291 results about "Murine model" patented technology

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 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 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 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 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.

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 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.

The application discloses application of aza-3 in resisting erythroleukemia, wherein the aza-3 is a compound obtained by modifying a ring of aza-3 with 3alpha-O-(Boc-proline); the application proves that the aza-3 can obviously inhibit HEL and K562 cell proliferation, reduce splenomegaly, improve anemia indexes (RBC, HGB and HCT) and splenic and hepatic pathological infiltration, and has no obvious toxic side effects on main organs such as heart, lung and kidney through in-vitro MTT experiment and a Friend virus-induced erythroleukemia mouse model.

The invention discloses an application of methylene blue in preparation of drugs for preventing and treating aortic dissection and aortic aneurysm, which proves that after methylene blue is orally taken in an aortic aneurysm mouse model, expansion of aortic diameter can be inhibited and occurrence rate of aortic dissection and aortic aneurysm can be reduced after methylene blue is given. Abnormal aorta dilatation of mice and disorder and fracture of elastic fibers caused by BAPN water drinking are improved. Therefore, the death rate of the BAPN-induced aortic dissection and aortic aneurysm mice can be reduced and the disease progress of the aortic dissection and aortic aneurysm can be delayed by giving the methylene blue, so that the expansion condition of the aorta of the mice is improved and the survival rate is increased.

The invention provides a construction method and application of a humanized MECP2 gene mouse model, and relates to the field of gene engineering. The model animal with the humanized hMECP2 gene is successfully prepared, the humanized hMECP2 protein can be normally expressed in the body of the model, and the model can be used for MECP2 gene function research and screening and evaluation of human MECP2 targeted drugs and therapies. The animal model prepared by the invention can be used for rapidly establishing more different MECP2 mutation humanized disease mouse models, and is applied to drug screening, drug effect research, related nervous system disease and tumor treatment and the like aiming at human MECP2 target sites, so that the research and development process of new drugs is accelerated, the time and the cost are saved, and the drug development risk is reduced. And a powerful tool is provided for researching the functions of the MECP2 protein and screening drugs.

The invention belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of MIGA2 serving as a target spot in screening or preparing a medicine for treating colorectal cancer. According to the invention, the correlation between MIGA2 and colorectal cancer progress is analyzed through large-queue bioinformatics; the influence of MIGA2 on the proliferation, migration and invasion ability of colorectal cancer cells is analyzed from an in-vitro cell model; analyzing a key molecular mechanism of MIGA2 playing a cancer inhibition function; the influence of MIGA2 on colorectal cancer tumor growth is analyzed in an in-vivo mouse model, the influence of MIGA2 mediated mitochondrial-endoplasmic reticulum contact on colorectal cancer tumor growth is analyzed, and it is verified in multiple dimensions that MIGA2 can become an effective treatment target of colorectal cancer.

The invention discloses a copper ion-kaempferol nano-composite and application thereof in treatment of inflammatory bowel disease, the obtained nano-composite has very strong stability and active oxygen scavenging ability, and has excellent oxidation resistance and anti-inflammatory ability, and the specific performance is as follows: the surface is negatively charged, and the nano-composite can specifically target the diseased region of intestinal inflammation, so that the copper ion-kaempferol nano-composite can be applied to treatment of inflammatory bowel disease. The intestinal mucosal barrier injury is effectively repaired, the imbalance state of intestinal flora is adjusted, and the intestinal inflammation microenvironment is remarkably improved; the antioxidant and anti-inflammatory capacities of cells can be enhanced by regulating and controlling a PI3K-Akt signal channel and a nuclear factor kappa B (NF-kappa B) signal channel; the compound shows an excellent treatment effect in mouse models of typical inflammatory bowel diseases such as ulcerative colitis and Crohn's disease and related complications of bowel diseases. The invention provides a new way for constructing a multi-target and multi-layer treatment platform for the inflammatory bowel disease of a natural product.

The application provides a construction method of a humanized keloid mouse model, comprising the following steps: BAC plasmid construction and preparation; superovulation of experimental mice and collection of zygotes; pronuclear microinjection of zygotes; post-injection embryo transplantation; genotype identification; breeding and genetic analysis; and verification of construction results of the humanized immune system by immunohistochemistry and immunofluorescence. In the application, peripheral blood mononuclear cells treated by sCD27 and skin around keloids (homologous cells and tissues) are transplanted into NSG-MHC-DKO immune-deficient mice with overexpression of CD70 genes, so that HLA rejection of different homologous immune cells and tissues can be avoided, the internal microenvironment of keloids and the interaction between the internal microenvironment and the immune system can be restored to the maximum extent, and the influence of immune factors on the occurrence and development of keloids can be realized in vitro. The application first discovers and verifies that the activation of the CD27-CD70 axis can promote the occurrence and development of keloids, and provides a suitable animal model for the research and development of anti-keloid drugs, especially immunotherapy.

