Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris water maze (MWM) tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience.

Breast cancer is the most common cancer among women and accounts for 23% of all female types of cancers. It is well recognized that breast cancer represents a heterogeneous group of tumors, and the molecular events involved in the progression to cancer remain undetermined. Moreover, available prognostic and predictive markers are not sufficient for the accurate determination of the risk for many breast cancer patients. Thus, it is necessary to discover new molecular markers for accurate prediction of clinical outcome and individualized therapy. In the present study, we performed omics-based whole-genome trancriptomic and whole proteomic profiling with network and pathway analyses of breast tumors to identify gene expression patterns related to clinical outcome. A total of 20 samples from tumors and 14 normal appearing breast tissues were analyzed using both gene expression microarrays and LC-MS/MS. We identified 585 downregulated and 413 upregulated genes by gene expression microarrays. Among these genes, HPX, POTEE and ApoA1 were the most significant genes correlated with the proteomic profile. Our data revealed that these identified genes are closely related to breast cancer and may be involved in robust detection of disease progression.

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Quantitative real-time PCR revealed that CREB and BDNF gene expression levels were significantly decreased in UCMS-exposed group, and this effect was significantly reversed by each of drugs tested. Our results seem to be test dependent and should be further investigated using different learning and memory tasks.

Objective:Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period.Materials and Methods:We analyzed gene expression levels of NF-κB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin’s lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using real-time polymerase chain reaction.Results:Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated.Conclusion:These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions.