1081results about "Compounds screening/testing" patented technology

The invention belongs to the technical field of biological medicines, and provides application of DRAM1 as a diagnosis and treatment target for resisting non-alcoholic fatty liver disease related hepatocellular carcinoma in preparation of a kit, a carrier and a medicine aiming at the problem of lack of effective treatment targets of NAFLD-related HCC. As a target spot for resisting the non-alcoholic fatty liver disease related hepatocellular carcinoma, the expression level of the DRAM1 in liver tissues of non-alcoholic fatty liver disease related hepatocellular carcinoma patients and mice is increased. According to the application disclosed by the invention, research is developed aiming at the effect of the DRAM1 in the generation and development of NAFLD-related HCC, the analysis of TCGA liver cancer queue data and a GSE164760 data set is taken as an entry point, the influence of the DRAM1 on the diagnosis and prognosis of the liver cancer is comprehensively analyzed, and verification is carried out through a mouse in-vivo experiment, so that a new thought and a new target spot are provided for clinical diagnosis and treatment of the liver cancer.

The invention belongs to the technical field of biology, and particularly relates to a cryptosporidium parvum infection immunosuppression mouse model and a construction method thereof. Aiming at the problem that the development of cryptosporidiosis drugs and vaccines is seriously limited due to the fact that no model for successfully infecting mice with cryptosporidium parvum exists at present, the invention provides the construction method of the cryptosporidium parvum infection immunosuppression mouse model, which comprises the following steps: firstly, carrying out gavage treatment on the mice for 4-7 days by adopting cyclophosphamide; constructing to obtain an immunosuppressive mouse; feeding PBS (Phosphate Buffer Solution) containing cryptosporidium parvum oocysts through the mouth, and infecting for 7-21 days; and when oocysts are continuously detected from excrement of the mouse and the content of the oocysts is higher than the infection amount, constructing the cryptosporidium parvum infection immunosuppression mouse model. The cryptosporidium parvum infection immunosuppression mouse model is successfully constructed, can be used for subsequent drug and vaccine development tests for cryptosporidium parvum diseases, and has a good application prospect.

The invention discloses a preparation method and application of a self-reactive animal model. An autoreactive animal model is constructed based on an SWHEL system, it is found through the model that MTCH2 is a key target for regulating and controlling B cell autoreactivity, deletion of MTCH2 will cause generation of a large number of autoreactive B cells subjected to antibody category conversion, the disease risk is increased, and a basis is provided for research of B cell autoreactivity related mechanisms.

The invention belongs to the technical field of biology, and particularly relates to an SLC44A1 gene and / or SLC44A5 gene knockout animal model as well as a construction method and application thereof. The construction method of the animal model comprises the following steps: deleting exon regions from the fourth exon region to the thirteenth exon region of the SLC44A1 gene and / or the second exon region of the SLC44A5 gene in mouse brain oligodendroglia cells in a high-efficiency manner by utilizing gene editing and a Cre-loxP recombinase system, so as to realize the knockout of a target gene. The animal model constructed by the invention can be used for researching the regulation mechanism of the choline transporters (SLC44A1 and SLC44A5) on myelin sheath formation, deeply knowing the biological functions of the choline transporters (SLC44A1 and SLC44A5), simulating the occurrence and development processes of human related diseases, revealing the pathogenesis of the related diseases, providing a new thought for prevention and treatment of brain myelin sheath dysplasia, and providing a new foundation for the prevention and treatment of brain myelin sheath dysplasia. And an effective drug or a treatment mode aiming at the disease is screened by utilizing a gene knockout animal model, so that a new choice is provided for clinical treatment of the disease.

The invention provides a hydrogel microneedle patch for treating oral ulcer and a preparation method, and belongs to the technical field of biomedical engineering. The technical problems that in the traditional oral ulcer administration process, medicine is difficult to retain at the focus for a long time, is easily scoured by saliva and is influenced by tongue and cheek movement are solved. According to the technical scheme, the method comprises the following steps: 1) designing and preparing a microneedle patch mold; (2) synthesizing drug-loaded polydopamine nano particles; (3) preparing a microneedle patch; and 4) evaluating the performance of the microneedle patch. The invention has the following beneficial effects: on one hand, the combination of the drug-loaded nanoparticles and the hydrogel microneedle array can reduce the dosage through drug sustained release; and on the other hand, the problems of high drug instability, low targeting property, poor bioavailability and hindering treatment effect are effectively solved, and the preparation can be widely applied to the fields of drug sustained release, wound healing, tissue engineering and the like.

