Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski’s rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Electrochemical sensor of carboxymethyl cellulose and photocatalytic degradation of Navy Blue dye by sonochemically synthesized Titanium oxide nanoparticles

Nanocrystalline titanium oxide nanoparticles (TiO2 NPs) were synthesized by using a low-cost sonochemical method. TiO2 NPs exhibited anatase phase and an average crystallite size of 40.64 ​nm, according to a powder X-ray diffraction (PXRD) investigation. SEM and TEM images revealed spherical shape, with asymmetric geometries for TiO2 NPs. The micrographs thoroughly corroborated the plate-like structure for the NPs. In order to confirm the average energy gap of TiO2 NPs, diffused reflectance spectroscopy (DRS) via Kubelka-Monk function was applied (3.66 ​eV). Navy blue dye was used to study the photocatalytic properties of NPs and discovered to be triggered at 590.9 ​nm. The photodegradation rate of NB dye decolorized up to 74.04% after 120 ​min of UV light exposure. The first order kinetics was indicated by a linear relationship between log C/Co and k. The demonstrated rates of photodecoloration for NB under UV light in the presence of scavengers AgNO3, ethanol, and ethylenediamine tetraacetic acid (EDTA), were found to be 65.50%, 61.46%, and 57.33%, respectively. Using the carbon paste electrodes and cyclic voltammetry (CV) in 0.1 ​N HCl solution, the electrochemical characteristics of the obtained sample were studied. The carboxymethyl cellulose sensor made from TiO2 NPs demonstrated a remarkable sensitivity of 0.08 A. The results showed a high recovery for lead with low% of RSD values. The TiO2 electrode is a promising electrode material for sensing applications due to its outstanding electrochemical performance

Exploration of Temperature Distribution through a Longitudinal Rectangular Fin with Linear and Exponential Temperature-Dependent Thermal Conductivity Using DTM-Pade Approximant

The present study elaborates on the thermal distribution and efficiency of a longitudinal rectangular fin with exponentially varying temperature-dependent thermal conductivity and heat transfer coefficient concerning internal heat generation. Also, the thermal distribution of a fin is comparatively studied for both exponentially varying temperature-dependent thermal conductivity and linearly varying temperature-dependent thermal conductivity. Further, the thermal distribution of a longitudinal fin is examined by using ANSYS software with different fin materials. Many physical mechanisms can be explained by ordinary differential equations (ODEs) with symmetrical behavior, the significance of which varies based on the perspective. The governing equation of the considered problem is reduced to a non-linear ODE with the assistance of dimensionless terms. The resultant equation is solved analytically using the DTM-Pade approximant and is also solved numerically using Runge-Kutta Fehlberg&rsquo;s fourth-fifth (RKF-45) order method. The features of dimensionless parameters influencing the fin efficiency and temperature profile are discussed through graphical representation for exponentially and linearly varying temperature-dependent thermal conductivity. This study ensures that the temperature field enhances for the higher magnitude of thermal conductivity parameter, whereas it diminishes for diverse values of the thermo-geometric parameter. Also, greater values of heat generation and heat transfer parameters enhance the temperature profile. Highlight: Thermal distribution through a rectangular profiled straight fin is examined. Linear and non-linear thermal properties are considered. The combined impact of conduction, convection, and internal heat generation is taken for modeling the energy equation of the fin. Thermal simulation is performed for Aluminum Alloy 6061 (AA 6061) and Cast Iron using ANSYS

Awareness about the future of artificial intelligence in healthcare among medical students in Kancheepuram District, Tamil Nadu

Introduction: Artificial Intelligence (AI) is expected to influence and has potential to improve various fields in medical care. They have capability of rapidly diagnosing various medical conditions and improve he treatment outcomes in various specializations. The study was done to find out the awareness of AI in Healthcare among medical students in Kancheepuram district, Tamil Nadu. Methodology: This is a descriptive cross-sectional study conducted among 100 medical students studying in a private medical college selected by simple random sampling. A pretested semi-structured questionnaire was used for data collection regarding the awareness of AI in Healthcare. Data was entered in Microsoft excel and analyzed by SPSS version 22. Results: Around 85% of the study participants were aware about Artificial Intelligence and 98% were about the attitude that it could improve healthcare. It was found that 82% of the study participants welcomed the idea of AI being used in Healthcare, while 7% were least accepting. The study participants were of the belief that the medical department which could benefit the most from use of AI were Radiology (38%) and Oncology (30%).&nbsp