Cell Biology and Toxicology最新文献

Breast cancer is a heterogeneous disease affecting women globally. Despite significant advancements in therapeutic interventions in recent years, breast cancer remains a leading cause of cancer-related morbidity in women. Breast cancer's diverse molecular subtypes and escalating complexities in targeted therapies underscore the imperative need to explore novel therapeutic targets. The obstruction of apoptosis and the suppression of cell death are hallmarks of malignant tumors. Cell death, a pivotal regulatory event during tumorigenesis, includes apoptosis, anoikis, autophagy, necroptosis, ferroptosis, pyroptosis, and cuproptosis. This review systematically dissects the molecular underpinnings of cell death pathways in breast cancer, offering novel mechanistic insights and therapeutic opportunities to inform clinical management strategies.

Lysine crotonylation (Kcr) has recently emerged as a distinctive post-translational modification with unique structural features and regulatory functions. Since its discovery in 2011, more than 10,000 histone and non-histone crotonylation sites have been identified, underscoring its widespread presence and evolutionary conservation. Crotonylation is dynamically regulated by "writers", "erasers", and "readers", linking metabolic state to chromatin regulation and protein activity. Increasing evidence indicates that dysregulated crotonylation contributes to tumor initiation, progression, metastasis, and therapy resistance across diverse cancer types. Mechanistically, crotonylation modulates gene expression, metabolic reprogramming, DNA repair, and stress responses by modifying both histones and key non-histone proteins. Advances in proteomic technologies have enabled systematic mapping of crotonylomes, facilitating the identification of novel diagnostic biomarkers and therapeutic targets. Here, we summarize current knowledge of the regulatory mechanisms and biological functions of protein crotonylation in cancer, highlight its roles across major tumor types, and discuss emerging opportunities for therapeutic intervention. A deeper understanding of crotonylation biology is expected to expand the epigenetic and metabolic landscape of cancer research and foster the development of precision oncology strategies.

Background: Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons. UBC9 is related to the formation of several cancers. Nevertheless, the function of UBC9 in PD and the potential mechanisms are vague.

Methods: MPP⁺-induced SH-SY5Y cells and MPTP-treated C57BL/6 mice were applied to induce PD models. Cell viability, proliferation and apoptosis were measured using CCK-8, EdU and Annexin V/PI staining, respectively. JC-1 staining and fluorescent probes DCFH-DA were employed to measure mitochondrial membrane potential and ROS production. The SOD, GSH and MDA content were determined by the commercially kits. SUMOylation of PINK1 were predicted by SUMOplot and verified by co-IP/Western blot. Mitophagy-related proteins, SUMO enzymes, and TH were analyzed by qRT-PCR/Western blot. LC3 expression was detected via immunofluorescence staining. Transmission electron microscopy was performed to detect autophagy. MPTP-induced brain injury was evaluated using Nissl staining, IHC and TUNEL assay. Motor function was observed via open field test and pole test.

Results: PINK1 and UBC9 were low-expressed in MPP⁺-induced SH-SY5Y cells. UBC9 mediated PINK1 SUMOylation. UBC9 overexpression promoted cell viability and reduced cells apoptosis in MPP⁺-stimulated SH-SY5Y cells, which was reversed after PINK1 silence or CsA treatment. Moreover, UBC9 overexpression counteracted MPP⁺-induced mitophagy, and oxidative stress. However, these findings were reversed by CsA or PINK1 silencing. PINK1 bound SUMO1 at the K522, K363 and K193 sites, further regulating cells viability and apoptosis. In MPTP-treated mice, UBC9 overexpression alleviated mitochondrial dysfunction and motor deficits via PINK1 SUMOylation.

Conclusion: UBC9 mediated mitophagy to attenuate MPP⁺/MPTP-induced neurotoxicity and oxidative stress by regulating PINK1 SUMOylation, suggesting that UBC9 may play a preventive role in PD progression.

