Publicaciones

Polyphenols often oscillate between antioxidant and pro-oxidant behaviours depending on structural motifs and context, yet the field still relies heavily on test-tube antioxidant assays that poorly predict cellular and clinical outcomes. This review (2015-2025) integrates chemistry, enzymology, and human data to frame polyphenols as modulators of redox signalling rather than mere radical scavengers. We first formalize the catechol/o-quinone-hydroquinone/p-quinone cycle and the role of NQO1 and Keap1/NRF2 thresholds. We then examine bioavailability, conjugation, and microbiota-derived metabolites (metabotypes), highlighting when the “active” species is a conjugate or a microbial derivative. We discuss safety through quinone speciation and adduct chemistry, and connect food processing (e.g., PPO-driven browning) with shifts in quinone pools. Contextual “levers” (pH, O2, Fe/Cu, oxidases) can flip antioxidant to pro-oxidant outputs, sometimes beneficial via hormesis and redox preconditioning. In humans, randomised trials and prospective cohorts point in a broadly consistent direction, although primary composite endpoints have often proved null, and observational associations should not be read as equivalent to trial evidence. Heterogeneous results across studies are largely explained by dose, adherence, metabotypes, matrix, and endpoint selection. We propose a practical dose-response framework and a reporting checklist to improve interpretation and translation. Recasting polyphenols as tuneable redox-signalling agents clarifies apparent contradictions across models and suggests precision-nutrition strategies (metabotype-aware) and food design approaches (PPO and quinone speciation) with potential in healthy ageing, muscle, and brain.

This study investigates occlusal microwear texture patterns of two sequential bioarchaeological populations from sites in western and northern India, each representing a different phase of the same culture: Juna Khatiya (Early Harappan, n = 12) and Rakhigarhi (Mature Harappan, n = 10). These populations, spanning the interval between approximately 3200 BCE and 1900 BCE, were both agro-pastoral, but showed intensified urbanization in the Mature Harappan phase, with concomitant increases craftsmanship and trade. It has been reported that rural peoples in India today consume less processed, more mechanically challenging foods than those living in cities, which has led to the hypothesis that dental microwear may be a useful proxy for tracking settlement pattern in bioarchaeological populations in South Asia. While lower microwear texture complexity was predicted to follow urbanization, recent analysis of two South Indian bioarchaeological populations actually showed the more rural sample to have lower microwear complexity (contra expectation). Here we reevaluate urbanization as a possible driver of microwear texture pattern for agricultural populations in India using two other well-studied populations in different parts of the country. Results indicate that in this case, as predicted, the more urbanized population did have lower microwear texture complexity. This suggests that in some cases, dental microwear texture may be useful as a measure of urbanization but also supports the notion that other factors play an important role in microwear patterning.

Nuclear factor erythroid 2-related factor 2 (NRF2) orchestrates antioxidant defence, electrophile detoxification, and stress recovery across tissues. This paper frames chronic disease vulnerability through the lens of NRF2 insufficiency, defined as reduced functional output of the antioxidant response element programme. We describe the mechanisms that blunt NRF2 signalling, including genetic variation in NFE2L2 and Keap1, epigenetic repression, post-translational degradation routes, and cumulative exposome pressures. Downstream consequences include impaired glutathione-centred buffering, mitochondrial dysfunction, proteostasis failure, inflammatory amplification, and heightened susceptibility to regulated cell death. Using an organ-by-endotype approach, we map recurring patterns across lung, liver, and metabolic tissues, cardiovascular and renal systems, brain, and barrier interfaces that shape systemic ageing phenotypes. Practical biomarkers are reviewed alongside lifestyle and exposome modification strategies, nutritional and nutraceutical approaches, and pharmacological interventions. Preclinical and human evidence for outcome improvement with NRF2 restoration is evaluated, and a risk-management framework addressing boundary conditions such as cancer progression and therapy resistance is proposed. We close with a research agenda prioritising causal study designs, reproducible scoring, and clinically meaningful endpoints to guide precision modulation of NRF2 in chronic disease.

