Are the promnestic effects of neurokinin 3 receptor mediated by hippocampal neurogenesis in a Aß-induced rat model of Alzheimer's disease?

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by cognitive dysfunction, memory loss and mood changes. Hippocampal neurogenesis has been suggested to play a role in learning and memory. Neurokinin 3 receptor (NK3R) has been shown to be prevalent in the hippocampus region. The aim of the project was to investigate the role of hippocampal neurogenesis in the promnestic effects of NK3R agonist administration in an amyloid beta-induced AD rat model. Wistar albino rats were divided into control, Alzheimer, NK3R agonist and Alzheimer + NK3R agonist groups. The open field (OF) test and Morris water maze (MWM) test were performed for locomotor activity and memory analysis. Peptide gene expression levels (Nestin, DCX, Neuritin, MASH1, Neun, BDNF) were analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR). In the OF test, the group-time relationship was found to be statistically different in the parameters of distance travelled and percentage of movement (p < 0.05). In MWM, the time to reach the platform and the time spent in the target quadrant were statistically significant between the groups (p < 0.05). Statistically significant differences were observed in gene expression levels (Nestin, DCX, Neuritin, MASH1) in the hippocampal tissue of rats between the groups (p < 0.05). NK3 receptor agonism favourably affected hippocampal neurogenesis in AD model rats. It was concluded that NK3 receptor agonism in the hippocampus, which is the first affected region in the physiopathology of AD, may be effective in both the formation of neural precursor cells and the reduction of neuronal degeneration. The positive effect of NK3R on cognitive functions may be mediated by hippocampal neurogenesis.

Reprograming cancer cells by a BODIPY G-quadruplex stabiliser.

A cationic BODIPY-based G-quadruplex-selective stabiliser is developed and shown to decrease cancer cell migration-invasion up to 90%. The expression of critical genes (HIF1α, VIM, CDH1) related to metastasis is modulated. The stabiliser reprograms hypoxia-adaptive metabolism and an 1.82-fold increase in O2 consumption, enabling back-to-normal switching of energy metabolism, is observed. Stabilisers with a strong G-quadruplex affinity (0.38 µM Kd) significantly contribute to small molecule anti-cancer approaches.

Downregulation of gene expression in hypoxic cancer cells by an activatable G-quadruplex stabiliser.

In the research, the modulation of gene expression with a novel G-quadruplex stabiliser was analysed. Activation by the removal of bulky hypoxia-responsive substituent enhances G-quadruplex stabilisation. Hypoxic MCF7 cells incubated with the stabiliser displayed significant downregulation of oncogenes c-myc, bcl-2, and hif-1α. This study presents the first hypoxia-activatable G-quadruplex stabilization and transcriptional regulation.

Apelin triggers macrophage polarization to M2 type in head and neck cancer.

Cancer comes after cardiovascular diseases in terms of mortality rate in the world. Chemotherapy, radiotherapy and surgical interventions are the current cancer treatment. Recently, it has been observed that immunotherapeutic approaches provide a significant improvement when used along with these interventions. The mononuclear system mainly consists of macrophages that play an active role in the pathology of many diseases because of having high plasticity capacities. Previous research suggested that they can be used as an alternative to cancer treatment. Aim was to investigate the effect of apelin on macrophage polarization in the tumor microenvironment. Mouse macrophage cell line RAW264.7 cells and head and were chosen for this study. The apelin expression was knockdown in neck cell carcinoma cell line SCCL MT1 cells using shRNA technique. SCCL MT1 cells having normal or suppressed apelin expression were co-cultured with mouse macrophage RAW264.7 cells. The effect of co-culturing on the expression of inflammatory genes in RAW264.7 cells was investigated. Suppressed apelin expression in SCCL MT1 cells resulted in elevated pro-inflammatory response in co-cultured macrophages. Expression of the IL1ß, IL6, and TNFα genes significantly increased, however anti-inflammatory cytokine levels were significantly decreased. However, in the control group, a downregulation was determined in pro-inflammatory genes, while an increase was observed in anti-inflammatory genes. The protein levels of these cytokines in concordance with the RT-PCR analysis. As a result of this study, apelin released from cancer cells was found to affect macrophage polarization. These results indicated that the apelin peptide may cause the intense presence of M2-type macrophages in the tumor niche, and the therapeutic approaches targeting of apelin in cancer cells may have a potential role in macrophage polarization.