The beneficial effects of vortioxetine on BDNF, CREB, S100B, ß amyloid, and glutamate NR2b receptors in chronic unpredictable mild stress model of depression.

BACKGROUND: Depression, one of the most significant mental disorders, is still poorly understood in terms of its pathogenetic mechanisms despite its well-recognized association with stress. OBJECTIVES: The current study's goal was to ascertain how the novel antidepressant drug vortioxetine (VOR) affected the BDNF (brain-derived neurotrophic factor), S100, amyloid ß (Aß), CREB (cAMP response element-binding protein), and NR2B, as well as its impact on depression-like behaviors, and tissue damage in an experimental rodent model of depression caused by chronic unpredictable stress. METHODS: We employed twenty-eight Wistar albino male rats, and we randomly divided them into four groups, each consisting of 7 rats: control, CUMS (chronic unpredictable mild stress), CUMS+vortioxetine (CUMS+VOR), and CUMS+fluoxetine (CUMS+FLU). Sucrose preference and forced swimming tests (SPT and FST, respectively), PCR, ELISA, and histopathological and immunohistochemical evaluation were made on brains. RESULTS: The behaviors of reduced immobility in the FST and increased sucrose preference were observed in the CUMS group and they improved in the groups treated with VOR and FLU. Compared with the control group, the group exposed to CUMS showed increased Aß and decreased BDNF, CREB, and S-100 expressions, as well as neuronal degeneration (p<0.001). VOR and FLU treatment ameliorate the findings. CONCLUSIONS: This study demonstrated significant ameliorative effects of VOR in an experimental model of chronic unpredictable depression to reduce brain tissue damage and depression-like behaviors in rats. Effects of CUMS on the brain and possible effects of VOR.

The Role of EREG, PTPN1, and SERPINB7 Genes in the Pathogenesis of Psoriasis: May SERPINB7 Be Protective and a Marker of Severity for Psoriasis?

INTRODUCTION: Psoriasis is a chronic inflammatory dermatological disease with complex pathogenesis in which many immune system cells, including keratinocytes, play a role. Many genes regulate the proliferation of keratinocytes and other immune cells that have essential roles in the pathogenesis of psoriasis. The expressions of EREG, PTPN1, and SERPINB7 genes were shown as upregulated in psoriatic skins in a few studies previously. OBJECTIVES: We aimed to evaluate the expressions of these genes in psoriatic lesional skin and compared them with non-lesional adjacent skin of the same patients and normal skin of healthy controls. RESULTS: Our results revealed that the expressions of EREG and PTPN1 genes were upregulated, whereas the SERPINB7 gene expression was down regulated in the psoriatic skin of the patients than normal skin of controls. Moreover, the expression level of the SERPINB7 gene was also negatively correlated with the severity of the disease among patients. CONCLUSIONS: According to our results, overexpression of EREG and PTPN1 genes, and decreased expression of SERPINB7 gene may lead to the development of psoriasis.

Malignancy-related mir-210, mir-373 and let-7 levels are affected in iron deficiency anemia.

Background: Hypoxia is the hallmark of iron deficiency anemia (IDA) and in hypoxic environment, significant changes are observed in malignancy-related microRNAs (miRNA). Our aim is to examine whether there is any difference in the levels of miR-210, miR-373 and let-7, which are directly related to malignancies in patients with IDA. Methods: Thirty-five female patients with IDA between the ages of 18-65 and 10 healthy controls were included in the study. Patients who received oral iron therapy, who had inflammatory disease, and who were pregnant were excluded from the study. Student t Test was used for comparing variables with normal distribution in two independent groups, and Mann-Whitney U Test was used for variables without normal distribution. Comparison of categorical data was made using the chi-square test. Results: The mean hemoglobin and ferritin level were 10,78±0,93 and 6.28±5,76 respectively. Plasma miR-210 expression were found as -7.27±2.23 and -6.15±0,88 in IDA and control group respectively (p = 0.022). Plasma miRNA-373 were -7.36±2,58 and -6,96±1,93 and let-7 expression were 2.14±2,15 and 3,57±2,21 in IDA and control group. (p = 0.65 and p = 0.20, respectively). Conclusions: Plasma miR-210 expression was significantly up-regulated and miR-373 and let-7 expression was down-regulated, though insignificantly, in IDA group.

Hypothalamic NR3C1 DNA methylation in rats exposed to prenatal stress.

