36 results about "Animal Disease Models" patented technology

The present invention discloses the application of a 1,7-dihydro-6H-purin-6-one compound in the preparation of an anti-pulmonary fibrosis drug, which relates to the technical field of biomedicine. The application of the 1,7-dihydro-6H-purin-6-one compound of the present invention in the preparation of an anti-pulmonary fibrosis drug detects the anti-pulmonary fibrosis pharmacological activity of the 1,7-dihydro-6H-purin-6-one compound after structural modification and transformation, tests the pharmacological activity of this type of compound in a variety of animal disease models, and provides data on the activity of preventing and treating different types of pulmonary fibrosis, confirming that they all have good activity, and the effect is significantly better than the clinically commonly used positive drug nintedanib, and the effect is also better than hypoxanthine analogs A, B, and C. The application of the 1,7-dihydro-6H-purin-6-one compound of the present invention in the preparation of an anti-pulmonary fibrosis drug can provide a new skeleton for the screening of new compounds for the preparation of anti-pulmonary fibrosis drugs, and lay a theoretical foundation for the development of new lead compounds.

The invention provides an establishment method and application of a non-human primate retinal pigment epithelium injury model, and belongs to the field of animal models. The method comprises the following steps: (1) performing anesthesia and mydriasis on a non-human primate; (2) attaching a full retinoscope to the cornea, and adjusting a slit lamp so that an operator can observe the macular fovea centralis, optic disc and upper and lower vascular arches of the non-human primate; and (3) carrying out photocoagulation on the photocoagulation area by using a laser photocoagulator, and ending the photocoagulation until 250-300 primary light spots appear in the photocoagulation area. The invention provides a method for constructing a non-human primate retinal pigment epithelium (RPE) injury model by using laser by taking a non-human primate as a model animal for the first time. The model forming rate of the RPE injury animal model constructed by the invention is stable, the injury caused by the RPE injury animal model is irreversible, and a stable animal disease model is provided for clinical research and development of new drugs related to dry age-related macular degeneration caused by RPE injury.

The invention relates to the technical field of animal disease models, and discloses a construction method of an intraocular hypertension animal model, comprising the following steps: step A, selecting an experimental animal; step B, preparing experimental instruments and reagents; c, in an anesthesia mode, deep anesthesia is carried out on the animal, and subsequent deep anesthesia is carried out; d, intraocular pressure measurement, wherein the basic intraocular pressure value is measured through anterior chamber injection. Step E, performing anterior chamber injection, and using ofloxacin antibiotic oculentum to prevent infection after an operation; and F, intraocular pressure measurement: measuring the change of the intraocular pressure value after the anterior chamber injection. According to the method, the natural pathological process of open-angle glaucoma is simulated by injecting IFN-beta into the anterior chamber, the situation that acute intraocular pressure rise is caused mainly by blocking an aqueous humor flow outlet channel like other models is avoided, and the method can better reflect the real situation of glaucoma diseases; in addition, the model avoids intraocular pressure change caused by anatomical structure change, so that the accuracy and reliability of the model are improved.

The invention discloses a construction and evaluation method of a PM2.5 induced chronic obstructive pulmonary disease acute exacerbation mouse model, and relates to the technical field of disease animal models. The invention aims to evaluate whether PM2.5 can induce acute exacerbation of COPD through a mouse model, a COPD model is established by adopting combined treatment of smoking and lipopolysaccharide (LPS), and an infectious AECOPD model is established by using common klebsiella pneumoniae (KP) nasal drop on the basis. Meanwhile, PM2.5 processing is added on the basis of the COPD model, and the effect of PM2.5 on acute exacerbation of COPD is evaluated. Through comparison with a classical model (an infectious AECOPD model), the potential effect of PM2.5 in induction of acute exacerbation of COPD is evaluated, and an important reference is provided for future research on an AECOPD animal model induced by air pollution.

