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Life (Basel, Switzerland) Sep 2023Understanding the mechanisms triggering the initiation of retinal regeneration in amphibians may advance the quest for prevention and treatment options for degenerating... (Review)
Review
Understanding the mechanisms triggering the initiation of retinal regeneration in amphibians may advance the quest for prevention and treatment options for degenerating human retina diseases. Natural retinal regeneration in amphibians requires two cell sources, namely retinal pigment epithelium (RPE) and ciliary marginal zone. The disruption of RPE interaction with photoreceptors through surgery or injury triggers local and systemic responses for retinal protection. In mammals, disease-induced damage to the retina results in the shutdown of the function, cellular or oxidative stress, pronounced immune response, cell death and retinal degeneration. In contrast to retinal pathology in mammals, regenerative responses in amphibians have taxon-specific features ensuring efficient regeneration. These include rapid hemostasis, the recruitment of cells and factors of endogenous defense systems, activities of the immature immune system, high cell viability, and the efficiency of the extracellular matrix, cytoskeleton, and cell surface remodeling. These reactions are controlled by specific signaling pathways, transcription factors, and the epigenome, which are insufficiently studied. This review provides a summary of the mechanisms initiating retinal regeneration in amphibians and reveals its features collectively directed at recruiting universal responses to trauma to activate the cell sources of retinal regeneration. This study of the integrated molecular network of these processes is a prospect for future research in demand biomedicine.
PubMed: 37895363
DOI: 10.3390/life13101981 -
Medical Science Monitor : International... Sep 2023Cinobufagin (CBF) is a bufadienolide, which is a major active ingredient of toad venom. In recent years, CBF has attracted increasing attention due to its highly potent...
Cinobufagin (CBF) is a bufadienolide, which is a major active ingredient of toad venom. In recent years, CBF has attracted increasing attention due to its highly potent and multiple pharmacological activities. To better understand the status of research on CBF, we collated recent studies on CBF to provide a valuable reference for clinical researchers and practitioners. According to reports, CBF exhibits extensive pharmacological properties, including antitumor, analgesic, cardioprotection, immunomodulatory, antifibrotic, antiviral, and antiprotozoal effects. Studies on the pharmacological activity of CBF have mainly focused on its anticancer activity. It has been demonstrated that CBF has a therapeutic effect on liver cancer, osteosarcoma, melanoma, colorectal cancer, acute promyelocytic leukemia, nasopharyngeal carcinoma, multiple myeloma, gastric cancer, and breast cancer. However, the direct molecular targets of CBF are currently unknown. In addition, there are few reports on toxicological and pharmacokinetic of CBF. Subsequent studies focusing on these aspects will help promote the development and application of CBF in clinical practice.
Topics: Humans; Amphibian Venoms; Bufanolides; Bone Neoplasms; Nasopharyngeal Neoplasms
PubMed: 37743616
DOI: 10.12659/MSM.940889 -
Nature Sep 2023Many animal- and plant-pathogenic bacteria use a type III secretion system to deliver effector proteins into host cells. Elucidation of how these effector proteins...
Many animal- and plant-pathogenic bacteria use a type III secretion system to deliver effector proteins into host cells. Elucidation of how these effector proteins function in host cells is critical for understanding infectious diseases in animals and plants. The widely conserved AvrE-family effectors, including DspE in Erwinia amylovora and AvrE in Pseudomonas syringae, have a central role in the pathogenesis of diverse phytopathogenic bacteria. These conserved effectors are involved in the induction of 'water soaking' and host cell death that are conducive to bacterial multiplication in infected tissues. However, the exact biochemical functions of AvrE-family effectors have been recalcitrant to mechanistic understanding for three decades. Here we show that AvrE-family effectors fold into a β-barrel structure that resembles bacterial porins. Expression of AvrE and DspE in Xenopus oocytes results in inward and outward currents, permeability to water and osmolarity-dependent oocyte swelling and bursting. Liposome reconstitution confirmed that the DspE channel alone is sufficient to allow the passage of small molecules such as fluorescein dye. Targeted screening of chemical blockers based on the predicted pore size (15-20 Å) of the DspE channel identified polyamidoamine dendrimers as inhibitors of the DspE/AvrE channels. Notably, polyamidoamines broadly inhibit AvrE and DspE virulence activities in Xenopus oocytes and during E. amylovora and P. syringae infections. Thus, we have unravelled the biochemical function of a centrally important family of bacterial effectors with broad conceptual and practical implications in the study of bacterial pathogenesis.
Topics: Animals; Bacterial Proteins; Cell Death; Fluorescein; Liposomes; Oocytes; Plant Cells; Plant Diseases; Porins; Protein Folding; Solutions; Water; Xenopus laevis; Osmolar Concentration
PubMed: 37704725
DOI: 10.1038/s41586-023-06531-5 -
Life (Basel, Switzerland) May 2024Urodelean amphibians can regenerate the tail and the spinal cord (SC) and maintain this ability throughout their life. This clearly distinguishes these animals from... (Review)
Review
Urodelean amphibians can regenerate the tail and the spinal cord (SC) and maintain this ability throughout their life. This clearly distinguishes these animals from mammals. The phenomenon of tail and SC regeneration is based on the capability of cells involved in regeneration to dedifferentiate, enter the cell cycle, and change their (or return to the pre-existing) phenotype during de novo organ formation. The second critical aspect of the successful tail and SC regeneration is the mutual molecular regulation by tissues, of which the SC and the apical wound epidermis are the leaders. Molecular regulatory systems include signaling pathways components, inflammatory factors, ECM molecules, ROS, hormones, neurotransmitters, HSPs, transcriptional and epigenetic factors, etc. The control, carried out by regulatory networks on the feedback principle, recruits the mechanisms used in embryogenesis and accompanies all stages of organ regeneration, from the moment of damage to the completion of morphogenesis and patterning of all its structures. The late regeneration stages and the effects of external factors on them have been poorly studied. A new model for addressing this issue is herein proposed. The data summarized in the review contribute to understanding a wide range of fundamentally important issues in the regenerative biology of tissues and organs in vertebrates including humans.
