28 results about "Phagocytosis" patented technology

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 the technical field of immune engineering, and in particular to a CD155-targeting antibody or antigen-binding fragment and a use thereof. The antibody comprises a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 23 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 24, or a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 25 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 26. The antibody has an excellent binding capability with CD155, and CAR-T cells constructed on the basis of the antibody have a significant killing capability against tumor cells expressing CD155, as well as an obvious cellular internalization effect, the capability of promoting the cytotoxic effect of NK cells, and the capability of promoting the phagocytosis effect of macrophages, thereby exhibiting an excellent anti-tumor effect.

The application belongs to the field of biological medicine, and relates to a drug-loaded nanovesicle and a preparation method and application thereof. The drug-loaded nanovesicle comprises: a vesicle core comprising siRNA capable of specifically targeting a silenced NR1D1 gene; and a vesicle membrane fused by red blood cell membranes, macrophage membranes, cardiolipin, cholesterol and lecithin. The drug-loaded nanovesicle can specifically target macrophages in the immune suppression stage of sepsis, and has an intracellular response release function. By inhibiting the expression of NR1D1, the drug-loaded nanovesicle restores the functions of BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axes, reestablishes the phagocytosis function of macrophages and the lysosome-dependent bacterial clearance capacity, significantly improves the survival rate of animals in a sepsis immune suppression model and reduces the bacterial load. Compared with a traditional electroporation method, the preparation method of the application significantly improves the encapsulation rate of siRNA.

The application belongs to the technical field of medical detection, and particularly relates to a polysaccharide contrast agent capable of renal metabolism and a preparation method thereof. The polysaccharide contrast agent has a structure as shown in formula (I), a particle size less than or equal to 8 nm, and can be rapidly metabolized through the kidney. The preparation method is to graft a metal macrocyclic ligand to a nano-crosslinked polysaccharide particle, and to prepare through a deprotection and metal ion chelation step. Since the contrast agent has the characteristic of renal metabolism, phagocytosis of the reticuloendothelial system is reduced, in vivo deposition of the contrast agent is reduced, and thus the biological safety is improved. Since a macrocyclic chelating ligand is used, good kinetic stability is achieved, the risk of in vivo metal ion deposition is reduced, and when applied to in vivo imaging, clear imaging of cardiovascular, lymph node, liver and other parts can be achieved. The preparation method is simple and easy to implement, reaction conditions are mild, is conducive to large-scale production and clinical transformation, and has a wide biomedical application prospect.

The application belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of umbilical cord blood plasma-derived extracellular vesicles and related bioactive molecules thereof in treatment of Alzheimer's disease. Specifically, the application isolates extracellular vesicles (UCBP-sEVs) from umbilical cord blood plasma, which has the effect of improving Alzheimer's disease. Further research finds that high enrichment of miR-16-2-3p therein is a key molecule for mediating treatment of Alzheimer's disease. miR-16-2-3p targets and inhibits expression of ROCK2, reduces phosphorylation level of TFEB and promotes nuclear translocation of the same, activates microglial autophagy-lysosome pathway, and thus promotes phagocytosis and degradation of intracerebral beta amyloid, and therefore has good practical application value.

This invention belongs to the field of nanocarrier and immunotherapy technology, specifically relating to a lipid nanoparticle targeting tumor-associated macrophages, a combined delivery method, and its application in tumor immunotherapy. The lipid nanoparticles targeting CD206 tumor-associated macrophages constructed in this invention are used for efficient in vivo delivery of multifunctional nucleic acid molecules, achieving immune regulation, gene editing, and anti-tumor therapy. This invention achieves targeted delivery and multifunctional synergistic effects through lipid particle design, nucleic acid sequence design, and in vitro and in vivo functional verification. Through in vivo delivery of ipLNPs, macrophages can simultaneously achieve: 1) expression of anti-PD-L1 antibodies, blocking immunosuppressive signals; 2) expression of HER2-CAR structures, enhancing phagocytosis and killing ability against tumors; and 3) remodeling of the tumor immune microenvironment through CRISPR / Cas9-mediated FN1 knockout. The lipid nanoparticles constructed using this invention can solve the problem of insufficient targeting of immune cells in the tumor microenvironment by traditional LNP delivery systems.

