MicroRNA Gene Networks in Oncogenesis

MicroRNAs are small non-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. They are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. Examination of tumor-specific microRNA expression profiles has revealed widespread deregulation of these molecules in diverse cancers. Several studies have shown that microRNAs function either as tumor suppressor genes or oncogenes, whose loss or overexpression respectively has diagnostic and prognostic significance. It seems that microRNAs act as major regulators of gene expression. In this review, we discuss microRNAs’ role in cancer and how microRNAs exert their functions through regulation of their gene targets. Bioinformatic analysis of putative miRNA binding sites has indicated several novel potential gene targets involved in apoptosis, angiogenesis and metastatic mechanisms. Matching computational prediction analysis together with microarray data seems the best method for microRNA gene target identification. MicroRNAs together with transcription factors generate a complex combinatorial code regulating gene expression. Thus, manipulation of microRNA-transcription factor gene networks may be provides a novel approach for developing cancer therapies

A Multi-Class Intrusion Detection System Based on Continual Learning

With the proliferation of smart devices, network security has become crucial to protect systems and data. In order to identify and categorise different network threats, this study introduces a flow-based Network Intrusion Detection System (NIDS) based on continual learning with a CNN backbone. Using the LYCOS-IDS2017 dataset, the study explores several continuous learning techniques for identifying threats including denial-of-service and SQL injection. Unlike previous approaches, this work treats intrusion detection as a multi-class classification problem, rather than anomaly detection. The findings show how continuously learning models may identify network intrusions with high recall rates and accuracy while generating few false alarms. This study contributes to the development of an adaptive NIDS that can handle attack classification simultaneously with detection, and that can be trained online without periodic offline training. Additionally, utilising the improved version of the dataset adds value to the research on LYCOS-IDS2017 by presenting results for untested models

MiR-27b targets PPARγ to inhibit growth, tumor progression, and the inflammatory response in neuroblastoma cells

The PPARγ nuclear receptor pathway is involved in cancer, but it appears to have both tumor suppressor and oncogenic functions. In neuroblastoma cells, miR-27b targets the 3′UTR of PPARγ and inhibits its mRNA and protein expression. miR-27b overexpression or PPARγ inhibition blocks cell growth in vitro and tumor growth in mouse xenografts. PPARγ activates expression of the pH regulator NHE1, which is associated with tumor progression. Lastly, miR-27b through PPARγ regulates NF-κB activity and transcription of inflammatory target genes. Thus, in neuroblastoma, miR-27b functions as a tumor suppressor by inhibiting the tumor-promoting function of PPARγ, which triggers an increased inflammatory response. In contrast, in breast cancer cells, PPARγ inhibits NHE1 expression and the inflammatory response, and it functions as a tumor suppressor. We suggest that the ability of PPARγ to promote or suppress tumor formation is linked to cell-type specific differences in regulation of NHE1 and other target genes

Improvement of the outcome of the saphenous vein graft when connected to the internal thoracic artery

Background: Since 2000, we have been grafting the right coronary artery system (RCAs) using the proximal portion of the right internal thoracic artery (RITA) as the inflow of the saphenous vein graft (SVG) to increase the number of patients undergoing beating heart complete myocardial revascularization. Methods: From 2000 to 2022, 928 consecutive patients underwent SVG on the RCAs. In 546 patients (58.8%), the inflow was the RITA (I-graft group), and in 382 patients (41.2%), the inflow was the aorta (Ao-graft group). The inclusion criteria were age ≤75 years, ejection fraction >35%, only one SVG per patient, bilateral internal thoracic arteries as a Y-graft on the left system (three-vessel disease, n = 817, 88.0%) or left internal thoracic artery on the left anterior descending artery and RITA + SVG on the RCAs (two-vessel disease, n = 111, 12.0%). Propensity matching identified 306 patients per group. After a median follow-up of 8 (5–10) years, graft patency was assessed by coronary computed tomographic angiography in 132 patients (64 in the I-graft group and 68 in the Ao-graft group). Results: Early results were similar in both groups. The I-graft group had higher 10-year survival and freedom from main adverse cardiac events (90.0 ± 2.0 vs. 80.6 ± 3.8, p = 0.0162, and 81.3 ± 2.7 vs. 64.7 ± 5.6, p = 0.0206, respectively). When RITA was the inflow, SVG had a higher estimated 10-year patency rate (82.8% ± 6.5 vs. 58.8% ± 7.4, p = 0.0026) and a smaller inner lumen diameter (2.7 ± 0.4 vs. 3.4 ± 0.6 mm, p < 0.0001). Conclusion: When the inflow is the RITA, SVG grafted to the RCAs (I-graft) may result in a higher patency rate and better outcome than when the inflow is the ascending aorta (Ao-graft). The continuous supply of nitric oxide by RITA may be the cause of the higher patency rate of the I-graft, which can behave like an arterial conduit

Profiling student smokers:a behavioral approach

The aim of the present study is to construct a coherent profile of student smokers in Greece, based on their behavioral and demographic characteristics. In this context, we collected data by administrating an anonymous self-completed questionnaire, which was answered by students of University and Technological Educational Institute (T.E.I.) of Patras. The final sample consists of 1,190 student smokers. For the purposes of the present study, principal component analysis was utilized to explore and detect the demographic and behavioral profiles of Greek student smokers. The factor solution identified 5 demographic factors and 14 behavioral factors. All factors were labeled, interpreted and discussed in the light of existing knowledge in order to understand better the consumer behavior of student smokers

