23 results about "Disease modelling" patented technology

This invention relates to a method for constructing a mouse orthotopic model of highly aggregated glioblastoma, belonging to the fields of biomedicine and experimental animal model technology. Glioblastoma cells are resuspended in a composite carrier of a specific ratio of matrix gel and serum-free culture medium, and a low-temperature injection technique is used. Utilizing the thermosensitivity of matrix gel in the mouse intracranial environment (i.e., its phase transition from liquid to gel at a certain temperature), precise colonization and physical locking of tumor cells at target coordinate points are achieved. This method improves upon existing glioblastoma mouse orthotopic model construction techniques that suffer from tumor cell diffusion and loss, low tumor formation rate, irregular tumor morphology, large intragroup variability, and needle reflux due to low viscosity of the inoculation carrier. It provides a good disease model for subsequent screening or evaluation of anti-glioblastoma drugs.

The application provides a trophoblast organ-on-chip system for simulating a maternal-fetal interface of a systemic lupus erythematosus model based on an organ chip and a construction method thereof, the system taking an organ chip as a carrier and comprising three core parts of a trophoblast organ, an endometrial chip and an SLE disease model. The application completes separation culture and characterization of the trophoblast organ, multi-cell co-culture construction and characterization of the endometrial chip, and then constructs a pathological model, and the three parts cooperatively form a three-dimensional maternal-fetal interface. The system can clearly observe the dynamic process of the trophoblast organ invading the endometrial chip, can detect the continuous secretion of hCG and SLE-related inflammatory factors, and breaks through the defects of the prior art model, such as low authenticity, inability to dynamically observe, single detection dimension and lack of standardization, and has both physiological and pathological adhesion and experimental repeatability, can multi-dimensionally characterize the cell phenotype and function of the maternal-fetal interface, and provides an in-vitro research platform for the pathological mechanism research of the SLE pregnancy-related abnormal maternal-fetal interface.

This invention discloses a skin organ-on-a-chip, relating to the fields of biomedical engineering and microfluidics. The chip includes a drive module integrating a reservoir with a fixed height difference, a culture layer with arrayed independent skin culture units, and a fluid layer separated by a porous membrane. The drive module utilizes the hydrostatic pressure generated by the liquid level difference to drive the culture medium to form a stable laminar flow in an optimized fluid channel network, achieving pump-free perfusion. This invention achieves stable pump-free drive through a reservoir with a fixed height difference; the integrated sealed structure eliminates the risk of contamination and ensures complete isolation between units; the simulation-optimized uniform flow channel network, in synergy with the drive, ensures high consistency in high-throughput parallel culture, enabling the chip to provide a long-term stable biomimetic perfusion microenvironment. A single experiment can efficiently complete multiple replicates and multi-condition transdermal drug screening, toxicity testing, and disease model construction, improving experimental throughput, data reliability, and ease of operation.

This invention discloses the application of a PDLIM2 gene overexpression viral vector in the preparation of drugs for treating podocyte disease, wherein the nucleotide sequence of the PDLIM2 gene is shown in SEQ ID NO:1. This invention is the first to discover and verify the core role of the PDLIM2 gene in podocyte protection, confirming its significant downregulation in DKD and FSGS disease models, and demonstrating through functional experiments that PDLIM2 overexpression can effectively stabilize the podocyte cytoskeleton, inhibit apoptosis, and reduce proteinuria, thus establishing it as a key target gene for the treatment of podocyte disease. This invention is the first to intervene at the gene level in the core link of podocyte damage—cytoskeleton stability. By specifically upregulating the expression of PDLIM2 in podocytes, it directly enhances their intrinsic cytoskeleton support and anti-damage ability, achieving a fundamental shift in treatment strategy from "symptomatic support" to "causal repair."

This invention discloses a high-performance computing-based system and method for evaluating colorectal cancer screening strategies, belonging to the field of medical information processing technology. It includes: a dual-pathway disease model module supporting both adenoma-carcinoma pathways and serrated adenoma pathways, modeled using age-dependent normal distribution progression time; an individualized risk scoring module integrating risk factors such as family history, inflammatory bowel disease, obesity, and diabetes; a screening strategy simulation module supporting combined screening strategies using different tools, employing compliance parameters specific to the Chinese urban population; a high-performance computing module using Numba JIT compilation technology for acceleration, multi-process parallel processing for further acceleration, and data structure optimization such as integer age to reduce memory usage; and a health economics evaluation module calculating indicators such as QALY, LYG, and ICER. This invention achieves significant performance improvements while maintaining model accuracy, greatly reducing simulation time for large-scale populations.

