533 results about "Murine model" patented technology

The invention provides a strain of lactobacillus plantarum YS-AG23 with high antioxidant activity, and a rhizoma polygonati and radix angelicae sinensis fermented product obtained by fermenting rhizoma polygonati and radix angelicae sinensis with the strain of lactobacillus plantarum YS-AG23. In a D-galactose induced premature ovarian failure mouse model, the fermentation product can regulate up the levels of antioxidant and stress protection genes SOD2 and HO-1 and an anti-aging gene SIRT1 by regulating down the expression of a key gene AGER of an inflammation and oxidative stress pathway, so that the oxidative stress and inflammatory response of model mouse ovarian tissues are remarkably reduced; meanwhile, the serum hormone level can be specifically adjusted, the serum estradiol (E2) level can be increased, the follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels can be reduced to be close to the normal range, the expression of anti-mullerian hormone (AMH) and hormone regulatory gene LHR of ovarian reserve markers can be up-regulated, the proliferative activity and estrogen secretion function of follicular granulosa cells can be improved, and the effect of preventing ovarian reserve is achieved. The wet weight of atrophic uterus and ovary of the model mouse is remarkably increased, uterine and ovary atrophy is effectively reversed, and the ovarian reserve function of the D-galactose induced premature ovarian failure model mouse is recovered. Besides, in an H2O2-induced human dermal fibroblast aging model, the yeast can improve the activity of aging cells in a concentration-dependent manner and reduce the level of reactive oxygen species (ROS) in the cells; in addition, by up-regulating the expression of a collagen synthesis key gene COL1A1 and down-regulating the expression of a cell senescence marker gene p16, skin cell senescence caused by oxidative stress can be effectively improved. In conclusion, the polygonatum sibiricum and angelica sinensis leavening can synchronously improve premature ovarian failure and skin cell senescence caused by oxidative stress by accurately regulating and controlling oxidative stress, inflammatory response and tissue function related genes, and has wide application potential.

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 belongs to the technical field of biological medicines, and particularly relates to application of a small molecule compound P7C3 in preparation of a pharmaceutical preparation for inhibiting hepatic fibrosis. According to the invention, a CCl4-induced hepatic fibrosis mouse model is used for verifying the treatment effect of P7C3 on hepatic fibrosis. Meanwhile, the influence of P7C3 on HSC activation and proliferation is verified, eIF4A1 is a direct target of P7C3 for inhibiting HSC activation, and P7C3 is a promising anti-hepatic fibrosis therapeutic drug and an effective eIF4A1 inhibitor.

The invention discloses application of amantadine in inhibition of ITGAV in preparation of medicines for treating dry age-related macular degeneration, and belongs to the technical field of biological medicines. At present, no report for researching the ITGAV gene in the dry AMD exists, the specific action mechanism is not clear, and amantadine adaptation diseases do not include the dry AMD; according to the application disclosed by the invention, the gene target ITGAV is screened from mutual hair generation of microglial cells and RPE cells in a retina microenvironment, and amantadine is used for inhibiting ITGAV protein to relieve the progress of AMD, so that a new thought is provided for treating dry AMD. Experiments show that amantadine can inhibit ITGAV and delay EMT transformation of RPE cells. In a dry AMD mouse model induced by sodium iodate, RPE cell damage can be remarkably relieved by intraocular injection of amantadine, and the structure and function of a retina layer are improved. These results indicate that it may function in early intervention of dry AMD.

The invention discloses an application of lactobacillus mucosa LMSJ001 or a metabolite agmatine of the lactobacillus mucosa LMSJ001 in preparation of a medicine for improving intestinal aging, and the application research of the lactobacillus mucosa LMSJ001 in a constructed aging mouse model finds that the lactobacillus mucosa LMSJ001 can be used for preparing a medicine for improving intestinal aging. Therapeutic gavage and application of Lactobacillus mucosa LMSJ001 in colon organs for intervention can significantly improve aging indexes, alleviate histological aging performance, promote intestinal peristalsis of aged mice, reduce secretion of inflammatory factors of the aged mice, improve intestinal epithelial barrier functions of the aged mice and improve intestinal dryness of the aged mice. The lactobacillus mucosa LMSJ001 can generate a metabolite agmatine through arginine decarboxylase, and agmatine can improve related indexes of proliferation and differentiation of intestinal stem cells and reduce expression of related indexes of senescence. Based on the unique functions, the lactobacillus mucosa LMSJ001 or the metabolite agmatine of the lactobacillus mucosa LMSJ001 can be cooperated or complemented with other means, is used for preparing pharmaceutical compositions or detection kits and the like, and has very wide application prospects.

