28 results about "Oligodendrocyte" patented technology

The present invention discloses the use of extracellular vesicles derived from oligodendrocytes carrying FTH1 in differentiating between multiple system atrophy and Parkinson's disease, belonging to the field of biomedical technology. The present invention utilizes fluorescently labeled CNPase antibodies and FTH1 antibodies to accurately detect extracellular vesicles derived from oligodendrocytes carrying FTH1 in plasma. By detecting the concentration of extracellular vesicles derived from oligodendrocytes carrying FTH1 (FTH1-positive) in plasma, it is possible to accurately distinguish between MSA patients, PD patients, and healthy individuals. This provides a highly effective biomarker for MSA diagnosis, improves the ability to diagnose MSA early and differentiate between MSA and PD, and effectively addresses the complexity and low sensitivity issues faced by traditional diagnostic methods.

The invention belongs to the technical field of biomedical materials, and particularly relates to astragaloside-loaded conductive hydrogel as well as a preparation method and application thereof. The preparation method comprises the following steps: uniformly mixing a methylacrylic anhydride gelatin aqueous solution with an organic solvent solution of astragaloside, and carrying out ultraviolet light cross-linking curing to form methylacrylic anhydride gelatin / astragaloside hydrogel; soaking the obtained hydrogel in hydrochloric acid containing a free radical initiator; then soaking and polymerizing in an aniline ethanol solution; and soaking and purifying to obtain the methylacrylic anhydride gelatin-polyaniline conductive hydrogel loaded with astragaloside. In-vitro experiments prove that the compound has a certain anti-inflammatory effect, can induce neural stem cells to be directionally differentiated into neurons and oligodendrocytes, and is beneficial to promoting nerve regeneration and myelin sheath formation; finally, in-vivo experiments prove that the composition can improve the athletic ability and tissue function recovery of SCI rats, and has a good application prospect.

To provide a method for generating oligocortical spheroids (OCS) from pluripotent stem cells (PSC).SOLUTION: A method comprises the steps for: a) generating a neurocortical spheroid (NCS) through neurocortical patterning of pluripotent stem cells; b) subjecting the neurocortical spheroid to timed exposure to defined oligodendrocyte lineage growth factors and / or hormones, to promote proliferation, survival and / or expansion of native oligodendrocyte progenitor cell (OPC) populations within the neurocortical spheroid, thereby generating the oligocortical spheroid, wherein the oligocortical spheroid contains oligodendrocyte progenitor cells capable of differentiating into myelinating oligodendrocytes (ODCs) that are capable of myelinating axons.SELECTED DRAWING: Figure 1-1

The invention belongs to the technical field of biological medicine, and particularly relates to a single-domain antibody VHH-L1 targeting LINGO-1 protein, and the amino acid sequence of the single-domain antibody VHH-L1 is shown as SEQ ID NO: 1. The single-domain antibody has nanomole-level high affinity and excellent specificity, can effectively block the interaction between LINGO-1 and ligands thereof, and remarkably promotes differentiation and myelination of oligodendroglia cells. The invention further provides a neural stem cell subjected to genetic engineering modification, and the neural stem cell can stably and continuously secrete the single-domain antibody VHH-L1. In a spinal cord injury animal model, the engineered stem cell shows an excellent treatment effect, can significantly promote motor function recovery, axon regeneration and myelin sheath repair, and effectively inhibits glial scar formation. The double advantages of cell therapy and long-acting protein delivery are fused, and a brand new efficient treatment strategy is provided for demyelination diseases such as multiple sclerosis and spinal cord injury.

