Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a tissue damage during reperfusion after an ischemic condition. I/R injury is induced by pathological cases including stroke, myocardial infarction, circulatory arrest, sickle cell disease, acute kidney injury, trauma, and sleep apnea. It can lead to increased morbidity and mortality in the context of these processes. Mitochondrial dysfunction is one of the hallmarks of I/R insult, which is induced via reactive oxygen species (ROS) production, apoptosis, and autophagy. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play a main regulatory role in gene expression. Recently, there are evidence, which miRNAs are the major modulators of cardiovascular diseases, especially myocardial I/R injury. Cardiovascular miRNAs, specifically miR-21, and probably miR-24 and miR-126 have protective effects on myocardial I/R injury. Trimetazidine (TMZ) is a new class of metabolic agents with an anti-ischemic activity. It has beneficial effects on chronic stable angina by suppressing mitochondrial permeability transition pore (mPTP) opening. The present review study addressed the different mechanistic effects of TMZ on cardiac I/R injury. Online databases including Scopus, PubMed, Web of Science, and Cochrane library were assessed for published studies between 1986 and 2021. TMZ, an antioxidant and metabolic agent, prevents the cardiac reperfusion injury by regulating AMP-activated protein kinase (AMPK), cystathionine-γ-lyase enzyme (CSE)/hydrogen sulfide (H2S), and miR-21. Therefore, TMZ protects the heart against I/R injury by inducing key regulators such as AMPK, CSE/H2S, and miR-21.

pH-responsive glucosamine anchored polydopamine coated mesoporous silica nanoparticles for delivery of Anderson-type polyoxomolybdate in breast cancer.

AIM: This study aimed to develop novel pH-sensitive Glucosamine (Glu) targeted Polydopamine (PDA) coated mesoporous silica (SBA-15) nanoparticles (NPs) for selective delivery of anticancer Anderson-type manganese polyoxomolybdate (POMo) to breast cancer. METHODS: The POMo@SBA-PDA-Glu NPs were prepared via direct hydrothermal synthesis of SBA, POMo loading, in situ PDA post functionalization, and Glu anchoring; the chemical structures were fully studied by different characterisation methods. The anticancer activity was studied by MTT method and Annexin V-FITC apoptosis detection kit. RESULTS: The optimised NPs had a hydrodynamic size (HS) of 195 nm, a zeta potential (ZP) of -18.9 mV, a loading content percent (LC%) of 45%, and a pH-responsive release profile. The targeted NPs showed increased anticancer activity against breast cancer cell lines compared to the free POMo with the highest cellular uptake and apoptosis level in the MDA-MB-231 cells. CONCLUSIONS: POMo@SBA-PDA-Glu NPs could be a promising anticancer candidate for further studies.

Biotin-Targeted Nanomicellar Formulation of an Anderson-Type Polyoxomolybdate: Synthesis and In Vitro Cytotoxicity Evaluations.

This study is aimed at developing a micellar carrier for an Anderson-type manganese polyoxomolybdate (TRIS-MnPOMo) to improve the potency and reduce the general toxicity. The biotin-targeted stearic acid-polyethylene glycol (SPB) polymeric conjugate was selected for the first time as a micelle-forming basis for the delivery of TRIS-MnPOMo to breast cancer cells. The cytotoxicity of TRIS-MnPOMo and its nanomicellar form (TRIS-MnPOMo@SPB) was evaluated against MCF-7, MDA-MB-231 (breast cancer cell lines), and HUVEC (normal cell line) in vitro using the MTT assay. The quantity of cellular uptake and apoptosis level were studied properly using standard methods. The hydrodynamic size, zeta potential, and polydispersity index of the prepared micelles were 140 nm, -15.6 mV, and 0.16, respectively. The critical micelle concentration was about 30 µg/mL, which supports the colloidal stability of the micellar dispersion. The entrapment efficiency was interestingly high (about 82%), and a pH-responsive release of TRIS-MnPOMo was successfully achieved. The micellar form showed better cytotoxicity than the free TRIS-MnPOMo on cancer cells without any significant heme and normal cell toxicity. Biotin-targeted nanomicelles internalized into the MDA-MB-231 cells interestingly better than nontargeted micelles and TRIS-MnPOMo, most probably via the endocytosis pathway. Furthermore, at the same concentration, micelles remarkably increased the level of induced apoptosis in MDA-MB-231 cells. In conclusion, TRIS-MnPOMo@SPB could profoundly improve potency, safety, and cellular uptake; these results are promising for further evaluations in vivo.