Promoting antihepatocellular carcinoma activity against human HepG2 cells via pyridine substituted palladium complexes: in vitro evaluation and QSAR studies.

Bis(4-(4-nitrobenzyl)pyridine)dichloropalladium(II), [PdCl2L12], bis(2-amino-5-bromopyridine)dichloropalladium(II), [PdCl2L22], bis(2,4-dimethylpyridine)dichloropalladium(II), [PdCl2L32], bis(3,4-dimethylpyridine)dichloropalladium(II), [PdCl2L42] were prepared. The spectroscopic techniques (FT-IR and 1H-NMR, 13C-NMR) were used to characterize the compounds. Theoretical calculations were used to validate the experimental results. The LanL2DZ-based DFT/B3LYP method was used to define the most stable possible molecular structure for the complexes. Potential energy distribution analysis was performed to determine the theoretical vibration bands of the complexes. Molecular electrostatic potential maps, boundary molecular orbitals and Mulliken charge distribution were used to determine the active sites of the molecules. The interaction mechanisms between the complexes and liver cancer protein were investigated via molecular docking. The study on the antiproliferative effects of these complexes on hepatocellular carcinoma cells (HepG2) showed that they are potent candidates for use against this liver cancer cell line.

The Role of Reduced Glutathione on the Activity of Adenosine Deaminase, Antioxidative System, and Aluminum and Zinc Levels in Experimental Aluminum Toxicity.

Aluminum (Al) is one of the most abundant element in the world. But aluminum exposure and accumulation causes serious diseases, related with free radicals. Reduced glutathione (GSH) is a tripeptide with intracellular antioxidant effects. This study aimed to investigate the role of GSH on adenosine deaminase (ADA), antioxidant system, and aluminum and zinc (Zn) levels in acute aluminum toxicity. In this study, Sprague-Dawley rats (n = 32) were used. The rats were divided into four equal groups (n = 8). Group I received 0.5 mL intraperitoneal injection of 0.9% saline solution (NaCI), Group II received single-dose AlCI3, Group III was given GSH for seven days, and Group IV was given AlCI3 single dose, and at the same time, 100 mg/kg GSH was given for seven days. At the end of the trial, blood samples were collected by cardiac puncture. Serum total antioxidant status (TAS) and Zn levels were lower in the aluminum-administered group than the control group. In contrast, plasma total oxidant status (TOS) and aluminum concentrations and ADA activity were found higher in the aluminum-administered group than in the control group. Unlike the other groups, group GSH administrated with aluminum was similar to the control group. As a result, GSH administration has a regulatory effect on ADA activity, antioxidant system, and Zn levels in experimental aluminum toxicity. In addition, GSH may reduce the oxidant capacity increased by Al administration and may have a tolerant role on the accumulated serum Al levels. But long-term experimental Al toxicity studies are needed to reach a firm conclusion.

Nanogold morphologies with the same surface chemistry provoke a different innate immune response: An in-vitro and in-vivo study.

Gold nanomaterials (GNMs) have unique optical properties with less antigenicity, and their physicochemical properties have strong relation with an immunological response at bio-interface including antigenicity. An interpretation of this correlation would significantly impact on the clinical and theranostic applications of GNMs. Herein, we studied the effect of GNMs morphology on the cytotoxicity (in-vitro), innate immune responses, hepatotoxicity, and nephrotoxicity (in-vivo studies) using gold nano-cups (GNCs), porous gold nanospheres (PGNSs) and solid gold nano particles (SGNPs) coated with the same ligand to ensure similar surface chemistry. The cytotoxicity was assessed via sulfo-rhodamine B (SRB) assay, and the cytotoxicity data showed that morphological features at nanoscale dimensions like surface roughness and hollowness etc. have a significant impact on cellular viability. The biochemical and histopathological study of liver and kidney tissues also showed that all GNMs did not show any toxicity even at high concentration (100 µL). The relative quantification of cytokine gene expression of TNF-α, IFN-γ, IL-4, 1L-6, and 1L-17 (against each morphology) was checked after in-vivo activation in mice. Among the different nanogold morphologies, PVP stabilized GNCs (PVP-GNCs) showed the highest release of pro-inflammatory cytokines, which might be due to their high surface energy and large surface area for exposure as compared to other nanogold morphologies studied. The pro-inflammatory cytokine release could be suppressed by coating with some anti-inflammatory polymer, i.e., inulin. The in-vitro results of pro-inflammatory (TNF-α, IL-1) cytokines also suggested that all GNMs may induce activation of macrophages and Th1 immune response. The in-vivo activation results showed a decrease in mRNA expression of the cytokines (TNF-α, IFN-γ, IL-4, 1L-6 and 1L-17). Based on these findings, we proposed that the shape and morphology of GNMs control their immune response at nano-bio interface, and it must be considered while designing their role for different biomedical applications like immuno-stimulation and bio-imaging.

Green Nanotechnology for Synthesis and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) nanoparticles for sustained bortezomib release using supercritical CO2 assisted particle formation combined with electrodeposition.

Carbon dioxide assisted particle formation combined with electrospraying using supercritical CO2 (scCO2) as an aid (Carbon Dioxide Assisted Nebulization-Electrodeposition, CAN-ED) was used to produce Bortezomib loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) P(3HB-co-3HHx) nanoparticles for sustained release. The morphology and structure of the prepared nanoparticles were investigated by SEM, TEM and FT-IR spectroscopy. Average diameter of particles obtained was 155nm and the average core sizes of P(3HB-co-3HHx) nanoparticles were between 6 and 13nm. The drug loading capacity, drug release and stability of Bortezomib loaded P(3HB-co-3HHx) nanoparticles were analyzed. The maximum loading capacity was achieved at pH=6.0 in phosphate buffer (K2HPO4/KH2PO4). It was found that temperature did not affect the stability of Bortezomib loaded nanoparticles and it was good both at 37°C and 4°C. This study pointed out that CAN-ED is a green method to produce P(3HB-co-3HHx) nanoparticles for pH responsive targeting of Bortezomib especially to parts of the body where size exclusion is not crucial.

Investigation of heavy metal content of Turkish tobacco leaves, cigarette butt, ash, and smoke.

A procedure for the determination of cadmium, copper, manganese, and zinc in Turkish tobaccos, which were of different origins, years, and grades, and in the butt, ash, and smoke, which were obtained by smoking the cigarettes that were prepared manually from the said tobaccos in a smoking apparatus, was devised as proposed. The collected samples were digested by wet ashing technique by using HNO3-HClO4 and were analyzed by flame atomic absorption spectrometry with satisfactory recoveries (94% to 98%). The regression coefficients were above 0.99, and the detection limits were in the range of 0.03-0.12 mg/L(-1). The performance and accuracy of the method was tested by analyzing "Certified Reference Material GBW 08501-Peach Leaves." The determined values were in agreement with the standard values for the heavy metals analyzed. Thus, it was concluded that the developed method could offer a wide range of application for establishing a relationship between the makeup and composition of tobacco plant, products, ash, smoke, and smoking.