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1.
Sci Rep ; 14(1): 22962, 2024 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-39362926

RESUMO

Snake venom C-type lectin-like proteins (CLPs) belong to the nonenzymatic proteins. To date, no CLP with both platelet and coagulation factors activating activities has been reported. In this study, a novel CLP, termed protocetin, with molecular weight of 29.986 kDa, was purified from the Protobothrops mucrosquamatus venom (PMV). It consists of α- and ß-chains, with 67% similarity in their N-terminal sequence. Protocetin activates glycoprotein Ib (GPIb) by binding to von Willebrand factor (vWF), inducing platelet aggregation. It also activates the intrinsic coagulation pathway by binding to coagulation factor IX. After injection of protocetin into mice at dose of 0.5 µg/g or 1.5 µg/g, it resulted in activation of platelets, a notable reduction in platelet count and prolonged tail bleeding time. Additionally, the plasma activated partial thromboplastin time (APTT) was significantly extended, and the fibrinogen concentration was markedly reduced. Thrombelastogram comfirmed the anticoagulation effect of protocetin. Notably, no microthrombosis was observed in tissues of lung, liver and kidney within 1 h after injection of protocetin into the mice at dose of 0.5 µg/g. This study revealed protocetin as a novel CLP from PMV that has dual functions in activating platelet and coagulation factor IX, thereby modulates coagulation in vivo. This work contributes to a better understanding of the structure and function of snake venom CLP.


Assuntos
Coagulação Sanguínea , Fator IX , Lectinas Tipo C , Agregação Plaquetária , Venenos de Serpentes , Fator de von Willebrand , Animais , Fator de von Willebrand/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Camundongos , Lectinas Tipo C/metabolismo , Fator IX/farmacologia , Fator IX/metabolismo , Venenos de Serpentes/farmacologia , Venenos de Serpentes/química , Agregação Plaquetária/efeitos dos fármacos , Humanos , Masculino
2.
J Proteomics ; : 105337, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39448027

RESUMO

Snake venom composition varies at different levels. To date, comparative venom studies have seldom taken into account the role of habitat type in the occurrence of snake venom variation. Here we investigated the presence of venom variation across different populations of the Iberian asp viper (Vipera aspis zinnikeri) inhabiting two contrasting habitats: natural vs. intensive agricultural. We used shotgun proteomics to describe the protein composition of the venoms of six adults from two distinct localities. Furthermore, to test whether local conditions and habitat can alter venom composition in this taxon, we compared the SDS-PAGE profiles of 40 adult venoms from six populations, three in natural habitats and three in intensive agricultural environments. The venoms were composed of 21 toxin families, of which five (CTL, PLA2, VEGF, svSP, and svMP) comprised 69-82 % of each proteome. The relative abundances of toxin families varied considerably at inter- and intra-population levels. Linear regression performed on non-metric multidimensional scaling values showed a significant effect of locality of origin and habitat type on the differences detected between individual SDS-PAGE venom profiles. Our results suggest the presence of regional variation in V. a. zinnikeri venom, potentially reinforcing the role of local pressures in shaping snake venom composition. SIGNIFICANCE: This work provides the first proteomic characterization of the venom of the Iberian asp viper, Vipera aspis zinnikeri, obtained by means of shotgun proteomics. The statistical analysis of 40 individual SDS-PAGE venom profiles highlights that venom variation in this taxon can be associated with geographical origin and habitat type of the area where each viper was collected. Our results suggest the presence of regional variation in V. a. zinnikeri venom, reinforcing the role that local pressures may play as drivers of snake venom variation.

