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competency of amphibians and reptiles and their potential role as reservoir hosts for rift valley fever virus.rift valley fever phlebovirus (rvfv) is an arthropod-borne zoonotic pathogen, which is endemic in africa, causing large epidemics, characterized by severe diseases in ruminants but also in humans. as in vitro and field investigations proposed amphibians and reptiles to potentially play a role in the enzootic amplification of the virus, we experimentally infected african common toads and common agamas with two rvfv strains. lymph or sera, as well as oral, cutaneous and anal swabs were collected f ...202033114178
toads prey upon scorpions and are resistant to their venom: a biological and ecological approach to scorpionism.in recent years, se brazil, the most populous region in the country with an estimated population of 88 million, has been experiencing an alarming increase in scorpions accidents (scorpionism), mainly caused by the yellow scorpion (tityus serrulatus), or "escorpião amarelo" in portuguese. this species is considered particularly dangerous to humans and can reproduce by parthenogenesis favouring rapid dispersal and colonization of new environments. since the 1940s, owing to the growing danger repre ...202032081637
stretch-excitation correlation in the toad heart.the activation sequence of the ventricular myocardium in ectotherms is a matter of debate. we studied the correlation between the ventricular activation sequence and the pattern of local stretches in 13 toads (bufo bufo). epicardial potential mapping was done with 56-lead sock array. activation times were determined as dv/dt min in each lead. initial epicardial foci of activation were found on the left side of the ventricular base, whereas regions on the apex and the right side of the base demon ...202033161379
morphological and histological abnormalities of the neotropical toad, rhinella arenarum (anura: bufonidae) larvae exposed to dexamethasone.dexamethasone (dex) is a glucocorticoid highly effective as an anti-inflammatory, immunosuppressant and decongestant drug. in the present study, a preliminary acute toxicity test was assayed in order to determinate dex median-lethal, lowest-observed-effect and the no-observed-effect concentrations (lc50, loec and noec, respectively) on the common toad embryos (rhinella arenarum). also, morphological and histological abnormalities from five body larval regions, liver melanomacrophages (mm) and gl ...202033112724
two new indole alkaloids from toad venom of bufo bufo gargarizans.two new indole alkaloids, bufotenidine b (2) and bufocarboline a (6), along with seven known indole alkaloids (1, 3-5, and 7-9) and three organic acids (10-12), were isolated from the water extract of toad venom. the structures of the new alkaloids were elucidated by extensive spectroscopic methods. the absolute configurations of 4, 6, and 8 were determined for the first time by electronic circular dichroism (ecd) calculations. the cytotoxic activity of all compounds was tested against human mal ...202033019706
the insecticidal activity of rhinella schneideri (werner, 1894) paratoid secretion in nauphoeta cinerea cocroaches.rhinella schneideri is a common toad found in south america, whose paratoid toxic secretion has never been explored as an insecticide. in order to evaluate its insecticidal potential, nauphoeta cinerea cockroaches were used as an experimental model in biochemical, physiological and behavioral procedures. lethality assays with rhinella schneideri paratoid secretion (rsps) determined the ld50 value after 24 h (58.07µg/g) and 48 h exposure (44.07 µg/g) (r2 = 0.882 and 0.954, respectively). acetylch ...202033019552
hybridization and introgression between toads with different sex chromosome systems.the growing interest in the lability of sex determination in non-model vertebrates such as amphibians and fishes has revealed high rates of sex chromosome turnovers among closely related species of the same clade. can such lineages hybridize and admix with different sex-determining systems, or could the changes have precipitated their speciation? we addressed these questions in incipient species of toads (bufonidae), where we identified a heterogametic transition and characterized their hybrid z ...202033014420
stressed tadpoles mount more efficient glucocorticoid negative feedback in anthropogenic habitats due to phenotypic plasticity.coping with anthropogenic environmental change is among the greatest challenges faced by wildlife, and endocrine flexibility is a potentially crucial coping mechanism. animals may adapt to anthropogenic environments by dampening their glucocorticoid stress response, but empirical tests of this hypothesis have provided mixed evidence. an alternative hypothesis is that a non-attenuated stress response and efficient negative feedback are favored in anthropogenic habitats. to test this idea, we non- ...202032889314
individual variation in cardiotoxicity of parotoid secretion of the common toad, bufo bufo, depends on body size - first results.anurans secrete a wide diversity of toxins from skin glands to defend themselves against predators and pathogens. bufonids produce potent poison in parotoid macroglands located in the postorbital region. parotoid secretion is a rich source of bioactive compounds with cardiotoxic, cytotoxic and hemolytic activity. poison content and toxicity may vary between species, populations, and among conspecifics inhabiting the same area. in the present paper, we pre-analyzed the individual variation in car ...202032862084
how to disinfect anuran eggs? sensitivity of anuran embryos to chemicals widely used for the disinfection of larval and post-metamorphic amphibians.emerging infectious diseases are major drivers of global and local amphibian biodiversity loss. therefore, developing effective disinfection methods to manage the impact of diseases in wild and captive "ark" populations are an important goal in amphibian conservation. while chemical disinfectants have been used safely and effectively in larval and adult amphibians infected with pathogenic microbes, their applicability to amphibian egg masses has remained untested. to bridge this gap, we exposed ...202032830870
toad venom antiproliferative activities on metastatic melanoma: bio-guided fractionation and screening of the compounds of two different venoms.melanoma is the most common cancer in young adults, with a constantly increasing incidence. metastatic melanoma is a very aggressive cancer with a 5-year survival rate of about 22-25%. this is, in most cases, due to a lack of therapies which are effective on the long term. hence, it is crucial to find new therapeutic agents to increase patient survival. toad venoms are a rich source of potentially pharmaceutically active compounds and studies have highlighted their possible effect on cancer cell ...202032785105
aminomethylphosphonic acid alters amphibian embryonic development at environmental concentrations.despite intense societal and scientific debates regarding glyphosate toxicity, it remains the most widely used herbicide. the primary metabolite of glyphosate, ampa (aminomethylphosphonic acid), is the main contaminant detected in surface waters worldwide, both because of the extensive use of glyphosate and because of other widespread sources of ampa (i.e., industrial detergents). studies on potential effects of glyphosate using environmentally relevant concentrations of ampa on non-target wildl ...202032771800