The present application relates to the technical fields of biological medicine and cellular immunotherapy, and particularly relates to a signal conversion receptor targeting IL-10, an engineered macrophage and application thereof. The signal conversion receptor is composed of an extracellular domain and a transmembrane domain and an intracellular domain derived from TLR9, and the extracellular domain sequentially comprises a signal peptide, a HA tag and a specific binding domain of an IL-10 receptor alpha subunit from N-terminal to C-terminal. The present application further prepares an engineered macrophage SR CAR-M capable of specifically recognizing IL-10 and converting it into a TLR9 activation signal, which can induce macrophages to polarize to M1 type and has excellent phagocytosis and killing capacity for bladder cancer, breast cancer, lung cancer and melanoma cells, and can be used for preparing related tumor treatment drugs, overcoming the common problems of existing cell therapy, such as easy exhaustion, difficult infiltration and easy inhibition in solid tumors, and having significant clinical transformation potential.

The application belongs to the field of stem cell biology and relates to a culture method of a 3D nerve immune organoid containing microglia cells, which comprises the following steps: S1, inducing induced pluripotent stem cells in ectoderm direction and mesoderm direction respectively to obtain nerve-like embryoid bodies and yolk sac-like embryoid bodies; S2, culturing the nerve-like embryoid bodies to make them differentiate into nerves to obtain nerve ring structures, re-digesting the nerve ring structures to obtain nerve progenitor cell single cells, and culturing the yolk sac-like embryoid bodies to make them generate macrophage progenitor cells; and S3, fusing the nerve progenitor cell single cells and the macrophage progenitor cells and continuing to culture to form the 3D nerve immune organoid containing microglia cells. The brain-like organoid of the application can realize the following functions: exploring the control of microglia cells on the proportion of progenitor cells in the development stage, the change of phagocytosis, the control on the number of mature neurons, the influence on cell proliferation and apoptosis, and simultaneously accepting external stimulation and making corresponding functional stress changes.

To provide a new technique for inhibiting formation of pigmented spots.SOLUTION: The present invention provides a pigmented spot formation inhibitor including vitamin B6 as an active ingredient.SELECTED DRAWING: None

The inventions relates to Immunoglobulin A (IgA) or a pharmaceutical composition comprising IgA for use in the treatment of an infectious disease of or in an immune privileged organ, such as the eye, fetus, placenta, central nervous system (CNS) and / or testicles caused by a bacterial, fungal, viral or parasitic infection, in particular caused by bacteria of the human microbiome. IgA-coated pathogens can be addressed by FCAR+ and / or CD11c+ innate immune cells, for example by phagocytosis, or by activation of the complement system. The use of IgA or a pharmaceutical composition comprising IgA in immune privileged sites is advantageous because in contrast to IgG, IgA-coated pathogens do not trigger activation of C1q, a protein used for the controlled pruning of synapses. This prevents neuronal damage in said immune privileged organ(s), while at the same time allowing an antibody-mediated immune response in said organs.

The application belongs to the technical field of biomaterial preparation, and particularly relates to a composite drug delivery system based on macrophage membranes and a preparation method and application thereof. The composite drug delivery system takes a lipid nanoparticle as a drug targeting delivery carrier, coats quercetin through an active phagocytosis mode, coats a macrophage membrane on the surface of the lipid nanoparticle, and constructs a quercetin lipid nanoparticle coated with a macrophage membrane (MCM@QU@LNP). The composite drug delivery system provided by the application can promote drug enrichment in RA lesions, improve local drug exposure, realize precise drug delivery in the RA part, has good biological safety, and reduces system toxicity.

There is provided a method of treating an immune cytopenia in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound of formula (I) wherein R1, R2, R3 and R4 are as defined herein.

Provided herein are chimeric antigen receptors, comprising an extracellular domain capable of binding to an antigen, an Fc region, a flexible linker, a transmembrane domain, and may further comprise at least one intracellular domain that is designed to increase the anti-tumor activities of granulocytes, macrophages, and dendritic cells by increasing their phagocytosis and / or proinflammatory cytokines secretion and / or antigen presentation. Provided herein are vectors and nucleic acid molecules encoding any of the chimeric antigen receptors described herein. Provided herein are methods to genetically engineer granulocyte-macrophage progenitors (GMPs) to express the chimeric antigen receptors described herein. The CAR-Fc-GMPs may be induced to differentiate into macrophages or granulocytes. Provided herein are macrophages and granulocytes that express a CAR-Fc prepared by any of the methods described herein. Provided herein is an immunotherapy method for treating a subject having cancer with GMPs or macrophages or granulocytes that express the chimeric antigen receptors described herein.

