Background and Aim: Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and their hepatogenic differentiated cells (HDCs) can be applied for liver injury repair by tissue grafting. Regenerative potentiality in liver cirrhosis models was widely investigated; however, immunomodulation and anti-inflammation in acute hepatitis remain unexplored. This study aimed to explore the immunomodulatory and evaluate twice intravenous (IV) or intrahepatic (IH) administration of either BM-MSCs or middle-stage HDCs on aflatoxin (AF) acute hepatitis rat model. Materials and Methods: BM-MSCs viability, phenotypes, and proliferation were evaluated. Hepatogenic differentiation, albumin, and a-fetoprotein gene expression were assessed. AF acute hepatitis was induced in rats using AFB1 supplementation. The transplantation of BM-MSCs or their HDCs was done either by IV or IH route. Hepatic ultrasound was performed after 3-weeks of therapy. Cytokines profile (tumor necrosis factor-α [TNF-α], interleukin [IL]-4, and IL-10) was assessed. Hepatic bio-indices, serum, and hepatic antioxidant activity were evaluated, besides examining liver histological sections. Results: Acute AFB1 showed a significant increase in TNF-α (p<0.01), liver enzyme activities (p<0.05), as well as decrease in IL-4, IL-10, and antioxidant enzyme activities (p<0.05). Cytokines profile was ameliorated in groups treated with IV and IH BM-MCs, showed a negative correlation between IL-4 and TNF-α (p<0.05), and a positive correlation between IL-10 upregulation and TNF-α (p<0.01). In IV HDCs treated group, positive correlations between IL-4 and IL-10 downregulation and TNF-α were observed. However, in IH HDCs group, a significant positive correlation between IL-4 and IL-10 upregulation and TNF-α, were recorded (p<0.05). In addition, IV BM-MSCs and IH HDCs treatments significantly increased antioxidant enzymes activity (p<0.05). IV and IH BM-MSCs significantly ameliorated liver transaminase levels, whereas IH HDCs significantly ameliorated alanine aminotransferase activity and nitric oxide concentration (p<0.05). Conclusion: The administration routes of BM-MSCs did not demonstrate any significant difference; however, the IH route of HDCs showed significant amelioration from the IV route. On the other hand, it showed noticeable anti-inflammatory and immunomodulatory improvements in aflatoxicosis rats. Therefore, it can be concluded that acute hepatitis can be treated by a noninvasive IV route without the expense of hepatogenic differentiation. Further research using clinical trials that address several problems regarding engraftment and potentiation are needed to determine the optimal manipulation strategy as well as to achieve better long-term effects.

Hepatocellular carcinoma (HCC) continues to be a serious issue because of its high morbidity and mortality in the absence of early identification and proper treatment. Increasing evidence reveals that long non-coding RNAs (lncRNAs) and micro RNAS (miRNAs) interact to form a gene regulatory network. Their interactions lead to a variety of complex diseases, such as HCC. So, the current study aims to assess whether the interaction between "HOTAIR, HOTTIP, and H19 as lncRNAs and miRNA-152 as a miRNA" has a significant role in the progression of HCV-genotype (4) patients to hepatocellular carcinoma, in order to employ them as noninvasive prognostic and diagnostic epigenetic biomarkers. By using the online computational tools, we predict the group of miRNAs that may interact with the group of lncRNAs under this investigation. 133 subjects were included in this study. A total of 103 chronic hepatitis C patients were divided into two groups: Group I (chronic liver disease “CLD” without HCC, n = 65) was classified into two subgroups: non-cirrhotic (30) and cirrhotic (35); Group II (CLD with HCC, n = 38). A control (healthy volunteer, n = 30). The expressions of the studied genes were analysed by real-time PCR. The study of lncRNAs has shown a consistent reverse correlation with miRNA-152 in line with the progression of the disease, which leads us to suggest that they should be used as noninvasive prognostic biomarkers for HCV-induced liver cirrhosis and HCC in HCV Genotype 4 patients. MiRNA-152 is not the only one that can interact with the lncRNAs that have been investigated, but there are others, such as miRNA-19a and miRNA-106a, that should be considered.

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Introduction: Simvastatin belongs to statins drugs that are used globally for lowering blood cholesterol level in cardiovascular patients. Simvastatin can be considered as life threatening agent, since prolonged usage may cause myotoxicity. Materials & methods: The present study was performed on 20 adult male rats which were divided into: Group I which was the control group that did not receive any treatments, and Group II which was the treated group that received 80 mg/kg b.wt/day of simvastatin for 46 days. All rats were submitted to bone marrow collection for the cytogenetics tests and gastrocnemoius muscles' biopsied were taken for the histochemical tests. Results: statistical analysis showed a non-significant increase in the mean of chromosomal aberrations (CAs) in the treated rats' cells comparing to the control samples. On the other hand, an observed non-significant decrease in the mean of total proteins (TP) content in rats' gastrocnemius muscles of Group II when compared to the control group. Whereas, noticed significant reduction in the mean of glycogen (Glyc.) content in rats' gastrocnemius muscles of the same group when compared to the control group. Conclusion: Simvastatin may lead to an increase in the incidence of (CAs) in bone marrow cells, and determination of TP and Glyc. content in skeletal muscle biopsies can be considered as indicators for muscle necrosis incidence. Recommendations: Simvastatin has to be prescribed carefully in patients suffering from hypercholesterolemia, precautions have to be taken into consideration since it may affect skeletal muscles' health and lead to muscle toxicity on the short or long run of usage.