A comprehensive preclinical assessment of Viekvin antivenom: Evaluation of neutralization efficacy and cross-reactivity toward European snake venoms.

Background/Objectives: The study investigated the anti-inflammatory potential of neolignan derivatives of dehydrodieugenol (CP1–CP5), focusing on the inhibition of secretory phospholipase A2 (sPLA2), a key enzyme in inflammation. Methods: Comprehensive quantitative docking analysis using four independent algorithms (PLP, ASP, ChemScore, GoldScore) revealed exceptional multitarget binding profiles for CP1 and CP2, with scores consistently above activity thresholds for acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2), and sPLA2 from Crotalus durissus terrificus in both monomeric (Mcdt) and quaternary (Tcdt) forms. Results: Among the compounds, CP1 demonstrated the highest predicted affinity (AChE: 78.5, COX-2: 83.8, sPLA2: 82.7–83.4) and most potent experimental activity, reducing sPLA2 catalytic velocity through mixed-type inhibition involving the active site (His47, Asp48) and Ca2+ binding loop. In vivo assays in sPLA2-induced paw edema demonstrated that CP1 and CP2 achieved remarkable anti-inflammatory effects (up to 68.3% reduction), significantly exceeding their protective potential by direct enzyme inhibition, confirming the multitarget mechanism. The strong correlation between predicted docking scores and paw edema reduction (R2 = 0.89, p < 0.01) creates a firm foundation for establishing structure–activity relationship explanations. Conclusions: These findings highlight an integrated mechanism involving: (1) partial sPLA2 modulation, (2) neuroimmune regulation via AChE inhibition, and (3) prostaglandin synthesis blockade through COX-2 inhibition. This multitarget approach, combined with the natural origin of the compounds, positions dehydrodieugenol derivatives as promising candidates for developing therapies against complex inflammatory diseases, offering significant advantages over single-target strategies.

Bothrops mattogrossensis Snake Venom: How Age and Sex Shape the Chemistry of the Envenoming.

Immunostimulatory effect of low molecular weight fraction from Bothrops jararacussu venom.

Recombinant expression of crotoxin and comparison to native crotoxin as immunogens for anti-crotalid antivenoms.

Proteomic and biochemical characterization of Bothrops pubescens (Serpentes: Viperidae) venom.

Mechanistic insights into NOBA hydrolysis by viper venom secreted phospholipase A2.

Elucidation of the composition structure and physicochemical stability of flaxseed oil bodies recovered from neutral and weak alkaline.

Iguratimod suppresses volume-sensitive outwardly rectifying anion channels via arachidonic acid accumulation.

PLA2R1-mediated ERK-Dependent ferroptosis: A key pathogenic mechanism in epileptic neuronal injury.

This study explores the application of immobilized phospholipase A1 (PLA1) on hollow double-layer mesoporous silica nanoparticles (PLA1@NH2/C8-HdlMS) for the degumming of crude arachidonic acid (ARA) oil for the first time. The immobilized enzyme was comprehensively characterized, and the reaction conditions were optimized via single-factor experiments. Under the optimized conditions (enzyme dosage 0.3% w/w, 35 °C, water addition 3%, and reaction time 90 min), PLA1@NH2/C8-HdlMS achieved a remarkable phosphorus removal rate of 97.9%, reducing the phosphorus content from 441.21 mg/kg to 9.29 mg/kg in 90 min (well below the food-grade standard of <10 mg/kg). The fatty acid composition of the oil remained almost unchanged, while the oxidative induction time of the degummed oil significantly improved by 42%. Notably, PLA1@NH2/C8-HdlMS demonstrated broad applicability across crude oils, with initial phosphorus contents ranging from 294.98 mg/kg to 537.44 mg/kg, and it maintained ~93% of its initial activity after 11 reuse cycles. Compared to traditional hydration degumming (with a phosphorus removal rate of 56.3%), this enzymatic method offers superior efficiency at lower temperatures, minimizing energy consumption and the thermal degradation of ARA. This green, efficient, and sustainable method for degumming heat-sensitive oils offers significant potential for the industrial application of high-quality functional oils by preserving PUFA integrity and reducing environmental impact.