The invention provides a composition with an instant and long-acting anti-aging effect and application thereof. The composition comprises a component A, a component B and a component C, the mass ratio of the raw materials is (1-10): (1-4): (0.05-0.2); the component A is prepared from the following components in parts by weight: 0.01 to 0.5 part of acetyl octapeptide-3, 0.01 to 0.5 part of dipeptide diaminobutyryl benzyl amide diacetate, 0.001 to 0.2 part of arginine / lysine polypeptide, 0.3 to 1 part of caprylyl glycol and 96 to 100 parts of water; the component B is prepared from the following components in parts by weight: 0.001 to 0.2 part of soluble collagen, 5 to 30 parts of glycerol, 0.01 to 0.5 part of sodium dihydrogen phosphate, 0.001 to 0.2 part of disodium hydrogen phosphate and 65 to 100 parts of water; and the component C is tripeptide-29. According to the invention, the quadruple wrinkle fading polypeptide is adopted to block wrinkles in a multi-target full-link manner, so that the product has a very good effect of fading various wrinkles in real time.

The invention provides a chronic hypoperfusion animal model construction method and application thereof, and relates to the technical field of biomedicine. The construction method of the chronic hypoperfusion animal model, provided by the invention, aims at brain capillary endothelial cells, and the constructed chronic hypoperfusion animal model is global and lasting brain hypoperfusion, has no infection or death risk and is low in cost. The animal model constructed by using the method is more convincing in the aspects of reperfusion research and drug curative effect evaluation.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The invention provides an application of WNT7B in construction of a myopia animal model. Homologous genes wnt7ba and wnt7bb of the WNT7B in the zebra fish are knocked out or knocked down by applying a CRISPR / Cas9 gene editing technology, an animal model of which the eye axis length is remarkably increased, the eyeball movement frequency is remarkably reduced and the light response is reduced is obtained, and the result shows that the WNT7B is related to the high myopia. The model provides a favorable tool for pathogenesis and drug screening of high myopia, and has a good application prospect.

The invention discloses a humanized osteoporosis mouse model and a construction method thereof, and belongs to the technical field of biotechnology and animal models. The invention aims at the core defects of large species difference, insufficient humanization degree, low pathological simulation degree, unstable phenotype and the like of the existing osteoporosis model. The humanized osteoporosis mouse model is constructed through five core steps of experimental animal pretreatment, collagen-nano hydroxyapatite bionic scaffold preparation and cell pre-implantation, immune-bone metabolism double-derived system construction, progressive osteoporosis induction and model identification and verification. According to the method, double-person origination of immune and bone metabolism systems is realized for the first time, the colonization rate and survival time of human cells are greatly improved, the pathological process of clinical postmenopausal osteoporosis is accurately simulated, the phenotype of the model is stable and uniform, the reactivity matching degree with clinical drugs is high, and the method can be widely applied to research and development of anti-osteoporosis drugs and research of pathological mechanisms.

The invention provides a dilated cardiomyopathy zebrafish model and a construction method and application thereof, and belongs to the technical field of biology.The dilated cardiomyopathy zebrafish model is constructed by overexpressing miR-16-5p in myocardial cells of zebrafish, and the sequence of miR-16-5p is shown as SEQ ID NO.1; the invention further provides a construction method of the dilated cardiomyopathy zebra fish model. The invention constructs the dilated cardiomyopathy zebrafish model of overexpression miR-16-5p in myocardial cells for the first time, and the dilated cardiomyopathy zebrafish model can be used for screening drugs for resisting dilated cardiomyopathy.

The invention discloses a method for establishing an animal model for age-related retinopathy caused by lipid metabolism disorder, and the animal model is obtained by specifically knocking out Lss genes from mouse retinal pigment epithelium (RPE) cells by means of a CRISPR / Cas9 gene editing technology. The age-related retinopathy model mouse constructed by the invention shows a retinopathy phenotype with retinal lipid deposition and reduced visual function at the age of 5 months, and the retinopathy is further aggravated along with the increase of the age of the mouse and is similar to the phenotype of age-related retinopathy related to lipid metabolism disorder clinically; and an ideal and effective animal model is provided for researching age-related retinopathy.

The invention relates to an application of a CTHRC1 inhibitor in preparation of a medicine for preventing and / or treating arthritis. Specifically, the invention provides application of an inhibitor or an antagonist of a CTHRC1 gene or a protein thereof, the inhibitor or the antagonist is used for preparing a composition or a preparation, and the composition or the preparation is used for (a) preventing and / or treating arthritis-related diseases; and / or (b) inhibiting cartilage cell senescence.