The present disclosure pertains to the field of animal disease models, specifically to a method for constructing an animal model of open-angle glaucoma. In this model, the pathogenesis of open-angle glaucoma is mimicked by inducing necroptosis in trabecular meshwork cells through the injection of IFN-γ into the anterior chamber. This process leads to the inhibition of trabecular meshwork activity and functional impairment, resulting in elevated intraocular pressure and subsequent optic nerve changes indicative of glaucoma. The pathophysiological alterations observed in the animal model closely resemble those seen in human open-angle glaucoma, including chamber angle opening, trabecular meshwork dysfunction, increased intraocular pressure, and loss of RGCs.

The application relates to a method for constructing a rat model of chronic obstructive pulmonary disease (COPD) related pulmonary arterial hypertension and application thereof, and belongs to the technical field of animal disease model construction. The method selects 6-8-week-old, 220+ / -10g healthy male SD rats, and all the rats are adaptively fed in a standard SPF level animal room for 7 days; then the rats are divided into a Con group and a COPD-PH group; the rats in the COPD-PH group are given 1mg / mL lipopolysaccharide by airway instillation on the first day and the 14th day; the rats are placed in a self-made whole-body inhalation smoking box for 1h every day from the 2nd day to the 13th day and from the 15th day to the 30th day; the rats enter a low-oxygen box for 8h every day during the light period from the 2nd day to the 13th day and from the 15th day to the 30th day; the rat model can simultaneously reproduce the characteristics of COPD and typical changes of pulmonary arterial hypertension, the right ventricular systolic pressure can be stably increased to 40-50mmHg, the right ventricular hypertrophy index can reach 0.40-0.50, the pulmonary vascular remodeling and inflammation are significant, and various indexes are stable and good in repeatability.

The invention belongs to the technical field of medical animal disease model modeling, and particularly discloses a dehydroepiandrosterone-induced mouse polycystic ovarian syndrome model under bisphenol A low-dose exposure, specifically, a preparation method of the model comprises the following steps: continuously injecting a mouse for 21 days according to the injection amount of dehydroepiandrosterone of 6mg / 100g; the method comprises the following steps: carrying out intragastric administration on a mouse by using 10 mg / kg of bisphenol A on the 15th day of injection of dehydroepiandrosterone, and continuously carrying out intragastric administration on the mouse for 7 days to obtain the polycystic ovarian syndrome model of the mouse at the childbearing age. According to the mouse model obtained by DHEA modeling at the early stage of adolescence and BPA exposure modeling at the late stage of adolescence, the disordered mood cycle, obesity and high T level are obviously changed; and the human PCOS disease environment and clinical phenotype can be truly simulated.

The present invention provides an engineered CRISPR enzyme and system for precise gene editing and its application, wherein the CRISPR enzyme has an amino acid sequence as shown in SEQ ID No: 1, and the gene editing system comprises a CRISPR fusion protein and a guide RNA component. The present invention is used for gene editing, gene targeting, gene cutting, preparation of gene-edited animals, establishment of animal disease models, establishment of disease tissues, preservation and transformation of animal genetic species resources of eukaryotic cells, achieving efficient gene editing, with predictable editing products and very few by-products, thus making up for the shortcomings of existing gene editing tools.

The present invention relates to the technical field of biomedicine and discloses use of a hypoxanthine derivative in the preparation of a drug for treating cardiomyopathy and / or myocardial fibrosis. By assaying pharmacological activities of structurally modified and altered hypoxanthine derivatives in treating cardiomyopathy and / or myocardial fibrosis, the pharmacological activities of such compounds were tested in various animal disease models, and data on activities for preventing and treating different types of cardiomyopathy and / or myocardial fibrosis were provided. It is proven that the hypoxanthine derivatives all have good activities, the effects are significantly superior to those of a clinically commonly used drug, nintedanib, and the effects are also significantly superior to those of hypoxanthine derivatives A, B, and C and other hypoxanthine derivatives in the prior art. The hypoxanthine derivative of the present invention can provide a novel skeleton for the screening of new compounds for the preparation of a drug for treating cardiomyopathy and / or myocardial fibrosis.

The present invention provides the use of chlorogenic acid in the preparation of a drug for preventing and treating aortic dissection. By establishing a recognized animal disease model, the pharmacological effects of chlorogenic acid are studied, and it is found and verified that chlorogenic acid has the effects of reducing the morbidity and mortality of aortic dissection; slowing down aortic dilation; and protecting the smooth muscle layer. This proves the use of chlorogenic acid in preventing and treating aortic dissection, and provides a solid pharmacodynamic basis for new clinical research and application of the drug.

