193 results about "Th polarization" patented technology

The invention relates to the technical field of medicines, in particular to a construction method and application of a photothermal conversion platform for treating osteoarthritis by regulating synovial macrophage polarization. According to the present invention, the M2 membrane-structured black phosphorus selenium carbon body (M2-BPSeC) photo-thermal nano-platform is innovatively provided, the triple functions of bionic targeting delivery, precise thermal control intervention and immune microenvironment remodeling are integrated, and the excellent synergistic treatment effect is represented in the in-vitro cell model and the OA animal model. The technology breaks through the technical bottleneck that traditional treatment is insufficient in targeting and single in intervention dimension, precise functional coupling of the physical thermal effect and immunoregulation is achieved for the first time, and a brand new strategy of targeting-temperature control-immunity integration is provided for osteoarthritis treatment. The efficient and controllable preparation process and the remarkable multi-dimensional treatment effect open up a new path for cartilage regeneration and immune balance regulation and control.

The invention discloses an alveolar macrophage glycyrrhetinic acid liposome and a preparation method thereof, and belongs to the field of biological medicines. The surface of glycyrrhetinic acid lipidosome is modified with alveolar macrophage targeting molecules, so that the lipidosome can specifically target M1 alveolar macrophages induced by lipopolysaccharide serving as a main component of the outer wall of gram-negative bacteria, entrapped glycyrrhetinic acid is ingested by the alveolar macrophages, M2 polarization is specifically induced, and the specific targeting effect is achieved. Lung inflammatory injury caused by gram-negative bacteria is reduced, lung tissue injury and fibrosis caused by excessive inflammation are prevented, and great significance is achieved for pneumonia caused by gram-negative bacteria.

The invention relates to the field of biological medicine, in particular to application of a reagent for measuring or regulating the expression level of HIF-1alpha in preparation of a kit for diagnosing or gout, the kit containing the reagent and a gout prediction device. The HIF-1alpha is applied as a gout diagnosis target and a treatment target for the first time, the polarization degree of Th17 cells in an inflammatory microenvironment of a gout patient can be specifically reflected, early dynamic monitoring of gout related inflammatory activities is achieved, polarization of Th17 cells and expression of related proinflammatory factors are inhibited in a targeted mode, and a new strategy is provided for prediction, diagnosis and treatment of gout.

The invention discloses an engineered macrophage and a pharmaceutical composition and application thereof, and CCM3 expression in the engineered macrophage is inhibited, so that the engineered macrophage is polarized towards the M2 direction or the engineered macrophage is an M2 type macrophage. Besides, the invention further develops a temperature-sensitive cell-loaded hydrogel preparation which can promote polarization of macrophages in the M2 direction by inhibiting expression of signal molecules CCM3 on adhesion spots, and the temperature-sensitive cell-loaded hydrogel preparation can promote bone defect immune osteogenesis through local injection.

The invention relates to a lung cancer organoid and peripheral blood source immune cell co-culture model and a construction method thereof. Specifically, the invention provides a construction method of a macrophage and tumor organoid co-culture model for evaluating anti-tumor activity, monocytes of autologous or allogeneic peripheral blood of a patient are induced and differentiated into high-purity macrophages in vitro, and the high-purity macrophages and lung cancer tumor organoid are subjected to three-dimensional co-culture in matrigel; the model aims at highly reducing a core interaction network of tumor cells and macrophages in TME; the dynamic change of the polarization state of the macrophage is simulated and observed; the problem that an organ-like model is incomplete due to immune component deficiency or spatial positioning distortion of an existing model is effectively solved, an experimental platform closer to the physiological state is provided for tumor immune microenvironment research, and therefore development of the tumor immune treatment field is promoted.

The invention belongs to the technical field of biological detection, and provides a multiple cell factor detection kit in macrophage polarization and a preparation method and application thereof, and the detection kit comprises a capture antibody, a detection antibody, a mixed protein standard substance, a diluent and a washing buffer solution. The capture system is used for preparing a capture antibody coupled with a fluorescence coding microsphere by coupling a biotinylated antibody with a fluorescence microsphere coated with biotin, and the detection system is used for preparing a fluorescence labeled antibody by coupling derivatized phycoerythrin PE-SMCC with a specific thioether bond of a sulfhydrylated antibody. The mixed protein standard substance adopts a freeze-drying protection system containing BSA, trehalose and the like. The single hole of the kit can synchronously detect multiple cell factors, the sample dosage is only 25 microliters, the kit is suitable for in-vitro tests of mouse mononuclear macrophage leukemia cell lines RAW264.7, compared with a traditional ELISA method, the efficiency is improved by 10 times, the cost is reduced, and the kit has the remarkable advantages of being high in throughput, wide in linear range and high in stability.

The invention relates to the technical field of medicines, in particular to application of a mesenchymal stem cell exosome in preparation of a thermoplegia neuroprotective agent. It is found through experiments that MSC-Exos can remarkably promote polarization conversion of microglial cells from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, and therefore damage, caused by heat stroke, to a central nervous system is relieved.