3.
BMJ Glob Health ; 9(10)2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39442939

RESUMO

INTRODUCTION: Snakebite envenoming (SBE) results in over 500 000 deaths or disabling injuries annually. Varespladib methyl, an oral inhibitor of secretory phospholipase A2, is a nearly ubiquitous component of snake venoms. We conducted a phase II clinical trial to assess efficacy and safety of oral varespladib methyl in patients bitten by venomous snakes. METHODS: This double-blind, randomised, placebo-controlled trial enrolled patients in emergency departments in India and the USA. Patients with SBE were randomly assigned (1:1) to receive varespladib methyl or placebo two times per day for 1 week. All patients received standard of care, including antivenom. The primary outcome was change in the composite Snakebite Severity Score (SSS) measuring the severity of envenoming, from baseline to the average composite SSS at 6 and 9 hours. RESULTS: Among 95 patients randomised August 2021 through November 2022, the most common snakebites were from Russell's vipers (n=29), copperheads (n=18) and rattlesnakes (n=14). The SSS improved from baseline to the average at 6 and 9 hours by 1.1 (95% CI, 0.7 to 1.6) in the varespladib group versus 1.5 (95% CI, 1.0 to 2.0) in the placebo group (difference -0.4, 95% CI, -0.8 to 0.1, p=0.13). While key secondary outcomes were not statistically different by treatment group, benefit was seen in the prespecified subgroup initiating study drug within 5 hours of bite (n=37). For this early treatment group, clinically important differences were observed for illness severity over the first week, patient-reported function on days 3 and 7 and complete recovery. No death or treatment emergent serious adverse event occurred. CONCLUSION: For emergency department treatment of snakebites, the addition of varespladib to antivenom did not find evidence of difference for the primary outcome based on the SSS. A potentially promising signal of benefit was observed in patients initiating treatment within 5 hours of snakebite.


Assuntos
Cetoácidos , Mordeduras de Serpentes , Humanos , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/terapia , Masculino , Feminino , Método Duplo-Cego , Adulto , Cetoácidos/uso terapêutico , Índia , Pessoa de Meia-Idade , Estados Unidos , Benzoatos/uso terapêutico , Benzoatos/efeitos adversos , Administração Oral , Adulto Jovem , Antivenenos/uso terapêutico , Antivenenos/efeitos adversos , Antivenenos/administração & dosagem , Adolescente , Resultado do Tratamento , Animais , Acetatos , Indóis
4.
Toxicon ; 250: 108120, 2024 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-39393539

RESUMO

Snakebite envenomation (SBE) is a neglected tropical disease (NTD) with an approximate 1.8 million cases annually. The tremendous figure is concerning, and the currently available treatment for snakebite envenomation is antivenom. However, the current antivenom has limited cross-neutralisation activity due to the variations in snake venom composition across species and geographical locations. The proteomics of medically important venomous species is essential as they study the venom compositions within and among different species. The advancement of sophisticated proteomic approaches allows intensive investigation of snake venoms. Nevertheless, there is a need to consolidate the venom proteomics profiles and distribution analysis to examine their variability patterns. This review systematically analysed the proteomics and toxicity profiles of medically important venomous species from Asia across different geographical locations. An interactive dashboard - Asiatic Proteomics Interactive Datasets was curated to consolidate the distribution patterns of the venom compositions, serve as a comprehensive directory for large-scale comparative meta-analyses. The population proteomics demonstrate higher diversities in the predominant venom toxins. Besides, inter-regional differences were also observed in Bungarus sp., Naja sp., Calliophis sp., and Ophiophagus hannah venoms. The elapid venoms are predominated with three-finger toxins (3FTXs) and phospholipase A2 (PLA2). Intra-regional variation is only significantly observed in Naja naja venoms. Proteomics diversity is more prominent in viper venoms, with widespread dominance observed in snake venom metalloproteinase (SVMP) and snake venom serine protease (SVSP). Correlations exist between the proteomics profiles and the toxicity (LD50) of the medically important venomous species. Additionally, the predominant toxins, alongside their pathophysiological effects, were highlighted and discussed as well. The insights of interactive toxico-proteomics datasets provide comprehensive frameworks of venom dynamics and contribute to developing antivenoms for snakebite envenomation. This could reduce misdiagnosis of SBE and accelerate the researchers' data mining process.