The present invention discloses a use of a hypoxanthine compound in preparing a drug for treating pulmonary fibrosis and relates to the technical field of biological medicines. In the use of the hypoxanthine compound in preparing the drug for treating the pulmonary fibrosis, through pharmacological activity detection for treatment of pulmonary fibrosis with hypoxanthine compounds subjected to structural modification and transformation, the pharmacological activities of such the compounds in various animal disease models are tested and data about the activities of preventing and treating different types of pulmonary fibrosis are provided, which proves that the hypoxanthine compounds have good activities, with an effect being obviously superior to that of a positive drug Nintedanib commonly used in clinic, and that of hypoxanthine analogues A, B, C and D as well as other hypoxanthine analogues in the prior art. The use of the hypoxanthine compound in preparing the drug for treating the pulmonary fibrosis can provide a novel skeleton for screening novel compounds for preparing drugs for treating pulmonary fibrosis and lay a theoretical foundation of developing a novel lead compound.

The present invention discloses a use of a hypoxanthine compound in preparing a drug for treating pulmonary fibrosis and relates to the technical field of biological medicines. In the use of the hypoxanthine compound in preparing the drug for treating the pulmonary fibrosis, through pharmacological activity detection for treatment of pulmonary fibrosis with hypoxanthine compounds subjected to structural modification and transformation, the pharmacological activities of such the compounds in various animal disease models are tested and data about the activities of preventing and treating different types of pulmonary fibrosis are provided, which proves that the hypoxanthine compounds have good activities, with an effect being obviously superior to that of a positive drug Nintedanib commonly used in clinic, and that of hypoxanthine analogues A, B, C and D as well as other hypoxanthine analogues in the prior art. The use of the hypoxanthine compound in preparing the drug for treating the pulmonary fibrosis can provide a novel skeleton for screening novel compounds for preparing drugs for treating pulmonary fibrosis and lay a theoretical foundation of developing a novel lead compound.

The present invention belongs to the field of biotechnology, and specifically relates to a Cacna1h mutant and its applications. The present invention first discloses a Cacna1h protein mutant, which has the following mutation compared with the wild-type Cacna1h protein: p.S1436P; this mutant is related to airway stenosis and can be used as a diagnosis and treatment target for airway stenosis. By detecting this mutant, airway stenosis can be diagnosed, monitored, evaluated for therapeutic efficacy, or prognosed, and the effect of preventing and treating airway stenosis can be achieved by reversing this mutant to the wild-type; moreover, this mutant can be used to construct an animal model of airway stenosis, which is more in line with the human gene mutation mode compared with the large gene fragment deletion in the traditional method, and the obtained animal model is more in line with the animal disease model of human diseases.

The present invention relates to the technical field of biomedicine and discloses use of a hypoxanthine derivative in the preparation of a drug for treating renal fibrosis and / or kidney disease. By assaying pharmacological activities of structurally modified and altered hypoxanthine derivatives for treating renal fibrosis and / or kidney disease, the pharmacological activities of such compounds were tested in animal disease models, and data on activities for preventing and treating renal fibrosis and / or kidney disease were provided. It is proven that the hypoxanthine derivatives have good activities, and the effects are significantly superior to those of clinically commonly used positive drugs nintedanib and losartan, and the effects are also significantly superior to those of hypoxanthine derivatives A, B, and C and other hypoxanthine derivatives in the prior art. The hypoxanthine derivative of the present invention can provide a novel skeleton for the screening of novel compounds for the preparation of a drug for treating renal fibrosis and / or kidney disease.

