Search Results (122)

Dermal drug delivery is a promising alternate route of drug administration, offering localized therapeutic effects, reduced systemic effects, and improved patient compliance. However, the skin’s intricate configuration, especially the stratum corneum (SC), presents formidable barriers, restricting drug permeation. This review summarizes biological, synthetic, and methodological models employed to study dermal absorption and permeability. Ex vivo human skin is a reference point, but limited availability and ethical constraints necessitate reliance on animal models, including porcine, rodent, rabbit, monkey, and even snake skin, each with unique advantages and drawbacks. Synthetic substitutes, e.g., reconstructed human epidermis and Strat-M^® membranes, provide reproducibility and economic practicality, though none fully mimic the barrier functions of human skin. Innovative analytical methods, including diffusion cells, skin-PAMPA, tape stripping, and advanced imaging techniques, enable quantitative, semi-quantitative, and qualitative insights into drug transport. Collectively, these tools support formulation optimization and aid regulatory bioequivalence assessments. However, challenges remain in correlating in vitro, ex vivo, and in vivo outcomes and in replicating the skin’s dynamic physiology. This review highlights current opportunities and limitations, emphasizing the need for more physiologically relevant models to advance safe, effective, and innovative dermal drug delivery systems. Full article

Introduction: Snakebite envenomation is recognized by the World Health Organization (WHO) as a neglected tropical disease. In Colombia, snakebites are frequent due to the diversity of ecosystems and snake species, and children represent a particularly vulnerable population. Objective: This study aimed to characterize the epidemiological and clinical behavior of snakebite envenomation in the pediatric population and to identify factors associated with its severity through the application of a multinomial logistic regression model. Methods: An exploratory analysis was conducted on 170 pediatric patients reported to the Public Health Surveillance System (SIVIGILA) and treated at San Jerónimo Hospital in Montería (HSJ). Sociodemographic and clinical data were collected, and a multinomial logistic regression model was applied to identify risk factors associated with the severity of envenomation. Results: Most cases occurred in children over 12 years of age (51.8%), and males were the most affected. The lower limbs were the most common site of the bite (87.6%). Bothrops was the main genus responsible. Non-medical practices, such as herbal poultices and potions, were reported in 28.2% of cases. Clinically, moderate envenomation was the most frequent (48.2%), with edema (88%) and pain (92%) as the main local manifestations, and nausea (36%) and vomiting (32%) as systemic manifestations. Cellulitis was the most common complication (24%). Student’s t-test showed a significant difference between complications and hospital stays lasting 3 to 7 days. The multinomial logistic regression explained 75% of the severity variability and showed that prior non-medical practices increased the risk of severe cases. Conclusions: Snakebite envenomation in children remains an important public health problem. The statistical model showed that non-medical practices are associated with a higher degree of severity. Full article

Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary component of venoms, are mainly accountable for haemotoxic and myotoxic effects. Although predominantly found in viper venoms, these enzymes are also present in varying levels in elapid snake venoms. Marimastat and prinomastat are matrix metalloprotease inhibitors initially developed as cancer therapies. Recently, extensive research has focused on these inhibitors to neutralise venom metalloproteases. However, their effects on different viper and elapid snake venoms remain unclear. Here, we report the sensitivity of seven elapid venoms (specifically, cobras) and 12 viper venoms to marimastat and prinomastat, utilising selective in vitro experiments and molecular docking analyses performed using representative metalloprotease (VAP2, a viper metalloprotease from the venom of Crotalus atrox and an elapid metalloprotease from the venom of Naja atra) structures. Both compounds inhibited the metalloprotease, fibrinogenolytic, and caseinolytic activities of most viper venoms. While prinomastat displayed prominent inhibitory effects on cobra venoms in these assays, marimastat demonstrated limited inhibitory effects on these venoms. These findings illustrate the role of matrix metalloprotease inhibitors in modulating metalloprotease activities across a range of viper and cobra venoms. Collectively, this study establishes the differential effects of marimastat and prinomastat on various levels of metalloproteases present in viper and elapid venoms. This will enhance understanding of the abundance of metalloproteases in snake venoms and their sensitivity to different matrix metalloprotease inhibitors. Full article

