Ribosome-inactivating proteins (RIPs) are a class of cytotoxic rRNA N-glycosylase, which widely exist in higher plants in different taxonomy, including many traditional Chinese medicinal materials and vegetables and fruits. In this paper, the traditional Chinese medicinal plants containing RIPs protein were sorted out, and their pharmacological effects and clinical applications were analyzed. Since many RIPs in traditional Chinese medicine plants exhibit antiviral and antitumor activities and show great clinical application potential, people's interest in these proteins is on the rise. This paper summarizes the possible mechanism of RIPs's anti-virus and anti-tumor effects, and discusses its potential problems and risks, laying a foundation for subsequent research on how to exert its anti-virus and anti-tumor effects.

Brassinin and camalexin belong to phytoalexins, plant compounds generated in the response to stress. Both compounds are known to be cytotoxic to several cancer cell lines, mainly by inducing oxidative stress and subsequent apoptosis. In the presented study, cytotoxic effects of brassinin and camalexin, individually and, for the first time, after combined exposure, on the cells of normal (CCD-Co18) and cancer (Caco-2) lines originated from colorectal tissues and their proapoptotic impact on Caco-2 cells were studied. The determined IC50 values indicate a clearly higher sensitivity of cancer cells to the tested substances, as well as a stronger cytotoxic effect of camalexin than brassinin. The synergistic effect of both phytoalexins was also demonstrated. Caspase-dependent and independent mechanisms were involved in the final effects. Both tested phytoalexins caused evident, concentration-dependent symptoms of oxidative stress in cancer cells, leading to apoptosis, but in the highest concentrations, also to necrosis. In case of camalexin, signs of pyroptosis were additionally detected.

Snake bites are a concerning health problem in Egypt and other tropical countries that are effectively managed with anti-snake venom (ASV). ASV has common reactive complications that are usually mild. Rarely, anaphylaxis and severe systemic reactions may occur following ASV. In this case report, we present a rare condition of Kounis syndrome, acute allergic myocardial infarction, in a young man during anaphylaxis following an allergic intradermal test of VACSERA snake antivenom.

Snakebite envenoming (SBE) is common in rural communities living in tropical regions that often have fragile and/or overwhelmed healthcare systems. The complex scenarios around SBE lead to a high number of deaths, disabilities, and long-term consequences in patients. Russell's viper (Daboia russelii) is one of the most medically important snake species in India, which causes devastating pathological conditions characterised by a wide range of clinical manifestations. This broad spectrum of symptoms requires additional therapeutic interventions beyond the classical antivenom administration. Hence, positive outcomes for patients affected by SBE can be achieved with a better understanding of previous experiences describing clinical manifestations and various therapeutic interventions including for rare and underreported conditions. Here, we report an SBE victim who developed partial segmental thrombosis in the corpus cavernosum following Russell's viper envenomation and its diagnostic and treatment approaches. The patients received 180 ml of antivenom to resolve the abnormalities in their haematological parameters. Despite antivenom treatment, they developed severe pain in their genital region, and subsequent ultrasound and magnetic resonance imaging confirmed segmental thrombosis in the corpus cavernosum, which required supportive measures. The treatment using low molecular weight heparin, rivaroxaban and non-steroidal anti-inflammatory drugs resolved segmental thrombosis. In conclusion, this case report exemplifies the development of a rare segmental thrombosis in corpus cavernosum and how the medical, scientific, and general community can benefit from documenting clinical manifestations, medically relevant insights into patient care and the management of underreported complications.

Oral and other cephalic glands have been surveyed by several studies with distinct purposes. Despite the wide diversity and medical relevance of the New World coral snakes, studies focusing on understanding the biological roles of the glands within this group are still scarce. Specifically, the venom glands of some coral snakes were previously investigated but all other cephalic glands remain uncharacterized. In this sense, performing morphological and molecular analysis of these glands may help better understand their biological role. Here, we studied the morphology of the venom, infralabial, rictal, and harderian glands of thirteen species of Micrurus and Micruroides euryxanthus. We also performed a molecular characterization of these glands from selected species of Micrurus using transcriptomic and proteomic approaches. We described substantial morphological variation in the cephalic glands of New World coral snakes and structural evidence for protein-secreting cells in the inferior rictal glands. Our molecular analysis revealed that the venom glands, as expected, are majorly devoted to toxin production, however, the infralabial and inferior rictal glands also expressed some toxin genes at low to medium levels, despite the marked morphological differences. On the other hand, the harderian glands were dominated by the expression of lipocalins, but do not produce toxins. Our integrative analysis, including the prediction of biological processes and pathways, helped decipher some important traits of cephalic glands and better understand their biology.

