578results about "Compounds screening/testing" patented technology

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 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

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 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 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 belongs to the technical field of animal model construction, and particularly relates to a non-alcoholic fatty liver disease mouse model based on humanized PNPLA3 I148M transgene as well as a construction method and application thereof, the construction method comprises the following steps: step i: designing CDS of a human gene and a key 3 'UTR element for patent medicine of a small nucleic acid drug in gene plasmid DNA of the constructed model; step ii, using Luc2 or iRFP to report gene expression in the gene plasmid DNA for constructing the model; and (iii) a disease model of the fatty liver disease induced by combining plasmid DNA transient transfer with high-fat diet. The mouse model constructed by the invention has the advantages that a specific exogenous gene expression signal of the liver is detected in real time through small animal living imaging, a human PNPLA3 protein is detected and overexpressed through serum ELISA, PNPLA3 I148M mRNA is detected and overexpressed through liver RT-qPCR, the phenotype of the non-alcoholic fatty liver disease of the liver is determined through 15-week-old pathology, and the whole process of modeling for 8 weeks does not need to be operated in a biosafety secondary laboratory.

The invention provides sgRNA for knocking out zebra fish pde6a and application of the sgRNA in visual diseases. According to the sgRNA provided by the invention aiming at a specific position, pde6a of the zebra fish can be knocked out or knocked down in a targeted manner by utilizing a CRISPR / Cas9 system. After pde6a is successfully knocked out or knocked down, a zebra fish model with impaired visual functions and normal retina development is obtained, and the model also has morphological changes such as shorter body length, smaller eyes and shorter inter-ocular distance and also shows a trend of increasing the length of an ocular axis. The zebrafish model provides an experimental tool and a model basis for the research of visual function related diseases.

The invention discloses a construction method and application of a bacterium-derived depression mouse model, and belongs to the technical field of biological medicines. The method comprises the following steps: randomly grouping SPF (specific pathogen free) grade C57BL / 6J experimental mice; using drinking water quadruple antibiotics or intragastric administration quadruple antibiotics to deplete mouse background intestinal flora; according to the method, a freshly prepared Eggera tarda bacterial liquid is applied to male mice of 7-9 weeks old in an intragastric administration manner, and the bacterial-derived depression mouse model is constructed. According to the construction method disclosed by the invention, by directly planting the Eggera tarda which has a definite causal relationship with the major depression, multivariable interference introduced by a traditional complex mental stress model is avoided, and a'bacterial origin 'animal model which is more single in variable, clearer in causal relationship and clearer in mechanism is constructed; and an efficient and reliable experimental tool is provided for accurately explaining the specific action mechanism of the'microorganism-intestine-brain axis' mediated by the Eggera tarda in the occurrence and development of the depression.

The invention belongs to the technical field of biomedical imaging, and particularly discloses an in-vivo imaging method of an SAPAP3 gene defect disease model, which is characterized in that an effective dose of an S1PR1 receptor targeted radioactive probe is injected into the body of the SAPAP3 gene defect disease model. According to the method, an S1PR1 receptor targeting radioactive probe is utilized, the technical bottleneck that in-vivo and dynamic observation of the S1PR1 receptor cannot be achieved through an existing in-vitro technology is solved, and an indispensable visual tool and a quantitative evaluation means are provided for studying the neurobiological mechanism of related mental diseases such as obsessive-compulsive disorder and accelerating research and development of related drugs.

The invention discloses a construction method and application of an animal model for evaluating cardiotoxicity of antitumor drugs, sodium carboxymethyl cellulose (CMC-Na) with extremely low cost is adopted to replace matrigel, a tumor-bearing mouse model with high stability can be constructed at low cost, and experimental verification shows that 4T1 cells are resuspended by using a 0.7% CMC-Na solution, and the tumor formation rate of subcutaneous inoculation reaches gt; 95%. The tumor microenvironment-mediated cardiac injury critical period is accurately captured, and the constructed tumor-bearing mouse model is the optimal tumor-bearing mouse model for evaluating the cardiotoxicity of an antitumor drug (adriamycin) in the tumor microenvironment in the third week after the mouse has a 50mm < 3 > tumor.

Plasma kallikrein binding proteins and methods of using such proteins are described.

The invention discloses a construction method and application of an animal model of Parkinson's disease, and relates to the technical field of animal models of neurodegenerative diseases. The animal model of the Parkinson's disease induces alpha-synuclein to be transmitted along an intestine-brain axis. The construction method comprises the following steps: (1) providing an SD (Sprague Dawley) rat; and (2) performing intragastric administration on the SD rat with rotenone according to the dosage of 30mg / kg / day, so as to obtain the animal model of the Parkinson's disease. The Parkinson's disease modeling method successfully simulates sequential transmission of alpha-syn along the intestine-brain axis, has the advantages of strong targeting, low death rate, endogenous pathology generation and the like, and provides a reliable platform for PD mechanism research and treatment development. According to the screening method of the medicine for treating the Parkinson's disease, the blocking effect of the medicine on PD pathology source transmission can be accurately evaluated by detecting the deposition amount of alpha-syn at multiple parts, and the defects of a traditional model are overcome; the method is suitable for research and development requirements of various drugs, and the application range is far better than that of a screening model only aiming at a single pathological link.

