Seasonal changes in physiological state and metabolism may influence snake venom composition and biological activity, yet these relationships remain poorly understood. This study investigated seasonal variation in venom composition and functional properties in Naja atra. Venom samples were collected from the same ten adult snakes during the active season and after approximately two months of overwintering. Venom yield, protein composition, and multiple biological activities were compared using quantitative proteomic profiling and functional assays. Proteomic quantification was based on scaled protein abundance values exported from Proteome Discoverer (version 3.3), with peptide and protein identification performed using the Sequest HT search engine. Overwintering was accompanied by body-weight loss and reductions in venom yield, with wet and dry venom yields decreasing by 37.75% and 30.06%, respectively. Proteomic analysis identified 178 protein entries in active-season venom (AV) and 163 in overwintering venom (HV), with 142 shared entries, indicating substantial conservation of the detectable venom protein repertoire alongside compositional changes. Three-finger toxins showed lower relative abundance during overwintering, whereas snake venom metalloproteinases and L-amino acid oxidase exhibited relatively higher representation. Functional assays revealed increased phospholipase A2 (PLA2) activity and decreased proteolytic activity in overwintering venom, whereas L-amino acid oxidase activity, nicotinic acetylcholine receptor (nAChR)-binding activity, cytotoxicity, and hemolytic activity remained largely comparable between groups. These findings indicate that overwintering is associated with reduced venom yield and selective remodeling of venom composition and function rather than uniform suppression of venom activity. Although the underlying mechanisms remain unresolved, this study highlights physiological state as an important consideration in understanding snake venom plasticity.

Patulin (PAT) is a mycotoxin that contaminates apples and apple products and is a recognised hepatotoxicant, but practical dietary countermeasures remain undefined. We asked whether lycopene (LYC), a carotenoid antioxidant, limits PAT-induced liver injury in mice. Male Kunming (KM) mice (n = 8 per group) received PAT at 15 μmol kg[-1] body weight (BW) per day (2.31 mg kg[-1] BW per day), LYC at 5, 20 or 40 mg kg[-1] BW per day, or both, by oral gavage for 28 days. PAT lowered food intake and terminal body weight, raised serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by 96.9 % and 52.0 %, increased hepatic malondialdehyde (MDA) by 76.4 %, and depressed total superoxide dismutase (SOD) activity. Blinded semi-quantitative scoring confirmed hepatocellular injury (0.63 in controls versus 7.75 in PAT-treated mice, out of 12). PAT also raised Grp78, Chop, Bax and lowered Bcl-2. Co-administered LYC attenuated every one of these changes. Protection saturated rather than scaling with dose: a composite hepatic injury index was attenuated by 50.3 %, 84.9 % and 78.3 % at 5, 20 and 40 mg kg[-1] BW. The gain between 5 and 20 mg kg[-1] BW was significant (P < 0.001), whereas no further benefit was obtained at 40 mg kg[-1] BW, the two highest doses being statistically indistinguishable (P = 0.24).Thus,the protective effect of LYC did not increase indefinitely with dose. These findings support bracketing the effective intake of LYC as a dietary countermeasure against PAT exposure.

Snake venom variability is a critical factor in antivenom production. Although several influencing factors have been studied, the impact of extraction interval on venom properties remains poorly understood. This study evaluated the effects of various extraction intervals on venom yield, the percentage of dry weight (%Dw), and composition in the monocled cobra (Naja kaouthia). Twenty-five captive snakes were randomly allocated to five groups, each undergoing a control extraction followed by a repeated extraction at 1, 4, 7, 10, or 14 days. Venom profiles were characterized using reversed-phase high-performance liquid chromatography (RP-HPLC) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Results indicated that while fresh venom yield remained stable across all intervals, %Dw significantly decreased in extractions performed between 1 and 10 days, returning to control levels only by day 14. RP-HPLC analysis revealed that early repeated extraction significantly reduced the relative abundance of long-chain α-neurotoxins-rich fraction, which contains the principal neurotoxic components of the venom. Conversely, fractions containing cytotoxins and phospholipase A2 (PLA2) showed a higher relative abundance in the 1-day repeated extraction. In conclusion, N. kaouthia requires a minimum recovery period of 14 days for most measured properties but not all of them approached the control level. These findings suggest that standardized venom extraction protocols may be important for maintaining a consistent dry venom production and representative toxin profile, which could potentially contribute to the quality and effectiveness of antivenom production.