The invention discloses a method for constructing a neurodevelopmental disorder animal model based on central nervous system myelin sheath function change and application, and belongs to the technical field of biological engineering. An Msl2 gene conditional knockout mouse model is constructed by adopting a gene engineering technology, the space-time specific knockout of a second exon of the Msl2 gene in a specific cell type is realized through a Cre-LoxP recombinase system, and the exon encodes a key enzyme activity region for catalyzing ubiquitination. Model construction is based on central nervous system oligodendrocyte / myelin sheath dysfunction, the behavior phenotype of the model is similar to the behavior of a typical neurodevelopment disorder animal, a brand new perspective is provided for exploring an etiology mechanism, model mice can be prepared on a large scale by performing directional mating on the gene modified mice, and the development of the model is promoted. And consistency of different experiment batches and reliable reproduction of experiment data are ensured.

In nerve diseases, cell dysfunction due to amyloid aggregate accumulation in nerve cells has attracted attention, but dysfunction of nerve axons responsible for neurotransmission is also considered to be one of the causes. However, no therapeutic agent that focuses on the repair and maintenance of nerve axons has been found. An object of the present invention is to provide a therapeutic agent that activates oligodendrocytes having a function of preserving nerve axons.SOLUTION: Transcriptome analysis with a psychotropic drug is carried out using an oligodendrocyte marker as an indicator, and it is found that the combined use of DPZ and NFN characteristically increases the expression of a transcriptional factor OLIG1 inducing the differentiation-maturation of the oligodendrocyte. Moreover, the drug concentration at this time was much lower than the expected clinical dose. The combined use of NFN and DPZ was observed to improve spatial memory in the mouse Y-maze test. The combination of NFN and DPZ can provide a novel treatment for cognitive and memory functions associated with neurological disorders.SELECTED DRAWING: None

The invention discloses a construction method of a mouse model capable of specifically photoactivating oligodendrocyte precursor cells, and belongs to the technical field of animal genetic engineering. On the basis of a Cre-loxP recombinase system, NG2 is selected as a specific promoter of oligodendrocyte precursor cells, an NG2-CreERT: cOpn5 mouse expressing photosensitive protein cOpn5 under specific driving of NG2 is constructed, and compared with a traditional method for injecting photosensitive protein cOpn5 through viruses, the mouse model can avoid tissue damage caused by the method; meanwhile, the method can also be used for functional research of the oligodendrocyte precursor cells, so that the research on the effect of the oligodendrocyte precursor cells in a nervous system is facilitated, and a new strategy and a new method can be possibly provided for treating related nervous system diseases and developing drugs of the related nervous system diseases.

This invention relates to the field of biomedical technology, and provides the application of compound LY2940094 in the preparation of drugs for treating demyelinating diseases of the central nervous system. This invention verifies through modern biological techniques that compound LY2940094 can promote the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), thereby promoting the regeneration of myelin in the central nervous system and thus treating demyelinating diseases of the central nervous system.

An object of the present invention is to provide a method of evaluating intercellular interactions in neuroinflammation using a co-culture containing human-derived neural cells capable of mimicking human brain functions. According to the present invention, there is provided a method of evaluating intercellular interactions in neuroinflammation, the method including a step of producing a co-culture containing at least two cells selected from the group consisting of human-derived astrocytes, human-derived neurons, human-derived microglia, and human-derived oligodendrocytes, a step of applying an inflammatory stimulation to a first cell contained in the co-culture, a step of detecting at least one selected from the group consisting of an inflammatory response marker in the cells contained in the co-culture, neural activity of the cells, and cell morphology, and a step of evaluating, over time, a change in at least one selected from the group consisting of the inflammatory response marker, the neural activity, and the cell morphology in the first cell and a second cell different from the first cell contained in the co-culture.

The application belongs to the technical field of biological drugs, and particularly relates to a preparation method of genetically modified human bone marrow mesenchymal stem cells and application thereof in treating nervous system diseases, in particular, multiple sclerosis. The human bone marrow mesenchymal stem cells are double-modified by brain-derived neurotrophic factor (BDNF) and anti-S1PR5 nanobody, so that the activity of the human bone marrow mesenchymal stem cells is improved, the survival of neurons or oligodendrocytes is promoted, cell apoptosis is inhibited, and myelin regeneration is promoted, and the human bone marrow mesenchymal stem cells can be applied to nervous system diseases, in particular, multiple sclerosis.