Assuntos
Proteômica , Mordeduras de Serpentes , Venenos de Serpentes , Animais , Proteômica/métodos , Venenos de Serpentes/química , Antivenenos , Ásia , Serpentes , Serpentes Peçonhentas
5.
Sci Rep ; 14(1): 25175, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39448652

RESUMO

With the growing popularity of autonomous vehicles (AVs), confirming their safety has become a significant concern. Vehicle manufacturers have combined the Android operating system into AVs to improve consumer comfort. However, the diversity and weaknesses of the Android operating system pose substantial safety risks to AVs, as these factors can expose them to threats, namely Android malware. The advanced behaviour of multi-data source fusion in autonomous driving models has mitigated recognition accuracy and effectualness for Android malware. To efficiently counter new malware variants, novel techniques distinct from conventional methods must be utilized. Machine learning (ML) techniques cannot detect every new and complex malware variant. The deep learning (DL) model is an efficient tool for detecting various malware variants. This manuscript proposes a Deep Learning-Based Improved Transformer Model on Android Malware Detection (DLBITM-AMD) technique for Internet vehicles (IoVs). The main aim of the presented DLBITM-AMD approach is to detect Android malware effectually and accurately. The DLBITM-AMD method performs a Z-score normalization process to convert the raw data into a standard form. Then, the DLBITM-AMD approach utilizes the binary grey wolf optimization (BGWO) model to select optimum feature subsets. An improved transformer is integrated with the RNN model and softmax to enhance classification for Android malware recognition. Finally, the snake optimizer algorithm (SOA) method is employed to select the optimum parameter for the classification method. An extensive experiment of the DLBITM-AMD method is accomplished on a benchmark dataset. The performance validation of the DLBITM-AMD technique portrayed a superior accuracy value of 99.26% over existing Android malware recognition models.

6.
Toxins (Basel) ; 16(10)2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39453204

RESUMO

Toxicofera reptile venoms are composed of several toxins, including serine proteases. These proteases are glycosylated enzymes that affect the prey's hemostatic system. Their actions extend across the coagulation cascade, the kallikrein-kinin system, and platelet activation. Despite their specificity for different substrates, these enzymes are homologous across all toxicoferans and display high sequence similarity. The aim of this review is to compile decades of knowledge about venom serine proteases, showing the diversity of biochemically and biophysically characterized enzymes, their structural characteristics, advances in understanding their origin and evolution, as well as methods of obtaining enzymes and their biotechnological applications.


Assuntos
Serina Proteases , Animais , Serina Proteases/metabolismo , Répteis , Humanos
7.
J Mech Behav Biomed Mater ; 160: 106786, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39461322

RESUMO

The scales of Xenopeltis hainanensis, a snake that can crawl in fields, valleys, and other places, can serve as inspiration for the design of scale-like bionic materials. We present a systematic morphological, microstructural, chemical, and mechanical analysis, including elastic modulus, hardness, and wear morphology of the scales to understand the friction basis for achieving the reptile requirements. At the surface level, a comb-like arrangement of microstructures on the ventral scales provides more surface area and reduces pressure. The separation of microstructures, along with the bending and delamination of collagen fibrils could contribute to energy dissipation, which helps prevent catastrophic failure at deeper structural levels. At the cross-sectional level, a greater thickness provides more distribution of stresses over a larger volume, reducing local deformation and increasing the resistance to damage. At the material level, the ventral scales show higher modulus (E = 384.65 ± 19.03 MPa, H = 58.67 ± 6.15 MPa) than other regions of snake scales, which is attributed to the increased thickness of the scales and the higher concentration of sulfur (S). The experimental results, combined with Energy-dispersive X-ray spectroscopy and SEM characterization, provide a complete picture of the fiction properties influenced by surface morphology and chemical composition during scratch extension of the Xenopeltis hainanensis scales.