Background: Although antivenom is the standard treatment for snakebite envenoming, its efficacy may be impacted by geographic variation in venom composition, emphasizing the need for region-specific antivenom development. Methods: We report a case of snakebite envenoming, in which the patient was bitten on the hand by a captive Malayan pit viper (Calloselasma rhodostoma) with typical clinical manifestations following. Antivenom (produced in Thailand) was administered at 33 and 39 h post-bite. Venom from the causative individual snake was collected for compositional analysis via SDS-PAGE. Enzymatic activity of the venom was evaluated through the degradation of casein and phospholipid substrates, along with the assessment of enzymatic inhibition by two regionally specific antivenoms produced in Vietnam (AV. Cr. VN.) and Thailand (AV. Cr. TL.). Results: The patient showed good recovery, with complete normalization by day 7. SDS-PAGE profiling of the venom revealed five major enzymes, with SVSP, SVMP and PLA₂ being the most abundant (16.7%, 40.11% and 26.11%, respectively). Antivenom inhibition tests revealed remaining casein percentages of 67.43% (AV. Cr. VN) and 59.35% (AV. Cr. TL). Blood agar assays indicated that phospholipase activity was reduced to 21.01% by AV. Cr. VN. and 23.30% by AV. Cr. TL. Conclusions: Our results show that the Vietnamese antivenom generated greater inhibitory activity against proteinases compared to the Thai product, underscoring the importance of using regionally specific antivenoms that are more effective against the venom profiles of locality-matched snake populations. Full article

Snake melons have been present for a millennia, despite their present limited use, and host a large degree of genetic and phytochemical diversity. The current study evaluated the genomic and biochemical diversity of Snake melon landraces of Cypriot and Greek origin, revealing significant degrees of genetic and mineral/phytochemical variation. Landraces showed a high potential for improving nutritional quality and a possible contribution to stress resilience. Whole-genome analysis highlighted a high degree of SNPs, InDels, SVs, and CNVs, especially in genotypes like Atzouri and ARI001024, indicating that functional variants influence phenotypic/chemical diversity. Biochemical profiling demonstrated great differences in the concentration of pigments, antioxidants, and minerals, with ARI001024 and ARI00894 exhibiting elevated levels of nutrients/phytochemicals. Hierarchical clustering and PCA analyses established relationships among traits, and reinforced the concept that these genotypes may offer valuable genetic resources for breeding programs under climate-resilient production schemes, emphasizing the need for conservation and further genomic characterization. Full article

Background/Objectives: Bioactive peptides derived from animal venoms, toxins, and secretions demonstrate considerable pharmacological potential for use in the management of diabetes mellitus—a highly prevalent metabolic disorder of substantial global health significance. This integrative review systematically evaluated the current evidence regarding the pharmacological mechanisms underlying the antidiabetic properties of these bioactive peptides. Methods: This study was guided by the research question “What are the mechanisms of action of peptides derived from animal venoms in modulating parameters associated with diabetes?” developed using the PECo framework. A comprehensive literature search was executed across Scopus, PubMed, and Web of Science, focusing on studies from the last five years. Out of 190 identified articles, 17 satisfied the inclusion criteria. Results: Twenty-eight distinct peptides were characterized, exhibiting structural diversity with 7–115 amino acid residues and molecular weights of 900–13,000 Da. These compounds were sourced from venomous taxa including sea anemones, marine snails, spiders, centipedes, scorpions, and snakes. Their antidiabetic mechanisms encompassed glucagon-like peptide-1 (GLP-1) receptor agonism, insulin receptor activation, potassium channel inhibition, glucose transporter type 4 (GLUT4) upregulation, and α-amylase inhibition. Sequence analyses revealed substantial homology among peptides with analogous mechanisms—notably Con-Ins and ILP-Ap04, plus SpTx1 and SsTx-4—suggesting that structural determinants underlie their functional characteristics. Toxicological evaluations of nine peptides demonstrated low-toxicity profiles despite originating from toxic venom, crucial for therapeutic development. Conclusions: These peptides exhibited exceptional pharmacological potency with effective doses in nanogram-to-nanomole per kilogram ranges. Collectively, our findings underscore the therapeutic potential of venom-derived peptides as innovative candidates for use in diabetes management. Full article