The invention discloses a myocardial cell systolic function analysis method, system and device and a medium. The method comprises the following steps: setting an import generation parameter based on a myocardial cell rhythmic systolic video sequence, splitting and reading frame by frame based on the myocardial cell rhythmic systolic video sequence, and converting to generate a grayscale image; calculating two adjacent frames of pixel point displacement vector fields based on the gray level image, acquiring flow field components in different directions based on the pixel point displacement vector fields, and converting to generate a time speed sequence curve; smoothing and filtering the processed signal based on a time-speed sequence curve, detecting and identifying a key time phase of a contraction period based on the time-speed sequence curve, and completing period judgment and inspection; and calculating contraction process kinetic parameters based on the period. According to the method, a one-key operation process of video import, pixel size setting, parameter calculation and result export is realized through a software interface, unmarked, high-throughput and automatic myocardial cell systolic function evaluation is realized, and technical support is provided for drug screening and disease model function research.

The application belongs to the technical field of biomedicine, and discloses a method for constructing a Channa argus bile stasis model. The application discloses application of rifampicin or a pharmaceutically acceptable salt thereof in construction of a fish liver injury model. The application discloses, for the first time, that the antibiotic rifampicin widely used in aquaculture is used to construct a fish liver injury model. The model is closer to the real scene of the use of a large amount of drugs when bacterial diseases break out in production practice. The injury type of the fish liver injury model is clearly directed to bile stasis, which fills the research blank of the disease model of the fish, and is different from common hepatocyte necrosis or fatty liver models.

This invention provides an application and method of lysophosphatidylcholine (LPC) in promoting early development of reconstructed embryos, belonging to the field of embryo engineering technology. The invention first prepares reconstructed embryos, then adds lysophosphatidylcholine to the culture system for culturing. Lysophosphatidylcholine effectively promotes early development of the reconstructed embryos; at an optimal concentration of 5 μM, the blastocyst development rate increases to 24.56%, providing a novel and operable biochemical intervention target to solve the problem of low reconstructed embryo culture efficiency. This invention not only fills the gap in our understanding of the mechanism of action of LPC in this field, but also achieves controllability and reproducibility of the technical solution through precise definition of the optimal concentration. It provides key parameters for establishing standardized culture procedures and provides a more solid foundation for downstream applications such as developmental biology research and disease model construction that rely on high-quality reconstructed embryos, significantly accelerating the process of related scientific discovery and application development.

The application discloses application of a TPP2 mutant zebrafish in an ASD neurodevelopment-related disease model and belongs to the technical field of biological medicines. It is found for the first time that a TPP2 gene deletion type zebrafish has the following phenotypes: developmental retardation, developmental deformity, abnormal motor function, social dysfunction, stereotyped behavior, anxiety-like behavior and the like, has the core characteristics of ASD-related neurodevelopment-related diseases and can be used as an animal model for researching ASD neurodevelopment-related diseases, thereby providing an effective approach for diagnosing or treating ASD neurodevelopment-related diseases.

The invention provides a molecular self-assembly integrin patch for regulating and controlling mechanical signals of cells as well as a preparation method and application of the molecular self-assembly integrin patch, and an extracellular matrix (ECM) bionic cell patch is constructed through a molecular self-assembly technology. According to the patch, a laminin-derived integrin binding ligand is extended and self-assembled through an N-terminal aromatic amino acid to form a fibrous nano network, and the patch has controllable nano-scale ligand distribution, network viscoelasticity and stability, and can specifically activate integrin beta1 at the top end of MSC (mesenchymal stem cell), so that a mechanical signal is conducted from a cell membrane to a cell nucleus. The process coordinates cytoskeleton reconstruction, nuclear deformation and chromatin rearrangement, and finally drives the MSC to efficiently differentiate into neuron-like cells under the condition of no exogenous gene or chemical induction, so as to express nerve markers such as TUBB3 and present functional characteristics such as spontaneous calcium transient. The cell patch can be widely applied to nerve regeneration, tissue engineering, disease model construction and intelligent biological material development.

