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BACKGROUND: Prostate cancer is known as one of the most prevalent health disorders in the male population globally. The aim of the current study was to evaluate the effects of separate and concomitant use of MK-2206 and salinomycin on prostate cancer cell line. METHODS: The antitumor potential of separate and concomitant use of MK-2206 and salinomycin was evaluated in a panel of prostate cancer cell line (PC-3). To get insights into the underlying mechanism of action, different assays including the rate of apoptosis, cell viability, and gene expression were performed in treated prostate cancer cells. RESULTS: A significant reduction was detected in the viability percentage of prostate cancer cells (p< 0.001) and the rate of Akt expression (p< 0.001) in all salinomycin, MK-2206, and salinomycin+MK-2206 groups compared to the negative control group. Furthermore, in comparison with the negative control group, there was a notable increase in both the rate of Bad expression (p< 0.001) and prostate cancer cells apoptosis after salinomycin, MK-2206, and salinomycin+MK-2206 treatments. Moreover, the concomitant use of salinomycin+MK-2206 revealed synergistic improvements regarding the viability of prostate cancer cells and the rate of the Akt and Bad expressions compared to the separate administration of salinomycin and MK-2206 (all p< 0.05) CONCLUSION: The findings of the present study may contribute to improving the efficacy of the therapies regarding the management of prostate cancer and providing a beneficial strategy in clinical trials.

Due to the rising prevalence of metabolic disorders, including type 2 diabetes (T2DM), new prevention and treatment strategies are needed. The aim was to examine the effect of astaxanthin (AST) on the major regulatory metabolism pathway SIRT-MAPK and fatty acid (FA) profile of plasma in patients with T2DM. This clinical trial included 68 T2DM patients randomly assigned to receive 10 mg/day of oral AST (n = 34) or placebo (n = 33) for 12 weeks. The expression level of SIRT1, AMPK activity, and the level of fatty acids in the serum were examined. The results showed that AST could modify the serum levels of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), particularly that of Arachidonic acid, from 11.31±0.35 to 8.52±0.72 %. Also, AST increased the expression and activity levels of SIRT1 and AMPK, respectively. Pearson analysis also revealed a significant association between AMPK activity and Linoleic acid serum (LA) levels (~ -0.604, p~0.013). AST can modify the FA profile of plasma by inducing metabolizing cells to uptake them. Also, it can activate the SIRT-AMPK pathway related to metabolism regulation., EXCLI Journal; 22:Doc502; ISSN 1611-2156

Marjan Tajik Kord,1 Fatemeh Pourrajab,1,2 Seyedhossein Hekmatimoghaddam3,4 1Department of Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 3Yazd Cardiovascular Research Center, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 4Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranCorrespondence: Seyedhossein Hekmatimoghaddam Tel + 0098-9133518314Fax + 0098-3517256458Email shhekmati2002@yahoo.comPurpose: There are two signal transduction pathways related to glucose metabolism in C2C12 mouse myoblast cells; one through AMP-activated protein kinase (AMPK), and the other through phosphoinositide 3-kinase (PI3K). Ginger is reported to have hypoglycemic effects. The aim of this study was to determine the exact mechanism of action of ginger in those pathways.Methods: C2C12 cells were seeded to four separate experimental groups; Control: treated with 50 μg/mL DMSO in the absence of any inhibitor; Treatment 1: treated with 50 μg/mL ethyl acetate ginger extract without any inhibitor; Treatment 2: treated with 50 μg/mL extract in the presence of 20 μM AMPK inhibitor; Treatment 3: treated with 50 μg/mL extract in the presence of 25 μM PI3K inhibitor. The amount of GLUT-4 protein (an important glucose transporter) was determined in cytosolic and membrane fractions using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting.Results: GLUT-4 concentration was significantly higher in the membrane fraction of cells treated with ethyl acetate ginger extract in the absence of any inhibitor in comparison with cells treated with this extract in the presence of each of the inhibitors (P-value < 0.05). GLUT-4 quantity in the membrane fractions in all groups was more than cytosolic fractions. The amount of GLUT-4 in membrane fraction of treated cells in the presence of PI3K inhibitor was higher than in the cells treated with this extract in the presence of AMPK inhibitor (P-value < 0.05).Conclusion: Ethyl acetate ginger extract affects the amount of GLUT-4 protein in membrane and cytosolic fractions of C2C12 myoblast cells mostly through AMPK pathway but less via PI3K.Keywords: glucose, metabolism, myoblasts, signal transduction

