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Toxicology Reports 2023Embelin is a hydroxybenzoquinone constituent of the Embelia species that has anti-disease properties. However, its toxicity, particularly the , acute, and developmental...
BACKGROUND
Embelin is a hydroxybenzoquinone constituent of the Embelia species that has anti-disease properties. However, its toxicity, particularly the , acute, and developmental toxicity profiles, has yet to be thoroughly investigated. Hence, this study aims to assess these toxicity profiles.
MATERIALS AND METHODS
and experimental studies were conducted on embelin isolated from the fruits of Vatke. toxicity predictions were computed using the ProTox model. The experiment was done by administering 5000 mg/kg of embelin to a single female albino Wistar rat, followed by three female rats in the absence of death, to determine the mean lethal dose (LD50). Afterwards, three groups of pregnant rats were treated with embelin at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg for the developmental toxicity test. Vehicle and control groups were used to compare the acute and developmental toxicity variables.
RESULTS
toxicity predicted that embelin is free from hepatotoxic, carcinogenic, mutagenic, and cytotoxic effects. No inhibitory effect on hERG channels was observed. It has an immunotoxic property and an inhibitory effect on the CYP2D6 enzyme. Since mortality and signs of toxicities were not observed after treatment with 5000 mg/kg, the mean lethal dose (LD) is determined to be > 5000 mg/kg. There was no significant difference in the morphological scores or number of somites among experimental animals. None of the embryonic systems possessed developmental delays. Nevertheless, the crown-rump length of the high-dose group became significantly shorter. Maternal food intake and weight gain exhibited significant dose-dependent differences between embelin-treated animals and controls. The number of implantations was significantly low in the treatment group, accompanied by a higher frequency of prior resorption.
CONCLUSION
Embelin is predicted to have a high probability of immunotoxicity potential and affect drug metabolism by inhibiting CYP2D6. In addition, it affects food intake, weight gain, and the number of implantations in pregnant rats. Therefore, it is highly recommended not to take embelin and embelin-rich plants during pregnancy. Further and studies need to be conducted to understand the mechanism behind the toxicity of embelin.
PubMed: 37362226
DOI: 10.1016/j.toxrep.2023.06.006 -
Systematic Parasitology Oct 2023Two species of sea lice are reported from the golden snapper Lutjanus johnii (Bloch) in Australian waters. One was represented by chalimus larvae, adult males and...
Caligid sea lice (Copepoda: Caligidae) from golden snapper Lutjanus johnii (Bloch) in Australian waters, with the recognition of Sinocaligus Shen, 1957 as a junior synonym of Caligus Müller, 1785.
Two species of sea lice are reported from the golden snapper Lutjanus johnii (Bloch) in Australian waters. One was represented by chalimus larvae, adult males and extremely slender females in which the genital complex is scarcely wider than the fourth pedigerous somite. These females are adult as they carry paired spermatophores and are identified as Caligus dussumieri Rangnekar, 1957 on the details of their appendages. Caligus dussumieri was formerly placed in the genus Sinocaligus Shen, 1957 but the characters supporting the validity of this genus are not robust, so it is here proposed to treat it as a junior subjective synonym of Caligus and transfer its species as: Caligus formicoides Redkar, Rangnekar & Murti, 1949, Caligus dussumieri Shen, 1957, Caligus caudatus (Gnanamuthu, 1950) new combination and Caligus timorensis (Izawa, 1995) new combination. All these species can be placed in the C. bonito-species group within Caligus. Caligus rivulatus Pilla, Vankara & Chikkam, 2012 is recognized as a junior subjective synonym of C. dussumieri. A new species, C. auriolus n. sp. is also described and this is placed in the C. diaphanus species-group. A key to species of this species-group is provided which indicates that C. auriolus n. sp. is most closely related to C. stromatei Krøyer, 1863 but the latter can be distinguished by the slender abdomen of the female and by the more complex myxal process on the maxilliped in the male.
Topics: Female; Male; Animals; Copepoda; Australia; Species Specificity; Fishes; Perciformes
PubMed: 37341922
DOI: 10.1007/s11230-023-10099-z -
Science Advances Jun 2023Two influential concepts in tissue patterning are Wolpert's positional information and Turing's self-organized reaction-diffusion (RD). The latter establishes the...
