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Introduction: Snakebite envenomation is a significant global health issue, with India bearing a substantial burden. Despite the development of guidelines, knowledge gaps and lack of training persist among healthcare workers (HCWs), contributing to high morbidity and mortality. This study aimed to evaluate the impact of the Snake Bite Life Support (SBLS) workshop on HCWs' knowledge, practices, self-efficacy, and advocacy skills in snakebite management.

Methods: A pre-post interventional study was conducted during the SBLS workshop at a tertiary care center in May 2024. HCWs' knowledge, practical skills, self-efficacy, and advocacy skills were assessed using standardized questionnaires and a modified General Self-Efficacy (GSE) scale, both before and after the workshop. Data were analyzed using SPSS v25.0, employing paired t-tests and Wilcoxon signed-rank tests for comparison.

Results: Forty-one HCWs completed the pre- and post-workshop assessments. Significant improvements were observed in knowledge, particularly in avoiding false positive 20-min whole blood clotting test (20WBCT) results (p = 0.020) and premedication for antivenom (p < 0.001). Participants reported a marked increase in self-efficacy across all GSE parameters and demonstrated enhanced advocacy intent in resource management, policy influence, and educational outreach. The workshop influenced practice changes, notably reducing the administration of antivenom in confirmed hump-nosed pit viper bites.

Conclusion: The SBLS workshop effectively enhanced HCWs' knowledge, management practices, self-efficacy, and advocacy intentions, emphasizing the need for integrating such training into healthcare education to drive systemic change in snakebite management and improve patient outcomes. Future studies should focus on long-term impacts and broader implementation.

Deoxynivalenol (DON), a mycotoxin that severely contaminates agri-food products can cause hepatotoxicity. Ferroptosis is an iron-dependent form of cell death, and the liver is an important organ for iron accumulation. 18beta-glycyrrhetinic acid (GA) has anti-ferroptosis and hepatoprotective effects. This study aimed to investigate the role of ferroptosis in the protective effects of GA against DON-induced hepatotoxicity in HepG2 cells and mice. The in vitro results revealed that DON (0.4 μM) decreased GPX4, SLC7A11, GCLC, NQO1, and Nrf2 expression; promoted TFR-1 expression and MDA, 4-HNE, and total ROS production; accelerated GSH depletion; and enhanced lipid ROS accumulation and Fe(II) overload, leading to ferroptosis. Pre-treatment with GA (0.4 and 6 μM) reversed these changes and alleviated DON-induced ferroptosis, thereby increasing cell viability and proliferation. In vivo results also showed that GA (10 mg/kg bw) pre-administration attenuated DON (2 mg/kg bw)-induced mouse liver injury, in part by inhibiting ferroptosis through reducing mitochondrial damage and lipid peroxidation. In addition, GA prevented erastin- and RSL3-induced ferroptosis by promoting GPX4 and SLC7A11 expression. Altogether, GA attenuated DON-induced hepatotoxicity by preventing ferroptosis via activation of GPX4-dependent pathway. The findings of this study provide a theoretical basis for the prevention of food mycotoxin toxicity.

Strychni Semen is the dried ripe seeds of the plant Strychnos nux-vomica L, and has great medicinal value and developmental potential.However, Strychni Semen is severely toxic, with adverse effects on the central nervous system, urinary system, and other organ systems, and severe cases can be life-threatening. The present study was to reveal the mechanism of nephrotoxicity induced by Strychni Semen and its alkaloid components using experiments. HK-2 cells were randomly divided into control, experimental, and inhibitor groups. The experimental group was divided into Strychni Semen (SS, 10 mg/mL), brucine (B, 8 μg/mL) and strychnine (S, 4 μg/mL) groups,and the inhibitor group was treated with 1 μm/L Apostatin-1. To detect the effects of each group of drugs on the expression of inflammatory cytokines, KIM-1 and TRADD downstream pathway-related proteins. Network pharmacology predicted that nephrotoxicity caused by Strychni Semen may be related to MAPK. Cell experiments showed that Strychni Semen and its alkaloids could induce the activation of the JNK and p38 pathways in the NF-κB and MAPK pathways, upregulate the activation and expression of caspase-3, promote the apoptosis of HK-2 cells, and enhance the production of the cytokines IL-6, IL-1β, and TNF-α and KIM-1. Apostatin-1 antagonises the apoptosis of HK-2 cells induced by Strychni Semen and its alkaloids and reduces the production of the above-mentioned cytokines. The results showed that Strychni Semen and its alkaloids can induce apoptosis of HK-2 cells by activating TRADD-mediated MAPK and NF-κB pathways, showing cytotoxicity to HK-2 cells. Thus, inhibiting TRADD can reduce apoptosis.

