Solid tumors, with their intricate cellular architecture and genetic heterogeneity, have long posed therapeutic challenges. The advent of the CRISPR genome editing system offers a promising, precise genetic intervention. However, the journey from bench to bedside is fraught with hurdles, chief among them being the efficient delivery of CRISPR components to tumor cells. Lipid nanoparticles (LNPs) have emerged as a potential solution. This biocompatible nanomaterial can encapsulate the CRISPR/Cas9 system, ensuring targeted delivery while mitigating off-target effects. Pre-clinical investigations underscore the efficacy of LNP-mediated CRISPR delivery, with marked disruption of oncogenic pathways and subsequent tumor regression. Overall, CRISPR/Cas9 technology, when combined with LNPs, presents a groundbreaking approach to cancer therapy, offering precision, efficacy, and potential solutions to current limitations. While further research and clinical testing are required, the future of personalized cancer treatment based on CRISPR/Cas9 holds immense promise.

The risk of diabetic cardiovascular complications is closely linked to the length of hyperglycemia exposure. Mitophagy plays a significant role in vascular endothelial injury. However, the specific mechanisms by which mitophagy contributes to endothelial injury during sustained hyperglycemia remain unclear. In diabetic ApoE^−/− mice and human umbilical vein endothelial cell (HUVEC) models, mitophagy is enhanced following short‐term and long‐term high‐glucose exposure. Short‐term high‐glucose exposure promotes Parkin‐mediated mitophagy and upregulates mitochondrial fission protein 1 (Fis1) expression, whereas long‐term high‐glucose exposure suppresses Parkin‐mediated mitophagy and downregulates Fis1. With prolonged high‐glucose exposure, Syntaxin 17 (STX17) translocates from the endoplasmic reticulum to the mitochondria, activating STX17‐mediated mitophagy. Silencing STX17 alleviates mitochondrial degradation, decreases reactive oxygen species (ROS) levels, enhances endothelial nitric oxide synthase (eNOS) phosphorylation, and reduces apoptosis. Silencing Fis1 accelerates the switching to STX17‐mediated mitophagy, worsening endothelial dysfunction, whereas Fis1 overexpression prevents this switching, reducing ROS and apoptosis and enhancing eNOS phosphorylation. In summary, these findings suggest that the switching from Parkin‐mediated to STX17‐mediated mitophagy drives vascular endothelial injury following long‐term hyperglycemic exposure, providing valuable insights into therapeutic strategies for diabetic cardiovascular complications.

We previously demonstrated that fatty acid-binding protein 3 (FABP3) is significantly upregulated in ischemic neurons, and its inhibition mitigates ischemic brain injury in mice and attenuates mitochondrial damage under rotenone-induced oxidative stress. These findings suggest a potential role for FABP3 in mitochondrial dysfunction in ischemic neurons, although the underlying mechanism remains unclear. In this study, we further investigated the role of FABP3 in mitochondrial injury and apoptosis in ischemic neurons. Our findings indicated that FABP3 deficiency significantly decreased infarct volume following middle cerebral artery occlusion/reperfusion (MCAO/R) in mice, improved cognitive and spontaneous activity deficits, and suppressed BAX activation and mitochondrial translocation, caspase-3 activation, and cytochrome c release. In HT22 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), FABP3 deficiency increased cell viability, reduced apoptosis, and alleviated the loss of mitochondrial membrane potential. Conversely, FABP3 overexpression further exacerbated mitochondrial dysfunction and apoptosis, effects that were partially reversed by the BAX inhibitor BAI1. Furthermore, FABP3 overexpression promoted abnormal mitochondrial lipid accumulation and increased lipid peroxidation. Both the mitochondria-targeted antioxidant MitoQ and the ferroptosis inhibitor Ferrostatin-1 alleviated FABP3 overexpression-induced mitochondrial damage and apoptotic signaling. Collectively, our findings suggest that FABP3 is an important promoter of cerebral ischemia–reperfusion injury. FABP3 may aggravate ischemic neuronal injury by promoting abnormal mitochondrial lipid accumulation and lipid peroxidation, thereby enhancing BAX-dependent mitochondrial apoptotic signaling. Targeting FABP3 may provide a potential therapeutic strategy for neuroprotection in ischemic stroke.