Thirty-one species of Micrurus (coral snakes) are distributed in Colombia. However, functional and proteomic analyses of their venoms have only been performed on six of them. Micrurus camilae is endemic to Colombia, and no information exists regarding its venom. The proteome of M. camilae venom, its biochemical and toxic activities, immunorecognition, and neutralization by commercial equine antivenoms and an experimental one prepared in rabbits are here reported. In addition, the phylogenetic position of M. camilae within the genus was explored. The venom was characterized by RP-HPLC, SDS-PAGE, and nESI-MS/MS, and functional analyses were performed using in vitro (proteolytic, coagulant, phospholipase A2, and L-amino acid oxidase activity) and in vivo (myotoxic, edematogenic, hemorrhagic) assays. Immunorecognition and neutralization were evaluated using ELISA and mouse lethality, respectively. To determine phylogenetic relationships, sequences of the mitochondrial ND4 gene from 48 Micrurus species were analyzed. The venom proteome revealed a PLA2-rich phenotype and identified 17 protein families, the four most abundant being PLA2, LAO, 3FTx, and MP. The myotoxic and hemorrhagic activities observed in mice correlated with the relative abundance of PLA2s and MPs, respectively. Furthermore, the i.p. lethal effect in mice was associated with only one fraction, a 3FTx. Two commercial equine antivenoms (INS-anticoral and ICP-anticoral) immunologically recognized both the whole venom and the chromatographic fractions by ELISA. However, they did not neutralize venom lethality in mice in a preincubation assay. On the other hand, the experimental rabbit antivenom was shown to recognize the whole venom and its fractions and, although it did not completely neutralize lethality, it prolonged mouse survival by several hours compared to the venom-only control. Our phylogenetic hypothesis showed M. camilae within the mipartitus group as a sister species of M. mipartitus.

We aimed to investigate the relationship of peripheral blood platelet-to-lymphocyte ratio (PLR), lipoprotein-associated phospholipase A2 (Lp-PLA2), monocyte-to-high-density lipoprotein ratio (MHR), systemic immune-inflammation index (SII), and Homocysteine (HCY) with risk of rupture for small to medium-sized intracranial aneurysms, and examine their combined value as potential predictive markers. We conducted a retrospective analysis of clinical data from 80 patients with intracranial aneurysms who underwent endovascular embolization from January 2022 to January 2025. Patients were divided into a ruptured group (n = 27) and an unruptured group (n = 53). Associations between biomarkers and rupture status were evaluated using univariate and multivariate logistic regression. A predictive nomogram was constructed and assessed using calibration, receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA), and bootstrap internal validation. Levels of PLR, Lp-PLA2, MHR, SII, and HCY were significantly higher in ruptured cases, while SOD and IL-10 were significantly lower (p < 0.05). In multivariable logistic regression, all five biomarkers were associated with rupture. The combined biomarker model showed high apparent discrimination (AUC = 0.969) and was internally validated using bootstrap resampling; however, given the small, single-center sample and the lack of adjustment for key clinical and morphological predictors, the model requires cautious interpretation and independent validation. PLR, Lp-PLA2, MHR, SII, and HCY were associated with rupture status in small to medium-sized intracranial aneurysms. A combined multi-biomarker nomogram showed strong apparent discrimination; however, the incremental value beyond established clinical and morphological predictors and the generalizability of this model need confirmation in larger, preferably multicenter cohorts.

Insect venoms can cause severe allergic reactions, including anaphylaxis, in sensitized individuals. In this study, we aim at preventing anaphylaxis mediated by the most abundant and dominant honeybee venom allergen phospholipase A2 (Api m 1) by blocking its interaction with allergic patient IgE. Therefore, we characterize selected Api m 1-specific nanobodies and identify two high-affinity binders with non-overlapping epitopes. Crystal structures of Api m 1/nanobody complexes reveal diametrically opposed epitopes, one of which involves the active site of Api m 1. Based on this background, we develop mono- and bispecific nanobody-human IgG1 Fc, which exhibits pronounced blocking of IgE binding and effector cell activation in blood samples from honeybee venom allergic patients and reduces systemic reactions in a mouse model of allergen-induced anaphylaxis. This work provides a rationale for using nanobody-based inhibitors to prevent Api m 1-mediated anaphylaxis in honeybee venom allergy.