Fibrinogen is a common target of SVMP and SVSP. These toxins can destructively cleave fibrinogen, leading to the depletion of its levels. Herein we comparatively describe the fibrinogenolytic activity of the venom of Bothrops and Crotalus snakes, viperids of high epidemiological importance in Brazil. Results emphasize species-specific differences in the degradation rate and the specificity of the preferentially degraded fibrinogen chains, reflecting the complexity of the coagulotoxic effects induced by envenomation.

Recent studies have shown that essential oils (EOs) extracted from medicinal and aromatic plants have herbicidal and/or insecticidal properties, helping to mitigate the toxicity experienced by living organisms exposed to pesticides. Moreover, the primary compounds isolated from these EOs also have the potential to reduce pesticide-induced damage. The present work aimed to evaluate the protective effects of Thymus numidicus (TNEO) and Lavandula stoechas (LSEO) against Deltamethrin-induced toxicity in female rabbits. The results obtained by GC/MS analysis showed that monoterpenes and oxygenated monoterpenes were the main components of the EOs extracted from the aerial parts of Thymus numidicus and Lavandula stoechas. The use of the pesticide Deltamethrin caused significant damage to the liver and kidneys (p < 0.05), together with blood disorders, signs of restlessness and tremors. However, females treated with TNEO showed better tolerance than the group treated with LSEO. The combination of both oils showed more pronounced protective effects. This suggests a potential synergistic effect in reducing deltamethrin-induced toxicity.

Snakebite envenoming in pregnant women is rare, accounting for approximately 0.5-1.8% of all snakebite cases. A thirty-year-old six months pregnant woman was admitted to Setthatirath Hospital in Vientiane Capital, Lao People's Democratic Republic two hours after a Malayan pit viper bite at her right lower leg. She developed extensive local swelling affecting the entire right leg and a severe coagulation disorder with clinical signs of bleeding, requiring ten blood transfusions. Due to antivenom shortage only one vial of Hemato Polyvalent snake antivenom produced at Queen Saovabha Memorial Institute (QSMI) in Bangkok, Thailand was given shortly after admission although the recommended initial dose in case of Malayan pit viper envenoming is at least three vials. The patient received ten units of fresh frozen plasma and six platelet transfusion without effect on the unmeasurable prothrombin time or the platelet count of less than 20,000/μl. On day nine, two additional vials of monovalent Malayan pit viper antivenom produced at QSMI were given which eventually normalized the coagulation disorder. There was no vaginal bleeding and repeated ultrasound examinations showed a single live intrauterine pregnancy with a foetal size consistent to a gestational age of 26 weeks. A healthy baby was born three months after the snakebite but the mother retained a permanent nervus peroneus paresis on her right lower leg.

Coagulation disorders are a primary symptom of envenomation caused by snakes belonging to the genus Bothrops. In the Northeast region of Brazil, the species Bothrops erythromelas and Bothrops leucurus are the main responsible for snakebite accidents. Due to the specific action of Bothrops venoms on several components of the coagulation cascade, the objective of this work was to characterize the coagulotoxic profile of B. erythromelas and B. leucurus venoms and the neutralizing potential of bothropic antivenom, considering that their venom are not used in the production of antivenom. Regarding the clotting components targeted by the venom of these species, B. leucurus samples had higher thrombin-like activity and ability to activate prothrombin, while the activation of Factor X was comparable between these two species. B.erythromelas and B. leucurus venom displayed α- and β-fibrinogenolytic activities, with the former presenting higher overall fibrinogenolytic activity. In contrast, B. erythromelas venom showed greater procoagulant activity on human plasma, assessed through the coagulation time induced by the venom samples and thromboelastometry. Bothropic antivenom inhibited the procoagulant potential of B. leucurus venom better than B. erythromelas. However, the ability of the antivenom to neutralize this activity is lower compared to that determined for the venom of B. jararaca, which is used for antivenom production. The results shown herein describe the procoagulant activity of B. leucurus and B. erythromelas venoms and highlight the differences regarding their procoagulant capacity on human plasma, contributing to a deeper understanding of the pathophysiology of the envenomation caused by these species.

Background: Radiotherapy is essential for the management of esophageal squamous cell carcinoma (ESCC). However, ESCC cells are highly susceptible to developing resistance to radiotherapy, leading to poor prognosis. Ursolic acid (UA) is a herbal monomer, has multiple medicinal benefits like anti-tumor. The impact of UA on the sensitivity of ESCC cells to radiotherapy is currently unclear.

