20 results about "Microglia" patented technology

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 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 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.

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.

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.

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.

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.

New use of 1-amino-3,5-dimethyladamantane hydrochloride in treating or preventing cognitive impairment, reducing microglia in the cortex and hippocampus, reducing neuron loss in the cortex and hippocampus, and ameliorating the mitochondrial dysfunction state. The cognitive impairment includes cognitive impairment in systemic lupus erythematosus, Parkinson's disease, lateral sclerosis, stroke, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, attention deficit hyperactivity disorder, sepsis-related encephalopathy, or mild cognitive disorder. The present application also provides a corresponding drug and a treatment or prevention method.

This invention provides a neurodevelopmental drug screening system and its applications based on a set of microglia markers. Specifically, this invention provides a neurodevelopmental supportive microglia subset that expresses markers of neurogenesis and development, as well as energy metabolism. This invention also provides a neurodevelopmental drug screening system and method using changes in the state of this cell subset as the core evaluation indicator. The system of this invention can sensitively and quantitatively reflect the regulatory effect of candidate drugs on the pro-neural maturation function of microglia in developmental brain injury, filling the technical gap in existing drug screening systems that lack "developmental immune-metabolic-synaptic linkage indicators."

Provided is to a compound or a pharmaceutically acceptable salt thereof for use in a composition for rejuvenating aged microglia, and a pharmaceutical composition for preventing or treating brain diseases containing the same. Also disclosed is the use of a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof to restore the phagocytic function of microglia that has been impaired by dexamethasone, thereby providing a rejuvenation composition for aged microglia that can be usefully applied as a pharmaceutical composition for preventing or treating brain diseases including neurodegenerative diseases, neuroinflammatory diseases, depression, and neuropsychiatric disorders.

The application belongs to the technical field of biological medicine, and discloses a spinal cord injury treatment drug based on a LINC00311 / miR-4318 / MYLK regulation axis and an application thereof, and aims to solve the technical problems of poor targeting and large side effects of the existing anti-inflammatory treatment of spinal cord injury. The effective component of the drug is an inhibitor of LINC00311, the inhibitor is selected from one or more of shRNA, siRNA, antisense oligonucleotide and CRISPRi system, can target the specific nucleotide sequence of LINC00311, and can be used in combination with miR-4318 mimic, and is administered by intrathecal injection, slow virus carrier delivery and the like. The in-vitro experiment proves that the inhibitor can significantly inhibit the release of TNF-alpha, IL-1beta, IL-6 and other pro-inflammatory factors by microglia cells; the in-vivo experiment shows that it can significantly improve the BBB motor function score of spinal cord injury rats, and reduce spinal cord tissue edema and necrosis. The application first discloses the mechanism of the LINC00311 / miR-4318 / MYLK ceRNA regulation axis in spinal cord injury, has the advantages of novel target, significant effect and high transformation potential, and provides a new scheme for the clinical treatment of spinal cord injury.

The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor member of the immunoglobulin super family which is able to bind Aβ peptide and 3-sheet fibrils. It is expressed in endothelial cells, smooth muscle cells, microglia and neurons, and is implicated in the transport of Aβ through the blood-brain barrier (BBB), oxidative stress-mediated neurotoxicity, and adverse microglia inflammatory responses. The interaction between RAGE and its ligands is thought to result in pro-inflammatory gene activation. Enhanced levels of RAGE ligands in Alzheimer's disease are thought to contribute to the cause of this disorder. Embodiments of the invention use the RAGE multi-ligand site as an anchoring loci for a conversion electron emitting compound rather than as a receptor to intrinsically activate or block inflammation through the RAGE intracellular cascade through activation of the RAGE cytoplasmic tail (ctRAGE) and mammalian diaphanous 1 (DIAPH1).

This invention discloses an engineered stem cell membrane biomimetic formulation, its preparation method, and its applications. The biomimetic formulation of this invention consists of core-shell structured drug-loaded nanoparticles. The core is a lipid polymer hybrid nanoparticle loaded with a drug for reprogramming microglia metabolism; the outer shell is an engineered stem cell membrane on which ligands that specifically target microglia are highly expressed. The engineered stem cell membrane-coated biomimetic formulation provided by this invention has a simple preparation process and features high drug loading capacity, controlled release, high blood-brain barrier penetration, and precise microglia targeting capability. It can achieve synergistic therapeutic effects through microglia energy metabolism reprogramming and has high clinical research value in the treatment of neurodegenerative diseases.

