31 results about "Developmental toxicity" patented technology

The invention provides biomarker profiles of metabolites and methods for screening chemical compounds including pharmaceutical agents, lead and candidate drug compounds and other chemicals using human stem-like cells (hSLCs) or lineage-specific cells produced therefrom. The inventive methods are useful for testing toxicity, particularly developmental toxicity and detecting teratogenic effects of such chemical compounds. Specifically, a more predictive developmental toxicity model, based on an in vitro method that utilizes both hSLCs and metabolomics to discover biomarkers of developmental toxicity is disclosed.

The invention provides biomarker profiles of metabolites and methods for screening chemical compounds including pharmaceutical agents, lead and candidate drug compounds and other chemicals using human stem-like cells (hSLCs) or lineage-specific cells produced therefrom. The inventive methods are useful for testing toxicity, particularly developmental toxicity and detecting teratogenic effects of such chemical compounds. Specifically, a more predictive developmental toxicity model, based on an in vitro method that utilizes both hSLCs and metabolomics to discover biomarkers of developmental toxicity is disclosed.

The invention relates to a kit for screening drug developmental toxicity based on a C / EBP[alpha]-IGF1R gene and an application thereof. The kit contains: primers for detecting expression of C / EBP[alpha] and IGF1R gene mRNA; drug acting object mammalian cell lines or differentiated cells, and cell lines or differentiated cells having a plasmid containing an IGF1R promoter and a luciferase reportergene transferred into cells; a cell lysate; and luciferase. The determination standard of the kit comprises improvement of intracellular C / EBP[alpha] gene expression of a to-be-screened compound, reduction of IGF1R gene expression, and reduction of the activity of the luciferase reporter gene in the cells containing the IGF1R promoter-reporter gene, and the to-be-screened compound is suggested tohave developmental toxicity. The kit is novel, efficient and reliable, and can be used for high-throughput drug screening, and is of great significance for rapid detection of drugs and other compoundswith developmental toxicity.

The invention provides biomarker profiles of cellular metabolites and methods for screening chemical compounds including pharmaceutical agents, lead and candidate drug compounds and other chemicals using human embryonic stem cells (hESC) or lineage-specific cells produced therefrom. The inventive methods are useful for testing toxicity, particularly developmental toxicity and detecting teratogenic effects of such chemical compounds.

The invention discloses a calculation method for predicting the embryonic development toxicity of chemicals based on dose-effect simplified transcriptome, and belongs to the field of predictive toxicology. According to the calculation method, high-throughput testing data is systematically integrated for grading calculation to predict the embryonic toxicity of the chemicals and identify the key toxicity mechanism of the chemicals. In the calculation method, relevant evidence between key events (KE) is taken as the basis, and the high-throughput molecular testing data like the dose-effect simplified transcriptome is utilized to conduct activation grading calculation on an adverse outcome pathway (AOP) related to zebra fish development. The calculation method is more efficient and sensitive than a traditional embryonic development toxicity test and realizes efficient toxicity prediction based on the chemical toxication mechanism; by determining the influence of the low-dose chemicals on the early embryo transcriptional level, the developmental toxicity effect in a longer life stage can be predicted, the toxication mechanism of the chemicals can be identified, and the chemicals with different toxication modes can be distinguished.

The invention provides a method for evaluating the developmental toxicity of environmental pollutants by utilizing the lengths of egg yolk extension parts of Danio rerio, and belongs to the technicalfield of environmental detection technology and toxicity research. The method comprises the steps of exposing Danio rerio embryos developed to 4-5 hpf to the environmental pollutants or a control culture solution, and counting the lengths of the egg yolk extension parts of the embryos, the ratio of the lengths of the egg yolk extension parts to the total length of egg yolk spheres and the extension parts or the ratio of the lengths of the egg yolk extension parts to the lengths of the embryos when the Danio rerio embryos are developed to 60-84 hpf; and when any one of the lengths of the yolk extension parts, the ratio of the lengths of the yolk extension parts to the total length of the yolk spheres and the extension parts, and the ratio of the lengths of the yolk extension parts to the lengths of the embryos of an environmental pollutant group is obviously different from that of a control group, indicating that the environmental pollutants have developmental toxicity. Compared with egg yolk sphere development and embryo development, the development of the yolk extension parts is more sensitive to the toxicity of the environmental pollutants, the developmental retardation toxicityeffect of lower-dose environmental pollutants can be effectively evaluated, and meanwhile, the method is simple, convenient and rapid to operate and high in detection sensitivity.

