Epigenomes

Background/Objectives: The oral–gut–lung axis represents a dynamic system where exosomes carrying mRNAs and non-coding RNAs might help to regulate microbiota and human cell crosstalk to establish transcriptional regulatory networks controlling cellular biological processes and signaling pathways. Methods: We conducted a comprehensive transcriptomic analysis to characterize the molecular cargo of extracellular exosomes in the context of gut and lung cancer. Results: By analyzing gut and lung exosomes cargo with our previous transcriptomic studies from tumoral and inflammatory tissues, we found that exosomes can transport key RNAs that codify specific receptors that facilitate pathogenic interaction with microorganisms and RNAs that are part of interacting gene and transcriptional regulatory networks that control the function of differentially expresses genes, all involved in biological processes like cell cycle, plasticity and growth regulation, invasion, metastasis, microenvironmental remodeling, epigenetic, and microbial and immunological modulation, during the unlocking of phenotypic plasticity for the acquisition of the hallmarks of cancer in the oral–gut–lung axis. Conclusions: Exosomal RNA regulation of transcriptional networks represents a pivotal axis in the interplay between inflammation and cancer, offering opportunities for innovative diagnostic and therapeutic approaches.

Human life expectancy has risen dramatically in the last century, but this demographic triumph has come at the cost of an explosion of non-communicable diseases (NCDs), threatening the sustainability of healthcare systems in aging, low-fertility societies. Evolutionary medicine provides a framework to understand, at least in part, this paradox. Many vulnerabilities to disease are not failures of design but the predictable outcomes of evolutionary trade-offs, constraints, and mismatches. Evolutionary mismatch theory explains how traits once advantageous in ancestral environments become maladaptive in modern contexts of abundance, sedentarism, and urbanization. The developmental origins of health and disease (DOHaD) concept describes how epigenetic plasticity in early life can buffer or amplify these mismatches, depending on whether adult environments align with developmental forecasts. Transgenerational epigenetic inheritance, even if still debated in humans, may further influence phenotypic plasticity, increasing or mitigating the mismatch. In evolutionary terms, the theories of mutation accumulation, antagonistic pleiotropy, and the disposable soma explain why longer lifespans, and ecological and social conditions profoundly different from those in which we developed, increase the likelihood that these costs are expressed clinically. Because most NCDs can be prevented and effectively controlled but not cured, efforts should prioritize quality of life for people, families, and communities. At the individual level, aligning lifestyles with evolved biology can mitigate risk, but the greatest leverage lies in population-level interventions. Urban health strategies represent a forward-looking attempt to realign modern environments with human biology. In this way, the concept of the evolutionary misfit becomes not just a diagnosis of maladaptation, but a guide for building healthier, more sustainable societies.

Quantum dots (QDs) have emerged as powerful tools in biomedical applications due to their unique optical and fluorescent properties which enable highly sensitive and multiplexed detection of biomolecules. Particularly in the field of epigenetic research, QDs are utilized as biosensors for monitoring changes in DNA methylation, microRNA (miRNA) expression, and histone modifications, providing a viable alternative to conventional assays. However, increasing evidence also suggests that QDs act as an epigenetic disruptor, altering epigenetic mechanisms and downstream cellular processes. This dual role raises important questions about the safety, reliability, and translational potential of QDs in clinical usage. Therefore, in this commentary we critically evaluate the advances of QD-based epigenetic sensing platforms while also providing insights into QD-based epigenetic dysregulation. We further discuss the current limitations and provide future directions to gain a better understanding of how QDs function to bridge the gap between their diagnostic potential and clinical integration.