Reprogramming Megakaryocytes for Controlled Release of Platelet-like Particles Carrying a Single-Chain Thromboxane A Receptor-G-Protein Complex with Therapeutic Potential.

In this study, we reported that novel single-chain fusion proteins linking thromboxane A (TXA) receptor (TP) to a selected G-protein α-subunit q (SC-TP-Gαq) or to α-subunit s (SC-TP-Gαs) could be stably expressed in megakaryocytes (MKs). We tested the MK-released platelet-linked particles (PLPs) to be used as a vehicle to deliver the overexpressed SC-TP-Gαq or the SC-TP-Gαs to regulate human platelet function. To understand how the single-chain TP-Gα fusion proteins could regulate opposite platelet activities by an identical ligand TXA, we tested their dual functions-binding to ligands and directly linking to different signaling pathways within a single polypeptide chain-using a 3D structural model.

Latest advancements in the study of the relationship between NSAIDs and three prostaglandin E2 synthases.

Tweetable abstract This work describes novel evidence of the relationship between NSAIDs and three prostaglandin E2 synthases.

Design, synthesis and characterization of lead compounds as anti-inflammatory drugs targeting mPGES-1 via enzymelink screening.

The objective of this study was to synthesize and validate a set of compounds that selectively inhibit mPGES-1, with the potential to be developed into a novel anti-inflammatory drug. The synthesized compounds were characterized using H NMR spectroscopy and LC-MS to confirm their structure. Cellular and enzymatic assays were used to demonstrate their inhibitory activity on prostaglandin E2 production.

Engineering 'Enzymelink' for screening lead compounds to inhibit mPGES-1 while maintaining prostacyclin synthase activity.

This study investigated our Enzymelinks, COX-2-10aa-mPGES-1 and COX-2-10aa-PGIS, as cellular cross-screening targets for quick identification of lead compounds to inhibit inflammatory PGE biosynthesis while maintaining prostacyclin synthesis. We integrated virtual and wet cross-screening using Enzymelinks to rapidly identify lead compounds from a large compound library. From 380,000 compounds virtually cross-screened with the Enzymelinks, 1576 compounds were identified and used for wet cross-screening using HEK293 cells that overexpressed individual Enzymelinks as targets.

Suppression of microRNA-16 protects against acute myocardial infarction by reversing beta2-adrenergic receptor down-regulation in rats.

microRNA-16 (miR-16) has been shown to be up-regulated in ischemic heart. Beta2-adrenoreceptor (β2-AR) exerts cardioprotective property in ischemic injury. This study aims to determine the effect of miR-16 in cardiac injury in rats and the possible involvement of β2-AR in this process.

Let-7a Is an Antihypertrophic Regulator in the Heart via Targeting Calmodulin.

MicroRNAs (miRNAs) have been emerged as important regulator in a multiple of cardiovascular disease, including arrhythmia, cardiac hypertrophy and fibrosis, and myocardial infarction. The aim of this study was to investigate whether miRNA let-7a has antihypertrophic effects in angiotensin II (AngII)-induced cardiac hypertrophy. Neonatal rat ventricular myocytes (NRVMs) were exposed to AngII for 36 h as a cellular model of hypertrophy; subcutaneous injection of AngII for 2 weeks was used to establish a mouse model of cardiac hypertrophy in vivo study.

Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21 Pathway.

In the present study, we demonstrated that bone marrow mesenchymal stem cells (BMSCs) of the 3rd passage displayed the senescence-associated phenotypes characterized with increased activity of SA--gal, altered autophagy, and increased G1 cell cycle arrest, ROS production, and expression of p53 and p21 compared with BMSCs of the 1st passage. Cholesterol (CH) reduced the number of SA--gal positive cells in a dose-dependent manner in aging BMSCs induced by HO and the 3rd passage BMSCs. Moreover, CH inhibited the production of ROS and expression of p53 and p21 in both cellular senescence models and decreased the percentage of BMSCs in G1 cell cycle in the 3rd passage BMSCs.

Expression signature of lncRNAs and their potential roles in cardiac fibrosis of post-infarct mice.

The present study aimed to investigate whether long non-coding RNAs (lncRNAs) are involved in cardiac fibrogenesis induced by myocardial infarction (MI). The differentially expressed lncRNAs and mRNAs in peri-infarct region of mice 4 weeks after MI were selected for bioinformatic analysis including gene ontology (GO) enrichment, pathway and network analysis. Left ventricular tissue levels of lncRNAs and mRNAs were compared between MI and sham control mice, using a false discovery rate (FDR) of <5%.