Dried toad skin (TS) and toad venom (TV) are the dried skin of the Bufo bufo gargarizans Cantor and the Bufo melanostictus Schneider, which remove the internal organs and the white secretions of the ...skin and retroauricular glands. Since 2005, cinobufacini preparations have been approved by the State Food and Drug Administration for use as adjuvant therapies in the treatment of various advanced cancers. Meanwhile, bufalenolides has been identified as the main component of TS/TV, exhibiting antitumor activity, inducing apoptosis of cancer cells and inhibiting cancer cell proliferation or metastasis through a variety of signaling pathways. However, clinical agents frequently face limitations such as inherent toxicity at high concentrations and insufficient tumor targeting. Additionally, the development and utilization of these active ingredients are hindered by poor water solubility, low bioavailability, and rapid clearance from the bloodstream. To address these challenges, the design of a targeted drug delivery system (TDDS) aims to enhance drug bioavailability, improve targeting within the body, increase drug efficacy, and reduce adverse reactions. This article reviews the TDDS for TS/TV, and their active components, including passive, active, and stimuli-responsive TDDS, to provide a reference for advancing their clinical development and use.Dried toad skin (TS) and toad venom (TV) are the dried skin of the Bufo bufo gargarizans Cantor and the Bufo melanostictus Schneider, which remove the internal organs and the white secretions of the skin and retroauricular glands. Since 2005, cinobufacini preparations have been approved by the State Food and Drug Administration for use as adjuvant therapies in the treatment of various advanced cancers. Meanwhile, bufalenolides has been identified as the main component of TS/TV, exhibiting antitumor activity, inducing apoptosis of cancer cells and inhibiting cancer cell proliferation or metastasis through a variety of signaling pathways. However, clinical agents frequently face limitations such as inherent toxicity at high concentrations and insufficient tumor targeting. Additionally, the development and utilization of these active ingredients are hindered by poor water solubility, low bioavailability, and rapid clearance from the bloodstream. To address these challenges, the design of a targeted drug delivery system (TDDS) aims to enhance drug bioavailability, improve targeting within the body, increase drug efficacy, and reduce adverse reactions. This article reviews the TDDS for TS/TV, and their active components, including passive, active, and stimuli-responsive TDDS, to provide a reference for advancing their clinical development and use.
Conquering the world in leaps and bounds Reilly, Stephen M.; Montuelle, Stephane J.; Schmidt, Andre ...
Functional ecology,
10/2015, Letnik:
29, Številka:
10
Journal Article
Recenzirano
Summary
While most frogs maximize jump distance as an escape behaviour, toads have traded jump distance for endurance with a strategy of hopping repeatedly. This strategy has enabled toads to expand ...across the continents as one of the most diverse groups of anurans. Multiple studies have revealed physiological endurance adaptations for sustained hopping in toads, however, the kinematics of their sequential hopping behaviour, per se, has not been studied.
We compared kinematics and forces of single hops and multiple hopping sequences and quantified field performance of hopping behaviours in free ranging toads of three species and discovered a novel aspect of locomotion adaptation that adds another facet to their exceptional terrestrial locomotor abilities.
We found that bouts of repeated hopping are actually a series of bounding strides where toads rotate on their hands and then land on their extended their feet and jump again without stopping. In addition, free‐ranging toads appear to use bounding locomotion more frequently than single hops. Bounding in toads has the advantage of maintaining velocity and producing longer jump distances. In comparison to single hops, cyclic bounding steps reduce energy expenditure and appear to provide limb loading dynamics better suited for potential cycling of elastic energy from stride to stride than would be possible with repeated single hops.
This is the first case of the common use of a bounding gait outside of mammals. Bounding adds a key terrestrial locomotor trait to the toad's phenotype that may help explain their history of global expansion and the challenges to modern faunas as introduced toads rapidly invade new ecosystems today.
Lay Summary
Aim
The amount of gene flow between parapatric species can be greatly variable depending on how species boundaries are maintained in respect to numerous genetic and ecological factors that affect the ...strength of reproductive isolation. We quantified this variability to understand its effect on the genetic integrity of a well‐studied pair of hybridizing amphibians.
Location
Central and Eastern Europe.
Taxa
The fire‐ and yellow‐bellied toads Bombina bombina and B. variegata.
Methods
We first complemented the mitochondrial phylogeography of European Bombina by barcoding additional populations and built MaxEnt species distribution models to identify the routes of post‐glacial colonization that led to hybrid zone formation. Second, we targeted the areas of parapatry in Poland and Ukraine to assess nuclear admixture by population genetics (PCA, Bayesian clustering) of allozyme and genomic markers (RAD‐seq). Third, we harvested the rich Bombina literature to thoroughly compare the extent of geographical introgression across 11 transitions altogether, using cline analyses when possible.
Results
We found sharp (2–11 km wide) but leaky transitions (geographically extensive traces of introgression) in all parapatric areas, either measured from a few allozymes or thousands of species‐diagnostic SNPs, and irrespective of the intraspecific lineages involved or the relative ages since first contact.