8.
Arch Razi Inst ; 79(2): 411-417, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39463715

RESUMO

Since around 100 years ago, the best treatment for millions of global snakebite victims has been polyclonal antivenoms. However, common antivenoms need continuous improvement to reduce rare, their side effects and get better performance. In the present study, Fab antivenom was produced through papain digestion of anti-cobra venom plasma, multi-step purification, and optimization, including ammonium sulfate precipitation and DEAE-cellulose column chromatography. Then, the existence of the corresponding Fab fragment antibody was seen and confirmed by SDS-PAGE method and double immunodifusion (Ouchterlony) test. In addition, the potency test in NIH laboratory mice revealed that each milliliter of the new Fab antivenom was able to neutralize 624 micrograms and (80LD50) of cobra venom, which is about 15% more efficient than the primary plasma of the same concentration, and 1.57 times more effective than the cobra antivenom found in commercial hexavalent antivenom of Razi Institute. According to the findings, it seems that this new Fab antivenom can be used as a new candidate for treatment of cobra snakebite victims.


Assuntos
Antivenenos , Venenos Elapídicos , Fragmentos Fab das Imunoglobulinas , Naja naja , Animais , Antivenenos/farmacologia , Camundongos , Mordeduras de Serpentes/tratamento farmacológico
9.
Biotechnol J ; 19(10): e202400348, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39380504

RESUMO

Oligoclonal antibodies, which are carefully defined mixtures of monoclonal antibodies, are valuable for the treatment of complex diseases, such as infectionss and cancer. In addition to these areas of medicine, they could be utilized for the treatment of snakebite envenoming, where recombinantly produced monoclonal human antibodies could overcome many of the drawbacks accompanying traditional antivenoms. However, producing multiple individual batches of monoclonal antibodies in an industrial setting is associated with significant costs. Therefore, it is attractive to produce oligoclonal antibodies by mixing multiple antibody-producing cell lines in a single batch to have only one upstream and downstream process. In this study, we selected four antibodies that target different toxins found in the venoms of various elapid snake species, such as mambas and cobras, and generated stable antibody-producing cell lines. Upon co-cultivation, we found the cell line ratios to be stable over 7 days. The purified oligoclonal antibody cocktail contained the anticipated antibody concentrations and bound to the target toxins as expected. These results thus provide a proof of concept for the strategy of mixing multiple cell lines in a single batch to manufacture tailored antivenoms recombinantly, which could be utilized for the treatment of snakebite envenoming and in other fields where oligoclonal antibody mixtures could find utility.


Assuntos
Anticorpos Monoclonais , Antivenenos , Proteínas Recombinantes , Antivenenos/imunologia , Animais , Humanos , Anticorpos Monoclonais/imunologia , Proteínas Recombinantes/genética , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/terapia , Cricetulus , Células CHO , Venenos Elapídicos/química , Venenos Elapídicos/imunologia , Elapidae
10.
Toxicon X ; 24: 100210, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39398349

RESUMO

Snakebites profoundly impact the rural population of tropical nations, leading to significant socio-economic repercussions. Polyvalent antivenom (PAV) therapy faces several limitations, including intra-specific variations and poor efficacy against some major toxins and low molecular mass, poorly immunogenic toxins, which contribute to increased mortality and morbidity rates. Innovative strategies for developing novel antivenoms are continuously explored to address these challenges. The present study focuses on designing of 17 epitope-string toxin-specific peptide immunogens from pharmacologically active major and/or poorly immunogenic toxins (snake venom metalloprotease, Kunitz-type serine protease inhibitor, phospholipase A2, three-finger toxin) from the venom of the 'Big Four' venomous snakes and Naja kaouthia (NK) in India. These custom peptide antibodies demonstrated robust immuno-reactivity against the venoms 'Big Four' and NK. When these antibodies were supplemented with commercial PAV at a defined ratio (formulated polyvalent antivenom or FPAV), it significantly enhanced the neutralization of snake venom enzymes and in vivo neutralization of lethality and pharmacological activities such as haemorrhage, necrosis, pro-coagulant, defibrinogenation, and myotoxicity of 'Big Four' and NK venoms compared to PAV in mice. The present study highlights a promising strategy for developing next-generation antivenoms using synthetic peptide-based immunogens, offering a targeted approach to address the limitations of current antivenom therapy.

