183 results about "Astrocyte cells" patented technology

The invention relates to the technical field of cytology, in particular to a grass carp brain astrocyte line and application thereof, the grass carp brain astrocyte line is preserved in China Center for Type Culture Collection on May 7, 2025, and the preservation number of the grass carp brain astrocyte line is CCTCC NO: C2025149. The grass carp brain astroglia cell line provided by the invention has the capability of efficiently proliferating GCRV-II, and the virus titer of the GCRV-II replicated in the cell line at least can reach 1.38 * 10 < 8 > pfu / mL or above; after the GCRV-II is blindly passed for 5 generations in a grass carp astroglia cell line, the grass carp can still have typical bleeding symptoms and death due to the virus. And the exogenous plasmid transfected grass carp brain astroglia cell line has similar transfection efficiency to commercial grass carp kidney cells. Therefore, the invention lays an important foundation for deep research of pathogenic mechanism of GCRV-II, vaccine preparation, antiviral drug screening and prevention and control of grass carp viral hemorrhagic disease.

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.

The present inventors have found a carbamoyl lipid having a cyclic group in a side chain, which can form lipid nanoparticles, and have revealed that the lipid nanoparticles containing, as a constituent, the carbamoyl lipid having a cyclic group in a side chain according to the present invention can express a protein in astrocytes or hepatocytes. The lipid nanoparticles containing, as a constituent, the carbamoyl lipid having a cyclic group in a side chain according to the present invention contain a nucleic acid inside thereof and are expected as a component of a pharmaceutical composition useful for prevention and / or treatment of an astrocyte-related disease.

The invention discloses an application of a hypoxia pretreated extracellular vesicle / miR-27b-3p in the treatment of ischemic stroke. The research proves that both the neuron-derived EV and H-EV can promote in-vivo and in-vitro MCAO repair. The two vesicles secreted by neuronal cells can significantly influence phenotypic change and apoptosis of astrocytes, wherein the effect of H-EV is more obvious than that of EV. Besides, the research result shows that H-EV secreted by neurons can regulate a PI3K / AKT signal channel by transmitting miR-27b-3p, so that astrocytes are promoted to be converted from the A1 phenotype to the A2 phenotype. The research of the invention provides a new therapeutic target and strategy for treating ischemic stroke.

The invention discloses a construction method of a conditional knock-down dynactin animal model of astrocytes and an application of the animal model of the conditional knock-down dynactin animal model of the astrocytes. According to the method, a Dctn1LoxP gene knock-in mouse is hybridized with an Aldh1l1-Cre / ERT2 transgenic mouse, a target genotype mouse is obtained through three rounds of breeding, 100mg / kg Tamoxifen is continuously injected into the intraperitoneal cavity of the 2-month-old mouse for 5 days, and specific knock-down of dynactin in brain and spinal astrocytes is realized, including knockout of p150Glue and reduction of DCTN4, p50 and Arp1alpha protein levels. The model has the advantages of being high in specificity, permanent in intervention aging and capable of covering multiple life stages, the defects of a traditional model are overcome, the model can be used for researching the influence of dynactin on astrocyte neurobiological functions, a reliable tool is provided for screening related targets of nervous system diseases, and the model has important application value.

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.

Synthetic nucleic acids are described that can be used for astrocyte-directed expression of heterologous nucleotide sequences, as well as methods of using same for astrocyte-directed expression of such nucleotide sequences for the treatment of neurodegenerative diseases.

The invention discloses a method for constructing astrocytes serving as a smoke disease model, and belongs to the technical field of crossing of stem cells and neuroscience. The method comprises the following steps: S1) reprogramming CD34 + cells in in-vitro PBMCs (peripheral blood mononuclear cells) of smoke disease patients carrying and not carrying RNF213p.R4810K mutation to obtain induced pluripotent stem cells; and S2) directionally inducing and differentiating the induced pluripotent stem cells into astrocytes through a neural progenitor cell way, wherein the obtained astrocytes are the astrocytes capable of being used as the smoke disease model. The astrocyte model prepared by the invention can be used for researching pathogenesis, nerve-blood vessel interaction process and blood-brain barrier (BBB) related functions of smoke diseases, and can be further applied to molecular typing of diseases and in-vitro function evaluation of candidate drugs.