A method and system of in vitro developmental toxicity testing comprising the steps of micropatterning an extracellular matrix; growing embryonic stem cells on the micropatterned extracellular matrix in the presence of mesoendermal induction and testing for change of the geometrical mesoendoderm structure in the presence or absence of a test compound wherein (1) a decrease in mesoendodermal differentiation and / or (2) a change in morphology of the geometrical mesoendoderm structure in the presence of the test compound compared to cells in the absence of the test compound indicates that the test compound is a developmental toxic agent.

This present invention provides rapid, reproducible, biomarker-based screening methods for the developmental toxicity testing of compounds. The methods are designed to identify the exposure level at which a test compound perturbs metabolism in a manner predictive of developmental toxicity. In particular, the perturbation of two metabolites, ornithine and cystine, is measured, wherein a ratio of the fold change in ornithine to the fold change in cystine of less than or equal to about 0.88 is indicative of the teratogenicity of a test compound.

The invention provides a method for evaluating the toxicity of cosmetic base materials to infant development by using zebrafish, which comprises the following steps: (1) equally selecting zebrafish embryos which develop for 24-72 hours from fertilization, exposing the zebrafish embryos in a plurality of groups of embryo culture solutions containing base materials with different gradient concentrations, and culturing for 72 hours, selecting a basic raw material concentration which has a hatching rate of more than 95% and does not cause zebrafish body organ injury and development malformation as a safe concentration; (2) averagely dividing zebrafish embryos developed for 24-72 hours from fertilization into a control group and a plurality of treatment groups, exposing the zebrafish in the treatment groups in an embryo culture solution with a safe-concentration basic raw material for culturing, and after culturing for 72 hours, measuring and evaluating heart rate, development malformation degree, ROS oxidative stress and growth and development related gene expression conditions, so as to obtain the zebrafish embryos. And evaluating the developmental toxicity of the to-be-detected basic raw material. The method disclosed by the invention is simple and convenient to operate, beneficial to large-batch raw material detection and screening work, and relatively high in accuracy.

The invention provides a method for evaluating the growth and development toxicity of triazole pesticides by using Drosophila melanogaster, belonging to the technical field of toxicity research, comprising: 1) placing the third instar larvae of Drosophila melanogaster in a container containing triazole pesticides Cultivate on solid medium, count the pupation rate, eclosion rate and body weight of Drosophila melanogaster every day; 2) place the third instar larvae of Drosophila melanogaster on solid medium to cultivate, count the pupation of Drosophila melanogaster every day rate, eclosion rate and body weight; 3) when the pupation rate, eclosion rate, body weight of the Drosophila melanogaster of described step 1) are compared with the pupation rate, eclosion rate, body weight of the Drosophila melanogaster of step 2), When there is a significant difference in any item, it indicates that triazole pesticides have growth and development toxicity. The method provided by the invention can accurately evaluate the growth and development toxicity of the triazole pesticides, and provide theoretical and experimental data support for the dosage and concentration of the triazole pesticides used rationally in agriculture.

The invention provides a method for detecting the developmental toxicity of chemicals, which at least includes the following steps: respectively inducing undifferentiated human embryonic stem cells to differentiate into cardiomyocytes under the culture conditions of the chemical to be tested and without the chemical to be tested; There is the expression level of MYL4 in the cardiomyocytes under the culture conditions of the chemicals to be tested and without the chemicals to be tested; The change in the expression level of MYL4 in is ID; according to the value of ID, combined with the Fisher discriminant function equation, the developmental toxicity of the chemical to be tested can be judged. The invention uses human embryonic stem cells to establish a developmental toxicity test model for the first time, and the developmental toxicity information of the compound can be obtained through in vitro tests in a relatively short period of time; the invention can quickly detect and prompt whether a certain chemical has developmental toxicity information for humans.

