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From the monotypic family Superstitioniidae, the scorpion Superstitionia donensis presents a high diversity of transcripts encoding non-disulfide-bridged peptides (NDBPs). In this study, five peptide sequences inferred from a previous venom gland transcriptomic analysis were selected based on sequence similarity and physicochemical properties associated with previously antimicrobial peptides. An additional peptide was designed to evaluate the effect of changes on selected physicochemical properties on its hemolytic and antimicrobial activity. The selected peptides were synthesized using Merrifield Solid-Phase peptide synthesis and evaluated form antimicrobial activity against Gram-negative and Gram-positive bacteria, belonging to the ESKAPE group and yeasts of the Candida and Cryptococcus genera, as well as for hemolytic and cytotoxic activity in mammalian cells. Some peptides showed antimicrobial activity against selected microbial strains, including Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Candida krusei, and Candida tropicalis, while limited or no activity was observed against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida glabrata. Notably, treatment with some selected peptides improved the survival of Galleria mellonella larvae infected with S. aureus, supporting their functionality in vivo, Peptide toxicity was also evaluated in human erythrocytes and two human cell lines, showing that some peptides with antimicrobial activity also exhibited hemolytic effects; however, they showed low cytotoxicity to cell lines at antimicrobial concentrations. Despite observed hemolytic activity, the relatively low cytotoxicity against human cell lines suggests potential for improvement through structural refinement. These results demonstrate that S. donensis NDBPs exhibit antimicrobial activity and hemolytic effect, and their sequences may serve as templates for further modification. Furthermore, the findings reveal that antimicrobial potency and cytotoxicity are influenced by sequence similarity, net charge, and hydrophobicity. Nevertheless, the physicochemical property values required to identify an optimal antimicrobial peptide remain poorly defined, as several parameters exhibit overlap between high- and low- performing candidates, which highlights a key challenge for their therapeutic development.

The effects on human health from exposure to cyanotoxins during cyanobacterial blooms have been reported worldwide. Accumulation of toxins in fish has been documented as a potential route of transfer to humans through the ingestion of contaminated food. In this study, we determined the magnitude of microcystin (MCYSTs) concentrations in six reservoirs in central Mexico to assess the potential risk of toxin transfer to humans through the consumption of fish. Physicochemical parameters, phytoplankton composition, and MCYSTs concentrations were analyzed in water, seston, and tissue of nine fish species with varying trophic habits were analyzed. We detected MCYSTs in all reservoirs, both dissolved and in seston, with the highest concentrations recorded in the Batán and Carmen reservoirs, where Microcystis was the dominant cyanobacterial genus. All fish species showed accumulation of MCYSTs, with Goodea atripinnis (phytoplanktivore) and Chirostoma jordani (zooplanktivore) exhibiting the highest concentrations in viscera and whole-body analyses. The estimated daily intake derived from consuming 100 g of contaminated fish frequently exceeded the WHO tolerable daily intake of 0.04 μg/kg body weight, indicating potential risks to human health. This finding evidences a widespread presence of hepatotoxic MCYSTs in reservoirs of central Mexico in water (regardless of the occurrence of visible blooms), seston, and accumulated in tissues of fish species. This study represents the first report of MCYSTs accumulation in fish tissue from different trophic habitats in reservoirs in central Mexico and emphasizes the need for ongoing cyanotoxin monitoring and management measures to mitigate risks to both aquatic ecosystems and human consumers.

LPS-induced chronic lung injury is a precursor to pulmonary fibrosis; however, the precise molecular mechanisms underlying this pathological progression remain incompletely elucidated. TRPC6 channel has been implicated in various forms of lung disease, yet its specific contribution to LPS-driven fibrogenic processes remains poorly defined. We investigated TRPC6 function in alveolar epithelial cell injury and fibrosis following LPS exposure. We found that LPS upregulated TRPC6 expression, causing calcium influx and ROS overproduction. These perturbations culminated in mitochondrial dysfunction and enhanced apoptotics. Concurrently, LPS triggered activation of the NLRP3 and AIM2 inflammasomes, thereby facilitating the maturation of IL-1β, and activated the TGF-β1/Smad signaling pathway, leading to pulmonary fibrosis. Notably, pharmacological inhibition of TRPC6 with BI-749327 ameliorated these pathological processes, whereas TRPC6 activation via OAG exacerbated them. Consistent with the in vitro observations, Trpc6-deficient (Trpc6^-/-) mice exhibited substantially attenuated pulmonary inflammation, epithelial injury, and fibrotic sequelae following LPS challenge. These protective effects were associated with diminished activation of both TGF-β1/Smad signaling and the NLRP3 and AIM2 inflammasomes, as well as reduced circulating levels of pro-inflammatory cytokines, including IL-1β and IL-6. Collectively, our findings identify TRPC6 as a pivotal mediator in LPS-induced pulmonary fibrosis by disrupting calcium homeostasis and activating NLRP3 and AIM2 inflammasomes, eventually resulting in TGF-β1/Smad-driven fibrotic remodeling. Thus, targeting TRPC6 may represent a promising therapeutic approach for mitigating chronic inflammation-associated pulmonary fibrosis.