Extracellular vesicles and / or exosomes (EVs) remain sparsely studied in hemorrhagic transformations, including stroke and intracranial hemorrhages and could provide key insights into stroke pathophysiology. We assessed plasma levels of neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in 58 patients 5, 15, and 30 days post-ischemic stroke along with 46 matched controls using sandwich immunoassays. Hemorrhagic transformation was a better predictor of ADE levels than lesion volume in linear regression models. These findings suggest that ADE levels are preferentially increased over the first month post-stroke compared to EVs from other neural cell types. ADEs may be of additional interest as biomarkers of blood-brain barrier breakdown to predict hemorrhagic transformation at earlier time points after stroke.

The invention belongs to the technical field of biological medicines, and particularly relates to application of Chi3l1 as a target spot in preparation of a medicine for preventing or treating secondary brain injury after cerebral hemorrhage. By integrating space transcriptomics and a mononuclear RNA sequencing technology, the spatial heterogeneity and cell type specificity of gene expression in ICH afterbrain tissue are deeply analyzed, a group of astrocyte subgroups AST1 with neuritis existing around hematoma in the acute stage after cerebral hemorrhage is identified, Chi3l1 is determined as a key inflammatory effect factor of the AST1 subgroups, and the AST1 subgroups with neuritis are used as the key inflammatory effect factor of the AST1 subgroups. And the influence of the gene on the phenotypic transformation of astrocytes and microglial cells is verified. The discovery provides an important theoretical basis for developing a treatment strategy of targeting Chi3l1, and is expected to improve neuroinflammatory response and neurological dysfunction after ICH by regulating and controlling expression of the AST1 subgroup and Chi3l1, and opens up a new direction for treatment of ICH.

The invention belongs to the technical field of medicines, and relates to injectable piezoelectric hydrogel for a spinal cord injury part as well as a preparation method and application of the injectable piezoelectric hydrogel. According to the hydrogel, methacrylated gelatin is used as a carrier, and a piezoelectric material MOF (at) PDA (at) M0, namely MP (at) M, of an enveloping porous structure is loaded in the hydrogel. The hydrogel can achieve dual functions under the ultrasonic action: (1) MP (at) M has piezoelectricity, ultrasonic mechanical energy is converted into electrical stimulation, calcium ion inward flow of astrocytes is triggered, mitochondria is promoted to be transferred from the astrocytes to neurons, and the mitochondrial function of the neurons is recovered; (2) the CD73 enzyme carried by the microglial cell membrane coated on the surface of the MP (at) M can degrade pro-inflammatory ATP (adenosine triphosphate) at the damaged part to generate adenosine, so that astrocytes are promoted to release lactic acid, and rapid energy support is provided for neurons. Mitochondrial transfer and energy supply are synchronously promoted through ultrasonic stimulation, neuronal plasticity is remodeled, spinal cord axon regeneration is promoted, and a new strategy is provided for spinal cord injury treatment.

This invention discloses a method for constructing a three-dimensional in vitro blood-brain barrier model with barrier function and its application, belonging to the biomedical field. The method includes: preparing a light-controlled biofunctionalized hydrogel with methacrylamide gelatin as the main framework; preparing a suspension of neurovascular matrix components using astrocytes and neurons; uniformly mixing the light-controlled biofunctionalized hydrogel and the neurovascular matrix component suspension to obtain a homogeneous cell-hydrogel composite solution, and preparing it into three-dimensional hydrogel microspheres; transferring the three-dimensional hydrogel microspheres to the bottom of a Transwell culture dish insert to form a stable neurolateral matrix layer; and adding a suspension of brain microvascular endothelial cells into the lower chamber of the Transwell culture dish. This invention achieves the synergistic effect of multiple bioactive substances, overcoming the shortcomings of the single bioactive substance loading method in the prior art.

The invention provides a polypeptide simulating Ascl1 and application thereof, and relates to the technical field of biomedicine, and the technical key point is that the polypeptide simulating Ascl1 is provided, the polypeptide is a TAT-Ascl1-EL-1 polypeptide, and the sequence of the TAT-Ascl1-EL-1 polypeptide is as shown in SEQ ID: NO 01. According to the application, through a verification experiment, the TAT-Ascl1-EL-1 polypeptide is successfully screened out, and in vitro, the polypeptide can be used for effectively reprogramming rat spinal cord reactive astrocytes into neuron-like cells; and a new selectable way is provided for the medical research on cell replacement treatment and cell regeneration after SCI.

Synthetic nucleic acids that can be used for astrocyte directed expression of heterologous nucleotide sequences are described. Also described are methods of using the same for the targeted expression of astrocytes of such nucleotide sequences for the treatment of neurodegenerative diseases.

