Sustainable Routed Mxene-Based Aminolyzed PU/PCL Film for Increased Oxidative Stress and a pH-Sensitive Drug Delivery System for Anticancer Therapy.

A remarkable challenge in the anticancer drug delivery system is developing an implantable system that can improve the chemotherapeutic effect. Polyurethane is an excellent implantable substrate, with flaws in hydrophobicity. We modified polyurethane via the chemical aminolysis technique to enhance the wettability and protein interaction. The created pores can release the rutin complex incorporated in the polyurethane matrix. In this work, the hybrid polymer matrix consists of Mxene synthesized via a sustainable and simple method by introducing a toxic-free MAX phase and etchants. The incorporation of Mxene and PCL can enhance physicochemical and biological compatibility. Sustainable Mxene increases oxidative stress, cell death, and antibacterial activity, which also resulted in the Mxene@APU/PCL film. Meanwhile, the drug release with respect to pH sensitivity was demonstrated in which Mxene and Mxene@APU/PCL films showed the highest release at pH 5.2; this indicates that the prepared Mxene and aminolyzed polyurethane can function according to the biological system and release the drug from the polymer matrix on slow degradation and swellability. The Mxene and Mxene@APU/PCL films showed 93.2% drug release with oxidative stress on THP-1 cells, which causes rupturing and apoptosis of cancerous cells. The Mxene@APU/PCL film can show great potential in future implantable anticancer drug delivery systems.

Cholecalciferol and metformin protect against lipopolysaccharide-induced endothelial dysfunction and senescence by modulating sirtuin-1 and protein arginine methyltransferase-1.

Endothelial cell activation through nuclear factor-kappa-B (NFkB) and mitogen-activated protein kinases leads to increased biosynthesis of pro-inflammatory mediators, cellular injury and vascular inflammation under lipopolysaccharide (LPS) exposure. Recent studies report that LPS up-regulated global methyltransferase activity. In this study, we observed that a combination treatment with metformin (MET) and cholecalciferol (VD) blocked the LPS-induced S-adenosylmethionine (SAM)-dependent methyltransferase (SDM) activity in Eahy926 cells. We found that LPS challenge (i) increased arginine methylation through up-regulated protein arginine methyltransferase-1 (PRMT1) mRNA, intracellular concentrations of asymmetric dimethylarginine (ADMA) and homocysteine (HCY); (ii) up-regulated cell senescence through mitigated sirtuin-1 (SIRT1) mRNA, nicotinamide adenine dinucleotide (NAD+) concentration, telomerase activity and total antioxidant capacity; and (iii) lead to endothelial dysfunction through compromised nitric oxide (NOx) production. However, these LPS-mediated cellular events in Eahy926 cells were restored by the synergistic effect of MET and VD. Taken together, this study identified that the dual compound effect inhibits LPS-induced protein arginine methylation, endothelial senescence and dysfunction through the components of epigenetic machinery, SIRT1 and PRMT1, which is a previously unidentified function of the test compounds. In silico results identified the presence of vitamin D response element (VDRE) sequence on PRMT1 suggesting that VDR could regulate PRMT1 gene expression. Further characterization of the cellular events associated with the dual compound challenge, using gene silencing approach or adenoviral constructs for SIRT1 and/or PRMT1 under inflammatory stress, could identify therapeutic strategies to address the endothelial consequences in vascular inflammation-mediated atherosclerosis.

Comparison of characteristics and biocompatibility of green synthesized iron oxide nanoparticles with chemical synthesized nanoparticles.

Iron oxide nanoparticles synthesis is an expanding area of research due of their magnetic properties and possible applications in several novel technologies. FeONPs are indispensable in the biomedical field for diagnosis, treatments and drug delivery and in bioremediation applications. The synthesis route of nanoparticles is a major concern because biological methods are eco-friendly, and chemical methods are considered toxic. The objective of this study is to synthesize FeONPs by two different methods and to compare their properties and efficiency in applications. FeONPs were synthesized and characterized by microscopic and various spectroscopic techniques. The synthesized FeONPs were screened for their cytotoxic activity on PBMCs using MTT assay and found to exhibit good biocompatibility. Moreover, the GS FeONPs exhibited potential antibacterial activities and meanwhile showed less toxicity in brine shrimp lethality assay. Hence, these nanoparticles are biocompatible, environmentally safe and can be utilized in many medical applications.

Identification of beta-sitosterol and stigmasterol in Bambusa bambos (L.) Voss leaf extract using HPLC and its estrogenic effect in vitro.

Focus of the study is to identify a safe alternate to Hormone Replacement Therapy by identifying the presence of ß-sitosterol and stigmasterol in the hydroalcoholic extract of Bambusa bambos using HPTLC and RP-HPLC-PDA; by evaluating the estrogenic effects of extract containing ß-sitosterol and stigmasterol on the growth of MCF-7 cells in vitro. Plant material was identified by DNA sequencing analysis. Presence of ß-sitosterol and stigmasterol was confirmed by HPTLC and direct RP-HPLC-PDA. Peaks with retention time about 19.13 and 21.16min were found to be stigmasterol and ß-sitosterol in extract. Extract was not cytotoxic to MCF-7 cells in any of the dilutions. It induced cell proliferation and all the dilutions except <500µg/ml have significantly increased cell multiplication. 15.6, 31.2, 62.5 and 125µg/ml of HEBB have shown influence on the proliferation rates similar to the standard 17ß-estradiol. The results suggest that HEBB might be used as a safe alternative to estrogen replacement therapies.