Histone acetylation: a key determinant of acquired cisplatin resistance in cancer.

Cisplatin is an alkylating class of chemotherapeutic drugs used to treat cancer patients. However, cisplatin fails in long-term treatment, and drug resistance is the primary reason for tumor recurrence. Hence, understanding the mechanism of acquirement of chemoresistance is essential for developing novel combination therapeutic approaches. In this study, in vitro cisplatin-resistant cancer cell line models were developed. Gene ontology and GSEA of differentially expressed genes between parental and resistant cells suggest that PI3K-AKT signaling, central carbon metabolism, and epigenetic-associated phenomenon alter in cisplatin-resistant cells. Further, the data showed that increased glucose transport, alteration in the activity of histone-modifying enzymes, and acetyl-CoA levels in resistant cells paralleled an increase in global histone acetylation. Enrichment of histone acetylation on effectors of PI3K-AKT and glycolysis pathway provides evidence of epigenetic regulation of the key molecules in drug resistance. Moreover, cisplatin treatment to resistant cells showed no significant changes in histone acetylation marks since drug treatment alters cell epigenome. In continuation, targeting PI3K-AKT signaling and glycolysis leads to alteration in histone acetylation levels and re-sensitization of resistant cells to chemo-drug. The data provide evidence of histone acetylation's importance in regulating pathways and cisplatin-resistant cells' cell survival. Our study paves the way for new approaches for developing personalized therapies in affecting metabolic pathways and epigenetic changes to achieve better outcomes for targeting drug-resistant cells.

Direct non-destructive trace and major elemental analysis in steel samples utilizing micro-focused bremsstrahlung radiation in X-ray fluorescence geometry.

Stainless steel is a very important technological material used in various industries. In this work, a simple non-destructive method is developed for major as well as trace elemental determination in stainless steel samples using micro-X-ray fluorescence (XRF) based technique. The utilization of full bremsstrahlung excitation in combination with micro-focused geometry substantially reduces the detection limit of different elements present in stainless steel. The developed methodology is capable of determining elemental concentrations down to 30-80 ppm level in stainless steel matrix without any requirement of cumbersome dissolution or separation procedure. Elements such as Si, P, S and Co were determined simultaneously at trace level using the developed micro-XRF based technique. At the same time this technique is also capable of analyzing elements which are present at percentage levels. Till now there is no such report showing the capability of lab-XRF based non-destructive technique for the analysis of both major as well trace elements down to such low concentration level to the best of our knowledge. Moreover, the methodology involved is very simple and straight forward. The analytical results obtained were very much satisfactory with good accuracy and precision.

Direct Multielemental Trace Determinations in Plutonium Samples by Total Reflection X-ray Fluorescence Spectrometry Using a Very Small Sample Amount.

A simple, safe, and sensitive method for direct multielemental trace determinations in plutonium samples using total reflection X-ray fluorescence (TXRF) spectrometry has been developed. A very small volume (2 µL) of the sample solutions was deposited on TXRF supports after separation of the plutonium matrix from these solutions. Since the amount of the plutonium deposited on the supports was in the ng level only fixed on the supports and the specimen spots were not disturbed during the sample preparation, the samples could be analyzed directly without putting the instrument in a glovebox. This approach avoided a cumbersome operation of the instrument in a glovebox, which is normally utilized for Pu-based samples using other techniques. Similarly, the requirement of small amounts of the samples minimized the radiation dose to the operator as well as a cumbersome problem of management of radioactive analytical waste of plutonium samples. The samples were analyzed using the TXRF spectra of the specimens, concentration of the internal standard Se or Ga and predetermined sensitivity values. The elemental detection limits for the elements K-Sr varied from 1.06 to 0.09 ng. The elements K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Sr, Ba, Tl, and Pb were analyzed at µg/mL level. The analytical results of TXRF determinations showed average relative standard deviation (RSD) value of 4.5% (1σ, n = 3) and the TXRF determined results deviated from the expected values by 5.9% on average for samples prepared by adding multielements in plutonium solutions. Two real plutonium samples were also analyzed in similar manner. For the real plutonium sample solution the average RSD values of TXRF determinations were 10.6% (1σ, n = 3) for the elemental concentrations in the range of 0.2 to 61 µg/mL. These values are comparable with conventional trace element analytical techniques with added advantages mentioned above.

Synthesis of oleic acid functionalized Fe3O4 magnetic nanoparticles and studying their interaction with tumor cells for potential hyperthermia applications.

In the present study, oleic acid (OA) functionalized Fe3O4 magnetic nanoparticles (MN) were synthesized following modified wet method of MN synthesis. The optimum amount of OA required for capping of MN and the amount of bound and unbound/free OA was determined by thermogravimetric analysis (TGA). Further, we have studied the effect of water molecules, associated with MN, on the variation in their induction heating ability under alternating current (AC) magnetic field conditions. We have employed a new approach to achieve dispersion of OA functionalized MN (MN-OA) in aqueous medium using sodium carbonate, which improves their biological applicability. Interactions amongst MN, OA and sodium carbonate were studied by Fourier transform infrared spectroscopy (FT-IR). Intracellular localization of MN-OA was studied in mouse fibrosarcoma cells (WEHI-164) by prussian blue staining and confocal laser scanning microscopy (CLSM) using nile blue A as a fluorescent probe. Results showed MN-OA to be interacting mainly with the cell membrane. Their hyperthermic killing ability was evaluated in WEHI-164 cells by trypan blue method. Cells treated with MN-OA in combination with induction heating showed decreased viability as compared to respective induction heating controls. These results were supported by altered cellular morphology after treatment of MN-OA in combination with induction heating. Further, the magnitude of apoptosis was found to be ~5 folds higher in cells treated with MN-OA in combination with induction heating as compared to untreated control. These results suggest the efficacy of MN-OA in killing of tumor cells by cellular hyperthermia.