[study on quality standard of bufonis venenum and its processed slice, toad venom powder].bufonis venenum(toad venom) is prepared from the dried secretion of bufo bufo gargarizans or b. melanostictus. toad venom powder is one of the processed slices of crude material toad venom. in the present study, the global quality control method and standard of toad venom and its processed slice, toad venom powder were established, including tlc identification, characteristic chromatogram and qams by hplc. the relative correction factor(rcf) was re-calculated and validated. the average rcfs of c ...202032489055
relationships between chemical defenses of common toad (bufo bufo) tadpoles and bacterial community structure of their natural aquatic habitat.many organisms synthesize secondary metabolites against natural enemies. however, to which environmental factors the production of these metabolites is adjusted to is poorly investigated in animals, especially so in vertebrates. bufadienolides are steroidal compounds that are present in a wide range of plants and animals and, if present in large quantities, can provide protection against natural enemies, such as pathogens. in a correlative study involving 16 natural populations we investigated h ...202032468489
inter-population variation in thermal sensitivity of the tropical toad duttaphrynus melanostictus, across a small spatial scale in sri lanka.inter-population disparities in a species have been shown to occur as an adaptation to different thermal regimes in the environment. we investigated the thermal sensitivities of the tropical toad duttaphrynus melanostictus (asia common toad) from two populations at different altitudes: nuwara-eliya - 1870 m, and polonnaruwa - 25 m, above mean sea level. the two locations were separated by what may be considered a short direct distance - 110 km. thermal sensitivity trials were conducted at six te ...202032364998
impacts of trace metals on african common toad, amietophrynus regularis (reuss, 1833) and depuration effects of the toad's enteric parasite, amplicaecum africanum (taylor, 1924) sampled within lagos metropolis, nigeria.the study aimed at assessing the depuration potentials of endoparasite, amplicaecum africanum on trace metals in its toad host, amietophrynus regularis at sites of significant anthropogenic perturbations within the lagos metropolis, in nigeria. a total of 120 toads of both sexes, alongside 45 soil samples were collected from each of three (3) stations labeled dumpsite, lagoon front and highrise, using hand nets and by hand-picking between february and october, 2018. the intestinal tissues sectio ...202032258456
mitochondrial costs of being hot: effects of acute thermal change on liver bioenergetics in toads (bufo bufo).global climatic warming is predicted to drive extreme thermal events, especially in temperate terrestrial environments. hence, describing how physiological parameters are affected by acute temperature changes would allow us to understand the energy management of organisms facing such non-predictable and constraining events. as mitochondria play a key role in the conversion of energy from food into atp but also produce harmful reactive oxygen species, the understanding of its functioning is cruci ...202032218742
effects of two little-studied environmental pollutants on early development in anurans.despite intensive ecotoxicological research, we still know relatively little about the ecological impacts of many environmental contaminants. filling these knowledge gaps is particularly important regarding amphibians, because they play significant roles in freshwater and terrestrial ecosystems, and their populations are declining worldwide. in this study, we investigated two pollutants that have been poorly studied in ecotoxicology despite their widespread occurrence in surface waters: the herb ...202032041031
ocular hypotonia and transient decrease of vision as a consequence of exposure to a common toad poison.the common toad produces venom (bufotoxin) that is produced in the parotid gland of the toad as well as in the skin. this toxic compound is a potent inhibitor of na+/k+-atpase activity. physiological effects of bufotoxin are similar to those of digitalis and cause increased heart rate and muscle contractions. ocular toxicity was described. a 67-year-old female patient was admitted to the emergency service because of sudden vision loss and a burning sensation in both eyes after she had been expos ...202032015920
the rhinella arenarum transcriptome: de novo assembly, annotation and gene prediction.the common toad rhinella arenarum is widely distributed in argentina, where it is utilised as an autochthonous model in ecotoxicological research and environmental toxicology. however, the lack of a reference genome makes molecular assays and gene expression studies difficult to carry out on this non-model species. to address this issue, we performed a genome-wide transcriptome analysis on r. arenarum larvae through massive rna sequencing, followed by de novo assembly, annotation, and gene predi ...202031974515
global metabolomic and lipidomic analysis reveal the synergistic effect of bufalin in combination with cinobufagin against hepg2 cells.chansu, which is prepared from the skin secretions of toad (bufo bufo gargarizans cantor), is widely used in traditional chinese medicine (tcm). being the principal bioactive constituents of chansu, bufalin (bfl) and cinobufagin (cbf) have been shown to possess anticancer properties. tcm confers bioactivities through the synergistic effect between potential active ingredients, so as to interfere with the development of the disease, and ultimately achieve the therapeutic effect. we found that the ...202031942794
artificial light at night alters the sexual behaviour and fertilisation success of the common toad.artificial light at night (alan) is an emerging pollution, that dramatically keeps on increasing worldwide due to urbanisation and transport infrastructure development. in 2016, it nearly affected 23% of the earth's surface. to date, all terrestrial and aquatic ecosystems have been affected. the disruption of natural light cycles due to alan is particularly expected for nocturnal species, which require dark periods to forage, move, and reproduce. apart from chiropterans, amphibians contain the l ...202031931411
potential pesticide exposure during the post-breeding migration of the common toad (bufo bufo) in a vineyard dominated landscape.two important drivers of the global amphibian decline are habitat destruction due to an intensification of farming and a related increase of pesticide applications. recent studies have shown that there might be an underestimated risk of pesticides on terrestrial amphibians. however, there are too few data on the terrestrial habitat use of amphibians in agricultural landscapes to estimate the exposure risk. to fill this knowledge gap, we used telemetry to investigate the post-breeding migration o ...202031855631
toxicity characterization and environmental risk assessment of mancozeb on the south american common toad rhinella arenarum.agricultural activity, especially the increasing use of pesticides, is considered one of the main reasons for the decline of amphibian populations. mancozeb (mcz) is one of the most used fungicides worldwide, despite its ancient use and toxicity demonstrated in different taxa. however, there is limited information about the effects of mcz in amphibians, which are keystones of riparian ecosystems. for species conservation purposes, it is essential to identify the most sensitive developmental peri ...202031838683
