37 results about "Microglial cell activation" patented technology

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

The invention discloses a preparation method and application of a sepsis-related encephalopathy model based on HLA II type gene humanized mice. According to the invention, HLA DP401 / DRA-IA beta- / -transgenic humanized mice are utilized, and the HLAII type gene humanized mouse sepsis model is prepared through mouse cecum seroperitoneal infection (CS) and meropenem intervention. The sepsis encephalopathy model can be comprehensively evaluated through indexes such as clinical score MSS, serum and hippocampal tissue inflammatory cytokine detection, hippocampal tissue microglial cell activation, hippocampal neuron spinous process change, transcriptomics, behavioral change and the like, and the sepsis encephalopathy model can be used for screening therapeutic drugs and therapeutic schedules; the HLA II type gene humanized mouse sepsis-related encephalopathy model provided by the invention can be used for infectious encephalopathy pathogenesis research, new drug research and development and safety evaluation.

The present invention relates to a pharmaceutical composition for preventing or treating degenerative brain diseases, the composition comprising prasugrel as an active ingredient. The composition containing prasugrel or a salt thereof according to the present invention has excellent neuroprotective activity and, in particular, can suppress MPP+-induced neurotoxicity and neuronal cell death, suppress LPS-induced microglial cell activation and cell migration, and has neuroinflammation inhibitory activity, and thus has the effect of preventing, alleviating, and treating various degenerative brain diseases including Parkinson's disease.

The invention belongs to the field of medicine, and discloses application of bilirubin in preparation of medicine for treating ischemic cerebrovascular diseases, and the bilirubin can improve cognitive impairment caused by the ischemic cerebrovascular diseases; the severity of demyelination caused by ischemic cerebrovascular diseases is improved, the area of cerebral infarction is reduced, and the severity of neurological impairment caused by ischemic cerebrovascular diseases is relieved; inflammation, caused by ischemic cerebrovascular diseases, in blood and brain tissues is relieved, and activation of B cells and mediated immune response are inhibited; the oxidative stress of B cells is improved; the microglial cell activation caused by ischemic cerebrovascular diseases is relieved; the neuroinflammation reaction caused by ischemic cerebrovascular diseases is relieved. Good clinical application values are realized.

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for relieving depression and clearing collaterals and a preparation, a pharmaceutical composition and application thereof. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 6-12 parts of radix bupleuri, 9-15 parts of radix curcumae, 6-12 parts of rhizoma acori graminei, 3-9 parts of fructus gardeniae, 3-9 parts of polygala tenuifolia, 9-15 parts of radix paeoniae rubra and 9-20 parts of cortex albiziae. The traditional Chinese medicine composition provided by the invention can be used for remarkably improving depression-like behaviors of mice with depression, reversing synaptic injury and improving the expression of synaptic associated proteins SYP and PSD-95. The anti-depression mechanism of the traditional Chinese medicine composition is that the traditional Chinese medicine composition has the effects of synergistically inhibiting activation of microglial cells and reducing the level of proinflammatory cytokines such as Tnf alpha, Il1beta and Il6, so that neuroinflammation is remarkably inhibited, and the traditional Chinese medicine composition has the advantages of novel formula, definite mechanism and definite curative effect for treating depression, particularly patients with anxiety and dysphoria symptoms.

The present application relates to a Pediococcus acidilactici capable of reducing the activation of hippocampal microglia cells and its application, belonging to the technical field of microorganisms. The Pediococcus acidilactici described in the present application is Pediococcus acidilactici CCFM1344, which was preserved in the Guangdong Microbial Culture Collection Center on September 12, 2023, with the preservation number GDMCC NO.63800. The preservation address is Building 59, 5th Floor, Guangdong Microbial Institute, 100 Middle Martyrs Road, Guangzhou. The Pediococcus acidilactici described in the present application can inhibit the over-activation of microglia cells caused by chronic stress, reduce the concentration of pro-inflammatory factors in the hippocampus of the brain, thereby relieving the activation of microglia cells in the hippocampus of the brain caused by chronic stress, and has excellent application prospects.