The application discloses a p-hydroxycinnamaldehyde modified sphingomyelin liposome and application thereof in anti-MRSA infection. The p-hydroxycinnamaldehyde is bonded with the sphingomyelin through a two-step esterification reaction to obtain a bonding product sphingomyelin-p-hydroxycinnamaldehyde, and the p-hydroxycinnamaldehyde modified sphingomyelin liposome is prepared through a film hydration method. The liposome provided by the application is spherical, and the particle size distribution is uniform. The sphingomyelin component in the liposome can effectively neutralize the exotoxin of MRSA, and relieve the damage of the exotoxin of MRSA to normal cells of the body. The p-hydroxycinnamaldehyde in the liposome can induce the M0 type and M2 type macrophages in the body to polarize into M1 type macrophages with stronger phagocytosis and killing ability, relieve the immunosuppression caused by MRSA infection, and enhance the clearance ability of the macrophages to MRSA. The liposome provided by the application has application prospects in the preparation of drugs or preparations for treating diseases caused by MRSA infection.

The invention discloses an application of an MSR1 inhibitor in preparation of an anti-tumor immunopotentiator. The MSR1 inhibitor is composed of doxylamine, trafenotide, dexrazoxane and clavulanic acid. The invention discloses application of an MSR1 inhibitor combined with an immune checkpoint inhibitor in preparation of a medicine for treating solid tumors. The MSR1 inhibitor disclosed by the invention is used as an anti-tumor immunopotentiator and is combined with an immune checkpoint inhibitor to treat solid tumors, so that the curative effect of tumor immunotherapy can be improved. The MSR1 inhibitor can induce tumor-related macrophages to be differentiated into anti-tumor subtypes, anti-tumor immunity is driven through phagocytosis and generation of cell factors, and a new method is provided for improving the curative effect of tumor immunotherapy.

The present invention provides a controlled-release pharmaceutical composition containing Indigo Naturalis or its main active ingredient, and a preparation method and use thereof. The controlled-release pharmaceutical composition includes micropellets. The micropellets include an active ingredient and one or more pharmaceutically acceptable excipients, the active ingredient includes Indigo Naturalis, indigo, indirubin, or any combination thereof; wherein the micropellets have an enteric outer layer. The controlled-release pharmaceutical composition provided by the present invention can alleviate the disease condition of inflammatory bowel disease, especially ulcerative colitis, and can reduce or avoid the phagocytosis of the active ingredient by intestinal macrophages, thereby reducing the effect on the patient's liver. The composition exhibits good stability and reduces side effects while maintaining therapeutic efficacy.

The present application provides antibodies, fusion proteins and their uses for treating coronavirus. The 6-HB interfering polypeptide in the fusion protein of the present application cooperates with the antibody portion or antigen binding fragment to prevent SARS-CoV or SARS-CoV-2 virus particles from fusing with cells, and to mediate phagocytosis of immune cells, clearing virus particles.

The application discloses preparation and application of anti-Fusobacterium nucleatum PknK and PknL protein monoclonal antibodies and belongs to the technical field of biotechnology. The application takes two virulence proteins PknK and PknL of the Fusobacterium nucleatum as immunogens, successfully prepares monoclonal antibodies against the serine / threonine protein kinases PknK and PknL of the Fusobacterium nucleatum through hybridoma cell fusion technology, and the two monoclonal antibodies against the PknK and PknL proteins of the Fusobacterium nucleatum have good safety, thereby providing a basis for clinical drug safety. More importantly, the antibodies can not only efficiently neutralize bacterial toxins and directly eliminate the pathogenicity of the Fusobacterium nucleatum, but also can be directly combined on the bacterial surface to enhance the recognition and phagocytosis efficiency of immune cells to the bacteria, thereby clearing pathogenic bacteria, and is expected to be developed into a drug for resisting the Fusobacterium nucleatum infection and has a very good application prospect.