The invention provides a pathogenic factor for neurodegenerative diseases and application of the pathogenic factor. The pathogenic factor for the neurodegenerative diseases is a PASP-GPR37-IL-6 signal axis. According to the application, the action mechanism of the PASP-GPR37-IL-6 signal axis serving as a neurodegenerative disease (especially Parkinson's disease) pathogenic factor is defined for the first time, the molecular path of neuroinflammation and neurodegenerative diseases regulated and controlled by the oligodendroglia through the signal axis is disclosed, and the research blank of participation of the oligodendroglia in PD pathogenesis in the prior art is filled.

This invention describes artificial expression constructs for regulating gene expression in target types of central nervous system cells. By using the artificial expression constructs of this disclosure, it is possible to express or modify the expression of synthetic genes in spinal motor neurons, including SpP1 spinal motor neurons, Parg spinal motor neurons, Ogdh1 spinal motor neurons, and ChAT spinal motor neurons; α motor neurons, including Chodl spinal motor neurons; γ motor neurons; spinal excitatory motor neurons, including Mafa excitatory neurons, Esrrg Trhr excitatory neurons, and Slc17a6 spinal excitatory neurons; spinal inhibitory neurons, including Slc6a5 spinal inhibitory neurons; whole spinal neurons, including Esrrg spinal motor neurons and types of neurons found throughout the spinal cord; cerebrospinal fluid contact neurons, including Poln spinal motor neurons; and non-neuronal cells of the spinal cord, including astrocytes and oligodendrocytes.

An embodiment of the present invention discloses a risk prediction system for an immune effector cell mediated neurotoxic syndrome (ICANS) and an application thereof, the system comprising: a processor and a memory coupled to the processor, the memory storing instructions, when the instructions are executed by the processor, the following steps are used: inputting a numerical value of an index into a prediction model to obtain an occurrence probability of the immune effector cell mediated neurotoxic syndrome; the prediction model comprises the following steps: by taking free DNA (cfDNA) traceability concentrations of oligodendrocytes A, B cells B and megakaryocytes C as prediction factors, establishing a risk prediction system formula of the immune effector cell mediated neurotoxic syndrome; the system can be used to assess the risk of immune effector cell mediated neurotoxic syndrome and possibly guide the selection of therapeutic regimens thereof.

This invention discloses the application of α-ketoglutarate in the preparation of agents that promote oligodendrocyte precursor cell differentiation, belonging to the field of biomedical technology. This invention is the first to use α-ketoglutarate in the preparation of drugs for the prevention and / or treatment of OPC differentiation disorders. Experimental results show that exogenous supplementation with α-ketoglutarate or its derivatives can regulate the differentiation level of OPCs under physiological conditions, effectively promote OPC differentiation, and improve symptoms such as decreased motor function and shortened lifespan caused by OPC differentiation defects. It demonstrates good efficacy and safety, and possesses high clinical application value.

The invention relates to the field of biomedicine, in particular to a mouse oligodendroglia precursor cell culture method which mainly comprises the following steps: taking cerebral cortex tissues of a 3-day-old mouse, cutting the cerebral cortex tissues into pieces, digesting the cerebral cortex tissues to obtain mixed glial cells, and inoculating and culturing the mixed glial cells; and after culturing for 10 days, carrying out mechanical oscillation on a shaking table (the rotating speed is 250rpm, and the time is 6 hours), and separating to obtain the oligodendrocyte precursor cells with high purity and high activity. The method is easy and convenient to operate and high in repeatability, a large number of mouse oligodendroglia precursor cells can be obtained only through a conventional, simple and cheap culture medium, and the cells have the continuous multiplication capacity, can be continuously passaged and have the capacity of being differentiated into mature oligodendroglia cells; the method can be widely applied to in-vitro research of special physiological functions and related biological mechanisms of the mouse oligodendrocyte precursor cells.

