Optimization of Antiviral Prodrug Properties Using Combinatorial Methods

Abstract

Some diacid biodegradable synthesis of aziduthymidine (AZT) were synthesized and applied to production of about 60 different derivatives.     

Structure-based protein design with deep learning

Since the first revelation of proteins functioning as macromolecular machines through their three dimensional structures, researchers have been intrigued by the marvelous ways the biochemical processes are carried out by proteins. The aspiration to understand protein structures has fueled extensive efforts across different scientific disciplines. In recent years, it has been demonstrated that proteins with new functionality or shapes can be designed via structure-based modeling methods, and the design strategies have combined all available information — but largely piece-by-piece — from sequence derived statistics to the detailed atomic-level modeling of chemical interactions. Despite the significant progress, incorporating data-derived approaches through the use of deep learning methods can be a game changer. In this review, we summarize current progress, compare the arc of developing the deep learning approaches with the conventional methods, and describe the motivation and concepts behind current strategies that may lead to potential future opportunities.     

Impact of High Deductible Health Plans on Diabetes Care Quality and Outcomes: Systematic Review

ObjectiveTo provide a review of the impact of high deductible health plans (HDHPs) on the utilizations of services required for optimal management of diabetes and subsequent health outcomes.MethodsSystematic literature review of studies published between January 1, 2000, and May 7, 2021, was conducted that examined the impact of HDHP on diabetes monitoring (eg, recommended laboratory and surveillance testing), routine care (eg, ambulatory appointments), medication management (eg, medication initiation, adherence), and acute health care utilization (eg, emergency department visits, hospitalizations, incident complications).ResultsOf the 303 reviewed articles, 8 were relevant. These studies demonstrated that HDHPs lower spending at the expense of reduced high-value diabetes monitoring, routine care, and medication adherence, potentially contributing to the observed increases in acute health care utilization. Additionally, patient out-of-pocket costs for recommended screenings doubled, and total health care expenditures increased by 49.4% for HDHP enrollees compared with enrollees in traditional health plans. Reductions in disease monitoring and routine care and increases in acute health care utilization were greatest in lower-income patients. None of the studies examined the impact of HDHPs on access to diabetes self-management education, technology use, or glycemic control.ConclusionAlthough HDHPs reduce some health care utilization and costs, they appear to do so at the expense of limiting high-value care and medication adherence. Policymakers, providers, and payers should be more cognizant of the potential for negative consequences of HDHPs on patients’ health.     

耐药细菌蛋白质的分泌——新抗攻击的靶点

几十年来,由于抗生素的大量使用,导致了细菌对很多药物的抗药性.为了克服细菌的抗药性问题,需要用新的思路去发掘新的抗生素,包括发掘细菌细胞中存在的抗生素作用的新靶点.蛋白质的分泌过程对于细菌是生死攸关的,它可能成为新药物的适合靶点.     

Portrait of the Patient as a Young Man: An Exploration of the Use of Photographs in Hospital

The display of personal photographs in hospital is a common practice that has yet to be rigorously examined. The photographs displayed are subject to interpretation by the viewer and may lead to misunderstandings or miscommunication if clarification of meaning is not sought. This paper explores a range of possible meanings that the display of photographs in hospital may hold, based on a case study of a 15 year old boy hospitalised with a life threatening illness. Further research is needed into the actual meanings attributed to the display of photographs in hospital by patients and family members.     

Pinocytic uptake and intracellular degradation of N-(2-hydroxypropyl)methacrylamide copolymers a potential drug delivery system

Synthetic ¹²⁵I-labelled N-(2-hydroxypropyl)methacrylamide copolymers containing four different, potentially degradable peptidyl side chains were incubated with rat visceral yolk sacs cultured in vitro. All copolymers were captured by fluid-phase pinocytosis and three of the side chains were susceptible to lysosomal hydrolysis, resulting in release of [¹²⁵I]iodotyrosine back into the culture medium. Uptake and degradation was completely inhibited by 2,4-dinitrophenol. The thiol-proteinase inhibitor leupeptin did not affect the rate of pinocytosis, but caused different degrees of inhibition of hydrolysis depending on side chain composition.     

Development of PEGylated serum albumin with multiple reduced thiols as a long-circulating scavenger of reactive oxygen species for the treatment of fulminant hepatic failure in mice

Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and d-galactosamine (LPS/d-GalN) into mice. The LPS/d-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, l-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure.     

The opioid systems - Panacea and nemesis

This mini-review outlines the opioid systems and their roles primarily as related to reward and compulsive drug/alcohol intake. The central role is taken by the mu-opioid receptor, target for opiate analgesics and also a central target in compulsive alcohol abuse, alcoholism. The mu-opioid receptor and the cognate opioid neuropeptides from proenkephalin and proopiomelancortin are members of a superfamily of opioid systems, each with unique and still to be defined roles in the central nervous system.