Acute destructive cholecystitis (ADC) remains a serious problem in abdominal surgery with high rates of complications and mortality. The traditional view of its pathogenesis as a consequence of obstruction and infection is insufficient. Modern data point to the key role of systemic disorders, particularly oxidative stress and endogenous intoxication, but their temporal dynamics and interrelationship in ADC are poorly understood. A comprehensive study of the temporal dynamics of oxidative stress (OS) and endogenous intoxication (EI) parameters in an experimental model of destructive cholecystitis. The experiment was conducted on 60 male rabbits with an ADC model created by ligation of the cystic duct and injection of a bacterial suspension. The animals were divided into 5 groups according to the sampling time point (baseline, 2, 5, 7, 10 days). Markers of lipid peroxidation (LPO) – diene conjugates (DC), ketodienes (KD), malondialdehyde (MDA); activity of the antioxidant system (AOS) – total antioxidant activity (TAA) and catalase; markers of EI – concentration of middle molecular weight peptides (MMWP) and phospholipase A2 activity; as well as the phospholipid composition of erythrocyte membranes were determined in erythrocyte membranes and blood plasma. A progressive activation of LPO was revealed: by day 7, the levels of DC, KD and MDA significantly increased by 2.9, 5.4 and 3.7 times, respectively, compared to the baseline (p&lt;0.001). By day 5, depletion of the AOS was recorded – a decrease in plasma TAA and catalase activity (p&lt;0.05), reaching a maximum by day 7 (a 3-fold decrease, p&lt;0.001). EI increased in parallel: the concentration of MMWP doubled by day 7 (p&lt;0.001), and phospholipase A2 activity increased 5-fold (p&lt;0.001). Strong positive correlations were established between LPO markers, MMWP and phospholipase A2 activity (r=0.63-0.78). The development of experimental destructive cholecystitis is characterized by a staged formation of a vicious cycle initiated by oxidative stress, which leads to depletion of the antioxidant system, activation of phospholipase A2, profound disruption of cell membrane structure, and an increase in endogenous intoxication.

Background: Non-invasive identification of coronary stenosis in stable coronary artery disease (CAD) patients lacking regional wall motion abnormalities (RWMA) remains challenging. This study aimed to develop and validate a myocardial work-derived nomogram for predicting significant coronary stenosis in these patients. Methods: In this retrospective study, 181 consecutive patients with angiographically confirmed CAD, preserved LVEF (≥55%), and no resting wall motion abnormalities were enrolled. Global myocardial work efficiency (GWE) was assessed using echocardiographic pressure-strain loop analysis. A multivariable-derived nomogram incorporating GWE and clinical biomarkers was developed and externally validated for predicting severe coronary stenosis. Results: The nomogram incorporating GWE, lipoprotein-associated phospholipase A2 (LP-PLA2), N-terminal pro brain natriuretic peptide (NT-proBNP), and serum creatinine (Scr) demonstrated favorable discrimination in both the training set (AUC 0.916, 95% CI 0.866-0.952) and validation set (AUC 0.911, 95% CI 0.853-0.951), with good calibration (mean absolute error: 1.9% vs 3.2% in training vs validation, respectively). Decision curve analysis confirmed clinical utility across all probability thresholds. Conclusions: Our nomogram provides a non-invasive tool for preoperative risk stratification and optimizes the use of invasive diagnostics in stable CAD patients without RWMA.

This systematic review aimed to assess whether lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with increased risk of complications in patients with diabetes mellitus (DM). We searched PubMed, Embase, Web of Science, and Scopus databases for studies fulfilling the inclusion criteria till 30 June 2025. The relationship between Lp-PLA2 and cardiovascular disorders (CVD), diabetic kidney disease (DKD), diabetic retinopathy (DR), diabetic neuropathy (DN), and lower extremity arterial disease (LEAD) was assessed using a qualitative and quantitative analysis. Twelve studies were included. The majority of studies were on DKD. Pooled analysis showed that high Lp-PLA2 was associated with significantly higher risk of DKD (OR: 1.01 95% CI: 1.01, 1.02 I2 = 93%) but not for CVD (OR: 1.11 95% CI: 0.97, 1.26 I2 = 88%), DN (OR: 2.02 95% CI: 0.40, 10.23 I2 = 88%) or DR (OR: 1.28 95% CI: 0.49, 3.34 I2 = 96%). Sensitivity analysis revealed non-significant results for DKD and CVD. Subgroup analysis for DKD showed that heterogeneity reduced to zero in cross-sectional studies, among those with <30% prevalence of DKD, and among those reporting adjusted data, but results also became non-significant across multiple subgroups. Limited evidence indicates that high Lp-PLA2 may be predictive of DKD in DM patients. However, the strength of the association is too low and the finding may not be relevant for clinical application. Lp-PLA2 was not found to predict CVD, DN, or DR, but with very scarce data. The high heterogeneity and non-significant results on sensitivity analysis limits the strength of the evidence. More robust studies are required to supplement the present evidence. https://www.crd.york.ac.uk/prospero/, PROSPERO CRD420251069254.

