Ferroptosis resistance in cancer cells: nanoparticles for combination therapy as a solution.

Ferroptosis is a form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation. Ferroptosis is currently proposed as one of the most promising means of combating tumor resistance. Nevertheless, the problem of ferroptosis resistance in certain cancer cells has been identified. This review first, investigates the mechanisms of ferroptosis induction in cancer cells. Next, the problem of cancer cell resistance to ferroptosis, as well as the underlying mechanisms is discussed. Recently discovered ferroptosis-suppressing biomarkers have been described. The various types of nanoparticles that can induce ferroptosis are also discussed. Given the ability of nanoparticles to combine multiple agents, this review proposes nanoparticle-based ferroptosis cell death as a viable method of circumventing this resistance. This review suggests combining ferroptosis with other forms of cell death, such as apoptosis, cuproptosis and autophagy. It also suggests combining ferroptosis with immunotherapy.

The effects of moderate-intensity aerobic exercise on cognitive function in individuals with stroke-induced mild cognitive impairment: a randomized controlled pilot study.

OBJECTIVE: To assess the impact of moderate-intensity aerobic exercise on working memory in stroke-induced mild cognitive impairment (MCI). DESIGN: Randomized, double-blind controlled study. SUBJECTS AND METHODS: Twenty MCI patients from the Fifth Affiliated Hospital of Guangzhou Medical University (December 2021 to February 2023), aged 34-79, 2-12 months post-stroke, were divided into an experimental group (EG) and a control group (CG), each with 10 participants. The EG underwent standard rehabilitation plus 40 minutes of aerobic exercise, while the CG received only standard therapy, 5 times weekly for 2 weeks. Working memory was tested using the n-back task, and overall cognitive function was measured with the MOCA and MMSE Scales before and after the intervention. RESULTS: The EG showed higher 3-back correctness (71.80 ± 14.53 vs 56.50 ± 13.66), MOCA scores (27.30 ± 1.57 vs 24.00 ± 3.13), and improved visuospatial/executive (4.60 ± 0.52 vs 3.30 ± 1.06) and delayed recall (4.30 ± 0.82 vs 3.00 ± 1.56) on the MOCA scale compared with the CG. CONCLUSION: Moderate-intensity aerobic exercise may enhance working memory, visuospatial/executive, and delayed recall functions in stroke-induced MCI patients.

Co-assembled nanocomplexes of peptide neoantigen Adpgk and Toll-like receptor 9 agonist CpG ODN for efficient colorectal cancer immunotherapy.

Cancer vaccines targeting tumor specific neoantigens derived from nonsynonymous mutations of tumor cells have emerged as an effective approach to induce antitumor T cells responses for personalized cancer immunotherapy. Despite the enormous potential of synthetic peptides as a common modality for neoantigen vaccines, their practical efficacy was limited due to their relatively low immunogenicity. Herein, we modify neoantigen peptide (Adpgk) derived from MC-38 colon carcinoma by supplementing ten consecutive positively-charged lysines (10 K-Adpgk) to obtain cationic polypeptide. And then we made them self-assemble with toll-like receptor 9 (TLR-9) agonist CpG oligodeoxynucleotides (CpG ODN) adjuvant directly forming antigen/adjuvant integrated nanocomplexes (PCNPs) through electrostatic interaction for potent tumor immunotherapy. The optimal formed PCNPs were around 175 nm with uniform size distribution and could maintain stability in physiological saline solution. CpG ODN and 10 K-Adpgk in the formed PCNPs could be effectively uptake by dendritic cells (DCs) and stimulate the maturation of DCs as well as improving the efficiency of antigen cross-presentation efficiency in vitro. Furthermore, the PCNPs vaccine could markedly improve neoantigen and adjuvant co-delivery efficiency to lymphoid organs and activate cytotoxic T cells. In addition, vaccination with PCNPs could not only offer prophylactic to protect mice from challenged MC-38 colorectal tumors, but also achieve a better anti-tumor effect in an established colorectal tumor model, and significantly prolong the survival rate of tumor-bearing mice. Therefore, this work provided a versatile but effective method for neoantigen peptide and CpG ODN co-assembly vaccine platform for efficient colorectal cancer immunotherapy.

A new di-O-prenylated flavone from an actinomycete Streptomyces sp. MA-12.

A new di-O-prenylated flavone, named 7,3'-di-(γ,γ-dimethylallyloxy)-5-hydroxy-4'-methoxyflavone (1), was isolated from the culture broth of the endophytic actinomycete Streptomyces sp. MA-12 isolated from the root of the semi-mangrove plant Myoporum bontioides A. Gray. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR experiments (COSY, HMQC, and HMBC). Primary bioassays showed that 1 at concentration of 0.25 mM had moderate inhibitory activity against three plant pathogenic fungi including Colletotrichum musae, Gibberella zeae (Schweinitz) Petch, and Penicillium citrinum Thom.