Publications

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.

Silymarin (Silybum marianum (L.) Gaertn. extract) is a widely used botanical for liver disease, yet clinical results remain inconsistent. Most mechanistic work uses supraphysiological aglycones, whereas humans are exposed predominantly to phase II conjugates that are strongly protein-bound and routed by transporters toward bile and the intestinal mucosa. We reframe silymarin activity through a spatial pharmacology lens, proposing three post-intake windows: early (0–2 h) conjugate-dominant exposure with localised β-glucuronidase-mediated reactivation; intermediate (2–8 h) enterohepatic recirculation pulses; and late (8–48 h) microbial catabolite contributions. Each window engages distinct signalling modules—Keap1/NRF2, NF-κB, and AMPK-mTOR-TFEB—via transient redox events (quinone cycling, micro-H2O2 relays) and proteostatic remodelling (autophagy/mitophagy). We synthesise human pharmacokinetic and clinical evidence—with emphasis on MASLD and alcohol-associated liver disease—and show how formulation, meal timing, and microbiome metabotype determine which windows are engaged. Finally, we propose minimum reporting standards and falsifiable hypotheses to reduce between-study heterogeneity and enable precision use of silymarin.

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious public health concern, particularly in Latin America, due to its high prevalence and the limited efficacy and safety of current treatments. To identify new potential therapeutic options, a library of 40 synthetic indole derivatives was screened for antiparasitic activity. The compounds were tested against both epimastigote and intracellular amastigote forms of T. cruzi using in vitro assays. While most of the molecules showed low or no activity, ten compounds exhibited promising effects with IC₅₀ values below 200 μM. The most active derivatives were further evaluated for cytotoxicity on mammalian cells. Among them, the compound I – 7b stood out with a selectivity index of 19.8 and was selected for further characterization. Subsequent assays revealed that this compound induced several cellular effects in the parasite, including ATP depletion, chromatin condensation, plasma membrane damage, reactive oxygen species (ROS) accumulation, and disruption of mitochondrial membrane potential (ΔΨm). These findings suggest that certain indole-based compounds may serve as promising scaffolds for the development of novel therapies against T. cruzi, contributing to the advancement of global health efforts targeting neglected tropical diseases.

Invasive alien species are one of the most severe threats to island biodiversity. An essential first step in addressing this issue is producing comprehensive inventories of alien species inhabiting them. However, cataloguing alien floras on remote islands is particularly challenging. Botanical surveys are often conducted only after substantial human-driven impacts on local ecosystems, including the introduction of invasive species, have already occurred. This raises the key question of how species’ native origin should be determined on islands with such a recent history of botanical documentation. Site-based methodologies offer a practical, replicable and context-sensitive approach to addressing these challenging knowledge gaps. Here, we present a comprehensive catalogue of the alien spermatophyte flora of Isla del Coco, an eastern Pacific island located approximately 500 km off the Central American mainland and facing the aforementioned challenges. Among the main contributions of this study, we apply an expert-based binary decision tree to classify the wild flora as native, wild alien, or cryptogenic, along with a separate inventory of cultivated species. Our classification system allowed us to identify 89 wild alien species (45.2% of the island’s total wild flora), 78 native species (39.6%), and 30 cryptogenic (15.2%). The naturalised-to-native ratio (0.5) suggests that the island remains highly susceptible to biological invasions. The profile of the alien flora closely resembles that of mainland Central America, with a predominance of unintentionally introduced species, underscoring the need for strict biosecurity measures at landing points. The methodology employed also indicates that site-based approaches may apply stricter criteria for defining native species than previous studies, thereby highlighting new research needs for Isla del Coco, such as clarifying the status of cryptogenic species and investigating the largely unexplored impacts of invasive alien plants.

Cellular redox biology is governed less by bulk oxidant load than by the coupled behaviour of ROS, RNS, and RSS within spatially restricted microdomains. Within these niches, redox information is written, edited, and erased through competing post-translational modifications, including sulphenylation (-SOH), S-nitrosylation (-SNO), and persulphidation (-SSH). Local proximity to sources such as mitochondria, NOX, and NOS platforms combines with buffering by SOD and peroxidases to shape which routes dominate. Editing by thioredoxin, glutaredoxin, and GSNOR, together with sulphane sulphur flux from trans-sulphuration enzymes and mitochondrial sulphide oxidation, sets the boundary between reversible redox eustress and pathological distress dominated by peroxynitrite chemistry and irreversible oxidation. Using a compartment-aware analytical template across cardiometabolic disease, neurodegeneration, cancer, chronic inflammation, ageing, and innate immunity, we identify recurring mechanistic patterns and explain why global biomarkers can mislead. We then propose context-matched biomarker panels and therapeutic levers, with antimicrobial peptides emerging as redox-modulated effectors of innate defence within this framework. Finally, we outline precision redox pharmacology that raises local distress thresholds without flattening physiological signalling, and we propose a trial-ready agenda centred on compartment-resolved pharmacodynamic anchors.

