Meinckeodom4911

The present study was conducted in order to investigate the pharmacological activities of three heterobimetallic coordination compounds [Cd(N-bishydeten)2][Ni(CN)4] (C1), [Cu2(N-bishydeten)2Co(CN)6].3H2O (C2), and K[Cd(N-bishydeten)Co(CN)6].1.5H2O (C3) (N-bishydeten = N,N-bis(2-hydroxyethyl)-ethylenediamine). This paper describes the ability of complexes to inhibit cell growth, cell migration and human topoisomerase I and to interact with DNA/BSA; this paper also evaluates the potential mechanisms of action exhibited by these compounds via the use of powerful measurement techniques. Studies on HT29, HeLa, C6 and Vero cells revealed that each compound demonstrated significant antiproliferative activity in conjunction with regressed cell migration velocity and caused apoptotic changes in morphology. There are strong data suggesting that the mechanisms of action exhibited by these compounds are associated with their DNA/BSA binding features. The IC50 and binding constant range for the compounds are 20-180 µM and 1.2-3.2 x 104 M-1, respectively. Moreover, we observed that these compounds alter the P53-Bcl-2 ratio and inhibit the relaxation activity of human topoisomerase I. Furthermore, a correlation between the antiproliferative effects of these compounds and their cytotoxic activity was observed. In conclusion, preliminary information demonstrates that these compounds have been found to exhibit effective antiproliferative activity against cancer cell lines, indicating that they are a potent candidate for further pharmacological study.In this study, the effect of topiramate, as an antiepileptic drug, was evaluated on morphine craving in rats. The conditioned place preference (CPP) test was used for this purpose. Repeated administration of morphine (10 mg/kg, i.p. check details for 4 days) induced significant CPP. Administration of topiramate (50 and 100 mg/kg, i.p. for 4 days) with each morphine administration decreased the acquisition of morphine-induced CPP. At the next step, the levels of extracellular signal-regulated kinase (ERK), p-ERK, cAMP responsive element binding (CREB), and p-CREB proteins were evaluated in hippocampus and cerebral cortex using western blot analysis. Following the repeated administration of morphine, the level of p-ERK protein markedly enhanced in both tissues, while topiramate could significantly reduce the phosphorylation of ERK in these brain regions. Additionally, the level of CREB and p-CREB proteins did not change in different groups. Memantine as a positive control reduced the acquisition of morphine-induced CPP. Also, memantine significantly decreased the level of p-ERK protein in hippocampus and cerebral cortex. These results demonstrated that topiramate can attenuate the acquisition of morphine-induced CPP in rats. This effect in part can be mediated through down regulation of p-ERK protein in hippocampus and cerebral cortex.3,4-methylenedioxymethamphetamine (MDMA) is one of the most widespread illegal drugs, that have been used particularly by young people in the 15-34 age group. MicroRNAs (miRNAs) are endogenously synthesized, non-coding, and small RNAs that post-transcriptionally regulate their target genes' expression by inhibiting protein translation or degradation. miRNAs are increasingly implicated in drug-related gene expressions and functions. Notably, there are no reports of miRNA variation in the human brain in MDMA abuse. We here present a miRNA profiling study - the first such study, to the best of our knowledge - into the post-mortem human brains of a sample of people with MDMA abuse, along with non-drug dependent controls. The miRNA profiling of nucleus accumbens (NAc) and ventral tegmental areas (VTA) was performed by microarray analysis. Subsequently, two candidate miRNA putative biomarkers were selected according to significant regional differential expression (miR-1202 and miR-7975), using quantitative reverse-transcription PCR (qRT-PCR). We showed that the expression level of miR-7975 was significantly lower in the VTA regions of the 30 MDMA users, as compared with the 30 control samples. Another significantly deregulated miR-1202 was down-regulated in the NAc regions of 30 MDMA samples in comparison to the control samples. Alteration of these miRNAs can potentially serve as novel biomarkers for MDMA abuse, and warrant further research in independent and larger samples of patients.Neuronal survival in multiple sclerosis (MS) and other demyelinating diseases depends on the preservation of myelin and remyelination of axons. Myelin protection is the main purpose to decrease myelin damage in the central nervous system (CNS). Ursolic acid (UA) as a natural product in apple is suggested to protect neural cells. This study is the first to demonstrate an effect for UA on CNS myelin loss induced by cuprizone toxin. In the current study, we hypothesized that daily treatment with UA in drinking water (1 mg/mL) prevents myelin damage by 6 weeks administration of CPZ in mice pellet which lead to corpus callosum axonal demyelination. We assessed the myelin content and the number of myelinating cells in corpus callosum by FluoroMyelin and luxol fast blue staining as well as by immunostaining against MBP and Olig2. Our finding indicated that UA could decrease the extent of demyelination area and enhanced myelin stain intensity within CC and protected oligodendrocyte lineage cells against cuprizone toxin. We could conclude that myelinated structures could be protected by UA in corpus callosum, which provide favorable evidence for the possibility of application of UA in demyelinating diseases and traumatic injuries.Mutational inactivation of p53 is a key player in the development of human cancer. Thus, retrieving the tumor suppressor activity of p53 gene is considered a novel strategy in cancer therapy. Current study aimed to investigate the anti-cancer potentials of botulinum toxin type-A (BTX-A) and captopril as a trial to shed light on effective anti-cancer therapy with lower side effects. Cytotoxic effect of captopril and BTX-A was determined using MTT assay against colon (HCT116) and prostate cancer (DU145) cells compared to their effect on normal vero cells. Anti-proliferation assay and anti-metastatic effect were carried out using trypan blue exclusion method and wound scratch migration test, respectively. The ability of test drugs to induce apoptosis in cancer cells was examined using real time PCR. Recorded data revealed that captopril exhibited a statistically significant cytotoxicity (P less then 0.05) to cancer cells (IC50 values of 1.5 and 1.2 mg/mL) with much lower toxicity to normal cells. At the same time, IC50 values post BTX-A treatment were 7.