The application provides application of an intermediodorsal or spider ovigorous granule toxin-VI protein in preparation of an anti-inflammatory reagent, which can inhibit M1 type macrophage activation, promote M2 type macrophage cell transformation, inhibit macrophage and microglia cell activation and inhibit LPS-induced inflammation. The intermediodorsal or spider ovigorous granule toxin-VI protein disclosed by the application can significantly inhibit excessive activation of inflammation in an LPS-induced inflammation model, has good anti-inflammatory effects on peripheral inflammation and neural inflammation, has good anti-inflammatory effects in in-vivo and in-vitro inflammation models, and experiments show that the intermediodorsal or spider ovigorous granule toxin-VI protein has no obvious toxic side effects on mice at an inflammation inhibiting dose, and has good clinical application prospects.

The invention belongs to the field of medicine, and discloses application of bilirubin in preparation of a medicine for treating central nervous system autoimmune diseases, the bilirubin can relieve the clinical symptom severity of the central nervous system autoimmune diseases, relieve the demyelination injury severity of the central nervous system autoimmune diseases, and improve the curative effect of the central nervous system autoimmune diseases. The composition can be used for relieving microglial cell activation in the central nervous system autoimmune diseases, relieving inflammatory cell infiltration in the central nervous system autoimmune diseases and relieving neuroinflammatory response in the central nervous system autoimmune diseases. Good clinical application values are realized.

A microorganism containing Bacteroides fragilis genes is used as an active ingredient in the preparation of pharmaceuticals, medical devices, or food for treating optic nerve damage. This delivers Bacteroides fragilis (or its functional components) into the gastrointestinal tract, which helps maintain the number of retinal ganglion cells and the thickness of the retinal nerve fiber layer, inhibits the activation of retinal microglia, inhibits the activation of retinal inflammatory pathways and the expression of inflammatory mediators, thereby protecting visual function.

To provide a specific therapeutic targeting system based on the control of microglial cell activation.SOLUTION: Provided is a method of decreasing microglial activation comprising contacting a microglial cell with an anti-CD3 antibody.SELECTED DRAWING: None

The application discloses a fusion protein CHC targeting soluble IL-17RD, a preparation method and application thereof. The fusion protein CHC is formed by connecting and fusing two sIL-17RD neutralizing nanobodies CQ5 and CQ13 with human serum albumin (HSA) through a linker, and the structure is CQ5-Linker-CHC-Linker-CQ13, and the amino acid sequence is shown as SEQ ID NO. 1. The application further provides a gene sequence coding the fusion protein and an adeno-associated virus AAV-PHP.eB carrier containing the gene. The neutralizing nanobody fusion protein can specifically bind and neutralize the biological function of sIL-17RD, regulate the brain vascular endothelial cell homeostasis by directly inhibiting the inflammatory response of brain vascular endothelial cells induced by TNF-alpha and indirectly inhibiting the activation of microglial cells. The application can be used for treating or preventing neurodegenerative diseases such as Alzheimer's disease, and has the effects of protecting vascular injury, improving learning and memory and cognitive impairment, reducing beta-amyloid plaque deposition, reducing neuron loss and glial cell activation and the like.

The invention relates to a compound indoleacetic acid and application of the compound indoleacetic acid as an active ingredient in preparation of medicines or foods for treating optic nerve injury, and the indoleacetic acid is given in vivo, so that the number of retinal ganglion cells and the thickness of a retinal nerve fiber layer are favorably maintained, and activation of retinal microglial cells is inhibited; retina inflammation pathway activation and inflammatory mediator expression are inhibited, so that the visual function is protected.

The microorganism contains the bacteroides fragilis gene, and the bacteroides fragilis gene is used as an active ingredient to be applied to preparation of medicine or food for treating optic nerve damage, the bacteroides fragilis (or functional components thereof) is delivered to gastrointestinal tracts, the number of retinal ganglion cells and the thickness of a retinal nerve fiber layer can be maintained, activation of retinal microglia cells is inhibited, and optic nerve damage is inhibited. Retina inflammation pathway activation and inflammatory mediator expression are inhibited, so that the visual function is protected.

The application relates to a compound indole acetic acid, and application of the compound indole acetic acid as an active ingredient in the preparation of a medicament or food for treating optic nerve damage. In vivo administration of the indole acetic acid is beneficial to maintaining the number of retinal ganglion cells and the thickness of the retinal nerve fiber layer, inhibiting the activation of retinal microglia cells, inhibiting the activation of a retinal inflammation channel and the expression of inflammatory mediators, and protecting visual function.

