176 results about "Microglia" patented technology

A device for modelling physiological and pathophysiological states of the brain is provided. The device comprises a hydrogel with micropattern channels having a length, width and depth. The micropattern channels comprise cells selected from the group consisting of neurons, astrocytes, microglia, oligodendrocytes, neuronal organoids, cancer cells, cancer spheroids, brain tumoral cells and combinations thereof.

The invention discloses a curcumin-loaded brain-targeted drug delivery system as well as a preparation method and application thereof. The delivery system comprises a carrier macrophage and a curcumin drug, the curcumin nano-drug is prepared by encapsulating curcumin with a lipoic acid modified cyclodextrin conjugate, then macrophages and the curcumin nano-drug are mixed, and co-incubation is carried out, so that the curcumin nano-drug is constructed. The brain-targeted macrophage drug delivery system loaded with curcumin is a multifunctional composite drug with brain targeting property for treatment of cerebral arterial thrombosis. A brain-targeted macrophage drug delivery system loaded with the curcumin nano-drug gathers in cerebral apoplexy tissues, phenotypic transformation of inflammatory microglial cells is promoted, and a pro-inflammatory microenvironment is improved; the oxidative stress pressure of the stroke part is improved; the two effects promote each other, the stroke microenvironment is improved, the functions of neuronal cells are saved, the synergistic nerve protection effect can be achieved in the aspect of treating ischemic cerebral apoplexy, and potential safety hazards are reduced.

The present invention relates to a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, comprising selexipag or a pharmaceutically acceptable salt thereof as an active ingredient. Selexipag inhibits the expression and production of pro-inflammatory or inflammatory cytokines in brain tissue, inhibits the activity of microglia or astrocytes, inhibits NLRP3 inflammasome activity and CDK6 expression, reduces amyloid plaques, increases the expression of the amyloid beta-degrading enzyme IDE, and inhibits the hyperphosphorylation of tau protein and the expression of tau kinase, and thus can be effectively used as a novel therapeutic agent for the prevention or treatment of degenerative brain diseases, cognitive disorders, learning disabilities, or memory disorders.

The invention relates to an extracellular vesicle composition for aiding sleep as well as a preparation method and application thereof. The composition comprises two or more of passion flower extracellular vesicles, chamomile extracellular vesicles and liquorice extracellular vesicles. According to the extracellular vesicle composition, a combined formula is adopted, and the CL-level of cells is improved, the expression level of GABA related proteins is improved, the expression of brain-derived neurotrophic factors (BDNF) of the cells is promoted, and the synaptic growth of neuronal cells is promoted in a multi-dimensional combined mode that the passiflora edulis is compounded with multiple Chinese herbal medicine extracellular vesicles; the sleep-aiding pillow has the advantages that multi-aspect efficient sleep-aiding effects can be realized, sleep time can be shortened, and sleep quality can be improved. Meanwhile, the extracellular vesicle composition disclosed by the invention adopts nano-scale raw materials, has good permeability, and is more easily absorbed and ingested by cells and skin to play a role.

The present invention relates to the field of nerve cell labeling methods and related animal model technologies, and specifically to a promoter of a lgals3bpb gene and its application in constructing a zebrafish model. The application of the promoter of the lgals3bpb gene in constructing a zebrafish model comprises the following steps performed in sequence: obtaining the promoter of the lgals3bpb gene through a PCR reaction; constructing an expression vector regulated by the promoter of the lgals3bpb gene; transferring the expression vector into zebrafish fertilized eggs, and obtaining a stable genetically modified zebrafish strain through culture, screening and multi-generation hybridization. This technical solution can solve the technical problem of the prior art due to the lack of a zebrafish animal model capable of locating and operating microglia, and creates conditions for studying microglia, conducting disease mechanism research, drug screening and drug efficacy testing, and has good application prospects.

The present invention relates to a method for generation of the immortalized microglia cells with knockout of endocannabinoid receptor gene. The cells are useful model for developing strategies to treat neurodegenerative diseases.

