Enhanced pharmacological activities of AKR1C3-activated prodrug AST-3424 in cancer cells with defective DNA repair.

AST-3424 is a novel and highly tumor-selective prodrug. AST-3424 is activated by AKR1C3 to release a toxic bis-alkylating moiety, AST 2660. In this study, we have investigated the essential role of DNA repair in AST-3424 mediated pharmacological activities in vitro and in vivo.

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.

Trends in dacryocystitis in China: A STROBE-compliant article.

The aim of the study was to review the distribution, current trends, and microbiological characteristics of bacterial pathogens isolated from dacryocystitis patients in China during the last 15 years.This is a retrospective multiple-center noncomparative case series. The medical records of 15,452 consecutive patients from 7 cities diagnosed as having dacryocystitis between 2002 and 2016 were reviewed.

Methylene Blue Attenuates Diabetic Retinopathy by Inhibiting NLRP3 Inflammasome Activation in STZ-Induced Diabetic Rats.

: This study aimed to investigate the regulatory effects of methylene blue (MB) on diabetic retinopathy (DR) and explored the molecular mechanisms of MB as a retina protection agent. : The thicknesses of retinal layers and permeability of the blood-retinal barrier (BRB) were measured by histology analysis, and the expression levels of NLRP3, ASC, procaspase-1, caspase-1, IL-1β, and IL-18 were measured by western blotting. Lentivirus-based knockdown of gene was used to confirm the role of NLRP3 inflammasome.

Nano-cage-mediated refolding of insulin by PEG-PE micelle.

Insulin aggregation has pronounced pharmaceutical implications and biological importance. Deposition of insulin aggregates is associated with type II diabetes and instability of pharmaceutical formulations. We present in this study the renaturation effect of PEG-PE micelle on dithiothreitol (DTT)-denatured insulin revealed by techniques including turbidity assay, circular dichroism (CD), thioflavinT (ThT) binding assay, bis-ANS binding assay, agarose gel electrophoresis and MALDI-TOF MS.

Poly(ethylene glycol)-mediated conformational alteration of α-chymotrypsin prevents inactivation of insulin by stabilizing active intermediates.

Proteolytic enzymes in the gut represent one of the biggest barriers against oral delivery of therapeutic proteins and peptides. In the current study, we explored the effect of poly(ethylene glycol) 400 (PEG 400), a commonly used crowding agent, on insulin degradation mediated by α-chymotrypsin (α-CT). Without PEG 400, insulin was quickly cleaved by α-CT to generate inactive degradation products.

A novel peptide from alpha5 helix of Asterina pectinifera cyclin B conjugated to HIV-Tat(49-57) with cytotoxic and apoptotic effects against human cancer cells.

A series of novel peptides from various motifs of Asterina pectinifera cyclin B and their derivatives conjugated to HIV-Tat(49-57) were designed and synthesized. Their bioactivities on two human cancer cell lines were determined. Among them, Tat-a5 (KAQIRAMECNILGRKKRRQRRR) exhibited significant cytotoxic effects on cancer cell lines EC-9706 and HCT-116.