11.
Acta Trop ; 260: 107426, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39393479

RESUMO

The effect of Bothrops atrox venom (BaV) on the maturation of bone marrow-derived dendritic cells (BMDCs) from mice was investigated, with a focus on selected cell markers, TAP1 expression, and the release of pro-inflammatory cytokines during this process. The objective was to evaluate BaV's impact on dendritic cell (DC) function, as DCs are pivotal in antigen presentation and responsible for initiating the immune response mediated by naïve T cells, as well as regulating the immune system. Bone marrow cells were obtained from Swiss mice, and hematopoietic precursors were differentiated into BMDCs using GM-CSF and IL-4. On the 7th day, BaV and LPS were introduced into the culture, and the cells were analyzed 24 h later. BaV's ability to stimulate BMDC maturation was assessed through the analysis of surface marker expression. The findings demonstrated that BMDCs are highly influenced by culture environment factors, such as GM-CSF and IL-4, and are sensitive to additional stimuli like LPS and BaV. Mature DCs exhibited elevated levels of critical markers for T cell activation, such as MHC-II, CD80, and CD86, displaying specific phenotypic characteristics. However, the observed reduction in MHC-II and CD86 expression following BaV exposure suggests a substantial impact on the immunological activation capacity of these cells, potentially interfering with the adaptive immune response. Furthermore, the selective release of cytokines, such as IL-6, but not TNF-α or IL-1ß, indicates differentiated modulation of inflammatory responses by DCs under various stimulation conditions.

12.
Heliyon ; 10(19): e38486, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39397979

RESUMO

Background: Long-snake moxibustion can improve hypothalamic-pituitary-adrenal (HPA) axis function in patients with kidney-yang deficiency (KYDS). 11ß-HSD1 controls the HPA axis by boosting CORT production via reductase activity. However, the interaction and mechanism of long snake moxibustion and 11ß-HSD1 remain unknown. This study examined the impact of lengthy snake moxibustion on the hypothalamus-pituitary-adrenal axis in KYDS rats. The potential significance of 11ß-HSD1 in this process was explored. Methods: Rats were randomly divided into two groups: the blank group and the experimental group. The KYDS model was established with an intramuscular injection of hydrocortisone. Rats were randomly assigned to four groups: model, sham intervention, long snake moxibustion, and long snake moxibustion plus 11ß-HSD1 inhibitor. Physical indicators included body weight, toe temperature, rectal temperature, and spontaneous movement. The serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and CORT were measured. Immunohistochemical examination reveals 11ß-HSD1 protein expression in the liver. Western blotting (WB) detected the levels of 11ß-HSD1, H6PDH and NADPH/NADP + protein in the liver. Results: The experimental rats' body weight, toe temperature, rectal temperature, time and frequency of spontaneous activity all dropped, as did their serum ACTH, CORT, and CRH levels. The protein expressions of 11ß-HSD1, H6PDH, and NADPH/NADP+ in the liver decreased significantly. Long-snake moxibustion improved HPA axis function in rats, boosting expression of 11ß-HSD1, H6PDH, and NADPH/NADP+. Adding an 11ß-HSD1 inhibitor to Long-snake moxibustion decreased its effect on the HPA axis. Conclusion: Long-snake moxibustion improves KYDS symptoms in rats by increasing 11ß-HSD1 expression and reductase activity, which regulates the HPA axis.

13.
Artigo em Russo | MEDLINE | ID: mdl-39435791

RESUMO

Motor neuron disease with isolated or predominant lesion of the lower motor neuron at one level of the pyramidal tract is a rare diagnostic finding. In the article, we analyze the case of a patient with asymmetric lesion of the inferior motor neuron at the cervical level: clinical manifestations, results of additional studies and dynamic observation of the patient. Special attention is paid to the MRI picture of changes in the pyramidal tracts in the cervical region, which have been called the «snake eyes¼ in the literature, and the impact of this finding on the diagnosis and prognosis of the disease.


