classification analysis of different samples are carried out. Secondly, the basic algorithms of SVM and KNN are tested, and the important indexes such as error rate and accuracy rate of the algorithms are tested to obtain the optimal parameters. Finally, the performance indexes of accuracy, precision, recall, and F1 of several complex classification algorithms are compared through the complex classification of SVM, KNN, KNN-PCA, SVM-PCA, SVM-RFE-SVM, and SVM-RFE-KNN at P=0. 01,0.05,0.001. SVM-RFE-SVM has the best classification effect and can be used as a gene chip classification algorithm to analyze the characteristics of genes.

Mycobacterial identification on homogenised biopsy facilitates the early diagnosis and treatment of laryngeal tuberculosis

IntroductionThe incidence of laryngeal tuberculosis has increased gradually in recent years. Laryngeal tuberculosis has strong infectivity and atypical clinical manifestations. Hence, establishing the early diagnosis of laryngeal tuberculosis is considered difficult, resulting in the high rate of misdiagnosis of laryngeal tuberculosis and increased rates of tuberculosis infection.ObjectiveThis study aimed to describe a case of laryngeal tuberculosis detected using the mycobacteria gene chips technology, facilitating the early diagnosis and the treatment of laryngeal tuberculosis.Case presentationA 27-year-old woman presented with a 7-day history of hoarseness, with a normal routine blood chemistry test and chest computed tomography results. Histological analysis of the vocal cord biopsy showed granulomatous inflammation and the negative acid-fast stain test. The mycobacteria gene chips method was used to directly examine the vocal cord tissue treated with homogenate, and the Mycobacterium tuberculosis was successfully identified. Thus, the early diagnosis of laryngeal tuberculosis and the drug sensitivity of rifampin and isoniazid were confirmed. The patient recovered after undergoing a 1-year standard anti-tuberculosis therapy.ConclusionsMycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.

Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response

Background: Variation in genes implicated in homocysteine and lipid metabolism systems may influence antidepressant response. This study was aimed to investigate how the MTHFR, ApoE and ApoA4 polymorphisms determine this response to treatment. Methods: A total of 281 Han Chinese patients received a single antidepressant drug (SSRI or SNRI) for at least 6 weeks. The Hamilton Depression Rating Scale (HDRS-17) was used to evaluate the severity of depressive symptoms and the therapeutic effects of the drug administered. Eight single nucleotide polymorphisms (SNPs) of MTHFR, ApoE and ApoA4 genes were detected using gene chips. Differences in clinical variables between the responders and non-responders, as well as between remission and non-remission groups, were examined using the independent samples t test and Pearson’s χ2 test. In addition, the associations of single loci and haplotypes with treatment response were analyzed. Results: Haplotype (C-A) in MTHFR (rsl801133 and rs1801131) was significantly associated with better antidepressant response in the 8-week antidepressant group overall (P = 0.0007), and in the male subgroup (P = 0.003), and SNRI subgroup (P = 0.001). The ApoE rs405509 C allele was significantly associated with worse antidepressant response in the 6-week male subgroup (P = 0.004), while the 405509 AA genotype was associated with better antidepressant efficacy in the 6-week group overall (P = 0.006) and male subgroup (P = 0.002). Haplotype (G-A) in APOE (rs7412 and rs405509) was significantly associated with better antidepressant response in 6-week male subgroup (P = 0.003), G-C haplotype was associated with better response in 6-week SNRI subgroup；APOA4 rs5092 G allele was associated with worse antidepressant response in 6-weeks male subgroup (P = 0.037), SNRIs subgroup (P = 0.097) and 8-weeks female subgroup (P = 0.045)；APOA4 rs5092 GG genotype was associated with worse antidepressant efficacy in 6-week SNRI subgroup (P = 0.008). Conclusions: The haplotype in MTHFR (rs1801131-rs1801133) C-A type was associated with better antidepressant efficacy, especially in males and in patients using SNRIs. The efficacy of antidepressants may be better in ApoE rs405509 A allele and AA genotype carriers, but worse in ApoA4 rs5092 G allele and GG genotype carriers.