Cyanobacteria can form harmful blooms in specific environmental conditions due to certain species producing toxic metabolites known as cyanotoxins. These toxins pose significant risks to public health and the environment, making it critical to identify and quantify them in food and water sources to avoid contamination. However, current screening methods only focus on a single class of cyanotoxins, limiting their effectiveness. Thus, fast and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed to analyze eighteen cyanotoxins simultaneously. A simplified extraction procedure using lyophilized samples of cyanobacterial biomass was also used, eliminating the need for traditional solid-phase extraction methods. This method uses multiple reaction monitoring and allows accurate determination and quantification of eighteen cyanotoxins, including anatoxin-a, homoanatoxin-a, cylindrospermopsin, deoxy-cylindrospermopsin, nodularin, guanitoxin, seven microcystins (RR, [D-Asp3] RR, LA, LR, LY, LW, and YR), and five saxitoxins (gonyautoxins - GTX-1&4, GTX-2&3, GTX-5), decarbamoylgonyautoxin (dcGTX-2&3), and N-Sulfocarbamoylgonyautoxin (C1&C2), all in a short acquisition time of 8 min. Therefore, this method provides a simple and efficient approach to identify and quantify harmful compounds produced by cyanobacteria. Hence, this represents the first method to detecting guanitoxin among cyanotoxins. By expanding the range of toxins analyzed, this method can help ensure high-quality food and drinking water and protect recreational users from exposure to cyanotoxins.

Wasp sting injuries pose a significant threat to public health, especially in areas with abundant trees. Mortality rates are alarmingly high, with reports indicating that up to 70% or more of cases result in multiple organ dysfunction syndrome (MODS). It is crucial for emergency and critical care physicians to promptly identify and implement effective measures to reduce the occurrence of MODS in patients who have been stung by wasps. Therefore, finding a reliable predictive indicator is of utmost importance. We conducted a retrospective study, and clinical data of 226 hospitalized patients with wasp sting from July 2013 to April 2023 in the First College of Clinical Medicine Science, China Three Gorges University were collected. The patients were divided into MODS group and non-MODS (NMODS) group, and the general data, clinical symptoms, laboratory indexes, and prognosis were compared between the two groups. The indicators with significant differences in univariate analysis were included in the multivariate Logistic regression analysis to analyze the independent risk factors for MODS. The value of systemic inflammatory response index (SIRI) in predicting the occurrence of MODS in wasp sting was analyzed by using the receiver operating characteristic curve (ROC curve). Of the 214 patients with wasp sting, 109 cases were in the NMODS group, and 105 cases were in the MODS group. The SIRI was 1.6 (0.7, 3.6) and 12.2 (5.2, 23.3) in the NMODS group and MODS group, respectively, with a significant difference between the two groups (P ＜ 0.001). SIRI was an independent risk factor for MODS in patients with wasp sting; the AUC of SIRI in predicting MODS in wasp sting was 0.886 (P ＜ 0.001), and the optimal cutoff value was 6.39, with a sensitivity of 71.43% and a specificity of 94.5%, which had prediction value. Allowing for early identification and enabling doctors to intervene and provide timely treatment. SIRI was defined as follows: SIRI = neutrophil count × monocyte count/lymphocyte count.

Acute kidney injury (AKI) is the main cause of death from Bothrops snakebite. Although many studies have investigated the nephrotoxicity induced by other Bothrops species, no study has assessed the renal alterations induced by intramuscular (i.m.) injection of Bothrops leucurus venom. In this study, we evaluated the nephrotoxicity induced by B. leucurus venom by analyzing renal function and histology. Wistar rats were submitted to i. m. injection of B. leucurus venom or saline and divided into two groups: Control group (C), rats submitted to i. m. injections of saline, and B. leucurus group (Bl), rats submitted to i. m. injections of B. leucurus venom (1 mg/kg). After venom or saline injection, serum and urine were collected to measure creatinine, albumin, sodium, and potassium levels. The glomerular filtration rate (GFR), urinary flow urinary, creatinine/serum creatinine ratio, and albuminuria-urinary creatinine ratio were determined. All rats were euthanized 72 h following the injections, and the kidneys were removed for histology and immunohistochemical studies. B. leucurus experimental envenoming was accompanied by an increase of 236% in serum creatine kinase activity in the Bl group. The weights of the right and left kidneys were, respectively, 26 and 22% higher in rats of the Bl group than in control rats. Regarding renal function, the Bl group showed a decrease of 37% in GFR compared to control group. The rats of the Bl group also presented increased cortical (8.20 ± 1.35) and medullar (6.17 ± 2.00) tubulointerstitial lesion area when compared to control group (0.02 ± 0.00) (1.20 ± 0.73), respectively. The number of macrophages was also higher in the renal cortex (6.66 ± 0.06) and medulla (1.22 ± 0.10) of rats from the Bl group when compared to control rats (1.04 ± 0.55), (0.65 ± 0.10), respectively. Our results indicate that B. leucurus venom promoted significant histological and functional renal alterations following intramuscular inoculation, which simulates the majority of snakebites observed in the clinical practice.