Assuntos
Imageamento por Ressonância Magnética , Doença dos Neurônios Motores , Tratos Piramidais , Humanos , Doença dos Neurônios Motores/diagnóstico por imagem , Doença dos Neurônios Motores/diagnóstico , Tratos Piramidais/diagnóstico por imagem , Neurônios Motores/patologia , Masculino , Pessoa de Meia-Idade , Feminino
14.
R Soc Open Sci ; 11(10): 240512, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39359468

RESUMO

As urbanization expands globally, human-wildlife interactions will inevitably increase. Here, we analysed 10 years of wildlife rehabilitation records of squamate (snake and lizard) reptiles (n = 37 075) from the Greater Sydney region, New South Wales, Australia, to explore their value to address management and conservation issues. Rescues were highly non-random regarding taxonomic focus, spatial occurrences and temporal trends due to the combined influence of (i) reptile phenology and behaviour and (ii) human perceptions of reptiles. Seasonal peaks in rescues reflect reptile and, to a lesser extent, human activity. Spatial patterns of rescues were informative about distributions and presence of easily identified taxa but were primarily driven by human presence. Larger squamate species were rescued more frequently, potentially reflecting a perception of greater danger or rescue priority. While uncommon species were often misidentified, accurate reports of these taxa may guide targeted surveys. The value of these data for conservation and management could be enhanced by emphasizing reptile identification training of volunteers and use of applications for informed species identification. Wildlife rehabilitation data offer a cost-effective means of quantifying thousands of human-reptile interactions, identifying foci (in both time and space) of human-wildlife conflict such as snakebite risk and roadkill-related reptile mortality.

15.
J Am Coll Emerg Physicians Open ; 5(5): e13296, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39371963

RESUMO

Objectives: North American coral snake envenomations can result in life-threatening neurotoxicity. Their bites are relatively rare, making large studies difficult. Using the National Poison Data System (NPDS), we sought to investigate the epidemiological trends and clinical outcomes associated with North American coral snake bites over a 17-year period. Methods: NPDS cases involving coral snakes from January 1, 2006, to December 31, 2022, were analyzed. Data collected included patient age, date, geographic location, clinical effects, treatments administered, and medical outcomes including incidence of "dry bites" (non-envenomation) and death. Results: During the 17-year period, a total of 1374 cases were reported and analyzed. Cases included adults (≥ 20 years), accounting for 80% (n = 1107), and pediatric patients (≤19 years), accounting for 20% (n = 267) of total cases. Out of 50 US states and District of Columbia, 20 states reported cases. Florida and Texas accounted for 90.5% of all bites (n = 1243) with April being the month with the most reported cases (n = 184). The most bites (n = 96) were reported in 2008 and the fewest (n = 69) in 2016. Male patients predominated for both pediatric (75.7%, n = 202) and adult cases (75.3%, n = 834). Moderate to major clinical outcomes were documented in approximately 30% of total cases; with no reported deaths. Moderate effect is defined as the patient exhibited symptoms as a result of the exposure that were more pronounced, more prolonged, or more of a systemic nature than minor symptoms. Major effect was defined as the patient exhibited symptoms as a result of the exposure that were life threatening or resulted in significant residual disability or disfigurement. The three most reported clinical effects were wound/sting, dermal irritation/pain, and edema. Antivenom was administered in 21% (n = 286) of total cases and 37% (n = 511) of patients were admitted to a critical care unit. Dry bites occurred in 7% (n = 100) of total cases. Conclusion: Coral snake bites were rare, but consistently reported. While bites were associated with significant morbidity in adult and pediatric patients, there were no deaths reported. Antivenom use declined over the study period but was not associated with an increase in morbidity. An increased incidence of intubations was seen in association with decreased antivenom use.

