Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and the antioxidant defense system, plays a central role in the pathophysiology of numerous diseases, including cardiovascular, neurodegenerative, and inflammatory disorders. This review explores the biochemical mechanisms of ROS-induced damage to lipids, proteins, cholesterol, and DNA, and analyzes both endogenous (enzymatic and non-enzymatic) and exogenous (nutritional) antioxidant systems that counteract oxidative damage. Key enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, alongside dietary antioxidants like vitamins C and E, polyphenols, and carotenoids, are highlighted for their protective roles. The dual antioxidant/pro-oxidant behavior of these compounds under varying physiological conditions is discussed. Furthermore, this paper reviews the cellular repair systems activated in response to oxidative injury and the biomarkers used to assess oxidative stress in clinical settings. Special attention is given to the implications of oxidative stress in cardiovascular and autoimmune diseases and the potential of antioxidant strategies in disease prevention and therapy. The findings underscore the importance of maintaining redox homeostasis and support further research into antioxidant-based interventions.

Hepatitis C, a liver inflammation caused by the hepatitis C virus (HCV), is treated with antiviral drugs. In this context, simeprevir (SIM) is an NS3/4A protease inhibitor used in HCV genotypes 1 and 4. It is orally administered and achieves high virological cure rates. Among adverse reactions associated with SIM treatment, photosensitivity reactions have been reported. In the present work, it is clearly shown that SIM is markedly phototoxic, according to the in vitro NRU assay using BALB/c 3T3 mouse fibroblast. This result sheds light on the nature of the photosensitivity reactions induced by SIM in HCV patients, suggesting that porphyrin elevation in patients treated with SIM may not be the only mechanism responsible for SIM-associated photosensitivity. Moreover, lipid photoperoxidation and protein photooxidation assays, using human skin fibroblasts (FSK) and human serum albumin (HSA), respectively, reveal the capability of this drug to promote photodamage to cellular membranes. Also, DNA photo lesions induced by SIM are noticed through comet assay in FSK cells. Photochemical and photobiological studies on the mechanism of SIM-mediated photodamage to biomolecules indicate that the key transient species generated upon SIM irradiation is the triplet excited state. This species is efficiently quenched by oxygen giving rise to singlet oxygen, which is responsible for the oxidation of lipids and DNA (Type II mechanism). In the presence of HSA, the photobehavior is dominated by binding to site 3 of the protein, to give a stable SIM@HSA complex. Inside the complex, quenching of the triplet excited state is less efficient, which results in a longer triplet lifetime and in a decreased singlet oxygen formation. Hence, SIM-mediated photooxidation of the protein is better explained through a radical (Type I) mechanism.

Dasatinib (DAS) is an anticancer drug employed in the treatment of certain hematological malignancies. Although DAS has been mainly developed for oral administration, it has recently garnered attention for its possible topical application. The use of topical drugs can cause photosensitivity, which is not listed as an adverse reaction for DAS. Since DAS absorbs UVA, it could potentially induce photosensitivity reactions and lead to oxidative damage to cellular targets. This study aims to investigate whether DAS exhibits phototoxic reactions on primary cellular targets in both solution and artificial skin, mimicking topical drug administration. It also examines the potential generation of highly reactive intermediates like organic radicals and ROS, which could trigger photosensitivity reactions. Upon DAS irradiation in the UVA region, the first transient species detected was the diradicaloid triplet excited state (³DAS∗) with an absorption maximum of around 490 nm, which was quenched by oxygen to produce singlet oxygen. Quenching experiments with linoleic acid and 3-methylindole indicated that radical-mediated (Type I) photosensitized damage to lipids and proteins is possible. However, the lack of triplet quenching with guanosine suggests that the Type II mechanism also plays a role in the photooxidation of biomolecules. Accordingly, the neutral red uptake phototoxicity test (photoirritation factor of 5) and the comet assay, revealed that this drug is photo(geno)toxic to cells. Moreover, investigations on lipid photoperoxidation, and protein and DNA photooxidation strongly support that different cellular compartments are potential targets for DAS-induced phototoxicity. Regarding its potential application in topical dermatological formulations, an O/W emulsion of DAS was prepared and tested in reconstructed human epidermis, and a significant phototoxicity was also demonstrated. Fortunately, this undesired side effect disappeared upon formulation of DAS along with a sunscreen. Thus, for topical treatments, the photosensitivity reactions induced by DAS can be prevented by using formulations including appropriate UVA filters.

Childhood obesity represents a growing global public health crisis, strongly driven by the widespread consumption of sugar-sweetened beverages (SSBs) and, increasingly, artificially sweetened beverages (ASBs). SSB intake drives excessive calorie consumption, reduces satiety, and disrupts hormones, leading to metabolic dysfunction such as insulin resistance and type 2 diabetes. Despite some regional declines, global consumption of SSBs remains high, with persistent socioeconomic disparities. Concurrently, ASBs, marketed as healthier alternatives, pose emerging metabolic and behavioral risks, such as gut microbiota disruption and altered appetite regulation, raising concerns about their long-term safety. Both beverage types displace nutritionally balanced food options in children’s diets and foster enduring preferences for sweetness, exacerbating poor dietary quality. Public health interventions targeting SSB reduction have demonstrated modest success; however, rising ASB use complicates prevention strategies. Effective mitigation of childhood obesity requires comprehensive approaches that emphasize reducing all sweetened beverage consumption, promoting water and whole-food hydration, and addressing the behavioral and environmental factors underlying unhealthy beverage choices to improve lifelong health outcomes.

Neuroblastoma (NB) is a highly heterogeneous pediatric tumor in which the extracellular matrix (ECM) critically influence tumor growth, cell lineage plasticity, and therapeutic resistance. However, the interplay of ECM remodeling with the traceable origin and fate of tumor cell phenotypes remains poorly understood. Pairedlike homeobox 2b (PHOX2B), a pivotal diagnostic marker reflecting the neuronal differentiation state of NB, was examined across multiple NB models. Our analysis revealed heterogeneous PHOX2B expression, including PHOX2B-negative foci, indicating intratumoral heterogeneity. To unravel the mechanisms underlying this behavior, we developed an integrated experimental platform combining orthotopic xenografts-derived from 2D cultures and 3D tyramine-modified gelatin/silk fibroin (GTA-sf) hydrogel systems-and computational image analysis. Original and NB models diverged in both cellular and microenvironmental features, despite all exhibiting PHOX2B-positive cells and reticulin fibers. Original tumors were identified as poorly differentiated NB, showing high PHOX2B expression, whereas SHSY5Y xenografts displayed mesenchymal-like PHOX2B-negative foci, in which SOX9 and vimentin marked plastic niches within a dense, aligned reticulin fiber network arranged in trabeculae. In contrast, SK-N-BE(2) and patient-derived xenograft (PDX1) tumors showed no upregulation of mesenchymal-type markers within PHOX2B negative niches and exhibited shorter, curved, and disorganized fibers. Unlike other models, PDX2 exhibited uniform PHOX2B expression without negative foci, characterized by thick fibrillar structures consistent with high matrix stiffness. Collectively, these findings demonstrate that PHOX2B heterogeneity and ECM stiffness, including fibrillar organization, interact in a model dependent manner to shape tumor architecture and microenvironmental remodeling. Unmasking these complex interactions is essential for identifying novel therapeutic vulnerabilities and improving clinical outcomes.