Sea urchin embryos exposed to thalidomide during early cleavage exhibit abnormal morphogenesis later in development

Reichard-Brown, Jan L.; Spinner, H; McBride, Katherine

doi:10.1002/bdrb.20215

Cited by 3 publications

(3 citation statements)

References 51 publications

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“…As a result, prior drug development, in-silico alternative approaches were chosen since they do not require animal testing and are even more timeconsuming and reasonable. Four sea urchin compounds were shown to have a low toxic effect and exhibit minimal PK properties in this study [35].…”

Section: Protein-ligand Contact Mappingmentioning

confidence: 74%

Compounds identified from the marine Sea Urchin (Diadema savignyi) as Potential Anti-Cancer Drug Candidate against Human Colorectal Cancer: A Bioinformatics Approaches

Molla

Aljahdali

2022

Preprint

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The occurrence of colorectal cancer is estimated to increase by 1.9 million people by 2020, making it the second most common chronic disease. Yet, no specific drug candidates for treating this cancer have been developed or made accessible. However, the nuclear transport receptor importin-11 transports β-catenin to the nucleus and regulates the proliferation of colorectal cancer cells. The inhibition of importin-11 can block the β-catenin nuclear import and the growth of APC-mutant colorectal cancer cells. As a result, this research aimed to discover natural anti-cancer drugs that can block the function of importin-11, inhibiting the progression of colorectal cancer. The structure of 19 compounds isolated from sea urchins was initially determined using gas chromatography-mass spectrometry (GC-MS). Consequently, a molecule docking, absorption, distribution, metabolism, and excretion (ADME) approach and a molecular dynamics (MD) simulation approach were used to screen the compounds. Four molecules were initially identified with PubChem: CID 11955, CID 605775, CID 608814, and CID 6432458. Pharmacokinetics and toxicity for all compounds have been evaluated. To confirm the stability of their binding to the target protein, each compound was assessed using MD simulation methods. An in silico method revealed the top four compounds that could have pharmacological interest with a higher affinity for the target protein. Altogether, we describe here that compounds from sea urchins show interesting anti-cancer activity against importin-11, which could potentially be used to develop an anti-CRC drug. Therefore, further experimental validation is recommended to ensure a comprehensive assessment of their mechanism of action.

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Section: Protein-ligand Contact Mappingmentioning

confidence: 74%

Compounds identified from the marine Sea Urchin (Diadema savignyi) as Potential Anti-Cancer Drug Candidate against Human Colorectal Cancer: A Bioinformatics Approaches

Molla

Aljahdali

2022

Preprint

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“…If it is a human teratogen, it has been described as idiosyncratic but weakly teratogenic (Shepard et al 2002 ). For decades, human teratogens have been used to induce dysmorphogenesis in developing sea urchins with the goal of studying the basic biology of the chemical perturbation (Hagström and Lönning 1973 ; Estus and Blumer 1989a , b ; Sconzo et al 1996 ; Qiao et al 2003 ; Buznikov et al 2007 ; Reichard-Brown et al 2009 ). These studies have been predicated on the idea that the developmental cell processes and functions of sea urchins and humans may share common chemical perturbations despite the difference in organs between the species (e.g., sea urchins lack liver, kidney, lung, and brain).…”

Section: Introductionmentioning

confidence: 99%

A model-based approach to designing developmental toxicology experiments using sea urchin embryos

et al. 2022

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The key aim of this paper is to suggest a more quantitative approach to designing a dose–response experiment, and more specifically, a concentration–response experiment. The work proposes a departure from the traditional experimental design to determine a dose–response relationship in a developmental toxicology study. It is proposed that a model-based approach to determine a dose–response relationship can provide the most accurate statistical inference for the underlying parameters of interest, which may be estimating one or more model parameters or pre-specified functions of the model parameters, such as lethal dose, at maximal efficiency. When the design criterion or criteria can be determined at the onset, there are demonstrated efficiency gains using a more carefully selected model-based optimal design as opposed to an ad-hoc empirical design. As an illustration, a model-based approach was theoretically used to construct efficient designs for inference in a developmental toxicity study of sea urchin embryos exposed to trimethoprim. This study compares and contrasts the results obtained using model-based optimal designs versus an ad-hoc empirical design.

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“…One of the many aspects that intrigue scientists is the variability of thalidomide teratogenesis among species ( Table 1 ). The most commonly used animal models, rat and mouse, do not develop the classic thalidomide embryopathy (TE) phenotype, identified in a range of organisms including zebrafish ( Siamwala et al, 2012 ), chicken ( Therapontos et al, 2009 ), frogs ( Fort et al, 2000 ), rabbits ( Fabro et al, 1967 ), sea urchins ( Reichard-Brown et al, 2009 ), and opossum ( Sorensen et al, 2017 ). Mice were tested even in a dose of 4,000 mg/kg and did not develop TE, whereas humans are sensitive to its teratogenesis in a dose of 0.5 mg/kg ( Cahen, 1966 ; Stephens and Fillmore, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative Genomics Identifies Putative Interspecies Mechanisms Underlying Crbn-Sall4-Linked Thalidomide Embryopathy

et al. 2021

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The identification of thalidomide–Cereblon-induced SALL4 degradation has brought new understanding for thalidomide embryopathy (TE) differences across species. Some questions, however, regarding species variability, still remain. The aim of this study was to detect sequence divergences between species, affected or not by TE, and to evaluate the regulated gene co-expression in a murine model. Here, we performed a comparative analysis of proteins experimentally established as affected by thalidomide exposure, evaluating 14 species. The comparative analysis, regarding synteny, neighborhood, and protein conservation, was performed in 42 selected genes. Differential co-expression analysis was performed, using a publicly available assay, GSE61306, which evaluated mouse embryonic stem cells (mESC) exposed to thalidomide. The comparative analyses evidenced 20 genes in the upstream neighborhood of NOS3, which are different between the species who develop, or not, the classic TE phenotype. Considering protein sequence alignments, RECQL4, SALL4, CDH5, KDR, and NOS2 proteins had the biggest number of variants reported in unaffected species. In co-expression analysis, Crbn was a gene identified as a driver of the co-expression of other genes implicated in genetic, non-teratogenic, limb reduction defects (LRD), such as Tbx5, Esco2, Recql4, and Sall4; Crbn and Sall4 were shown to have a moderate co-expression correlation, which is affected after thalidomide exposure. Hence, even though the classic TE phenotype is not identified in mice, a deregulatory Crbn-induced mechanism is suggested in this animal. Functional studies are necessary, especially evaluating the genes responsible for LRD syndromes and their interaction with thalidomide–Cereblon.

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Sea urchin embryos exposed to thalidomide during early cleavage exhibit abnormal morphogenesis later in development

Cited by 3 publications

References 51 publications

Compounds identified from the marine Sea Urchin (Diadema savignyi) as Potential Anti-Cancer Drug Candidate against Human Colorectal Cancer: A Bioinformatics Approaches

Compounds identified from the marine Sea Urchin (Diadema savignyi) as Potential Anti-Cancer Drug Candidate against Human Colorectal Cancer: A Bioinformatics Approaches

A model-based approach to designing developmental toxicology experiments using sea urchin embryos

Comparative Genomics Identifies Putative Interspecies Mechanisms Underlying Crbn-Sall4-Linked Thalidomide Embryopathy

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