comparative toxicity of two different dimethoate formulations in the common toad (rhinella arenarum) tadpoles.dimethoate (d) are among the most commonly used organophosphates insecticides in the world. to evaluate the toxicity of two d formulations were selected as test organisms tadpoles of rhinella arenarum. this toad species has an extensive neotropical distribution and is easy to handle and acclimate to laboratory conditions. the tadpoles were exposed in an acute assay for 48 h to d soluble concentrates (dsc) and emulsifiable concentrates (dec). the 48 h-lc50 (95% confidence limits) value of dsc was ...202031740980
neofoleyellides boerewors n. gen. n. sp. (nematoda: onchocercidae) parasitising common toads and mosquito vectors: morphology, life history, experimental transmission and host-vector interaction in situ.anuran filarial nematodes are restricted to two comparatively small subfamilies (icosiellinae and waltonellinae) of the filariae that currently comprise six genera and 41 recognised species. however, the life histories of only five anuran filarial nematodes, proposed as an ancestral group based on molecular phylogenetic studies, have been elucidated. furthermore, data on the natural vectors (in situ) and parasite transmission is limited. in the current study we elucidate the life history of neof ...202032087248
a new method for the estimation of minimum adult frog density from a large-scale audial survey.audial surveys of anuran amphibians (frogs, toads and similar) are cost-effective and allow for the coverage of large areas, but they are usually regarded as unsuitable for population size estimations due to imperfect detection. our study demonstrated a method for obtaining minimum adult population size estimates from vocalising anuran counts by using sex ratios, life history and vocalising behaviour parameters from other studies. we collected data from 2016 to 2018 for seven taxa on 65 plots (e ...202032451461
influence of substrate types and morphological traits on movement behavior in a toad and newt species.inter-patch movements may lead to genetic mixing, decreasing both inbreeding and population extinction risks, and is hence a crucial aspect of amphibian meta-population dynamics. traveling through heterogeneous landscapes might be particularly risky for amphibians. understanding how these species perceive their environment and how they move in heterogeneous habitats is an essential step in explaining metapopulation dynamics and can be important for predicting species' responses to climate change ...201930643673
the toad fly lucilia bufonivora: its evolutionary status and molecular identification.the blow fly genus lucilia is composed largely of saprophages and facultative myasis agents, including the economically important species lucilia cuprina (wiedemann) (diptera: calliphoridae) and lucilia sericata (meigen). only one species is generally recognized as an obligate agent of myiasis, lucilia bufonivora moniez, and this is an obligate parasite of toads. lucilia silvarum (meigen), a sister species, behaves mainly as a carrion breeder; however, it has also been reported as a facultative ...201930091469
geographic body size variation of a tropical anuran: effects of water deficit and precipitation seasonality on asian common toad from southern asia.two previous studies on interspecific body size variation of anurans found that the key drivers of variation are the species' lifestyles and the environments that they live in. to examine whether those findings apply at the intraspecific level, we conducted a study of the asian common toad (duttaphrynus melanostictus), a terrestrial anuran distributed in tropical regions. the body size of toads from 15 locations, covering the majority of their geographic range, and local environmental data were ...201931706264
protein identification from the parotoid macrogland secretion of duttaphrynus melanostictus.bufonid parotoid macrogland secretion contains several low molecular mass molecules, such as alkaloids and steroids. nevertheless, its protein content is poorly understood. herein, we applied a sample preparation methodology that allows the analysis of viscous matrices in order to examine its proteins.201931467513
predator-induced changes in the chemical defence of a vertebrate.1. inducible defences are ubiquitous in the animal kingdom, but little is known about facultative changes in chemical defences in response to predators, especially so in vertebrates. 2. we tested for predator-induced changes in toxin production of larval common toads (bufo bufo), which are known to synthesize bufadienolide compounds. 3. the experiment included larvae originating from three permanent and three temporary ponds reared in the presence or absence of chemical cues of three predators: ...201931408536
the protection of indolealkylamines from lps-induced inflammation in zebrafish.toad skin came from bufo bufo gargarizans cantor and bufo melanostictus schneider. as the traditional chinese medicine, it had the effect of clearing away heat and detoxification. in traditional applications, toad skin was often used for the treatment of cancer and inflammation. total indolealkylamines (iaas) from this medicine were proved the main compounds exert anti-inflammatory activity in our previous research.201931356965
[correlative study of bufogenin constituents in venom of bufo bufo gargarizans].as known,simultaneous determination of various chemical indicators is one of the future trends in quality control of traditional chinese medicines because of the extremely complex chemical compositions. this project is to screen the quality markers that can accurately control the quality of the bufonis venenum by exploring the intrinsic correlation of components. in this study,venom of bufo bufo gargarizans from 17 different sources were used as research samples,and the contents of 7 bufogenin w ...201931342712
meteterakis asansolensis sp. nov. (nematoda: heterakidae) in duttaphrynus melanostictus (schneider, 1899) (amphibia: anura: bufonidae) from asansol coalfield area, paschim bardhaman, west bengal, india.meteterakis asansolensis sp. nov. (nematoda: heterakidae) recovered from the rectum of asian common toad, duttaphrynus melanostictus (schneider, 1899), collected from asansol coalfield area in paschim bardhaman district of west bengal, india, is described and illustrated. this species is characterised by the presence of a precloacal sucker, a gubernaculum and two equal and similar spicules (0.31-0.32 mm in length). this species differs from other reported species of the oriental region by morpho ...201931263327
bufothionine exerts anti-cancer activities in gastric cancer through pim3.gastric cancer (gc) is the fourth most common cancer globally. bufothionine is a major active constituent of cinobufacini (huachansu), which is extracted from the skin and parotid venom gland of the toad bufo bufo gargarizans cantor. it exhibits anti-cancer activities in vitro. however, whether bufothionine exerts anti-cancer activities against gc is unknown. this study was designed to evaluate the efficacy of bufothionine in vitro and in vivo.201931260686
chemical defense of toad tadpoles under risk by four predator species.many organisms use inducible defenses as protection against predators. in animals, inducible defenses may manifest as changes in behavior, morphology, physiology, or life history, and prey species can adjust their defensive responses based on the dangerousness of predators. analogously, prey may also change the composition and quantity of defensive chemicals when they coexist with different predators, but such predator-induced plasticity in chemical defenses remains elusive in vertebrates. in th ...201931236221