Methods: The impact of UA and ionizing radiation (IR) on the viability of TE-1 and KYSE30 cells was assessed by the MTT assay. EdU staining, flow cytometry, clone formation, Wound healing and Transwell assay detected the biological properties of ESCC cells. FerroOrange, DCFH-DA, and kits to detect the influences of UA and/or IR treatment on cellular ferroptosis. The levels of p53/solute carrier family 7a member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway proteins were detected by Western blot. Additionally, a subcutaneous graft tumor model was constructed in nude mice.

Results: 10 μM UA reduced the viability and induced death of ESCC cells. UA enhanced the impacts of IR by suppressing cell proliferation, migration and invasion, inducing cell death, and causing cell cycle arrest. Ferroptosis inhibitor impaired the inhibitory impacts of UA and IR on the biological properties of ESCC cells. The combination of UA and IR led to ferroptosis through the modulation of the p53/SLC7A11/GPX4 pathway, and UA enhanced the responsiveness of ESCC cells to IR both in vitro and in vivo.

Conclusion: UA inhibits the malignant biological behavior of ESCC by modulating ferroptosis through the p53/SLC7A11/GPX4 pathway, and enhances the sensitivity of ESCC cells to IR.

SARS-CoV-2 is from the enveloped virus family responsible for the COVID-19 pandemic. No efficient drugs are currently available to treat infection explicitly caused by this virus. Therefore, searching for effective treatments for severe illness caused by SARS-CoV-2 is crucial. Scorpion venoms are significant sources of peptides with pharmaceutical potential, including antivirals. Although some studies have determined the antiviral effects of some scorpion peptides on other members of the Coronaviridae family, a few anti-SARS-CoV-2 effects of these peptides have been reported until now. This study assessed the antiviral effects of five predicted antimicrobial peptides with potential for antiviral activities from the Iranian yellow scorpion "Odontobuthus doriae" by computational methods. These peptides were selected from the cDNA library that our research team constructed. A 3D model of peptides was designed with I-TASSER. The models were refined using a 200 ns Molecular Dynamics (MD) simulation using Gromacs 2021.2 software. Refined models were Docked with the RBD domain of SARS-CoV-2 spike protein using HADDOCK software. The docking of human ACE2 peptide with the RBD domain was also assessed. The docked complexes (RBD-peptide and RBD-ACE2) were refined again by a 100 ns MD simulation and then analyzed. The results from molecular docking after molecular dynamics simulation showed that ODAMP2 and ODAMP5 after stabilizing analysis and according to MMPBSA results (with -59.24 kcal/mol and -51.82 kcal/mol, respectively) have a strong binding affinity to the RBD domain of COVID-19 spike protein compared to human ACE2 and some other studied components. Therefore, this peptide can be an excellent candidate for use as an agent to inhibit the RBD domain of SARS-COV2 virus in clinical studies for medicinal purposes after in vitro and in vivo laboratory evaluations.

This study investigated the effects of a novel bombesin-related peptide (BR-b), derived from the skin of the Chaco tree frog (Boana raniceps), on glucose homeostasis in non-obese and hypothalamic-obese male rats. Hypothalamic obesity was induced in neonatal rats through high-dose administration of monosodium glutamate (MSG; 4 g/kg), while control animals (CTL) received an equimolar saline solution. At 70 days of age, both MSG and CTL groups underwent an oral glucose tolerance test (OGTT; 2 g/kg) with or without prior intraperitoneal administration of BR-b at doses of 0.5 or 1.0 mg/kg, delivered 5 min before the glucose challenge. At 75 days of age, pancreatic islets were isolated and exposed to glucose in the presence or absence of BR-b (1.0 or 5.0 μM). MSG-treated rats developed obesity, hyperinsulinemia, and insulin resistance. BR-b administration exacerbated glucose intolerance during the OGTT, particularly at the 1.0 mg/kg dose, with more pronounced effects observed in the CTL group. Insulin secretion from pancreatic islets was influenced by both obesity status and glucose concentration. In islets from CTL rats, BR-b (5 μM) reduced insulin release under non-stimulatory glucose conditions but enhanced insulin secretion at stimulatory glucose levels. Conversely, in islets from MSG-obese rats, BR-b exhibited an inhibitory effect on insulin release at basal glucose concentrations, while the insulinotropic response to high glucose was abolished. In summary, BR-b administration shortly before the OGTT impaired glucose tolerance and modulated insulin secretion from pancreatic islets in a glucose-dependent manner in non-obese rats. These effects were attenuated or absent in MSG-obese rats, indicating that hypothalamic obesity alters the metabolic responses to bombesin-related peptides.