The prevention, treatment, and rehabilitation of spinal cord injury (SCI) have always posed significant medical challenges. After mechanical injury, disturbances in microcirculation, edema formation, and the generation of free radicals lead to additional damage, impeding effective repair processes and potentially exacerbating further dysfunction. In this context, inflammatory responses, especially the activation of macrophages, play a pivotal role. Different phenotypes of macrophages have distinct effects on inflammation. Activation of classical macrophage cells (M1) promotes inflammation, while activation of alternative macrophage cells (M2) inhibits inflammation. The polarization of macrophages is crucial for disease healing. A non-coding RNA, known as microRNA (miRNA), governs the polarization of macrophages, thereby reducing inflammation following SCI and facilitating functional recovery. This study elucidates the inflammatory response to SCI, focusing on the infiltration of immune cells, specifically macrophages. It examines their phenotype and provides an explanation of their polarization mechanisms. Finally, this paper introduces several well-known miRNAs that contribute to macrophage polarization following SCI, including miR-155, miR-130a, and miR-27 for M1 polarization, as well as miR-22, miR-146a, miR-21, miR-124, miR-223, miR-93, miR-132, and miR-34a for M2 polarization. The emphasis is placed on their potential therapeutic role in SCI by modulating macrophage polarization, as well as the present developments and obstacles of miRNA clinical therapy.

Photothermal therapy (PTT) presents unique advantages, including high temporal and spatial controllability and relatively few toxic side effects. Active targeting modifications of photothermal agents can deliver nanoprobes to tumors more efficiently, reducing toxic side effects while improving efficacy. In this work, the polyphenols, gallic acid, folic acid (FA), hyaluronic acid (HA), and Fe(III) were selected to prepare a self-photothermal nanoplatform Ga/Fe/HA/FA based on polyphenol-metal self-assembly. The self-assembly process synchronously integrated the targeting molecules, folic acid and hyaluronic acid, layer by layer in a polyphenol-metal network, thus realizing the "layer-by-layer targeting" effect. Compared with the traditional targeting modification, the self-assembly multitargeting modification strategy effectively avoided the complicated experimental steps of traditional targeting modification. Meanwhile, it mitigated the off-target risk during blood circulation and improved tumor-targeting efficiency, ultimately augmenting the effectiveness of photothermal therapy.

Gastrodin, a bioactive ingredient extracted from the Chinese herb Gastrodia gastrodia, has shown potential therapeutic effects in cardiovascular diseases, but its specific role in myocardial infarction is unclear. This study investigated the protective effect of gastrodin on myocardial infarction and its potential mechanism. By clamping the left coronary artery, we created a model of myocardial infarction in C57BL/6J mice. For 14 days, mice in the control and myocardial infarction groups received a daily dose of 100 mg/kg gastrodin. Gastrodin significantly improved cardiac dysfunction in mice with myocardial infarction, decreased heart weight/body weight (HW/BW) and heart weight/tibial length (HW/TL) ratios, and inhibited mRNA expression levels of cardiac fibrosis biomarkers (Collagen Type I (Col1), Collagen Type III (Col3), Matrix Metalloproteinase-2 (MMP-2), Matrix Metalloproteinase-9 (MMP-9)). In addition, gastrodin also inhibited the activity of apoptosis marker Caspase 3, decreased the Bax/Bcl2 mRNA ratio, decreased the expression of pro-inflammatory factors (Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6)) and pro-inflammatory adhesion molecule Monocyte Chemoattractant Protein-1 (MCP1), and promoted the expression of angiogenesis marker Cluster of Differentiation 31 (CD31). RNA sequencing and Rt-qPCR analysis showed that gastrodin treatment significantly up-regulated the expression of genes related to cell proliferation (Cyclin-Dependent Kinase 1 (CDK1), Threonine Tyrosine Kinase (TTK), Cyclin B2 (CCNB2), Polo-Like Kinase 1 (PLK1)), and promoted the proliferation of human aortic endothelial cells (HAECs). These findings suggest that gastrodin can effectively reduce the pathological changes of myocardial infarction by inhibiting inflammation, reducing apoptosis, and promoting endothelial cell proliferation, thus providing a new strategy for the prevention and treatment of myocardial infarction.

Restless legs syndrome (RLS) is a common sensorimotor disorder with limited treatment options and incompletely understood pathophysiology. Genome-wide association studies have identified numerous risk loci, but translating these findings into causal genes and therapeutic targets remains challenging. We performed a proteome-wide association study (PWAS) integrating RLS genome-wide association study (GWAS) data from FinnGen with two brain pQTL datasets (ROSMAP and Banner). We validated the identified proteins using TWAS, SMR, and colocalization analyses using brain pQTL and eQTL datasets. To further investigate peripheral protein associations, we performed SMR using plasma pQTL data from the UK Biobank Pharma Proteomics Project (UKB-PPP). We also conducted a phenome-wide association study (PheWAS) to screen for potential off-target effects of the prioritized genes, followed by drug prediction using DSigDB and molecular docking. PWAS identified GLO1, along with GRWD1 and MAP2K5, as significantly associated with RLS. GLO1 was identified by brain-based SMR (p = 0.0001), colocalization (PP.H4 = 0.96), TWAS (p = 0.048), and was confirmed by plasma-based SMR (p = 3.16 × 10⁻⁹) as the only protein associated with RLS. PheWAS analysis, without associations for 783 non-RLS phenotypes, confirmed the specificity of GLO1. Among 27 predicted GLO1-targeting compounds, Gambierol had the strongest binding affinity (−8.3 kcal/mol). This proteogenomic study identifies GLO1 as a prioritized causal gene and promising drug target for RLS, combining brain and plasma data to provide new insights into pathogenesis and candidate drug development.