Ursolic acid promotes microglial polarization toward the M2 phenotype via PPARγ regulation of MMP2 transcription.

Microglia, which are the primary inflammatory cells of the brain, can undergo phenotypic switching between M1 and M2 polarization, which have opposing effects on inflammation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor family of ligand-inducible transcription factors, and PPARγ is known to regulate M2 macrophage polarization. Previous studies have shown that the natural pentacyclic triterpenoid ursolic acid (3β-hydroxy-urs-12-en-28-oic acid; UA) influences microglial activation.

PEGylated amphiphilic polymeric manganese(II) complexes as magnetic resonance angiographic agents.

Currently, the most commonly used clinical magnetic resonance imaging (MRI) contrast agents, Gd(III) chelates, have been found to be associated with nephrogenic systemic fibrosis (NSF) in renally compromised patients. Toxicity concerns related to Gd(III)-based agents prompted intensive research toward the development of safe, efficient, and long-cycle non-Gd contrast agents. Herein, three amphiphilic polymeric manganese (Mn) ligands (mPEG-P(L-a-HMDI)-mPEG, mPEG-P(L-a-HMDI)-mPEG and mPEG-P(L-a-HMDI)-mPEG) were synthesized, and then end-capped respectively with different molecular weights of polyethylene glycol monomethyl ether (mPEG 1 kD, 2 kD and 4 kD) to obtain amphiphilic polymer Mn ligands.

Comparative analysis of variation in the quality and completeness of local outbreak control plans for SARS-CoV-2 in English local authorities.

Background: Local outbreak control plans (LOCPs) are statutory documents produced by local authorities (LAs) across England. LOCPs outline LAs' response to Coronavirus Disease 19 (COVID19) outbreaks and the coordination of local resources, data and communication to support outbreak response. LOCPs are therefore crucial in the nation's response to COVID-19.

Dual regulation of osteoclastogenesis and osteogenesis for osteoporosis therapy by iron oxide hydroxyapatite core/shell nanocomposites.

Osteoporosis is a skeletal disorder resulted in significant structural and functional changes, arousing a wide concern for the high prevalence and cost. Imbalance between osteoclastogenesis and osteogenesis have been verified as a main pathology etiology and considered an efficient therapy target in both clinical and pre-clinical studies. In recent years, inorganic nanomaterials have shown provable activities on osteoclastogenesis inhibition and osteogenesis promotion, respectively.

Iron oxide nanoparticles promote vascular endothelial cells survival from oxidative stress by enhancement of autophagy.

Dextran-coated superparamagnetic iron oxide nanoparticles (Dex-SPIONs) are excellent magnetic resonance imaging contrast agents for disease diagnosis and therapy. They can be delivered to target tissues mainly though vascular endothelium cells, which are major targets of oxidative stress. In cardiovascular cells, autophagy serves primarily on a pro-survival approach that protects the cells from oxidative stress even some autophagy inducers have been developed for adjuvant therapy of cardiovascular disorders.

Thymoquinone reduces cardiac damage caused by hypercholesterolemia in apolipoprotein E-deficient mice.

Background: Hypercholesterolemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that thymoquinone protected rats from doxorubicin-induced cardiotoxicity and cardiac damage. The aim of this study was to investigate the possible protective effects of thymoquinone against cardiac damage in apolipoprotein E knockout (ApoE) mice.

Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling.

Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP] ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption.

Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.

Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention.