Sandra Lucía Teniente

Type 2 diabetes mellitus (T2D) represents over 90% of diabetes cases globally, posing a growing public health crisis with an estimated 783 million adults projected to be affected by 2045. This condition arises from a complex interplay of insulin resistance, progressive pancreatic β-cell dysfunction, and chronic low-grade inflammation, strongly influenced by genetic predisposition, obesity, sedentary lifestyle, and poor dietary habits. While genome-wide association studies (GWAS) have identified key susceptibility loci, including TCF7L2, PPARG, and KCNJ11, these varian0ts explain only ~10% of T2D heritability, underscoring the critical role of gene–environment interactions. This review synthesizes current evidence on the genetic, nutrigenomic, and epigenetic mechanisms underlying T2D pathogenesis and progression. We examine how dietary components, such as flavonoids, terpenoids, alkaloids, and bioactive compounds from natural products, modulate gene expression via transcription factors and influence insulin sensitivity, oxidative stress, and inflammation. Furthermore, we explore the emerging role of epigenetic modifications, including DNA methylation, histone acetylation, and chromatin remodeling, in mediating the lasting effects of hyperglycemia and environmental factors on T2D risk. The potential of epigenetic biomarkers for early diagnosis, patient stratification, and personalized therapy is discussed. Finally, we highlight how next-generation sequencing and artificial intelligence, particularly machine learning and deep learning models, are advancing multi-omics data integration, enabling improved T2D subtype classification, prognosis prediction, and the development of precision nutrition and pharmacoepigenetic strategies.

Introduction: Gold nanoparticles synthesized using plant extracts (green synthesis) are promising nanomaterials for cancer therapy due to their enhanced stability and bioactive properties. This study aimed to synthesize gold nanoparticles functionalized with polyphenols from pomegranate husk and coffee pulp and evaluate their antiproliferative and cytotoxic effects in human cancer (HeLa, A549) and non-transformed (HeK-293) cell lines. Methods: Gold nanoparticles were synthesized using ethanolic extracts of pomegranate husk and coffee pulp, individually and in a 1:1 mixture (PH-AuNPs, CP-AuNPs, Mx-AuNPs). Characterization was performed using FT-IR spectroscopy and size analysis. Antiproliferative effects were assessed via the MTT assay, and cytotoxicity was measured using the Lactate Dehydrogenase assay in cells treated with 10, 100, and 1000 μg/mL of each nanoparticle type. Results: The nanoparticles exhibited characteristic FT-IR bands associated with polyphenolic compounds and had an average particle size of 28 nm. PH-AuNPs, CP-AuNPs, and Mx-AuNPs demonstrated significant antiproliferative effects against HeLa and A549 cells in a concentration- dependent manner. No significant cytotoxicity was observed in Hek-293 cells, indicating selectivity toward cancerous cells. Discussion: The findings suggest that polyphenol-functionalized gold nanoparticles selectively inhibit cancer cell proliferation without harming non-transformed cells. This aligns with previous research on green-synthesized nanoparticles and highlights the potential of pomegranate and coffee byproducts in enhancing therapeutic specificity. Conclusion: Gold nanoparticles fortified with pomegranate husk and coffee pulp polyphenols exhibit promising antiproliferative effects in cancer cells while sparing healthy cells, supporting their potential as targeted anticancer agents. Further research should explore in vivo efficacy and mechanistic pathways.

Polyphenols are a broad group of bioactive phytochemicals with powerful antioxidant, anti-inflammatory, immunomodulatory, and antiviral activities. Numerous studies have demonstrated that polyphenol extracts obtained from natural sources can be used for the prevention and treatment of cancer. Pomegranate peel extract is an excellent source of polyphenols, such as punicalagin, punicalin, ellagic acid, and caffeic acid, among others. These phenolic compounds have antineoplastic activity in in vitro models of cervical cancer through the regulation of cellular redox balance, induction of apoptosis, cell cycle arrest, and modulation of different signaling pathways. The current review summarizes recent data from scientific reports that address the anticancer activity of the predominant polyphenol compounds present in PPE and their different mechanisms of action in cervical cancer models.