The invention relates to an isopentenyl-alpha-pyrone dimer Hyperumonates D-F as well as a preparation method and application thereof, and belongs to the field of medical chemistry, the isopentenyl-alpha-pyrone dimer Hyperumonates D-F is obtained by extracting and separating from leaves and branches of Hypericum monogynum for the first time, and the structural formula of the isopentenyl-alpha-pyrone dimer Hyperumonates D-F is D-F. The invention further discloses a preparation method of the isopentenyl-alpha-pyrone dimer Hyperumonates D-F. The isopentenyl-alpha-pyrone dimer Hypericumonates D-F has the advantages that the compounds D-E have remarkable inhibition effects on generation of NO in mouse microglial cells (BV-2 cells) induced by lipopolysaccharide (LPS), the activity of the compounds D-E is higher than that of positive medicine minocycline, and the compounds D-E have application potentials in the field of neuroinflammation medicines, and the invention also relates to a pharmaceutical composition which comprises the isopentenyl-alpha-pyrone dimer Hypericumonates D-F and can be used for preparing medicines for treating neuroinflammation. And pharmaceutically acceptable auxiliary materials, wherein the pharmaceutical composition has the effect of resisting neuroinflammation.

The invention provides an application of gastrodin in preparation of a medicine for treating peripheral neuropathy. According to the application disclosed by the invention, gastrodin can inhibit neuroinflammation mediated by microglia by inhibiting activation of an NF-kB / NLRP3 inflammasome signal channel, so that release of inflammatory factors is reduced, and neuropathy induced by bortezomib is relieved.

Methods for treating Alzheimer's disease and other neurodegenerative disorders in which the capacity of microglia and / or astrocytes has been altered and impaired are described. The method comprises the step of carrying out brain targeting on PD-L1 by using a brain targeting nanogel which is loaded with a PDL1 antibody and is functionalized by two specific targeting ligands. The nanogel can successfully cross the blood brain barrier to release the antibody, reduce the expression of PD-L1 in the brain, and maintain the integrity of BBB at the same time.

The present disclosure relates to organoids and particularly to brain organoid models. The brain organoids include neurons, microglia, astrocytes, and blood vessels. The brain organoid models can be used to create models for Alzheimer's Disease. Methods of using the brain organoids for drug discovery are also described.

This invention belongs to the field of pharmaceutical technology, specifically relating to a quinazoline-azaindole compound, its preparation method, and its application in treating Alzheimer's disease. The quinazoline-azaindole compound of this invention regulates NF-κB by inhibiting DYRK1A. k B. A series of signaling pathways, including PI3k-Akt, achieve anti-neuroinflammatory effects; quinazoline-azaindole compounds can reduce the expression of inflammatory factor-related genes in an LPS-induced BV2 microglial inflammation model, thereby reducing the levels of inflammatory factors in the hippocampus and cortex, alleviating neuronal pathological damage caused by neuroinflammation, and improving cognitive impairment caused by neuroinflammation; in summary, quinazoline compounds inhibit DYRK1A and downregulate NF-κB signaling pathways. k It can reduce the expression and release of inflammatory factors, improve brain tissue pathology, and alleviate cognitive impairment through signaling pathways such as B, and has significant clinical application value.

The invention belongs to the field of biomedicine technology and discloses the application of Gastrodia elata Blume derived nano-extracellular vesicles in the preparation of drugs for the prevention and / or treatment of subarachnoid hemorrhage (SAH). The Gastrodia elata Blume-derived nano-extracellular vesicles of this invention are obtained from separation of Gastrodia elata Blume by water extraction. The ingredients of this invention are natural, none of toxic side effects and with good biocompatibility and safety. Therefore, this invention has broad application prospects. The invention uses Gastrodia elata Blume-derived nano-extracellular vesicles to conduct in vitro and in vivo experiments and finds that it can inhibit the activation of microglia after subarachnoid hemorrhage by inhibition of the transformation of microglia into M1 phenotype and promoting the transformation of microglia into M2 phenotypic transformation which has significant effect in treating SAH, and can be used to prepare drugs for preventing and / or treating subarachnoid hemorrhage.