effect-based environmental monitoring for thyroid disruption in swedish amphibian tadpoles.it is well-known that the metamorphosis process in amphibians is dependent on thyroid hormones. laboratory studies have shown that several environmental contaminants can affect the function of thyroid hormones leading to alterations in the amphibian metamorphosis. the basic idea of the present study was to elucidate if the amphibian metamorphosis might be a useful tool as biomarker for effect-based environmental monitoring, examining wild tadpoles for potential thyroid hormone disruption. a labo ...201931222463
differences in ocular media transmittance in classical frog and toad model species and its impact on visual sensitivity.the transmittance properties of the cornea, lens and humours of vertebrates determine how much light across the visible spectrum reaches the retina, influencing sensitivity to visual stimuli. amphibians are the only vertebrate class in which the light transmittance of these ocular media has not been thoroughly characterised, preventing large-scale comparative studies and precise quantification of visual stimuli in physiological and behavioural experiments. we measured the ocular media transmitta ...201931171601
fatal phaeohyphomycosis due to exophiala sp. infection in a free-living common toad bufo bufo.a wild adult female common toad bufo bufo found dead in scotland in september 2016 was observed to have hepatomegaly, a large soft tissue mass in the coelomic cavity (2.7 g, 3.5 × 2.3 × 1.8 cm) and numerous dark-red papules (1-2 mm diameter) in the skin and subjacent tissue over the back and dorsal aspects of the limbs. histopathological examination identified marked hepatitis and coelomitis associated with pigmented fungal hyphae, which are results consistent with a diagnosis of phaeohyphomycos ...201930997881
negative effects of parasitic lung nematodes on the fitness of a neotropical toad (rhinella horribilis).pathogens are increasingly implicated in amphibian declines but less is known about parasites and the role they play. we focused on a genus of nematodes (rhabdias) that is widespread in amphibians and examined their genetic diversity, abundance (prevalence and intensity), and impact in a common toad (rhinella horribilis) in panama. our molecular data show that toads were infected by at least four lineages of rhabdias, most likely rhabdias pseudosphaerocephala, and multiple lineages were present ...201930859923
toads phenotypically adjust their chemical defences to anthropogenic habitat change.despite the well-documented effects of human-induced environmental changes on the morphology, physiology, behaviour and life history of wild animals, next to nothing is known about how anthropogenic habitats influence anti-predatory chemical defence, a crucial fitness component of many species. we investigated the amount and composition of defensive toxins in adult common toads (bufo bufo) captured in natural, agricultural and urban habitats, and in their offspring raised in a common-garden expe ...201930816222
changes in toxin quantities following experimental manipulation of toxin reserves in bufo bufo tadpoles.possessing toxins can contribute to an efficient defence against various threats in nature. however, we generally know little about the energy- and time-demands of developing toxicity in animals, which determines the efficiency of chemical defence and its trade-off with other risk-induced phenotypic responses. in this study we examined how immersion into norepinephrine solution inducing the release of stored toxins, administration of mild stress mimicking predator attack or simple handling durin ...201930684072
transcriptional analysis of tyrosinase gene expression during bufo bufo development.tyrosinase (ec.1.14.18.1.) is a widespread enzyme, in the phylogenetic scale, that produces melanin, from bacteria to man, by using as substrates monophenols, o-diphenols and molecular oxygen. in this work we have confirmed and demonstrated that during bufo bufo development tyrosinase activity and gene expression first occur at developmental stages 17-18 (tail bud-muscular response) as detected by a spectrophotometric assay and qrt-pcr. as expected, also during b. bufo development tyrosinase gen ...201930655714
description of a new species of rhabdias stiles and hassall, 1905 (nematoda, rhabdiasidae) in duttaphrynus melanostictus (schneider, 1899) from west bengal, india.the purpose of this article is to describe a new species of rhabdias stiles and hassall, 1905 from west bengal, india. rhabdias bengalensis sp. nov. (nematoda, rhabdiasidae) recovered from the lungs of asian common toad, duttaphrynus melanostictus (schneider, 1899), collected from illambazar town, birbhum district of west bengal, india.201930645738
indication of spatially random occurrence of chlamydia-like organisms in bufo bufo tadpoles from ponds located in the geneva metropolitan area.occurrence of bacteria belonging to the order chlamydiales was investigated for the first time in common toad (bufo bufo) tadpole populations collected from 41 ponds in the geneva metropolitan area, switzerland. a chlamydiales-specific real-time pcr was used to detect and amplify the chlamydiales 16s ribosomal rna-encoding gene from the tails of 375 tadpoles. we found the studied amphibian populations to host chlamydia-like organisms (clos) attributable to the genera similichlamydia, neochlamydi ...201930622711
testing an hypothesis of hybrid zone movement for toads in france.hybrid zone movement may result in substantial unidirectional introgression of selectively neutral material from the local to the advancing species, leaving a genetic footprint. this genetic footprint is represented by a trail of asymmetric tails and displaced cline centres in the wake of the moving hybrid zone. a peak of admixture linkage disequilibrium is predicted to exist ahead of the centre of the moving hybrid zone. we test these predictions of the movement hypothesis in a hybrid zone betw ...201930609055
urban environment and reservoir host species are associated with batrachochytrium dendrobatidis infection prevalence in the common toad.human-induced changes of the environment, including landscape alteration and habitat loss, may affect wildlife disease dynamics and have important ramifications for wildlife conservation. amphibians are among the vertebrate taxa most threatened by anthropogenic habitat change. the emerging fungal pathogen batrachochytrium dendrobatidis (bd) has caused extinctions and population declines in hundreds of anuran species globally. we studied how the urban landscape is associated with the prevalence o ...201932132271
an amphibian species pushed out of britain by a moving hybrid zone.classical theory states that hybrid zones will be stable in troughs of low population density where dispersal is hampered. yet, evidence for moving hybrid zones is mounting. one possible reason that moving zones have been underappreciated is that they may drive themselves into oblivion and with just the superseding species remaining, morphological and genetic signals of past species replacement may be difficult to appreciate. using genetic data (32 diagnostic single nucleotide polymorphisms) fro ...201931643124
artificial light at night disturbs the activity and energy allocation of the common toad during the breeding period.the presence of artificial light at night (alan) is currently a global phenomenon. by altering the photoperiod, alan may directly affect the physiology and behaviour of many organisms, such as the timing of daily rhythms, hormonal regulation, food intake, metabolism, migration and reproduction. surprisingly while it is known that alan exposure strongly influences health of humans and laboratory animals, studies on wildlife remain scarce. amphibians are one of the most nocturnal groups of vertebr ...201930746151
