Results for the control group indicated that the players' PA metrics (cadence F(19, 360) = 1.43, p = 0.11; heart rate F(19, 360) = 1.16, p = 0.29; oxygen consumption F(19, 360) = 0.83, p = 0.67) were stable during the exergame. Results for the experimental group demonstrated the effects of time on the players' PA metrics and revealed significant associations between the change in the players' situational interest dimensions and PA metrics (cadence F(19, 800) = 26.30, p < 0.01; heart rate F(19, 800) = 19.77, p < 0.01; oxygen consumption F(19, 800) = 10.04, p < 0.01). An approach using a design-based exergame may be a relevant strategy for promoting levels of PA that yield positive health-related outcomes among college students. An approach using a design-based exergame may be a relevant strategy for promoting levels of PA that yield positive health-related outcomes among college students.In the present study, with the aim of improving the permeability of methotrexate (MTX) to the brain, the lipophilic MTX prodrugs containing the ester functional moiety were synthesized. The chemical structure of synthesized prodrugs was characterized and confirmed by FT-IR, NMR and mass spectral studies. Based on the results of in vitro cytotoxic studies, all of the synthesized prodrugs led to decrease in the IC50 in 72 h on U87 cancer cell line and the best result was observed for dihexyl methotrexate (MTX-DH) in comparison with free MTX, which led to decrease the IC50 amount up to 6 folds. In addition, in vivo toxicity on Artemia salina (A. salina) showed that the lipophilic MTX prodrugs have been able to partially mask the toxic profile of free MTX, at the same concentrations. These findings were also in compliance with hemolysis assay results, which confirm that the conjugates has not made the drug more toxic. Furthermore, in vivo study in rat model, was employed to determine the simultaneous drug concentration in brain and plasma. According to the obtained results, the brain-to-plasma concentration ratios (Kp values) of MTX-DH and dioctyl methotrexate (MTX-DO) groups were significantly higher compared with free MTX. Moreover, the uptake clearance of MTX by brain parenchyma increased significantly (3.85 and 9.08-time increased for MTX-DH and MTX-DO prodrugs, respectively). These findings indicate that the synthesized lipophilic MTX prodrugs are non-toxic and able to enhance brain penetration of MTX.Polyvinyl alcohol (PVA) is a biodegradable semicrystalline synthetic polymer that has been used for biomedical applications for several years. In the pharmaceutical area, PVA has been widely used to prepare solid dispersions to improve the solubility of drugs. Furthermore, it has been demonstrated that PVA is highly biocompatible and non-toxic in in-vitro and in-vivo studies. Several reports provided in this review suggest a promising strategy for cancer treatment. Thus far, the current therapy includes a combination of surgery, chemotherapy, and radiotherapy, the effectivity can be limited due to the heterogeneous manifestations of the disease, dose-related toxicity, and side effects. A promising strategy is the implementation of a targeted therapy using hydrogels, microparticles, or nanoparticles (NPs), capable of encapsulating, protecting, transporting, and targeted administration of a therapeutic agent. Considering the relevance of the PVA in conjunction with their copolymers, it has become a promising biodegradable material to build novel functional composites used in the fabrication of hydrogels, microparticles, nanoparticles, and nanocomposites for drug delivery systems in cancer treatment.The objective of present study is to develop bilayer abuse-deterrent extended-release tablets (ADERTs) using propranolol HCl as model drug for opioids overdose crisis. Bilayer ADERTs were fabricated by direct compression and formulated with polymer matrix in extended-release drug layer coupled with alkalizing and aversive agents in fast-disintegrating pH modifying layer. Various alkalizing agents, like magnesium hydroxide, aluminum hydroxide, calcium carbonate, and calcium hydroxide, were evaluated for their abuse-deterrent potential via in-vitro drug release and extraction studies. https://www.selleckchem.com/products/4sc-202.html Based on the outcomes, magnesium hydroxide was selected as an alkalizing agent, since it raised the pH of dissolving media near to pKa of the drug studied in this investigation. The formulated bilayer ADERTs with magnesium hydroxide provided similar drug release profiles as compared to conventional extended-release tablets for single-unit ingestion. However, upon ingestion of multiple-unit bilayer ADERTs, the fast-disintegrating pH modifying layer increases pH of dissolving media, while extended-release layer increases micro-environmental pH within tablets. Retarding drug release owing to low solubility of basic drug at higher pH was observed. Therefore, the application of alkalizing agent has impact on pH-dependent solubility of drug like opioids and demonstrate its useful potential to be incorporated in bilayer ADERTs for opioids overdose crisis. Patients with systemic lupus erythematosus (SLE) have a high burden of cardiovascular disease (CVD) of multifactorial origin. The aim of this systematic review is to analyze the role of the interferon I (IFN-I) signature and fibroblast growth factor-23 (FGF-23) in patients with SLE or cutaneous lupus erythematosus (CLE) herein. We conducted a systematic literature search in PubMed and Scopus using keywords for major adverse cardiovascular events (MACE) and intermediate outcomes (endothelial dysfunction, subclinical atherosclerosis, platelet activation) associated with IFN-I or FGF-23 in patients with SLE and CLE. 4745 citations were screened, of which 12 studies were included. IFN-I was associated with MACE in two third of the studies and the association was strongest for cardiac events. An association of IFN-I was found in all studies investigating impaired vascular function, but only in 50% (respectively 40%) of reports examining the relation of IFN-I and platelet activation (respectively subclinical atherosclerosis).