The invention discloses an application of an inhibitor for targeted inhibition of a COLLAGEN pathway in a drug for treating Alzheimer's disease (AD) related to exposure of micro-nano plastic particles (MNPs). The research shows that the exposure of the MNPs can activate a COLLAGEN signal channel among astrocytes, microglia and neurons, promote COL1A1 / COL1A2-ITGA1 / ITGB1 mediated abnormal cell communication, cause the M1 type polarization of the microglia, the activation of the p38-MAPK channel of the neurons and the deposition of A beta, and further accelerate the progress of AD (Alzheimer's disease). The pathway is blocked by knocking down the ligand COL1A1 in astrocytes, so that neuroinflammation can be remarkably reduced, A beta accumulation can be inhibited, and the cognitive function can be improved. The invention provides a new molecular target for the treatment of the MNPs related AD.

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.

Described herein are methods and compositions for treating a disease, e.g. cancer (including solid tumors), using glial cells (e.g. microglia cells and / or astrocytes) and / or macrophages (e.g., CNS-associated macrophages) infected with an oncolytic virus (e.g., vaccinia virus). The methods and compositions provided herein demonstrate a synergistic anti-cancer effect.

The present disclosure provides a cyclic peptide derivative, a method for producing the same, and a composition. The present disclosure relates to a compound for modulating nervous system cell activity. More specifically, the compound of the present disclosure is capable of modulating the proliferation activity of astrocytes. The compound of the present disclosure has the effect of enhancing the proliferation activity of astrocytes. The features provided by the present disclosure can be used for a cyclic peptide derivative for modulating nervous system cell activity and a method for producing said cyclic peptide derivative.

The invention belongs to the technical field of biological medicines, and relates to application of an HIF-1alpha inhibitor in preparation of a product for inducing transformation of astrocytes from a pro-inflammatory type to an anti-inflammatory type. The invention reveals that activation of an HIF-1 signal channel is an important mechanism for driving neuroinflammatory response and pro-inflammatory A1 type astrocyte formation, and inhibition of HIF-1 activation can effectively promote generation of neuroprotective A2 type astrocytes. By applying the HIF-1alpha small-molecule inhibitor KC7F2 to astrocytes, HIF-1alpha activation is blocked, and the astrocytes are promoted to be converted from a proinflammatory A1 phenotype to an anti-inflammatory A2 phenotype, so that inflammatory response is inhibited, neurotoxicity is reduced, and a neuron microenvironment is improved. The invention provides a novel intervention strategy based on HIF-1alpha signal regulation and control, and a novel theoretical basis and a novel potential drug treatment scheme are provided for treatment of nervous system injury and related neurodegenerative diseases.

Disclosed are means, methods, and compositions of matter useful for treatment of oncological indications through stimulation of protective anti-cancer immunity. In one embodiment the invention discloses the unexpected effect of astrocytes to augment immune stimulating activities of dendritic cells. In one embodiment dendritic cells are pulsed with tumor lysates and subsequently co-cultured with astrocytes in the presence of toll-like receptor agonists.

An application of Bone Marrow Mesenchyml Stem Cell Exosomes (BMSC-Exos) in treating Parkinson's disease (PD) is provided, wherein the BMSC-Exos are generated by stimulating BMSCs with a culture solution and extracted from the culture solution after passage; and the culture solution of the BMSCs is an α-MEM culture solution containing FBS and PS. The BMSC-Exos can greatly improve a motor function of a model mouse with PD, protect dopaminergic neurons of the model mouse with PD, improve an olfactory function of the model mouse with PD, and also inhibit the activation of olfactory astrocytes of the model mouse with PD.

The present invention provides, in part, protein-drug conjugates for delivering a molecular cargo (e.g., a polynucleotide, a polypeptide, a liposome, or a lipid nanoparticle) to a targeted tissue (e.g., brain), the protein-drug conjugates comprising an anti-fibroblast growth factor receptor 3 (FGFR3) (e.g., a polypeptide, a liposome, or a lipid nanoparticle) conjugated to the molecular cargo. The present invention relates to human FGFR3 (e.g., human FGFR3) antigen binding proteins (e.g., scFv, Fab). The invention provides methods for treating various diseases or conditions, such as neurological diseases, with the conjugates.

The present invention belongs to the technical fields of biomedicine and molecular biology, and specifically relates to the application of astrocyte exosomes and melatonin pretreatment in the treatment of optic nerve injury. The present invention explores the effects on retinal and visual behavioral changes in mice after ONC by establishing an ONC model and treating with exosomes derived from astrocytes (EVs) and exosomes derived from astrocytes pretreated with melatonin (MT-EVs). The results show that exosome treatment can improve the survival rate of RGCs, and at the same time, visual behavioral tests verify its certain effect on the long-term vision improvement of mice. Moreover, compared with EVs, MT-EVs have better effects, have important clinical value, and also provide new ideas for exosome transplantation therapy, so it has good practical application value.

