Background and Aim: Genetic factors play a significant role in the onset and progression of coronary artery disease (CAD). PIK3C2A may contribute to the development of acute coronary syndrome (ACS) by affecting blood glucose levels and oxidative stress. The expression levels of TXNIP were significantly higher in patients with unstable angina pectoris. However, the situation is different in ACS. In the current study, we aim to investigate the role of PIK3C2A and TXNIP as independent risk factors for chronic stable angina (CSA) and ACS. Subjects and Methods: This study involved 215 subjects (60 patients with CSA, 55 patients with ACS, and 100 controls). All subjects were exposed for assaying gene expressions of PIK3C2A and TXNIP by quantitative real-time polymerase chain reaction. Results: It was found that TXNIP was upregulated, whereas PIK3C2A was downregulated in patients with CAD compared to the control group. PIK3C2A was significantly downregulated in patients with ACS compared to that in patients with CSA (p < 0.001), but TXNIP was not (p = 0.7). TXNIP was significantly upregulated in STEMI-ACS patients compared to CSA (p = 0.045) and NSTEMI ACS (p = 0.046), among non-diabetic (p = 0.023) smokers (p = 0.036) with hypertension (p = 0.005) and hypercholesterolemia (p = 0.001). ROC (receiver operating characteristic) curve analysis revealed that PIK3C2A (0.981; p < 0.001; 98.18) was the most sensitive mRNA for discriminating ACS from control, followed by TXNIP (0.775; p < 0.001; 70.91). However, for discriminating ACS from CSA combined mRNAs, (PIK3C2A + TXNIP) (0.893; p < 0.001; 98.18) and PIK3C2A (0.892; p < 0.001; 81.82) are promising biomarkers. On the other hand, the most sensitive mRNA for differentiating CSA from control is mRNAs (PIK3C2A + TXNIP) (0.963; p < 0.001; 95), then TXINP (81.3; p < 0.001; 93.33), and finally, PIK3C2A (0.782; p < 0.001; 81.67). In the multivariate regression model, PIK3C2A ((p = 0.002), 0.118 (0.031–0.445)) and smoking status ((p = 0.034); 0.151 (0.026–0.866)) were independent variables for ACS. Moreover, PIK3C2A ((p < 0.013); 0.706 (0.614–0.812)), Hb ((p = 0.013); 0.525 (0.317–0.871)), and total cholesterol ((p = 0.04); 0.865 (0.784–0.955)) were significantly (p < 0.05) and independently related to the prognosis of CSA. Furthermore, PIK3C2A ((p = 0.002), 0.923 (0.877–0.971)), TXNIP ((p = 0.001); 2.809 (1.558–5.064)) the body weight ((p = 0.033); 1.254 (1.018–1.544)) were independently associated with CSA. Conclusions: Our study concluded that the dysregulated mRNA PIK3C2A and TXNIP gene expressions may be useful in diagnosis of CAD and prediction of ACS development.

Diabetic cardiomyopathy (DC) is a serious health issue. MicroRNA-155b expression dysregulation might be involved in the fibrotic cycle in DC. L-Arginine (l-arg) is reported to have a preferable impact on the cardiovascular system. We aimed to understand the pathogenesis of DC and to detect the potential protective effect of l-arg through modulation of apoptosis, inflammation, fibrosis, and miR-155b expression. This study comprised four groups of forty adult male rats (10 rats in each group): diabetics, l-arg diabetics, l-arg, and controls. Blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), body weight, and cardiac hypertrophy index (HW/BW ratio) were assessed. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) was done. Expressions of toll-like receptor-4 (TLR4), pro-inflammatory interleukin 1 beta (IL-1β), interleukin 6 (IL-6), anti-inflammatory interleukins (IL-4, IL-13), apoptotic markers (bcl-2, bax) and microRNA-155b were measured by real-time PCR. Myocardial light, electron microscopic and morphometric studies were performed. Results showed a significant decrease in cardiac hypertrophy (HW/BW = 0.0030 ± 0.0002 mg/g), echocardiographic parameters (LVEF = 54.12 ± 1.628% and LVFS = 20.40 ± 0.541%), hemodynamic parameters (HR = 411.0 ± 9.684 bpm, SBP/DBP = 84 ± 4.998/60 ± 3.062 mmHg) and downregulation of the expression of IL-4, IL-13, IL- 1β, IL-6 and TLR4 in the l-arg diabetic group compared to diabetic rats. Additionally, restoration of normal appearance of most cardiac myofibrils, intact blood vessels, decreased cardiac fibrosis and upregulation of bax expression were observed. Expression of microRNA-155b increased by 0.007 for each gram increase in blood glucose (>1.45, it showed 100% specificity and 96.7% sensitivity). In conclusion, microRNA-155b upregulation is associated with enhancement of the transcription of inflammatory cytokines and apoptotic genes. L-arginine may be a useful protective strategy for DC through modulation of apoptosis, inflammation, and fibrosis, in addition to regulating the expression of miR-155b.

