Delacruzsimonsen0395

Humans are exposed to various xenobiotic electrophiles on a daily basis. Electrophiles form covalent adducts with nucleophilic residues of proteins. Redox signaling, which consists of effector molecules (e.g., kinases and transcription factors) and redox sensor proteins with low pKa cysteine residues, is involved in cell survival, cell proliferation, quality control of cellular proteins and oxidative stress response. Herein, we showed that at a low dose, xenobiotic electrophiles selectively modified redox sensor proteins through covalent modification of their reactive thiols, resulting in activation of a variety of redox signaling pathways. However, increasing the dose of xenobiotic electrophiles caused non-selective and extensive modification of cellular proteins involved in toxicity. Of interest, reactive sulfur species (RSS), such as hydrogen sulfide (H2S), cysteine persulfide (CysSSH), glutathione persulfide (GSSH) and even synthetic polysulfide (e.g., Na2S4), readily captured xenobiotic electrophiles, forming their sulfur adducts, which was associated with inactivation of the electrophiles. Our findings suggest that an adaptive response through redox signaling activation and RSS-mediated electrophile capturing is involved in the regulation of electrophilic stress.The true central aim of pharmaceutical research and education is to strive for the patient's satisfaction, i.e., "for the sake of the patient". Our research focuses to bridge the gap between the ideal and current situation in pharmaceutical science. We also investigated/questioned the united roles of pharmacists and pharmacies, with the ambition of changing the work culture of pharmacists. This paper reviews the history of our research and discusses the future of pharmaceutical research and education.Organoselenium compounds have attracted significant interest because of their use as important reagents in organic syntheses and potential biological activities, necessitating the development of simple and general synthetic methods. This article reviews our studies to develop of copper-catalyzed C-Se bond formation reactions via cross coupling and C-H activation. A number of unsymmetrical and symmetrical diaryl selenides were synthesized via Se-arylation of diaryl diselenides or selenium powder with triarylbismuthanes under aerobic conditions, achieving moderate to excellent yields. When the reaction of triphenylbismuthane with elemental Se was monitored with gas chromatography, diphenyl diselenide and diphenyl selenide formation was confirmed. Subsequently, 1-pot 2-step reactions were performed under mild conditions to obtain 3-selanyl imidazo[1,2-a]pyridines from triarylbismuthanes and diimidazopyridyl diselenides, which were generated from imidazo[1,2-a]pyridines and Se powder, in good to excellent yields. It should be noted that all three aryl groups in the bismuth and both selanyl groups in the diaryl diselenide generated from the selenium source were transferred to the coupling products. Cu-catalyzed tandem cyclization of 2-(2-iodophenyl)imidazo[1,2-a]pyridines with selenium for the synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines is also described herein. The molecular structure of the tetracyclic compound features nearly coplanar rings, and the maximum absorption is red-shifted compared to those of imidazo[1,2-a]pyridine and benzoselenophene.The lens of the eye is an avascular and anuclear tissue that serves to focus objects on the retina. Cataract is opacity within the clear lens that changes the transparency and refractive index of the lens causing significant visual impairments. These impairments can severely restrict the ability to carry out daily activities. Cataracts is common among elderly person occurring in more than 80% of patients aged 80 or older. Notably, we have recently identified key compounds that are effective against cataract formation. Presbyopia is also an ocular disease that typically develops in people over the age of 45 while affecting almost 100% of people over the age of 65. Recent research suggests that age-related changes in hydrostatic pressure of the lens controlled by Na/K ATPase contribute to the development of presbyopia. In the lens, Na/K ATPase has been shown to be regulated by transient receptor potential cation channels, vanilloid 1 (TRPV1) and 4, thus suggesting the potential role of TRPV1 and TRPV4 in the development of presbyopia. This review article summarizes data obtained from our laboratory with my colleagues highlighting the critical role of aquaporin 0 (AQP0) in maintaining a healthy lens redox environment, key molecules that delay the onset of cataract in vivo, as well as potential mechanisms of lens hydrostatic pressure control that may be associated with presbyopia.This review, based on my research work, introduces and summarizes the synthesis and characterization of novel cyclic compounds containing aminobenzenesulfonamide. The review discusses the (1) development of sequential Nicholas and Pauson-Khand reactions for the synthesis of unique polyheterocyclic compounds, (2) production of 2-aminobenzenesulfonamide-containing cyclononyne (ABSACN) as a multifunctional click cycloalkyne agent, and (3) improvement of the intramolecular Pauson-Khand reaction of the nitroarene-enyne substrate for the synthesis of cyclopenta[c]piperidine alkaloids. This research work will facilitate the discovery of sulfonamide or sultam-based functional molecules and pharmaceuticals. Thus, I believe that aminobenzenesulfonamide derivatives are versatile and valuable chemical moieties not only in organic syntheses but also in the pharmaceutical industry. If you are interested in the details of this topic, please refer to the original papers.Objectives　We hypothesized that the motivation for improving physical function could be increased by increasing the awareness of social role expectations among frail community-dwelling older adults through an intervention based on the Community-as-Partner (CAP) model. We also developed a program for supporting community activities to prevent frailty, utilizing the CAP model. Program feasibility was assessed by implementing it under the local government's frailty prevention service.Methods　The CAP-based program consisted of a "learning period," a "regional issue extraction period," and a "practice period," scheduled once a week for four months. Public health nurses and/or physical therapists assisted with the program. The intervention was conducted with a cohort study of community-dwelling older adults. About 160 participants identified as frail and pre-frail on the Kihon Checklist were recruited. Tamoxifen Program feasibility was assessed through participation rate, number of pre-frail and frail individuals, and drop-out rate; scores of a pre-post intervention questionnaire assessing the understanding of frailty and regional resources; and behavioral change stage on frailty prevention.