Inverse relationship between the level of miRNA 148a-3p and both TGF-ß1 and FIB-4 in hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a major health burden globally. Dysregulation of miRNA 148a-3p is engaged in carcinogenesis. TGF-ß is a profibrogenic cytokine. This study assesses the expression level of miRNA 148a-3p and its relationship with serum TGF-ß1 and fibrosis index based on four factors (FIB-4) in Egyptian patients with HCV-associated HCC. SUBJECTS: and Methods: The study included 72 HCC patients with HCV, 48 HCV cirrhotic patients, and 47 healthy controls. Serum TGF-ß1 was assessed by ELISA and the expression of miRNA 148a-3p was measured by RT-PCR. RESULTS: Patients with HCC had lower plasma miRNA 148a-3p, higher serum TGF-ß1, and higher FIB-4 levels than patients with cirrhosis and controls. miRNA 148a-3p discriminated HCC either from control (AUC: 0.997, 95.83% sensitivity, 85.11% specificity) or from cirrhosis (AUC: 0.943, 91.67% sensitivity, 81.25% specificity). Moreover, it distinguished metastatic from nonmetastatic patients (AUC: 0.800, 88.89% sensitivity, 60.0% specificity). The decreased miRNA 148a-3p and the increased TGF-ß1 levels were related to distant metastasis, multinodular lesions, advanced TNM stage, and BCLC score (C). A negative correlation between miRNA 148a-3p and each of FIB-4 and TGF-ß1 was detected. The decreased miRNA 148a-3p was associated with poor overall survival and poor progression-free survival. CONCLUSION: An inverse relationship between miRNA 148a-3p and both TGF-ß1 and FIB-4 was observed, which could be involved in HCC pathogenesis. Moreover, this miRNA is a potential diagnostic and prognostic biomarker for HCC.

Evaluation of Serum Total Immunoglobulin E, Interleukin-17 and Pentraxin-3 as Biomarkers for Chronic Rhinosinusitis With Nasal Polyposis.

BACKGROUND: Different biomarkers are detectable in cases of chronic rhinosinusitis with nasal polyposis (CRSwNP) with need for evaluation of their diagnostic and prognostic roles. OBJECTIVE: To assess the serum levels of total IgE, interleukin-17 and Pentraxin-3 in patients with CRSwNP and correlate them with the clinical evaluation using Sino-Nasal Outcome Test (SNOT-22), radiological evaluation using Lund - Mackay (LM) computed tomography scan score, and polyposis recurrence. METHODS: This cross-sectional comparative study was carried out on fifty patients with CRSwNP and twenty-five age and gender matched healthy volunteers as control group. Patients were assessed clinically by SNOT-22 and radiologically by LM score. Blood samples of patients and controls were analyzed for serum levels of total immunoglobulin E (IgE), Interleukin-17 (IL-17) and Pentraxin-3 (PTX-3). The correlation between the serum levels of every two markers of the study markers was assessed. The levels of the three biomarkers were correlated with SNOT-22 and LM scores and polyp recurrence with assessment of their sensitivity and specificity to diagnose CRSwNP. RESULTS: This study showed significantly higher values of the three biomarkers in patients group compared with control group (p < 0.001 for all). There were significant positive correlations between the levels of the three markers and SNOT 22 and LM scores (p < 0.001 for all) and with recurrence of polyposis (p < 0.001, p = 0.005 and p = 0.032 respectively). Agreement (sensitivity and specificity) for these markers to diagnose patient group was statistically significant (p < 0.001 for all). There was a significant positive correlation between every two markers of the study markers. CONCLUSION: Serum levels of total IgE, IL-17 and PTX-3 are important biological markers for diagnosis and follow up of cases of CRSwNP with high sensitivity and specificity in detection of such cases. They should be included in the routine laboratory workup for cases of CRSwNP.

The Human Genetic Variants CYP2J2 rs2280275 and EPHX2 rs751141 and Risk of Diabetic Nephropathy in Egyptian Type 2 Diabetic Patients.

BACKGROUND: Diabetic nephropathy (DN), the primary driver of end-stage kidney disease, is a problem with serious consequences for society's health. Single nucleotide polymorphisms (SNPs) can define differences in susceptibility to DN and aid in development of personalized treatment. Giving the importance of epoxyeicosatrienoic acids (EETs) in kidney health, we aimed to study the association between two SNPs in the genes controlling synthesis and degradation of EETs (CYP2J2 rs2280275 and EPHX2 rs751141 respectively) and susceptibility of type 2 diabetes mellitus (T2DM) patients to develop DN. PATIENTS AND METHODS: Two hundred subjects were enrolled and categorized into three groups: group I (80 T2DM patients with DN), group II (60 T2DM patients without DN) and group III (60 healthy controls). Urea, creatinine, albumin/creatinine ratio (ACR), and eGFR were measured for all participants. Genotyping of CYP2J2 rs2280275 and EPHX2 rs751141 was done by real time PCR. RESULTS: There was no significant difference between the studied groups regarding CYP2J2 rs2280275. In contrast, EPHX2 rs751141 was associated with increased risk of DN under a dominant model (GG vs GA+AA: OR=0.375; 95% CI (0.19-0.75), P=0.006) in unadjusted model and after adjustment for age and sex (OR=0.440; 95% CI (0.21-0.92), P=0.029), recessive model (AA vs GG+GA: OR=0.195; 95% CI (0.05-0.74), P=0.017) and additive model (GA vs GG+AA): OR=0.195; 95% CI (0.05-0.74), P=0.017). CONCLUSION: CYP2J2 rs2280275 was not associated with DN predisposition. However, EPHX2 rs751141 could be a genetic marker for development and progression of DN among Egyptian T2DM patients.