Myocardial infarction (MI) is a fatal condition that causes damage to the heart muscle by abruptly stopping blood flow and oxygenation. Mitochondrial transcription factor A (TFAM) and mitochondrial DNA copy number (mtDNA CN) show an increased rate of association with development of several human diseases and malignancies. This paper, therefore, aims to identify the possible relation among mtDNA CN and its regulating gene TFAM (expression of the gene and rs1937 polymorphism) as markers in myocardial infarction among Egyptians. A total of 200 participants were enrolled and divided into two groups. Group 1 included 100 myocardial infarction patients with ST-segment elevation (STEMI) recruited from from the Coronary Care Unit (CCU) of Menoufia University Hospitals, while group 2 included 100 Controls. Blood samples were collected from all participants immediately after diagnosis of MI and before beginning therapy. TFAM SNP (rs1937) was determined by the allelic discrimination TaqMan technique, and mtDNA CN and TFAM gene expression were detected using real-time quantitative PCR in 100 MI patients and 100 controls. TFAM mRNA expression and mtDNA copy number were profoundly reduced in MI patients than controls. Analysis of genotype showed that the TFAM rs1937 variant distribution was in Hardy-Weinberg equilibrium. The C allele and the GC genotype were substantially more frequent in the patients’ cohort (p = 0.006 and 0.005, respectively). The GC genotype of the TFAM polymorphism (rs1937) showed a preliminary association with MI in STEMI patients. Limitations of this study are the absence of longitudinal pre-MI or post-recovery data. TFAM mRNA expression and mtDNA copy number were measured in whole blood without adjustment for leukocyte subpopulations or platelet counts. Small number of C carriers of TFAM rs1937 variant and absence of CC genotype limited statistical power and requires replication in larger Egyptian cohort. These findings suggest that decreased TFAM gene expression and mtDNA CN were significant biomarkers associated with acute myocardial infarction in STEMI patients.

Gastric cancer ranks fourth in both incidence and mortality worldwide. Several genes influence its genesis and progress. The expression of MBNL3, PXN genes, and lncRNA PXN-AS1-L was evaluated in gastric tissue samples from 75 gastric cancer patients and 75 controls by RT-PCR. MBNL3, PXN, and lncRNA PXN-AS1-L expressions were considerably raised among cancerous gastric tissue than in nearby normal tissue and normal tissue from controls (p < 0.001). LncRNA PXN-AS1-L and MBNL3 had the highest sensitivity (92.00 % and 90.67 %, respectively), with PXN sensitivity of 81.33 % for differentiation of the cancer tissue from adjacent normal tissue, while PXN and lncRNA PXN-AS1-L had the highest sensitivity (98.67 % and 92.00 %, respectively), with 89.33 % for MBNL3 as discriminators between gastric cancer tissue and normal tissue from controls. Between metastatic and non-metastatic patients, MBNL3 and PXN were the highest differentiating markers (sensitivity = 87.50 % and 83.33 %, respectively). MBNL3, PXN, and lncRNA PXN-AS1-L were reliable predictors of gastric cancer (p = 0.004, p = 0.009, and p = 0.001, respectively), but only MBNL3 and lncRNA PXN-AS1-L were significant predictors for mortality (p = 0.026 and p = 0.043, respectively). The elevated expressions were linked to lower overall and progression-free survival rates. MBNL3, PXN, and lncRNA PXN-AS1-L expression levels can diagnose and predict gastric cancer and discriminate between metastatic and non-metastatic patients. The expression level of MBNL3 and lncRNA PXN-AS1-L can predict gastric cancer mortality. Higher expression of MBNL3 and PXN was linked to aggressive gastric cancer and low overall and progression-free survival rates.

Background: The most prevalent autoimmune thyroid condition, Hashiomoto’s Thyroiditis (HT), affects around 10% of people globally. This study investigates the expression of two genes: interferon gamma gene (IFNG) and zinc finger and AT-hook domain containing gene (ZFAT) with their long noncoding RNAs: interferon gamma antisense RNA 1 (IFNG-AS1) and Zinc finger antisense 1 (ZFAT-AS1) respectively in peripheral blood from HT cases and controls. Methods: Patients from the Menoufia University Hospitals’ Internal Medicine and Endocrinology Department participated in our case-control study. Seventy five HT patients and seventy five controls provided blood specimens. All subjects had their serum thyroglobulin antibody (anti-TG), thyroid peroxidase antibody (anti-TPO), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and lipid profile evaluated. Real-time PCR was used to measure IFNG, lncRNA IFNG-AS1, ZFAT, and lncRNA ZFAT-AS1 expressions. Results: Body mass index, triglycerides, low-density lipoprotein cholesterol (LDLc), total cholesterol, TSH, anti-TG, anti-TPO levels, lncRNA IFNG-AS1, lncRNA ZFAT-AS1 and IFNG expression levels were significantly elevated in HT cases. High-density lipoprotein cholesterol (HDLc), free T3, free T4 and ZFAT expression levels were considerably lower in patients. Among the studied markers, IFNG showed the highest diagnostic sensitivity, followed by lncRNA IFNG-AS1 in discriminating HT cases from controls. In HT cases, IFNG showed significant positive correlations with anti-TPO and lncRNA IFNG-AS1. IFNG, lncRNA IFNG-AS1, ZFAT and lncRNA ZFAT-AS1 were significant independent predictors for HT. Conclusions: HT was significantly associated with upregulated IFNG, lncRNA IFNG-AS1 and lncRNA ZFAT-AS1 with downregulated ZFAT gene, so they can be potently used as independent diagnostic and predictor markers for HT. Expression of the studied genes was correlated with thyroid autoantibodies and seem to be directly engaged in Hashimoto’s thyroiditis pathogenesis.