The invention relates to the technical field of animal disease models, in particular to a modeling method of a Crohn disease mouse model, which comprises the following steps: step 1, drinking a mouse to be injured with 0.5-2% dextran sodium sulfate aqueous solution, and continuously feeding the mouse with animal feed for 3-10 days as an injury period; step 2, drinking the mouse subjected to DSS injury with purified water, and continuously feeding the mouse with animal feed for 6-20 days as a recovery period; and step 3, sequentially adopting the step 1 and the step 2 as a DSS injury cycle on the mouse in the step 2, and circularly treating for 1-4 times to obtain the Crohn disease mouse model. According to the invention, an animal model of high-protein diet combined with low-concentration DSS enteritis injury of young mice is established, and clinical phenotypes of Crohn's disease are more fully simulated, including the characteristics that intestinal inflammation which is difficult to repair still continuously exists after DSS administration is stopped, penetrating fibrosis repair is accompanied by slow and acute inflammatory cell infiltration, and'beaded 'lymphatic follicular hyperplasia and the like.

The present invention relates to the technical field of biomedicine. Disclosed is use of a hypoxanthine derivative in the preparation of a drug for treating peritoneal diseases. By detecting the pharmacological activity of structurally modified and engineered hypoxanthine derivatives in treating peritoneal diseases, the pharmacological activity of such compounds is tested in various animal disease models, and data on their activity in preventing and treating different types of peritoneal diseases are provided, confirming that the hypoxanthine derivatives all exhibit good activity. The effect is significantly better than that of a commonly used clinical drug, nintedanib, and the effect is also significantly better than that of hypoxanthine derivatives A, B, and C, and other hypoxanthine derivatives in the prior art. The hypoxanthine derivatives provided in the present invention can offer a novel scaffold for the screening of new compounds for the preparation of drugs for treating peritoneal diseases, laying a theoretical foundation for the development of novel lead compounds.

The invention relates to the technical field of medical animal disease models, in particular to a method for establishing a gene point mutation non-human primate model.According to the method, editing is conducted through a CRISPR / Cas9 gene editing system, and finally a non-human primate model carrying CHD8c.3724Cgt is obtained; according to the cynomolgus monkey with T (p.Arg1242Ter) point mutation, different types of point mutations occur at the 3724th basic group of the CHD8 gene, the mutation of T enables arginine (Arg) at the 1242nd site to be replaced by a termination codon to form truncated protein, so that the dosage of CHD8 protein haploid coded by the gene is insufficient. The animal model for simulating human CHD8 mutation related nervous system diseases is constructed and can be used as an ideal research model for researching autism related phenotypes caused by insufficient haplodose, and a foundation is laid for revealing a neurological dysfunction mechanism and exploring a potential treatment strategy.

The invention relates to the technical field of biological medicines, and discloses an application of an inoxanthine derivative in preparation of a medicine for treating peritoneal diseases, the pharmacological activity of the compound is tested in various animal disease models by detecting the pharmacological activity of the inoxanthine derivative subjected to structure modification and transformation in treatment of peritoneal diseases, and the application of the inoxanthine derivative in preparation of the medicine for treating peritoneal diseases is provided. The invention also provides data of activity of preventing and treating different types of peritoneal diseases, which proves that the compound has good activity, the effect is obviously superior to that of a clinically common drug nintedanib, and the effect is also obviously superior to that of hypoxanthine derivatives A, B and C and other hypoxanthine derivatives in the prior art. The hypoxanthine derivative provided by the invention can provide a novel skeleton for screening a novel compound for preparing a medicine for treating peritoneal diseases, and lays a theoretical foundation for developing a novel lead compound.

The invention relates to the field of animal disease models, and discloses an improved progressive immune checkpoint inhibitor related myocarditis mouse model as well as a construction method and application thereof. The construction method of the model comprises the steps that 0.1 mL of a Freund's complete adjuvant mixed solution is subcutaneously injected into a mouse on the 0th day and the 7th day, and the solution contains 0.25 mg of a mouse cardiac troponin I immunogenic peptide fragment; the method is characterized in that a PD-1 inhibitor and a CTLA-4 inhibitor are jointly injected into a mouse in a caudal vein mode at the frequency of one time every two days from the eighth day, the injection dosage of each drug is 5 mg / kg per time, and the injection process is carried out for 5 times in total. According to the application, cardiac inflammation caused by ICIs drugs is induced through combined use of various reagents, and a disease outcome stage of a patient in the real world is perfectly simulated through dose control and injection method improvement, so that a bedding effect is achieved for clinical research and drug test.