The application discloses application of a recombinant MBL2 protein in preparation of a medicine for treating metabolic disorder associated liver disease (MAFLD), wherein the amino acid sequence of the recombinant MBL2 protein is shown as SEQ ID NO. 1, or is an active variant or fragment with at least 95% homology and retaining natural immune regulation and metabolic regulation functions. The application provides a brand-new drug action target and treatment mechanism, and fills the blank of MAFLD specific therapy. MAFLD is the result of multiple attacks, and single-pathway drugs often have poor effects. The recombinant MBL2 protein provided by the application has multiple biological functions: it can remove damage signals through the phagocytosis function of macrophages, reduce inflammation through the regulation of macrophage polarization, and improve insulin resistance and promote lipid metabolism through the activation of the AMPK pathway in the liver.

The application discloses a new application of m6A modified gene GAS6 and its receptor MERTK in rheumatoid arthritis. Multi-omics integrated analysis of synovial tissue and peripheral blood mononuclear cells of RA patients reveals common dysregulation of transcriptomics and epitranscriptomics, highlighting genes with both differential expression and m6A modification, which are enriched in processes such as phagocytosis, Th17 differentiation and cell aging. Among these genes, GAS6 shows the most significant m6A hypermethylation and expression up-regulation, and is verified as a key effector molecule interacting with MERTK / AXL receptor. Functional experiments show that GAS6 and MERTK synergistically promote the malignant phenotype of RA fibroblast-like synoviocytes, enhance their proliferation, migration, inflammatory cytokine secretion and anti-apoptotic ability.

The application discloses a cell monomolecular mechanical force sensor for detecting a cell phagocytosis process, a preparation method and application thereof, and the sensor comprises a microsphere substrate and a plurality of double-stranded DNA mechanical probes modified on the surface of the microsphere substrate; the probes are composed of a first single-stranded DNA and a partially complementary second single-stranded DNA, and form a FRET or fluorescence quenching pair; when a cell exerts a pulling force on the probes through receptor-ligand interaction during phagocytosis or wrapping of the microsphere and the pulling force exceeds a preset melting threshold, the double-stranded DNA is melted or conformationally changed and a fluorescence signal change is generated, so that detection of a single-molecule level mechanical force at a phagocytosis interface is realized. By adjusting a geometric conformation and sequence design of the probes, a probe library with different melting force thresholds can be constructed, quantitative analysis and spatial distribution characterization of mechanical forces during phagocytosis are realized. The application can truly simulate a three-dimensional phagocytosis interface, and provides an effective tool for revealing a mechanism of blood flow mechanics regulating endothelial cell phagocytosis behavior and drug screening related to diseases.

This invention belongs to the field of lipid nanoparticle preparation technology, specifically relating to a zwitterionic modified lipid nanoparticle, its preparation method, and its application. The zwitterionic modified lipid nanoparticle includes a lipid nanoparticle matrix and a lipid derivative modified on its surface, wherein the lipid derivative is a zwitterionic modified polypeptide; and the zwitterion is DSPE-PEG. The lipid nanoparticles of this invention possess a strong hydration layer, which can significantly reduce the production of APA in vivo, avoiding the ABC effect associated with repeated injections. In the presence of APA in vivo, it can reduce the impact of APA on the interaction between liposomes and immune cells, reduce the phagocytosis and clearance of lipid nanoparticles by the mononuclear phagocytic system, and prolong blood circulation time. Even with high levels of APA in vivo, it can still accumulate at the tumor site, further improving the therapeutic effect and providing an effective strategy to avoid the ABC effect.

The application discloses a kind of based on flat Halbach array's magnetophoresis device and method, two push rod type linear stepping motors in device are set in guide rail two ends by L type push rod, L type push rod top is equipped with stage, the telescopic rotary motor is respectively arranged on the stage, telescopic rotary motor vertically connects magnet plate, third telescopic rotary motor is arranged in rear end of one of magnet plate, vertical guide rail groove and horizontal guide rail groove are equipped on one of magnet plate, control module is connected with each motor.The application utilizes the high gradient magnetic field advantage of flat Halbach array, combines the accurate control ability of motor, utilizes the automatic uniform field and gradient field conversion function of device, cooperates with the microscope with image acquisition function, realizes the observation of degree of automatic cell phagocytosis magnetic particle, does not need to additionally equip multiple sets of magnetic field device, it is convenient to operate and can effectively protect cell activity, adapts biomedical detection, analysis detection and other multi-field magnetic field application needs.

