Hilal Acidereli

Interferon regulatory factor‐5 (IRF5) is a transcription factor and has essential cellular mechanisms as a tumour suppressor gene. IRF5 protein function is irregular in various human cancers, and its role in prostate cancer is also unknown. This study presents the first evidence that IRF5 expression is controlled with androgen receptor (AR) signalling interaction and stem cell factors (Nanog, Oct4, Sox2) in prostate cancer. Human prostate cancer cell lines (PC3, DU145 and LNCaP) were transfected plasmids and assessed for cellular localization of IRF5 and AR interaction with IF‐staining. Co‐immunoprecipitation and ChIP assay were used to detect the IRF5 and AR protein‐protein interaction and IRF5 stem cell factors protein‐gene interaction. The target relation between IRF5, AR, CREB, p300, ISRE, ARE and NF‐кB was tested by luciferase assay. IRF5 was low expressed in androgen‐dependent prostate cancer cells and tissues. The analysis of human prostate cancer clinical samples supports the interaction of IRF5 and AR in a pathological role, as IRF5 expression is down‐regulated in the tumours' advanced stages. Tumour suppression mechanism of IRF5 and SOX2 levels in cells reduces and causes AR acetylation. Those affect the prostate cancer mechanism by modifying the cellular response in the signal pathway. IRF5 can be promising for treating androgen‐dependent prostate cancers and is a therapeutic protein for new drug studies.

Taxane‐based chemotherapy drugs (cabazitaxel, docetaxel, and paclitaxel) are microtubule inhibitors, which are effectively and frequently used to treat metastatic prostate cancer (PCa). Among these, cabazitaxel is offered as a new therapeutic option for patients with metastatic castration‐resistant PC as that are resistant to other taxanes. Here, we investigated the cellular and molecular changes in response to cabazitaxel in comparison with docetaxel and paclitaxel in androgen‐independent human PCas. The androgen‐independent human PCa cell lines, PC3 and DU145, were treated with 1 to 5nM cabazitaxel, docetaxel, or paclitaxel, and assessed for cell viability (MTT assay), colony forming ability and migration (scratch assay). The induction of apoptosis was determined through measurement of mitochondrial membrane potential (JC‐1 assay) and caspase‐3 activity assay. The protein expression changes (caspase‐3, caspase‐8, Bax, Bcl‐2, β‐tubulin, nuclear factor‐κB [NF‐κB/p50, NF‐κB/p65], vascular endothelial growth factor, WNT1‐inducible signaling pathway protein‐1 [WISP1], transforming growth factor β [TGF‐β]) in response to drug treatment were screened via western blotting. Under our experimental conditions, all taxanes significantly reduced WISP1 and TGF‐β expressions, suggesting an anti‐metastatic/antiangiogenic effect for these drugs. On the other hand, cabazitaxel induced more cell death and inhibited colony formation compared to docetaxel or paclitaxel. The highest fold change in caspase‐3 activity and Bax/Bcl‐2 ratio was also detected in response to cabazitaxel. Furthermore, the induction of β‐tubulin expression was lower in cabazitaxel‐treated cells relative to the other taxanes. In summary, cabazitaxel shows molecular changes in favor of killing PCa cells compared to other taxanes, at least for the parameters analyzed herein. The differences with other taxanes may be important while designing other studies or in clinical settings.

In this study, bimetallic platinum–rhodium nanocomposites supported on graphene oxide (PtRh@GO) were synthesized and used as a catalyst in the dimethylamine borane (DMAB) dehydrogenation. The synthesized PtRh@GO catalyst was characterized using spectral and microscopic methods. The characterization studies revealed that the obtained PtRh@GO nanomaterials were nano-sized and exhibited a monodisperse distribution on GO. As a result of the catalytic studies, it was determined that the dehydrogenation reaction of dimethylamine borane depends on the temperature, amount of catalyst, and substrate. Additionally, some kinetic data and activation parameters were investigated for the dimethylamine dehydrogenation of DMAB with the help of PtRh@GO. The kinetic and activation parameters showed that the PtRh@GO catalyst could be used effectively. The activation energy (E_a) was found to be 17 ± 2 kJ mol⁻¹ for the dimethylamine borane dehydrogenation. Using previously performed studies, comparison studies for the turnover frequency (TOF) value of the PtRh@GO catalyst in the dimethylamine borane reaction showed that the obtained PtRh@GO catalyst could be used effectively with a higher TOF (274.6 h⁻¹) value. In addition, DFT computations were utilized on the structure of PtRh@GO in order to investigate the activity of the catalyst. The experimental data have been supported by the theoretical results based on DFT.

In this paper, we present platinum/ruthenium nanoparticles supported on Vulcan carbon (PtRu@VC) as a nanocatalyst for the dehydrogenation of dimethylamine-borane (DMAB) in aqueous solution under mild conditions. PtRu@VC nanocatalyst was fabricated using the alcohol-reduction techniques which is a facile and effective method. The prepared PtRu@VC nanocatalyst exhibited a good stabilization and an effective catalytic activity for hydrogen evolution from the DMAB dehydrogenation in water at room temperature. The composition of PtRu@VC nanocatalyst was investigated using different analytical techniques inductively coupled plasma optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (P-XRD) and X-ray photoelectron spectroscopy (XPS). A monodispersedPt/Ru metals distributions on VC (as supporting material) were revealed by TEM and HR-TEM analyses. The mean particle size of PtRu@VC nanocatalyst was found to be 3.15 ± 0.76 nm. XPS analysis for PtRu@VC nanocatalyst showed that almost Pt-Ru metals were found to be the metallic state. Catalytic experimental results showed that PtRu@VC nanocatalyst has a high catalytic activity with an excellent turn-over frequency (TOF_initial) value of 14926.2 h⁻¹ (248.77 min⁻¹) in the dehydrogenation of DMAB in water at room temperature. Additionally, in the paper, we report some different kinetic data obtained from different experimental parameters of temperature, catalyst and substrate concentrations conducted for DMAB dehydrogenation in water catalyzed with PtRu@VC nanocatalyst.

