Characterization of AST-001 non-clinical pharmacokinetics: A novel selective AKR1C3-activated prodrug in mice, rats, and cynomolgus monkeys.

AST-001 is a chemically synthesized inactive nitrogen mustard prodrug that is selectively cleaved to a cytotoxic aziridine (AST-2660) via aldo-keto reductase family 1 member C3 (AKR1C3). The purpose of this study was to investigate the pharmacokinetics and tissue distribution of the prodrug, AST-001, and its active metabolite, AST-2660, in mice, rats, and monkeys. After single and once daily intravenous bolus doses of 1.

Impact of macrophage differentiation on hematopoietic function enhancement by Shenzhu ErKang Syrup.

Shenzhu Erkang Syrup (SZEK) is a traditional Chinese medicine that improves spleen and stomach function, tonifying the Qi and activating the blood; however, its therapeutic effects in hematopoietic dysfunction and their underlying mechanism remain unexplored. In this study, mice were given cyclophosphamide (100 mg/kg) by intraperitoneal injections for three days to produce hematopoietic dysfunction model. We investigated the hematopoietic effect and mechanism of SZEK in mice with hematopoietic dysfunction via histopathological examination, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting combined with intestinal flora and serum metabolomics analysis.

Multi-network granular hydrogel with enhanced strength for 3D bioprinting.

Granular hydrogels are a kind of bulk hydrogel that are densely assembled by microparticles, showing great potential in 3D bioprinting. To develop a granular hydrogel-based bioink with enhanced strength, the present study combined methacryloylated gelatin (GelMA) with granular hydrogel to fabricate a compound bioink. Poly (γ-glutamic acid) (PG) microspheres and hydroxy propyl chitosan (CSPO) microspheres were fabricated, respectively, and self-assembled via charge interaction between microspheres to form a granular hydrogel after adding GleMA solution.

Uncovering the Pathogenesis of Orofacial Clefts Using Bioinformatics Analysis.

Objective: Many genes have been found to be associated with the occurrence of the orofacial clefts (OFC). The links between these pathogenic genes are rarely studied. In this study, bioinformatics analysis were performed in order to find associations between OFC- related genes and provide new ideas for etiology study of OFCs.

SIRT1 Antagonizes Oxidative Stress in Diabetic Vascular Complication.

Diabetic mellitus (DM) is a significant public health concern worldwide with an increased incidence of morbidity and mortality, which is particularly due to the diabetic vascular complications. Several pivotal underlying mechanisms are associated with vascular complications, including hyperglycemia, mitochondrial dysfunction, inflammation, and most importantly, oxidative stress. Oxidative stress triggers defective angiogenesis, activates pro-inflammatory pathways and causes long-lasting epigenetic changes to facilitate the development of vascular complications.

Assessing the impacts of signal coordination on the crash risks of various driving cohorts.

Introduction: Signal coordination has been wildly implemented on urban arterials to improve traffic efficiency. The impacts of signal coordination on traffic safety, however, are largely overlooked, particularly on crash propensities of driver-vehicle cohorts, which will vary due to changing traffic flow patterns.

Method: The paper aims to compare crash risks of various driving cohorts (measured by relative crash involvement ratio) on arterials with and without signal coordination with quasi-induced exposure technique, which has been well developed in estimating crash risks for driver-vehicle characteristics (i.

Microscopic evaluation of traffic safety at signal coordinated intersections: A before-after study.

Objective: This research aims to evaluate the safety impacts of signal coordination on signalized intersections and provide a scientific basis to design and improve signal control and management from a traffic safety perspective.

Methods: A kernel regression model is adopted to evaluate the safety performance of intersections before and after implementing the signal coordination strategy. By using this statistical method, the authors identify the nonlinear relationship between crash frequency and the crash's spatial location and examine the discrepancy of crash spatial distributions between the coordination and noncoordination conditions at disaggregated levels, such as time of day and crash type.

Hydrogel-Forming Microneedle Arrays Allow Detection of Drugs and Glucose In Vivo: Potential for Use in Diagnosis and Therapeutic Drug Monitoring.

We describe, for the first time the use of hydrogel-forming microneedle (MN) arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) (11.1% w/w) and poly(ethyleneglycol) 10,000 daltons (5.

Senegalin: a novel antimicrobial/myotropic hexadecapeptide from the skin secretion of the African running frog, Kassina senegalensis.

Amphibian skin is a rich and unique source of novel bioactive peptides most of which are endowed with either antimicrobial or pharmacological properties. Here, we report the identification and structural characterization of a novel peptide, named senegalin, which possesses both activities. Senegalin is a hexadecapeptide amide (FLPFLIPALTSLISSL-NH2) of unique primary structure found in the skin secretion of the African running frog, Kassina senegalensis.