PubMed: 38792615
DOI: 10.3390/life14050594 -
BioRxiv : the Preprint Server For... Jan 2024Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger...
Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals.
PubMed: 37987010
DOI: 10.1101/2023.09.28.559989 -
Philosophical Transactions of the Royal... Mar 2024Thyroid hormones (TH) are central hormonal regulators, orchestrating gene expression and complex biological processes vital for growth and reproduction in variable... (Review)
Review
Thyroid hormones (TH) are central hormonal regulators, orchestrating gene expression and complex biological processes vital for growth and reproduction in variable environments by triggering specific developmental processes in response to external cues. TH serve distinct roles in different species: inducing metamorphosis in amphibians or teleost fishes, governing metabolic processes in mammals, and acting as effectors of seasonality. These multifaceted roles raise questions about the underlying mechanisms of TH action. Recent evidence suggests a shared ecological role of TH across vertebrates, potentially extending to a significant portion of bilaterian species. According to this model, TH ensure that ontogenetic transitions align with environmental conditions, particularly in terms of energy expenditure, helping animals to match their ontogenetic transition with available resources. This alignment spans post-embryonic developmental transitions common to all vertebrates and more subtle adjustments during seasonal changes. The underlying logic of TH function is to synchronize transitions with the environment. This review briefly outlines the fundamental mechanisms of thyroid signalling and shows various ways in which animals use this hormonal system in natural environments. Lastly, we propose a model linking TH signalling, environmental conditions, ontogenetic trajectory and metabolism. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.
Topics: Animals; Receptors, Thyroid Hormone; Thyroid Hormones; Vertebrates; Fishes; Amphibians; Mammals
PubMed: 38310932
DOI: 10.1098/rstb.2022.0511 -
International Journal of Molecular... Jul 2023Nitric oxide (NO) is a key signaling molecule in almost all organisms and is active in a variety of physiological and pathological processes. Our understanding of the... (Review)
Review
Nitric oxide (NO) is a key signaling molecule in almost all organisms and is active in a variety of physiological and pathological processes. Our understanding of the peculiarities and functions of this simple gas has increased considerably by extending studies to non-mammal vertebrates and invertebrates. In this review, we report the nitric oxide synthase () genes so far characterized in chordates and provide an extensive, detailed, and comparative analysis of the function of NO in the aquatic chordates tunicates, cephalochordates, teleost fishes, and amphibians. This comprehensive set of data adds new elements to our understanding of Nos evolution, from the single gene commonly found in invertebrates to the three genes present in vertebrates.
Topics: Animals; Chordata; Nitric Oxide; Nitric Oxide Synthase; Invertebrates; Vertebrates
PubMed: 37446358
DOI: 10.3390/ijms241311182 -
ELife Mar 2024Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger...
Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles, and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile, and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals.
Topics: Animals; Caspase 1; Caspases; Gasdermins; Inflammasomes; Amphibians; Reptiles; Birds
PubMed: 38497531
DOI: 10.7554/eLife.92362 -
Scientific Data Sep 2023Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative...
Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative genomics, and evolution. The brain, which serves as the material basis of consciousness, learning, memory, and behavior, is the most complex and advanced organ in axolotl. The modulation of transcription factors is a crucial aspect in determining the function of diverse regions within the brain. There is, however, no comprehensive understanding of the gene regulatory network of axolotl brain regions. Here, we utilized single-cell ATAC sequencing to generate the chromatin accessibility landscapes of 81,199 cells from the olfactory bulb, telencephalon, diencephalon and mesencephalon, hypothalamus and pituitary, and the rhombencephalon. Based on these data, we identified key transcription factors specific to distinct cell types and compared cell type functions across brain regions. Our results provide a foundation for comprehensive analysis of gene regulatory programs, which are valuable for future studies of axolotl brain development, regeneration, and evolution, as well as on the mechanisms underlying cell-type diversity in vertebrate brains.
Topics: Animals; Ambystoma mexicanum; Ascomycota; Brain; Chromatin; Learning; Mesencephalon; Single-Cell Gene Expression Analysis
PubMed: 37709774
DOI: 10.1038/s41597-023-02533-0 -
Philosophical Transactions of the Royal... Jul 2023As a class of vertebrates, amphibians, are at greater risk for declines or extinctions than any other vertebrate group, including birds and mammals. There are many... (Review)
Review
As a class of vertebrates, amphibians, are at greater risk for declines or extinctions than any other vertebrate group, including birds and mammals. There are many threats, including habitat destruction, invasive species, overuse by humans, toxic chemicals and emerging diseases. Climate change which brings unpredictable temperature changes and rainfall constitutes an additional threat. Survival of amphibians depends on immune defences functioning well under these combined threats. Here, we review the current state of knowledge of how amphibians respond to some natural stressors, including heat and desiccation stress, and the limited studies of the immune defences under these stressful conditions. In general, the current studies suggest that desiccation and heat stress can activate the hypothalamus pituitary-interrenal axis, with possible suppression of some innate and lymphocyte-mediated responses. Elevated temperatures can alter microbial communities in amphibian skin and gut, resulting in possible dysbiosis that fosters reduced resistance to pathogens. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.
Topics: Animals; Amphibians; Climate Change; Heat-Shock Response; Introduced Species; Knowledge; Mammals
PubMed: 37305907
DOI: 10.1098/rstb.2022.0132