Expert Reviews in Molecular Medicine最新文献

Erythrocytes play a crucial role in human life and are a good model for single-cell ageing research. Therefore, the mechanism of erythrocyte ageing has been a serious concern for researchers. Here, we investigate the ageing mechanism of human erythrocytes in circulation with a new approach. We first try to discover all the factors that affect erythrocyte ageing from the existing findings about the interactions of erythrocytes with the environment during circulation and the resulting alterations in the cells during their ageing process. Then, we define the main events in erythrocyte ageing according to the incidence and strength of the interactions and the magnitude of the biophysical and biochemical alterations induced by these interactions. With the main events as a guide for tracking the ageing process and analysing the causes and consequences of the events taking place during erythrocyte ageing, we depict the pathways and framework of the ageing mechanism. We hope that understanding the ageing mechanism of erythrocytes will help people to have a deep insight into the biophysical and biochemical processes of cell ageing and their molecular basis. Additionally, it may offer solutions to different fundamental and practical problems related to erythrocyte ageing, storage lesions, transfusion and diseases.

Background: Digestive system cancers (DSCs) constitute a significant number of cancer cases and are closely associated with modifiable risk factors.

Objective: This umbrella review synthesizes evidence from meta-analyses on the association between dietary polyphenol consumption and the risk of DSCs, addressing limitations in the literature and identifying optimal polyphenol types and doses.

Methods: Following Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Scopus and Web of Science until April 2025, using specific keywords related to polyphenols and DSCs. Eligible studies included meta-analyses that examined polyphenol intake and DSC risk. The quality was assessed via the AMSTAR 2 and GRADE framework. Statistical analyses were performed using RStudio, employing random-effects models based on the heterogeneity metrics.

Results: Data from six meta-analyses, encompassing 27 effect sizes, revealed a statistically significant 11% reduction in the risk of DSCs associated with polyphenol consumption (RR: 0.89; 95% CI: 0.85-0.93; I²: 63%). Subgroup analysis revealed significant risk reductions for specific polyphenol classes: flavonols (22%), quercetin (22%), anthocyanidins (16%), flavan-3-ols (12%) and isoflavones (9%). Publication bias was evident, but adjustments using the trim-and-fill method still indicated a 13% overall reduction in risk (RR: 0.87; 95% CI: 0.83-0.92; I²: 64%).

Conclusions: Our findings support the protective role of dietary polyphenols against DSCs, particularly flavonols and quercetin, suggesting that further investigations into the optimal intake levels and mechanisms of action are needed. These findings underscore the potential of dietary modification as a strategy for DSC prevention.

Cervical cancer remains a major global health burden. Despite standard-of-care therapies, 30-50% of locally advanced-stage patients develop treatment resistance, leading to recurrence and mortality. While tumour-intrinsic mechanisms (e.g., DNA methylation, cancer-associated fibroblasts) explain only partial resistance heterogeneity, emerging evidence identifies the microbiome as a critical modulator of therapeutic efficacy. This review synthesizes recent advances demonstrating that vaginal microbial dysbiosis, characterized by Lactobacillus iners enrichment and L. crispatus depletion, drives resistance through lactate-mediated metabolic rewiring, immune checkpoint stabilization and drug metabolism alteration. Longitudinal studies reveal dynamic microbiome trajectories during therapy, with geographic variations (notably HIV co-infection in sub-Saharan Africa) further modulating treatment responses. We critically evaluate microbiome-based interventions, from probiotics to engineered bacteria, including synthetic biology-driven precision microbiome therapies, and establishing standardized multi-centre trial protocols. Bridging mechanistic insights with clinical application represents a paradigm shift towards microbiome-informed cervical cancer management.

Background: Polyploid Giant Cancer Cells (PGCCs) are a malformed subpopulation of tumor. They play a crucial role in metastasis, recurrence, and therapy resistance. However, the inconsistent model systems and a lack of standardization have hindered mechanistic understanding and clinical translation. This review highlights the pluralistic research for clinical application by methodically analyzing various model systems used in PGCC research to fill the gap in the literature.

Methods: As of November 2025, scholarly literature gathered from Google Scholar, PubMed, and ScienceDirect focused on examining the development, characteristics, and functional involvement of PGCCs in cancer.

Results: In vitro approaches, although limited in their physiological relevance, enable detailed mechanistic studies and facilitate the screening of drugs. Ex vivo tumor explants and organoids preserve patient-specific traits with translational potential, while in vivo models, such as Drosophila and mouse xenografts, provide insight into PGCC function in complex tissue environments. By mapping model capabilities against PGCC research priorities, we demonstrate that no single system comprehensively recapitulates PGCC biology, necessitating integrated, multi-model experimental strategies that we outline in this study. More specifically, integrating patient-derived organoids with lineage-traced xenografts and single-cell omics enables continuous tracking of PGCC development and functional diversity, facilitating mechanistic studies of metastasis, drug resistance, and identification of clinical biomarkers for patient stratification.

Conclusion: Considering the current lack of PGCC-targeted therapies, the convergence of model modification and the development of single-cell and imaging capabilities indicates significant progress toward therapeutically relevant findings. The ongoing development of these models is thus crucial for translating PGCC biology into predictive diagnoses and effective treatment methods.