The invention discloses an application of APOE as a target in preparation of a medicine for preventing and / or treating uveitis, the medicine comprises an APOE inhibitor, and the APOE inhibitor is used for inhibiting expression or activity of APOE protein so as to reduce microglial cell mediated inflammatory response. The invention discloses a key effect of APOE in uveitis pathogenesis, especially in microglial cell activation, for the first time, and provides a brand new drug target for treatment of uveitis; the inhibitor aiming at APOE can intervene in abnormal activation of microglial cells from the source, and possibly has better specificity and fewer side effects than a traditional immunosuppressor; meanwhile, the invention lays a solid theoretical and experimental foundation for developing a new generation of drugs for targeted therapy of uveitis.

The invention relates to the field of medicines, in particular to taraxasterol and application of taraxasterol salt in preparation of drugs for preventing and / or treating septic encephalopathy. According to the taraxasterol disclosed by the invention, the movement ability of a balance beam experiment in neurological function scoring of a brain trauma mouse can be improved, and the neurological function scoring including a movement experiment and a sensory experiment can be reduced; the traditional Chinese medicine composition can reduce the permeability of Evans blue in brain tissues, improve the short-term lesion volume after sepsis brain injury, relieve encephaledema and inhibit microglial cell activation and immune cell infiltration. Cell experiments prove that the taraxasterol can reduce neuroinflammation mediated by microglial cells, reduce expression of inflammatory factors such as TNF-alpha (tumor necrosis factor-alpha), IL-6 (interleukin-6) and IL-1beta (interleukin-1beta), and reduce neuron damage.

This invention provides a composition comprising, as an active ingredient, a turmeric-derived ingredient, which is useful for treatment, prevention, or amelioration of Alzheimer's disease. This invention relates to a composition for treatment of Alzheimer's disease, a composition for suppression of brain nerve cell death, a composition for suppression of microglia activation induced by amyloid β peptide, or a composition for suppression of PGE2, TNF-α, or IL-1β production induced by amyloid β peptide comprising, as an active ingredient, a turmeric extract extracted with at least one extraction solvent selected from water and a hydrophilic organic solvent or at least one of termeronol A and termeronol B.

The invention discloses a method for inhibiting microglial cell activation through Mfn2. According to the method, expression of Mfn2 in microglial cells is up-regulated by applying lactic acid or analogues thereof, so that activation of an NF-kappa B inflammation pathway is inhibited, the mitochondrial function is improved, and then activation of the microglial cells is relieved. Experiments prove that lactic acid promotes Mfn2 expression through histone lactic acid modification (such as H3k18la), and high-intensity intermittent training (HIIT) can improve obesity-related hypothalamic inflammation and systemic metabolic disorder through the mechanism. The invention provides a new strategy for treatment of obesity and related metabolic diseases.

The invention relates to the technical field of medical application, in particular to application of quercetin or derivatives thereof in preparation of drugs for preventing and / or treating offspring neurodevelopment disorder diseases caused by respiratory virus infection during pregnancy. The medicine comprises quercetin or a pharmaceutically acceptable quercetin derivative of the quercetin, and the quercetin derivative is a compound for improving the solubility or bioavailability of the quercetin through structural modification. The medicine blocks fetal microglial cell activation and macrophage subgroup imbalance induced by viruses by targeting maternal decidua natural killer cells (dNK), and treats filial generation neurodevelopment disorder diseases caused by infection of various pregnancy respiratory viruses such as influenza viruses, respiratory syncytial viruses (RSV), coronaviruses and the like. And the quercetin derivative can improve the bioavailability of quercetin through glycosylation, esterification or prodrug modification and the like, and has a wide clinical application prospect.

