276 results about "Microglial cell" patented technology

The invention discloses a scorpion anti-inflammatory polypeptide as well as a screening method and application thereof, and belongs to the technical field of traditional Chinese medicinal material polypeptides. The scorpion anti-inflammatory polypeptide is one of G4, G5 and G17. The method comprises the following steps: detecting a scorpion buthus martensii polypeptide extract through nanoElute 2 nanoliter liquid phase separation, timsTOFPro2 mass spectrometry and BPS Novor search analysis, screening a scorpion buthus martensii polypeptide, and further synthesizing the screened candidate polypeptide by adopting a solid-phase synthesis method; the effect of the synthesized candidate polypeptide on inhibiting microglial cell inflammation is evaluated through a qPCR method, and then the scorpion buthus martensii anti-inflammatory polypeptide is screened out. The Buthus martensii Karsch anti-inflammatory polypeptides G4, G5 and G17 screened by the method, especially G5, can significantly inhibit microglial cell inflammation and present concentration dependence, a theoretical basis is provided for medicinal development of Buthus martensii Karsch polypeptides, and a potential anti-neuroinflammation mechanism of the Buthus martensii Karsch polypeptides is disclosed.

The invention discloses application of amantadine in inhibition of ITGAV in preparation of medicines for treating dry age-related macular degeneration, and belongs to the technical field of biological medicines. At present, no report for researching the ITGAV gene in the dry AMD exists, the specific action mechanism is not clear, and amantadine adaptation diseases do not include the dry AMD; according to the application disclosed by the invention, the gene target ITGAV is screened from mutual hair generation of microglial cells and RPE cells in a retina microenvironment, and amantadine is used for inhibiting ITGAV protein to relieve the progress of AMD, so that a new thought is provided for treating dry AMD. Experiments show that amantadine can inhibit ITGAV and delay EMT transformation of RPE cells. In a dry AMD mouse model induced by sodium iodate, RPE cell damage can be remarkably relieved by intraocular injection of amantadine, and the structure and function of a retina layer are improved. These results indicate that it may function in early intervention of dry AMD.

The invention relates to a phenylpropanoid compound as well as a preparation method and application thereof, in particular to a phenylpropanoid compound extracted from pleione bulbus pseudobulb as well as a preparation method and application thereof, and belongs to the technical field of medicines. The invention provides a method for preparing 10 new compounds from pleione bulbocodioides pseudobulb as a raw material for the first time, systematically evaluates the anti-neuroinflammation activity of pleione bulbocodioides pseudobulb, and clarifies the application of pleione bulbocodioides pseudobulb in development and treatment of central nervous system diseases. According to the invention, abnormally activated BV-2 microglial cells induced by LPS (Lipopolysaccharide) are adopted, and the NO release amount is taken as an index, so that the effect of the compound 1-10 on inhibiting excessive activation of the microglial cells is preliminarily evaluated. The result shows that the novel compounds 1-10 can inhibit the release of LPS-induced BV-2 microglial cell NO. Therefore, the compound prepared in the invention can be applied to development of drugs for treating central nervous system diseases.

The present invention relates to a model mouse with a microglia-specific vitamin D binding protein (VDBP) gene knocked out and a construction method therefor. The construction method comprises the following steps: constructing a VDBPloxp / loxp gene mouse; hybridizing the VDBPloxp / loxp gene mouse with a Cre / ERT2 gene mouse to obtain a Cre+ / --VDBP+ / + gene mouse, wherein the microglia of the Cre / ERT2 gene mouse carry Cre gene; and inducing the expression of the Cre gene in the Cre+ / --VDBP+ / + gene mouse to obtain the model mouse with a microglia-specific VDBP gene knocked out. According to the construction method, a VDBP in the microglia of the model mouse can be specifically knocked out on the basis of Cre-loxP recombination, specific knockdown of the expression of the gene of the VDBP in the microglia is achieved, and the knockdown efficiency reaches 80% or more, facilitating more detailed study of the function of the molecule in the brain.