To corroborate the ontogenetic shift in the venom composition of the Mexican Black-tailed Rattlesnake (Crotalus molossus nigrescens) previously reported through the census approach, we evaluated the shift in the protein profile, lethality, and proteolytic and phospholipase activities of four venom samples obtained in 2015, 2018, 2019, and 2021 from one C. m. nigrescens individual (CMN06) collected in Durango, Mexico. We demonstrated that the venom of C. m. nigrescens changed from a myotoxin-rich venom to a phospholipase A2 and snake venom metalloproteinase-rich venom. Additionally, the proteolytic and phospholipase activities increased with age, but the lethality decreased approximately three times.

Methotrexate (MTX) is an antimetabolite used to treat inflammatory diseases, autoimmune disorders and some malignancies. However, it has some life-threatening side effects such as nephrotoxicity which limit its clinical applications. That motivated the attention to seek for a defensive material to improve the outcomes of methotrexate while minimizing both renal and non-renal toxicity. Both honey (H) and olive oil (OO) are bioactive substances widely used as nutraceuticals that exhibited a potent therapeutic and antioxidant properties. This study aimed to assess the possible protective effect of H and OO intake either singly or together against the biochemical and structural Methotrexate-induced nephrotoxicity in rats. The study was conducted on 56 adult albino rats, they were divided into seven groups (n = 8): group 1 received only distelled water (negative control), group 2 received H (1.2 g/kg/day), group 3 received OO (1.25 ml/kg/day), group 4 received a single intraperitoneal injection of MTX (20 mg/kg), group 5 received MTX and H, group 6 received MTX and OO, group 7 received MTX, H and OO together. At the end of the experiment (2 weeks), all rats were sacrificed, and blood samples were assessed for kidney function tests. Kidney tissues were evaluated for several antioxidant parameters including Malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Tissues were also processed for histological and immunohistochemical assessments. Results revealed that both H and OO improved the kidney function markers, histopathological and immunohistological changes due to Methotrexate-induced renal damage. Additionally, both substances also redeemed the oxidative damage of the kidney by decreasing MDA and increasing anti-oxidant enzymatic activities. Such effects were more apparent when the two substances were given together. Ultimately, our results proof that H and OO amiolerate the Methotrexate-induced nephrotoxicity in rats, thus they can be used as an adjuvant supplements for patients requiring methotrexate therapy.

Snake envenomation is well known to cause grievous pathological signs, including haemorrhagic discharge, necrosis, and respiratory distress. However, inflammatory reactions are also common envenoming manifestations that lead to successive damage, such as oedema, ulceration, lymphadenectasis, systemic inflammatory response syndrome (SIRS) and even multiple organ dysfunction syndrome (MODS). Interference with the inflammatory burst is hence important in the clinical treatment of snake envenomation. Here, we summarize the typical snake toxins (or venoms) that cause inflammatory reactions and the underlying signaling pathways. In brief, inflammatory reactions are usually triggered by snake venom phospholipase A2 (svPLA2), snake venom metalloprotease (SVMP), snake venom serine protease (SVSP) and C-type lectin/snaclec (CTL) as well as disintegrin (DIS) via multiple signaling pathways. They are nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), janus kinase/signal transducer and activator of transcription (JAK-STAT) and phosphoinositide 3-Kinase/protein kinase B (PI3K/PKB also called PI3K-AKT) signaling pathways. Activation of these pathways promotes the expression of pro-inflammatory molecules such as cytokines, especially interleukin-1β (IL-1β) which causes further inflammatory cascades and manifestations, such as swelling, fever, pain, and severe complications. Remarkably, almost half of introduced snake toxins (or venoms) have anti-inflammatory effects through blocking these pathways and suppressing the expression of pro-inflammatory molecules. Investigation of affected inflammation-related signaling pathways is meaningful to achieve better clinical treatment.