Disclosed herein are methods for treating autoimmune diseases using anti-CD19 antibodies, specifically the treatment of neuromyelitis optica spectrum disorder using VIB551, an affinity-optimized, humanized, defucosylated IgG1κ monoclonal antibody. TIFF2022529743000026.tif137153

The invention discloses an application of silibinin in enhancing the immunomodulatory function of stem cells, and relates to the technical field of biological medicines. The silybin is applied to the composition for enhancing the immunoregulation function of the stem cells, the composition comprises the silybin and umbilical cord-derived mesenchymal stem cells, and the immunoregulation function of UC-MSCs is enhanced by adjusting the interaction of ICOS / ICOSL axes based on the combined action of the silybin and the umbilical cord-derived mesenchymal stem cells. The silybin disclosed by the invention is competitively combined with the ICOS, so that the interaction of the ICOS / ICOSL is blocked, and the immune regulation function of the umbilical cord-derived mesenchymal stem cells is remarkably enhanced; therefore, the UC-MSCs show a stronger immunosuppression effect in both in-vitro and in-vivo experiments; silybin not only acts on an ICOS / ICOSL axis, but also inhibits secretion of inflammatory factors through a PI3K / AKT signal channel, so that a multi-mechanism synergistic treatment effect is achieved.

The invention discloses construction and application of a Primrose syndrome non-human animal model, and belongs to the technical field of animal models and disease research. According to the invention, through a CRISPR / Cas9 technology, a codon CAC for coding 596th histidine in a No.14 exon of a mouse Zbtb20 gene is subjected to site-directed mutagenesis into CGC for coding arginine, and a hybrid mouse model for simulating pathogenic point mutation (p.H596R) of human Primrose syndrome is constructed. The model can stably reproduce key clinical phenotypes of the Primrose syndrome, including overgrowth after adult, serum IGF-1 rise, memory dysfunction and anxiety behaviors, and shows abnormal hippocampal neuronal development and synaptic transfer related pathways and the like. The invention provides an important experimental tool for deeply revealing the pathological mechanism of Primrose syndrome, developing drug screening and treatment intervention research and the like.

The invention discloses a traditional Chinese medicine composition for treating recurrent urinary tract infection as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from 30-90 parts of astragalus membranaceus, 3-9 parts of cordyceps mycelia, 12-36 parts of rhizoma anemarrhenae, 10-30 parts of golden cypress and 6-18 parts of cinnamon. According to the pathogenesis characteristics of recurrent urinary tract infection and the principle of treatment based on syndrome differentiation of traditional Chinese medicine, the optimal raw material composition and dosage part ratio are obtained through screening, simplification and optimization of a large number of experiments, and the traditional Chinese medicine composition can remarkably improve the frequent micturition symptom, bacterial load and bladder pathological injury of rUTI mice. In addition, the drug-containing serum can promote migration of the SV-HUC-1 cells and reduce the level of inflammatory factors secreted by co-culture of the SV-HUC-1 cells and the UTI89 cells; the adhesion and internalization of the UTI89 to the cells are reduced. In addition, according to different bacterial strains and mouse modeling results, it is found that the modeling rate is obviously increased in a mode of enhancing infection every 24 hours, a recurrent urinary tract infection model of UTI89 infected C57BL / 6J is constructed, and a stable model is provided for screening drugs for treating recurrent urinary tract infection.

Provided herein are screening methods and animal models relevant to ocular diseases such as age-related macular degeneration (AMD), e.g., for use in identifying candidate therapeutics for treating or preventing ocular diseases such as AMD. Also provided herein are compounds / compositions useful for killing or inhibiting the growth of microorganisms such as Bacillus megaterium. Further provided herein are methods of using the compounds / compositions to treat infections with microorganisms such as Bacillus megaterium, as well as to treat or prevent diseases or conditions associated with such infections, such as AMD.

The invention belongs to the technical field of construction methods of disease animal models, and particularly relates to a construction method and application of a renal syndrome hemorrhagic fever mouse model. According to the HTNV infected mouse model established by the method disclosed by the invention, the symptom of the experimental mouse is close to the clinical symptom of a severe hemorrhagic fever with renal syndrome after challenge, the complete lethality and repeatability are high, and the HTNV infected mouse model has the advantages of simple operation, low cost and high efficiency. The method can be used for research on the HTNV pathogenic mechanism and immune mechanism and research and development of antiviral drugs and vaccines, and has great application value for perfecting an HTNV full-chain prevention and control system.