This invention belongs to the field of pharmaceutical formulation technology, specifically disclosing a hydrogen storage composite metal-organic framework, its preparation method, and its applications. The preparation method of the hydrogen storage composite metal-organic framework includes the following steps: adjusting a gallic acid solution to alkalinity, adding magnesium chloride hexahydrate and reacting, centrifuging the magnesium-gallic acid metal-organic framework material to obtain Mg-GA-MOF; mixing Mg-GA-MOF with anhydrous ethanol, adding anhydrous sodium tetrachloropalladate solution in ethanol, equilibrating the solution, and slowly adding anhydrous sodium tetraborate solution in ethanol to obtain Pd / Mg-GA-MOF; and then loading with hydrogen. This invention utilizes both the porous microstructure of the MOF to physically adsorb hydrogen and the Pd nanoparticles embedded in the framework structure to chemically adsorb hydrogen. The combination of these two methods significantly improves the hydrogen loading efficiency of Pd / Mg-GA-MOF while exhibiting good biocompatibility. Furthermore, cell experiments show that Pd / Mg-GA-MOF can effectively scavenge various ROS and inhibit the inflammatory response of microglia, demonstrating high clinical application potential in stroke repair.

This invention relates to Gastrodia elata oligopeptides for relieving neuroinflammation, their preparation method, and applications. Belonging to the field of food-medicine homologous active peptides, this invention aims to address the problem of relieving neuroinflammation. The key technical points are: S100. Adding a complex glycosidase to a Gastrodia elata powder solution for the first enzymatic hydrolysis; S200. Adding a complex protease to the solution after the first enzymatic hydrolysis for the second enzymatic hydrolysis, obtaining Gastrodia elata hydrolysate; S300. Performing aqueous two-phase extraction on the Gastrodia elata hydrolysate, and collecting the supernatant from the aqueous two-phase extraction to obtain the Gastrodia elata oligopeptides. This invention prepares Gastrodia elata oligopeptides with high gastrodin content through aqueous two-phase extraction combined with complex enzymatic hydrolysis. These oligopeptides inhibit the transformation of microglia to an anti-inflammatory state, thereby relieving neuroinflammation and protecting neurons. They can be applied in foods or health products that alleviate neurological diseases caused by neuronal damage.

This invention presents a polyketide compound, its preparation method, and its applications. The polyketide compound Dinemasone D was isolated from the solid-state fermentation product of *Phaeosphaeria poagena*. The polyketide compound Dinemasone D obtained in this invention exhibits a strong inhibitory effect on lipopolysaccharide (LPS)-induced NO production in BV-2 microglia, with an IC50 value of [missing value]. 50 The value was 13.8 ± 0.4 μM, close to the level of quercetin.

The application discloses a method for high-throughput screening of compounds promoting degradation of mitochondria of inflammatory microglia cells, and belongs to the technical field of biological medicine screening. The method comprises the following steps: stimulating microglia cells to establish a mitochondrial accumulation model by using an inflammation inducer; adding a candidate drug and the inflammation inducer into the cells for incubation; adding a mitochondria-specific fluorescent probe for dark staining; detecting the average fluorescence intensity of the cells by using flow cytometry; and taking the fluorescence intensity of a positive control group as a baseline, if the average fluorescence intensity of a candidate drug treatment group is significantly reduced, it is indicated that the compound has the activity of promoting degradation of mitochondria of inflammatory microglia cells. The method can realize high-throughput, rapid and objective quantitative screening, is suitable for large-scale drug screening, and provides an effective tool for developing drugs for relieving neural inflammation.

The application discloses a kind of gold palladium-nitrogen doped carbon ribbon decorated g-C3N4 Nanosheet and its preparation method and application, UFR-NC is doped in g-C3N4 / To form g-C3N4 / UFR-NC composite nanomaterial;With g-C3N4 / UFR-NC composite nanomaterial as carrier, gold palladium shell core particle is loaded on g-C3N4 / UFR-NC composite nanomaterial to obtain gold palladium-nitrogen doped carbon ribbon decorated g-C3N4 Nanosheet.The gold palladium-nitrogen doped carbon ribbon decorated g-C3N4 Nanosheet of the application has multiple enzyme-like activities, good photocatalytic hydrogen production and hydrogen storage and release performance;At the same time, under the enhancement of 808 nm near-infrared light, it has multiple enzyme-like activities, high hydrogen storage and release performance.Oxidative stress damage in vivo can be reduced and neuroinflammation is inhibited, and in the treatment of Parkinson's disease, Alzheimer's disease, brain trauma, cerebral apoplexy and other microglia-mediated neuroinflammatory encephalopathy, there is obvious therapeutic effect.