18 results about "Disease mechanisms" patented technology

This invention belongs to the field of vertebrate technology, specifically relating to a method for constructing a complex inflammatory animal model in middle-aged and elderly individuals and its related applications. The method includes: selecting adult animals for adaptive feeding, daily subcutaneous injection of D-galactose to establish a susceptibility to aging and oxidative stress, and administering sodium dextran sulfate (DSS) solution within a specific time window to induce intestinal inflammation, forming a complex inflammatory state through gut-hepatic axis interactions. The constructed animal model simultaneously exhibits intestinal inflammatory damage, abnormal hepatic oxidative stress, and aging-related characteristics, realistically simulating the pathological process of gut-hepatic axis dysfunction in middle-aged and elderly individuals. This model is suitable for screening and evaluating drugs, medical nutrition products, and functional foods that improve gut-hepatic axis dysfunction, providing a reliable technical platform for research on related disease mechanisms and the development of interventional substances.

The invention relates to the technical field of molecular biology and precision medical treatment, and relates to a molecular marker for predicting FOLFOX chemosensitivity and application thereof. A patient-derived colorectal cancer organoid biological sample library is constructed, the heterogeneity of in-vitro drug reaction is analyzed and evaluated through transcriptome, clinical groups sensitive to FOLFOX chemotherapy can be accurately recognized, a molecular marker prediction system containing 11 genes is obtained through further screening, and the molecular marker prediction system is used for predicting the FOLFOX chemotherapy. The method effectively overcomes the technical defect of lack of accurate prediction of colorectal cancer chemosensitivity at present, and has important value in the aspects of revealing disease mechanisms and guiding personalized treatment.

This invention relates to a method for disease therapeutic target discovery and drug prediction based on multi-omics networks and deep learning models, belonging to the interdisciplinary field of bioinformatics and artificial intelligence drug discovery. The method includes: integrating genomic expression profiles and common molecular interaction data from disease and control groups to construct a candidate whole-genome network; refining the network based on expression profile data through systematic modeling and the AIC criterion to obtain the real molecular interaction network; extracting the core network using the master network projection method and identifying key targets through pathway analysis; predicting candidate drugs interacting with the targets using a pre-trained deep neural network model; and finally screening potential therapeutic drugs based on multi-dimensional criteria such as regulatory ability, sensitivity, and toxicity. This invention achieves a complete integration from disease mechanism analysis to drug prediction, and is particularly suitable for complex diseases such as atopic dermatitis. It can systematically discover precise targets and efficiently predict repositionable drugs, significantly improving R&D efficiency.

The application discloses a virtual cell analysis platform based on cell disturbance data. The platform comprises three parts: a large language model data preprocessing system, a database and an online analysis platform, and a direction matching algorithm. The large language model data preprocessing system comprises an automatic data information extraction and retrieval tool, an automatic data file download tool, a large language model analysis engine and a gene expression data acquisition and feature extraction tool. The application can automatically preprocess the original data by applying the large language model data preprocessing system to the target scientific problem, and then store the data in the database. The characteristic direction matching algorithm is combined to output the drugs and key targets related to the target data set. The efficiency of target point and drug screening is improved. The application is suitable for large-scale omics data mining and disturbance analysis, accelerates the drug research and development, disease mechanism and translational medicine research process, and reduces the research and development cost.

The application discloses a virtual cell analysis platform based on cell disturbance data. The platform comprises three parts: a large language model data preprocessing system, a database and an online analysis platform, and a direction matching algorithm. The large language model data preprocessing system comprises an automatic data information extraction and retrieval tool, an automatic data file download tool, a large language model analysis engine and a gene expression data acquisition and feature extraction tool. The application can automatically preprocess the original data by applying the large language model data preprocessing system to the target scientific problem, and then store the data in the database. The characteristic direction matching algorithm is combined to output the drugs and key targets related to the target data set. The efficiency of target point and drug screening is improved. The application is suitable for large-scale omics data mining and disturbance analysis, accelerates the drug research and development, disease mechanism and translational medicine research process, and reduces the research and development cost.