BACKGROUND: Human and animal studies have indicated that maternal prenatal stress (PS) has molecular and behavioral effects during pregnancy and early life. The present study aimed to evaluate the epigenetic changes of the NR3C1 gene involved in the HPA axis in the hypothalamic tissues of rats exposed to PS induced by chronic unpredictable mild stress (CUMS). Behavioral and molecular effects of these changes on the next generation were also assessed. METHODS AND RESULTS: CUMS protocol was used to generate stress in pregnant Wistar rats. To determine the effects of stress on anhedonia and movement, sucrose preference test, forced swimming test, and open field test were performed. Following these behavioral experiments, bisulfite sequencing PCR for DNA methylation levels of the NR3C1 gene, RT-qPCR for mRNA levels, and Western blot techniques for protein analysis were used in the hypothalamic tissue of sacrificed rats. Depression-like behaviors were evident in the behavioral tests of stress-exposed mothers and pups. In PS-exposed pups, hypothalamic NR3C1 promoter methylation was higher, and NR3C1 mRNA levels and NR3C1 protein levels were lower compared with controls, regardless of sex. CONCLUSION: Our results confirm the relationship between PS and epigenetic changes of HPA axis-related genes and show that NR3C1 gene methylation status in pups is sensitive to PS during pregnancy. Environmental maternal stress may have transgenerational effects that are potentially associated with adverse outcomes in the pups.

Possibility of paclitaxel to induce the stemness-related characteristics of prostate cancer cells.

BACKGROUND: Drug resistance poses a crucial problem in the treatment of prostate cancer. Recent studies have shown that chemotherapy agents may cause cancer cells to acquire stem cell-like properties, resulting in drug resistance and, eventually, treatment failure. OBJECTIVES: To evaluate whether long-term paclitaxel exposure causes an increase in the stem cell-like properties of prostate cancer cells. MATERIAL AND METHODS: Paclitaxel-resistant PC-3 cells were generated from parental PC-3 cells by treating them with increasing concentrations of paclitaxel. The expression levels of the stem cell markers NANOG, C-MYC, CD44, and ABCG2 were evaluated using quantitative real-time polymerase chain reaction (RT-qPCR). A sphere formation assay was performed to test the potential of the cells to behave as stem cells, and a wound healing assay was carried out to evaluate migration ability of the cells. RESULTS: The expression levels of C-MYC and NANOG were significantly higher in paclitaxel-resistant PC-3 cells compared to the parental PC-3 cells. However, there was no significant increase in the expression of CD44 or ABCG2. In addition, the sphere-forming capacity and migration ability of resistant PC-3 cells were increased. CONCLUSIONS: The results of the current study indicate that paclitaxel exposure may increase the stem cell-like properties of PC-3 prostate cancer cells.

Low-penetrance susceptibility variants and postmenopausal oestrogen receptor positive breast cancer.

The risk of breast cancer (BC) in women is high and many factors including genetic factors increase the risk for the disease. It is revealed that the variations of low-penetrance susceptibility genes are important for carcinogenesis as they interact with the environmental and hereditary factors. Recently, the list of BC-associated common single nucleotide polymorphisms (SNPs) and chromosomal loci in low-penetrance susceptibility genes have been expanded in genomewide association studies. FGFR2, LSP1, MAP3K1, TGFB1, TOX3, 2q35 and 8q loci variations are some examples for these common SNPs. These SNPs and their association with BC risk was investigated in many different populations. Therefore in this study, we aimed to evaluate low-penetrance susceptibility SNPs; namely FGFR2 rs1219648, rs2981579, rs2981582; MAP3K1 rs889312; TOX3 rs3803662; LSP1 rs909116, rs3817198 and SLC4A7 rs4973768 together, for the firsttime in Turkish postmenopausal oestrogen receptor positive BC cases. Following the DNA isolation, multiplex PCR and matrix-assisted laser desorption/ionization mass spectrometry with time of flight measurement (MALDI-TOF) based SNP analysis were performed. MAP3K1 rs889312 SNP demonstrated the strongest association with BC risk among the other low penetrant SNPs, it was also associated with BC risk in a dominant model. Only in a ressesive model, TOX3 rs3803662 was associated with BC risk. In addition, rs4973768 CC and rs909116 CC genotypes are correlated with higher tumour size which is not reported in the literature as yet; on the other hand there are no associations between any of the other SNP genotypes and clinopathological parameters. In our opinion, MAP3K1 rs889312 may be a good BC susceptibility biomarker candidate for Turkish population.