The invention belongs to the technical field of biological medicine, and particularly relates to an extracellular vesicle drug delivery system, a preparation method thereof and application of the extracellular vesicle drug delivery system in treatment of Alzheimer's disease. According to the invention, one or more of stilbene glucoside, emodin, kaempferol, resveratrol and quercetin are used for regulating and controlling the expression of miRNA (micro Ribonucleic Acid) related to the disease progress in the extracellular vesicles, and the result shows that one or more of miR-let-7c-5p, miR-486-5p, miR-132-3p, miR-160b and miR-129-5p is remarkably up-regulated, and one or more of miR-342-3p, miR-16-5p and miR-125b-5p is remarkably down-regulated. The regulated extracellular vesicles can be used for treating Alzheimer's disease, relieving Tau protein abnormal phosphorylation, reducing amyloid protein beta deposition, inhibiting microglial cell activation, protecting neuronal cells and relieving memory deficits.

The invention provides multifunctional bionic hydrogel as well as preparation and application thereof in traumatic brain injury treatment, and belongs to the field of biomedical materials. The preparation method comprises the following steps: combining polydopamine modified hemoglobin nanoparticles with curcumin-based carbon quantum dots with anti-inflammatory activity, and embedding into bionic hyaluronic acid-collagen double-network hydrogel, so as to prepare the multifunctional bionic hydrogel. The hydrogel can effectively relieve neuron hypoxia, reduce apoptosis, promote the polarity of microglial cells to be converted into anti-inflammatory phenotype, and significantly down-regulate the expression of S100A8, thereby inhibiting pathological neural immune crosstalk. In a traumatic brain injury model, hydrogel implantation improves the pathological microenvironment, enhances endogenous nerve regeneration, and ultimately results in significant neurological function and cognitive recovery. The multifunctional bionic hydrogel prepared by the invention has a good application prospect in preparation of materials for preventing and / or treating traumatic brain injury.

The invention discloses a nasal delivery multistage targeting bionic nano drug delivery system as well as a preparation method and application of the nasal delivery multistage targeting bionic nano drug delivery system. According to the drug delivery system, a black phosphorus nanosheet with an active oxygen scavenging effect is used as an inner core carrier, a neuroprotective agent fingolimod hydrochloride FTY720 and polydimethyldiguanide PolyMet are loaded, and a microcolloid cell membrane and a mitochondrial membrane are modified on the surface of the preparation; the nano drug delivery system is applied to treatment of cerebral arterial thrombosis reperfusion injury, can overcome the blood brain barrier, can quickly enter the brain through nasal administration, realizes efficient delivery of drugs, remarkably reduces the cerebral infarction area, reduces the brain inflammation level, protects nerve cells, greatly relieves cerebral arterial thrombosis reperfusion injury, and has application prospects.

The invention belongs to the field of application materials, and particularly relates to Ber-ApoEVs and preparation and application thereof.The Ber-ApoEVs comprise ApoEVs and Ber supported by the ApoEVs, the ApoEVs are bone marrow mesenchymal stem cell-derived apoptosis vesicles, and the Ber is berberine and a derivative thereof. Researches show that brand new Ber-ApoEVs play a synergistic neuroprotective role in the aspects of regulating and controlling polarization of microglial cells, release of inflammatory factors, p38 / MAPK signals and the like, neuroinflammation caused by retinal ischemia reperfusion (IR) can be relieved, retinal neuron apoptosis can be inhibited, and the Ber-ApoEVs can be used for treating glaucoma.