The invention discloses a calculation method for predicting the embryonic developmental toxicity of chemicals based on dose-effect simplified transcriptome, and belongs to the field of predictive toxicology. The invention predicts the embryotoxicity of chemicals and identifies the key toxicity mechanism of chemicals by systematically integrating high-throughput test data for scoring calculation. The calculation method of the present invention is based on the correlation evidence between key events (KE), and utilizes dose-effect simplified transcriptome and other high-throughput molecular test data to perform activation scoring calculation on zebrafish development-related harmful outcome pathway (AOP). The invention is more efficient and sensitive than the traditional embryonic developmental toxicity test, realizes efficient toxicity prediction based on the mechanism of chemical toxicity, and can predict the development of longer life stages through the influence of low-dose chemicals on the transcription level of early embryos Toxic effect, identify the toxic mechanism of chemicals, and distinguish chemicals with different toxic modes.

A method and system of in vitro developmental toxicity testing comprising the steps of micropatterning an extracellular matrix; growing embryonic stem cells on the micropatterned extracellular matrix in the presence of mesoendermal induction and testing for change of the geometrical mesoendoderm structure in the presence or absence of a test compound wherein (1) a decrease in mesoendodermal differentiation and / or (2) a change in morphology of the geometrical mesoendoderm structure in the presence of the test compound compared to cells in the absence of the test compound indicates that the test compound is a developmental toxic agent.

A method and system of in vitro developmental toxicity testing comprising the steps of micropatterning an extracellular matrix; growing embryonic stem cells on the micropatterned extracellular matrix in the presence of mesoendodermal induction and testing for change of the geometrical mesoendoderm structure in the presence or absence of a test compound wherein (1) a decrease in mesoendodermal differentiation and / or (2) a change in morphology of the geometrical mesoendoderm structure in the presence of the test compound compared to cells in the absence of the test compound indicates that the test compound is a developmental toxic agent.

The invention relates to a kit for screening drug developmental toxicity based on a C / EBP[alpha]-IGF1R gene and an application thereof. The kit contains: primers for detecting expression of C / EBP[alpha] and IGF1R gene mRNA; drug acting object mammalian cell lines or differentiated cells, and cell lines or differentiated cells having a plasmid containing an IGF1R promoter and a luciferase reportergene transferred into cells; a cell lysate; and luciferase. The determination standard of the kit comprises improvement of intracellular C / EBP[alpha] gene expression of a to-be-screened compound, reduction of IGF1R gene expression, and reduction of the activity of the luciferase reporter gene in the cells containing the IGF1R promoter-reporter gene, and the to-be-screened compound is suggested tohave developmental toxicity. The kit is novel, efficient and reliable, and can be used for high-throughput drug screening, and is of great significance for rapid detection of drugs and other compoundswith developmental toxicity.

The invention discloses a method for testing the developmental toxicity of environmental estrogens to silkworms, which comprises the following steps: firstly, the 5th instar silkworm larvae containing a series of concentrations of test substances are starved for 2 hours by oral gavage injection; Stomach of the silkworm was dissected to obtain tissues and organs. Toxicity endpoints include glutathione reductase activity coefficient and anti-superoxide anion free radical activity in silkworm midgut. The toxicity of the test substance to silkworm development was determined by comparing the toxicity endpoints of the exposure group and the control group. To study the effects of environmental estrogen 4‑nonylphenol on midgut development in silkworm larvae to determine its dose-effect relationship on developmental toxicity in silkworm larvae. By adopting the technical scheme of the invention, multiple biological effect endpoints can be produced on the environmental estrogen nonylphenol, and the potential risk of silkworm exposed to the estrogen environmental concentration level can be evaluated, which is a relatively fast, simple and sensitive detection method.