The invention belongs to the technical field of biology, and particularly relates to a Cacna1h mutant and application thereof. The invention discloses a Cacna1h protein mutant for the first time, and compared with a wild type Cacna1h protein, the Cacna1h protein mutant has the following mutations: p.S1436P; the mutant is related to the airway stenosis and can be used as a diagnosis and treatment target of the airway stenosis, diagnosis, monitoring, curative effect evaluation or prognosis evaluation can be performed on the airway stenosis by detecting the mutant, and the effect of preventing and treating the airway stenosis can be achieved by reversing the mutant into a wild type; the mutant can be used for constructing an airway stenosis animal model, compared with gene large fragment deletion in a traditional method, the mutant is more in line with a human gene mutation mode, and the obtained animal model is more in line with an animal disease model of human diseases.

The invention relates to a mutant protein related to Alzheimer's disease, a disease model and a pharmaceutical composition. The mutant protein is characterized in that phenylalanine at the 237th site of an amino acid sequence of PSEN1 protein is mutated into leucine (PSEN1p.F237L), and the mutant protein is associated with the Alzheimer's disease. The invention finds that the mutation affects the interaction of PSEN1 protein and calcium channel proteins (such as SERCA2 and RyR2), resulting in neuron calcium homeostasis imbalance, energy metabolism disorder and endoplasmic reticulum stress. The invention constructs a neuron animal disease model based on the mutation, simulates the pathological process of Alzheimer's disease, and is used for drug mechanism research and screening. Meanwhile, the invention provides a pharmaceutical composition aiming at a PSEN1 mutation related pathological process, and the pharmaceutical composition is used for improving calcium ion homeostasis, mitochondrial dysfunction and endoplasmic reticulum stress. The scheme provided by the invention can be used for Alzheimer disease pathogenic mechanism research, drug screening and treatment strategy development.

The invention belongs to the field of bioengineering and biomedicine, further relates to construction and introduction of an animal disease model, and particularly relates to a humanized gene mutation pathogenic model as well as preparation and application thereof. According to the invention, a mouse-based humanized COL2A1p.G204A mutation pathogenic model is constructed by using a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system through an optimized sgRNA (single guide ribonucleic acid) and a homologous recombination template (donor). The mouse model not only can be used for researching the pathogenic reason of COL2A1p.G204A mutation, but also can be used for developing a gene therapy scheme of the mutation type and the like.

The invention relates to the technical field of biological medicines, and discloses an application of an inosine derivative in preparation of medicines for treating non-alcoholic fatty liver diseases and hepatic fibrosis, and the pharmacological activity of the inosine derivative subjected to structural modification and transformation in treatment of the non-alcoholic fatty liver diseases and / or hepatic fibrosis is detected. The pharmacological activity of the compound is tested in various animal disease models, and data for preventing and treating different types of non-alcoholic fatty liver diseases and / or hepatic fibrosis activity is provided, so that the compound is proved to have good activity, and the effect is obviously superior to that of a clinically common positive drug nintedanib; the effect is obviously superior to those of hypoxanthine derivatives A, B and C and other hypoxanthine derivatives in the prior art. The hypoxanthine derivative disclosed by the invention can provide a novel skeleton for screening a novel compound for preparing a medicine for treating the non-alcoholic fatty liver disease and / or hepatic fibrosis, and lays a theoretical foundation for developing a novel lead compound.

The invention provides an application of chlorogenic acid in preparation of a medicine for preventing and treating aortic dissection, and the pharmacological action of chlorogenic acid is studied by establishing a recognized animal disease model to find and verify that chlorogenic acid has the effects of reducing the morbidity and mortality of the aortic dissection; the aortic dilatation is retarded; the application of chlorogenic acid in prevention and treatment of aortic dissection is proved, and a solid pharmacodynamic basis is provided for new clinical research and application of the medicine.