The invention discloses application of lycium barbarum polysaccharide in preparation of a medicine for inhibiting methylamphetamine-induced nerve injury, and relates to the technical field of biological medicines. It is found and proved that lycium barbarum polysaccharide can inhibit methylamphetamine-induced nerve injury, and the effect is remarkable. From the aspect of cell survival, the survival rate of the microglial cells pretreated by the lycium barbarum polysaccharide after METH stimulation is obviously improved. In the molecular mechanism, the lycium barbarum polysaccharide can effectively lower the protein expression level of the METH-induced pyroptosis marker, the content of inflammatory factors IL-1beta and IL-18 can be reduced, and the release of lactic dehydrogenase is reduced. The result shows that the lycium barbarum polysaccharide can alleviate inflammatory response by inhibiting NLRP3 / ASC pathway mediated microglial cell pyroptosis, thereby inhibiting METH-induced nerve injury. The invention provides a new direction for developing METH neurotoxicity intervention medicines.

The invention relates to the technical field of medicines, in particular to application of a mesenchymal stem cell exosome in preparation of a thermoplegia neuroprotective agent. It is found through experiments that MSC-Exos can remarkably promote polarization conversion of microglial cells from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, and therefore damage, caused by heat stroke, to a central nervous system is relieved.

The invention relates to biomedical engineering, and discloses a biochip screening method of a therapeutic agent based on intestinal brain axis regulation and application thereof. The screening method comprises the following steps: performing intestinal wall cell culture or microglial cell culture by adopting a metasurface plasmon resonance biochip of which the surface is subjected to bionic treatment to obtain an intestinal wall cell adherent chip board or a microglial cell adherent chip board; the method comprises the following steps: adding a culture medium containing a chemotherapeutic drug or lipopolysaccharide into a cell-adherent chip board for culture I, then removing the culture medium, adding a therapeutic agent to be detected for culture II to obtain a culture solution, and detecting the cell repair effect of intestinal wall cells or microglial cells in the culture solution, and screening to obtain a therapeutic agent with a repairing effect on intestinal wall cells and / or microglial cells. The screening method can be used for efficiently and accurately screening the therapeutic agent with dual effects of intestinal regulation and neuroprotection from a plurality of therapeutic agents to be detected, and can be used for dynamically monitoring and exploring the interaction condition of the therapeutic agent and cells on line in an unmarked and real-time manner.

The invention discloses application of eugenin in preparation of a medicine for treating cerebral arterial thrombosis, and belongs to the technical field of medicines. An in-vivo middle cerebral artery occlusion model is adopted, after reperfusion is conducted for 24 h, the cerebral infarction volume and movement coordination function defect of a mouse are detected to evaluate the treatment effect of eugenin, and activation of microglial cells and survival of neuronal cells are observed through immunofluorescence to clarify the action way of eugenin. Pharmacological activity shows that eugenin can obviously reduce the cerebral infarction volume of a model mouse, improve pathological damage of cells and promote recovery of a motion coordination function, and the action way of eugenin is to promote survival of neuronal cells and inhibit activation of microglial cells. Research results indicate that eugenin has the effect of resisting cerebral arterial thrombosis and can be used as a candidate medicine for developing the cerebral arterial thrombosis resisting medicine.

The application relates to the technical field of biological medicine and fundus disease treatment, in particular to application of Acbd3 in treatment of fundus diseases. It is found that the mRNA expression level and the protein expression level of Acbd3 in the retina of a fundus disease model mouse are significantly higher than those of a control group. After an Acbd3 inhibitor is used, the inflammatory reaction and neuron apoptosis in the retina of the fundus disease model mouse are significantly relieved, abnormal activation of Muller cells and microglia cells can be reduced, and a damaged blood-retina barrier can be repaired.

The invention belongs to the technical field of biological medicine, and relates to application of a compound D25, in particular to application of a small molecule compound D25 in preparation of a product for preventing or treating Alzheimer's disease (AD), and the structural formula of the compound is shown in the specification. Experiments prove that the small molecule compound D25 can pass through a blood brain barrier, can induce autophagy, can relieve pathological characteristics of an AD mouse model and improve cognitive impairment of the AD mouse model, can reduce the proportion of disease-related microglial cells by recovering the morphology of the microglial cells and improving the A beta phagocytosis capacity of the microglial cells, has the potential of promoting neuronal growth and increasing the number of protrusions, and can be used for preparing a medicine for treating the disease-related microglial cells. Therefore, AD can be effectively treated, the safety is high, the effect is achieved, and the application prospect is great.

