The cerebroprotection and prospects of FNDC5/irisin in stroke.

Stroke, the leading cause of disability and cognitive impairment, is also the second leading cause of death worldwide. The drugs with multi-targeted brain cytoprotective effects are increasingly being advocated for the treatment of stroke. Irisin, a newly discovered myokine produced by cleavage of fibronectin type III domain 5, has been shown to regulate glucose metabolism, mitochondrial energy, and fat browning. A large amount of evidence indicated that irisin could exert anti-inflammatory, anti-apoptotic, and antioxidant properties in a variety of diseases such as myocardial infarction, inflammatory bowel disease, lung injury, and kidney or liver disease. Studies have found that irisin is widely distributed in multiple brain regions and also plays an important regulatory role in the central nervous system. The most common cause of a stroke is a sudden blockage of an artery (ischemic stroke), and in some circumstances, a blood vessel rupture can also result in a stroke (hemorrhagic stroke). After a stroke, complicated pathophysiological processes lead to serious brain injury and neurological dysfunction. According to recent investigations, irisin may protect elements of the neurovascular unit by acting on multiple pathological processes in stroke. This review aims to outline the currently recognized effects of irisin on stroke and propose possible directions for future research.

Silver Nanoparticles Encapped by Dihydromyricetin: Optimization of Green Synthesis, Characterization, Toxicity, and Anti-MRSA Infection Activities for Zebrafish (Danio rerio).

To achieve the environmentally friendly and rapid green synthesis of efficient and stable AgNPs for drug-resistant bacterial infection, this study optimized the green synthesis process of silver nanoparticles (AgNPs) using Dihydromyricetin (DMY). Then, we assessed the impact of AgNPs on zebrafish embryo development, as well as their therapeutic efficacy on zebrafish infected with Methicillin-resistant Staphylococcus aureus (MRSA). Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) analyses revealed that AgNPs possessed an average size of 23.6 nm, a polymer dispersity index (PDI) of 0.197 ± 0.0196, and a zeta potential of -18.1 ± 1.18 mV. Compared to other published green synthesis products, the optimized DMY-AgNPs exhibited smaller sizes, narrower size distributions, and enhanced stability. Furthermore, the minimum concentration of DMY-AgNPs required to affect zebrafish hatching and survival was determined to be 25.0 µg/mL, indicating the low toxicity of DMY-AgNPs. Following a 5-day feeding regimen with DMY-AgNP-containing food, significant improvements were observed in the recovery of the gills, intestines, and livers in MRSA-infected zebrafish. These results suggested that optimized DMY-AgNPs hold promise for application in aquacultures and offer potential for further clinical use against drug-resistant bacteria.

Au-Fe3O4 Janus nanoparticles for imaging-guided near infrared-enhanced ferroptosis therapy in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is insensitive to conventional therapy due to its highly invasive nature resulting in poor therapeutic outcomes. Recent studies have shown multiple genes associated with ferroptosis in TNBC, suggesting an opportunity for ferroptosis-based treatment of TNBC. However, the efficiency of present ferroptosis agents for cancer is greatly restricted due to lack of specificity and low intracellular levels of H2O2 in cancer cells. Herein, we report a nano-theranostic platform consisting of gold (Au)-iron oxide (Fe3O4) Janus nanoparticles (GION@RGD) that effectively enhances the tumor-specific Fenton reaction through utilization of near-infrared (NIR) lasers, resulting in the generation of substantial quantities of toxic hydroxyl radicals (•OH). Specifically, Au nanoparticles (NPs) converted NIR light energy into thermal energy, inducing generation of abundant intracellular H2O2, thereby enhancing the iron-induced Fenton reaction. The generated •OH not only lead to apoptosis of malignant tumor cells but also induce the accumulation of lipid peroxides, causing ferroptosis of tumor cells. After functionalizing with the activity-targeting ligand RGD (Arg-Gly-Asp), precise synergistic treatment of TNBC was achieved in vivo under the guidance of Fe3O4 enhanced T2-weighted magnetic resonance imaging (MRI). This synergistic treatment strategy of NIR-enhanced ferroptosis holds promise for the treatment of TNBC.

Crosstalk Between Matrix Metalloproteinases and Their Inducer EMMPRIN/CD147: a Promising Therapeutic Target for Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is characterized by the disruption of cerebrovascular integrity, resulting in hematoma enlargement, edema formation, and physical damage in the brain parenchyma. Primary ICH also leads to secondary brain injury contributed by oxidative stress, dysregulated immune responses, and proteolysis. In this context, matrix metalloproteinases (MMPs) represent a ubiquitous superfamily of structurally related zinc-dependent endopeptidases capable of degrading all components of the extracellular matrix. They disrupt the blood-brain barrier and promote neuroinflammation. Importantly, several MMP members are upregulated following ICH, and members may have different functions at specific periods in ICH. Hence, the modulation and function of MMPs are more complex than expected. Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that induces the production of MMPs. In this review, we systematically discuss the biology and functions of MMPs and EMMPRIN/CD147 in ICH and the complex crosstalk between them.