The present invention provides a method for constructing brain glioma organoids capable of preserving an immune microenvironment. The culture medium, culture system and method provided by the present invention overcome the shortages that, with the prolonging of culture time, a large number of tumor immune cells are lost and the tumor immune microenvironment is greatly damaged in current glioblastoma organoid models, and can more completely preserve the tumor microenvironment of glioblastoma for a longer time, and greatly retain the heterogeneity of organoid tissue. The present invention is suitable for constructing a new generation of glioblastoma organoid models, and provides more reliable research tools for tumor microenvironment research of glioblastoma, tumorigenesis mechanism research, drug efficacy screening, and the development and application of disease models.

The application provides an animal model of high-oxygen-induced retinal neovascular disease and a preparation method thereof. The method comprises the following steps: placing a mouse born for 3-7 days in an environment with an oxygen concentration of 75-85%, and maintaining for 10-30 days. The method can successfully induce a long-acting retinal neovascular disease model, has a high modeling rate, fewer complications, more persistent retinal neovascular lesions, and a model duration of 55 days. The animal model provides a more optimal model for exploring long-acting anti-retinal neovascular related drugs.

The application provides a construction method of a zebrafish model of diabetic cerebral hemorrhage sequelae for high-throughput drug screening, and belongs to the technical field of biotechnology.The first zebrafish model capable of comprehensively simulating the complex pathological phenotypes of clinical diabetic cerebral hemorrhage sequelae is successfully constructed, and the blank of the research model in the field is filled.The pathological changes of the model are highly consistent with the symptoms of the patients with clinical diabetic cerebral hemorrhage sequelae, such as glucose metabolism disorder, pancreatic beta cell damage, cerebral vascular injury and hemorrhage, brain cell apoptosis, inflammatory reaction and behavior abnormality, and the limitation that the existing single disease model cannot simulate the synergistic pathogenesis of diabetes and cerebral hemorrhage is overcome, so that a reliable experimental animal model is provided for high-throughput screening of active ingredients against the disease.

The present application relates to the technical field of Parkinson's disease model construction of zebrafish, and specifically discloses a method for constructing a Parkinson's disease model of zebrafish induced by artificial sweetener neotame and application thereof, and the technical points are as follows: the method comprises the following steps: mixing neotame with water to obtain a neotame aqueous solution mother liquor with a mass concentration of 1 g / L; diluting the mother liquor into a working solution with a mass concentration of 1-100 mg / L by using breeding water; and breeding zebrafish in the working solution for 4 weeks to obtain a Parkinson's disease animal model of zebrafish induced by neotame. The present application also provides a model constructed by the method, an evaluation method of the model and application thereof. The model can be used for research on nervous system diseases, screening of neotame neurotoxicity, evaluation of neotame neurotoxicity in food and high-throughput screening of anti-Parkinson drugs.

This invention specifically relates to a method for establishing and applying a zebrafish psoriasis model. The technical solution of this invention utilizes the characteristics of zebrafish—short developmental cycle, ease of rearing, and convenient live observation—effectively shortening the experimental cycle and reducing modeling and screening costs. Simultaneously, this invention establishes standardized induction conditions and quantitative evaluation indicators, improving the stability of disease model construction and the accuracy of drug efficacy evaluation. It provides a live model tool that conforms to the 3R principles of animal protection for research on the pathogenesis of psoriasis and high-throughput preclinical screening of related drugs.

The present application belongs to the technical field of biology, and particularly relates to a construction of a retinal pigment degeneration disease model and application thereof. The construction method of the present application adopts a gene editing technology to make the 3rd exon of the CNGA1 gene of a non-human animal model to be mutated, and a retinal pigment degeneration disease model simulating a human c.253delC mutation can be constructed. The retinal pigment degeneration disease model can well simulate the disease caused by the mutation in the human body, and provides a good animal model for mechanism research and drug screening of the disease.

This invention relates to the fields of regenerative medicine, disease models, and drug screening, and particularly to a high-throughput method and application for constructing human kidney organoids that simulate the pathological characteristics of lupus nephritis. The kidney organoids are mixed and cultured with plasma from lupus nephritis patients in low-adsorption multi-well plates. This invention utilizes a standardized process to prepare human kidney organoids in high throughput, and then stimulates them with plasma from lupus nephritis patients, thereby rapidly and in large quantities constructing disease models in vitro that simulate the severity of individual patients' diseases and reproduce key pathological features (such as podocyte damage and inflammatory fibrosis). This platform provides a closed-loop research tool for lupus nephritis research, from "clinical samples" to "in vitro models" and then to "clinical validation."

