20 results about "Astrocyte cells" patented technology

The application discloses application of T1R3 agonist sucralose in relieving Alzheimer's disease and related cognitive impairment, and aims at brain glucose metabolism disorder and cognitive decline problem, and the application takes sucralose as the only pharmaceutical active ingredient, corrects brain glucose metabolism disorder through targeting brain astrocyte sweet taste receptor T1R3, and then treats and relieves neurodegenerative diseases. The application is proved by animal experiments that cognitive dysfunction of AD model mice can be improved in a full range of molecular mechanisms, cell functions, tissue metabolisms and whole behavior, and a variety of dosage forms and medication strategies can be selected, and the application has good in-vivo safety and clinical transformation potential.

The present application belongs to the field of biomedical technology, and particularly relates to a cell-derived extracellular matrix and a preparation method and application of a cell culture plate coated with the cell-derived extracellular matrix. The present application cultures human astrocytes in a cell culture plate, and makes the human astrocytes secrete extracellular matrix. After the human astrocytes are added into a cell lysate for cell removal treatment, nucleic acid fragmentation treatment is performed to obtain the cell-derived extracellular matrix. The present application has relatively simple operation, short time period, and can realize batch production of extracellular matrix without external virus carrying and stable components. The obtained cell-derived extracellular matrix is resistant to storage, has good stability, is highly similar to a natural brain environment when coated on a cell culture plate, has good biocompatibility with cells, can be applied to tissue repair and regeneration as an ideal biomedical material, can regulate the progress and efficiency of human dermal fibroblast HDF transdifferentiation into neurons, and can obtain in-vitro survival neurons.

The present application relates to the technical field of biotechnology, and particularly discloses a composition and a method for reprogramming astrocytes into functional neurons. The composition for reprogramming astrocytes into functional neurons comprises a compound PT109B. The composition for reprogramming astrocytes into functional neurons provided in the present application can reprogram astrocytes into functional neurons, and effectively solves the problems of a large number of small molecules and complicated steps in the current chemical reprogramming technology.

Methods and compositions for manipulating metabolism in astrocytes to improve astrocytic and neuronal function, as well as individual pathology hallmarks and symptoms during the development of neurodegeneration by increasing PPARα expression and activity specifically in astrocytes within the central nervous system to treat a variety of neurodegenerative conditions including but not limited to conditions involving neuronal lipid dysregulation, oxidative damage, accumulation of β-amyloid or other protein aggregates, dementia, and motor dysfunction. Also provided are methods of treating peripheral metabolic dysfunction associated with neurodegenerative conditions.

This invention relates to mutants of the adeno-associated virus (AAV) capsid protein. Recombinant viral vectors carrying mutants of the AAV1 capsid protein can be used for the specific expression of the introduced gene in astrocytes at the site of spinal cord injury lesions.

The application discloses application of an S1PR1 selective agonist SAR247799 in preparation of a drug for treating neuromyelitis optica spectrum disorders. The SAR247799 can up-regulate S1PR1 expression of astrocytes, activate an S1PR1 signal path of the astrocytes, inhibit AQP4-IgG and complement-mediated damage of the astrocytes, reduce loss of AQP4, GFAP and ALDH1L1 in a lesion area of brain tissue of a neuromyelitis optica spectrum disorder model mouse, and relieve pathological damage of the neuromyelitis optica spectrum disorder model. In-vivo and in-vitro experiments prove that the SAR247799 can effectively inhibit AQP4-IgG and complement-dependent cytotoxicity effects and promote survival of the astrocytes. The application provides a novel, efficient and specific targeted drug for clinical treatment of the neuromyelitis optica spectrum disorder.

This disclosure relates to adeno-associated virus variants capable of performing astrocyte-specific gene transfer. Administration of a recombinant viral vector containing nucleic acid encoding an AAV capsid protein mutant according to this disclosure enables the transfer and expression of therapeutic genes into specific astrocytes, thus demonstrating significant efficacy in the prevention or treatment of brain diseases.