Mitochondrial fission protein 1 (FIS1) is present in the cytoplasm and can be transported to the outer mitochondrial membrane. It can interact with DRP1 (Dynamin-Related Protein 1) to mediate mitochondrial fission and fusion, and most of the studies on FIS1 have centered on FIS1-DRP1 mitochondrial fission. However, more and more studies are now showing that FIS1 is not only involved in mitochondrial fission, but also plays a role in mitophagy, peroxisomal dynamics, and lysosomes. Post-translational modification (PTM) of proteins enables proteins to perform distinct functions and exhibit diverse properties, thereby creating multiple possibilities for many proteins. The post-translational modification of FIS1 protein is associated with the occurrence of many diseases. Environmental pollution has become a serious public health problem that affects people's health. The role of FIS1 in human health caused by environmental pollutants is worth in-depth study and exploration.

Thyroid cancer treatment and bacterial infection management have long been challenging due to the limited effectiveness and side effects of conventional therapies. Here, we introduce molybdenum nitride (Mo₂N) nanomaterials as an innovative platform for dual-functional photothermal therapy, combining anti-tumor and antibacterial treatments. Mo₂N nanoparticles with an average diameter of ~ 2.45 nm were synthesized and systematically characterized. Upon near-infrared (NIR) laser exposure, Mo₂N demonstrated efficient photothermal conversion (efficiency ≈ 31.8%), leading to significant temperature elevation. In vitro studies confirmed a selective cytotoxic effect, with Mo₂N-mediated PTT inducing significant death in thyroid cancer cells while having a minimal impact on normal endothelial cells. In vivo, this platform led to significant tumor growth inhibition and accelerated healing of MRSA-infected wounds. Additionally, Mo₂N exhibited substantial antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) under NIR irradiation, showcasing its effectiveness in combating bacterial infections. The combined anti-tumor and antibacterial actions of Mo₂N suggest a promising strategy for dual-functional photothermal therapy, where the photothermal effect not only inhibits tumor growth but also effectively eliminates bacterial infections during treatment. These findings indicate that Mo₂N-based photothermal therapy can serve as a versatile, multi-functional therapeutic tool, presenting a significant advancement in both oncology and infectious disease treatment.

Optic nerve injury represents a common pathological basis underlying various blinding diseases and remains without effective regenerative therapies. The review focuses on three key mechanisms: the inflammatory microenvironment, epigenetic dysregulation, and ionic imbalance, clarifying their temporal dynamics and mutual interactions after injury. It highlights the major factors that limit retinal ganglion cell (RGC) axonal regeneration and synaptic remodeling.Within this framework, representative single and dual mechanism nanodelivery strategies in murine and nonhuman primate models are analyzed, focusing on tissue targeting, therapeutic time windows, and functional outcomes to define their applicability and limitations.The review further summarizes the design principles, pharmacological performance, and engineering optimization of tri mechanistic synergistic platforms that integrate biomimetic membranes, targeting peptides, and stimuli responsive materials. For translational application, an AI assisted framework is proposed for target identification and time window optimization, combined with a closed loop control system that unifies sensing, drug delivery, and evaluation. Key requirements for formulation consistency and quality control are also discussed. The main contribution lies in establishing a unified conceptual framework describing the interplay among the three mechanisms, providing systematic evaluation criteria for nanodelivery strategies, and outlining operational AI driven closed loop platforms with engineering standards. These advances collectively offer a foundation for developing intelligent, precise, and personalized interventions in optic nerve regeneration.

Gastric cancer (GC) continues to be a fatal disease globally, largely due to the lack of dependable molecular indicators enabling early diagnosis and therapeutic intervention. Single-cell transcriptomic analysis revealed significant enrichment of DAZAP1 in proliferating and malignant gastric epithelial cells. Using a combined analysis of single-cell and bulk RNA-seq datasets, we further recognized DAZAP1 as a putative oncogene correlated with poor clinical outcomes in GC. Functional experiments demonstrated that DAZAP1 promotes tumor proliferation, cell cycle progression, and chemotherapy resistance in vitro and in vivo. Mechanistically, DAZAP1 bound and stabilized USP34 mRNA, leading to increased USP34 protein expression, which in turn mediated the deubiquitination and stabilization of the oncoprotein PIN1. This subsequently resulted in activation of the MAPK signaling pathway, driving GC progression and chemoresistance. Furthermore, we revealed that DAZAP1 expression is post-transcriptionally regulated by m6A modification through the demethylase ALKBH5, which protects DAZAP1 mRNA from YTHDF2-mediated degradation. Collectively, our findings establish the ALKBH5/DAZAP1/USP34/PIN1/MAPK axis as a key regulatory mechanism in gastric tumorigenesis and chemoresistance, underscoring DAZAP1 as a promising candidate for therapeutic and diagnostic applications in GC.

