EXCLI Journal最新文献

Cancer is a multifactorial disease with cellular proliferative molecular networks and immune evasion properties. The well-known cancer intra- and inter-tumoral heterogeneity presents a notable limitation of the current histological and diagnostic techniques. Thus, biasing the risk of invasiveness and restricting its broader application in oncology in prognostic, survival, and treatment response differences between patients. Monolayer cell cultures have been a consistent in vitro model in cancer research throughout time. However, this system fails to replicate the complex pathogenesis of this disease, as key mechanisms underlying initiation, metastasis, drug resistance, and recurrence remain poorly understood. 3D culture models are presented as the most suitable model to better reflect the patient's tumor development. Some methods to introduce the third dimension into cell cultures is by promoting cell-cell interactions to give 3D cell structures, using scaffolds to promote growth beyond monolayers and introducing microfluidic platforms to the system. The present review provides an overview of different techniques to develop 3D culture models in oncology, the advantages compared between monolayer cell cultures, their applications, limitations, and applicability in oncology research. See also the graphical abstract(Fig. 1).

Breast cancer (BC), characterised by its diverse subtypes and molecular heterogeneity, remains a major challenge in oncology. Despite advances in chemotherapy, such as doxorubicin (Dox), limitations persist due to toxicity and drug resistance. Pigment epithelium-derived factor (PEDF) is a multifunctional protein with unique anti-tumour properties. The aim here was to elucidate metabolic reprogramming in human BC cell lines using a metabolomics approach. Untargeted gas chromatography-quadrupole mass spectrometry (GC/Q-MS) was employed to identify the metabolic alterations in BC cell lines MCF-7 (ER-positive) and MDA-MB-231 (TNBC) following treatment with PEDF, Dox, and their combination (Dox+PEDF) in comparison to untreated controls. Statistical models were employed using a combination of multivariate and univariate analyses, including partial least squares discriminant analysis (PLS-DA) and one-way ANOVA, applied by MetaboAnalyst and SIMCA software. To address the potential for multiple-testing errors, false discovery rate (FDR)-adjusted p-values were calculated to ensure robust statistical reliability. The overall analysis revealed significant metabolic alterations across the treatment groups, with distinct patterns emerging in carbohydrate, lipid, and amino acid metabolisms. In MCF-7 cells, PEDF combined with Dox significantly decreased cystine levels and modulated aspartic acid and lipid-related metabolites, indicating potential shifts in redox homeostasis and membrane composition. In MDA-MB-231 cells, the combination treatment significantly reduced glucose-6-phosphate and lactate levels, suggesting remodeling of glycolytic flux and redox balance. Furthermore, the combination of PEDF and Dox influenced amino acid and lipid metabolism. Pathway enrichment and correlation analyses revealed significant perturbations in glutathione metabolism, energy pathways, and lipid signaling, with notable differences between the two cell lines. Combining Dox and PEDF induced coordinated changes in metabolic networks, suggesting synergistic and antagonistic mechanisms that impact multiple biochemical pathways. These findings underline the importance of combining PEDF with chemotherapy to improve treatment outcomes in BC. See also the graphical abstract(Fig. 1).

The post-publication scrutiny of the literature occasionally reveals errors that have filtered past the scrutiny of peer reviewers and editors. Microscopes, as used in scanning electron microscopy (SEM), form an integral part of the evidence-based methodology of many biomedical studies. A 2025 preprint (DOI: 10.31219/osf.io/4wqcr) claimed that a body of literature in indexed and ranked journals may have published potentially incorrect microscopy (SEM)-based evidence, noting that in about 2400 cases, the model or maker of SEM microscopes, as indicated in the text (e.g., in the methodology section), do not match information indicated in the figures or micrographs. One possible explanation may be that those analyses and/or equipment may have been outsourced to third-party services, although the outsourcing was not declared. Homing in on a sub-set of that preprint's 2400 cases, looking specifically at 23 of the 94 papers published in the mega open access journal, Heliyon, that were flagged in that exposé, textual descriptors in the methods section were compared against SEM descriptors in figures' micrographs. Only two papers showed an unequivocal discord between textual and figure descriptors related to SEM at the level of model and maker, while 16 of the 23 papers had no methodological description of SEM in the methods section. Heliyon editors need to investigate these omissions and discrepancies, and correct the articles accordingly, wherever applicable. See also the graphical abstract(Fig. 1).

Aging is a highly intricate biochemical process. There is strong evidence suggesting that organismal aging, age-dependent diseases, and cellular senescence are related to the mammalian target of rapamycin (mTOR) signaling pathway. The signaling pathway of mTOR has become a prominent regulatory hub, managing crucial cellular activities that significantly affect lifespan and longevity. The mTOR is involved in controlling cell growth and metabolism in response to both internal and external energy signals as well as growth factors. The interaction between mTOR and cellular homeostasis is crucial in the aging process. This extensive review summarizes the most recent findings on mTOR inhibitors in the context of aging, highlighting their complex interactions with cellular systems, effect on longevity, and potential as therapeutic approaches for age-related diseases. Rapamycin and rapalogs (analogs of rapamycin), which have been proven to be effective mTOR inhibitors, have the ability to reduce the aging process in several model species while also enhancing metabolic health and stress responses. Despite cellular factors, mTOR inhibitors have revealed a potential path for therapeutics in age-related illnesses. These results suggest mTOR inhibitors as potential therapies to address the complex aspects of age-related diseases. However, obstacles stand in the way of clinical translation. Further research is required to improve dosing protocols, reduce potential side effects, and target mTOR inhibitors precisely at specific tissues. In summary, the mTOR signaling pathway is an important node in the intricate web of aging and its associated disorders.

G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contributed to the development of many successful examples of compounds with excellent anticancer activities. Therefore, it is important to investigate ligands targeting G4-quadruplexes in natural products such as dietary polyphenols and their derivatives. In this review, we provide an overview of the latest research on natural compounds, with especial emphasis on dietary polyphenols, as G4-quadruplex targeted ligands. We also discuss dietary polyphenols' structural chemistry that could facilitate their characterization as G4 ligands, highlighting their potential in the development of anticancer drugs. Finally, we explore polyphenols' potential mechanisms of action in regulating epigenetic machinery through G4 binding, thereby providing insights for the development of safe and effective therapeutical tools against cancer.