The invention provides a GelMA microneedle patch loaded with chromogenic gold nano bipyramids and a preparation method thereof.The method comprises the steps that citric acid, chloroauric acid and a CTAC solution are mixed, then sodium borohydride is added, and a seed solution is obtained through stirring and standing; mixing chloroauric acid, silver nitrate, hydrochloric acid and CTAB (cetyltrimethyl ammonium bromide), and sequentially adding ascorbic acid and the seed solution to obtain a growth solution; carrying out centrifugation, morphology regulation and chemical etching purification to obtain a chromogenic gold nano bipyramid solution; the preparation method comprises the following steps: reacting gelatin with methacrylic anhydride in PBS, dialyzing and freeze-drying to obtain GelMA; dissolving GelMA in the gold nanoparticle bipyramid solution, and adding a photoinitiator LAP to obtain a mixed precursor solution; and the GelMA microneedle patch loaded with the gold nano bipyramid is prepared through mold casting, centrifugation, ultraviolet light crosslinking and drying demolding. The microneedle extraction and gold nano bipyramid color development integrated scheme is initiated, blood sampling is not needed, the dermis interstitial fluid is extracted in a minimally invasive mode through the microneedle, detection pain and trauma are reduced, the cross infection risk of blood treatment is avoided, and the microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle microneedle

Described are compositions and methods for increasing opioid therapy efficacy and ameliorating opioid use disorder. The compositions and methods target Ptchd1 or neuronal cholesterol.

The invention discloses an engineered macrophage and a pharmaceutical composition and application thereof, and CCM3 expression in the engineered macrophage is inhibited, so that the engineered macrophage is polarized towards the M2 direction or the engineered macrophage is an M2 type macrophage. Besides, the invention further develops a temperature-sensitive cell-loaded hydrogel preparation which can promote polarization of macrophages in the M2 direction by inhibiting expression of signal molecules CCM3 on adhesion spots, and the temperature-sensitive cell-loaded hydrogel preparation can promote bone defect immune osteogenesis through local injection.

The invention relates to a construction method of a thyroid-related eye disease animal model, and belongs to the technical field of biology. The invention provides a thyroid-associated ophthalmopathy animal model construction method, which comprises: (1) separating and purifying in vitro peripheral blood collected from a thyroid-associated ophthalmopathy patient to obtain an exosome; and (2) injecting the exosome into a to-be-modeled animal to prepare the thyroid-associated ophthalmopathy animal model. According to the invention, exosomes are extracted from in-vitro peripheral blood of patients with thyroid-associated ophthalmopathy and are injected into animals, so that the thyroid-associated ophthalmopathy animal model with a plurality of pathological characteristics such as orbital tissue inflammatory response, fibrosis, orbital lesion, thyroid dysfunction and the like is successfully constructed; the method can be widely applied to pathological mechanism research of thyroid-related eye diseases and screening and evaluation of thyroid-related eye disease treatment drugs.

The invention provides a construction method and application of a dilated cardiomyopathy animal model, belongs to the technical field of biological medicine and animal genetic model construction, and provides a novel dilated cardiomyopathy zebrafish model which is constructed by specifically overexpressing a truncated dnajb6b gene long isomer fragment in zebrafish myocardial cells. The nucleotide sequence of the gene segment is as shown in SEQ ID NO. 1; the invention also provides a construction method and application of the dilated cardiomyopathy zebra fish model, and further discovers application of 4-phenylbutyric acid in preparation of drugs for treating dilated cardiomyopathy.

The invention belongs to the technical field of biology, and particularly relates to a human metapneumovirus mouse adapted strain and application thereof. Compared with a wild strain, the strain has higher susceptibility to animals; the strain can be used for treating BALB / c mice and can cause typical clinical symptoms and even death, for example, after the strain infects the BALB / c mice, the disease symptoms are obvious, the weight of 83% infected mice is severely reduced to 75% or below and reaches the humanity killing standard, and the death rate reaches 50% or above 4 days after the strain infects the BALB / c mice; the strain can be used for constructing a cell model or an animal model of human metapneumovirus infection or diseases caused by the human metapneumovirus infection, and is further used for screening drugs for preventing and / or treating the human metapneumovirus infection or the diseases caused by the human metapneumovirus infection. In addition, the strain can also be used for preparing medicines for preventing and / or treating human metapneumovirus infection or diseases caused by the human metapneumovirus infection, preparing antibodies or antiserum for resisting the human metapneumovirus and the like.