Acanthamoeba spp. are ubiquitous protozoa and the causative agents of severe human infections, including granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The lack of standardised and fully effective treatments highlights the urgent need for novel therapeutic agents. In this study, we evaluated the in vitro amoebicidal activity of 8 cyanoacrylamide derivatives (QOET) against three different strains of Acanthamoeba: A. castellanii Neff, A. griffini and A. polyphaga. Among the tested compounds, QOET-112 and 114 displayed the lowest IC50 values against both the trophozoite and cyst stages compared to the other derivatives. Furthermore, these compounds demonstrated low cytotoxicity against the murine macrophage cell line J774A.1. Analysis of the mode of action evidenced that both cyanoacrylamides triggered programmed cell death (PCD) and autophagy in A. griffini trophozoites. Additionally, these compounds induced severe cytoskeletal alterations, specifically characterised by the disorganisation and disruption of the actin and tubulin networks.

Laurinterol, a halogenated sesquiterpene produced by red algae of the genus Laurencia, is one of the most characteristic compounds within the laurane and cyclolaurane families. This review compiles and examines current knowledge on laurinterol, integrating evidence on its occurrence, biosynthesis, biological activities, and structural features. Within a functional and ecological framework, laurinterol is proposed as an archetypal Smart Secondary Metabolite (SSM), a concept that reflects the convergence of structural singularity, high abundance within its biosynthetic context, broad biological activity, multi-target interactions, and ecological or chemotaxonomic relevance. This perspective highlights its role in adaptive processes within producing organisms and associated trophic networks. Laurinterol exhibits a broad bioactivity profile, including antimicrobial, antimycobacterial, cytotoxic, antiparasitic, enzyme inhibitory, antifouling, and insecticidal or repellent effects. Structure–activity relationship (SAR) studies remain limited and are mainly developed in specific models, particularly against Naegleria fowleri. The current intellectual property landscape related to laurinterol, including patent applications, granted patents, and technological development trends, is also examined. Overall, this review positions laurinterol as a structurally distinctive and functionally relevant marine metabolite within chemical ecology and marine natural products research.

Laurinterol, a halogenated sesquiterpene produced by red algae of the genus Laurencia, is one of the most characteristic compounds within the laurane and cyclolaurane families. This review compiles and examines current knowledge on laurinterol, integrating evidence on its occurrence, biosynthesis, biological activities, and structural features. Within a functional and ecological framework, laurinterol is proposed as an archetypal Smart Secondary Metabolite (SSM), a concept that reflects the convergence of structural singularity, high abundance within its biosynthetic context, broad biological activity, multi-target interactions, and ecological or chemotaxonomic relevance. This perspective highlights its role in adaptive processes within producing organisms and associated trophic networks. Laurinterol exhibits a broad bioactivity profile, including antimicrobial, antimycobacterial, cytotoxic, antiparasitic, enzyme inhibitory, antifouling, and insecticidal or repellent effects. Structure–activity relationship (SAR) studies remain limited and are mainly developed in specific models, particularly against Naegleria fowleri. The current intellectual property landscape related to laurinterol, including patent applications, granted patents, and technological development trends, is also examined. Overall, this review positions laurinterol as a structurally distinctive and functionally relevant marine metabolite within chemical ecology and marine natural products research.

Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) and Nuclear Factor kappa B (NF-κB) are central regulators of redox balance and inflammation, and in healthy tissues, their activities are tightly coordinated. Classical models emphasise an antagonistic relationship in which NRF2-driven antioxidant programmes limit the oxidative cues that sustain NF-κB signalling, while inflammatory cascades can restrain cytoprotective responses when robust host defence is required. Increasing evidence from experimental systems and human tumours indicates that this antagonism is frequently relaxed in cancer. Chronic exposure to reactive oxygen species (ROS), cytokines, hypoxia, and mechanical distortion reconfigures the shared regulatory module formed by these transcription factors, allowing stable co-activation rather than mutual exclusion. In many malignancies, NRF2 and NF-κB become simultaneously active, generating hybrid transcriptional states that integrate antioxidant, inflammatory, metabolic, and survival programmes within the same tumour ecosystem.