receptor-specific crosstalk between prostanoid e receptor 3 and bombesin receptor subtype 3.bombesin receptor subtype 3 (brs-3) is a gpcr that is expressed in the cns, peripheral tissues, and tumors. our understanding of brs-3's role in physiology and pathophysiology is limited because its natural ligand is unknown. in an attempt to identify this ligand, we screened toad skin ( bufo bufo gargarizans cantor) extracts and identified prostaglandins as putative ligands. in brs-3-transfected human embryonic kidney (hek) cells, we found that prostaglandins, with prostaglandin e2 (pge2) being ...201829401613
comparative analysis of hydrophilic ingredients in toad skin and toad venom using the uhplc-hr-ms/ms and uplc-qqq-ms/ms methods together with the anti-inflammatory evaluation of indolealkylamines.toad skin and toad venom, as two kinds of chinese medicine, are prepared from bufo bufo gargarizans cantor and bufo melanostictus 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 (iaa ...201830591646
ethnopharmaceutical knowledge in samogitia region of lithuania: where old traditions overlap with modern medicine.modern ethnopharmaceutical studies are still quite unusual in northern europe. data regarding the medicinal use of plants, animals, and fungi and also of spiritual rituals of healing is obtained mostly from ethnographic and folkloric sources in lithuania. the aim of this study was to assess the ethnopharmaceutical knowledge regarding traditional use of natural substances for medicinal purposes in the samogitia region and compare with prior research conducted 10 years prior in the same region.201830458833
two new 19-norbufadienolides with cardiotonic activity isolated from the venom of bufo bufo gargarizans.two new 19-norbufadienolides (1 and 2) and one new 14,15-epoxy bufadienolide (3) alongside 16 known bufadienolides (4-19) were isolated from bufonis venenum that originated from the skin and parotid venom glands of an asiatic toad (bufo bufo gargarizans cantor). the structures of these bufadienolides were elucidated based on the interpretation of their hresims and nmr data. compound 1, which had a unique peroxide, was established through extensive single-crystal x-ray diffraction. the two 19-nor ...201830385402
bufonid herpesvirus 1 (bfhv1) associated dermatitis and mortality in free ranging common toads (bufo bufo) in switzerland.here we report the discovery and partial characterization of a novel herpesvirus tentatively named bufonid herpesvirus 1 (bfhv1) from severe dermatitis in free ranging common toads (bufo bufo) in switzerland. the disease has been observed in toads every year since 2014, in spring, during the mating season, at different and distant locations. the virus is found in the skin and occasionally in the brain of infected toads. the genome of the virus is at least 158 kb long and contains at least 152 op ...201830283010
cloning, prokaryotic expression and function of the bufo bufo gargarizans 3β-hydroxysteroid dehydrogenase (3βhsd) gene.bufadienolides, one kind of steroids, are the major active component secreted by ear-side gland of bufo species. preliminary studies on high-throughput transcriptome sequencing about b. bufo gargarizans showed that the expression of 3β-hydroxysteroid dehydrogenase (3βhsd) in ear-side gland was nearly 20 times higher than that in liver. the enzyme 3βhsd is an essential step in the biosynthesis of steroid such as progesterone, estrogens and androgens in steroidogenic tissues. accordingly, 3βhsd is ...201830170058
[study on quality control method of toad venom based on characteristic chromatogram and qams].toad venom (chansu) is prepared from the dried secretion of parotid gland and skin gland from bufo bufo gargarizans or b. melanostictus. up to now, much attention shall be paid to the poor quality of commercial toad venom because of the adulteration. so, it is urgent to establish a scientific and perfect quality control method to improve the quality of toad venom and guarantee its safety and effectiveness in clinical application. the different batches of toad venom samples were assayed by high p ...201830111043
blood biomarkers of common toad rhinella arenarum following chlorpyrifos dermal exposure.chlorpyrifos (cpf) is a broad spectrum pesticide commonly used for insect control, has great affinity for lipids and is thus a potential for bioaccumulation in aquatic organisms. the aim of this study was to evaluate the toxicity of cpf using the common toad rhinella arenarum via dermal uptake in plastic bucket to simulate their natural exposition in ponds. r. arenarum toads were exposed individually to solutions containing a nominal concentration of a commercial formulation of cpf insecticide ( ...201831719786
rhabdias bufonis (rhabdiasidae) from the lung of the african common toad, amietophrynus regularis (bufonidae) in egypt: new data on the basis of light and scanning electron microscopic study.rhabdias sp. (rhabdiasidae) is a nematode parasite of family rhabdiasidae infecting the lung of amphibians. the present study provides new morphological details for rhabdias bufonis isolated from the lungs of the african common toad, amietophrynus regularis based on observations of light and scanning electron microscopy (sem).201830042901
widespread vulnerability of malagasy predators to the toxins of an introduced toad.invasive species are a key factor contributing to the global decline of biodiversity, and understanding the underlying mechanisms is crucial to mitigate detrimental effects [1]. one such mechanism is the introduction of invasive species with defensive strategies, such as novel toxins, that can disrupt native predator communities [2]. disruption of such communities can produce trophic cascades, impacting a diverse array of taxa [2]. madagascar, a globally significant biodiversity hotspot, has rec ...201829870701
identification of <10 kd peptides in the water extraction of venenum bufonis from bufo gargarizans using nano lc-ms/ms and de novo sequencing.skins of anurans (frogs and toads) are rich sources of bioactive peptides. however, the peptides secreted by the skin glands of bufo gargarizans, the most common toad in china, remained unexplored to date. here, a strategy combines lc-ms/ms, rna sequencing and bioinformation analysis was applied to unravel the peptides in the bufo gargarizans secretions. data-dependent lc-ms/ms acquisitions of intact peptides followed by automated chromatographic alignment, de novo analysis, database and homolog ...201829800903
cinobufacini inhibits epithelial-mesenchymal transition of human hepatocellular carcinoma cells through c-met/erk signaling pathway.cinobufacini, an aqueous extract from the skins and parotid venom glands of the toad bufo bufo gargarizans cantor, is a well known traditional chinese medicine widely used in clinical cancer therapy in china. its therapeutic effect is especially pronounced in liver cancer. however, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (hcc) cells are still not very clear. here, we investigated the effects and mechanisms of cinobufacini on inhibiting hepg2 cells invasio ...201829794405
seasonal migrations, body temperature fluctuations, and infection dynamics in adult amphibians.risks of parasitism vary over time, with infection prevalence often fluctuating with seasonal changes in the annual cycle. identifying the biological mechanisms underlying seasonality in infection can enable better prediction and prevention of future infection peaks. obtaining longitudinal data on individual infections and traits across seasons throughout the annual cycle is perhaps the most effective means of achieving this aim, yet few studies have obtained such information for wildlife. here, ...201829761041