A model that closely resembles human excessive myopia can be prepared by mounting a minus lens (2) and a protector (4) to a juvenile mouse, the minus lens having an angle and a width adjustable in response to growth of the mouse. Further, this model analysis shows that myopia induction causes endoplasmic reticulum stress in a sclera and the endoplasmic reticulum stress induces myopia. Furthermore, it is revealed that an endoplasmic reticulum stress suppressant, particularly, phenylbutyrate and tauroursodeoxycholic acid act as a myopia prevention / suppression agent.

The invention discloses application of compound fresh bamboo juice in a young group cough model, and relates to the field of medicines.The application comprises the following steps that S1, a cough model is constructed by adopting young beagles, and whether the cough model is successfully constructed or not is verified through behavioral observation, hematological analysis, CT examination and alveolar lavage analysis of the young beagles; and S2, evaluating the efficacy and safety of the successfully constructed young beagle by using a compound fresh bamboo juice. According to the invention, a technical system for evaluating the efficacy of the compound fresh bamboo juice in the cough model of the young beagle is established by taking the young beagle as a research object. In a puppy beagle model, the compound fresh bamboo juice shows good safety, and the medicine remarkably improves target symptoms. The results provide powerful support for the potential curative effect of the compound fresh bamboo juice in children.

Disclosed herein are monoclonal antibodies and antigen-binding fragments thereof capable of selectively inhibiting TGFβ1 with high potency. Related compositions, methods and therapeutic use are also disclosed.

The invention provides a hypertrophic cardiomyopathy zebrafish model and a construction method and application thereof, and belongs to the technical field of biology, the hypertrophic cardiomyopathy zebrafish model is constructed by overexpressing miR-29a in myocardial cells of zebrafish, and the sequence of the miR-29a is shown as SEQ ID NO.1; the invention further provides a construction method of the hypertrophic cardiomyopathy zebra fish model. The hypertrophic cardiomyopathy zebrafish model Tg (cmlc2: miR-29a, EGFP) with overexpression of miR-29a in myocardial cells is constructed for the first time, and the hypertrophic cardiomyopathy zebrafish model Tg (cmlc2: miR-29a, EGFP) can be used for screening drugs for resisting hypertrophic cardiomyopathy.

The invention relates to the field of biology, and provides a human immortalized pancreatic cancer fibroblast as well as a preparation method and application thereof.The human immortalized pancreatic cancer fibroblast comprises three cell strains which are all primary fibroblast cells extracted from tumor tissues of pancreatic ductal adenocarcinoma patients, the human pancreatic cancer fibroblast cell strain CAFPC-2209131, the human pancreatic cancer fibroblast cell strain CAFPC-2209132 and the human pancreatic cancer fibroblast cell strain CAFPC-2303221 are classified and named as the human pancreatic cancer fibroblast cell strain CAFPC-2209131, the human pancreatic cancer fibroblast cell strain CAFPC-2209132 and the human pancreatic cancer fibroblast cell strain CAFPC-2303221 respectively, the human pancreatic cancer fibroblast cell strain CAFPC-2209132 and the human pancreatic cancer fibroblast cell strain CAFPC-2303221 are all Cell STR identification and immunofluorescence detection prove that the cell strain is a fibroblast cell strain. After the tumor-associated fibroblast and pancreatic cancer cells are co-cultured, the proliferation ability of the tumor cells is obviously enhanced, and the sensitivity of the tumor cells to a chemotherapeutic drug gemcitabine is reduced. A new thought is provided for diagnosis and treatment of pancreatic cancer, and based on the pancreatic cancer in-vitro co-culture model established in vitro, the application has important significance for researching the effect and related mechanisms of fibroblasts in the pancreatic cancer tumor microenvironment.

The invention relates to a multiple myeloma model with extramedullary lesion as well as a construction method and application thereof. The multiple myeloma model is obtained by injecting bone marrow mononuclear cells (BMMC) of a multiple myeloma patient into an hIL-6NSG mouse. The invention provides a new model of multiple myeloma with extramedullary lesion, which not only is beneficial to research on gene pathway and mechanism of the multiple myeloma, but also lays a foundation for research on tumor recurrence, preclinical drug screening, effect evaluation and the like, and has great significance in promoting disease healing.