[Object] An object of the invention is to provide a carbamoyl lipid having a cyclic group at a side chain, a lipid nanoparticle containing the lipid, and a pharmaceutical composition thereof.[Solution] The present inventors have found a carbamoyl lipid having a cyclic group at a side chain which can form a lipid nanoparticle and elucidated that a lipid nanoparticle containing the carbamoyl lipid having a cyclic group at a side chain of the invention as a component can express a protein in an astrocyte or a liver cell. Moreover, a lipid nanoparticle containing the carbamoyl lipid having a cyclic group at a side chain of the invention as a component is expected to be a component of a pharmaceutical composition which encapsulates a nucleic acid and which is useful for preventing and / or treating an astrocyte-related disease. 

This invention belongs to the field of biomedical technology and relates to the application of PAX8 gene inhibitors in the preparation of drugs for treating optic nerve degeneration. The PAX8 gene inhibitor is a shRNA that targets and inhibits the PAX8 gene or a vector expressing a shRNA that targets and inhibits the PAX8 gene. The vector uses the astrocyte-specific promoter gfabc1d. Experiments have demonstrated that by specifically inhibiting PAX8 expression in astrocytes, axoplasmic transport obstruction in the optic nerve is relieved, optic nerve degeneration is alleviated, and a new gene therapy strategy is provided for the protective treatment of optic nerve degeneration in glaucoma.

This invention belongs to the field of organ-on-a-chip technology, providing a blood-brain barrier / neuronal co-culture chip, an organ-on-a-chip, its construction method, and applications. The blood-brain barrier / neuronal co-culture chip provided by this invention includes a reservoir, vascular endothelial channels, a hydrogel chamber, and a brain region microenvironment channel. The vascular endothelial channels are used for seeding brain microvascular endothelial cells; the hydrogel chamber is used for seeding brain perivascular cells and astrocytes, and exchanges substances with the vascular endothelial channels through a porous membrane; the brain region microenvironment channel is used for seeding neurons, constructing a three-dimensional neuronal network growth environment. Using this blood-brain barrier / neuronal co-culture chip as the chip body, the construction of the blood-brain barrier, the glial support microenvironment, and the three-dimensional developmental space of neurons can be realized, achieving dynamic interaction between the blood-brain barrier and the neuronal microenvironment. It has broad application prospects in the study of the mechanisms of nervous system diseases and the evaluation of nervous system drugs.

This invention discloses an active immunization animal model of neuromyelitis optica spectrum disorder and its construction method. The construction method includes: extracting a membrane protein retaining the native conformational epitope of AQP4 from cells overexpressing AQP4-M23 as an immunogen; emulsifying the immunogen with an adjuvant and then actively immunizing non-human mammals to induce the production of autoantibodies against the AQP4 conformational epitope, thereby constructing an active immunization animal model of neuromyelitis optica spectrum disorder. This invention uses an AQP4 membrane protein rich in conformational epitopes as an immunogen, overcoming the limitation of traditional linear peptides in inducing pathogenic autoantibodies in wild-type mice. It successfully constructs an active immunization animal model capable of mimicking the core pathological features of human neuromyelitis optica spectrum disorder (including AQP4 loss and astrocyte damage), providing an important experimental platform for research on the pathogenesis of neuromyelitis optica spectrum disorder and drug screening.

The application discloses a neurotransmitter regulation interaction relationship model construction method and system, relates to the technical field of computational neuroscience, and comprises the following steps: constructing a neuron multimodal neurotransmitter co-release dynamics unit, defining small molecule neurotransmitter and neuropeptide respective vesicle pool state variables, and establishing a coupling release equation based on calcium dependence and regulatory protein selectivity, and outputting two types of neurotransmitter spatiotemporal release source terms; inputting the spatiotemporal release source terms into a three-dimensional brain space structure embedded with a receptor density map, solving a volume conduction equation, and generating a dynamic concentration field of a whole brain range of modulating neurotransmitters; according to a corresponding relationship between the dynamic concentration field and the local receptor density, calculating diffuse modulation input received by the neuron; based on the concentration of a specific modulating neurotransmitter in the dynamic concentration field, driving state evolution of an astrocyte cell unit, and outputting a concentration of a regulatory neurotransmitter released by the astrocyte cell; and integrating point-to-point synapse input, diffuse modulation input and the concentration of the regulatory neurotransmitter released by the astrocyte cell.