We provide compositions and methods to enhance the anti-cancer specificity of chimeric antigen receptor natural killer cells (CAR-NK) by activating them against cancer antigens while inhibiting them against human leukocyte antigen DR (HLA-DR). HLA-DR is reportedly lost or downregulated in a substantial proportion of hematologic malignancies. An anti-HLA-DR inhibitory CAR (iCAR) is provided to effectively suppress NK cell activation against HLA-DR-expressing cells. Dual CAR-NK cells, which co-express the anti-CD19 or anti-CD33 activating CAR and the anti-HLA-DR iCAR, can preferentially target HLA-DR-negative cells over HLA-DR-positive cells in vitro. The HLA-DR-mediated inhibition is positively correlated with both iCAR and HLA-DR densities. Surrounding cells that express HLA-DR do not affect the target selectivity of the dual CAR-NK cells. We have confirmed that HLA-DR-positive cells are resistant to dual CAR-NK cell-mediated killing in a xenograft mouse model. This can be used for enhancing CAR-NK and CAR-T cell specificity against malignancies with HLA-DR loss.

This invention relates to a novel compound derived from nutmeg and an anticancer composition comprising the same. The present invention isolates several novel compounds derived from nutmeg extract and confirms that most of these novel compounds exhibit cytotoxic activity against various cancer cell lines. Five compounds (3, 4, 6, 9, and 11) were identified as having high cytotoxic activity against gastric and colorectal cancers. In particular, the compound represented by chemical formula 3 was confirmed to not only effectively induce apoptosis by regulating the cell cycle of cancer cells but also effectively inhibit tumor growth in xenograft mouse models, thus making it an effective anticancer composition.

The invention discloses a targeting peptide for blocking combination of IL-17A and IL-17RA / RC and application thereof, the targeting peptide is selected from AZS-1, AZS-2, AZS-3, AZS-4 and AZS-5 or a combination of any one of AZS-1, AZS-2, AZS-3, AZS-4 and AZS-5 and IBP, the amino acid sequence of AZS-1 is as shown in SEQ ID NO: 1, the amino acid sequence of AZS-2 is as shown in SEQ ID NO: 2, the amino acid sequence of AZS-3 is as shown in SEQ ID NO: 3, the amino acid sequence of AZS-4 is as shown in SEQ ID NO: 4, and the amino acid sequence of AZS-5 is as shown in SEQ ID NO: 5. The amino acid sequence of the AZS-5 is as shown in SEQ ID NO: 5, and the amino acid sequence of the IBP is as shown in SEQ ID NO: 6. The targeting peptide provided by the invention has good tolerance, can generate effective interaction with the surface of a target protein, can realize specific binding with IL-17A, has relatively high blocking ability, can effectively improve symptoms of liver and kidney cell injury, cell edema and skin injury caused by psoriasis after being applied to a psoriasis mouse model, and has a good application prospect. The compound has a good application prospect in treatment and / or adjuvant therapy of IL-17A-mediated inflammatory diseases.

The invention discloses ICA1L derived peptide and application thereof in relieving Alzheimer disease A beta pathology. The amino acid sequence of the ICA1L derived peptide is shown as SEQ ID NO.01. The invention further discloses a preparation method of the ICA1L derived peptide. The compound can be combined with low-density lipoprotein receptor associated protein 1 (LRP1), inhibit K48 connection type ubiquitination of the LRP1 and prevent degradation through a proteasome pathway, so that the protein level of the LRP1 is stabilized, and the expression of beta-site APP lyase 1 is reduced to reduce the generation and deposition of beta-amyloid protein. In vitro, the peptide shows good biocompatibility and cell uptake ability; in vivo, the peptide has blood-brain barrier permeability, can be positioned in neurons, can significantly reduce hippocampus and cortex A beta plaque deposition in a 5xFAD mouse model through caudal vein injection, reduces BACE1 and beta-CTF levels, and improves the cognitive function. The invention further discloses an ICA1L-LRP1 regulatory axis, and a new strategy is provided for treatment of the Alzheimer's disease.

The invention discloses an application of MetAP2 as a target spot in a drug for reducing drug resistance of multiple myeloma cells. According to the invention, expression of mRNA and protein of MetAP2 in MM drug-resistant cells is increased; when the protein expression of MetAP2 in the MM cells is exogenously changed, the sensitivity of the MM cells to BTZ can be changed; the lifetime of a myeloma mouse model established by using the MM cell for knocking down the MetAP2 is obviously prolonged, and the bone destruction condition is effectively improved. The invention provides a new solution thought for clinically inhibiting tumor growth and improving drug resistance of multiple myeloma, and has important clinical significance and transformation value.

This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition, its preparation method, and its uses. By mass parts, the raw materials of the traditional Chinese medicine composition include: 20-60 parts of Acorus calamus, 30-50 parts of Citrus aurantium, 20-60 parts of Benzoin, and 40-100 parts of Catechu. The traditional Chinese medicine composition of this invention has simple and natural components, and clear efficacy. It can effectively reduce the levels of XOD, SUA, CRE, BUN, TNF-α, IL-6, D-Lac, and DAO in the serum of a mouse model of gout, and significantly reduce the renal index, demonstrating good efficacy in treating hyperuricemia and / or gout.