73 results about "Microglia" patented technology

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.

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 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 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 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.

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.

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.

This invention discloses a method for preparing and applying an AIE probe for long-term two-photon imaging of the cerebrovascular system in awake mice. The probe is prepared by assembling an AIE precursor with DSPE-mPEG2000-Mal into nanoparticles, followed by coupling with the cell-penetrating peptide TAT. This probe exhibits excellent photostability, long-term vascular retention, good biocompatibility, and neuroimmunocompatibility. In awake mouse models, it can achieve three-dimensional imaging of cerebrovascular systems at depths exceeding 500 micrometers and stably labels blood vessels for up to 35 days without activating microglia. This probe supports multi-scale imaging from acute hemodynamics to long-term structural remodeling, providing a powerful tool for neurovascular research.

The invention provides a neuroinflammation dual-targeting sound-sensitive liposome as well as a preparation method and application thereof. The neuroinflammation dual-targeting sound-sensitive liposome comprises a liposome, a sound-sensitive agent entrapped in the liposome and an antibody modified on the surface of the liposome, the sound-sensitive agent is benzothiadiazole-triphenylamine, and the structural formula of the sound-sensitive agent is shown in the specification. And the antibody comprises an anti-TMEM119 antibody and an anti-NAT antibody. The neuroinflammation dual-targeting sound-sensitive liposome can target sympathetic neurons and microglial cells at a neuroinflammation part, has a neural immune regulation effect under ultrasonic activation, can be used for preparing a diagnosis and treatment agent for diagnosis and treatment integration of myocardial ischemia reperfusion injury, and realizes diagnosis and treatment integration of myocardial ischemia reperfusion injury.

The present application relates to a multifunctional hydrogel for treating traumatic brain injury and a preparation method and application thereof. The preparation method of the hydrogel comprises the following steps: step 1, dissolving a tetracycline drug in a buffer to prepare a tetracycline drug solution; step 2, adding a multi-arm polyethylene glycol with a double bond end group into the solution prepared in step 1 to form a solution containing the multi-arm polyethylene glycol with a double bond end group and the tetracycline drug; step 3, adding a multi-sulfhydryl compound into the solution prepared in step 1 to form a solution containing the multi-sulfhydryl compound and the tetracycline drug; and step 4, mixing the solutions prepared in steps 2 and 3 to prepare the hydrogel. In the acute phase, the active oxygen rapidly increases to make the hydrogel release more drugs to regulate the inflammatory environment and play a neuroprotective role, and in the chronic phase, the hydrogel continuously releases drugs to continuously regulate the anti-inflammatory polarization of microglia cells, enhance neural plasticity and restore nerve function.

The invention discloses application of a nutritional composition to improvement of anxiety and memory ability, and belongs to the field of nutrient substance research. According to the nutritional composition containing the lactose-N-neotetraose and the 2 '-fucosyllactose provided by the invention, through the synergistic effect of the lactose-N-neotetraose and the 2'-fucosyllactose, the mood disorder and the reduction of memory and recognition ability can be improved, and the mood disorder and the reduction of memory and recognition ability are caused by maternal immune abnormal activation. Furthermore, the composition can improve the activity of neurons by inhibiting the transition activation of brain microglial cells, and help is provided for improving mood disorder and memory and recognition ability decline. A new thought is provided for development of products for improving offspring emotional disorder and memory and recognition ability decline caused by maternal immune activation.

Provided herein are methods for reducing reactive microglia in a subject. Further provided herein are methods for treating a neurological disease, disorder, or condition in a subject. In some cases, the methods involve administering a 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor to the subject. In some cases, the 15-PGDH inhibitor can penetrate the blood-brain barrier.

The application discloses an anti-inflammatory hydrogel as well as a preparation method and application thereof; the anti-inflammatory hydrogel is obtained by cross-linking four-arm polyethylene glycol thiol, eight-arm polyethylene glycol maleimide and metal coordination nanoparticles in a PBS buffer solution; the metal coordination nanoparticles are modified with diphosphonate, minocycline hydrochloride and Mg 2+ The metal coordination is composed of magnesium ions, phenolic hydroxyl groups on the minocycline hydrochloride and diphosphonate groups on the diphosphonate. The anti-inflammatory hydrogel has the performances of responding to a spinal cord injury microenvironment, releasing the anti-inflammatory drug minocycline hydrochloride, inhibiting the polarization of macrophages / microglia to M1 type and the like, can better play the drug effect of anti-inflammation and promoting spinal cord injury repair, has the advantages of convenient operation, no harmful by-products and the like, and has a wide application prospect.

This invention relates to the field of pharmaceutical technology, specifically to a 6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazoline-4-amine derivative, its preparation method, and its applications. This invention utilizes a "conformation-locking" and "drug-likeness optimization" strategy to optimize the 4-position side chain of quinazoline into conformationally defined structures such as dihydroindanol and fluoropiperidine, thereby reducing P-gp recognition through conformational rigidity. Simultaneously, the introduction of groups such as cyclopropylformyl groups reduces off-target toxicity, thus broadening the therapeutic window. The 6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazoline-4-amine derivative provided by this invention simultaneously achieves potent DYRK1A inhibition, high kinase selectivity, low microglial cytotoxicity, significant anti-neuroinflammatory effects, good blood-brain barrier permeability, and oral bioavailability. Furthermore, it is a novel small-molecule inhibitor that can be validated for cognitive improvement in AD animal models, possessing significant clinical value and urgent application needs.

The invention relates to a phenanthrene type norditerpenoid, a preparation method thereof and an application of the phenanthrene type norditerpenoid in a medicine for preventing and treating neuroinflammation in the technical field of biological medicines, and the phenanthrene type norditerpenoid is extracted from Leucodendron hainanense and is a norditerpenoid component with a gem-dimethyl 6 / 6 / 6 tricyclic phenanthrene type structure. The extraction method comprises the following steps: firstly, extracting a dried medicinal material of Hainan acalypha australis with ethanol with the mass concentration of 95%, and then filtering, concentrating under reduced pressure and drying to obtain a 95% ethanol extract; adding water to disperse, and sequentially extracting with petroleum ether, ethyl acetate and n-butyl alcohol to obtain extracts of corresponding parts; and finally, performing chromatographic separation and purification on the ethyl acetate part. The phenanthrene type norditerpenoid disclosed by the invention can be used for inhibiting the release of an inflammatory factor NO of BV-2 neural microglial cells; the invention has important significance on the development of drugs for treating neuroinflammation diseases.

The application provides application of a hydroxy pentylbenzoic acid double ester compound L-NRB in treatment of Parkinson's disease. Animal model test proves that L-NRB can effectively improve the MPTP-induced Parkinson's disease mouse behavior index, increase the content of DA and its metabolites DOPAC and HVA in the brain, inhibit the loss of dopamine neurons in the substantia nigra and striatum, inhibit the expression of inflammatory factors and the activation of astrocytes and microglia in the substantia nigra; meanwhile, L-NRB can also inhibit the activity of MAO-B in the striatum. L-NRB has no toxic side effects in vivo and in vitro; has the advantages of high safety, small dosage, long-term stability and the like, and is suitable for further development for actual clinical treatment.