Ipomoea carnea, an invasive plant widespread in tropical and subtropical regions, contains the toxic alkaloids swainsonine and calystegines, which induce lysosomal dysfunction, neurodegeneration, and neuroinflammation. Menthol, a cyclic terpene alcohol from peppermint oil, exhibits antioxidant, anti-inflammatory, and neuroprotective properties. This study is the first to investigate the neuroprotective efficacy of menthol against neurotoxicity induced by I. carnea leaf extract in rats, with a novel focus on the pyroptosis pathway. Twenty-four male Sprague Dawley rats were divided into four groups: control, I. carnea extract (15 mg/kg, oral), I. carnea extract plus menthol (5 mg/kg, i.p.), and I. carnea extract plus menthol (10 mg/kg, i.p.) for 8 weeks. I. carnea extract significantly reduced feed intake, body weight gain, feed efficiency, brain weight, and dopamine and serotonin levels in serum and brain, while increasing oxidative stress markers (MDA, NO), inflammatory cytokines (IL-6, TNF-α), and pyroptosis-related gene expression (Casp-1, Casp-3, Casp-11, NLRP-3, GSDMD, IL-1β, IL-18). Histopathology revealed marked ischemic neuronal changes, vacuolation, and malacia. Notably, we provide the first evidence that I. carnea triggers pyroptotic cell death in the brain, and that menthol dose-dependently suppresses this pathway. Correlation analyses further revealed strong inter-relationships among oxidative stress, inflammasome activation, and neurotransmitter depletion. Menthol co-administration, especially at 10 mg/kg, prevented these alterations, attenuated oxidative stress and neuroinflammation, prevented the upregulation of pyroptosis-related genes, and preserved neuronal architecture. These findings demonstrate that menthol exerts significant neuroprotection through modulation of oxidative stress, inflammation, and the newly identified pyroptosis pathway, positioning it as a promising candidate for mitigating plant alkaloid-induced neurotoxicity.

Fungal species produce various secondary metabolites with carcinogenic and genotoxic properties, including aflatoxins, ochratoxins, fumonisins, sterigmatocystin, and griseofulvin. Acute or chronic exposure to these mycotoxins through contaminated food and feed can cause DNA damage, chromosomal instability, and epigenetic changes, ultimately leading to cancer. This review focuses on IARC-classified carcinogenic mycotoxins and their contribution to cancer development by disrupting the DNA damage response (DDR), thereby affecting apoptosis, cell cycle regulation, and genomic stability. Current knowledge of co-exposure to mycotoxins, host susceptibility, and validated biomarkers remains limited, particularly regarding the regulation of DDR genes. This necessitates more in-depth mechanistic and epidemiological research. Network analysis of host genes associated with mycotoxins in the CTD, integrated with DDR-related genes curated from CancerSEA, identified candidate DDR-associated genes implicated in pathways related to cell cycle regulation, DNA repair, oxidative stress response, and apoptosis. These findings represent database-derived associations and computational prioritization, rather than evidence of causal mechanistic roles in mycotoxin-induced carcinogenesis. Enrichment analysis using the Enrichr tool further identified the association between mycotoxin-associated DDR genes and cancer. In brief, this review enhances the understanding of the role of mycotoxins in DDR mechanisms and their potential contribution to cancer development, thereby providing a basis for improved molecular and translational approaches to address the associated health risks.

