الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
The prevalence of nonalcoholic steatohepatitis (NASH) is increasing over time and is rapidly becoming one of the most chronic liver diseases. Accumulating data showed that changes in the gut microbiota and Hippo signaling pathway dysregulation along with epigenetic, and genetic modulation are implicated in NASH pathogenesis. Therefore, the present study aimed to utilize bioinformatics to construct a genetic-epigenetic RNA panel targeting the Hippo signaling pathway and related to hepatocyte regeneration in NASH pathogenesis. As well as, to establish an experimental NASH animal model to evaluate the prophylactic efficacy of gut microbiota-based treatments and their potential modulatory effects on the generated co-regulatory RNA panel in NASH animals. At First, different databases were used at both genetic and epigenetic levels, as a consequence, mRNA (YAP1, LATS1, and NF2) – miRNA (miR-1205) – lncRNA (SRD5A3-AS1) co-regulatory panel was constructed. Histopathological, biochemical, molecular and immunohistochemistry analyses were then used to investigate the effects of multi-strain probiotic mixture “Flora 20–14 Ultra Strength” or prebiotic inulin fiber “Greena” on high sucrose high fat (HSHF) diet-induced NASH in rats. These treatments were administered daily either alone or together, along with the HSHF diet for 12 weeks. The data revealed that gut microbiota-based treatments had the ability to modulate the expression of the constructed RNA panel through YAP1 mRNA and miR-1205 downregulation and LATS1 and NF2 mRNAs, and lncRNA SRD5A3-AS1 upregulation. Moreover, the applied treatments could ameliorate both liver functions and lipid panel, and thereby ameliorated inflammation and fibrosis, that reflected by decreased levels of hepatic IL6 and TGFβ1. Such explanation was also confirmed from the results of the histological and immunohistochemistry studies where a significant reduction in α-SMA together with a noticeable increase in LATS1/2 protein expression levels were detected in liver sections of treated animals compared to the untreated NASH controls. In conclusion, gut microbiota-based treatments were efficient to restrict cell proliferation and diminish the metabolic and pathological disturbances observed in the applied NASH animal model. The observed effects were correlated with modulation of the retrieved Hippo signaling pathway-related RNA panel.