The present invention relates to a composition comprising HAPLN1 as an active ingredient for preventing or treating senile degenerative brain diseases. Specifically, recombinant human HAPLN1 protein (rhHAPLN1) lowers the protein level of p16 in cultured human astrocytes to inhibit cellular senescence caused by the accumulation of beta amyloid peptides, and further inhibits phosphorylation (p-p38 MAPK) of p38 MAPK protein, thereby also having the possibility of inhibiting inflammatory responses associated with the onset of Alzheimer's disease and Parkinson's disease. In addition, the recombinant human HAPLN1 protein (rhHAPLN1) exhibits significant memory and learning improvement effects in in vivo experiments performed using a mouse acute Alzheimer's disease model, and thus can be expected to exhibit preventive and therapeutic effects against Alzheimer's disease that may occur with aging and the like. In addition, the inhibitory effect of the rhHAPLN1 protein on cellular senescence and inflammatory responses of astrocytes can provide a very important clue for establishing prevention and treatment strategies not only for aging itself but also for brain functions, motor behaviors, memory, seizures, dementia, brain tumors, and the like.

The present invention relates to the field of biotechnology, and discloses a composition and method for rapidly reprogramming astrocytes into induced neurons, wherein the composition is composed of the small molecule PT109B and one of the PDE family inhibitors. The method comprises the following steps: S1, culturing astrocytes to maturity, so that the cell fusion of the astrocytes is 60%-80%; S2, replacing the culture medium of the astrocytes with a culture medium containing the composition, and continuing to culture for at least 3 days. The present invention combines the small molecule PT109B with the PDE inhibitor to rapidly reprogram astrocytes into induced neurons within 3 days, which not only solves the problems of the large number of small molecule compounds used in the chemical reprogramming technology in the prior art, the complicated steps, and the long cycle, but also completely avoids the risks associated with genetic manipulation, providing a breakthrough solution for the radical treatment of NDDs.

The present invention provides, in part, a protein-drug conjugate comprising an anti-fibroblast growth factor receptor 3 (FGFR3) (e.g., human FGFR3) antigen-binding protein (e.g., scFv, Fab) conjugated to a molecular cargo (e.g., a polynucleotide, a polypeptide, a liposome, or a lipid nanoparticle), for delivering the molecular cargo to a target tissue (e.g., the brain). Methods are provided for treating various diseases or disorders, such as neurological disorders, with the conjugate.

A method for detection or monitoring status of traumatic brain injury (TBI) and / or spinal cord injury (SCI) in a subject is provided. In one embodiment, the method comprises contacting a specimen of bodily fluid obtained from the subject with reagents for assaying for a marker of TBI selected from aldolase C (ALDOC) and brain lipid binding protein (BLBP / FABP7), or a trauma-specific break down product (BDP) of ALDOC or BLBP / FABP7. The method further comprises measuring the amount of marker present in the specimen as compared to a control sample, and determining the presence of TBI or SCI when an elevated amount of marker is present in the specimen compared to the control sample. Optionally, the method further comprises measuring the amount of glutamine synthetase (GS), astrocytic phosphoprotein PEA-15 (PEA15), αB-crystallin (CRYAB / HSP27), a trauma-specific proteolytic cleavage product of ALDOC, GS, PEA15, or CRYAB, or any combination of two or more thereof.

The invention belongs to the technical field of medicines, and particularly relates to preparation of CD73 positive NK cells of umbilical cord blood from different starting sources and application of the CD73 positive NK cells to treatment of Alzheimer's disease. The CD73 + NK cells differentiated from different initial cell types (CD34 positive cells, CD3 negative / CD56 positive cells and CD56 negative cells) of umbilical cord blood are studied, it is found that all the initial cell types of umbilical cord blood sources can be differentiated into the CD73 + NK cells, 34 +-73-NK cells show a higher growth rate, 56-73-NK cells show higher cytotoxicity, and the CD73 + NK cells can be differentiated into the CD73 + NK cells. And the overall effect of the 56-73-NK cell is superior to that of the 34 < + >-73-NK cell. Further research shows that the CD73 + NK can inhibit activation of STZ injection mouse hippocampal microglia and astroglia, so that the neuroinflammation of the hippocampal is reduced, and a new solution is expected to be provided for treatment of AD.

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.