Experimental investigation for nonalcoholic fatty pancreas management using probiotics.

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) presents a pressing challenge within the domain of metabolic disorders, necessitating further exploration to unveil its molecular intricacies and discover effective treatments. Our focus was to delve into the potential therapeutic impact of ZBiotic, a specially engineered strain of probiotic B. subtilis, in managing NAFP by targeting specific genes linked with necroptosis and the TNF signaling pathway, including TNF, ZBP1, HSPA1B, and MAPK3, along with their upstream epigenetic regulator, miR-5192, identified through bioinformatics. METHODS: Rats were subjected to either a standard or high-fat, high-sucrose diet (HFHS) for eight weeks. Subsequently, they were divided into groups: NAFP model, and two additional groups receiving daily doses of ZBiotic (0.5 ml and 1 ml/kg), and the original B. subtilis strain group (1 ml/kg) for four weeks, alongside the HFHS diet. RESULTS: ZBiotic exhibited remarkable efficacy in modulating gene expression, leading to the downregulation of miR-5192 and its target mRNAs (p < 0.001). Treatment resulted in the reversal of fibrosis, inflammation, and insulin resistance, evidenced by reductions in body weight, serum amylase, and lipase levels (p < 0.001), and decreased percentages of Caspase and Nuclear Factor Kappa-positive cells in pancreatic sections (p < 0.01). Notably, high-dose ZBiotic displayed superior efficacy compared to the original B. subtilis strain, highlighting its potential in mitigating NAFP progression by regulating pivotal pancreatic genes. CONCLUSION: ZBiotic holds promise in curbing NAFP advancement, curbing fibrosis and inflammation while alleviating metabolic and pathological irregularities observed in the NAFP animal model. This impact was intricately linked to the modulation of necroptosis/TNF-mediated pathway-related signatures.

Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model.

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis. METHODS: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding. RESULTS: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals. CONCLUSION: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.

Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis. METHODS: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding. RESULTS: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals. CONCLUSION: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.

Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death.

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.

Circulatory Endothelin 1-Regulating RNAs Panel: Promising Biomarkers for Non-Invasive NAFLD/NASH Diagnosis and Stratification: Clinical and Molecular Pilot Study.

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).

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study.

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.

The Impact of Comorbidities on the Outcomes of Egyptian COVID-19 Patients: A Follow-Up Study.

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.