This invention relates to a method for constructing a polycystic kidney disease (PCD) model and its applications. The method involves overexpressing the MYCN gene in a target animal to obtain a PCD model that leads to PCD-related phenotypes. The method includes the following steps: obtaining a first strain of mice with Rosa26 knock-in overexpressing the CAG-LSL-HA tag-MYCN-IRES-BFP-Wpre-polyA gene; obtaining a second strain of mice by inserting Cre-WPRE-polyA into the start codon of the Pax8 gene; and crossing the first and second strains of mice to obtain a MYCN-overexpressing PCD model. This invention employs various experimental methods for validation, including histopathological analysis, immunohistochemical staining, and Western blotting. The model provided by this invention overcomes the limitations of existing in vitro cell models, organoids, and existing animal models in terms of limited phenotypes. The established MYCN-overexpressing PCD animal model exhibits stable disease progression and a short disease cycle, which not only helps to elucidate the disease mechanism but also serves as an ideal platform for drug screening and efficacy evaluation.

This invention relates to an in vitro method for mapping the spatiotemporal electrophysiological dynamics and spatial transcriptional profiles of cells in a functional neuronal cell ensemble. This in vitro method includes simultaneously recording and analyzing spatial data of molecular activity and electrical network activity at the level down to individual cells using high-density electrobiosensors, spatial transcriptomics, optical imaging, and advanced computational strategies. The invention also relates to: methods for identifying the composition of a functional neuronal ensemble; methods for monitoring the spatiotemporal electrophysiological dynamics and transcriptional profiles of cells in a functional neuronal cell ensemble; methods for monitoring the cellular composition of a functional neuronal ensemble; methods for identifying compounds that influence spatial electrophysiological and transcriptional dynamics; and / or methods for identifying the cellular composition of a functional neuronal cell ensemble based on detected dynamics; and devices thereof. This invention allows for a better understanding of disease mechanisms, the identification of therapeutic targets, and the development of new drugs and treatment regimens.

This invention discloses a monoclonal antibody against Oit3 protein in mouse hepatic sinusoidal endothelial cells or its antigen-binding fragment and its applications, belonging to the fields of biotechnology and medical immunology. The monoclonal antibody or its antigen-binding fragment comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region contains HCDR1, HCDR2, and HCDR3 with amino acid sequences as shown in SEQ ID NO. 3~SEQ ID NO. 5; the light chain variable region contains LCDR1, LCDR2, and LCDR3 with amino acid sequences as shown in SEQ ID NO. 8~SEQ ID NO. 10. This monoclonal antibody and the recombinant fluorescent antibody exhibit high affinity and high specificity, and can be effectively applied to enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunofluorescence detection. They can serve as important antibody tools for basic research on mouse hepatic sinusoidal endothelial cells and for exploring the mechanisms of liver diseases. Based on its variable region sequence, a recombinant fluorescent antibody, Oit3-scFv-GFP, was also constructed. This recombinant fluorescent antibody enables one-step direct immunofluorescence staining, providing a convenient tool for in situ visualization of mouse hepatic sinusoidal endothelial cells.

The application provides an animal brain metabolite identification method based on mass spectrometry imaging technology and application, and establishes a mouse brain tissue slice endogenous metabolite DESI-MSI analysis method based on mass spectrometry imaging technology, which comprises the following steps: after preparing metabolite control sample imaging samples and brain tissue slice imaging samples, multiple animal brain tissues are attached to the same glass slide, mass spectrometry imaging condition optimization is carried out by using the control sample imaging samples, and mass spectrometry imaging analysis is carried out by using the brain tissue slice imaging samples; the image of the biological sample is divided into multiple structure regions in combination with tissue morphological characteristics; for the structure regions, multivariate statistical analysis is carried out to obtain different metabolites in different structure regions; metabolite identification is carried out based on parent ions and characteristic daughter ion profiles; and the method is used for disease mechanism research and drug intervention effect evaluation on diseases.

