沈阳药科大学

Starvation therapy (ST), which aims to hinder the rapid proliferation of cancer cells by depriving oxygen and nutrients, has been considered an ideal approach for cancer treatment. However, the limitations of traditional ST schemes, such as low targeting efficacy, undesired systemic side effects, elevated tumor hypoxia, induced drug resistance, and increased tumor metastasis risk, limit clinical applications. To overcome these challenges, numerous nanomedicines have been engineered in recent years to advance ST-driven antitumor therapy. Against this backdrop, there is an urgent need to summarize the latest advances in advanced nanomaterial-enabled cancer starvation therapy. Herein, we aim to highlight the emerging breakthroughs at the intersection of ST, nanotechnology, and cancer treatment in this rapidly evolving field. This review focuses on several ST-related inducible strategies, including nutrient supply regulation, key nutrient deprivation, and some emerging approaches. Furthermore, it highlights the synergistic benefits of combining ST with other therapeutic modalities, including phototherapy, chemodynamic therapy, chemotherapy, ferroptosis, gas therapy, and immune therapy. Finally, the existing challenges and future perspectives on the clinical ST of tumors are discussed.

Polydopamine (PDA) exhibits unique advantages in the treatment of oxidative damage owing to its melanin-mimetic structure, abundant redox-active functional groups, and excellent biocompatibility. Distinct from conventional antioxidant molecules, PDA-based nanoplatforms can efficiently eliminate reactive oxygen species (ROS) via hydrogen atom transfer and electron transfer mechanisms, while relying on the dynamic redox cycling of catechol/quinone moieties to achieve sustained antioxidant activity. However, systematic summaries of PDA-based antioxidant nanoplatforms remain relatively limited. Therefore, this review provides a comprehensive overview of the antioxidant mechanisms of PDA and its associated physicochemical properties, with particular emphasis on the design strategies of diverse PDA-based nanoplatforms, including solid, mesoporous, hollow, doped, and coated architectures, as well as the effects of structural features, particle size, composition, and surface charge on their antioxidant performance. In addition, recent research progress is systematically categorized around core pathological challenges, including breaking ROS-inflammation feedback loops, overcoming biological delivery barriers, remodeling regenerative microenvironments, and regulating programmed cell death.

Lipid metabolism imbalance and inflammation are important mechanisms driving osteoporosis. Gushudan (GSD) has the effect of tonifying the kidney and strengthening bones. However, the preventive mechanism of GSD against postmenopausal osteoporosis (PMOP) by modulating lipid metabolism remains to be further elucidated. A multi-omics strategy integrating lipidomics, transcriptomics, network pharmacology, and molecular docking was developed to investigate the potential mechanistic targets and pharmacodynamic material basis of GSD in preventing PMOP. Firstly, lipidomics analysis employing the dual-MS platform of UHPLC-Q-Orbitrap HRMS and UHPLC-MS/MS demonstrated that GSD improved the disorder of the lipid-inflammatory crosstalk mechanism involving glycerophospholipids and arachidonic acid in PMOP rats. Secondly, the combined analysis of lipidomics and network pharmacology predicted that Pla2g2a might be a potential mechanistic target linking lipid metabolism disorder to PMOP. Furthermore, high-throughput RNA sequencing transcriptomics was conducted to reveal that GSD significantly regulated 49 differentially expressed genes in PMOP rats, with the reversed genes (represented by Pla2g2a) markedly enriched in the arachidonic acid metabolism pathway. Finally, molecular docking was used to screen four active ingredients: przewaquinone A, naringenin, salvianolic acid D, and tricin, which were found to target Pla2g2a. In conclusion, this work achieved multi-dimensional cross-analysis by integrating multiple approaches, suggesting that GSD might ameliorate the lipid-inflammatory crosstalk disorder in PMOP rats by downregulating Pla2g2a expression, thereby restoring bone homeostasis. These findings provide new research clues and a potential target basis for the mechanistic investigation of PMOP.

A machine learning (ML)-assisted strategy has been applied to optimize nitrogen-doped carbon dots (N-CDs) synthesized via a solvothermal route using glutathione, urea, and formamide as the specific precursor system. A dataset of 250 samples was constructed through systematic experimentation and data augmentation to train XGBoost, Random Forest, and LightGBM models for predicting fluorescence intensity. Among these models, XGBoost showed the best predictive performance with an R2 value of 0.9032. Model analysis suggested that urea dosage, the GSH-to-urea ratio, and reaction temperature were the most influential factors within the investigated parameter space. Guided by the ML-assisted optimization, the obtained N-CDs had an average particle size of 3.64 nm, a quantum yield of 8.99

N-(1,3-Dimethylbutyl)-N’-phenyl-p-phenylenediamine (6PPD) is a widely used rubber antioxidant and an emerging environmental pollutant, yet its hepatotoxic potential and the underlying role of metabolic activation remain poorly understood. Here, we integrated metabolite profiling, liver microsomal incubations, chemical oxidation synthesis, and mouse primary hepatocytes and animal exposure to examine the metabolic and toxicological outcomes of 6PPD. A total of 54 metabolites were identified in mice, including phase I oxidation products and phase II conjugates. Importantly, the reactive metabolite p-benzoquinone diimide (6PPD-QDI) was detected and shown to form conjugates with biological thiols. In microsomal incubations containing glutathione (GSH), N-acetylcysteine (NAC), or cysteine conjugates, 6PPD produced the corresponding conjugates, supporting the generation of 6PPD-QDI. The conjugate formation was NADPH-dependent and substantially suppressed by the CYP3A inhibitor ketoconazole, indicating that CYP3A mediates the bioactivation of 6PPD. In vivo, identical GSH and NAC conjugates were detected in bile and urine of exposed mice, and hepatic proteins contained dose-dependent protein adduction at cysteine residues. In primary hepatocytes, 6PPD induced concentration- and time-dependent cytotoxicity associated with GSH depletion and protein adduction, which was mitigated by CYP3A inhibition or thiol supplementation. Notably, CYP3A4-overexpressing HepG2 cells exhibited enhanced susceptibility to cytotoxicity and protein adduction compared to wild-type cells.