molecular mechanisms underlying the antimetastatic activity of bufalin.bufalin is a monomer compound extract from chansu, which is a traditional chinese medicine obtained from the skin and parotid venom glands of toads, such as bufo bufo gargarizans cantor and bufo melanostictus schneider. chansu had been used in traditional chinese medicine for >1,000 years due to its cardiac, anti-inflammatory and anticancer properties. previous studies identified bufalin as the main anticancer compound of chansu, and recent evidence has corroborated its anticancer properties. bu ...201829732152
a matter of proportion? associational effects in larval anuran communities under fish predation.in batesian mimicry, a species lacking defences against predators benefits from mimicking the aposematic signal of a defended species, while the model may incur the costs of reduced defensive efficacy. similar reciprocal indirect effects may emerge even when the signal is not mimicked; termed associational effects, such interactions are well known in plants sharing herbivores but have received little attention in animal studies. we investigated associational interactions in a system where unequa ...201829713808
endocrine disruptors in breeding ponds and reproductive health of toads in agricultural, urban and natural landscapes.many chemical pollutants have endocrine disrupting effects which can cause lifelong reproductive abnormalities in animals. amphibians are the most threatened group of vertebrates, but there is little information on the nature and quantity of pollutants occurring in typical amphibian breeding habitats and on the reproductive capacities of amphibian populations inhabiting polluted areas. in this study we investigated the occurrence and concentrations of endocrine disrupting chemicals in the water ...201829710633
evaluating movement patterns and microhabitat selection of the japanese common toad (bufo japonicus formosus) using fluorescent powder tracking.bufo japonicus formosus (eastern-japanese common toad) is endemic to eastern japan. as with many japanese amphibians, little is known about its terrestrial life, especially during the nonbreeding season. this species persists even in highly disturbed urban areas where many other amphibian species have already been extirpated. an understanding of how such species use habitats within remnant landscapes may help to inform management strategies for the conservation of urban ecosystems. we examined t ...201829623783
bufadienolides induce p53-mediated apoptosis in esophageal squamous cell carcinoma cells in vitro and in vivo.bufadienolides are a type of cardiotonic steroids isolated from the skin and parotid venom glands of the toad bufo bufo gargarizans cantor, and exhibit wide-spectrum anticancer activities. however, the effects and mechanisms of bufadienolides on esophageal squamous cell carcinoma (escc) cells remain unknown. in the present study, the anticancer activities of two bufadienolides, bufotalin and bufalin, were examined in vitro and in vivo. the results demonstrated that bufotalin and bufalin effectiv ...201829434851
toxic activity and protein identification from the parotoid gland secretion of the common toad bufo bufo.anuran toxins released from the skin glands are involved in defence against predators and microorganisms. secretion from parotoid macroglands of bufonid toads is a rich source of bioactive compounds with the cytotoxic, cardiotoxic and hemolytic activity. bufadienolides are considered the most toxic components of the toad poison, whereas the protein properties are largely unknown. in the present work, we analysed the cardio-, myo-, and neurotropic activity of extract and the selected proteins fro ...201829382576
effects of host species and environmental factors on the prevalence of batrachochytrium dendrobatidis in northern europe.the fungal pathogen batrachochytrium dendrobatidis (bd) poses a major threat to amphibian populations. to assist efforts to address such threats, we examined differences in bd host infection prevalence among amphibian species and its relations to both local environmental factors in breeding habitats and landscape variables measured at three scales (500, 2000 and 5000 m radii) around breeding sites in southernmost sweden. we sampled 947 anurans of six species in 31 ponds and assessed their infect ...201830359384
characterization of the adaptive morphology of japanese stream toad (bufo torrenticola) using geometric morphometrics.the order anura (frogs and toads) is a group of amphibians and contains over 6500 extant species living in a variety of environments. each frog species evolved body form adaptive for living and breeding in their own habitats. in japan, four taxa of bufo are living: western-japanese common toad (bufo japonicus japonicus), eastern-japanese common toad (b. japonicus formosus), miyako toad (b. gargarizans miyakonis) and japanese stream toad (b. torrenticola). the former three taxa breed in still wat ...201829417890
evaluation in situ of genotoxicity and stress in south american common toad rhinella arenarum in environments related to fluorite mine.little attention has been paid to the impact of wastewater generated by mining activities on fluoride. in this study, we evaluated the hematology responses of common south american toad rhinella arenarum inhabiting natural and artificial environments associated with a fluorite mine from central argentina. we analyzed three sampling stations associated with the fluorite mine: (i) los cerros negros stream (cn), which runs on granitic rock with a high fluorite content; (ii) los vallecitos stream (l ...201728634794
amphibian and reptile road-kills on tertiary roads in relation to landscape structure: using a citizen science approach with open-access land cover data.amphibians and reptiles are among the most endangered vertebrate species worldwide. however, little is known how they are affected by road-kills on tertiary roads and whether the surrounding landscape structure can explain road-kill patterns. the aim of our study was to examine the applicability of open-access remote sensing data for a large-scale citizen science approach to describe spatial patterns of road-killed amphibians and reptiles on tertiary roads. using a citizen science app we monitor ...201728651557
distribution of nadph-diaphorase reactivity in the central nervous system of the common toad (bufo bufo).we examined the distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (nadph-d)-reactive elements in the central nervous system (cns) of the common toad, bufo bufo. the investigation involved adult male and female toads collected during the breeding season. labeled neurons of different morphological appearances (weakly or darkly stained, unipolar, bipolar, and multipolar) and fibers were observed across all subdivisions of the amphibian brain. overall, a similar distribution of ...201729208411
phylogeographic and population insights of the asian common toad (bufo gargarizans) in korea and china: population isolation and expansions as response to the ice ages.the effects of ice ages on speciation have been well documented for many european and north american taxa. in contrast, very few studies have addressed the consequences of such environmental and topographical changes in north east asian species. more precisely, the korean peninsula offers a unique model to assess patterns and processes of speciation as it hosts the northern- and eastern-most distribution limit of some widespread asian taxa. despite this, studies addressing phylogeographic patter ...201729201561