This disclosure relates to cell therapy approaches for treating progranulin (PGRN) deficiencies with human induced pluripotent stem cell (hiPSC)-derived cells. Advantageously, the hiPSC-derived cells (e.g., microglia progenitor cells) described herein can cross-correct PGRN deficiencies in damaged or diseased cells while reducing the amount of endogenous cell ablation that is needed, as demonstrated by experimental results showing restoration of PGRN levels in GRN mutant cells and brain organoids.

The present invention relates to an exosome composition for improving sleep quality, comprising lavender exosomes, chamomile exosomes, and saffron exosomes. The exosome composition can increase the expression of GABA-related proteins in neurons, promote brain-derived neurotrophic factor (BDNF) expression in neurons, promote synaptic growth in neurons, increase CL levels in neurons, and inhibit the levels of inflammatory factors in microglia. The exosome composition can improve sleep quality caused by various physical discomforts, achieving a more pronounced effect than extracts of the same herbal remedies.

The invention discloses application of biphenyl lactone compounds in treatment of Alzheimer's disease, and belongs to the field of medicine. According to the present invention, in the oleic acid treatment combined APOE4 point mutation microglial cells, the benzene lactone compound Graphislactone A can improve the abnormal lipid droplet accumulation, inhibit the microglial cells from generating inflammatory factors, and further protect the neuronal function; meanwhile, in-vivo AD mouse model experiments prove that the benzolactone compound Graphislactone A can improve cognitive impairment of AD mice and reduce abnormal accumulation of lipid droplets in brain and expression of inflammatory factors, can be used as an active ingredient of medicines for treating AD, and has wide application.

To provide compositions and methods for penetration, distribution and response of targeting particles in malignant brain tumors.SOLUTION: Described herein are nanoparticle conjugates that demonstrate enhanced penetration into tumor tissue (e.g., brain tumor tissue) and diffusion within the tumor interstitium, e.g., for treatment of cancer. Further described are methods of targeting tumor-associated macrophages, microglia, and / or other cells in a tumor microenvironment using such nanoparticle conjugates. Moreover, diagnostic, therapeutic, and theranostic (diagnostic and therapeutic) platforms featuring such nanoparticle conjugates are described for treating targets in both the tumor and surrounding microenvironment, thereby enhancing the efficacy of cancer treatment. Use of the nanoparticle conjugates described herein with other conventional therapies, including chemotherapy, radiotherapy, immunotherapy, and the like, is also envisaged.SELECTED DRAWING: None

The invention discloses a marine galactooligosaccharide lipid as well as a preparation method and application thereof, and belongs to the field of marine biological resource utilization and drug development. According to the invention, a marine red algae polysaccharide degradation technology and high efficiency of reductive amination aliphatic chain modification are combined together for the first time, and modification of saturated aliphatic chains with different lengths of marine galactooligosaccharides with different polymerization degrees is realized. Cellular level pharmacodynamic evaluation proves that the marine galactooligosaccharide lipid can significantly inhibit release of nitric oxide in microglial cells and expression of inflammatory factors such as interleukin-6 and tumor necrosis factor alpha, and has neuroinflammation inhibition activity; meanwhile, proliferation of tumor cells U87MG and GL261 can be remarkably inhibited, and the compound has certain anti-tumor potential and can be used for preparing drugs for preventing and / or treating neuroinflammation and anti-tumor related diseases. Therefore, the marine galactooligosaccharide lipid prepared by the invention has relatively high clinical application value and development prospect.

The present invention relates to a composition for preventing, ameliorating or treating central nervous system diseases, comprising a peptidomimetic compound (NIP001) containing hydrophilic arginine and a hydrophobic histidine derivative. In the present invention, the peptidomimetic compound comprising hydrophilic arginine and a hydrophobic histidine derivative was confirmed to effectively inhibit inflammatory responses in microglia and to have the effect of improving the cognitive function of mice with scopolamine-induced cognitive impairment, and thus can be used as a targeted therapeutic agent for central nervous system diseases.