Two small peptides were purified from the venom of the vermivorous cone snail, Conus tessulatus, and evaluated for neuroactivity. Structural characterization by Edman sequencing and mass spectrometry revealed that the two peptides, named ts3b and ts3c, are 14 amino acids long and can be classified as mini-M conotoxins under framework III, M-superfamily, M2 branch. Native samples of ts3b and ts3c caused temporary swimming paralysis in fish, yet elicited distinct responses in the dorsal root ganglion (DRG) assay and the Constellation Pharmacology platform. Peptide ts3b caused mild sluggishness and shaking in young mice and irreversible, indirect excitation in a primary culture of DRG neurons. Furthermore, nanomolar concentration of native ts3b affected small diameter peptidergic nociceptors (PNs) and c-low threshold mechanoreceptors (C-LTMRs) in the DRG. Interestingly, ts3c caused an irreversible block in cultured DRG neurons, primarily affecting capsaicin-sensitive PN cells and capsaicin-insensitive non-peptidergic nociceptors (NPNs). The bioactivities suggest that ts3b and ts3c may target distinct ion channels or receptors. Two ts3b toxiforms were also identified as ts3b Asn15 toxiform and ts3b Ser7Arg, Asn15 toxiform. The toxiforms have a similar loop pattern, post-translational modifications, and cysteine framework with ts3b. Native ts3b and the toxiforms caused mild lethargy in mice. Peptide ts3b and ts3c are the first neuroactive mini-M conotoxins described from C. tessulatus. Few neuroactive conotoxins have been reported under the M-2 branch, and these compounds may have novel molecular and pharmacological targets due to their diverse structural conformations.

Tifton 68 (Cynodon nlemfuensis) is a cyanogenic forage grass that may also contribute to dietary sulfur exposure. Young Tifton 68 was introduced into a 32-animal dairy herd. Within approximately 2 days, neurological disease was recognized; eight cattle were affected and four died. Affected cattle developed visual and postural deficits, hypermetria, intention tremors, recumbency, and convulsions. The forage produced a rapid positive reaction in the qualitative sodium picrate paper test. Neuropathological examination of one cow revealed bilateral pseudolaminar cortical neuronal necrosis with selective deep gray-matter and cerebellar injury. The outbreak was strongly associated with Tifton 68, but cyanide exposure was not analytically confirmed and total sulfur exposure was not determined, leaving cyanide exposure and sulfur-associated polioencephalomalacia as competing etiological hypotheses.

Approximately 294 million people live within 10-km grid cells containing recent, georeferenced records of Nicotiana glauca, a widely naturalized poisonous plant associated with severe anabasine-mediated intoxication. Although this spatial overlap does not represent direct human exposure, it highlights the broad geographic extent of potential human-plant encounters. However, it remains unclear whether readily observable plant characteristics, such as developmental stage, leaf morphology, or seasonal condition, can reliably identify plants with consistently low foliar anabasine concentrations. We combined a field survey in three Brazilian localities and longitudinal sampling at one of these localities with comparative phylogenetic and global occurrence analyses to address this question across within-species, evolutionary and geographic scales. All 174 field and longitudinal determinations yielded non-zero estimates, despite substantial quantitative variation among localities and individuals. Within the sampled plants, neither juvenile leaf size, adult collection state nor sampled calendar month identified a condition with consistently low foliar anabasine concentrations. Across 54 Nicotiana species, foliar anabasine showed significant phylogenetic structure (Blomberg's K = 0.59-1.11; Pagel's λ = 0.86-0.93), with consistently elevated standardized scores in Nicotiana section Noctiflorae. Nicotiana glauca ranked second in the cross-study foliar consensus, behind N. noctiflora, but its geographic distribution was markedly broader: 1243 one-degree grid cells across 66 countries, 12.8 times the occupied-cell breadth of the next most widespread high-scoring species. Together, these findings show that the toxicological significance of N. glauca arises from the convergence of persistent foliar anabasine occurrence across sampled conditions, lineage-associated high concentrations and an unusually broad global distribution, rather than from chemical constancy alone.