The invention discloses a substance for targeted inhibition of IRF1 gene expression and application thereof. The substance comprises nucleic acid for specifically silencing the IRF1 gene. The nucleic acid is siRNA (small interfering Ribonucleic Acid) containing the following sequence or a cloning vector for transcriptional coding of the following sequence: 5 '-TCACCAAGAACCAGGAA-3'. The siRNA is applied to preparation of drugs for regulating differentiation and apoptosis of oligodendrocyte precursor cells and drugs for promoting remyelination and repairing spinal cord injury. According to the invention, IRF1 is taken as a molecular intervention target, and IRF1 expression is reduced or inhibited, so that apoptosis of oligodendrocyte precursor cells is significantly inhibited, differentiation and maturation of the oligodendrocyte precursor cells are promoted, and the purpose of promoting myelin sheath recovery of spinal cord injury is achieved.

The present disclosure relates to targeted bispecific transferrin receptor 1 (TfR-1) antibodies and methods of use thereof. In particular, provided herein are oligodendrocyte- and neuron-targeting bispecific TfR-1 antibodies and methods of use thereof.

The invention provides a preparation method and application of an Slc44a1b gene knockout zebrafish myelin sheath development disorder model, and belongs to the technical field of biology. The Slc44a1b gene knockout zebrafish strain is constructed for the first time, the blank of Slc44a1 family gene zebrafish mutants is filled, simulation of myelin sheath disorder caused by Slc44a1b deletion in a living body transparent model is achieved for the first time, and the defect that a mammal model cannot be imaged in real time is overcome. A brand new model is provided for studying the function of the Slc44a1 family gene in vertebrates, and a gene editing resource library of zebrafish myelin sheath study is enriched; and meanwhile, by utilizing the living imaging advantage of the zebra fish, the dynamic influence of the SLC44A1 on zebra fish oligodendrocyte maturation and myelin sheath formation is disclosed, and a key experimental evidence is provided for understanding a molecular network of myelin sheath development.

The present invention relates to use of slow-releasing hydrogen sulfide organic donor ADT-OH drugs in the differentiation of neural precursor cells. ADT-OH can induce more directed differentiation of neural precursor cells into neurons and oligodendrocytes and less differentiation into astrocytes, promote the axon growth of neurons, and reduce the death of neural precursor cells, thereby providing a direction for the transplantation of neural precursor cells to repair damaged nerves. ADT-OH will likely become a new drug target for the clinical treatment of nervous system diseases.

The present application belongs to the field of animal models, and more specifically, a method for constructing an autism spectrum disorder mouse model by BAF155 conditional knockout mode is disclosed. By constructing a specific knockout BAF155 mouse, the effect of knockout BAF155 on OL development and myelination is observed. Further proved by the behavior experiment, the deletion of BAF155 in oligodendrocyte precursor cells will lead to the appearance of the core and characteristic ASD-like behavior phenotype of mice mainly with social preference disorder and repetitive stereotyped behavior. Therefore, the present application successfully constructs a new genetic molecular defect ASD animal model, and the advantage lies in that the target is clear, a single genetic molecular defect can be induced to study ASD, and a suitable and matched animal model for ASD caused by mutation of BAF155 is provided, which is helpful for precise diagnosis and subsequent intervention strategy.

The present application relates to nerve growth factor inducible protein or its gene in the preparation of treating spinal cord injury drug application. The present application proves that the lentivirus of overexpressing nerve growth factor inducible protein gene can promote the regeneration of oligodendrocytes, and then can effectively improve the recovery of motor function of spinal cord injury animal model through cell experiment and animal experiment.

