111 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 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.

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 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.

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.

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 invention discloses an application of a Ptbp2 accelerant in treatment of cerebral arterial thrombosis. It is found for the first time that overexpressed Ptbp2 can remarkably improve the neurological function of a mouse with the cerebral arterial thrombosis, reduce the infarct volume and relieve neuroinflammation mediated by microglia, and the overexpressed Ptbp2 can be used for effective treatment of the cerebral arterial thrombosis. The invention provides a theoretical basis for research and development of drugs for treating cerebral arterial thrombosis, opens up the application of the Ptbp2 accelerant, provides a brand new method for treating cerebral arterial thrombosis, and has a wide application prospect in the technical field of cerebral arterial thrombosis treatment.

The application provides an application of an NEDD8 inhibitor in preparation of anxiolytic drugs. The application proves through experiments that inhibition of NEDD8 by means of gene editing or inhibition of NEDD8 by a compound can exert an anxiolytic effect. The NEDD8 inhibitor can reduce inflammatory activation of microglia and reduce anxiety, and provides a new strategy for research and development of anxiolytic drugs.

The invention discloses oligopeptide and application thereof in preparation of a medicine for treating and / or relieving pain. The amino acid sequence of the oligopeptide disclosed by the invention comprises a derivative sequence formed by additionally arranging 1-3 amino acids at the N end and / or C end of the amino acid sequence shown as Tyr-Pro-Arg, especially Tyr-Pro-Arg-Arg (YPRR, YR4), and a gastrointestinal tract digestion product Tyr-Pro-Arg (YPR, YR3) of the oligopeptide. The oligopeptide not only can relieve acute pain induced by a mouse thermal drifting model, but also can relieve chronic pain induced by a rat sciatic nerve chronic compression injury model and a tibia bone cancer pain model, and meanwhile, the oligopeptide obviously inhibits CCI-induced spinal astrocyte, microglia and neuron activation; therefore, the compound has important development and application values in the aspects of central sensitization inhibition and analgesia.

2-Pentadecyl-2-oxazoline (also known as palmitoylethanolamide oxazoline or PEA-OXA) is used to counteract hyperalgesia induced by the most common opioids (OIH) associated with microglial hyperactivation. In particular, PEA-OXA is administered to humans and animals to prevent or treat some of the adverse effects of opioids by controlling immune hyperactivation. The PEA-OXA is administered separately, sequentially or jointly with the opioid.

The invention discloses an application of sunitinib in preparation of a medicine for treating secondary injury caused by intracranial hemorrhage. It is found for the first time that sunitinib can act on a CSF-1R / PI3K / Akt axis, pathological activation and pro-inflammatory response of microglial cells are effectively inhibited, the normal phagocytic function and lipid metabolism balance of the microglial cells are remarkably recovered, myelin sheath damage around hematoma is effectively relieved, and the neurological function score, the movement coordination ability and the exploration behavior of ICH mice are remarkably improved; the progress of secondary injury caused by intracranial hemorrhage is hindered from multiple dimensions, the curative effect is superior to that of a positive control drug pecetinib (PLX3397), and a brand new molecular target and an interference strategy are provided for comprehensive treatment of ICH.

This invention discloses a method for constructing and evaluating a homeostatic neuroinflammatory microenvironment model. In this invention, brain microvascular endothelial cells and microglia are seeded into the methacrylamide gelatin layer and the paper fiber layer of a methacrylamide gelatin-paper fiber composite membrane (GCC), respectively, and co-cultured for 24–96 hours without LPS stimulation to form a homeostatic neuroinflammatory microenvironment model. The 24-hour GCC group… TNF-alpha Compared to the PET group, CX3CL1 decreased by about 60% and remained at a low level for 72 hours; CX3CL1 increased by nearly 3 times in the GCC group; based on the evaluation of 4 / 10 / 70 kDa graded probes, GCC showed better restriction on 10 kDa than PET, exhibiting molecular weight-dependent permeation characteristics opposite to PET. The homeostatic neuroinflammatory microenvironment model proposed in this application is suitable for simulating the blood-brain barrier in early pathological conditions, and can be used for anti-inflammatory drug screening and research on neurodegenerative diseases, showing good application prospects.

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.

An aquatic liposome encapsulating a natural compound is provided, wherein an average particle size (a median particle size) of the aquatic liposome encapsulating the natural compound ranges from 80 nm to 200 nm. A manufacturing method of an aquatic liposome encapsulating a natural compound is provided and includes performing an ultrasonic oscillation after mixing the aquatic liposome and the natural compound, so that the natural compound is encapsulated in the aquatic liposome. Experiments are conducted to prove that the aquatic liposome encapsulating the natural compound could effectively enter microglia and retinal pigment epithelium cells to relieve the inflammatory response and hinder the apoptosis.