Two influential concepts in tissue patterning are Wolpert's positional information and Turing's self-organized reaction-diffusion (RD). The latter establishes the patterning of hair and feathers. Here, our morphological, genetic, and functional-by CRISPR-Cas9-mediated gene disruption-characterization of wild-type versus "scaleless" snakes reveals that the near-perfect hexagonal pattern of snake scales is established through interactions between RD in the skin and somitic positional information. First, we show that ventral scale development is guided by hypaxial somites and, second, that ventral scales and epaxial somites guide the sequential RD patterning of the dorsolateral scales. The RD intrinsic length scale evolved to match somite periodicity, ensuring the alignment of ribs and scales, both of which play a critical role in snake locomotion.
Topics: Animals; Somites; Diffusion; Feathers; Hair; Locomotion
PubMed: 37315141
DOI: 10.1126/sciadv.adf8834 -
Journal of Comparative Physiology. B,... Aug 2023The kinetics of myosin controls the speed and power of muscle contraction. Mammalian skeletal muscles express twelve kinetically different myosin heavy chain (MyHC)... (Review)
Review
The kinetics of myosin controls the speed and power of muscle contraction. Mammalian skeletal muscles express twelve kinetically different myosin heavy chain (MyHC) genes which provides a wide range of muscle speeds to meet different functional demands. Myogenic progenitors from diverse craniofacial and somitic mesoderm specify muscle allotypes with different repertoires for MyHC expression. This review provides a brief synopsis on the historical and current views on how cell lineage, neural impulse patterns, and thyroid hormone influence MyHC gene expression in muscles of the limb allotype during development and in adult life and the molecular mechanisms thereof. During somitic myogenesis, embryonic and foetal myoblast lineages form slow and fast primary and secondary myotube ontotypes which respond differently to postnatal neural and thyroidal influences to generate fully differentiated fibre phenotypes. Fibres of a given phenotype may arise from myotubes of different ontotypes which retain their capacity to respond differently to neural and thyroidal influences during postnatal life. This gives muscles physiological plasticity to adapt to fluctuations in thyroid hormone levels and patterns of use. The kinetics of MyHC isoforms vary inversely with animal body mass. Fast 2b fibres are specifically absent in muscles involved in elastic energy saving in hopping marsupials and generally absent in large eutherian mammals. Changes in MyHC expression are viewed in the context of the physiology of the whole animal. The roles of myoblast lineage and thyroid hormone in regulating MyHC gene expression are phylogenetically the most ancient while that of neural impulse patterns the most recent.
Topics: Animals; Myosin Heavy Chains; Phylogeny; Muscle, Skeletal; Muscle Fibers, Skeletal; Myosins; Marsupialia
PubMed: 37277594
DOI: 10.1007/s00360-023-01499-0 -
PLoS Genetics Jun 2023Four SIX homeoproteins display a combinatorial expression throughout embryonic developmental myogenesis and they modulate the expression of the myogenic regulatory...
Four SIX homeoproteins display a combinatorial expression throughout embryonic developmental myogenesis and they modulate the expression of the myogenic regulatory factors. Here, we provide a deep characterization of their role in distinct mouse developmental territories. We showed, at the hypaxial level, that the Six1:Six4 double knockout (dKO) somitic precursor cells adopt a smooth muscle fate and lose their myogenic identity. At the epaxial level, we demonstrated by the analysis of Six quadruple KO (qKO) embryos, that SIX are required for fetal myogenesis, and for the maintenance of PAX7+ progenitor cells, which differentiated prematurely and are lost by the end of fetal development in qKO embryos. Finally, we showed that Six1 and Six2 are required to establish craniofacial myogenesis by controlling the expression of Myf5. We have thus described an unknown role for SIX proteins in the control of myogenesis at different embryonic levels and refined their involvement in the genetic cascades operating at the head level and in the genesis of myogenic stem cells.
Topics: Mice; Animals; Homeodomain Proteins; Cell Differentiation; Somites; Muscle Development; Gene Expression Regulation, Developmental; Muscle, Skeletal
PubMed: 37267426
DOI: 10.1371/journal.pgen.1010781 -
MethodsX 2023Due to the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) without a medical prescription and their frequent prevalence in aquatic habitats, there are...
