Dysfunction of the lysosome and autophagy–lysosome pathway is closely associated with various diseases, such as neurodegenerative diseases, non-alcoholic fatty liver disease (NAFLD), etc. Additionally, chloroquine is a clinically widely used drug for treating malaria and autoimmune diseases, but long-term or high-dose administration may lead to significant toxic side effects. Attapulgite (ATT), a natural nanomaterial with excellent adsorption capacity and biocompatibility, herein demonstrated a novel biological function in regulating the lysosomal and autophagy–lysosome pathway. ATT could be effectively internalized into lysosome-related acidic compartments. Further study revealed that ATT could restore lysosomal pH, activate cathepsin D, alleviate autophagy blockage in chloroquine-treated cells, and reduce chloroquine-elicited cell death. In a cell model related to Huntington’s disease, treatment with ATT reinforced the degradation of the mutant huntingtin proteins by increasing cathepsin D maturation and autophagy flux. ATT could also promote lipid droplet clearance in hepatocytes with palmitic acid-induced steatosis, reduce hepatic lipid accumulation, and improve fasting blood glucose in high-fat-diet-induced NAFLD mice. These findings establish ATT as a lysosomal modulator, providing a foundation for its therapeutic potential in mitigating the adverse effects associated with long-term chloroquine use, especially improving neurodegenerative and metabolic disorders.

Mutations in the p53 gene are frequently observed in various cancers, prompting the initiation of efforts to restore p53 function as a therapeutic approach several decades ago. Nevertheless, only a limited number of drug development initiatives have progressed to late-stage clinical trials, and to date, no p53-targeted therapies have received approval in the USA or Europe. This situation can be attributed primarily to the characteristics of p53 as a nuclear transcription factor, which lacks the conventional features associated with drug targets and has historically been considered “undruggable”. In recent years, however, several promising strategies have emerged, including the enhanced iterations of previous approaches and novel techniques aimed at targeting proteins that have traditionally been considered undruggable. There is a growing interest in small molecules that can restore the tumor-suppressive functions of mutant p53 proteins, and the development of drugs specifically designed for particular p53 mutation types is currently underway. Other approaches aim to deplete mutant p53 or exploit vulnerabilities associated with its expression. Additionally, genetic therapy strategy and approaches have rekindled interest. Advances in mutant p53 biology, compound mechanisms, treatment modalities, and nanotechnology have opened up new avenues for p53-based therapies. However, significant challenges remain in clinical development. This review reassesses the progress in targeting p53-mutant cancers, discusses the obstacles in translating these approaches into effective therapies, and highlights p53-based therapies via nanotechnology.

Due to their high biocompatibility, biodegradability, and facile surface functionalization, phospholipid vesicles as carriers have garnered significant attention in the realm of disease diagnosis and treatment. On the one hand, phospholipid vesicles can function as probes for the detection of various diseases by encapsulating nanoparticles, thereby enabling the precise localization of pathological changes and the monitoring of disease progression. On the other hand, phospholipid vesicles possess the capability to selectively target and deliver therapeutic agents, including drug molecules, genes and immune modulators, to affected sites, thereby enhancing the sustained release of these agents and improving therapeutic efficacy. Recent advancements in nanotechnology have led to an increased focus on the application of phospholipid vesicles in drug delivery, biological detection, gene therapy, and cell mimics. This review aims to provide a concise overview of the structure, characteristics, and preparation techniques of phospholipid vesicles of varying sizes. Furthermore, we will summarize the latest research developments regarding their use as nanomedicines and gene carriers in disease treatment. Additionally, we will elucidate the potential of phospholipid vesicles in facilitating the internalization, controlled release, and targeted delivery of therapeutic substrates. Through this review, we aspire to enhance the understanding of the evolution of phospholipid vesicles within the biological field, outline prospective research, and address the forthcoming challenges associated with phospholipid vesicles in disease diagnosis and treatment.

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory c

Four novel pyranone derivatives were isolated from fungi associated with the marine sponge species Aspergillus versicolor. The planar structures of these compounds were elucidated through comprehensive spectroscopic techniques, including HRESIMS, UV, IR, and 1D and 2D NMR. The absolute configuration of compound 1 was determined via X-ray diffraction, while that of compound 3a was determined using electronic circular dichroism (ECD) spectroscopy. Furthermore, all compounds were evaluated for their cytotoxic activity against human lung carcinoma cells (A549). At 30 μM, only compound 2 exhibited slight cytotoxic activity, with an inhibition rate of (46 ± 3.63)%, compared to doxorubicin (positive control, (86 ± 1.81)%). In DPPH free radical scavenging assays, compound 2 demonstrated a superior capacity than other derivatives, with a scavenging rate of (21.5 ± 3.03)% at 0.6 mg/mL, though still lower than vitamin C ((38.4 ± 2.96)%). Compounds 1, 3a, and 3b exhibited diminished scavenging activities, with rates of (16.1 ± 1.32)%, (13.6 ± 1.60)%, and (15.2 ± 2.79)%, respectively.