The invention relates to a construction method of a Parkinson-brain organ and application of the Parkinson-brain organ in Parkinson treatment drug screening. The invention discovers that the brain organ can be simply, conveniently and quickly induced to form a Parkinson-brain organ capable of being used for screening Parkinson treatment drugs by treating the brain organ with MPTP, and a basis is provided for quickly screening the Parkinson treatment drugs. According to the application, the obtained Parkinson-brain organ is applied to screening a proper therapeutic drug from reduced triterpenoids, a good effect of Schinensilactone M in treatment of Parkinson's disease is found, formation of alpha-synuclein oligomers is remarkably reduced, activation of microglial cells and release of related inflammatory factors are effectively inhibited, and the Schinensilactone M can be used for treating Parkinson's disease, so that the Schinensilactone M can be used for treating Parkinson's disease. A new compound selection with a novel structure and a unique action mechanism is provided for prevention and treatment of Parkinson's disease.

The invention discloses an application of PPIF as a target in preparation of a medicine for preventing and / or treating uveitis, the medicine comprises a PPIF inhibitor, and the PPIF inhibitor is used for inhibiting expression or activity of PPIF protein so as to reduce microglial cell mediated inflammatory response. The invention discloses the key effect of PPIF in the uveitis pathogenesis, especially in microglial cell activation, for the first time, and provides a brand new drug target for treatment of uveitis; an inhibitor aiming at PPIF can intervene in abnormal activation of microglial cells from the source, and possibly has better specificity and fewer side effects compared with a traditional immunosuppressor; meanwhile, the invention lays a solid theoretical and experimental foundation for developing a new generation of drugs for targeted therapy of uveitis.

The invention discloses an oxygen supply nutrition delivery micro-fluidic brain organ chip and a preparation method thereof, and belongs to the technical field of biomedical engineering and micro-fluidic organ chips, and the preparation method comprises the following steps: performing oxidative stress treatment on microglial cells, inoculating the microglial cells into an organ culture cavity, and inoculating neurons subjected to hypoxia and ischemia treatment into a peripheral nerve culture cavity; establishing concentration distribution of inflammatory factors or injury related factors through a nutrition mixing matrix and a distribution branch so as to simulate a difference microenvironment between the adjacent end and the far end of a focus; performing time sequence evaluation on the interaction process of microglial cell activation and neuron damage by combining morphological observation and molecular detection; and establishing concentration distribution of inflammatory factors or injury-related factors between the two cavities through a nutrition mixing matrix, and obtaining morphology and molecular readout according to a time sequence of 24-72 hours so as to reproduce the interaction process of microglial cell activation and neuron injury.

Adeno-associated virus (AAV) gene therapy vectors express a therapeutic protein or RNA that treats a genetic defect in a cell. The present disclosure provides AAV gene therapy vectors that additionally express an anti-inflammatory protein or peptide. When the provided AAV gene therapy vectors are used in methods of treatment of. for example. neurodegenerative diseases. the therapeutic protein / RNA treats the genetic defect within the cells directly transduced by the AAV vectors while the anti-inflammatory protein / peptide is secreted by the transduced cells into the intercellular milieu and treats microglial activation associated with the neuroinflammatory component of the neurodegenerative diseases. The therapeutic protein and anti-inflammatory protein / peptide can be expressed as fusion protein in which the two are separated in the fusion protein by a self-cleaving peptide. The provided AAV gene therapy vectors and methods are thus useful in treating neurological and neurodegenerative disorders.

The present application relates to the technical field of health-care foods and particularly relates to the use of tremella polysaccharides in preparing products for preventing and treating high-fat diet induced anxiety. It is found by researches in the present application that tremella polysaccharides can relieve the weight gaining of mice fed by high-fat diet, reduce the weights of the liver and fat, inhibit microglial cell activation and neuritis in the hippocampus, balance the intestinal flora, and have an excellent improvement effect on preventing and treating anxiety of mice caused by high-fat diet feeding. The present application verifies that tremella polysaccharides have the effect of preventing and treating high-fat diet induced anxiety and thus can be used to prepare products for preventing and treating high-fat diet induced anxiety. Therefore, as a nutritional intervention strategy for high-fat diet induced anxiety disorders, tremella polysaccharides are of great significance for assisting in preventing and relieving high-fat diet induced anxiety disorders.