This invention provides a kit comprising: (1) a pharmaceutical composition containing a therapeutically effective amount of eugenol hydrochloride and a pharmaceutically acceptable carrier; and (2) a detection reagent for detecting vasoactive intestinal peptide (VIP) mRNA and / or protein. This invention reveals for the first time that eugenol hydrochloride (HH) has a highly effective therapeutic effect on specific Parkinson's disease patients characterized by abnormally elevated VIP levels. The pharmaceutical composition and kit of this invention can specifically reduce the expression of pro-inflammatory VIP, thereby precisely intervening in the VIP-mediated microglial-related neuroinflammatory pathway, thus significantly treating Parkinson's disease and providing a novel targeted treatment option for the clinical intervention of Parkinson's disease.

The application discloses a preparation method of FTY720-loaded platelet membrane biomimetic nanobubbles, and belongs to the technical field of biological medicines. The platelet membrane biomimetic nanobubbles are composed of a platelet membrane, a nanobubble core and an S1P receptor immunomodulatory drug FTY720. The biomimetic nanobubbles have good biocompatibility and targeting property, can be quickly and efficiently adhered to damaged blood vessels, thrombus and inflammation and other lesion sites of cardiovascular and cerebrovascular diseases after injection, can effectively induce the M2 anti-inflammatory phenotype conversion of immune cells such as macrophages and microglia in the lesions through the controllable release of FTY720, can reduce the adhesion of other immune cells such as T lymphocytes, can regulate the balance of pro-inflammatory / anti-inflammatory reactions, can reduce the lesion area, can improve the immune regulation treatment effect of cardiovascular and cerebrovascular diseases, and can reduce the side effects of FTY720.

This invention relates to a novel substance with in vitro anti-inflammatory activity, its preparation method, and its application. The present invention provides a novel substance with in vitro anti-inflammatory activity, its preparation method, and its application. The molecular formula of hemerocallicin A is C2. 23 H 28 O 10 Methods: 1. Hemerocallis flowers were extracted with 80% ethanol aqueous solvent; 2. The concentrated extract after removing ethanol by rotary evaporation was dispersed in water and loaded onto a D101 macroporous resin column; 3. The fraction was eluted with 50% ethanol from the macroporous resin, and then purified by silica gel column chromatography, gel column chromatography, and preparative high-performance liquid chromatography to obtain hemerocalin A. Hemerocalin A is used to prepare anti-inflammatory drugs. The IC50 of hemerocalin A in this invention inhibited the release of the pro-inflammatory factor NO from LPS-stimulated mouse microglia (BV2) by [the method described in the original text]. 50 The value was 13.3 μmol / L, indicating that it has good in vitro anti-inflammatory activity. This invention belongs to the field of research on effective components of natural drugs.

The present invention relates to a biomarker to predict the prognosis of neurodegenerative diseases, and a use thereof, and, more particularly, to: a marker composition for prognosis prediction of neurodegenerative diseases, comprising miRNA-214 and / or miRNA-34c; a composition and a kit for prognosis prediction of neurodegenerative diseases, comprising an agent for measuring the expression level of the miRNAs; and a method for predicting the prognosis of neurodegenerative diseases by using the marker. It has been identified that the miRNA-214 and / or miRNA-34c according to the present invention can regulate phagocytic capacity modulator of microglia, NKCAP1 so that the prognosis of neurodegenerative diseases can be predicted, and thus it is expected that the present invention can be effectively used as a biomarker for predicting the prognosis of neurodegenerative diseases.

This invention discloses the application of *Meconopsis spp.* extract in the preparation of anti-Alzheimer's drugs, relating to the field of pharmaceutical preparation technology. The process involves taking dried whole *Meconopsis spp.* herb powder, soaking it in a 0.5% hydrochloric acid-70% ethanol solution for 24 hours, then percolating to extract the extract. The percolate is collected, concentrated under reduced pressure until no alcohol odor remains, diluted with pure water, and then successively defatted with petroleum ether, extracted with ethyl acetate for polyphenols, and extracted with water-saturated n-butanol for alkaloids. The n-butanol layer and the aqueous layer are collected and dried under reduced pressure to obtain the *Meconopsis spp.* extract. The *Meconopsis spp.* extract of this invention can simultaneously act on two core pathological aspects of Alzheimer's disease: on the one hand, it significantly inhibits fibrotic aggregation (inhibition rate up to 61.3%), preventing the formation of neurotoxic plaques; on the other hand, it effectively inhibits microglia-mediated neuroinflammatory responses (NO production inhibition rate up to 74.5%), reducing the damage of the inflammatory microenvironment to neurons.

The invention belongs to the field of new application of medicines, and particularly relates to application of N-phenylpiperazine derivatives in preparation of medicines for treating neuroinflammation. It is found for the first time that the N-phenylpiperazine derivative AD-X can improve the neuroinflammation of mice by activating microglia in hippocampus and prefrontal cortex of the mice, and has a certain function of treating the neuroinflammation. The invention provides a novel lead compound for screening medicines for treating neuroinflammation.