德岛文理大学

Arsenic (As), an environmental toxicant commonly found in groundwater, exerts its toxic effects primarily through oxidative stress. Selenium (Se) plays a crucial role in counteracting oxidative stress by promoting the synthesis of Se-containing antioxidant enzymes, such as glutathione peroxidases (GPx). To elucidate the impact of As on cellular Se metabolism, we investigated the effects of inorganic arsenic on cultured cells (HT-1080, Jurkat, and SH-SY5Y). Our findings indicate that As(III) disrupts Se metabolism and inhibits Se-induced GPx expression. By comparing different Se sources (selenoprotein P, selenocysteine, and selenite), we determined that As(III) primarily interferes with Se metabolism downstream of selenite, an inorganic form of Se. Notably, exposure to As(III) reduced Se incorporation into RNA, suggesting inhibition of Sec-tRNASec synthesis, a critical step in selenoprotein biosynthesis. Additionally, As(III) increased cellular susceptibility to ferroptosis, a form of oxidative stress-driven lipid peroxidation-mediated cell death primarily regulated by GPx4. Supporting this, genetic deletion of PRDX6, a recently identified regulator of cellular Se metabolism, further suppressed selenoprotein expression and exacerbated As(III)-induced ferroptosis. These findings provide new insights into the toxicological mechanisms of As compounds, highlighting their role in disrupting Se metabolism and potentially mitigating the side effects associated with arsenic-based anticancer therapies.

Background:In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision. Objective:This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration. Methods:We recruited 191 fifth-year pharmaceutical students during the 2022-2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate students' awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results. Results:Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505-0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=-0.504, 95% CI -0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI -0.148 to -0.193; P=.004), and communication (r=0.221, 95% CI -0.151 to -0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics. Conclusions:This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy students' professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients.

In solid-phase oligonucleotide (ON) synthesis, a capping step is beneficial for obtaining a pure full-length ON. Acetic anhydride (Ac2O) is widely used as a conventional capping reagent. However, several problems associated with acetyl capping have been reported. In this study, we developed a novel phosphoramidite-type capping reagent, ethano N,N-dicyclohexylphosphoramidite (EDCP), which was obtained as an easy-to-handle crystalline solid. EDCP, with a sterically accessible phosphorus atom, exhibited a higher capping ability than Ac2O and diethyl N,N-diisopropylphosphoramidite, which was previously reported as a phosphoramidite-type capping reagent. Furthermore, capping-derived byproducts were not detected during solid-phase ON synthesis using EDCP. These results indicate that EDCP is a useful capping reagent that can serve as an alternative to Ac2O and has potential applications in ON synthesis.

The Euphorbia greenwayi essential oil (EGEO) was analyzed by GC-MS, and 17 components were identified, accounting for 99.70%, predominantly monoterpene (98.28%). The major components were limonene (26.46%), α-pinene (18.50%), 1,8-cineole (25.62%), β-pinene (6.52%), and γ-terpinene (4.36%). Antioxidant potential was evaluated using DPPH and ABTS radical scavenging assays. The EGEO exhibited dose-dependent activity, with respective IC50 values of 417.7 and 448.8 mg/L, indicating moderate antioxidant capacity. Cytotoxic activity was assessed on THLE-2 (normal liver), MCF-7 (breast cancer), and HepG2 (liver cancer) cells. The EGEO exhibited negligible cytotoxicity toward THLE-2 cells (> 93% viability at 0.1-500 µg/mL), while showing pronounced cytotoxicity against MCF-7 cells (IC50 = 166.65 µg/mL) and moderate activity against HepG2 cells (IC50 = 328.03 µg/mL), highlighting selective antiproliferative effects. Molecular docking further substantiated the anticancer potential of EO constituents. Limonene demonstrated the strongest binding affinity against aurora kinase A (-10.586 kcal/mol) and the tumor suppressor PTEN (-6.397 kcal/mol), outperforming other tested monoterpenes. It established key interactions with hinge (Ala273), DFG motif residues in aurora A, and P-loop residues (Cys124, Arg130) in PTEN, positioning it as a dual-target lead compound. Sabinene also showed favorable binding to aurora A (-9.964 kcal/mol) but was less active toward PTEN. These findings suggested that EGEO possesses promising antioxidant and anticancer properties, with limonene emerging as a potential multitarget therapeutic agent for oxidative stress-related and proliferative disorders.

2 '-O,4 '-C-Ethylene-bridged nucleic acid (ENA) is a promising chemical modification for oligonucleotide (ON) therapeutics. Thus, ENA analogs bearing functional groups on the ethylene bridges were designed to explore new candidates for ON therapeutics. Specifically, the phosphoramidite of 2 '-O,4 '-C-ethylene-bridged 5-methyluridine (ENA-T-CO2Me) bearing a methoxycarbonylmethyl group on the bridge was synthesized and it was incorporated into ONs using an automated ON synthesizer. The methoxycarbonyl moieties in the ONs were subsequently converted into carboxylic acid equivalents, such as carboxyl and carbamoyl groups, by the corresponding base treatment in a post-synthetic approach. Duplex-forming ability and nuclease stability of ONs with these ENA analogs were evaluated. Among the analogs, the carboxymethyl-substituted analog (ENA-T-CO2H) highly stabilized a duplex with single-stranded RNA and exhibited the greatest resistance to degradation by 3 '-exonuclease.