16.
J Pharm Biomed Anal ; 252: 116512, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39405783

RESUMO

Snake melon (Cucumis melo var. flexuosus, CM) is a gourd with health-promoting nutritional traits and unexplored phytochemicals. This study aims to comprehensively investigate the phytoconstituents in the fruits, leaves, roots, seeds, and stems of CM, using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Consequently, 118 metabolites were identified, encompassing phenolic compounds, flavonoids, megastigmanes, lignans, cucurbitacins, and fatty acids. Multivariate data analysis revealed differences in the metabolite composition of CM organs and correlated these variations with the potential in-vitro anti-inflammatory properties assessed against RAW 264.7 macrophages through the down-regulation of cyclo-oxygenase-Ⅱ, nuclear factor-kappa B, and tumor necrosis factor-α. The results indicated that leaf and seed extracts showed the highest anti-inflammatory activity due to their enrichment in several flavonoids, phenolic glycosides, and a megastigmane. These findings emphasize the health benefits of CM organs as potential functional foods and functional food by-products, serving as a natural source for developing new anti-inflammatory agents.

17.
J Biol Chem ; : 107910, 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39433128

RESUMO

Proteins belonging to the CAP superfamily are present in all kingdoms of life and have been implicated in various processes, including sperm maturation and cancer progression. They are mostly secreted glycoproteins and share a unique conserved CAP domain. The precise mode of action of these proteins, however, has remained elusive. Saccharomyces cerevisiae expresses three members of this protein family, which bind sterols in vitro and promote sterol secretion from cells. This sterol-binding and export function of yeast Pry proteins is conserved in the mammalian CRISP proteins and other CAP superfamily members. CRISP3 is an abundant protein of the human seminal plasma and interacts with alpha-1-B glycoprotein (A1BG), a human plasma glycoprotein that is upregulated in different types of cancers. Here we examined whether the interaction between CRISP proteins and A1BG affects the sterol-binding function of CAP family members. Co-expression of A1BG with CAP proteins abolished their sterol export function in yeast and their interaction inhibits sterol-binding in vitro. We map the interaction between A1BG and CRISP2 to the third of five repeated immunoglobulin-like (Ig) domains within A1BG. Interestingly, the interaction between A1BG and CRISP2 requires magnesium, suggesting that coordination of Mg2+ by the highly conserved tetrad residues within the CAP domain is essential for a stable interaction between the two proteins. The observation that A1BG modulates the sterol-binding function of CRISP2, has potential implications for the role of A1BG and related Ig domain containing proteins in cancer progression and the toxicity of reptile venoms containing CRISP proteins.

18.
Clin Toxicol (Phila) ; : 1-8, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316835

RESUMO

INTRODUCTION: Envenomation after a North American rattlesnake (Crotalus spp. and Sistrusus spp.) bite is associated with substantial morbidity. Arizona reports the highest number of rattlesnake envenomations annually in the United States. We evaluated the performance of poison and drug information centers for snakebite surveillance, compared with the hospital and emergency department discharge database. We used both datasets to improve the characterization of epidemiology, healthcare costs, and clinical effects of snakebite envenomations in Arizona. METHODS: We identified patients with a snakebite during 2017-2021 using Arizona hospital and emergency department discharge data and snakebite consults with two regional Arizona poison centers. Patients were matched using name and birthdate. The performance of poison center data for snakebite surveillance was evaluated using the percentage of snakebite patients in hospital and emergency department discharge data that consulted with poison centers. Patient demographics, healthcare characteristics, clinical effects, and context of snakebite events were described using both datasets. RESULTS: In total, 1,288 patients with a snakebite were identified using the Arizona hospital and emergency department discharge data, which resulted in 953 (74%) consultations with poison centers. The median age of patients was 48 years (IQR 28-62 years), and they were predominantly male (66%), White (90%), and non-Hispanic (84%). The median billed charges were US$ 84,880 (IQR US$ 13,286-US$ 168,043); the median duration of a healthcare stay was 34 h (IQR 13-48 h), and 29% of patients were transferred between healthcare facilities. Among 953 consulted poison center calls for a snakebite, a median of 14 vials of antivenom was administered per patient; 375 (60%) bites occurred near the home, and 345 (43%) patients were bitten on a lower extremity. One death was identified. DISCUSSION: Snakebites in Arizona can cause severe morbidity and require extensive healthcare resources for treatment. Poison centers are valuable for monitoring venomous snakebites in Arizona. CONCLUSIONS: Using hospital and emergency department discharge data with poison center records can improve public health surveillance data regarding snakebite epidemiology and human-snake interaction information and be used to tailor interventions to increase awareness of snake encounters and prevent snakebites.