The invention belongs to the field of biological medicines, and particularly relates to application of loganic acid in preparation of a medicine for treating arthritis. Specifically, through experimental research of a collagen-induced arthritis mouse model, the loganin acid is found to be capable of remarkably relieving arthritis symptoms, relieving joint swelling, synovitis and cartilage injury in a dose-dependent manner, and reducing the levels of proinflammatory factors TNF-alpha and IL-6 in plasma. By further combining 16S rRNA sequencing analysis, the loganic acid can remarkably regulate the intestinal microbiota structure of arthritis mice, increase the abundance of Lactobacillus murinus in the intestinal tract and promote the generation of tryptophan metabolite indole-3-acetic acid, so that the effect of resisting rheumatoid arthritis is achieved through an intestinal flora dependent mechanism. Therefore, the invention provides a new application of loganin acid in preparation of a medicine for treating arthritis, and the compound has further research and application values as a potential small molecule medicine.

The application discloses a method for constructing a mouse model of atherosclerosis induced without high-fat diet, and relates to the technical field of disease model construction.The mouse model construction method provided by the application obtains a mouse model that spontaneously exhibits atherosclerosis symptoms without high-fat diet induction.The mouse model of atherosclerosis induced without high-fat diet can be used for researching the pathogenesis of atherosclerosis and screening and evaluating drugs for atherosclerosis.

The invention belongs to the technical field of biological medicine, and provides CKS1B serving as an immunotherapy response prediction biomarker and application of the CKS1B, and according to the application, CKS1B serves as an immunotherapy response marker, and a CKS1B inhibitor is combined with an active component to treat a model mouse. In-vitro cell experiments are adopted to evaluate the immunotherapy prediction effect of the CKS1B as a biomarker on esophageal squamous carcinoma, a Cks1b overexpression tumor mouse model, a homologous mouse model and a human immune reconstruction mouse model are established, and a CKS1B inhibitor is combined with active ingredients to treat the two models; results show that the CKS1B inhibitor combined with the active component can promote removal of esophageal squamous carcinoma cells by CD8 + T cells, inhibit interferon signal channels and antigen presentation, effectively recover immune response, inhibit tumor cell proliferation and significantly reduce tumor volume, so as to achieve the purpose of treating esophageal squamous carcinoma.

The invention provides an application of liquiritin in preparation of a PPAR gamma receptor partial agonist. Through a structure-based high-throughput virtual screening technology, it is found that liquiritin can be used as a partial agonist of a PPAR gamma receptor, and the relative activation efficiency of liquiritin is 35.9% of that of rosiglitazone; in-vitro experiments prove that liquiritin can remarkably promote glucose uptake and consumption of HepG2 cells and does not induce adipocyte differentiation; in-vivo experiments prove that liquiritin can effectively improve the blood glucose level of an insulin resistance mouse model induced by high fat diet and reduce the level of serum proinflammatory factors. Compared with thiazolidinedione compounds, liquiritin not only can relieve and treat insulin resistance or related metabolic diseases, but also does not cause adverse reactions such as weight gain, fat accumulation and myocardial hypertrophy, provides a new candidate compound for developing safe and effective anti-diabetic drugs, and has a wide application prospect.

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 belongs to the technical field of medical instruments, and discloses a surgical instrument for building a traumatic brain injury mouse model.The surgical instrument comprises a tube blade, a limiter, a holding piece and a vacuum device, the tube blade is used for rotationally cutting into brain tissue of a mouse, the limiter is movably installed on the tube blade in the axial direction of the tube blade, and the vacuum device is arranged on the holding piece; the limiting device is used for abutting against the skull of the mouse, the holding piece is provided with an airflow channel, one end of the holding piece is connected with the pipe blade, one end of the airflow channel is communicated with the pipe blade, and the vacuum device is connected to the other end of the holding piece and connected with the other end of the airflow channel. According to the surgical instrument for building the traumatic brain injury mouse model, the problems that an injury area is uncontrollable and a focus area is difficult to quantify and unify in the current traumatic brain injury mouse model building process can be solved, so that the success rate and efficiency of model building are improved to the maximum extent.

