Role of MAML1 in targeted therapy against the esophageal cancer stem cells

Abstract Background Esophageal cancer is the sixth-leading cause of cancer-related deaths worldwide. Cancer stem cells (CSCs) are the main reason for tumor relapse in esophageal squamous cell carcinoma (ESCC). The NOTCH pathway is important in preservation of CSCs, therefore it is possible to target such cells by targeting MAML1 as the main component of the NOTCH transcription machinery. Methods In present study we isolated the CD44+ ESCC CSCs and designed a MAML1-targeted therapy to inhibit the NOTCH signaling pathway. CSCs were isolated using magnetic cell sorting utilizing the CD44 cell surface marker. Several stem cell markers were analyzed in the levels of protein and mRNA expression. The isolated CSCs were characterized in vivo in NUDE mice. Biological role of MAML1 was assessed in isolated CD44+ CSCs. A drug resistance assay was also performed to assess the role of MAML1 in CD44+ CSCs with 5FU resistance. Results The CD44+ CSCs had ability to form tumors in NUDE mice. MAML1 silencing caused a significant decrease (p = 0.019) and ectopic expression caused a significant increase in migration of CD44+ CSCs (p = 0.012). Moreover, MAML1 silencing and ectopic expression significantly increased and decreased 5FU resistance, respectively (p < 0.05). MAML1 silencing significantly increased the number of cells in G1 phase (p = 0.008), and its ectopic expression significantly increased the number of CD44+ CSCS in S phase (p = 0.037). Conclusions MAML1 may be utilized for targeted therapy with a low side effect to eliminate the CD44+ CSCs through inhibition of canonical NOTCH pathway in ESCC patients

Efficacy of an herbal compound in decreasing steatosis and transaminase activities in non-alcoholic fatty liver disease: Efficacy of an herbal compound in decreasing steatosis and transaminase activities in non-alcoholic fatty liver disease

Hepatoprotective effects of many herbal agents have been reported in animal studies and clinical trials. In this study, five hepatoprotective plants with potent antioxidant, anti-inflammatory, and hypolipidemic effects were chosen to prepare a polyherbal compound for managing NAFLD. Sixty patients with NAFLD were randomly divided into treatment and control groups (2:1 ratio). Both group were advised to take healthy diet and exercise. The treatment group also received herbal capsules containing 400 mg of the mixture of&nbsp;Anethum graveolens,&nbsp;Citrus aurantium,&nbsp;Cynara scolymus, Portulaca oleracea, and&nbsp;Silybum marianum&nbsp;(2 capsules, thrice daily, for two months). The liver ultrasound and biochemical markers including the serum lipids, liver enzymes, and glucose were evaluated before starting the study and at the end of the treatment. Thirty patients in the treatment group and sixteen patients in the control group completed the study. The herbal compound significantly decreased the serum level of alanine transaminase (ALT), aspartate transaminase (AST), and total cholesterol. Treatment with the herbal compound significantly improved the grade of the fatty liver, but no significant change was found in the control group. In conclusion, the formulated herbal compound appeared to be effective in biochemical improvement and decreasing the grade of the fatty liver in the patients with NAFLD

Effect of vitamin D supplementation on chronic liver disease: systematic literature review

Introduction: It is long known that vitamin D deficiency was common in patients with liver disease, but little is known on the therapeutic effects of vitamin D, especially in patients with chronic liver disease. In this study, we aimed to systematically review the literatures and study the evidences in which the effects of vitamin D supplementation had been investigated on the severity of chronic liver disease or liver cirrhosis.Methods: A systematic literature search was performed by using the following key terms “vitamin D supplementation” and “chronic liver disease” in the PubMed, Scopus and Google scholar to find relevant articles. After collecting the eligible documents, data were extracted and described based on the purpose of this review.Result: Of total 196 articles found, only 7 relevant documents with 518 studied patients were included. The results of this study showed that the levels of 25(OH) D were considerably lower in patients with chronic liver disease. Findings showed that vitamin D supplementation can rise up the mean serum level of 25(OH) D in patients with severe vitamin D deficiency, especially patients with liver cirrhosis.Conclusion:The results of this review showed that vitamin D deficiency is associated with the severity of liver disease and may have prognostic value in the assessment of liver disease. Also, it was shown that vitamin D supplementation may be helpful for the treatment of liver disease at least in certain groups of patients