The invention discloses a biomarker for diagnosing Alzheimer's disease as well as a screening method and application thereof, relates to the technical field of biomarkers for Alzheimer's disease, and aims to solve the technical problems that the Alzheimer's disease lacks dynamic pathological monitoring indexes and stereoisomeric modification is difficult to systematically detect. According to the invention, the stereoisomeric modification level of peptide fragments KLDLSNVQSK and AKTDHGAEIVYK is used as the core biomarker for the first time, the modification level is remarkably related to the Braak staging of AD, and a detection method and a combined diagnosis model containing the marker are provided. A novel molecular target with high correlation and dynamic monitoring potential is provided for AD, the model diagnosis precision is remarkably improved, and a brand new solution is provided for disease mechanism research and drug development.

The application provides a method for synchronously detecting multiple cell death modes in a tissue slice based on multiplex immunofluorescence, and belongs to the technical field of biological detection. The application realizes the synchronous labeling and visualization of multiple cell death modes in a single tissue slice, significantly improves the detection efficiency and saves precious samples; by integrating key biomarkers covering main cell death modes in the same detection system, a self-defined interpretation scheme based on multi-marker expression combination is constructed, effectively reducing the error caused by non-specific expression of a single marker, improving the reliability and rationality of the death mode classification, and providing a general solution for rapid screening of complex cell death networks. The application is suitable for anticancer drug efficacy evaluation, combination drug regimen screening and disease mechanism research, and has important scientific research value and clinical conversion prospect.

This invention provides a method for predicting protein methylation sites that integrates quantum and region-aware technologies, comprising the following steps: Step 1, obtaining protein sequences as data sources and constructing training and independent test sets respectively; Step 2, constructing multimodal features for each protein sequence using a three-way nested scattering network, fusing the multimodal features to obtain an optimized fused feature tensor; Step 3, inputting the optimized fused feature tensor into a RaQMeNet network model to perform methylation site prediction. This invention not only significantly outperforms existing technologies in terms of performance indicators but also possesses stronger adaptability, stability, and interpretability. It can be widely applied in multiple bioinformatics and biomedical fields such as protein functional annotation, disease mechanism research, and drug target discovery, demonstrating promising application prospects and commercial value.

The application discloses a preparation method of cat induced pluripotent stem cells, which comprises the following steps: constructing piggyBac transposon plasmids carrying cat source OCT4, SOX2, KLF4 and c-MYC four factors in series, piggyBac transposon plasmids carrying cat source or pig source NANOG and LIN28 two factors in series and piggyBac transposon plasmids carrying monkey kidney virus SV40LT plasmids, and transfecting the plasmids into cat fetal fibroblasts; picking up cloned cells with embryonic stem cell morphologies, and carrying out subculture of cell clones meeting the characteristics of embryonic stem cells through identification and screening, so that the cat induced pluripotent stem cells are obtained. The preparation method of the cat induced pluripotent stem cells is safe, efficient and has good differentiation potential, lays a scientific foundation for researching in-vitro culture conditions of feline ESCs and establishment of feline iPSCs, and lays a scientific foundation for further cultivating cloned cats and gene modified cats and researching in related disease mechanisms, screening drugs and regeneration and repair.

This invention discloses a AIPL1 A gene mutation-related congenital amaurosis animal model, its construction method, and its application. The method includes: S1, constructing a humanized... AIPL1 S2, a homologous recombination vector with a point mutation of c.421 C>T (p.Q141X) knocked in; S3, Cas9 mRNA, gRNA1, gRNA2 and the homologous recombination vector are injected into animal zygotes to perform homologous recombination, resulting in transfected zygotes; S4, the transfected zygotes are transplanted into the uterus of pseudopregnant animals to reproduce offspring, and offspring are selected from the offspring. AIPL1 Homozygous animals with the c.421 C>T (p.Q141X) point mutation were obtained, thus yielding the aforementioned... AIPL1 A gene mutation-related congenital amaurosis animal model. The animal model of this invention exhibits the clinical phenotype of Leber congenital amaurosis type 4 (LCA4) from 12 days after birth; while heterozygous mice do not show a significant phenotype, consistent with... AIPL1 The clinical phenotype and inheritance pattern of LCA caused by the c.421 C>T (p.Q141X) gene mutation demonstrate the effectiveness and reliability of the animal model of this invention, providing a basis for understanding the genetic model of LCA. AIPL1 Animal models provide a reliable basis for studying the disease mechanisms and drug screening of mutation-related LCA.