Acanthamoeba infections are hindered by limitations including prolonged treatment duration, cytotoxicity, limited efficacy against the resistant cystic stage, and a high rate of recurrence. Antimicrobial peptides (AMPs) demonstrate broad-spectrum antimicrobial activity, rapid mechanism of action, low potential for inducing resistance, and efficacy against both trophozoite and cyst forms, highlighting their potential as promising alternatives in the treatment of these infections. Herein, we report the amoebicidal activity of various peptides derived from cathelicidins and piscidins against Acanthamoeba castellanii Neff. Afterwards, the impact of the most effective peptide on the clinical features of a clinical strain of Acanthamoeba castellanii was evaluated using a fluorescence imaging system. Peptide OH_KR34 was the most active against A. castellanii Neff with an IC₅₀ values of 2.00 ± 0.58 µM. OH_KR34 was able to inhibit the clinical strain of A. castellanii (L10) with an IC50 of 5.75 ± 0.30 μM. We demonstrated that the peptide OH_KR34 (related to OH-CATH) induces cytoskeletal damage and trigger apoptosis-like process by disrupting cell membrane permeability, mitochondrial dysfunction and DNA fragmentation. This antimicrobial peptide could therefore offer a potential target to develop new anti-parasitic drugs.

Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling have substantially expanded the experimental evidence, while generative artificial intelligence now enables de novo design of peptide immunogens and multi-epitope antigens under precisely controlled constraints. This review approaches how these complementary developments are transforming peptide vaccine research, moving beyond classical reverse vaccinology and conventional epitope prediction toward integrated, data-driven design frameworks. We discuss key generative model architectures and conditioning strategies aligned with vaccine objectives, including approaches that account for structural presentation, antigen processing and population-level human leukocyte antigen (HLA) diversity. Central to this perspective is the requirement for rigorous experimental validation and for strengthening the computational–experimental feedback loop through iterative in vitro and in vivo testing informed by systems-level immune readouts. We highlight representative applications spanning infectious diseases, cancer immunotherapy and vector-borne vaccinology, and we outline major technical and translational challenges that must be addressed to enable robust real-world deployment. Finally, we propose future directions for precision peptide vaccinology, emphasizing standardized functional benchmarks, the development of richer curated datasets linking sequence space to immune outcomes, and the early incorporation of formulation and delivery constraints into generative design pipelines.

The concept of “Smart Secondary Metabolites” is introduced here to describe a privileged class of natural products defined by structural originality, biosynthetic adaptability, and broad interaction potential with biological systems. Elatol, a halogenated sesquiterpene chiefly produced by Laurencia red seaweeds and occasionally accumulated by their consumers, exemplifies this concept with remarkable clarity. Its biosynthesis unfolds from farnesyl diphosphate via γ-bisabolane cations, bromochlorination, and stereoselective cyclization to chamigrene scaffolds, generating both (+)- and (–)-enantiomers, two metabolites with clearly distinct potential ecological roles and pharmacological profiles. This review synthesizes the current state of knowledge on elatol’s distribution, biosynthetic origins, ecological relevance, and therapeutic potential. Elatol serves as a multifunctional chemical mediator, fulfilling defensive, communicative, and regulatory roles whose intensity shifts in response to herbivory, biofouling, temperature, and salinity. In parallel, its potent activities against infectious, metabolic, and neoplastic diseases highlight its growing value as a drug lead, reflected in a rising number of patent claims. Altogether, elatol emerges as a model Smart Secondary Metabolite whose ecological sophistication and biochemical versatility position it as a promising scaffold for marine-derived drug discovery.

Cathelicidins, a diverse family of host defence peptides (HDPs) in vertebrates, are recognized for their potential in combating resistant microorganisms and their varied biological functions. While extensive studies have focused on mammalian cathelicidins, those in reptiles remain largely unexplored. In this study, we conducted a genome mining analysis that identified 287 cathelicidin genes across reptilian orders Testudines and Squamata. Of these genes, we identified 219 complete cathelicidin protein sequences and 68 cathelicidin-like gene copies that appear to be pseudogenes or gene fragments lacking intact open reading frames. We established for the first time a classification for reptile cathelicidins of the cited orders based on their sequence and structure, observing six types for Testudines and six for Squamata, suggesting a common ancestral lineage. Furthermore, we investigated the genomic arrangement of these cathelicidin genes, uncovering that they are grouped into clusters with variability in the gene number and in their organization. Cathelicidin derived mature peptides were classified into nine groups based on their sequences and physicochemical properties. This comprehensive study enhances the understanding of the cathelicidin family in reptiles, clarifying their genomic organization and describing the different types present. These classifications pave the way for future studies on the functions and specialization of each identified cathelicidin group. Moreover, they enable potential structure-activity studies of the peptides, establishing a foundation for differentiating their key features.