Main conclusion
Bombina species are permeable to gene flow despite selection against hybrids that retards but cannot ultimately prevent putatively neutral introgression into the parental gene pools. Although local hybrid swarms face genetic assimilation, the species’ integrities remain intact due to their large geographical ranges and ecological differentiation that enforces tight boundaries regardless of the biogeographical attributes of the contacts. Opposing the great variability of introgression patterns found between cryptic species, these results support that gene flow should not be viewed as a force of despeciation when reproductive isolation involves multiple intrinsic and extrinsic barriers.
Animal poisons and venoms are comprised of different classes of molecules displaying wide-ranging pharmacological activities. This review aims to provide an in-depth view of toxin-based compounds ...from terrestrial and marine organisms used as diagnostic tools, experimental molecules to validate postulated therapeutic targets, drug libraries, prototypes for the design of drugs, cosmeceuticals, and therapeutic agents. However, making these molecules applicable requires extensive preclinical trials, with some applications also demanding clinical trials, in order to validate their molecular target, mechanism of action, effective dose, potential adverse effects, as well as other fundamental parameters. Here we go through the pitfalls for a toxin-based potential therapeutic drug to become eligible for clinical trials and marketing. The manuscript also presents an overview of the current picture for several molecules from different animal venoms and poisons (such as those from amphibians, cone snails, hymenopterans, scorpions, sea anemones, snakes, spiders, tetraodontiformes, bats, and shrews) that have been used in clinical trials. Advances and perspectives on the therapeutic potential of molecules from other underexploited animals, such as caterpillars and ticks, are also reported. The challenges faced during the lengthy and costly preclinical and clinical studies and how to overcome these hindrances are also discussed for that drug candidates going to the bedside. It covers most of the drugs developed using toxins, the molecules that have failed and those that are currently in clinical trials. The article presents a detailed overview of toxins that have been used as therapeutic agents, including their discovery, formulation, dosage, indications, main adverse effects, and pregnancy and breastfeeding prescription warnings. Toxins in diagnosis, as well as cosmeceuticals and atypical therapies (bee venom and leech therapies) are also reported. The level of cumulative and detailed information provided in this review may help pharmacists, physicians, biotechnologists, pharmacologists, and scientists interested in toxinology, drug discovery, and development of toxin-based products.
Toxins from toads have long been known to contain rich chemicals with great pharmaceutical potential. Recent studies have shown more than 100 such chemical components, including peptides, steroids, ...indole alkaloids, bufogargarizanines, organic acids, and others, in the parotoid and skins gland secretions from different species of toads. In traditional Chinese medicine (TCM), processed toad toxins have been used for treating various diseases for hundreds of years. Modern studies, including both experimental and clinical trials, have also revealed the molecular mechanisms that support the development of these components into medicines for the treatment of inflammatory diseases and cancers. More recently, there have been studies that demonstrated the therapeutic potential of toxins from other species of toads, such as Australian cane toads. Previous reviews mostly focused on the pharmaceutical effects of the whole extracts from parotoid glands or skins of toads. However, to fully understand the molecular basis of toad toxins in their use for therapy, a comprehensive understanding of the individual compound contained in toad toxins is necessary; thus, this paper seeks to review the recent studies of some typical compounds frequently identified in toad secretions.
Amphibians inhabit a wide variety of habitats and environments, such as arboreal, terrestrial and freshwater aquatic ecosystems, and are considered among the vertebrate classes to exhibit one of the ...most diverse distributions. Their life histories, behaviour and diversity play vital roles in assessing environmental and evolutionary theories. The mitochondrial 16S rRNA gene sequence analysis has been widely used in molecular taxonomy and is frequently used in systematic analyses of families and genera. This study examines taxonomic relationships among 18 specimens of the Arabian toad (Sclerophrys arabica) and the Dhofar toad (Bufo dhufarensis) from Al Madinah Province, Saudi Arabia by estimating phylogenetic relationships using the mitochondrial 16S ribosomal RNA gene (16S rRNA). Results indicate the presence of four new lineages of toads among the samples in this study. The generated phylogenetic tree grouped all samples of Arabian toad in one clade, while the Dhofar toad samples were divided into three subclades. This is the first study to be reported the genetic diversity of Al Madinah Province toads.
Toad skin and toad venom, as two kinds of Chinese medicine, are prepared from
Cantor and
Schneider. However, they display distinct properties in traditional application, and the hydrophilic ...ingredients are the possible distinguishing chemicals between them. In this work, 36 and 22 hydrophilic components were characterized from toad skin and venom, respectively, by UHPLC-HR-MS/MS, including amino acids, nucleosides, polypeptides, and indolealkylamines (IAAs). Among them, 15 compounds were unambiguously confirmed by comparison with standards. The CID-MS/MS fragmentation behaviors of seven indolealkylamine references were investigated to ascertain three types of structures. Subsequently, 11 high abundance contents of hydrophilic ingredients were determined from 11 batches of toad skin and 4 batches of toad venom by UPLC-QqQ-MS/MS. The quantitative results showed that the content of main IAAs in toad venom was much higher than in skin. In addition, the
-methyl serotonin (free IAA), bufothionine (combined IAA), and total IAAs sample were selected for anti-inflammatory evaluation in lipopolysaccharide (LPS) stimulated zebrafish embryo models. The obvious anti-inflammatory activities of IAAs were observed, especially for the free IAAs. This study illustrated IAAs were the main distinct hydrophilic components that probably lead to the difference between toad skin and toad venom in traditional applications.