Fatemeh Pourrajab,1,2 Mohamad Reza Zare-Khormizi,3 Seyedhossein Hekmatimoghaddam,4,5 Azam Sadat Hashemi4,6 1Nutrition and Food Security Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2Department of Clinical Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 3School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 4Hematology & Oncology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 5Department of Laboratory Sciences, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 6Department of Pediatrics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranCorrespondence: Seyedhossein HekmatimoghaddamDepartment of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranTel +0098(913)3518314Email shhekmati2002@yahoo.comAzam Sadat HashemiDepartment of Pediatrics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranTel +0098(913)1532465Email drazamhashemi@yahoo.comAbstract: Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabolites impart unique properties in the interaction with each of the intracellular targets and metabolic enzymes whereby resulting in unique clinical activity. To date, most of the combinations have used a targeted agent combined with standard agents such as anthracyclines, cytarabine, or hypomethylating agents to improve the outcome. Rational combinations of DNA damage-inducing therapies with DNA methyltransferase and histone deacetylase inhibitors synergistically enhance the DNA damage, growth inhibition and apoptosis of myeloid cells. This review makes a thorough look at current antineoplastic agents for AML with emphasis on its genetics and molecular mechanisms of action and the role of combination regimens.Keywords: antineoplastic agents, drug therapy, combination, genetics, leukemia, myeloid, acute, molecular targeted therapy

Over the past years, several zoonotic viruses have crossed the species barrier into humans and have been causing outbreaks of severe, and often fatal, respiratory illness. The 21st century has seen the worldwide spread of three recognized coronaviruses (CoVs) which can cause pneumonia and severe acute respiratory symptoms (SARSs), SARS, MERS, and recently SARS-CoV-2. Herein, it is raising concerns about the dissemination of another new and highly lethal pandemic outbreak. Preparing for a pandemic outbreak involves a great deal of awareness necessary to stop initial outbreaks, through recognizing the molecular mechanisms underlying virus transmission and pathogenicity. CoV spike protein S is the key determinant of host tropism and viral pathogenicity which can undergo variations and makes the CoV a highly pathogenic and diffusible virus capable of sustained human-to-human transmission and spread easily. The three mentioned CoVs exhibit some similarities in S protein whereby constitute a promising target for the development of prophylactics and therapeutics in the future.

Fatemeh Pourrajab,1,2 Mohamad Reza Zare-Khormizi,3 Azam Sadat Hashemi,4 Seyedhossein Hekmatimoghaddam4,5 1Department of Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2Nutrition and Food Security Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 3School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 4Hematology & Oncology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 5Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranCorrespondence: Fatemeh PourrajabDepartment of Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8915173149, IranEmail mina_poorrajab@yahoo.comAbstract: The most common acute leukemia in adults is acute myeloid leukemia (AML). The pathophysiology of the disease associates with cytogenetic abnormalities, gene mutations and aberrant gene expressions. At the molecular level, the disease manifests as changes in both epigenetic and genetic signatures. At the clinical level, two aspects of AML should be taken into account. First, the molecular changes occurring in the disease are important prognostic and predictive markers of AML. Second, use of novel therapies targeting these molecular changes. Currently, cytogenetic abnormalities and molecular alterations are the common biomarkers for the prognosis and choice of treatment for AML. Finding a panel of multiple biomarkers is a crucial diagnostic step for patient classification and serves as a prerequisite for individualized treatment strategies. Furthermore, the most important way of identifying relevant targets for new treatment approaches is defining specific patterns or a spectrum of driver gene mutations occurring in AML. Then, an algorithm can be established by the use of several biomarkers, to be used for personalized medicine. This review deals with molecular alterations, risk stratification, and relevant therapeutic decision-making in AML.Keywords: acute myeloid leukemia, AML, genetic characterization, risk stratification

Human mesenchymal stem cells (hMSCs) have remarkable potential for use in regenerative medicine. However, one of the great challenges is preserving their potency for long time. This study investigated the effect of miRNA ectopic expression on their proliferation and also on the expression level of Parp1 as an epigenetic switch preserving pluripotency in hMSCs. A cationic liposome was prepared as an efficient carrier for miRNA delivery. The miRNA loading efficiency and physical stability of vesicles were measured, and their scanning electron microscopic shapes determined. hMSCs were transfected with miR-302a and miR-34a followed by assessment of their proliferation potency with MTT assay and measurement of the expression of Parp1 by quantitative polymerase chain reaction (QPCR). Cell transfection with miR-302a and miR-34a efficiently and differentially affects the proliferation potency of hMSCs and the expression level of Parp1 as the key epigenetic factor involved in pluripotency. While miR-302a increases Parp1 expression, miR-34a suppresses it significantly, showing differential effects. Our results demonstrated that miRNA-based treatments represent efficient therapeutic systems and hold a great promise for future use in regenerative medicine through modification of hMSC pluripotency and epigenome., EXCLI Journal;Vol. 17 2018