In recent years, the pufferfish Lagocephalus lagocephalus has been recorded with unusual frequency in coastal areas of the Canary Islands. The most notable episodes occurred in March and November 2017, when numerous shoals were observed along the coasts of the Western Canary Islands. A toxicological study of these episodes was carried out, analyzing liver, kidney, gonads, skin, and muscle of a representative population. In all toxic samples (33.3% and 41.7% of specimens in March and November 2017, respectively), only the liver extract showed toxicities, using a mouse biological assay (MBA). The toxicological profile was determined by UHPLC-MS-MS, identifying saxitoxin (STX) and tetrodotoxin (TTX) congeners. This analytical methodology was optimized to determine 26 marine toxins. Thus, in the March 2017 episode, the toxicological profile was characterized by the co-occurrence of tetrodotoxins (TTX and 4-epiTTX) and paralytic shellfish toxin (PST) analogues (dcSTX, dcneoSTX, and doSTX); however, STX and neoSTX emerged as the dominant toxins in specimens collected during the November 2017 episode. The results show that L. lagocephalus in the Canary Islands presents a variable and dynamic toxicological profile, strongly influenced by environmental factors. These findings highlight the need for continued monitoring and for analytical approaches capable of capturing this complexity and assessing potential risks to public health.

In recent years, the pufferfish Lagocephalus lagocephalus has been recorded with unusual frequency in coastal areas of the Canary Islands. The most notable episodes occurred in March and November 2017, when numerous shoals were observed along the coasts of the Western Canary Islands. A toxicological study of these episodes was carried out, analyzing liver, kidney, gonads, skin, and muscle of a representative population. In all toxic samples (33.3% and 41.7% of specimens in March and November 2017, respectively), only the liver extract showed toxicities, using a mouse biological assay (MBA). The toxicological profile was determined by UHPLC-MS-MS, identifying saxitoxin (STX) and tetrodotoxin (TTX) congeners. This analytical methodology was optimized to determine 26 marine toxins. Thus, in the March 2017 episode, the toxicological profile was characterized by the co-occurrence of tetrodotoxins (TTX and 4-epiTTX) and paralytic shellfish toxin (PST) analogues (dcSTX, dcneoSTX, and doSTX); however, STX and neoSTX emerged as the dominant toxins in specimens collected during the November 2017 episode. The results show that L. lagocephalus in the Canary Islands presents a variable and dynamic toxicological profile, strongly influenced by environmental factors. These findings highlight the need for continued monitoring and for analytical approaches capable of capturing this complexity and assessing potential risks to public health.

Skytanthus acutus Meyen (Apocynaceae), commonly known as ‘Cuerno de cabra,’ is an endemic species from northern Chile that grows in dune and desert habitats of the Atacama region. This study evaluated the antiproliferative activity of an ethanolic extract from its aerial parts against six human tumour cell lines (A549, HBL-100, HeLa, SW1573, T-47D, and WiDr), yielding GI50 values of 16–28 µg/mL. Bioassay-guided fractionation resulted in the isolation of three compounds: the pentacyclic triterpenoids betulinic acid (BA) and oleanolic acid (OA), reported for the first time in this species, and the monoterpene alkaloid β-skytanthine N-oxide (SN), whose biological activity is described here for the first time. OA showed greater potency (GI50: 3.6–7.2 µM) than BA (GI50: 14–84 µM) and induced cytostatic and apoptotic effects in HeLa cells, highlighting S. acutus as a promising source of anticancer triterpenoids.