The invention discloses application of an Hspa5 inhibitor in preparation of a medicine for preventing or treating anxiety disorder. An anxiety mouse model is constructed through chronic constraint stress (CRS), and in combination with medial amygdala kernel (MeA) transcriptome sequencing and qPCR verification, it is found that the endoplasmic reticulum molecular chaperone Hspa5 is remarkably up-regulated in the anxiety state. Furthermore, an Hspa5 specific inhibitor HA15 is locally injected into a MeA brain region, so that the anxiety-like behavior induced by the CRS is remarkably improved, and the exploration time of an open field experiment central region, the exploration time of an open arm of an elevated cross labyrinth and the exploration time of a bright box of a bright-dark box experiment are prolonged. The invention discloses the function of Hspa5 as a novel anti-anxiety target for the first time, and provides a direct experimental basis and a transformation direction for developing a novel anti-anxiety drug which is non-monoamine and targets an endoplasmic reticulum homeostasis.

The invention relates to a construction method of an atopic dermatitis mouse model. The method sequentially comprises the following steps: screening mice, feeding the mice in an SPF (specific pathogen free)-level animal house by adopting an illumination and darkness alternating period, and freely taking standard feed and drinking water; after the animals adapt to the environment, the animals are divided into a model group and a control group, and the control group is only subjected to first sensitization treatment; the model group is subjected to first-time sensitization treatment and maintenance treatment, the interval between the first-time sensitization treatment and the maintenance treatment is 4 days, and the maintenance treatment is performed for three times per week and is totally 16 days continuously. According to the method disclosed by the invention, the mouse model which is highly similar to human atopic dermatitis in immunology, pathology and molecular level is successfully established, the limitations of poor repeatability, incomplete pathological characteristics, single immunoreaction type and the like of the existing model are overcome, and an effective experimental platform is provided for disease research and new drug development.

The invention discloses application of dikafen phenolic acid and ester derivatives thereof in preparation of medicines for treating pulmonary fibrosis. On an MRC-5 cell model induced by TGF-beta1, the bikafen phenolic acid and the multiple ester derivatives thereof show the activity of inhibiting alpha-SMA and COL1A1 protein expression; on a bleomycin-induced pulmonary fibrosis mouse model, the dimethyl ester derivative of the dikafen phenolic acid shows a good protective effect on experimental animals. Therefore, the dicafen phenolic acid and the ester derivative thereof have good application in the field of preparation of medicines for treating pulmonary fibrosis diseases.

Methods and systems are provided for training a machine learning algorithm using at least one hardware processor to identify one or more predictive drug molecule features and / or predictive genetic biomarkers for cancer treatment. In some embodiments, the method uses at least one cancer drug discovery data set to train at least one learning algorithm in a predictive model, and uses a xenograft mouse model to validate the predictive model, and feeds back a biological response to the predictive model to further train the learning algorithm.

The invention belongs to the technical field of biological medicine, and relates to application of a compound D25, in particular to application of a small molecule compound D25 in preparation of a product for preventing or treating Alzheimer's disease (AD), and the structural formula of the compound is shown in the specification. Experiments prove that the small molecule compound D25 can pass through a blood brain barrier, can induce autophagy, can relieve pathological characteristics of an AD mouse model and improve cognitive impairment of the AD mouse model, can reduce the proportion of disease-related microglial cells by recovering the morphology of the microglial cells and improving the A beta phagocytosis capacity of the microglial cells, has the potential of promoting neuronal growth and increasing the number of protrusions, and can be used for preparing a medicine for treating the disease-related microglial cells. Therefore, AD can be effectively treated, the safety is high, the effect is achieved, and the application prospect is great.

The application belongs to the field of neuropharmacology and medicine, and particularly relates to application of taurine cholic acid in preparation of a drug for preventing or treating Alzheimer's disease. Through animal model experiment verification, the A beta lateral ventricle injection is used to prepare an AD mouse model, and after oral administration of TCA for 2 weeks, cognitive behavior and pathological indexes are significantly improved.

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.