A gypsum karst sinkhole at Westeregeln (north-central Germany) was filled during the Late Pleistocene, first by fluvial flooding, then by solifluctation, and finally with wind-transported loess. Pleistocene mollusks and bones of snakes, birds, micro- and macromammals, and hyena coprolites were accumulated, often mixed in gravel or sand layers with Middle Paleolithic artifacts, whereas ice wedges reach deep into the sinkhole. The high amount of small flint debris prove on-site tool production by using 99% local Saalian transported brownish-to-dark Upper Cretaceous flint, which could have been collected from the Bode River gravels near-site. Only a single quartzite and one jasper flake prove other local gravel sources or importation. A large bifacial flaked knife of layer 4 dates to the early/middle Weichselian/Wuermian (MIS 5-4), similar to two triangular handaxes in the MTA tradition and an absolutely dated woolly rhinoceros bone (50,310 + 1580/−1320 BP). A cold period of Late Pleistocene glacial mammoth steppe megafauna is represented, but the material is mostly strongly fragmented and smashed by humans. Neanderthal camp use on the gypsum hill is indicated also by small charcoal pieces, burned bone fragments, and fire-dehydrated flint fragments. Crocuta crocuta spelaea (Goldfuss) hyenas are well known from Westeregeln, with an open-air commuting den site, which was marked with feces. Full article

This study compared the yield, percentage solids, electrophoretic profile, gelatinolytic activity, and brine shrimp lethality of Bitis arietans venom prepared using freeze-drying and desiccator drying. Bitis arietans venom was collected from snakes at Bioken snake farm, Kenya, whereafter it was pooled and divided into two parts. Part 1 was desiccator dried venom (DDV) while part 2 was freeze-dried venom (FDV). The yield and percentage solids in DDV and FDV were compared using Welch’s Student’s t-test and the dried venoms were subsequently subjected to sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), 2D electrophoresis, gelatin in-gel zymography, and brine shrimp lethality assays. Mean venom yield and percentage solids did not differ between DDV and FDV (p = 0.5647 and p = 0.4676, respectively). SDS-PAGE and two-dimensional (2D) electrophoresis revealed similar protein profiles for DDV and FDV, showing bands and spot clusters within molecular weight ranges of ~16 kDa to >150 kDa and pH ranging from 3.5 to 9.5. Enzyme zymography revealed comparable gelatinolytic activity between DDV and FDV. However, the brine shrimp lethality assay indicated significantly higher toxicity in DDV (LC₅₀: 86.57 μg/mL) compared to FDV (LC₅₀: 460.37 μg/mL). DDV also showed greater lethality than FDV at 100 μg/mL (p = 0.0416) and 1000 μg/mL (p = 0.0008) but not at 10 μg/mL (p = 0.2465). These findings suggest that DDV exhibits higher toxicity in brine shrimp larvae than FDV, although both drying methods result in similar yields, percentage solids, venom profile, and gelatinolytic activity. Further research is necessary to investigate the mechanism behind this difference and its implications for antivenom production and long-term stability of venom. Full article