Identifying genomic regions linked to yield and quality is crucial for sorghum (Sorghum bicolor L.) improvement, but limited studies on its genome and diversity hinder breeding efforts. This study aimed to identify phenotypic variance and common quantitative trait nucleotides (QTNs) associated with genomic regions linked with grain yield and quality traits. The experiment was conducted during the 2020 and 2021 growing seasons across three Ethiopian agroecological zones-wet intermediate (Jimma), dry lowland irrigated (Melkassa), and natural drought-prone lowland (Miesso)-using a diverse panel of 358 Ethiopian sorghum landraces. Grain yield reflected both genetic and environmental effects, while the other traits were mainly under genetic control. A multi-locus genome-wide association study (ML-GWAS) was conducted using 209,572 high-quality single-nucleotide polymorphism markers. A total of 27 stable QTNs were identified across six environments using multiple ML-GWAS models. Five QTNs were associated with grain yield, nine with protein content, seven with 1000-seed weight, and six with amylopectin. Two QTNs, S01_65245223 and S09_50940522, were notable in grain yield, with candidate genes encoding a universal stress protein (Sobic.001G363100) and an E3 ubiquitin ligase (Sobic.009G153100), involved in stress response and protein turnover. For protein content, S01_1332500 and S05_53371984 localized with genes encoding EMC2 (Sobic.001G014800) and HVA22-like storage proteins (Sobic.005G121200 and Sobic.005G121300), key for protein folding and accumulation. Note that 1000-seed weight, QTNs S03_3571908 and S01_73998261 were linked to a phospholipase A1 (Sobic.003G038000) and a peptidyl-prolyl isomerase/E3 ligase (Sobic.001G466700), supporting seed filling and growth regulation. For amylopectin, S04_62662803 and S08_53120256 corresponded to GBSSI/SSIIa (Sobic.004G284400) and APS reductase (Sobic.008G118900), central to starch biosynthesis and redox regulation. Multi-locus GWAS revealed stable QTNs for yield and grain quality in sorghum, validating known and novel loci as targets for breeding resilient, biofortified cultivars.

Glaucoma is a neurodegenerative disease that affects the optic nerve and retinal ganglion cells. The two most common forms, primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEG), are associated with ocular hypertension caused by impaired aqueous humor (AH) outflow but have specific ocular and systemic features that may determine their diagnosis and treatment. To identify these features, we compared AH composition in patients using a multiomics approach. Total reflection X-ray fluorescence analysis revealed an increase in zinc and calcium concentrations more pronounced in PEG. Nuclear magnetic resonance study identified common metabolomic changes involving amino acids (Ala, Glu, His, Lys, Tre) and tricarboxylic acid cycle components (citrate and succinate). Targeted liquid chromatography-tandem mass spectrometry data demonstrated shared elevation of oxidative stress-related oxylipins (9/13-HODE, 9-HOTrE) and POAG-specific changes in phospholipase A2 products (DHA, lyso-PAF) and inflammatory prostaglandins (PGE2 and 15d-PGJ2). POAG featured secretion of proteins controlling intraocular pressure (angiotensinogen) and trabecular meshwork outflow (myocilin and cystatin C) and altered levels of neurotrophic factors (PEDF, VGF). Our data highlight novel AH biomarkers distinguishing POAG from PEG (15d-PGJ2, VGF) and demonstrate that they have specific triggers and responses to ocular hypertension but share common mechanisms, such as oxidative stress, mitochondrial dysfunction, and zinc and calcium toxicity.

Therapeutic potentials of Cerastes cerastes venom: A comprehensive review of bioactive molecules and biomedical applications.