Microglial spatial heterogeneity remains a crucial yet poorly studied question in light of potential cell-directed therapies for Alzheimer`s disease (AD). Little is known about the dynamics of spatially distinct microglia states, which are either adjacent or non-associated with the plaque site, and their selective contributions to neurodegeneration in vivo. So far, research has essentially focused on pathology-associated microglia. Here, we combined novel multicolor fluorescence fate mapping, single-cell transcriptional analysis, epigenetic profiling, advanced immunohistochemistry and computational modelling to comprehensively characterize the relation of plaque-associated and non-plaque- associated microglia during neurodegeneration. This approach enabled us to identify and characterize non-plaque-associated microglia as a unique and highly dynamic microglial state in a mouse model of AD. Non-plaque-associated microglia modulate network expansion, quickly adapt to environmental cues and their transition to plaque-associated microglia can be specifically modulated during disease, contrary to their reputation as a passive bystander subpopulation. This description of the dynamics of spatially segregated microglial states and their distinct molecular features may therefore open promising new avenues for state-specific therapeutic interventions during neurodegeneration.

A promoter on an AAV vector was changed to an Iba1 promoter, and a configuration that combined a miR-9 complementary sequence (miR-9T) and a miR-129 complementary sequence (miR-129T) was adopted. An exogenous gene was clarified to be efficiently and specifically expressed in microglia by using this vector, resulting in that an AAV vector that could efficiently and specifically express an exogenous gene in microglia of the central nervous system, was found.

This invention relates to diselenylene-bridged mesoporous silica nanoparticles loaded with baicalin and their applications. The invention constructs a ROS-responsive, microglia-inspired Ba@Se-MSN&BV2 nanoplatform targeting the secondary phase of spinal cord injury. The BV2 cell membrane-mediated enrichment at the injury site, combined with the diselenylene-triggered, on-demand release of baicalin, enables targeted intervention in a highly oxidative and pro-inflammatory microenvironment. In vitro and in vivo studies show that Ba@Se-MSN&BV2 can alleviate oxidative stress and mitochondrial dysfunction, inhibit apoptosis, promote axonal and neuronal survival, and improve motor circuit function. This invention provides a new therapeutic target and research direction for neuroinflammatory injuries driven by redox homeostasis disruption, with significant clinical application prospects and social value.

The application discloses a new use of Leonurine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating radiation-induced brain injury, specifically, providing a safe and effective therapeutic drug for iron death, neuroinflammation, neuron damage and lipid metabolism disorder accompanying the radiation-induced brain injury, solving the technical problem of lack of specific treatment means in the prior art, and having a wide clinical application prospect. Experiments adopt a C57BL / c mouse 30 Gy whole brain X-ray radiation model, and results show that Leonurine can significantly improve the body weight decrease and survival rate of the model mice, reduce the serum IL-6 and IFN-alpha levels, inhibit the activation of microglial cells in the cerebral cortex and hippocampus, protect and repair damaged neurons, and improve the ultrastructure of mitochondria and synapses; meanwhile, the expression of GPX4 and SLC7A11 proteins in the brain tissue is up-regulated, the GSH content is increased to inhibit iron death, and the levels of GPE, GPS and GPC related to lipid metabolism are restored.

