Hongzhao Qi

Myocardial infarction (MI) remains a major cause of cardiovascular morbidity, and effective strategies to prevent adverse remodeling are limited. Here, we identify piR‐1873 as a cardioprotective piRNA that is down‐regulated in MI patients, mouse models, and H ₂ O ₂ ‐treated cardiomyocytes. Serum piR‐1873 levels correlated with MI biomarkers, suggesting its potential as a complementary biomarker, with an area under the curve (AUC) of 0.8389. Mechanistically, piR‐1873 directly targeted Usp2 and inhibited RIP1/RIP3/MLKL‐mediated necroptosis. To achieve efficient delivery, we developed ultrasound (US)‐responsive piRNA nanoparticles (piR‐NPs) consisting of a perfluorohexane (PFH) phase‐change core loaded with piR‐1873 and coated with a cardiomyocyte membrane shell. In vitro, piR‐NPs enhanced piR‐1873 delivery and suppressed cardiomyocyte necroptosis, with US further improving these effects. In MI mice, piR‐NPs accumulated in infarcted myocardium, and US enhanced nanoparticle retention, resulting in improved cardiac function, reduced fibrosis, and attenuated necroptosis without detectable systemic toxicity. Collectively, this study reveals the diagnostic and therapeutic potential of piR‐1873 and establishes a biomimetic, US‐triggered piRNA delivery platform for MI treatment.

Cisplatin is widely employed in the treatment of gastric cancer (GC). However, the resistance mechanisms exhibited by GC cells often result in suboptimal clinical outcomes associated with cisplatin therapy. Autophagy, a self-degradative cellular process, plays a complex dual role in regulating tumor cell death and survival. In recent years, significant attention has been directed toward the relationship between autophagy and cisplatin resistance in GC, fostering the development of various autophagy-related drugs and potential targets aimed at enhancing the sensitivity of GC cells to cisplatin. Nevertheless, a comprehensive analysis of the correlations among relevant studies is still lacking. This review synthesizes recent research examining the impact of autophagy on cisplatin resistance in GC cells, with particular emphasis on existing drugs and potential therapeutic drugs/targets. It briefly explores the fundamental processes of autophagy and clarifies the relationship between autophagy mechanisms and GC. Furthermore, it summarizes the available drugs and potential candidates that can either enhance or inhibit autophagy, thereby improving GC cell sensitivity to cisplatin, alongside their underlying mechanisms. Additionally, it consolidates pertinent research findings to present a more thorough understanding of the intricate relationships between autophagy and cisplatin resistance in GC cells. We hope this review will encourage researchers to investigate novel mechanisms of cisplatin resistance in GC cells, discover new targeted therapies, and propose innovative strategies to tackle this challenge.

Periodontitis is a widespread chronic inflammatory disease characterized by pathogenic bacterial biofilms and a hypoxic microenvironment, which together im

Glioblastoma (GBM) (IDH-wildtype), the most prevalent and malignant primary brain tumor in adults, continues to pose a major therapeutic challenge in neuro-oncology. Despite significant advancements in cancer diagnosis and treatment technologies, conventional therapies remain largely ineffective against this tumor, urgently necessitating breakthrough treatment strategies. This comprehensive review critically examines recent advances in targeting ferroptosis, an iron-dependent form of non-apoptotic cell death mediated through reactive oxygen species (ROS) accumulation and lipid membrane peroxidation, for therapeutic intervention in GBM. The key aspects analyzed encompass the unique molecular mechanisms that distinguish ferroptosis from apoptosis and necrosis, along with its regulatory networks in GBM. The analysis also explores the therapeutic potential of targeting critical ferroptosis pathways, including dysregulated iron metabolism, impaired antioxidant defenses, and abnormal lipid peroxidation. Additionally, it examines the synergistic effects and molecular basis of combining ferroptosis inducers with chemo-radiotherapy or immunotherapy. Finally, the study highlights innovative applications of nano-drug delivery technologies in overcoming blood-brain barrier (BBB) limitations and enhancing the precision of ferroptosis-targeted therapy. Notably, this review provides a comprehensive analysis of the interplay between ferroptosis regulation and the tumor immune microenvironment, highlighting a promising ‘ferroptosis-immunotherapy’ combination strategy with clinical translation potential for GBM treatment. While challenges persist regarding incomplete understanding of regulatory networks and nanocarrier biosafety issues, this review not only provides a theoretical framework for comprehending ferroptosis-mediated anti-GBM mechanisms but also outlines future research directions, including in-depth dissection of ferroptosis signaling hubs, development of intelligent nano-delivery systems, and establishment of preclinical safety evaluation protocols. These findings are expected to provide revolutionary therapeutic targets for achieving precision treatment of GBM.

Periodontal bone destruction caused by periodontitis presents a significant clinical challenge. Optimal regeneration of periodontal bone shall progress through three distinct physiological stages: 1) formation of a blood clot; 2) recruitment of stem cells to the clot; and 3) osteogenic differentiation of the stem cells. In this context, the present study proposes a hollow carboxymethyl chitosan (CMCS)/sodium alginate (SA)/CaCO₃ microparticles (CACC) hydrogel. Its formation utilizes temporal differences in cross‐linking between the outer and inner regions. The results indicate that the hollow structure of the CACC hydrogel enhances blood clot formation and stability. Additionally, the hydrogel facilitates the migration of human‐derived periodontal ligament stem cells (PDLSCs) and MC3T3‐E1 cells through the release of calcium ions (Ca²⁺). Furthermore, it supports osteogenic differentiation of both PDLSCs and MC3T3‐E1 cells by upregulating osteogenesis‐related proteins. In conclusion, by leveraging the cross‐linking and entanglement properties of polymers, a hollow hydrogel that sequentially regulates the three critical stages of periodontal bone regeneration is developed. Notably, this hydrogel effectively preserves blood clots, an often‐overlooked aspect of bone repair, within its hollow structure. This innovation encourages the advancement of biomaterials that more closely mimic the natural repair process.