This invention relates to the field of biomedical technology, and more particularly to a tumor vaccine based on bacterial outer membrane vesicles and tumor-associated glycoantigens, its preparation method, and its application. The tumor vaccine provided by this invention induces increased levels of IL-6 and TNF-α secretion in RAW 264.7 and DC 2.4 cells in vitro, promoting phagocytosis and maturation; in vivo, it induces the maturation of T cells and DC cells in the spleen and lymph nodes, significantly inhibiting tumor growth. The tumor vaccine achieves stable antigen loading, induces a strong immune response, significantly inhibits tumor growth, and demonstrates good efficacy and safety in mouse models.

The application discloses application of a large-mouth black bass stomach polypeptide in preparation of an antioxidant and / or immunoregulation product, relates to the field of bioactive peptides, and is characterized in that the large-mouth black bass stomach polypeptide is a polypeptide product obtained by alkaline protease enzymolysis of large-mouth black bass stomach, and components with molecular weights less than 3000 Da account for more than 98% of the total peptide amount. The polypeptide has significant DPPH free radical, hydroxyl free radical and ABTS cationic free radical scavenging capacity and reducing capacity, can promote macrophage proliferation, enhance phagocytosis, promote nitric oxide secretion, up-regulate immune-related cytokine expression, and play an immunoregulation role through activation of P38 and P44 MAPK signal pathways. The application realizes high-value utilization of large-mouth black bass processing by-products, has high product safety, and has a wide application prospect.

The application discloses a kind of chimeric antigen receptor macrophages and preparation method thereof.To the problem that traditional T cell costimulatory domain is not matched with macrophage signal pathway, the application provides a CAR structure specially designed for the biological characteristics of macrophage.The chimeric antigen receptor expressed by the CAR-M cell includes at least one costimulatory domain selected from Ncr1, TLR5, Rage and Tim4, and the CAR structure is composed of CD22 scFv extracellular antigen recognition region, CD8 alpha hinge region, transmembrane region, the costimulatory domain and CD3 zeta intracellular signal domain in sequence.By constructing the recombinant expression plasmid of pB vector skeleton and inserting P2A-EGFP expression monitoring element, RAW264.7 macrophages are transfected by using Zeta life transfection reagent, and the CAR positive rate can reach more than 97% by flow cytometry or confocal microscopy verification.The application realizes the efficient activation of phagocytosis, antigen presentation and microenvironment remodeling functions specific to macrophages, and significantly improves the application potential of CAR-M in solid tumor treatment.

The present application relates to a kind of mannose modified macrophage targeted nanoparticles and its preparation method and application, and the nanoparticles include mannose-soy protein peptide copolymer and its loaded bioactive substance, wherein the mass ratio of soy protein peptide and mannose in the mannose-soy protein peptide copolymer is (1-3):(1-2), and the mass ratio of the mannose-soy protein peptide copolymer and bioactive substance is (20-60):1.Compared with the prior art, the bioactive substance-loaded nanoparticles of the present application are mannose-modified, the wall material used has good biocompatibility and high safety, the preparation method is simple, easy to control and operate, and there is no toxic organic solvent residue, which can significantly promote the phagocytosis of active substances by macrophages, improve the bioavailability of bioactive substances and promote the activity change of macrophages.

This invention belongs to the field of biotechnology, specifically relating to a method for preparing a titanium-based prosthetic coating with both antibacterial and cell burial regulation functions, and its application. The preparation method of the titanium-based prosthetic coating in this invention includes the following steps: adding (DOPA)6-PEG5-DBCO lyophilized powder to Tris-HCl buffer to prepare a mixture; immersing a pretreated titanium rod in the mixture to obtain a titanium rod with (DOPA)6-PEG5-DBCO covalently bonded to its surface; immersing the obtained titanium rod in a metal ion aqueous solution and soaking it in the dark for 6-24 hours to obtain a surface-loaded (DOPA)6-PEG5-DBCO / Mn solution. 2+ / Cu 2+ A titanium rod with a bimetallic coordination coating is then immersed in an N3-GLP-1RA solution, and after a light-protected reaction, the titanium-based prosthesis coating is obtained. The coating of this invention exhibits excellent biocompatibility and can promote osteogenic differentiation of bone marrow mesenchymal stem cells.