The invention discloses an application of mRNA (messenger Ribonucleic Acid) for coding p16 protein in preparation of a medicine for treating pancreatic cancer. The mRNA for coding the p16 protein comprises a nucleic acid sequence as shown in SEQ ID NO.1-3. The invention also provides an application of the mRNA for coding the p16 protein and a universal RAS inhibitor daraxonrasib in the preparation of a medicine for treating pancreatic cancer in combination with the mRNA for coding the p16 protein and the universal RAS inhibitor daraxonrasib. Further, the mRNA encoding the p16 protein can be entrapped in a lipid nanoparticle. Experiments show that the function of CDKN2A is recovered by delivering p16 mRNA, the sensitivity of pancreatic cancer cells to the daraxonrasib can be enhanced, the drug resistance of the daraxonrasib can be reversed, and a remarkable synergistic anti-tumor effect is shown in various pancreatic cancer mouse models. The invention provides a new combined treatment strategy for the treatment of pancreatic cancer, especially pancreatic ductal adenocarcinoma.

The application discloses a LYTAG-Gem compound for enhancing the anti-tumor effect of gemcitabine and application thereof, relates to the technical field of biological medicine, and particularly relates to a gemcitabine (Gem) targeted delivery system based on a lysosome targeting chimera (LYTAC) and application thereof in enhancing the anti-tumor process. 2+ The system is assembled from heavy chain ferritin, Ni 2+ , NTA-PEG5000-DBCO and a targeting ligand TPP-1-N3 in a specific mass percentage, can efficiently load Gem and form a nano compound with a particle size of about 59-79 nm, the system targets tumor cells through heavy chain ferritin, and realizes site-specific release of Gem in cells by means of an endocytosis-lysosome pathway mediated by the LYTAC structure, in-vivo pharmacodynamic experiments show that the LYTAC-Gem compound can significantly inhibit the tumor growth of a KPC pancreatic cancer mouse model, molecular mechanism research further reveals that the LYTAC-Gem compound can down-regulate the expression of PD-L1 protein in tumor tissues, and it is indicated that the LYTAC-Gem compound has the potential to activate an anti-tumor immune response, and the application provides a novel targeted delivery strategy for overcoming the toxic side effects and tumor drug resistance of gemcitabine.

The present disclosure relates to animal models that express human tryptophanyl-tRNA synthetase (hWARS) knock-in. These animal models are highly susceptible to enterovirus infection, including but not limited to EV-D68 and EV-A71 infection. Also disclosed are screening methods and compounds that utilize these animal models.

This invention discloses a fusion protein targeting the urokinase-type plasminogen activator receptor and its application in the field of anti-aging. The fusion protein is composed of a hepatocyte growth factor active domain and a humanized anti-uPAR single-domain antibody linked by a flexible linker peptide, and its specific amino acid sequence is SEQ ID NO:3. This fusion protein can specifically bind to uPAR, which is highly expressed on the surface of senescent cells, with intramolar affinity, achieving targeted delivery of the hepatocyte growth factor active domain. In vitro experiments have demonstrated that this protein can significantly reverse the aging phenotype of human fibroblasts, effectively reduce aging-related β-galactosidase activity, p16INK4a protein expression, and interleukin-6 secretion, and promote cell proliferation. In a rapidly aging mouse model, this protein can systematically improve age-related physiological functional decline. The fusion protein of this invention achieves specific targeting and efficient treatment of senescent cells, providing a new solution for the development of anti-aging drugs.

The application discloses a kind of composition with immunoregulation and anti-aging function and preparation method thereof, and core component is marine collagen peptide, fusion polypeptide CPF-1, targeting senescent cell monoclonal antibody mAb Senolix, five gallate acyl glucose (PGG) and Hericium erinaceus polysaccharide.Fusion polypeptide CPF-1 is designed by domain fusion strategy, with collagen binding, immune activation and antibacterial function;Monoclonal antibody mAb Senolix targets the surface antigen p16^(INK4a) of senescent cell, and removes senescent cell by ADCC effect.The composition significantly improves immune cell activity, promotes collagen synthesis and reduces chronic inflammation through the synergistic effect of multiple components, and shows excellent immunoregulation and anti-aging effect in in vitro cell model and immunosuppressed mouse model, and can be used for developing immune enhancer, anti-aging drug or functional food.

