Publications

Background

Cellular redox regulation is increasingly recognised as a spatially organised network in which oxidant production, thiol buffering, and selective signalling operate within compartment-specific microdomains rather than as uniform cellular processes. However, peptide-mediated mechanisms that actively define these local redox environments have not previously been integrated into a unified conceptual framework.

Objective

This review introduces the concept of peptide redox networks, defined as peptide or protein systems whose local abundance, oxidation state, or proteolytic processing directly determines the amplitude, spatial confinement, or propagation of redox signalling within specific cellular microdomains. We evaluate the evidence supporting this framework and discuss its implications for mechanistic research and clinical translation.

Main Content

We synthesise current knowledge on glutathione, histidine-containing dipeptides, mitochondria-targeted peptides, and mitochondrial-derived peptides as complementary regulators of cellular redox homeostasis. Particular emphasis is placed on compartment-specific redox set points, NADPH-dependent buffering, ferroptosis vulnerability, mitochondrial quality control, and regulated thiol signalling. We further examine recent advances in redox proteomics, isotope tracing, and proteoform-aware analytical strategies, highlighting methodological challenges that influence data interpretation. Based on these considerations, we propose operational criteria for defining peptide redox network components, establish minimum reporting recommendations to improve reproducibility, and identify experimental approaches capable of distinguishing adaptive redox regulation from irreversible oxidative dysfunction.

Biological invasions are a major threat to global biodiversity, with a particular strong impact on oceanic islands and their unique and fragile biotas. However, the complexity of the processes underlying invasions has prevented the identification of general patterns explaining why some plant species successfully establish and spread beyond their native ranges. Here, we investigate Darwin's naturalization conundrum in the most species-rich angiosperm family of the Canary Islands, considering two invasion stages at the archipelago and island levels.

In this work, we report the synthesis and structural characterization of a novel organometallic bipyridine-based atropisomer featuring two (S)-BINOL-derived units, each functionalized with a ferrocene moiety and linked by a 4,4′-disubstituted 2,2′-bipyridine bridge. Although the molecule appears symmetric, single-crystal X-ray diffraction establishes its axial chirality, as demonstrated by Flack x = −0.020(14) and Hooft x = 0.013(18) parameters. The bipyridine core, sterically hindered by the bulky ferrocenyl groups, imposes a rigid atropisomeric structure. To better understand this behavior, a new Cu(II) complex is presented to examine how peripheral substitution affects the accessibility and coordination capacity of the bipyridine core; these factors ultimately dictate the solid-state atropisomerism and rigidity of the resulting multinuclear architecture.

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.

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.

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.

Polyphenols act in humans through authentic metabolites, including regio-isomeric glucuronides/sulphates, O-methylated forms, and microbiota products (urolithins, γ-valerolactones, equol), that reach targets by spatiotemporally gated exposure. Vectorial transport (MRP2/BCRP/P-gp), enterohepatic cycling, and β-glucuronidase hubs create early, surface-proximal microbursts of aglycone/catechol, whereas microbiota metabolites arrive systemically 6–24 h later. Signalling emerges from a continuum of weak noncovalent modulation, conditionally gated electrophile/redox relays (catechol → o-quinone, reversible Michael adduction plus signalling-range H2O2), and PTM cascades (phosphorylation → acylation → proteostasis) that reprogram NRF2/Keap1, NF-κB/IKK, AMPK/MAPK/PI3K-Akt, SIRT1/HDACs, PPARγ, AhR, and TFEB according to where and when metabolites appear. We provide methods and standards to dose isomer-resolved metabolites at physiological free concentrations (nM-low µM) in transport-competent systems, with PK-informed sampling across seconds–minutes, 15/60/240 min, and 6–24 h, and we outline a research agenda (reference panels, spatial exposure atlases, metabotype-stratified trials, safety windows). Framed this way, polyphenols shift from vague “antioxidants” to programmable dietary signals that enable precision nutrition targeting transcription-factor and proteostasis programmes in vivo.