The application belongs to the technical field of biological medicine, and particularly relates to application of (E)-BCI hydrochloride in preparation of a medicine for treating sepsis. The application provides application of (E)-BCI hydrochloride in preparation of the medicine for treating sepsis. (E)-BCI hydrochloride regulates a DRD1 gene through targeting, quiets an interferon stimulation storm, reduces abnormal activation of astrocytes, reduces a level of an inflammatory factor, improves expression of a nerve activity gene, and provides a non-antibiotic dependent medicine for sepsis treatment from a new target point of regulating inflammation and immune balance, and is particularly suitable for systemic inflammatory response syndrome caused by various causes such as infection, operation and trauma, and has a wide clinical application prospect.

This invention discloses an Isl1-mimicking polypeptide, TAT-Isl1-ELE-1, containing 40 amino acids and consisting of a TAT sequence that promotes polypeptide entry into cells, a linker peptide, and a target sequence. The target sequence is amino acids 121-141 of the human Isl1 protein. The TAT-Isl1-ELE-1 polypeptide possesses Isl1-like functions and can effectively reprogram mouse spinal cord reactive astrocytes into motor neuron-like cells. Based on the amino acid sequence and spatial structure of this polypeptide, a novel small molecule drug can be designed, which can be synthesized in large quantities and is easy to operate clinically. This provides a new and viable approach for cell replacement therapy and regenerative medicine research after spinal cord injury (SCI), thereby achieving better SCI repair and functional reconstruction effects.

This invention relates to the field of biomedical image processing technology, specifically a two-dimensional cellular two-photon image analysis system and method, comprising: an image preprocessing subsystem for acquiring and preprocessing calcium imaging video to obtain feature-enhanced images; a subcellular segmentation subsystem for segmenting the image into subcellular structures using a hybrid detection strategy, wherein the hybrid detection strategy consists of manual annotation and adaptive thresholding; and a calcium response feature extraction and analysis subsystem for detecting the fluorescence curve of the calcium response and extracting calcium response event parameter features from the segmented image. This solution can segment astrocytes of different morphologies, distinguish subcellular structures, and employ adaptive thresholding for calcium response detection and analysis, thereby improving segmentation accuracy and analysis efficiency while reducing manual and time costs.

Disclosed herein are novel transcription factors for promoting reprogramming of, and / or for direct conversion of, an astrocyte to a neuron. Further provided are polynucleotides encoding the transcription factors, as well as DNA targeting composition to activate expression of the transcription factor. The DNA targeting compositions may include a Cas9 protein or fusion protein, and at least one gRNA. Further provided are methods of treating a neurodegenerative disease or neurodegenerative injury.

This invention discloses a method for constructing an in vitro model of senescent astrocytes, belonging to the interdisciplinary fields of cell biology, neuroscience, and biomechanics. The method includes: isolating and culturing primary astrocytes; performing adherent cell culture on the obtained primary astrocytes; and applying a compressive stress of 3-10 kPa to the adherent astrocytes for induced culture to obtain a model of senescent astrocytes. By simulating the changes in the mechanical microenvironment during brain tissue aging, the model successfully induces astrocytes into a senescent state using continuous vertical compressive stress. The constructed model can be used to screen anti-aging drugs or drugs for treating neurodegenerative diseases.

A method of differentiating nonhuman primate induced pluripotent stem cells (iPSCs) into astrocytes may include providing a modified vector comprising a piggyBac vector backbone configured to express SOX9 and NFIB. The piggyBac vector backbone may include terminal inverted repeats and transposase recognition sites that support stable genomic integration of the inserted differentiation factor genes. Introduction of the vector into nonhuman primate iPSCs, such as Macaca fascicularis iPSCs, may initiate transcriptional programs associated with astrocyte-lineage commitment and maturation. Expression of SOX9 and NFIB may facilitate the formation of astrocytic morphology and the development of molecular features associated with astrocytes, including process elaboration and lineage-specific marker expression. The method may further include culturing the transfected cells under conditions that support astrocytic differentiation and expansion, resulting in populations of astrocytes or induced astrocytes suitable for research, disease modeling, and / or therapeutic applications.

The inventors have discovered carbamoyl lipids with cyclic groups on their side chains capable of forming lipid nanoparticles, and have elucidated that lipid nanoparticles composed of carbamoyl lipids with cyclic groups on their side chains can express proteins in astrocytes or hepatocytes. Furthermore, lipid nanoparticles composed of carbamoyl lipids with cyclic groups on their side chains encapsulating nucleic acids are expected to be a component of pharmaceutical compositions useful for the prevention and / or treatment of astrocyte-related diseases.