Rayless goldenrod (Isocoma spp.) and white snakeroot (Ageratina altissima) poison livestock, wildlife and humans. The suggested toxin for both plants is tremetone, a mixture of benzofuran ketones. However, plant tremetone concentrations often do not correlate with poisoning, and they have not been identified in contaminated milk that poisons nursing neonates. This suggests there may be unidentified metabolites or toxins. Previous studies using various cell culture and large animal models have been inconsistent with varying animal response that often require large doses. The objective of this work is to document the toxicity of rayless goldenrod in California white leghorn chicks, a susceptible small animal model, that would require relatively small amounts of plant material or purified toxins. Four groups of 15 chicks were gavaged with finely ground I. pluriflora at rates of 0, 1%, 2% or 3% of their bodyweight per day for 7 days. After 7 exposure days the chicks were euthanized, necropsied and tissues were collected, fixed and examined microscopically. Myocyte damage was evaluated using clinical signs, weight gain, serum biochemical changes, and histologic lesions and scores. The 3% group had focally extensive myocyte degeneration and necrosis most severely affecting leg muscles (semitendinosus, iliotibialis, peroneus longus and gastrocnemius). This was supported by serum biochemical changes and reduced weight gains. These findings indicate young chicks are a sensitive model of toxicity that may be useful to better identify the rayless goldenrod and white snakeroot toxins, including those unidentified toxins of transmammary poisoning.

Scorpion stings envenomation (SSE) is a growing medical concern in Brazil, particularly in the state of Minas Gerais, which has recorded a significant number of incidents. This study aimed to investigate the potential predictors of scorpion sting incidence and evaluate the cost-effectiveness of interventions in Minas Gerais. Generalized Estimating Equations (GEE) models were constructed using socioeconomic and environmental variables as predictors and scorpion sting incidence as the response variable. The analysis revealed that mean annual temperature and major land use type were significant predictors of scorpion sting incidence, while precipitation and socioeconomic variables showed no relationship with incidence. The total number of cases and annual incidence of scorpion stings overlapped with regions experiencing higher forest conversion and agricultural land use, as well as higher temperatures. The estimated Disability-Adjusted Life Years (DALY) for scorpion sting incidents in Minas Gerais was substantial, indicating the need for effective prevention and treatment measures. The cost per DALY averted varied among municipalities, with some requiring minimal investment while others needing significant funding to address the scorpion risk. Mean annual temperature emerged as the main risk factor for scorpion stings, contributing to increased costs associated with antivenom treatment. These findings highlight the importance of considering environmental factors and implementing targeted interventions to mitigate scorpion sting incidents and reduce associated morbidity and mortality.

Phospholipases A2 (PLA2s) are main components of snake venoms. Several snake species possess endogenous PLA2 inhibitors in their circulating blood, which are generally known as sbPLIs (an acronym for snake blood phospholipase A2inhibitors). The sbPLIs are categorized in three classes (alpha, beta or gamma) depending on the existence of distinguishing protein domains in their structure. The Crotalus durrissus terrificus venom has a highly neurotoxic PLA2 - crotoxin (CTX) - in its composition and the self-protection of the snake is mainly ensured by a sbγPLI named CNF (standing for Crotalusneutralizing factor). In an attempt to find smaller molecules able to inhibit the catalytic activity of CTX, in the present study we used linear peptide arrays to identify CNF segments possibly involved in the interaction with the toxin. Five reacting segments were identified as possible interacting regions. The target peptides were synthesized and located in the in silico CNF structure. Although all of them are exposed to the solvent, high concentrations were needed to inhibit the PLA2 activity of the whole venom or CTX. Limitations of the methodology employed and particular characteristics of CTX inhibition by CNF are discussed.

In this work, we examined the neuromuscular blockade caused by venoms from four South-American coralsnakes (Micrurus altirostris - MA, M. corallinus - MC, M. spixii - MS, and M. dumerilii carinicauda - MDC) and the ability of varespladib (VPL), a phospholipase A2 (PLA2) inhibitor, to attenuate this blockade. PLA2 activity was determined using a colorimetric assay and a fixed amount of venom (10 μg). Neurotoxicity was assayed using a single concentration of venom (10 μg/ml) in mouse phrenic nerve-diaphragm (PND) preparations mounted for myographic recordings and then subjected to histological analysis. All venoms showed PLA2 activity, with MS and MA venoms having the highest (15.53 ± 1.9 A425 nm/min) and lowest (0.23 ± 0.14 A425 nm/min) activities, respectively. VPL (292 and 438 μM) inhibited the PLA2 activity of all venoms, although that of MA venom was least affected. All venoms caused neuromuscular blockade, with MS and MDC venoms causing the fastest and slowest 100% blockade [in 40 ± 3 min and 120 ± 6 min (n = 4), respectively]; MA and MC produced complete blockade within 90-100 min. Preincubation of venoms with 292 μM VPL attenuated the blockade to varying degrees: the greatest inhibition was seen with MDC venom and blockade by MS venom was unaffected by this inhibitor. These results indicate that PLA2 has a variable contribution to coralsnake venom-induced neuromuscular blockade in vitro, with the insensitivity of MS venom to VPL suggesting that blockade by this venom is mediated predominantly by post-synaptically-active α-neurotoxins.