Benzo(a)pyrene (BaP) is a common environmental pollutant from combustion sources that promotes oxidative stress, neuroinflammation and disruption of blood-brain barrier (BBB). However, its contribution to worsening traumatic brain injury (TBI) remains unclear. In this study, we aimed to assess the contribution of BaP to secondary injury in TBI. By integrating data from e.g., the Comparative Toxicogenomics Database, GeneCards, and Online Mendelian Inheritance in Man, 121 overlapping core targets were identified between BaP and TBI. Enrichment analyses via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, combined with protein-protein interaction networks and topological algorithms (degree, closeness centrality, betweenness centrality, average shortest path length, topological coefficient and partner of multi-edged node pairs), highlighted five hub genes (TP53, EGFR, AKT1, ACTB, and TNF) implicated in mitogen-activated protein kinase signaling, oxidative stress, and neuroinflammation. Molecular docking showed strong binding affinities of BaP to these hub proteins, with energies from -9.3 to -12.1 kcal/mol, tighter than co-crystal ligands and existing protein-binding drugs. Molecular dynamics simulations confirmed interaction stability through low root-mean-square deviation (< 0.5 nm), fluctuation, and radius of gyration values. Calculation of binding free energies using MM-PBSA validated the strong binding affinity between BaP and binding pockets of each hub genes. Toxicity prediction analysis revealed an oral LD₅₀ of 316 mg/kg for BaP, with high probabilities for neurotoxicity, BBB permeability, carcinogenicity, and mutagenicity, associated with aryl hydrocarbon receptor activation. These findings reveal a "neurovascular homeostasis disruption" network underlying BaP-exacerbated TBI pathology and highlight potential targets to reduce pollution-related risks in TBI management.

Diquat (DQ) is a potent, non-selective herbicide which can result in severe poisoning and a high mortality if ingested accidentally or intentionally. Diquat poisoning can cause extensive damage to multiple organs, including the intestines, liver, kidneys, brain, and other organs. As there are no specific antidotes available for DQ poisoning, the current therapeutic strategies are essentially restricted to blood purification therapy and supportive care. Numerous studies on the molecular mechanisms and potential therapeutic agents have been conducted over the past few decades. However, there has been no comprehensive summary or analysis of these findings. This review extensively investigates the molecular mechanisms underlying DQ-induced organ injury, with a particular focus on the major signaling pathways. In addition, searches were conducted in PubMed and Web of Science using the following search terms: "diquat"[tiab] OR "diquat"[MeSH Terms]. A total of 166 eligible papers published over the past 35 years were selected. Consequently, more than seventy potential therapeutic agents with protective effects against DQ-induced toxicity are summarized and analyzed. In the future, it will be essential to conduct preclinical research and clinical trials to extrapolate these findings to humans.

Copper-cysteamine nanoparticles (Cu-Cy NPs) represent an innovative approach for cancer therapy due to their unique ability to be activated by multiple physical and chemical stimuli. This review systematically evaluates studies investigating Cu-Cy NPs in combination with chemical agents and diverse energy sources, including X-rays, UV light, microwaves, and ultrasound. A comprehensive literature search in PubMed, Scopus, and Web of Science up to August 2025 identified 18 relevant studies encompassing both in vitro and in vivo experiments. Across these studies, Cu-Cy NPs consistently suppressed tumor growth and triggered cancer cell death by generating reactive oxygen species (ROS) and enhanced therapeutic effects when combined with co-treatments such as disulfiram, potassium iodide, and other adjunct therapies. The multi-modal activation of Cu-Cy NPs, along with their ability to enhance existing therapeutic approaches, demonstrates a novel strategy in cancer treatment that integrates chemical and physical mechanisms for maximal efficacy. These findings underscore the nanoparticles' potential to transform current oncology strategies, offering targeted, versatile, and personalized therapeutic options. Continued investigation is essential to fully elucidate their mechanisms, optimize treatment protocols, and translate these promising preclinical results into safe and effective clinical applications.