Due to the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) without a medical prescription and their frequent prevalence in aquatic habitats, there are major health and environmental issues. NSAIDs have been found in surface water and wastewater in concentrations ranging from ng/L to μg/L all over the world. The purpose of this study was to determine the relationship between NSAIDs (diclofenac, ketoprofen, paracetamol and ibuprofen) exposure and associated adverse effects in the assessment of indirect human health risks posed by (zebrafish) and Environmental Risk Assessment (ERA) of these NSAIDs in aquatic environments. Therefore, the objectives of this study were to (i) reveal abnormality endpoints of early developmental stages, after exposure of zebrafish and (ii) perform an ecological risk assessment of aquatic organisms upon exposure to NSAIDs detected in surface waters based on the risk quotients (RQs) method. According to the toxicity data collected, all of the malformations appeared after diclofenac exposure at all concentrations. The most notable malformations were the lack of pigmentation and an increase in yolk sac volume, with EC values of 0.6 and 1.03 mg/L, respectively. The results obtained for the ERA revealed RQs higher than 1 for all the four NSAIDs chosen, posing ecotoxicological pressure in aquatic environments. Overall, our findings provide a critical contribution to the formulation of high-priority actions, sustainable strategies and strict regulations that minimize the negative effects of NSAIDs on the aquatic ecosystem.•To determine the LC, lethal conditions such as coagulation, absence of heartbeat and blood flow, absence of tail separation and development of somites were taken into account.•The EC was calculated using sublethal parameters such as blood coagulation, pericardial edema, yolk sac edema or hypertrophy.•The 4 compounds present a high risk individually and in mixture with a RQ >> 1.
PubMed: 37251652
DOI: 10.1016/j.mex.2023.102215 -
Insects May 2023(Hymenoptera: Eulophidae) is a globally intrusive pest. Despite extensive research into the physiological responses of this pest, our understanding of the molecular...
(Hymenoptera: Eulophidae) is a globally intrusive pest. Despite extensive research into the physiological responses of this pest, our understanding of the molecular mechanisms still needs to be improved. We want to accurately investigate the expression of 's target genes, so it is imperative to select fitting reference genes. In this study, eight housekeeping genes' stability (, , , , , , , and ) was tested under five different experimental conditions, including male or female adults, somites (head, thorax, and abdomen), temperatures (0 °C, 25 °C, and 40 °C), diets (starvation, clear water, 10% honey water, sap), and pesticides (acetone was used as a control, imidacloprid, monosultap). Gene stability was calculated using RefFinder, which integrates four algorithms (the ∆Ct method, geNorm, NormFinder, and BestKeeper). The findings implied that and were the most accurate when comparing sexes. For analyzing different somites, and were ideal; the and were perfect for analyzing at different temperatures. The combination of and helped to analyze gene expression in different diets, and and were suitable for various pesticide conditions. Overall, this research offers a complete list of reference genes from for precise analysis of target gene expression, which can improve the trustworthiness of RT-qPCR and lay the foundation for further investigations into the gene function of this pest.
PubMed: 37233084
DOI: 10.3390/insects14050456 -
Frontiers in Oncology 2023MAP4K4 is a serine/threonine kinase that belongs to the MAP kinase family and plays a critical role in embryogenesis and cellular migration. It contains approximately... (Review)
Review
MAP4K4 is a serine/threonine kinase that belongs to the MAP kinase family and plays a critical role in embryogenesis and cellular migration. It contains approximately 1,200 amino acids and has a molecular mass of 140 kDa. MAP4K4 is expressed in most tissues where it has been examined and its knockout is embryonic lethal due to impaired somite development. Alterations in MAP4K4 function have a central role in the development of many metabolic diseases such as atherosclerosis and type 2 diabetes, but have recently been implicated in the initiation and progression of cancer. For example, it has been shown that MAP4K4 can stimulate the proliferation and invasion of tumor cells by activating pro-proliferative pathways (such as the c-Jun N-terminal kinase [JNK] and mixed-lineage protein kinase 3 [MLK3] pathways), attenuate anti-tumor cytotoxic immune responses, and stimulate cell invasion and migration by altering cytoskeleton and actin function. Recent experiments using RNA interference-based knockdown (miR) techniques have shown that inhibition of MAP4K4 function reduces tumor proliferation, migration, and invasion, and may represent a promising therapeutic approach in many types of cancer such as pancreatic cancer, glioblastoma, and medulloblastoma, among others. Over the last few years, specific MAP4K4 inhibitors such as GNE-495 have been developed but have not yet been tested in cancer patients. However, these novel agents may be useful for cancer treatment in the future.