amphibian recovery after a decrease in acidic precipitation.we here report the first sign of amphibian recovery after a strong decline due to acidic precipitation over many decades and peaking around 1980-90. in 2010, the ph level of ponds and small lakes in two heavily acidified areas in southwestern scandinavia (aust-agder and østfold in norway) had risen significantly at an (arithmetic) average of 0.14 since 1988-89. parallel with the general rise in ph, amphibians (rana temporaria, r. arvalis, bufo bufo, lissotriton vulgaris, and triturus cristatus) ...201729164539
differing long term trends for two common amphibian species (bufo bufo and rana temporaria) in alpine landscapes of salzburg, austria.this study focuses on the population trends of two widespread european anuran species: the common toad (bufo bufo) and the common frog (rana temporaria). the basis of this study is data gathered over two decades of amphibian fencing alongside roads in the austrian state of salzburg. different statistical approaches were used to analyse the data. overall average increase or decrease of each species was estimated by calculating a simple average locality index. in addition the statistical software ...201729121054
comparing pseudo-absences generation techniques in boosted regression trees models for conservation purposes: a case study on amphibians in a protected area.boosted regression trees (brt) is one of the modelling techniques most recently applied to biodiversity conservation and it can be implemented with presence-only data through the generation of artificial absences (pseudo-absences). in this paper, three pseudo-absences generation techniques are compared, namely the generation of pseudo-absences within target-group background (tgb), testing both the weighted (wtgb) and unweighted (utgb) scheme, and the generation at random (rdm), evaluating their ...201729107997
[advance on quality control of toad venom and its key influence factors].toad venom (chansu) is prepared from the dried secretion of bufo bufo gargarizans or b. melanostictus. it is not only one of the famous and expensive traditional chinese medicines(tcms) from animal origin, but also one of 28 kinds of toxic tcms to be required for special management issued by the state council of the people's republic of china. chansu contains the rich bufadienolides and indole alkaloids, and displays various bioactivity including cardiotonic, anti-tumor, analgesia, and local ane ...201728994527
hybrid zone formation and contrasting outcomes of secondary contact over transects in common toads.much progress in speciation research stems from documenting patterns of morphological and genetic variation in hybrid zones. contrasting patterns of marker introgression in different sections of the contact can provide valuable insights on the relative importance of various evolutionary mechanisms maintaining species differences in the face of hybridization and gene flow and on hybrid zone temporal and spatial dynamics. we studied species interactions in the common toads bufo bufo and b. spinosu ...201728752635
arginine derivatives of dicarboxylic acids from the parotid gland secretions of common toad bufo bufo-new agonists of ionotropic γ-aminobutyric acid receptors.compounds activating γ-aminobutyric acid type a receptor were isolated from the toad bufo bufo venom as a result of chromatographic separation. analysis of the structure of these compounds by mass spectrometry and nuclear magnetic resonance showed that they are arginine derivatives of dicarboxylic acids and represent suberylarginine, pimeloylarginine, and adipoylarginine.201728726106
chronic exposure to a glyphosate-based herbicide makes toad larvae more toxic.chemical pollutants can exert various sublethal effects on wildlife, leading to complex fitness consequences. many animals use defensive chemicals as protection from predators and diseases, yet the effects of chemical contaminants on this important fitness component are poorly known. understanding such effects is especially relevant for amphibians, the globally most threatened group of vertebrates, because they are particularly vulnerable to chemical pollution. we conducted two experiments to in ...201728679726
standardize or diversify experimental conditions in ecotoxicology? a case study on herbicide toxicity to larvae of two anuran amphibians.despite a steeply increasing number of ecotoxicological studies on the effects of pesticides on nontarget organisms, studies assessing the adequacy and reliability of different experimental approaches have remained scarce. we scrutinized effects of a glyphosate-based herbicide on larvae of two european anuran amphibians by estimating species-specific lc50 values, assessing how an additional stress factor may influence outcomes, and investigating whether replicate experiments yielded qualitativel ...201728660298
isolation and identification of l/d-lactate-conjugated bufadienolides from toad eggs revealing lactate racemization in amphibians.three pairs of bufadienolide l/d-lactate epimers (1-6) were isolated from the eggs of the toad bufo bufo gargarizans. the structures were elucidated by using spectroscopic methods, x-ray diffraction analysis and a modified mosher's method. compounds 1-6 represent the first occurrence of lactate-conjugated bufadienolides in nature, and illustrate the existence of an enzyme-controlled epimerization from l- to d-lactate in amphibians. the biosynthetic pathways, in which two key enzymes might be inv ...201728639665
age- and environment-dependent changes in chemical defences of larval and post-metamorphic toads.chemical defences are widespread in animals, but how their production is adjusted to ecological conditions is poorly known. optimal defence theory predicts that inducible defences are favoured over constitutive defences when toxin production is costly and the need for it varies across environments. however, if some environmental changes occur predictably (e.g. coupled to transitions during ontogeny), whereas others are unpredictable (e.g. predation, food availability), changes in defences may ha ...201728610604
n-methyl serotonin analogues from the bufo bufo toad venom interact efficiently with the α7 nicotinic acetylcholine receptors.two low-molecular-weight compounds were isolated from the parotid gland secret of the toad bufo bufo, which by absorption spectra and hplc-ms/ms chromatography data correspond to di- and trimethyl derivatives of serotonin (5-hydorxytryptamine): bufotenine (confirmed by counter synthesis) and bufotenidine (5-htq). in experiments on competitive radioligand binding, these compounds showed a higher affinity and selectivity for neuronal α7 nicotinic acetylcholine receptors compared with the muscular ...201728421441
toxins and pharmacologically active compounds from species of the family bufonidae (amphibia, anura).among amphibians, 15 of the 47 species reported to be used in traditional medicines belong to the family bufonidae, which demonstrates their potential in pharmacological and natural products research. for example, asian and american tribes use the skin and the parotoid gland secretions of some common toads in the treatment of hemorrhages, bites and stings from venomous animals, skin and stomach disorders, as well as several types of cancers.201728034659
age-dependent changes in sensitivity to a pesticide in tadpoles of the common toad (bufo bufo).the worldwide en masse application of pesticides and the frequently reported malign effects on several non-target organisms underpin the importance of ecotoxicological research on these anthropogenic pollutants. previous studies showed that sensitivity to herbicides can vary widely depending on additional stress factors, on the species and even on the population investigated. however, there is little information about how sensitivity changes during ontogeny, and how the duration of exposure is l ...201728365461