The invention relates to hydroxylated polyamide-amine dendrimer integrated drug-loaded nanogel as well as a preparation method and application thereof. The drug-loaded nanogel comprises third-generation polyamide-amine dendrimer integrated nanogel modified by double bonds and high-density hydroxyl groups, MnO2 nanoparticles and quercetin, wherein the nanogel is loaded with MnO2 nanoparticles in situ, and quercetin is physically wrapped in the nanogel. The drug-loaded nanogel disclosed by the invention can enhance a blood-brain barrier penetrating effect, regulate microglial cells and neurons in a double-target manner and remodel a brain inflammation microenvironment, so that neuroinflammation and dyskinesia of a Parkinson's disease model mouse are relieved, and the curative effect of the Parkinson's disease is improved. The compound has good development prospect and application value in treatment of Parkinson's disease or other neurodegenerative diseases.

This invention provides the application of triptolide in the preparation of drugs for treating microglial inflammation-related neuroimmunological disorders. Experiments show that triptolide significantly inhibits the expression, migration, phagocytosis, and morphological activation of microglial inflammatory factors, and exerts an anti-microglial inflammatory effect in animal models. Through DARTS technology combined with siRNA screening, ACOX1 was identified as its key target, and the direct binding between the two was verified by CETSA, SPR, and molecular docking.

The present invention relates to a use of a methylated peptide as a therapeutic agent for degenerative brain diseases. Specifically, it has been confirmed that the methylated peptide according to the present invention exhibits improved solubility, bioavailability, phagocytosis by microglia, and anti-inflammatory efficacy compared to a conventional unmodified peptide, and exhibits excellent amyloid beta reduction efficacy compared to a conventional unmodified peptide in an animal model of degenerative brain diseases. Therefore, the methylated peptide according to the present invention can be usefully used as an active ingredient of a composition for preventing or treating degenerative brain diseases and cognitive impairment, learning disability, or memory impairment associated therewith.

The application discloses application of PTN in preparation of products for treating cognitive impairment caused by severe infection. The inhibitor of PTN provided by the application can inhibit chronic neuroinflammation, thereby preventing and inhibiting formation and development of late cognitive impairment caused by severe infection, and meanwhile, inhibition of expression or function of PTN can effectively block damage of infiltrating macrophages to microglia cells, thereby providing a new direction for treatment of related diseases.

The invention relates to a tobacco exosome as well as a preparation method and application thereof. The tobacco exosome comprises nicotine, lipid composition, a small molecule compound and protein, and in the tobacco exosome, the concentration of the nicotine is higher than 1 ng / mL. The tobacco exosome prepared by the invention can effectively inhibit inflammatory activity induced by microglial cells LPS, inhibit secretion of inflammatory factors PGE2 and transcriptional expression of iNOS, IL-1beta and IL-6. In a mouse neuroinflammation model experiment, the tobacco exosome prepared by the invention can improve behavioral changes of a mouse neuroinflammation model, and the improvement effect is better than that of other plant exosomes, such as potato exosomes.

The invention discloses application of radix polygoni multiflori preparata polysaccharide in preparation of a medicine for treating and / or preventing ischemia-reperfusion injury, and belongs to the technical field of medicines. According to the invention, an SD rat cerebral ischemia reperfusion in-vivo model is constructed, and the body weight change, neurological behavior change, cerebral ischemia area and microglial cell number of a stroke rat caused by the prepared fleece flower root polysaccharide are observed and detected. Results show that the radix polygoni multiflori preparata polysaccharide can remarkably improve neurobehavioral dysfunction of cerebral ischemia reperfusion rats, reduce the cerebral infarction rate and promote cognitive behavior ability recovery in the later period of cerebral apoplexy. The prepared fleece flower root polysaccharide can be used as a medicine for preventing cerebral arterial thrombosis and repairing after cerebral apoplexy, and an effective solution is provided for preventing and treating cerebral apoplexy.