Mycotoxins such as ochratoxin A (OTA) are hazardous chemicals produced from fungi that frequently contaminate feed ingredients, and this contamination can result in significant economic loss, disease and death. Given the persistent nature of OTA, this study was designed to provide effective and potentially scalable strategies to mitigate acute OTA toxicity using organoclay. The study explores the adsorption behavior of OTA on active binding surfaces of four organoclay composites that were synthesized by modifying sodium bentonite clay surfaces with different amounts of a hydrophobic quaternary ammonium compound (QAC). This modification serves to immobilize and stabilize the QAC. The study evaluates key thermodynamics, kinetics and binding markers including the Gibbs free energy (ΔG), adsorption capacity, enthalpy (ΔH), and binding affinity of these clays for OTA. Additionally, the protective role of these organoclays was evaluated using a sensitive ecotoxicology model. At gastric pH (pH 2), the organoclays demonstrated high adsorption capacities for OTA ranging between 0.34 and 0.51 mol kg^-1 versus parent clay (0.20 mol kg^-1). At intestinal pH (pH 6), the organoclay binding capacities were higher than the parent clay indicating that the modification of parent clay with QAC played a critical role in improving its adsorptive performance for OTA. Thermodynamic parameters indicated that the binding reaction was exothermic and thermodynamically favorable with ΔG values between -23.40 and -28.07 kJ mol^-1 and ΔH values ranging from -13.76 kJ mol^-1 to -24.31 kJ mol^-1. Importantly, organoclay treatment protected hydra from OTA lethality by 95% to 100%. These findings established the proof-of-concept that OTA interactions with organoclay resulted in the prevention of OTA toxicity in hydra. Based on these findings, further studies are warranted to justify the applications and efficacy of these organoclays for short-term treatment during acute outbreaks of ochratoxicosis.

Legal use of herbal health products must comply with quality and safety standards required by health regulatory authorities in order to protect consumers from risks associated with misidentification, falsification and undesirable toxic effects. Some plant-derived compounds can act as CYP450 inhibitors, potentially leading to herb-drug interactions and, in some cases, direct hepatotoxicity, particularly when CYP450-mediated bioactivation is involved. There is a critical need to develop reliable and efficient screening assays to identify potential CYP450 inhibitors in such complex mixtures and hepatotoxicity risks associated to CYP450 metabolization. In this context, we propose associating a HepaRG cell-based test with suitable qualitative and quantitative phytochemical analyses. A case study was conducted using Tinospora crispa (T. crispa) stems harvested in Laos ("boraphet"). This herb is traditionally used for its antidiabetic effects and is known to cause hepatotoxicity, most likely due to the presence of furanoditerpenoids bioactivated by cytochromes. A Molecular Networking-based UHPLC-(HRMS)² fingerprint of furanoditerpenoids was established by analysing methanolic extracts, enriched fractions of a representative sample and standards, by applying the bioinformatic Feature-Based Molecular Networking workflow. The fingerprinting model enabled identification and comparison between three samples harvested from nearby geographical locations (Hinboun, Yommalath and Nakaiy) through the detection of fourteen furanoditerpenoids. Four of them were identified as borapetosides A-D, eight had not yet been isolated, and were tentatively assigned. Borapetoside C content, determined by UHPLC-UV is proposed as an assay for the quality control of T. crispa stems. The CYP3A4 inhibitory activities of the methanol extracts and of borapetoside C were measured in a HepaRG cell model, which is a validated model for studying CYP450 inhibitory effects. All extracts and borapetoside C exhibited CYP3A4 inhibition. This work highlights the interest in including a HepaRG cell-based test in the T. crispa stem specification to assess the toxicity of herbal constituents associated with CYP450 inhibition.