climate change promotes hybridisation between deeply divergent species.rare hybridisations between deeply divergent animal species have been reported for decades in a wide range of taxa, but have often remained unexplained, mainly considered chance events and reported as anecdotal. here, we combine field observations with long-term data concerning natural hybridisations, climate, land-use, and field-validated species distribution models for two deeply divergent and naturally sympatric toad species in europe (bufo bufo and bufotes viridis species groups). we show th ...201728348926
neogene amphibians and reptiles (caudata, anura, gekkota, lacertilia, and testudines) from the south of western siberia, russia, and northeastern kazakhstan.the present-day amphibian and reptile fauna of western siberia are the least diverse of the palaearctic realm, as a consequence of the unfavourable climatic conditions that predominate in this region. the origin and emergence of these herpetofaunal groups are poorly understood. aside from the better-explored european neogene localities yielding amphibian and reptile fossil remains, the neogene herpetofauna of western asia is understudied. the few available data need critical reviews and new inte ...201728348925
arenobufagin activates p53 to trigger esophageal squamous cell carcinoma cell apoptosis in vitro and in vivo.esophageal squamous cell carcinoma (escc) is often diagnosed at late incurable stage and lacks effective treatment strategy. bufadienolides are cardiotonic steroids isolated from the skin and parotid venom glands of the toad bufo bufo gargarizans cantor with novel anticancer activity. however, there is little information about the effects and action mechanisms of bufadienolides on escc cells. in this study, the in vitro and in vivo anti-escc activities of bufadienolides, including bufalin (bu) a ...201728280360
bufospirostenin a and bufogargarizin c, steroids with rearranged skeletons from the toad bufo bufo gargarizans.bufospirostenin a (1) and bufogargarizin c (2), two novel steroids with rearranged a/b rings, were isolated from the toad bufo bufo gargarizans. compound 1 represents the first spirostanol found in animals. compound 2 is an unusual bufadienolide with a cycloheptatriene b ring. their structures were elucidated by spectroscopic analysis, single crystal x-ray diffraction analysis, and computational calculations.201728256122
comprehensive two-dimensional normal-phase liquid chromatography × reversed-phase liquid chromatography for analysis of toad skin.an analytical two-dimensional normal-phase liquid chromatography × reversed-phase liquid chromatography (2d nplc × rplc) system was constructed with a newly developed thermal evaporation assisted adsorption (teaa) interface. this novel teaa interface with heating temperature above solvent boiling point allowed fast removal of organic nplc solvent and successfully solved the solvent incompatibility problem between nplc and rplc. the system achieved rapid on-line solvent exchange between the two d ...201728231875
feeding behavior of mimomyia (etorleptiomyia) luzonensis (ludlow, 1905) (diptera, culicidae) in peninsular malaysia.mosquitoes are vectors of various human diseases in the tropics including yellow fever, dengue, malaria and west nile virus. mosquitoes can act as vectors between wildlife and humans, which is particularly important for diseases where wild animals serve as reservoirs of parasites in the absence of human infections. research has mainly focused on the medical impacts of anopheles, aedes, mansonia and culex, however, very little attention has been directed towards other mosquito genera, especially ...201728359829
[influence of the concentration of dissolved oxygen on embryonic development of the common toad (bufo bufo)].several series of experiments investigating the influence of dissolved oxygen concentrations on the growth rates and mortality in the embryogenesis of the common toad bufo bufo were carried out. the experiments showed that, when the eggs develop singly, the lack of oxygen does not lead to an increase in mortality by the time of hatching and results only in a change in the dynamics of mortality: mortality occurs at an earlier stage of development than in the conditions of normal access to oxygen. ...201626859970
mapping the relative probability of common toad occurrence in terrestrial lowland farm habitat in the united kingdom.the common toad (bufo bufo) is of increasing conservation concern in the united kingdom (uk) due to dramatic population declines occurring in the past century. many of these population declines coincided with reductions in both terrestrial and aquatic habitat availability and quality and have been primarily attributed to the effect of agricultural land conversion (of natural and semi-natural habitats to arable and pasture fields) and pond drainage. however, there is little evidence available to ...201626841108
deep genetic structure and ecological divergence in a widespread human commensal toad.the asian common toad (duttaphrynus melanostictus) is a human commensal species that occupies a wide variety of habitats across tropical southeast asia. we test the hypothesis that genetic variation in d. melanostictus is weakly associated with geography owing to natural and human-mediated dispersal facilitated by its commensal nature. phylogenetic and population genetic analyses of mitochondrial and nuclear dna sequence variation, and predictive species distribution modelling, unexpectedly reco ...201626763213
proliferative events and apoptotic remodelling in retinal development of common toad (bufo bufo).proliferation and apoptosis are fundamental processes in the development of the retina, and a proper balance of the two phenomena is crucial to correct development of the organ. despite intense investigation in different vertebrates, only a few studies have analyzed the cell death and the cell division quantitatively in the same species during development. here we studied the time course of apoptosis and proliferation in the retina of common toad, bufo bufo, and discuss the findings in an evolut ...201626541902
concordant morphological and molecular clines in a contact zone of the common and spined toad (bufo bufo and b. spinosus) in the northwest of france.hybrid zones are regions where individuals of two species meet and produce hybrid progeny, and are often regarded as natural laboratories to understand the process of species formation. two microevolutionary processes can take place in hybrid zones, with opposing effects on population differentiation. hybridization tends to produce genetic homogenization, reducing species differences, whereas the presence of mechanisms of reproductive isolation result in barriers to gene flow, maintaining or inc ...201628018475
inhibitory effect of bufalin on retinoblastoma cells (hxo-rb44) via the independent mitochondrial and death receptor pathway.cinobufacini (huachansu) is a chinese medicine prepared from the skin of bufo bufo gargarizans cantor (bufonidae), and has long been used in traditional chinese medicine. in the present study, the anti-retinoblastoma constituent bufalin obtained from cinobufacini was investigated. treatment of human retinoblastoma (hxo-rb44) cells with bufalin induced apoptosis which was accompanied by a decrease in mitochondrial membrane potential, activation of caspase-9, caspase-8 and caspase-3, as well as ch ...201627904697
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