Profiling student smokers:a behavioral approach

The aim of the present study is to construct a coherent profile of student smokers in Greece, based on their behavioral and demographic characteristics. In this context, we collected data by administrating an anonymous self-completed questionnaire, which was answered by students of University and Technological Educational Institute (T.E.I.) of Patras. The final sample consists of 1,190 student smokers. For the purposes of the present study, principal component analysis was utilized to explore and detect the demographic and behavioral profiles of Greek student smokers. The factor solution identified 5 demographic factors and 14 behavioral factors. All factors were labeled, interpreted and discussed in the light of existing knowledge in order to understand better the consumer behavior of student smokers

Changes of blood biochemistry in the rabbit animal model in atherosclerosis research; a time- or stress-effect

<p>Abstract</p> <p>Background</p> <p>Rabbits are widely used in biomedical research and especially as animal models in atherosclerosis studies. Blood biochemistry is used to monitor progression of disease, before final evaluation including pathology of arteries and organs. The aim of the present study was to assess the consistency of the biochemical profile of New Zealand White rabbits on standard diet from 3 to 6 months of age, during which they are often used experimentally.</p> <p>Methods and results</p> <p>Eight conventional male 3-month-old New Zealand White rabbits were used. Blood samples were taken at baseline, 1, 2 and 3 months later. Plasma glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol concentrations, and alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and malondialdehyde were measured. Statistically significant time-related changes were observed in glucose, total cholesterol and triacylglycerol, which were not correlated with aortic lesions at 6 months of age. Similarly, hepatic enzyme activity had significant time-related changes, without a corresponding liver pathology.</p> <p>Conclusions</p> <p>Age progression and stress due to single housing may be the underlying reasons for these biochemistry changes. These early changes, indicative of metabolic alterations, should be taken into account even in short-term lipid/atherosclerosis studies, where age and standard diet are not expected to have an effect on the control group of a study.</p

Comparative antilipidemic effect of N-acetylcysteine and sesame oil administration in diet-induced hypercholesterolemic mice

<p>Abstract</p> <p>Background</p> <p>There is an increasing number of novel antilipidemic therapies under consideration. The putative hypolipidemic effect of N-acetylcysteine (NAC) and sesame oil was studied in a mouse model of dietary-induced hypercholesterolemia.</p> <p>Methods</p> <p>Male C57bl/6 mice were assigned to the following groups: (NC) control group, (HC) group receiving test diet supplemented with 2% cholesterol and 0.5% cholic acid for 8 weeks, (HCN) group receiving the test diet with NAC supplementation (230 mg/kg p.o.) and (HCS) group fed the test diet enriched with 10% sesame oil. Total serum cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were assayed at the beginning and at the end of the experiment. Total peroxides and nitric oxide (NO) levels were measured in the serum at the end of the experiment. Hepatic and aortic lesions were evaluated by haematoxylin-eosin staining.</p> <p>Results</p> <p>Higher serum levels of total and LDL-cholesterol were recorded in all groups fed the high cholesterol diet. The HCN group presented reduced lipid levels compared to HC and HCS groups. No differences were observed between HCS and HC groups. Peroxide content in serum was markedly increased in mice consuming high cholesterol diet. NAC and sesame oil administration led to a significant decrease of serum lipid peroxidation in the levels of control group, whereas only NAC restored NO bioavailability. In terms of liver histology, the lesions observed in HCN group were less severe than those seen in the other high cholesterol groups.</p> <p>Conclusion</p> <p>Co-administration of NAC, but not sesame oil, restored the disturbed lipid profile and improved hepatic steatosis in the studied diet-induced hypercholesterolemic mice. Both agents appear to ameliorate serum antioxidant defense.</p

MicroRNA-124 Regulates STAT3 Expression and Is Down-regulated in Colon Tissues of Pediatric Patients With Ulcerative Colitis

Background & Aims - Altered levels and functions of microRNAs (miRs) have been associated with inflammatory bowel diseases (IBDs), although little is known about their roles in pediatric IBD. We investigated whether colonic mucosal miRs are altered in children with ulcerative colitis (UC). Methods - We used a library of 316 miRs to identify those that regulate phosphorylation of STAT3 in NCM460 human colonocytes incubated with interleukin-6. Levels of miR-124 were measured by real-time PCR analysis of colon biopsies from pediatric and adult patients with UC and patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza-2’-deoxycytidine. Methylation of the MIR124 promoter was measured by quantitative methylation-specific PCR. Results - Levels of phosphorylated STAT3 and the genes it regulates (encoding VEGF, BCL2, BCLXL, and MMP9) were increased in pediatric patients with UC, compared to control tissues. Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3 phosphorylation by ≥75% in NCM460 cells; miR-124 had the greatest effect. miR-124 was downregulated specifically in colon tissues from pediatric patients with UC and directly targeted STAT3 mRNA. Levels of miR-124 were decreased whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC, compared to those with inactive disease. Furthermore, levels of miR-124 and STAT3 were inversely correlated in mice with experimental colitis. Downregulation of miR-124 in tissues from children with UC was attributed to hypermethylation of its promoter region. Incubation of HCT-116 colonocytes with 5-aza-2’ deoxycytidine upregulated miR-124 and reduced levels of STAT3 mRNA. Conclusions - MiR-124 appears to regulate the expression of STAT3. Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3, which could promote inflammation and pathogenesis of UC in children