Genetically modified zebrafish, in which mutation combinations frequently identified in human AML are stably expressed in the stem cell population of the fish, are provided. The combination of mutations result in morphologic, cytochemical and molecular changes of its blood cells that are remarkably similar to those in human AML. The zebrafish model provides a foundation for the study of AML initiation and progression and a high throughput in vivo drug screening platform to identify personalized therapies for AML based on specific mutation combinations. The method of drug screening includes contacting embryos or adult fish containing mutations as disclosed herein, with a test agent, at test concentrations and test intervals to determine the therapeutic effect if any, of the test agent.

The application discloses application of a CCL15 neutralizing antibody in preparation of a medicine for inhibiting growth of liver cancer, and comprises the following steps: S1, constructing a mouse liver cancer PDX model and performing passage; S2, randomly dividing the immunodeficient mouse after passage into a control group and an experimental group, and performing dosing treatment on the control group and the experimental group every three days; S3, PDX model tumor tissue evaluation, stripping tumor tissues after 11 times of dosing of the control group and the experimental group, and respectively observing and recording the volume and weight of the tumor tissues of the control group and the experimental group; the method for inhibiting growth of liver cancer provided by the application, CCL15 acts on the stellate cells to activate the stellate cells and make the expression spectrum of the stellate cells change significantly, the CCL15 neutralizing antibody has an anti-tumor effect in the liver cancer PDX model through injection, and tumor-derived CCL15 can indirectly promote growth of liver cancer cells by activating the hepatic stellate cells.

A method and device are provided for evaluating hair growth treatments by applying markers to a hair area at different times to measure pre-treatment hair volume and post-treatment hair volume. By comparing changes in hair volume within one or more hairs, an effectiveness of the hair regrowth treatment can be measured.

The application belongs to the technical field of biotechnology, and particularly relates to a human metapneumovirus mouse-adapted strain and application thereof. Compared with wild strains, the strain can exhibit stronger susceptibility to animals, and can cause typical clinical symptoms and even death. For example, after the strain infects BALB / c mice, the disease symptoms are obvious, 83% of the mice have a severe decrease in body weight to below 75% after infection, and have reached the humane killing standard. Four days after the strain infects BALB / c mice, the mortality rate is above 50%. The strain can be used to construct a cell model or an animal model of human metapneumovirus infection or a disease caused by the human metapneumovirus, and is further used to screen drugs for preventing and / or treating human metapneumovirus infection or a disease caused by the human metapneumovirus. In addition, the strain can also be used to prepare drugs for preventing and / or treating human metapneumovirus infection or a disease caused by the human metapneumovirus, and to prepare antibodies or antisera against the human metapneumovirus.

The invention discloses a mouse liver cancer cell line with a high lung metastasis characteristic as well as a construction method and application thereof, and belongs to the technical field of biology and oncology. The cell is preserved in China Center for Type Culture Collection on February 4, 2026, the preservation address is Wuhan University, Wuhan, China, and the preservation number is CCTCC NO: C202621. The PNV-LM3 cell line provided by the invention is constructed by combining a PTEN KO and NRAS G12V mutated hydrodynamic tail vein injection model with tail vein injection in-vivo domestication, a mouse liver cancer model is successfully induced to generate lung metastasis, and the lung metastasis tendency of the cell line is greatly enhanced. Compared with a traditional Hepa1-6 cell line, the PNV-LM3 cell line has the advantages that the lung metastasis process of the liver cancer is more accurately and efficiently reproduced, and a more real experimental platform is provided for research of a liver cancer metastasis mechanism.

The invention belongs to the technical field of medical experimental animal models, and particularly relates to a construction method of a rabbit ear acne model for studying acne pathogenesis and drug curative effect. A healthy New Zealand large-ear white rabbit is selected, a testosterone solution is subcutaneously injected to induce endocrine disorder, oleic acid is smeared at an opening of an external auditory canal on the inner side of an ear, dermatobacterium acnes suspension is subcutaneously injected, and whether acne-like lesions such as erythema, papule and comedo appear on the skin of the ear or not is observed. The method is easy and convenient to operate, low in cost, good in repeatability, capable of simulating the pathological process of human acne and suitable for acne pathogenesis research and drug screening.

Methods for identifying agents or manipulations that modulate copper (Cu) dyshomeostasis in an Mblac1- or swip-10-dependent manner, and for identifying agents that support Cu-dependent neuronal health in a subject are provided.

The application relates to a construction method of a Mettl3 transgenic mouse model with specific knockout, enriches the understanding of the function and action mechanism of Mettl3 in mature pancreatic islet beta cells, and provides a new thought and target for the pathogenesis and treatment of diabetes.