19.
Cureus ; 16(8): e66934, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39280490

RESUMO

Introduction Accidental and intentional poisoning is a major cause of morbidity and mortality. Pesticide poisoning is particularly common in India, where a large percentage of the population works in agriculture. This study aims to evaluate admission profiles, management trends, and outcome status among poisoning cases in a tertiary care hospital. Methodology A prospective observational study was carried out from May to July 2022 in the medicine ward of a tertiary care hospital, which is associated with a government medical college. Demographic characteristics, history of poisoning, clinical presentation at the time of admission, and intervention for treatment were recorded once the patient was diagnosed with poisoning or when there was a suspicion. Data regarding outcomes was also collected from this section. The appropriateness of the decontamination, support, and specific treatments was assessed. The collected data was subjected to descriptive statistical analysis. Results The most common agent was pesticides, involved in 44 (43.56%) cases out of a total of 101 poisoning cases, with the predominant subtype being organophosphate. Bites accounted for 18 (17.82%) cases, mainly snake bites. Household products were responsible for eight (7.92%) cases, and medicinal products for four (3.96%) cases. Decontamination, when indicated, was properly applied in 98 (97.02%) cases; supportive treatments were administered in 95 (94.05%) cases; and specific detoxifying measures were taken in 59 (58.41%) cases. A majority of the patients (60, or 59.41%) reached the hospital within three hours of poisoning, which dramatically reduced morbidity and mortality. Conclusion In summary, the study indicates that pesticide poisoning is prevalent in rural India, and, as such, there is an urgent need for appropriate regulation of agrochemicals and behavioural education to protect farmers. On average, the appropriateness of decontamination and supportive treatments was high (i.e., >85%), reflecting adequate initial responses. In contrast, the low level of appropriateness for specific treatments highlights gaps regarding institutional medical protocols and training. There is a need to educate the public about timely medical intervention, which can help in decreasing the mortality and morbidity associated with cases of poisoning.

20.
Artigo em Inglês | MEDLINE | ID: mdl-39285908

RESUMO

Glioblastoma (GB) is the most common type of malignant tumor of the central nervous system, responsible for significant morbidity and with a 5-year overall relative survival of only 6.8%. Without advances in treatment in the last twenty years, the standard of care continues to be maximum safe resection, Temozolomide (TMZ), and radiotherapy. Many new trials are ongoing, and despite showing increased progression-free survival, these trials did not improve overall survival. They did not consider the adverse effects of these therapies. Therefore, an increasing number of bioprospecting studies have used snake venom molecules to search for new strategies to attack GB selectively without producing side effects. The present review aims to describe GB characteristics and current and new approaches for treatment considering their side effects. Besides, we focused on the antitumoral activity of snake venom proteins from the Viperidae family against GB, exploring the potential for drug design based on in vitro and in vivo studies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. In January 2024, a systematic search was performed in the PubMed, EMBASE, and Web of Science databases from January 2000 to December 2023. Search terms were selected based on the population/exposure/outcome (PEO) framework and combined using Boolean operators ("AND", "OR"). The search strategy used these terms: glioblastoma, glioma, high-grade glioma, WHO IV glioma, brain cancer, snake venom, Viperidae, and bioprospection. We identified 10 in vivo and in vitro studies with whole and isolated proteins from Viperidae venom that could have antitumor activity against glioblastoma. Studies in bioprospecting exploring the advantage of snake venom proteins against GB deserve to be investigated due to their high specificity, small size, inherent bioactivity, and few side effects to cross the blood-brain barrier (BBB) to reach the tumor microenvironment.

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