The application discloses an oxygen and nutrient delivery microfluidic brain organ chip and a preparation method thereof, and belongs to the technical field of biomedical engineering and microfluidic organ chip, which comprises the following steps: inoculating microglial cells treated by oxidative stress into an organoid culture cavity, and inoculating neurons treated by ischemia and hypoxia into a peripheral nerve culture cavity; a concentration distribution of inflammatory factors or damage-related factors is established through a nutrient mixing matrix and a distribution branch, so that a difference microenvironment of a lesion adjacent part and a distal end is simulated; a time sequence evaluation on an interaction process of microglial cell activation and neuron damage is performed in combination with morphological observation and molecular detection; the concentration distribution of the inflammatory factors or the damage-related factors is established between the two cavities through the nutrient mixing matrix, morphological and molecular readouts are acquired in a time sequence of 24 to 72 hours, so that the interaction process of the microglial cell activation and the neuron damage is reproduced.

The invention discloses an application of an NNT overexpression lentivirus in preparation of drugs for spinal cord injury and microglial cell activation, and belongs to the technical field of biological medicines, the NNT overexpression lentivirus is shown as SEQ ID NO.1; nNT overexpression inhibits microglial cell activation by relieving oxidative stress of microglial cells and relieves prognosis injury degree and inflammatory response, so that understanding of spinal cord injury cells and molecular mechanisms can be improved, a new theoretical insight is provided for effective management of spinal cord injury, a treatment target is determined, and the application prospect is wide. In addition, understanding of molecular mechanisms of abnormal activation of small glial cells in spinal cord injury can be improved, and rehabilitation and treatment are promoted.

The invention relates to the technical field of health food, in particular to application of tremella polysaccharide in preparation of a product for preventing and treating anxiety caused by high fat diet. Researches find that tremella polysaccharide can reduce weight gain of mice fed with high-fat diet, reduce liver and fat weight, inhibit microglial cell activation and neuroinflammation in hippocampus and balance intestinal flora, and has an excellent improvement effect on prevention and treatment of anxiety of mice caused by high-fat diet feeding. The application verifies that the tremella polysaccharide has the effect of preventing and treating the anxiety caused by the high-fat diet, can be applied to preparation of products for preventing and treating the anxiety caused by the high-fat diet, serves as a strategy for nutrition intervention on the anxiety disorder caused by the high-fat diet, and has important significance on auxiliary prevention and improvement of the anxiety disorder caused by the high-fat diet.

The invention discloses an application of 1-O-acetyl-4R, 6S-inula flower lactone in preparation of a medicine for preventing and treating neuroinflammation, and researches find that 1-O-acetyl-4R, 6S-inula flower lactone (AB) is connected with kinase by targeting PDZ, so that inflammatory response is reduced, oxidative stress is reduced, mitochondrial balance can be maintained, and neuroinflammation is inhibited; in a cell experiment, AB can inhibit lipopolysaccharide induced BV-2 microglial cell activation, reduce release of inflammatory factors such as microglial cell tumor necrosis factor-alpha and interleukin-6, inhibit mitogen activated protein kinase and influence an AMP dependent protein kinase signal channel; in animal experiments, AB can relieve mouse neuroinflammation induced by LPS and improve brain neuron damage. AB can be used for developing medicines for preventing and treating neuroinflammation, has no obvious toxic and side effects, and has the advantages of low dosage, safety, oral administration and the like.

The invention belongs to the technical field of biological medicine, and provides application of ruminococcus lividus to preparation of medicine for preventing or treating children obesity-related cognitive impairment in order to solve the problem that the biological mechanism associated with children obesity and cognitive impairment is still not clear at present. The active ruminococcus is specifically used for inhibiting microglial cell activation and reducing neuroinflammation by metabolizing D-piperidine acid, so that the prevention or treatment of obesity-related cognitive impairment of children is realized. Experimental research finds that colonization of lively ruminococcus in a mouse model can reverse obesity-induced cognitive impairment, inhibit activation of microglial cells in the brain and relieve neuroinflammation; therefore, the active ruminococcus has the therapeutic potential of relieving obesity-related cognitive impairment of children.

Described are methods for the treatment of disorders associated with microglial activation, including neurodegenerative diseases and immunomodulatory diseases, particularly immunomodulatory diseases of the eye. Generally, the methods include administering a therapeutically effective amount of an IGF1 or IGF1R antibody or antigen binding fragment thereof, or an IGF1R agonist, as described herein, to a subject who is in need of, or who has been determined to be in need of, such treatment.