In the face of growing demand for emergency treatment in mass casualty incidents involving acute hemorrhagic shock, disaster sites often suffer from limited search and rescue manpower and inadequate medical detection capabilities. With the rapid development of robot technology, the deployment of robots provides greater flexibility and reliability in disaster emergency response and search and rescue work, which can effectively address the shortage of search and rescue forces and medical resources at disaster sites. This paper introduces a snake-like robot designed for the rapid triage of casualties with hemorrhagic shock. Through a structural design combining active wheels and orthogonal joints, the robot integrates the advantages of high-speed mobility of wheeled robots with the high flexibility of jointed robots so as to adapt to the complex environments typical of search and rescue scenarios. Meanwhile, the end of the robot is equipped with a visible light camera, an infrared camera and a voice interaction system, which realizes the rapid triage of casualties with hemorrhagic shock by collecting visible light, infrared and voice dialog data of the casualties. Through Webots software simulation and outdoor site simulation experiments, seven indicators of the designed snake-like search and rescue robot are verified, including walking speed, minimum passable hole size, climbing angle, obstacle-surmounting height, passable step size, ditch-crossing width and turning radius, as well as the effectiveness of collecting visible light images, infrared images and voice dialog data of the casualties. Full article

Three-finger toxins (3FTxs) from snake venom are the most abundant toxin family of mini non-enzymatic proteins, comprising 40–70% of the venom proteome. Despite their common three-finger structural scaffold, 3FTxs exhibit diverse pharmacological functions. Other than neurotoxins, they also include analgesic acid-sensing ion channel blockers, sodium and potassium channel modulators, integrin- and G-protein-coupled-receptor-targeting ligands, and gamma-aminobutyric acid type A receptor modulators that collectively span pain, cardiovascular, oncologic, and neurologic indications. However, in this fast-growing 3FTx family, there are several hundred 3FTxs whose functions have not yet been determined. Here, we systematically analyzed over 550 amino acid sequences of 3FTxs. Based on their structural features, we have classified them into more than 150 distinct subgroups. This updated information on this novel 3FTx toolkit will provide an unexplored library of investigational ligands and pharmacophores with potential therapeutic and diagnostic leads, as well as research tools. Thus, this review will provide new impetus in toxin research and pave the way for the design of potent, selective ligands for new sets of target receptors, ion channels, and enzymes. Full article

Differences in venom within snake species can affect the efficacy of antivenom, but how this variation manifests across broad geographical scales remains poorly understood. Naja atra envenoming causes severe morbidity in China, yet whether intraspecific venom variation exists across mainland regions is unknown. We collected venom samples from seven biogeographical regions (spanning > 2000 km latitude). Venom lethality, systemic toxicity (organ damage biomarkers and coagulopathy), and histopathology of major organs were assessed. Neutralization by antivenom and label-free quantitative proteomics (LC-MS/MS) were also performed. The results revealed a non-uniform LD₅₀, with venom from Yunnan exhibiting the highest lethality (2.1-fold higher than venom from Zhejiang, p < 0.001). Commercial antivenom showed lower neutralization efficacy against the venom from the Yunnan, Guangxi, and Guangdong regions. Regarding organ damage and coagulopathy, venom from Yunnan caused severe liver damage, while venom from the Zhejiang region induced significant coagulopathy. Finally, proteomic profiles identified 175 proteins: venom from Yunnan was dominated by phospholipases, contrasting with eastern regions (Anhui/Zhejiang: cytotoxins CTXs > 30%). Venom from Guangdong contained higher levels of the weak neurotoxin NNAM2 (5.2%). Collectively, significant geographical divergence exists in Chinese Cobra venom composition, systemic toxicity, and antivenom susceptibility, driven by differential expression of key toxins. Our study provides a molecular basis for precision management of snakebites, and we call for optimized antivenom production tailored to regional variations. Full article