The invention belongs to the field of animal models, and particularly relates to a construction method and application of a demyelination animal model. The construction method comprises the steps that a titanium dioxide nano-particle solution is injected into a model animal in a gavage mode, the single-time gavage dosage of titanium dioxide nano-particles is 0.1 mg / kg-10 mg / kg, gavage is carried out for 1-3 times every day, and gavage lasts for 20-60 days. According to the invention, from the perspective of cell migration, titanium dioxide nanoparticles are utilized to intervene in a model animal, migration of oligodendrocyte precursor cells is inhibited, inflammatory reaction and oxidative stress reaction are induced, body demyelination is caused, and the multiple sclerosis demyelination animal model is successfully constructed. The modeling method provided by the invention has the advantages of high modeling rate, typical pathological expression, simplicity and convenience in operation, short modeling period and survival rate up to 100%, and can be applied to the fields of pathogenesis research and pathological characteristic research of demyelination diseases, screening, preparation or efficacy evaluation of related therapeutic drugs and the like.

The present invention generally relates to a method for producing induced oligodendrocyte-lineage cells (OLGs) and using the cells for treatment. The induced oligodendrocyte-lineage cells (OLGs) can be used for cell therapy, particularly for demyelination diseases.

The invention discloses an application of taurine in treatment of hair growth matrix bleeding of premature infants, and relates to a new application of taurine in preparation of a medicine for preventing or improving white matter injury after the hair growth matrix bleeding (GMH) of the premature infants. The medicine takes taurine as an active ingredient and is administered in manners of intraperitoneal injection and the like, and the preferable dosage is 120 mg / kg / day. In-vivo and in-vitro experiments show that the taurine can remarkably reverse mitochondrial dysfunction of oligodendrocyte precursor cells (OPCs) after GMH, and by activating PINK1 / Parkin mediated mitochondrial autophagy and promoting survival and maturation of the OPCs, myelin sheath formation and tissue structures are improved, and finally sensory movement and cognitive function recovery are promoted. The invention provides a strategy which is novel in mechanism and easy in clinical transformation for preventing and treating secondary white matter injury after GMH.

The invention discloses a research method of a DNA (Deoxyribose Nucleic Acid) methylated transferase regulation mechanism of oligodendrocyte myelin sheath abnormality, and belongs to the technical field of detection research. The method comprises the following steps: S1, constructing a gene knockout mouse and a gene overexpression mouse through a gene editing technology, and setting a normal mouse as a control group; s2, separating and culturing the oligodendroglia cells; and S3, detecting the activity of the methylated transferase, the DNA methylation level and the myelin sheath index of the oligodendroglia cells. The invention focuses on a brand-new research method of a DNA methylated transferase regulation mechanism aiming at oligodendrocyte myelin sheath abnormality, and aims at deeper and more accurate analysis of the regulation mechanism by taking a mouse as an experimental model. According to the method, advanced molecular biology technology, cell biology technology and bioinformatics analysis means are integrated, and a set of comprehensive and systematic solution is provided for related research.

Oligonucleotide conjugates are provided herein that inhibit or reduce expression of target genes in the oligodendrocytes of the central nervous system. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and / or conditions associated with expression of an oligodendrocyte target gene in the CNS.

The present invention addresses the problem of providing a method for evaluating intercellular interaction in neuroinflammation using a co-culture containing human nervous system cells capable of mimicking human brain functions. According to the present invention, provided is a method for evaluating the intercellular interaction of neuroinflammation, the method comprising: a step for producing a co-culture comprising at least two types of cells selected from the group consisting of human astrocytes, human nerve cells, human microglial cells, and human oligodendrocytes; a step for applying an inflammatory stimulus to a first cell included in the co-culture; a step for detecting at least one substance selected from the group consisting of intracellular inflammatory response markers, cellular neural activity, and cellular morphology included in the co-culture; and a step for evaluating, over time, a change in at least one type selected from the group consisting of the inflammatory response marker, the neural activity, and the cellular morphology in the first cell and a second cell different from the first cell included in the co-culture.