The application discloses a kind of organ chip manufacturing and application of simulating liver fibrosis microenvironment interaction, belong to biomedical engineering technical field.Technical points: the chip includes chip main body, be provided with culture chamber of being divided into upstream chamber and downstream chamber on chip main body, culture chamber upper part is inverted conical column shape, lower part is cylindrical, chip main body is also provided with liquid flow hole, liquid flow channel and check valve, liquid flow channel is connected upstream and downstream chamber, check valve controls liquid flow one-way flow;Chip also includes chip chamber with outer edge and membrane with hole, can place organoid or acellular matrix skeleton.The application places different organoids or acellular matrix skeleton by upstream and downstream chamber, utilizes one-way liquid flow to simulate the action sequence of different components in liver fibrosis process, solves the problem that existing model simulation reality is poor, cannot accurately study cell interaction, long-term culture is difficult, sample separation is difficult, etc., can be used for liver fibrosis mechanism research, drug screening and disease model construction, with simulation real, strong universality, operation is convenient and the like advantages.

As a result of dedicated studies, the present inventors succeeded in discovering, for the first time, that fibrogenesis could be suppressed at the physiological tissue level by inhibiting sulfation at position 4 or 6 of GalNAc, which is a sugar that constitutes sugar chains. Furthermore, the present inventors conducted studies using various disease model animals, and as a result, successfully demonstrated that inhibitors of sulfation at position 4 or 6 of GalNAc had therapeutic effects on diseases caused by tissue fibrogenesis (tissue fibrogenic disorders).

The application belongs to the technical field of cell engineering and cell differentiation regulation, and discloses a method for directionally inducing secretion function cells from iPSCs and application thereof. The method takes the initial state of iPSCs and the potential of secretion function as cores, and constructs a pretreatment-induction differentiation integrated system. By screening and passing, iPSC clones with specific adhesion characteristics and enzyme sensitivity are enriched, and an iPSC population with enhanced secretion function potential is obtained. In the differentiation initiation stage, a culture system containing a Rock inhibitor is used in combination with laminin modified culture surface to maintain the intercellular connection state and realize the synchronous response of the induction signal. Then, the directionally induced differentiation is carried out by adding induction factors in stages, and the obtained cells are screened and purified to prepare high-purity secretion function cells. The prepared cells can be widely applied to drug screening, cell therapy and disease model construction, and provide technical support for the large-scale preparation of clinical-grade secretion function cells.

The application discloses a microfluidic pig intestinal tract-vascular-liver multi-organ chip and a construction method and application thereof, and belongs to the cross field of microfluidic chips and organoid technology. The chip performs three-dimensional and dynamic series type co-culture on a pig intestinal tract organoid, pig vascular endothelial cells and a pig liver organoid, and constructs an in-vitro pig liver-intestinal circulation microphysiological system containing a complete 'intestinal tract absorption-blood circulation-liver metabolism' channel. The application can not only highly simulate the microstructure and interactive function of pig intestinal tract and liver tissues, but also can be used for establishing a time-controllable intestinal-liver combined injury and repair model. Compared with a traditional static cell co-culture technology, the application can more simulate in-vivo dynamic physiological and pathological processes, has high specificity and accuracy, and provides a powerful standardized in-vitro platform for the research on the nutrition metabolism of large livestock animals, the evaluation of drugs and the construction of disease models.

The application belongs to the technical field of disease model construction, and particularly relates to a construction method of an animal model of primary cardiomyopathy and application thereof. The construction method of the animal model of primary cardiomyopathy provided by the application shows typical characteristics of primary cardiomyopathy, such as a reduced ratio of heart weight to body weight, a reduced ratio of heart weight to tibia length, a decreased cardiac ejection fraction, a decreased left ventricular short axis shortening rate, a decreased left ventricular end-diastolic diameter and left ventricular end-systolic diameter, and a significantly increased area of cardiac fibrosis. The animal model can be used in research on primary cardiomyopathy and screening of drugs for treating primary cardiomyopathy, and has a wide application prospect.