No abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the major seeds of liver cirrhosis and hepatocellular carcinoma. There is no convenient reliable non-invasive early diagnostic tool available for NAFLD/NASH diagnosis and stratification. Recently, the role of cytosolic sensor, stimulator of interferon genes (STING) signaling pathway in pathogenesis of nonalcoholic steatohepatitis (NASH) has been evidenced in research. We have selected EDN1/TNF/MAPK3/EP300/hsa-miR-6888-5p/lncRNA RABGAP1L-DT-206 RNA panel from bioinformatics microarrays databases related to STING pathway and NAFLD/NASH pathogenesis. We have used reverse-transcriptase real-time polymerase chain reaction to assess the expression of the serum RNAs panel in NAFLD/NASH without suspicion of advanced fibrosis, NAFLD/with NASH patients with suspicion of advanced fibrosis and controls. Additionally, we have assessed the diagnostic performance of the Ribonucleic acid (RNA) panel. We have detected upregulation of the EDN1 regulating RNAs panel expression in NAFLD/NASH cases compared to healthy controls. We concluded that this circulatory RNA panel could enable us to discriminate NAFLD/NASH cases from controls, and also NAFLD/NASH cases (F1, F2) from advanced fibrosis stages (F3, F4).

Background: Non-alcoholic steatohepatitis ((NASH) is the progressive form of (non-alcoholic fatty liver disease) (NAFLD), which can progress to liver cirrhosis and hepatocellular carcinoma. There is no available reliable non-invasive diagnostic tool to diagnose NASH, and still the liver biopsy is the gold standard in diagnosis. In this pilot study, we aimed to evaluate the Nod-like receptor (NLR) signaling pathway related RNA panel in the diagnosis of NASH. Methods: Bioinformatics analysis was done, with retrieval of the HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA panel based on the relation to the NLR-signaling pathway. Hepatitis serum markers, lipid profile, NAFLD score and fibrosis score were assessed in the patients’ sera. Reverse transcriptase real time polymerase chain reaction (RT-PCR) was done to assess the relative expression of the RNA panel among patients who had NAFLD without steatosis, NAFLD with simple steatosis, NASH and healthy controls. Results: We observed up-regulation of Lnc-SPARCL1-1:2 lncRNA that led to upregulation of miR-6881-5P with a subsequent increase in levels of HSPD1, MMP14, and ITGB1 mRNAs. In addition, ROC curve analysis was done, with discriminative cutoff values that aided discrimination between NASH cases and control, and also between NAFLD, simple steatosis and NASH. Conclusion: This pilot study concluded that HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 panel expression has potential in the diagnosis of NASH, and also differentiation between NAFLD, simple steatosis and NASH cases.

Objectives. This study evaluated the clinical manifestation of COVID-19 and adverse outcomes in patients with comorbidities (outcome: death). Methods. A comparative follow-up investigation involving 148 confirmed cases of COVID-19 was performed for a month (between April and May 2020) at Qaha Hospital to describe the clinical characteristics and outcomes resulting from comorbidities. Participants were divided into two clusters based on the presence of comorbidities. Group I comprised cases with comorbidities, and Group II included subjects without comorbidity. Survival distributions were outlined for the group with comorbidities after the follow-up period. Results. Fever (74.3%), headache (78.4%), cough (78.4%), sore throat (78.4%), fatigue (78.4%), and shortness of breath (86.5%) were the most prevalent symptoms observed in COVID-19 patients with comorbidities. Such patients also suffered from acute respiratory distress syndrome (37.8%) and pneumonia three times more than patients without comorbidities. The survival distributions were statistically significant (chi-square = 26.06, p ≤ 0.001 ). Conclusion. Multiple comorbidities in COVID-19 patients are linked to severe clinical symptoms, disease complications, and critical disease progression. The presence of one or more comorbidities worsened the survival rate of patients.

Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (HSPD1/TNF/MMP14/ITGB1) mRNAs and their upstream noncoding RNA regulators (miRNA-6881-5P and lnc-SPARCL1-1:2) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (HSPD1/TNF/MMP14/ITGB1) mRNAs and their epigenetic regulators (miRNA-6881-5P and lnc-SPARCL1-1:2). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (HSPD1, TNF, MMP14, and ITGB1) mRNAs—(miRNA-6881-5P—(lnc-SPARCL1-1:2) RNA panel.