The public health crisis of the novel coronavirus disease (COVID-19) is alarming since January 2020. COVID-19 genome (SARS-CoV-2) is related to other highly pathogenic coronaviruses SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus). Amino acid substitutions in some of SARS-CoV-2 proteins resulted in mutations proposing more virulent and contagious properties for this novel virus. Coronavirus penetrates the host cell via endocytosis and once infected, immune responses are triggered to fight against the pathogen. Innate immune response activates major transcription factors to secrete proinflammatory cytokines and type 1 interferon response (T1INF) to induce antiviral immunity. While adaptive immunity initiates cascade of B-cells antibody mediated and T-cells cellular mediate immunities, several mechanisms are raised by SARS-CoV-2 to evade host immune response. Consequently, a surge of proinflammatory cytokines, known as cytokine storm (CS) are released. Failure to manage CS results in several pathological complications as acute respiratory distress syndrome (ARDS). Although researches have not discovered an effective treatment against SARS-CoV-2, recent therapeutic approaches recommending the use of anti-inflammatories in combination with antivirals and some repurposed drugs for COVID-19 patients. Future medications should be designed to target essential hallmarks in the CS to improve clinical outcomes.
Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel.
BackgroundEarly detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this poorly diagnosed widely-spread disease. Dysregulation in microRNA (miRNAs) expression is associated with HCC progression. MethodsThe objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE- miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424 and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV and 72 HCV-associated HCC patients using real time PCR (qPCR).ResultsThere was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. While miR-199a and miR-183 showed differential expression in cirrhotic relative to non-cirrhotic patients. A panel of 5 miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity).ConclusionMiR-142, miR-183, miR-199a, miR-224 and miR-424 novel panel could serve as non-invasive biomarker for HCC early prediction in chronic HCV patients.
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