The invention relates to a construction method and application of an ANGPTL3 overexpression laying hen fatty liver hemorrhagic syndrome model, and the construction method comprises the following steps: (1) respectively integrating a transposon element carrying a chicken ANGPTL3 coding gene and a transposase gene into an adenovirus vector, and obtaining a recombinant adenovirus by using a virus packaging system; (2) punching the chick embryos developed for 4 days (E4) by adopting an equatorial plane windowing method; (3) introducing the recombinant adenovirus into an E4 chick embryo body in a microinjection manner; and (4) hatching to laying hens to prepare the laying hen fatty liver hemorrhagic syndrome model. The animal disease model is constructed on poultry through protein overexpression for the first time, and the laying hen fatty liver hemorrhagic syndrome model does not need to be fed with high-fat feed and has the advantages of being accurate in animal model construction, remarkable in fatty liver characterization and high in efficiency. The method has a great application value in research on the fatty liver hemorrhagic syndrome of laying hens and drug development and screening of poultry.

The invention discloses a construction method of an ischemic nerve injury animal model, and belongs to the technical field of animal disease models.The method comprises the steps that juvenile zebrafish serves as a research object, and after being treated with a cobalt chloride aqueous solution, the juvenile zebrafish is subjected to behavioral detection and brain Hamp; e, dyeing and red blood cell red fluorescence labeling detection to realize multi-dimensional evaluation; according to the method, the model organism of the juvenile zebrafish is applied, the limitation of a traditional mammal model is broken through, the experiment cost is greatly reduced, meanwhile, the reliability of the model is improved by adopting a behavior-tissue-blood flow multi-dimensional evaluation system, and high-throughput screening is adapted by relying on the characteristics of the juvenile zebrafish; and an efficient tool is expected to be provided for research and development and mechanism research of neuroprotective drugs.

A use of an RIPK1 inhibitor in the prevention and treatment of vascular injury and diabetes. Specifically provided are a method for regulating the levels of spermidine and acetylated spermidine and a use of the RIPK1 inhibitor in the prevention and treatment of related diseases caused by decreased levels of spermidine and acetylated spermidine due to arylamine N-acetyltransferase 2 deficiency or other reasons, including aging, diabetes, and other diseases with vascular injury. It has been demonstrated by means of a related animal disease model that the inhibition of RIPK1 kinase activity can treat vascular injury in the animal model, and related diseases and symptoms caused by vascular injury, such as weight gain, inflammation, insulin resistance, impaired glucose tolerance, lipid and amino acid metabolism disorders, and pancreatitis, thereby providing a novel and effective intervention for the treatment of human vascular injury, aging, and diabetes-related diseases and symptoms.

The invention relates to the field of animal disease models, and discloses a construction method and application of a GJB2 gene p.V37I point mutation animal model, the GJB2 gene of a normal animal is changed, and the 37th site codon GTG of the GJB2 gene is mutated into ATA, so that the animal model with the same mutation as the human GJB2 gene p.V37I point mutation is obtained. According to the invention, a CRISPR / Cas9 editing technology is utilized, double-base modification is accurately carried out, and a knock-in mouse model of which a specific gene is mutated into p.V37I is constructed instead of pure c.109Ggt; a base mutation is knocked in. Further research finds that the animal model has delayed progressive hearing loss, and the animal model can be used as a novel animal model for exploring the occurrence and development etiology and mechanism of the hearing loss related to p.V37I point mutation of the GJB2 gene; the mutation animal model is closer to actual mutation of human amino acid, the accuracy and correlation of research are improved, and the potential of basic research and clinical application is further improved.

The application relates to the technical field of animal disease models, and discloses a pathological myopia animal model establishment method and application without eye intervention, which comprises the following steps: using a Hemin solution to intervene in an animal to obtain a pathological myopia animal model. The method can establish a pathological myopia animal model.

The application discloses an adenine deaminase, an adenine base editor comprising the same and application thereof. The adenine deaminase has one or more amino acid mutations at positions 29, 84, 108 and 145 of an amino acid sequence as shown in SEQ ID NO: 1. The adenine base editor of the application comprises a nuclease and the adenine deaminase, can effectively destroy the non-specific binding of the adenine deaminase to a substrate base, narrow the editing window to 1-2 bases, maintain a high editing activity, change the structure pocket caused by the mutation, make the adenine deaminase unable to recognize cytosine as a substrate, finally completely eliminate the independent cytosine editing event existing in the ABE, keep a low indel, improve the safety, promote the application in precision medicine, animal disease model preparation, crop genetic breeding and the like, and have great application value.