22 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 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.

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.

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 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 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 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 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 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.

This invention belongs to the field of biomedical technology and discloses the application of the SSRP1 gene as a target in the preparation of drugs for the prevention or treatment of NMOSD. These drugs contain components that target and interfere with the SSRP1 gene or its expression. This invention creatively discovers the application of the SSRP1 gene as a target in the preparation of drugs for the prevention or treatment of NMOSD. Knockdown of SSRP1 can alleviate motor balance impairment in NMOSD, improve the severity of demyelination damage in NMOSD, improve the myelin regeneration microenvironment in NMOSD, alleviate microglial activation caused by NMOSD, alleviate microglial-mediated neuroinflammation in NMOSD, and alleviate microglial ferroptosis in NMOSD. Therefore, it can be applied to the preparation of drugs for the treatment of NMOSD and has good clinical application value.

The invention discloses puerarin lipidosome with ginsenoside Rh2 as a lipid membrane material and a preparation method and application of the puerarin lipidosome, the membrane material cholesterol of the lipidosome is replaced with the lipidosome (Rh2-Pue-LP) of ginsenoside Rh2 de-entrapped puerarin, the Rh2-Pue-LP can inhibit and activate a JAK2-STAT3 signal channel, so that transcription of NLRP3 is inhibited, and the lipidosome has the advantages that the lipidosome can be used for preparing the puerarin lipidosome with the ginsenoside Rh2 as the lipid membrane material; the traditional Chinese medicine composition can be used for inhibiting microglial cell activation and neuronal apoptosis, effectively penetrating through a complete blood brain barrier (BBB), reaching a focus part and playing a role in neuroprotection.

The invention discloses application of sulodexide in preparation of a medicine for treating sepsis-related encephalopathy, and belongs to the technical field of biological medicine. According to the application disclosed by the invention, the effect of preventing and / or treating sepsis-related encephalopathy of sulodexide is found for the first time; animal experiments prove that sulodexide improves cognitive impairment of a patient with sepsis-related encephalopathy by improving the survival rate of the patient with sepsis-related encephalopathy, inhibits brain neuroinflammation of the patient with sepsis-related encephalopathy, reduces brain tissue damage of the patient with sepsis-related encephalopathy, and improves the curative effect of the patient with sepsis-related encephalopathy. According to the present invention, with the application of the compound in the prevention and / or treatment of the sepsis-related encephalopathy, the microglial cell excitation of the sepsis-related encephalopathy patient can be inhibited, and the HMGB1 and / or RAGE pathway of the sepsis-related encephalopathy patient can be inhibited so as to prevent and / or treat the sepsis-related encephalopathy, such that the new idea is provided for the preparation of the sepsis-related encephalopathy product, and the wide application prospect is provided.

This invention relates to the field of biomedical technology and provides the application of ginsenoside Rg2 in the preparation of drugs for treating multiple sclerosis (MS). Ginsenoside Rg2 exerts its therapeutic effect on MS through the following mechanisms: reducing the expression levels of pro-inflammatory factors, promoting regulatory T cell differentiation, and inhibiting the infiltration of immune cells into the central nervous system; inhibiting NLRP3 signaling pathway activation and reducing neuronal pyroptosis; preventing the immune system from destroying myelin and reducing the ratio of demyelinated area to white matter area; upregulating oligodendrocyte transcription factor expression, promoting oligodendrocyte precursor cell proliferation and differentiation, and promoting myelin regeneration; and inhibiting microglia activation. This invention solves the problems of limited efficacy, significant side effects, only delaying progression, and limited administration methods of existing drugs.

The invention discloses application of lactobacillus rhamnosus to preparation of a product for treating hippocampus injury caused by chronic fatigue. The invention discloses that the lactobacillus rhamnosus BD4047 has good neuron and synaptic protection capability for the first time, and can improve hippocampus neuron damage caused by chronic fatigue, increase the density of hippocampus neuron dendritic spines, increase the length of the dendritic spines and increase the number of branch intersection points of the dendritic spines; the synaptic injury caused by chronic fatigue is improved, the synaptic gap width is reduced, the thickness of a synaptic compact region is increased, the length of a synaptic active region is prolonged, the increase of the number of synaptic vesicles and the increase of the number of SYP spots are promoted, and a remarkable synaptic repair effect is achieved; in addition, mouse hippocampus microglial cell activation caused by chronic fatigue can be inhibited, hippocampus injury caused by chronic fatigue and diseases related to the hippocampus injury can be comprehensively improved, and therefore the composition has a wide prospect.

The invention discloses a method for regulating a hippocampus immune balance mechanism of a stress depression mouse through electroshock, and relates to the field of nerves and spirit. Comprising the following steps: constructing a chronic unpredictable mild stress CUMS depression-like mouse model, and performing intervention by adopting electroshock pricking ECS; depression-like behaviors are evaluated through behavioral tests, including a sweet water preference experiment, an open field experiment and a tail suspension experiment; the method comprises the following steps: collecting hippocampus tissues of a mouse, and detecting the level of inflammatory factors and the polarization state of microglial cells by using ELISA, Western blot and an immunofluorescence technology; and evaluating the activation of the microglial cells by combining PET-CT scanning with a [< 18 > F] DPA-714 tracer agent. By integrating clinical, animal and cell experiments, the invention reveals that ECT recovers the balance of microglial cells M1 / M2 through a Chuk / NF-kB signal channel, thereby relieving the depressive symptom.