PubMed: 37223681
DOI: 10.3389/fonc.2023.1162835 -
Neurotoxicology Jul 2023Zebrafish is known for its widespread neurogenesis and regenerative capacity, as well as several biological advantages, which turned it into a relevant animal model in...
Zebrafish is known for its widespread neurogenesis and regenerative capacity, as well as several biological advantages, which turned it into a relevant animal model in several areas of research, namely in toxicological studies. Ketamine is a well-known anesthetic used both in human as well as veterinary medicine, due to its safety, short duration and unique mode of action. However, ketamine administration is associated with neurotoxic effects and neuronal death, which renders its use on pediatric medicine problematic. Thus, the evaluation of ketamine effects administration at early stages of neurogenesis is of pivotal importance. The 1-41-4 somites stage of zebrafish embryo development corresponds to the beginning of segmentation and formation of neural tube. In this species, as well as in other vertebrates, longitudinal studies are scarce, and the evaluation of ketamine long-term effects in adults is poorly understood. This study aimed to assess the effects of ketamine administration at the 1-4 somites stage, both in subanesthetic and anesthetic concentrations, in brain cellular proliferation, pluripotency and death mechanisms in place during early and adult neurogenesis. For that purpose, embryos at the 1-4 somites stage (10.5 h post fertilization - hpf) were distributed into study groups and exposed for 20 min to ketamine concentrations at 0.2/0.8 mg/mL. Animals were grown until defined check points, namely 50 hpf, 144 hpf and 7 months adults. The assessment of the expression and distribution patterns of proliferating cell nuclear antigen (PCNA), of sex-determining region Y-box 2 (Sox 2), apoptosis-inducing factor (AIF) and microtubule-associated protein 1 light chain 3 (LC3) was performed by Western-blot and immunohistochemistry. The results evidenced the main alterations in 144 hpf larvae, namely in autophagy and in cellular proliferation at the highest concentration of ketamine (0.8 mg/mL). Nonetheless, in adults no significant alterations were seen, pointing to a return to a homeostatic stage. This study allowed clarifying some of the aspects pertaining the longitudinal effects of ketamine administration regarding the CNS capacity to proliferate and activate the appropriate cell death and repair mechanisms leading to homeostasis in zebrafish. Moreover, the results indicate that ketamine administration at 1-4 somites stage in the subanesthetic and anesthetic concentrations despite some transitory detrimental effects at 144 hpf, is long-term safe for CNS, which are newly and promising results in this research field.
Topics: Animals; Child; Humans; Ketamine; Zebrafish; Anesthetics, Dissociative; Cell Death; Cell Proliferation; Embryo, Nonmammalian
PubMed: 37196828
DOI: 10.1016/j.neuro.2023.05.008 -
Frontiers in Cell and Developmental... 2023Members of the Eya family, which are a class of transcription factors with phosphatase activity, are widely expressed in cranial sensory organs during development....
Members of the Eya family, which are a class of transcription factors with phosphatase activity, are widely expressed in cranial sensory organs during development. However, it is unclear whether these genes are expressed in the taste system during development and whether they play any role in specifying taste cell fate. In this study, we report that is not expressed during embryonic tongue development but that -expressing progenitors in somites or pharyngeal endoderm give rise to tongue musculature or taste organs, respectively. In the -deficient tongues, these progenitors do not proliferate properly, resulting in a smaller tongue at birth, impaired growth of taste papillae, and disrupted expression of in the papillary epithelium. On the other hand, is specifically expressed in endoderm-derived circumvallate and foliate papillae located on the posterior tongue during development. In adult tongues, is predominantly expressed in IPR3-positive taste cells in the taste buds of the circumvallate and foliate papillae, while is persistently expressed in these papillae at higher levels in some epithelial progenitors and at lower levels in some taste cells. We found that conditional knockout of in the third week or 2 knockout reduced Pou2f3, Six1 and IPR3 taste cells. Our data define for the first time the expression patterns of and during the development and maintenance of the mouse taste system and suggest that and may act together to promote lineage commitment of taste cell subtypes.
PubMed: 37181748
DOI: 10.3389/fcell.2023.1126968