Identification of miRNA signatures and their therapeutic potentials in prostate cancer

Molecular Biology Reports - Herein, we identified miRNA signatures that were able to differentiate malignant prostate cancer from benign prostate hyperplasia and revealed the therapeutic potential...     

Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells

Fourteen new naphthalene-based thiosemicarbazone derivatives were designed as anticancer agents against LNCaP human prostate cancer cells and synthesized. MTT assay indicated that compounds 6, 8 and 11 exhibited inhibitory effect on LNCaP cells. Among these compounds, 4-(naphthalen-1-yl)-1-[1-(4-hydroxyphenyl)ethylidene)thiosemicarbazide (6), which caused more than 50% death on LNCaP cells, was chosen for flow cytometric analysis of apoptosis. Flow cytometric analysis pointed out that compound 6 also showed apoptotic effect on LNCaP cells. Compound 6 can be considered as a promising anticancer agent against LNCaP cells owing to its potent cytotoxic activity and apoptotic effect.     

Topotecan Treatment and Its Toxic Effects on Hematologic Parameters and Trace Elements

The aim of this study was to investigate the effects of topotecan, a topoisomerase I-inhibiting anticancer agent, on hematologic parameters and serum levels of trace elements. The study was conducted on three groups consisting of 16 and 18 rabbits in the study groups and 15 rabbits in the control group. Rabbits in group I (n = 16) received high-dose topotecan intravenously (i.v.; 0.5 mg/kg once daily), while rabbits in group II (n = 18) received low-dose topotecan i.v. (0.25 mg/kg once daily) for 3 days. The 15 rabbits comprising the control group did not receive topotecan. Serum samples were collected from each rabbit on the first day, before the treatment, and on the 15th day of treatment. Erithrocytes, hemoglobin, white blood cell count, thrombocyte count, and trace elements such as selenium, copper, lead, zinc, and cobalt were analyzed. Hemoglobin levels and erythrocyte counts were lower in both study groups than in the control group. However, thrombocyte and leukocyte counts were similar in all three groups (p > 0.005). Serum trace element levels (copper, lead, zinc, and cobalt) did not differ significantly between groups. However, serum selenium levels were significantly lower in both study groups than the control group (p < 0.001). The results revealed that topotecan treatment causes a decrease in erythrocyte counts and hemoglobin levels due to bone marrow suppression, and these effects must be taken into account during treatment. In addition, selenium supplementation might be helpful in cancer patients receiving topotecan to increase the effect of the chemotherapeutic agent.     

The Role of Epigenetic Regulation and Pluripotency‐Related MicroRNAs in Differentiation of Pancreatic Stem Cells to Beta Cells

In this study, we aimed to research the effects of class‐I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI‐MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. As a result the valproic acid, is an inhibitor of class‐I HDACs, caused the highest beta cell differentiation in PI‐MSCs. However, the cells in this group were at early stages of differentiation. Glucose co‐administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional. Moreover, reduction in the levels of pluripotency factors that Oct3/4, c‐Myc, and Nanog were parallel to beta cell differentiation. Also, the levels of HDAC1 and acetylated H3/H4 were increased and methylated H3 was decreased by VPA treatment. In addition, we have detected over expression in genes of miR‐18a‐5p, miR‐19b‐5p, miR‐30d‐3p, miR‐124, miR‐146a‐5p, miR‐184, miR‐335, and miR‐433‐5p in parallel to beta cell differentiation. As the conclusion, this study is important for understanding the epigenetic mechanism that controls the beta cell differentation and it suggests new molecules that can be used for diagnosis, and treatment of diabetes. J. Cell. Biochem. 119: 455–467, 2018. © 2017 Wiley Periodicals, Inc.     

Restriction fragment length polymorphism analysis and direct sequencing for determination of HBV genotypes in a Turkish population

The aim of this study was to analyze the restriction fragment length polymorphism and direct sequencing results in genotyping of hepatitis B virus from a Turkish population in a clinical virology laboratory. Serum samples of 54 chronic hepatitis B patients attending the Ege University Hospital were studied. Sequences of partial S gene PCR products were analysed and RFLP was performed. Fifty-three isolates could be identified by direct sequencing as genotype D. One sample needed to be cloned and determined as genotype D. Forty-two isolates were genotyped as D with RFLP according to published determinative patterns. Twelve isolates had undefined patterns. Eight of them suggested a mixture of isolates with different patterns and cloning of these samples confirmed the presence of heterogeneous isolates. Four isolates with undefined pattern were determined as genotype D by direct sequencing. All the studied isolates were genotype D. The results of this studied population suggest that RFLP is suitable for HBV genotyping in a routine clinical virology laboratory setting. However sequence analysis and even cloning may be needed to clarify indeterminate results.     

