Low expression of integrin signaling pathway genes is associated with abdominal aortic aneurysm: a bioinformatic analysis by WGCNA.

OBJECTIVE: An abdominal aortic aneurysm (AAA) is a potentially fatal disease associated with a high risk of rupture. AAA is pathologically distinguished by atherosclerotic thrombosis, immune cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. Given that there are no effective target treatments, once ruptured, AAA leads to high mortality with few long-term survivors. The goal of this study is to identify novel key pathways and hub genes involved in AAA formation with the aim of providing promising therapeutic targets for AAA. MATERIALS AND METHODS: The transcriptome sequencing matrix of GSE47472 and GSE57691 were obtained from the GEO database. These datasets were further merged for differential expression analysis, weighted gene co-expression network analysis (WGCNA), and functional enrichment analysis in R (v4.0.2). A co-expression network was constructed with Cytoscape (v3.8.0) to generate the top 30 hub genes. Hub Genes with high clinical traits and potential values were further verified using a receiver operating characteristic (ROC) curve and qPCR analysis. RESULTS: A total of 745 differentially expressed genes were screened and 14 gene co-expression modules were established. Among these 14 modules, pink modules with a total of 118 genes showed the strongest correlation with AAA pathogenesis. Subsequently, 78 genes associated with a highly relevant clinical trait and the top 30 hub genes were intersected to generate 22 genes. Gene ontology functional enrichment analysis of the 22 genes revealed abnormal expression of genes relating to cell-matrix adhesion and integrin-mediated signaling pathway. LAMA5, ITGA8, ITGA1, and FERMT2 were associated with the integrin-mediated signaling pathway and cell-matrix adhesion while ACTN1 and CX3CL1 were simply associated with the latter. Low expressions of LAMA5, ACTN1, ITGA8, ITGA1, and FERMT2 were further verified through qPCR in a mouse model of AAA. CONCLUSIONS: Low expression of partial genes in the integrin signaling pathway was implicated in the function loss of mediated cell-matrix adhesion, which may offer novel targets for therapeutic intervention against AAA.

The perioperative complications and short-term death in endovascular treatment for acute stroke induced by extracranial carotid occlusion: a systematic review and a meta-analysis.

OBJECTIVE: Endovascular treatment (EVT) has been demonstrated superior to pharmacological thrombolysis in acute ischemic stroke (AIS) induced by extracranial internal carotid artery occlusion. This paper aims to summarize clinical evidence about EVT and assess its efficacy and safety on acute extracranial carotid occlusion. MATERIALS AND METHODS: We systematically reviewed all studies that reported endovascular therapy as carotid stenting, stent retriever, aspiration, and angioplasty for acute extracranial carotid occlusion. Literature retrieval was performed in PubMed, Embase, and Cochrane library, dated from January 1st, 2005 to December 31st, 2020. The primary endpoint was a favorable outcome rate. Major secondary endpoints were SICH incidence, 90-day mortality rate, and complications. Meta-analysis and subgroup analysis were conducted to identify predictors for prognosis. This systematic review has been registered in PROSPERO (CRD42020181154) on July 18, 2020. RESULTS: 10 studies with 620 patients were included in total. Endovascular approach presented a favorable outcome rate of 0.47 (0.37, 0.56), an acceptable 90-day mortality rate of 0.16 (0.13, 0.19), and a mild SICH rate of 0.07 (0.05, 0.10). Age and NIHSS at admission were negatively associated with favorable outcome, with odds ratio of 0.95 (0.92, 0.98) and 0.74 (0.62, 0.88) respectively. Lower age (p=0.049) and aspiration thrombectomy (p=0.041) predicted less SICH events. In subgroup in which time window > 6 hours, endovascular therapy presented similar encouraging results, with favorable outcome rate of 0.59 (0.51, 0.66), 90-day mortality rate of 0.11 (0.07, 0.17), and SICH rate of 0.04 (0.02, 0.09). CONCLUSIONS: EVT can effectively improve neurological function and reduce 90-day mortality for acute extracranial carotid occlusion patients without increasing the risk of symptomatic intracranial hemorrhage. Endovascular therapy is safe to perform from 6 to 24 hours after symptom onset.

Abnormal expression and mechanism of miR-330-3p/BTG1 axis in hepatocellular carcinoma.

OBJECTIVE: Increasing evidence has suggested that microRNAs (miRNAs) played critical roles in cancer development by acting as a tumor suppressor or tumor-promoting genes. However, the role of microRNA-330-3p (miR-330-3p) in hepatocellular carcinoma (HCC) is still unknown. This study aimed to investigate the expression and role of miR-330-3p in hepatocarcinogenesis. PATIENTS AND METHODS: A total of 30 human hepatocellular carcinoma tissues and adjacent normal tissues were obtained from 30 hepatocellular carcinoma patients. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was carried out to measure the expression of miR-330-3p in HCC tissues and cell lines. The relation between B-cell translocation gene 1 (BTG1) and miR-330-3p was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Cell Counting Kit-8 (CCK-8), flow cytometry analysis, and transwell assay were used to determine cell viability, apoptosis, cell migration, and invasion, respectively. In addition, the mRNA and protein expression of Cyclin D1, Bcl-2, Bax, and matrix metalloproteinase (MMP)9 were detected using qRT-PCR and Western blotting. RESULTS: We found that miR-330-3p expression was up-regulated in HCC tissues and cell lines. BTG1 was a direct target of miR-330-3p and it was down-regulated in HCC tissues and cell lines. Moreover, down-regulation of miR-330-3p suppressed HCCLM3 cell viability, migration, invasion, and enhanced cell apoptosis, while the tumor-suppressive effects were reversed by BTG1-siRNA. In addition, miR-330-3p inhibitor decreased the expression of Cyclin D1, Bcl-2, and MMP9 while enhanced the expression of Bax. Meanwhile, BTG1-siRNA led to the opposite effects. CONCLUSIONS: The data suggested that miR-330-3p acted as a tumor gene in HCC by targeting BTG1 and it might be a potential therapeutic target for the HCC treatment.

[Selection of high avermectins producing strain and identification of avermectin B1].

Three types of colony, powdery gray, white and bald, were isolated from Streptomyces avermitilis ATCC31272. Among them, only the powdery grey one produces avermectins. Sa-76 strain was selected from the powdery grey strain by mutation with high energy electric flow, and its avermectins titer attainde 100 micrograms/mL in shaking flask. Avermectin B1 was extracted and purified from the mycelia of Sa-76, and identified by UV, IR, 1H-NMR, 13C-NMR and mass spectra. After Sa-76 strain was treated twice with NTG, a strain named Sa-76-8 was selected with avermectins titer over 2000 micrograms/mL. The Sa-76-8 strain was treated with NTG once again, and a high avermectins producing strain named as Sa-76-9 with avermectins titer up to 3500-4000 micrograms/mL was selected.

Effects of acute methamphetamine administration on spacing in paired rats: investigation with an automated video-analysis method.

1. Effects of acute methamphetamine administration on spacing and locomotor activity were investigated in paired rats using a computer-assisted automated video-analysis method. 2. Both 0.1 and 1 mg/kg of methamphetamine significantly increased the spacing in comparison with saline. This alteration in behavioral interaction by methamphetamine may serve as one of the animal models of social withdrawal. 3. A significant increase in locomotor activity was found after 1 mg/kg of methamphetamine. 0.1 mg/kg dosage was accompanied by a locomotor change of a lesser degree and shorter duration. 4. The difference with respect to the dose dependency and the time course indicates that the changes in these two behavioral indices by methamphetamine may have different underlying mechanisms.