MicroRNAs are important regulators in the growth and metastasis of ovarian cancers. Many assays were established to identify the role of miR-144-3p in ovarian cancer cells and its interaction with COX-2 and chemokines (CXCR4 and CXCL12). The ovarian cancer cells (OVCAR-3 and SKOV-3) were transfected with Anti-miR-144 to downregulate the miR-144-3p and cultured for 36 h. We herein examined the cell viability, colony formation, cell migration, COX-2 reporter activity, the protein expressions of CXCR4, CXCL12, COX-2, VEGF, Caspase-3, BAX and Bcl-2. We have observed that the suppression of miR-144-3p significantly increased the cell proliferation and migration and decreased the apoptosis. Moreover, the downregulation of miR-144-3p markedly increased the COX-2, CXCR4, CXCL12 and VEGF expression in OVCAR-3 and SKOV-3 ovarian cancer cells. In conclusion, miR-144-3p may play important roles in the regulation of chemokine receptor CXCR4 and its ligand CXCL12 in the progressive ovarian tumors expressing COX2. These data suggests that miR-144 has the novel therapeutic targets for the cancer therapy and cancer prevention.

Herein, we report a facile method for the preparation of polypyrrole-multi walled carbon nanotube hybrid material including Pt nanoparticles (Pt@PPy-MWCNT NPs) and the use in methylamine borane (MeAB) for hydrolysis reaction at mild conditions. The prepared catalyst of Pt@PPy-MWCNT NPs was characterized by some advanced analytical methods. The catalytic experiments showed the Pt@PPy-MWCNT NPs can catalyze MeAB in aquatic solution with high catalytical performance at mild conditions. The reaction rate of catalytic hydrolysis with Pt@PPy-MWCNT NPs was found to be -d[CH₃NH₂BH₃]/dt = + d[H₂]/3dt = k_obs[Pt@PPy-MWCNT]^1.19 [MeAB]^0.88. The TOF value for the hydrolysis of MeAB catalyzed with Pt@PPy-MWCNT NPs was detected to be 10234.2 1/h (170.57 1/min) which is very high compared with TOF values found for other catalysts. Enthalpy, entropy and activation energy for the hydrolysis of MeAB were calculated to be 31.57 kJ mol⁻¹, −119.97 J mol⁻¹ K and 34.27 kJ mol⁻¹, respectively.

Several metal nanoparticle based catalysts have been synthesized for catalyzing the hydrogen production process by hydrolysis of methylamine-borane (MeAB). However, there was only one study that catalyzes the producing of hydrogenvia the methanolysis of MeAB, and it was carried out by our research group. For this reason, in this work, a new catalyst system entitled by single-walled carbon nanotube (SWCNT) supported bimetallic platinum-ruthenium nanoparticles were developed and called as PtRu@SWCNT. These NPs were characterized by several techniques (XRD, XPS, Raman, and TEM), and they were performed for the methanolysis of MeAB with high catalytic activity. The prepared PtRu@SWCNT NPs were also tested in the methanolysis of MeAB at different parameters including different temperatures, catalyst and substrate concentrations, and reusability performance. Experimental results revealed that the new PtRu@SWCNT NPs had excellent catalytic activity and reusability for removing of hydrogen from the methanolysis of MeAB at ambient conditions. According to the obtained data, the turnover frequency is 136.25 mole H₂/mole PtRu × min, and the activation energy (Ea) is 17.29 kJ/mole. More than 99% of conversion was observed at room temperature.

Background: Potential targets for prostate cancer therapy are urgently needed for curative of patients. Cyclosporine-A (CsA), an immunosuppressive and a selective cyclooxygenase-2 (COX-2) inhibitor, exerts antitumor activity. However, the molecular effects of CsA is not fully understood in prostate cancer. In this research, we sought to determine role and mechanism of CsA in prostate cancer. Materials and methods: PC3 and DU145 cells were treated with CsA time (12, 24, 48 h) and dose dependent (2.5, 10, 25 μM) and cell survival, migration, colony formation, expression of apoptosis related proteins/genes using MTT assay, scratch assay, Western blotting/qPCR. At the same time, cells treated with CsA to test on the effects of COX-2 promoter activity using luciferase reporter plasmid. Lastly, functional role in the CsA treatment prostate cancer cells were interrogated for relationship of TGFβ, Akt, caspases and COX-2. Results: These study findings provided direct evidences that the CsA induced apoptosis and downregulated migration. Conclusions: CsA downregulated Akt as well as COX-2 and upregulated TGFβ, resulting in the suppression of cell migration which was augmented a potential therapeutic of CsA in prostate cancer cells.