Snake-related injuries (SRI) in Malaysia are a medical emergency. SRI may be accompanied by wound infection requiring medical and surgical intervention. Despite its clinical relevance, local epidemiological and microbiological data remain limited in Malaysia. This was an observational analysis conducted on 72 hospitalised patients with wound infections following snake-related injuries who received consultation from the Remote Envenomation Consultancy Services (RECS). Data were collected using a standardised collection form. Among 559 hospitalised SRI cases, 72 patients (12.9%) developed wound infections. Males accounted for 70.8%, and most patients with wound infections were young adults aged 18 to 44. The most frequent symptoms were swelling (91.7%) and erythema (69.4%). SRI from Naja species were the most frequently identified cause of wound infections. Bacterial cultures were positive in 15.3% of cases, with Enterococcus species being the most frequently identified. Amoxicillin/clavulanate was the most used antibiotic. Wound debridement was performed in 27.8% of cases. Most patients were hospitalised for more than 5 days, and the most common outcome was healed with a scar (34.7%). No mortality was reported. This study emphasises the need for accurate clinical assessments to distinguish between venom-induced inflammation and subsequent bacterial infection. Although the culture-positive rate was low, the presence of pathogens such as Enterococcus species, which are often resistant to standard antibiotics, emphasises the need for cultures and sensitivity testing in snakebite-related infections. Early antivenom therapy, adequate antibiotic usage, and prompt surgical intervention, such as debridement, will improve patient outcomes. These findings provide useful local insights for clinical guidelines and for better management of wound infections following snake-related injuries in Malaysia.

Chactas exsul (Werner, 1939) is a specialized, saproxylic scorpion belonging to the diverse family Chactidae, inhabiting the humid tropical forests of Costa Rica and Panama. Characterized by robust pedipalps and a relatively small telson, C. exsul primarily relies on mechanical immobilization for prey capture, though it may utilize venom during challenging encounters. Despite its evolutionary importance, the venom of most of its members remains largely uncharacterized. In this study, we provide a comprehensive proteomic and biochemical analysis of the venom of C. exsul from the Caribbean lowlands of Costa Rica. Our results reveal a venom peptidome dominated by putative scorpine-like antimicrobial peptides, calcins, and orphan components such as La1-like peptides. Sodium channel-modulating toxins (NaTxs) and common non-buthid potassium toxins (α- and κ-KTx) were not identified. The protein fraction exhibited significant complexity, featuring metalloproteinases, serine proteinases, phospholipases A2, and two putative hyaluronidase isoforms, among others. CAP-domain secretory proteins show several variants in the venom. These findings suggest a dual-functional trophic and, probably, defensive strategy: with a peptide fraction likely targeting insect-specific K[+] and Ca[2+] channels, which could induce paralysis, while the enzymatic cocktail could facilitate toxin maturation and spreading, as well as tissue predigestion. These activities and the role of putative scorpines as antimicrobials against soilborne pathogens inhabiting humid microhabitats remain to be determined.

The venom of the slender black scorpion Centruroides nigrescens, from the State of Guerrero México, was fractionated by Sephadex G-50 gel filtration, followed by carboxymethyl cellulose ion separation and high-performance liquid chromatography, permitting to obtain two new peptides toxic to arthropods. The estimate LD50 of the soluble venom for the insect Acheta domesticus was 11.1 μg/g body weight, and for the arthropod Armadillidium vulgare was 61.1 μg body weight. The amino acid sequence of toxin Cnige1 (toxic to A. domesticus and A. vulgare) contains 65 amino acids, with a molecular mass of 7273.37 mass units, whereas toxin Cnige2, toxic to A. domesticus, contains 68 amino acids, with a molecular mass of 7548.81 units. Both peptides are well packed, containing 8 cysteines, which in the native venoms are forming 4 disulfide bridges each. The amino acid sequences found, for both novel toxins, shows some similarities to other known scorpion arthropod toxins. This venom is not toxic to mammalians, using mice as model, but contains many peptides as shown by mass spectrometry, for which the full primary structure and function are not known.