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•15 Bufotes species dissected by genomics and multiple genetic/biometric datasets.•Widespread mitochondrial replacements and the super-cryptic species concept.•Diverse but asymmetric ...origins of allopolyploid hybrid species.•A discontinuous speciation continuum across 10 pairs of hybridizing lineages.•Major taxonomic revisions, including the descriptions of two new species.
The radiation of Palearctic green toads (Bufotes) holds great potential to evaluate the role of hybridization in phylogeography at multiple stages along the speciation continuum. With fifteen species representing three ploidy levels, this model system is particularly attractive to examine the causes and consequences of allopolyploidization, a prevalent yet enigmatic pathway towards hybrid speciation. Despite substantial efforts, the evolutionary history of this species complex remains largely blurred by the lack of consistency among the corresponding literature. To get a fresh, comprehensive view on Bufotes phylogeography, here we combined genome-wide multilocus analyses (RAD-seq) with an extensive compilation of mitochondrial, genome size, niche modelling, distribution and phenotypic (bioacoustics, morphometrics, toxin composition) datasets, representing hundreds of populations throughout Eurasia. We provide a fully resolved nuclear phylogeny for Bufotes and highlight exceptional cyto-nuclear discordances characteristic of complete mtDNA replacement (in 20% of species), mitochondrial surfing during post-glacial expansions, and the formation of homoploid hybrid populations. Moreover, we traced the origin of several allopolyploids down to species level, showing that all were exclusively fathered by the West Himalayan B. latastii but mothered by several diploid forms inhabiting Central Asian lowlands, an asymmetry consistent with hypotheses on mate choice and Dobzhansky-Muller incompatibilities. Their intermediate call phenotypes potentially allowed for rapid reproductive isolation, while toxin compositions converged towards the ecologically-closest parent. Across the radiation, we pinpoint a stepwise progression of reproductive isolation through time, with a threshold below which hybridizability is irrespective of divergence (<6My), above which species barely admix and eventually evolve different mating calls (6–10My), or can successfully cross-breed through allopolyploidization (>15My). Finally, we clarified the taxonomy of Bufotes (including genetic analyses of type series) and formally described two new species, B. cypriensis sp. nov. (endemic to Cyprus) and B. perrini sp. nov. (endemic to Central Asia). Embracing the genomic age, our framework marks the advent of a new exciting era for evolutionary research in these iconic amphibians.
Objective
To report the clinical presentations, treatments and outcomes of toad toxicity in domestic cats in Southeastern Queensland, Australia.
Methods
This report describes a retrospective study of ...190 cases of cane toad (Rhinella marina) toxicity in cats in south‐eastern Queensland, Australia. All cases were presented for veterinary treatment between 2011 and 2020 at four specialist veterinary emergency centres in Southeast Queensland, Australia. Cane toad toxicity was diagnosed based on a history of exposure and clinical signs.
Results
Domestic short‐hair breeds accounted for 53.6% of the cases. Presentation was seasonal with the highest incidence over the warmer months of the year (November – March). Hypersalivation was described in 96.3% (183/190), tachypnoea in 34.2% (65/190) and altered behaviour in 18.4% (35/190) of cases. Seizures occurred in 1% of cases. Of the 190 cases, 6.3% (12/190) were hospitalised and 0.5% (1/190) were euthanised and overall 99.5% (189/190) survived hospital discharge.
Clinical significance
Cane toad toxicity is relatively common in cats in Southeast Queensland and following buccal lavage the prognosis for recovery was excellent.
We present a high‐quality genome assembly for the Asiatic toad (Bufo gargarizans) and explore the evolution of several large gene families in amphibians. With a large genome assembly size of 4.55 Gb, ...the chromosome‐scale assembly includes 747 scaffolds with an N50 of 539.8 Mb and 1.79% gaps. Long terminal repeats (LTRs) constitute a high proportion of the genome and their expansion is a key contributor to the inflated genome size in this species. This is very different from other small amphibian genomes, but similar to that of the enormous axolotl genome. The genome retains a large number of duplicated genes, with tandem (TD) and proximal duplications (PD) the predominant mode of duplication. A total of 122 gene families have undergone significant expansion and were mainly enriched in sensory perception of smell and bitter taste. The CYP2C subfamily, which plays an important role in metabolic detoxification, specifically expanded via TD and PD in the Asiatic toad and the cane toad (true toads). Most of Na+/K+‐ATPase genes experienced accelerated evolution along Bufonid lineages and two amino acid sites involving toad‐toxin resistance were found to experience positive selection. We also revealed a dynamic evolution of olfactory and vomeronasal receptor gene families which was likely driven by the water‐to‐land transition. The high‐quality genome of the Asiatic toad will provide a solid foundation to understand the genetic basis of its many biological processes.
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