The invention relates to a method for producing an animal model of heart failure. The method comprises the step of weakening or deleting DDB1 protein function in myocardial cells of the animal model. The present application demonstrates that nuclear DDB1 co-agglomerates with MEF2C to control NAD + biosynthesis as well as ion homeostasis genes in the heart, and the lack of which results in the development of HFpEF. Development of HFpEF in a'double strike 'mouse model can be reversed through AAV-mediated DDB1 overexpression in myocardial cell nucleuses. Therefore, it is detected that DDB1 coordinates NAD + biosynthesis and ion homeostasis to protect the heart from being affected by ejection fraction retention heart failure caused by obesity, and the scheme of the application has therapeutic significance on treatment of obesity / diabetes HFpEF.

Cannabidiol, or a pharmaceutically acceptable prodrug, derivative, salt, or solvate thereof, for use in treating or preventing recurrent pericarditis is disclosed. The effectiveness of cannabidiol in attenuating the levels of interleukin-1β (IL-1β) and IL-6, and the transcription of pro-IL-1β and NLRP3 mRNA in in vitro models are disclosed. Also disclosed are experiments showing cannabidiol to be effective in preventing an increase in the pericardial space (which is an indicator of pericardial effusion) and the pericardial thickness in an in vivo mouse model of pericarditis.

The invention belongs to the technical field of disease model construction, and particularly relates to a construction method of a chronic myelogenous leukemia mouse model with conditional human EZH2 overexpression and RUNX1 knockout. According to the invention, a chronic myelogenous leukemia mouse transgenic mouse model with conditional human EZH2 overexpression and RUNX1 knockout is successfully constructed, the model is induced to be converted from a chronic stage to a sudden change stage, and particularly, the model is a transgenic mouse model which is positive in Lyz2-CreERT2 / EZH2 / RUNX1 and carries BCR-ABL and SCL-tTA. It is proved that a human EZH2 conditional overexpression and RUNX1 knockout chronic myelogenous leukemia mouse transgenic mouse model has feasibility and importance for research on conversion from CML CP to BC samples, and a molecular mechanism for conversion from chronic myelogenous leukemia to a sudden change stage is revealed for research. And a new animal model and a new research idea are provided for understanding of disease progression and development of a new treatment strategy.

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.

This invention discloses the application of platelet-reactive protein-4 (THBS4) in the diagnosis and treatment of endometriosis. Through bioinformatics integration analysis, clinical sample validation, and in vitro and in vivo experiments, this invention confirms that THBS4 is significantly highly expressed in both ectopic lesions and peripheral blood of patients with endometriosis, and its expression level is positively correlated with disease severity. The area under the receiver operating characteristic (AUC) curve for THBS4 alone in diagnosing endometriosis is 0.930, significantly superior to cancer antigen 125 (CA125); the AUC for the combined diagnosis of THBS4 and CA125 reaches 0.968. Simultaneously, silencing the THBS4 gene effectively inhibits the proliferation, migration, and invasion of human endometrial stromal cells, and significantly reduces the volume and fibrosis area of ​​ectopic lesions in a mouse model of endometriosis. This invention provides a highly sensitive and specific new biomarker for the non-invasive or minimally invasive early diagnosis of endometriosis, and provides new targets and candidate drugs for non-hormone-dependent targeted therapy.

The invention relates to the technical field of medicines, and discloses a bifidobacterium longum strain GZBAI 01 and application thereof in degradation of benzoic acid and prevention or treatment of colorectal cancer. The strain is separated from faeces of healthy people, genomics identification is carried out, the metabolic profile of the strain is measured through metabonomics, the strain can convert benzoic acid with carcinogenic risk into protocatechuic acid with antitumor activity through unique metabolic capability, meanwhile, the function of regulatory T cells (Treg) in tumor drainage lymph nodes can be inhibited, differentiation of CD8 + T cells is promoted, and the tumor drainage lymph nodes can be inhibited. Therefore, the colorectal cancer is prevented through double ways of eliminating cancerogen and generating therapeutic agents. A colorectal cancer mouse model and a subcutaneous tumor mouse model verify that the strain can significantly reduce the number and volume of tumors, and shows a benzoic acid conversion effect superior to that of other strains in vivo and in vitro, and a new way is provided for prevention and treatment of colorectal cancer.