The invention relates to an ultrasonic response bionic piezoelectric nano-drug for treating epilepsy as well as a preparation method and application of the ultrasonic response bionic piezoelectric nano-drug. The ultrasonic response bionic piezoelectric nano-drug comprises hafnium-based piezoelectric nano-particles UIO-66-NH2 etched by sulfuric acid, an anti-epileptic drug, a microglial cell membrane and transferrin receptor targeting peptide, wherein the anti-epileptic drug is loaded in hafnium-based piezoelectric nanoparticles etched by sulfuric acid to form a drug loading core; the microcolloid cell membrane coats the outer surface of the drug loading core; the transferrin receptor targeting peptide is connected to a microglial cell membrane. The ultrasonic response bionic piezoelectric nano-drug is high in brain entering efficiency, stable in drug release amount and clear in preparation method path, is suitable for targeted delivery of various anti-epileptic drugs and treatment and research of nervous system diseases such as epilepsy, can adopt an intravenous injection administration mode and non-invasive administration, can avoid injury caused by an operation, and has a good application prospect. The electrical stimulation is generated in vivo without implanting and taking out the electrode, so that secondary injury and infection are avoided.

The invention discloses an application of abscisic acid in preparation of a medicine for improving secondary brain injury after cerebral hemorrhage, the abscisic acid can relieve neuroinflammation and improve neurological function recovery by repairing microglial cell lysosome functions, enhancing phagocytic ability and promoting hematoma removal, and a new medicine strategy is provided for cerebral hemorrhage treatment.

The invention discloses an application of a pyruvate dehydrogenase kinase (PDKS) inhibitor in preparation of a composition for treating Alzheimer's disease (AD), and particularly discloses an application of the PDKs inhibitor in preparation of the composition for treating the AD. According to the invention, the level of oxidative phosphorylation (OXPHOS) of microglial cells is obviously enhanced, the inflammatory response of the microglial cells is effectively reduced, the migration and aggregation capabilities of the microglial cells are obviously improved, the capability of the microglial cells to phagocytize and degrade extracellular beta-amyloid protein (A beta) plaque is obviously enhanced, the cognitive function defect of AD model mice is effectively improved, and the application of the microglial cells in the treatment of the AD model mice is promoted. The preparation is simple, and the application is wide.

The invention provides a 3-hydroxypyrone derivative as well as a preparation method and application thereof, the compound can effectively inhibit release of proinflammatory cytokines in lipopolysaccharide-induced microglial cells, inhibit release of NO by the lipopolysaccharide-induced microglial cells, inhibit apoptosis of polysaccharide-induced microglial cells, and inhibit apoptosis of lipopolysaccharide-induced microglial cells. The compound has excellent anti-neuroinflammation activity and neuroprotective effect, the activity of the compound is superior to that of positive controls such as curcumin and hydrocortisone, and the compound can be used for preventing and / or treating neuroinflammation and neurodegenerative diseases.

The invention discloses a construction method of a human-derived HMC3 microglial cell line modified strain (named SIRT2-KD HMC3) for treating Alzheimer's disease (AD). The cell strain is obtained by knocking down an SIRT2 gene through genetic engineering. The invention also discloses a method for producing LEVs by using the cell strain, the cell strain can form an M2 anti-inflammatory form in a culture process, and the microvesicles LEVs-sh-SIRT2 are obtained by collecting a culture solution and adopting an ultra-high speed centrifugation method. A preclinical animal test (AD mode mouse APP / PS1) result shows that the LEVs prepared by the invention can effectively regulate and control inflammatory response and promote phagocytosis. After nasal administration, the LEVs can smoothly penetrate through a blood brain barrier to enter a hippocampus and are taken by microglial cells, so that chemotactic and phagocytic activities of the microglial cells are promoted, deposition of A beta in the brain is reduced, cognitive impairment of experimental animals is remarkably improved, and the medicine has a wide application prospect in the field of AD innovative treatment.

The present invention provides methods and compositions for the generation of microglial progenitor cells and microglial cells from pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells. The present invention also provides cells produced using such methods, and both methods of treatment and methods of drug screening that use such cells. Also provided are various tissue culture media, tissue culture media supplements, and kits useful for the generation of human microglial progenitor cells and human microglial cells.