The effect of pretreatment or combined treatment of quercetin on menadione toxicity in rat primary mixed glial cells in vitro

Neurons and glia are highly susceptible to reactive oxygen species that play a key role in various neurodegenerative diseases. Menadione, a synthetic derivative of vitamin K, induces reactive oxygen generation. Quercetin one of the most ubiquitous bioflavonoids in food of plant origin, has strong antioxidant activities on different cell types, however recent studies demonstrated that it has also prooxidant and cytotoxic potentials. We examined the action of pre- and co-treatment of quercetin on menadione induced glial toxicity. The primary mixed glial cells obtained from 1 to 3 day old rat brain were pretreated with 10, 25, 100 or 250 μM quercetin for 1 h, washed out and 10, 25, 50, 75 or 100 μM menadione was added for 6 h. The other group of cells was treated with respective doses of quercetin combined simultaneously with the same doses of menadione for 6 h. The cells were washed and incubated for additional 24 h for recovery period and the viability was measured by using MTT assay. Menadione was dose-dependently toxic to glia cells and pretreatment with respective quercetin doses for 1 h could not eliminate this toxicity. Although 10 and 25 μM quercetin combined with 10 and 25 μM menadione could not change, 100 and 250 μM quercetin together with 10 or 25 μM menadione for 6 h increased further the menadione induced toxicity. We conclude that when combined with menadione, quercetin at high doses could be toxic to primary rat glia cells in culture.     

Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties,differentiation potential and immunophenotypic markers

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into many lineages. Although the growing interest in BM-MSCs has led to a number of characterization studies, some important biochemical and immunohistochemical properties are still lacking. In this study, morphological and immunophenotypic properties of BM-MSCs were examined in detail. Differentiation potential and growth kinetics of adult rat BM-MSCs were also determined. Immunohistochemistry and RT-PCR results indicated that BM-MSCs expressed myogenic (desmin, myogenin, myosin IIa, and α-SMA), neurogenic (γ-enolase, MAP2a,b, c-fos, nestin, GFAP and beta III tubulin), and osteogenic (osteonectin, osteocalcin, osteopontin, Runx-2, BMP-2, BMP-4 and type I collagen) markers without stimulation towards differentiation. These expression patterns indicated why these cells can easily differentiate into multiple lineages both in vitro and in vivo. Ultrastructural characteristics of rBM-MSCs showed more developed and metabolically active cells.     

Pragmatic assessment of exercise in routine care using an MDHAQ: associations with changes in RAPID3 and other clinical variables

BackgroundExercise is associated with major benefits in patients with rheumatic diseases for both cardiovascular and rheumatic status. However, information about exercise generally is not collected systematically in routine rheumatology care. A multidimensional health assessment questionnaire (MDHAQ), which was designed for busy clinical settings, includes a query about exercise status. We analyzed possible associations between change in MDHAQ exercise scores and other MDHAQ measures in patients with various rheumatic diseases over one year.MethodsIn one rheumatology clinical setting, all patients, regardless of diagnosis, complete an MDHAQ before seeing a rheumatologist. The MDHAQ includes scores for physical function, pain, and patient global estimate, compiled into an index, routine assessment of patient index data (RAPID3), as well as a self-report joint count and a query about exercise. Patients were classified into four groups according to their exercise status at baseline and one year later as: EXER-Yes (regular exercise), EXER-Yes; EXER-No (no regular exercise), EXER-Yes; EXER-Yes, EXER-No; and EXER-No, EXER-No. These groups were compared using the chi square and Kruskal-Wallis tests and analysis of variance (ANOVA).ResultsPatients who reported regular exercise at baseline were younger, had higher formal education, and better clinical status than other patients. The EXER-No, EXER-Yes group had greater improvement in other MDHAQ variables than patients in the other three groups. By contrast, the EXER-Yes, EXER-No group was the only group with poorer status one year later.ConclusionsThe MDHAQ exercise query indicates that regular exercise is associated with better clinical status. Patients in the EXER-No, EXER-Yes group reported the best clinical improvement, although it is not known whether exercise preceded or followed the improved clinical status.