Methods are described for treatment of Alzheimer's Disease as well as other neurodegenerative disorders in which microglia and / or astrocyte abilities have been altered and impaired. Methods include brain-targeting of PD-L1 using a brain targeted nanogel loaded with PDL1 antibody and functionalized with two particular targeting ligands. The nanogels can successfully cross the blood brain barrier to release the antibody and reduce PD-L1 expression in the brain while preserving the integrity of the BBB.

The invention relates to the technical field of biological pharmacy, in particular to application of miR-3470b in preparation of a medicine for treating Parkinson's disease. The effect and mechanism of the miR-3470b carried by the exosome in DA cell protection are found for the first time through cell and animal experiments. By inhibiting the synthesis of the exosome and observing the information carried by the exosome, the effect of protecting DA cells is achieved; secondly, screening and verifying that the main miRNA carried in the exosome is miR-3470b through miRNA-seq, and exploring that the specific mechanism of the exosome for protecting the DA cells is that the co-cultured DA cells are protected through targeting GREM1; and finally, further verifying that the exosome miR-3470b secreted by the SIX2 overexpressed microglial cells has a protection effect on DA cells through in-vivo experiments, and can improve the motor ability of PD mice. According to the invention, a new target and thought can be provided for a strategy of treating PD by loading miRNA on the exosome.

This invention discloses a heterozygous sesquiterpene tricyclic epoxy compound derived from the strain *Arthrum oligosporum*, its preparation method, and its applications, belonging to the field of natural product chemistry. This invention provides a heterozygous sesquiterpene tricyclic epoxy compound derived from *Arthrum oligosporum* (… A.oligospora ) AOL_ s00210g57 Anthrobotrisin D, a novel heterozygous sesquiterpene tricyclic epoxy compound from a gene knockout strain, has been shown in vitro to possess excellent anti-inflammatory activity, significantly inhibiting lipopolysaccharide-induced inflammatory responses in mouse microglia. It exhibits a clear dose-dependent inhibitory trend at multiple levels, including NO release, protein and mRNA expression of inflammatory factors (TNF-α, IL-1β, IL-6), and iNOS protein and mRNA expression. Furthermore, at a concentration of 33 μM, its anti-inflammatory effect is comparable to that of the clinically proven positive drug dexamethasone, and in some aspects, it is even superior. This invention not only provides a new lead compound for the development of anti-inflammatory drugs but also opens up new directions for developing new drugs from the unique microbial resource of nematode-preying fungi.

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 discloses a strain of lactobacillus acidophilus for treating chronic cerebral ischemia, which is preserved in the China Center for Type Culture Collection (CCTCC) and has the preservation number of CCTCC NO: M 20251505. Animal experiments show that the strain can reduce the death rate of chronic cerebral ischemia model mice and improve neurological impairment, motion coordination and spatial learning and memory ability of the chronic cerebral ischemia model mice. Mechanism research shows that the strain can increase histone acetylation and BDNF secretion by inhibiting the activity of astrocyte HDAC1, and meanwhile, can inhibit an NF-kappa B signal channel and reduce inflammatory factor release by activating a microglial cell GPR120 receptor, so that a neuroprotective effect is achieved through an'intestine-brain axis'. The invention provides a new candidate strain for the development of microbial preparations for preventing and / or treating chronic cerebral ischemia and related cognitive impairment.

This invention relates generally to neurodegenerative diseases and conditions (e.g., Alzheimer's disease) characterized with dysfunctional energetic function, unregulated microglia phagocytic activity and other related de-regulated biological functions. This invention further relates to methods and compositions for treating such neurodegenerative diseases and conditions with pharmaceutical compositions comprising one or more of agents capable of protecting neurons from cell death and unregulated microglia phagocytic activity.