This invention discloses a lipid droplet fluorescent probe, Lipi-om, its preparation method, and its applications, belonging to the field of bioimaging and fluorescent probe technology. The technical solution includes a lipid droplet fluorescent probe, Lipi-om, with a molecular structure of electron donor-electron acceptor-electron donor. This lipid droplet fluorescent probe can perform high-resolution imaging of intracellular lipid droplets under SIM conditions, enabling the tracking of lipid droplet distribution and dynamic behavior, including lipid droplet fusion and division processes. Simultaneously, this probe can be used in conjunction with the mitochondrial probe PK Mito Deep Red to visualize the dynamic and stable contact processes between lipid droplets and mitochondria. This allows for the study of organelle interactions and the distribution and dynamic behavior of lipid droplets in living cells, and can be used for the visual analysis of lipid droplet-mitochondrial interactions, possessing significant application value in cell biology and disease mechanism research.

This invention relates to the field of single-cell functional analysis and microfluidic chip technology, and discloses a kit and method for in-situ sequential quantitative detection of secreted and intracellular proteins in the same single cell. The kit includes: a microcavity array chip; a secreted protein capture antibody barcode chip and an intracellular protein capture antibody barcode chip; a plastic clamp; a bioaffinity modification reagent; secreted protein standards, intracellular protein standards, secreted protein detection antibody stock solution, and intracellular protein detection antibody stock solution; a fluorescent conjugate, antibody buffer, antibody blocking solution, cell lysis buffer, and cell washing buffer. The method of this invention, through a sequential detection process of first capturing and incubating secreted proteins, followed by in-situ lysis to capture intracellular proteins, achieves high-throughput, high-sensitivity, and high-specificity in-situ sequential quantitative detection of secreted and intracellular proteins in the same single cell without cell transfer or loss of spatial location information. It can establish a correlation analysis of "intracellular signaling pathway activation - external functional output" in single cells, providing a powerful tool for disease mechanism research, drug screening, and immunotherapy evaluation.

This invention relates to a device for in-situ extraction and real-time detection of single-cell contents, comprising: a nanoparticle extraction unit, including a glass capillary and an alumina nanoparticle membrane integrated at the front end of the glass capillary; a nanopore sensing unit, disposed within the glass capillary, including a glass nanopore membrane and a phospholipid bilayer supported on its surface, wherein functionalized protein nanopores are embedded in the phospholipid bilayer; and a signal acquisition unit, including two electrodes located at the rear and front ends of the glass capillary, respectively, which provide voltage to the nanopore sensing unit and record in real time the characteristic current signal generated by target molecules passing through the nanopores. This invention integrates a nanoparticle membrane for cell contents extraction and a functionalized protein nanopore sensor for small molecule recognition and monitoring, providing technical support for studying cellular dynamics, disease mechanisms, and drug responses.

This application relates to the biomedical field and discloses a method for constructing and using a co-culture system for colorectal and liver organoids. The method involves optimizing the culture conditions for human colorectal and liver organoids separately, and then seeding both types of organoids into a co-culture environment to form a stable co-culture system. This system can simulate the physiological environment of the colorectum and liver in vivo and can be used to screen drugs that affect the colorectal-liver axis, assess the potential toxicity of drugs during metabolism, and also provides an important experimental tool for exploring disease mechanisms and developing novel treatment strategies.