The invention discloses an mGluR5 small-molecule allosteric modulator and application thereof in inhibition of neuroinflammation, and belongs to the technical field of neuropharmacology and anti-inflammatory drug research, two mGluR5 small-molecule allosteric modulators are obtained by virtual screening through an allosteric pocket targeting mGluR5, the structural formulas of the two mGluR5 small-molecule allosteric modulators are shown in the specification, and the structural formula of the mGluR5 small-molecule allosteric modulators is shown in the specification. The mGluR5 micromolecule allosteric modulator can be used for inhibiting microglial cell inflammation, and can effectively relieve LPS-induced microglial cell NO release.

The application provides application of dimethyl itaconate in prevention and treatment of chronic stress-induced anxiety. The application finds that dimethyl itaconate can inhibit excessive activation of microglial cells in a stress state, improve mitochondrial structure and function abnormalities of the microglial cells, and reduce expression of a lysosome marker CD68, so as to inhibit central nervous inflammation, maintain central nervous immune homeostasis, prevent and relieve anxiety-like behavior induced by chronic stress, and effectively prevent and relieve occurrence and development of chronic stress-induced anxiety (generalized anxiety disorder).

The present application relates to a kind of microglial cell P2Y6R target point inhibitor and its application, belong to biological medicine technical field.For the problems such as lack of effective treatment means for retinal pigment degeneration, abnormal activation of microglial cell accelerates course and lack of specific intervention target point, the application of inhibitor with P2Y6R as target point in preparation treatment retinal pigment degeneration drug is proposed, especially siRNA and shRNA for knocking down microglial cell P2ry6 gene are provided, and AAV vector containing microglial cell specific promoter is constructed, the specific silencing of P2ry6 in retina is realized.The present application can significantly inhibit abnormal activation of microglial cell and inflammatory response, reduce photoreceptor apoptosis, improve retina structure and visual function, and provide a new strategy for targeted treatment of retinal pigment degeneration.

The invention relates to the technical field of biological medicine, and particularly discloses a macrophage membrane coated plateau encephaledema drug carrier and a preparation method and application thereof, and the macrophage membrane coated plateau encephaledema drug carrier is composed of a nanoparticle core and a macrophage membrane shell layer wrapping the core; the nanoparticle core comprises an ROS-responsive carrier material and carbon monoxide release molecules MnCO entrapped in the ROS-responsive carrier material; the content of phosphatidylserine in the shell layer of the macrophage membrane is not less than 5 mol% of the total phospholipid of the membrane. According to the invention, a bionic delivery system of ROS response type MnCO nanoparticles coated with a macrophage membrane is constructed, phosphatidylserine on the surface of the membrane is utilized to actively activate a microglial cell Trem2 receptor, a positive feedback cycle of targeting phagocytosis-CO release-Trem2 up-regulation is formed, and at the same time, fatty acid oxidative metabolism reprogramming is promoted by means of degraded membrane lipid, so that the biomimetic delivery system is used for preparing the ROS response type MnCO nanoparticles. And multi-mechanism synergistic efficient brain-targeted therapy is realized.

This invention relates to the application of LAG3 agonists in the preparation of drugs for hematoma clearance after intracerebral hemorrhage (ICH) and the application of LAG3 in regulating hematoma clearance after ICH, belonging to the field of biomedical technology. This invention utilizes a mouse ICH model to first inject a LAG3 neutralizing antibody (C9B7W) via orthotopic injection, clarifying that LAG3 can regulate the phagocytic function of microglia after ICH and participate in hematoma clearance, revealing its potential molecular target for enhancing microglia phagocytic function and promoting hematoma clearance. Furthermore, overexpression of LAG3 after ICH is demonstrated. Lag3 The study confirmed that enhanced phagocytic function of microglia accelerated hematoma clearance, demonstrating that LAG3 agonists can be used as drugs for hematoma clearance after intracerebral hemorrhage. The experimental results of this invention make it possible to apply LAG3 to the prognostic treatment of ICH, thereby advancing basic and clinical research on endogenous hematoma clearance after 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.