The invention relates to an establishment method and application of in-vitro intestinal inflammation models of mice of different ages, and relates to the technical field of biology. According to the invention, young, adult, middle-aged and old wild type (WT) and TLR4 gene deletion type (TLR4 <- / ->) mice are selected, colon tissues are cultured in vitro, inflammatory response is induced by using interleukin-1beta (IL-1beta) stimulation, an age-related intestinal inflammation model is constructed, the inflammation phenotype of the mouse model and the activity of a TLR4 / MyD88 / NF-kappa B signaling pathway are determined by comparing WT and TLR4 <- / ->, and the age-related intestinal inflammation model is constructed. The core function of the TLR4 in regulating age-dependent intestinal barrier dysfunction is defined, a regulatory network of the TLR4 in intestinal immune aging and flora-host interaction is disclosed, and an age personalized medical strategy is promoted. According to the invention, an efficient and customizable multi-age in-vitro intestinal inflammation model is constructed, and an innovative platform is provided for mechanism analysis and intervention drug screening of TLR4 targeted therapy and age-related intestinal diseases.

The present disclosure provides a method of producing a non-human mammalian animal model comprising human neural tissue, the method comprising introducing a first human neural organoid into a central nervous system location of a newborn non-human mammal; and allowing the newborn non-human mammal to mature to produce the non-human mammalian animal model comprising human neural tissue. The present disclosure provides a method of modeling a neuropsychiatric disorder. The present disclosure also provides a method of determining the effectiveness of a candidate agent on a neuropsychiatric disorder. The present disclosure provides a method for altering the behavior of a mammal. Also provided are non-human mammalian animal models comprising human neural tissue.

The invention relates to the field of bioengineering, in particular to a bilateral cleft lip mouse model based on Pitx2-Cre conditional knockout of Bmp4 as well as a construction method and application of the bilateral cleft lip mouse model. The invention aims to construct a stable bilateral cleft lip mouse model. Experiments find that the Bmp4 gene is expressed in the epithelium of the frontal nose process and the maxillary process at the early lip stage in E9.25. The spatio-temporal expression mode of the Pitx2 gene in the early primordium epithelium is highly consistent with the spatio-temporal expression mode of the Bmp4 gene. Based on this, the inventor constructs a Bmp4 gene knockout model driven by an endogenous Pitx2 gene promoter, and finds that the mouse model shows a 100% bilateral cleft lip phenotype. Compared with the reported Netin-Cre, the Nestin-Cre has the advantages that the Nestin The bilateral cleft lip model constructed by the method is more stable, can better represent genetic diseases of human cleft lip, and has important research significance.

The invention belongs to the technical field of biological medicine, and particularly relates to a construction method of a heat-syndrome zebrafish model, the model and application. The construction method comprises the following steps: adding a hot drug into a fluorescent zebrafish embryo for induction; the preparation method of the heat medicine comprises the following steps: S1, weighing traditional Chinese medicine heat syndrome whole-formula medicinal materials; s2, after water is added, heating and boiling are conducted, and suction filtration is conducted after reflux extraction; s3, repeating the step S2 twice; s4, combining the three filtrates, and freeze-drying after rotary evaporation to obtain traditional Chinese medicine heat syndrome whole-formula powder; and S5, dissolving to obtain the hot medicine. According to the construction method, the number of macrophages at the inflammation part of the zebra fish is remarkably increased, so that immune overexpression is caused, and the heat-syndrome zebra fish model is successfully obtained. The construction method disclosed by the invention is simple and convenient to operate, short in modeling time, high in experimental efficiency and easy to observe modeling indexes, and can be used for researching pathogenesis and treatment methods of the heat syndrome, screening drugs or vaccines for preventing or treating the heat syndrome and testing the safety and effectiveness of the drugs.

The invention provides a construction method and application of a transgenic animal model with osteoclast specific deletion, and belongs to the technical field of gene engineering. The invention provides a method for constructing an animal model of an osteoclast expression diphtheria toxin receptor, and particularly provides a method for constructing the animal model of the osteoclast expression diphtheria toxin receptor by using a Cre-loxP method. According to the method, the diphtheria toxin receptor is specifically expressed in the osteoclast, and the osteoclast can be specifically deleted by injecting the diphtheria toxin. The animal model of the osteoclast expression diphtheria toxin receptor prepared by the method can stably inherit after being established, is economical and reliable, can provide important theoretical and practical guidance for bone tumor treatment, also provides powerful animal model support for research of bone tumor growth correlation, and has a wide application prospect. Technical conditions are provided for screening, developing, preventing or treating medicines for bone tumors.