Path flow always plays a critical role in extracting vehicle travel patterns and reflecting network-scale traffic features. However, the comprehensive topological structure of urban road networks induces massive route choices, so frequent travel routes have been gradually regarded as an ideal countermeasure to represent traffic states. Widely used license plate recognition (LPR) devices can collect the abundant traffic features of all vehicles, but their sparse spatial distributions restrict the conventional models in frequent travel identification. Therefore, this study develops a network reconstruction method to construct a topological network from the LPR dataset, avoiding the adverse effects caused by the sparse distribution of detectors on the road network and further uses the Snake algorithm to fully utilize the road network structure and traffic attributes for clustering to obtain various travel patterns, with frequent routes under different travel patterns finally identified based on Steiner trees and frequent item recognition. To address the sparse spatial distribution of LPR devices, we utilize the word2vec model to extract spatial correlations among intersections. A threshold-based method is then applied to transform the correlation matrix into a reconstructed network, connecting intersections with strong vehicle transition relationships. This community structure can be interpreted as representing different travel patterns. Consequently, the Snake algorithm is employed to cluster intersections into distinct categories, reflecting these varied travel patterns. By leveraging the word2vec model, the detector installation rate requirement for Snake is significantly reduced, ensuring that the clustering results accurately represent the intrinsic relevance of traffic roads. Subsequently, frequent routes are identified from both macro- and micro-perspectives using the Steiner tree and Frequent Pattern Growth (FP Growth) algorithm, respectively. Validated on the LPR dataset in Changsha, China, the experiment results demonstrate that the proposed method can effectively identify travel patterns and extract frequent routes in the sparsely installed LPR devices. Full article

In the management of cholangiocarcinoma, effective biliary drainage and accurate diagnosis are vital to allow further treatment. Confirmation of tissue diagnosis and molecular characterization is also required to guide future treatment options including surgery and chemotherapy as well as the possible use of personalized treatments that target specific mutations present within individual tumours. Initial CT or MRI scans may be followed by endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) to obtain tissue samples. However, these methods often fall short due to difficulty in accessing entire bile duct strictures. SpyGlass cholangioscopy can improve diagnosis, yet may fail to provide sufficient tissue for molecular characterization. Here we present a perspective on the development of snake-like agile robots with integrated optical imaging and Raman spectroscopy. These robots could improve the mapping of the biliary tree and the precision of biopsy collection and allow tissue analysis in situ, as well as facilitating stenting to restore the flow of bile. A multidisciplinary approach that brings together clinicians, pathologists, and engineers is required to develop these new robotic technologies and improve patient outcomes. Full article

Background: Snake envenomation is a major public health issue in Nigeria, primarily due to bites from Echis ocellatus, Naja nigricollis, and Bitis arietans. Understanding their venom composition is essential for effective antivenom development. This study characterizes and compares the venom proteomes of these snakes using iTRAQ-based proteomics, focusing on key toxin families and their relative abundances. Methods: Venom samples were ethically collected from adult snakes, pooled by species, lyophilized, and stored for proteomic analysis. Proteins were extracted, digested with trypsin, and labeled with iTRAQ. Peptides were analyzed via mass spectrometry, and data were processed using Mascot and IQuant for protein identification and quantification. Results: E. ocellatus and B. arietans venoms had similar profiles, rich in C-type lectins, serine proteases, and phospholipase A₂s. These comprised 17%, 11%, and 5% in E. ocellatus and 47%, 10%, and 7% in B. arietans, with metalloproteinases dominating both (53% and 47%). In N. nigricollis, three-finger toxins (9%) were most abundant, followed by metalloproteinases (3%). All species shared four core protein families, with N. nigricollis also containing four uncharacterized proteins. Conclusions: This study highlights venom compositional differences, advancing snake venom biology and informing targeted antivenom development. Full article

How humans perceive and interact with other animal species is critical in enhancing conservation initiatives. The study recorded and analyzed people’s knowledge and perceptions of birds of prey and their interactions in three rural communities in Paraíba, Brazil. The data were collected by face-to-face interviews using semi-structured questionnaires. One hundred ninety-one people were interviewed, and 19 species were recorded. Based on the answers to the questionnaires, the species are considered omens of climatic/ecological and supernatural events. They are important in the maintenance of ecosystems (predation of rodents and snakes and feeding on dead animals). However, most birds of prey are killed because they cause damage by preying upon domestic animals or for being associated with bad omens. The diversity of information listed here shows the need for complex and interdisciplinary studies to understand the human dimensions of knowledge and relationships between people and birds, contributing to species conservation and encouraging coexistence between people and birds of prey. Full article