The invention relates to the technical field of medical chemistry and tumor treatment, in particular to application of a novel NOX4 inhibitor ZZU026 and derivatives thereof in tumor resistance and immune response change. The preparation method of the ZZU026 comprises the following steps: replacing N, N-dimethylamino on a benzene ring of GKT137831 with morpholinyl; methoxyl is introduced into the core skeleton. The ZZU026 has a remarkable inhibiting effect on NOX4, has the functions of inhibiting tumor growth, new vascularization and immune-related diseases, regulating and controlling polarization of macrophages and the like, and can inhibit phenotype transformation of macrophages from M1 to M2 and finally inhibit proliferation and immune escape of lung cancer cells; the ZZU026 and the derivatives thereof can be prepared into drugs, health care products, tablets, particles, capsules, oral liquid or injection, and can be used for treating lung cancer and other tumors.

The invention discloses an immunomodulatory composition based on a cordycepin-selenium nano chelate and a preparation method thereof, and belongs to the technical field of biological medicines.The immunomodulatory composition is characterized in that 15-25 nm zero-valent selenium nano particles are chelated through hydroxyl of cordycepin and N7 site bidentate coordination, and a stable five-membered ring structure with the molar ratio is formed; the preparation method comprises the following steps: reducing sodium selenite in an inert atmosphere to generate selenium colloid, chelating the selenium colloid with a cordycepin ethanol solution, and carrying out ultrafiltration and freeze-drying to obtain the product. The invention aims to solve the problems of fuzzy structure, inconsistent batch, uncontrollable immunomodulatory function and the like caused by non-specific mixing in the prior art, and the composition can bidirectionally regulate and control IRF3 pathways, promote polarization of M2 type macrophages and proliferation of Treg cells, and has a clear immunomodulatory mechanism and excellent stability.

The application discloses a kind of nanoparticles for tumor sonodynamic combined individualized immunotherapy and its preparation method and application, belong to the field of biological medicine.The nanoparticles for tumor sonodynamic combined individualized immunotherapy are double-shell core structure nanoparticles formed by inner core and shell, and the inner core is formed by self-assembly of TLR3 agonist Poly (I:C), L-arginine and polylysine, and the shell is hyaluronic acid layer HA-Ce6 conjugated with photosensitizer Ce6.It is found through experiment verification that the nanoparticles can target tumor, generate reactive oxygen species to kill tumor cells under the action of ultrasound, promote M1 macrophage polarization and produce NO release at the same time, play the role of antitumor and immune effect, and realize the combined application of sonodynamic and NO gas therapy.The nanoparticles for tumor sonodynamic combined individualized immunotherapy can trigger systemic immune response, inhibit primary tumor, produce immune memory effect, and prevent tumor metastasis and recurrence.

The invention relates to the technical field of biology, in particular to a preparation method and application of a bionic nano regulator. The invention provides a bionic nano regulator. The nano regulator comprises a therapeutic drug; the therapeutic drug is prepared from Ce6 and SB525334. And extruding the bacterial outer membrane vesicles and the PLGA encapsulating the Ce6 and SB525334 medicines to obtain the bionic nano regulator. Under photodynamic therapy, the bionic nano regulator can be recognized, taken and delivered to tumor tissues by neutrophils. The bionic nano regulator can regulate and control polarization of neutrophil to an anti-tumor N1 type, promote the neutrophil to release neutrophil elastase, specifically kill tumor cells and reverse a tumor immunosuppression microenvironment. Under the combined treatment of photodynamic-immunotherapy, the biomimetic nano regulator obviously inhibits tumor growth and enhances the anti-tumor immune response of the body.

The present invention relates to a method of producing macrophages. The macrophages are produced from monocytes harvested from a subject by incubating said monocytes in a medium comprising a Colony Stimulating Factor 1 Receptor (CSF-1R) agonist. Before monocytes are harvested, the subject is treated with G-CSF. The macrophages produced by the method are capable of being polarised to a pro-restorative, anti-inflammatory and / or anti-fibrotic phenotype. The invention also relates to methods of treating inflammatory diseases comprising administering the macrophages produced by the method to a subject.

The present invention discloses a tumor immune microenvironment-regulated light-activated ferroptosis nanoparticle, a preparation method, and an application thereof, relating to the field of biomedicine technology. The preparation method comprises the following steps: dissolving albumin and ferritin in water, adjusting the pH to alkaline, adding a photosensitizer and lipoic acid, mixing, then adding a solvent, performing a mixing reaction, then adding a cross-linking agent, continuing the reaction, and then centrifuging and drying to obtain the tumor immune microenvironment-regulated light-activated ferroptosis nanoparticle. The tumor immune microenvironment-regulated light-activated ferroptosis nanoparticle reverses the tumor immunosuppressive microenvironment by inducing ferroptosis of tumor cells, activating dendritic cells, and regulating the M1 polarization of M2 tumor-associated macrophages, thereby enhancing the effect of tumor immunotherapy.

The invention belongs to the field of biological medicine, and particularly relates to application of soluble B7-H5 in preparation of a Crohn disease detection reagent. According to the invention, the level of soluble B7-H5 (sB7-H5) in serum of a patient suffering from Crohn's disease (CD) is deeply analyzed by using an ELISA (Enzyme-Linked Immunosorbent Assay) technology. Studies find that sB7-H5 in serum of a CD patient is remarkably and highly expressed and is positively correlated with a disease activity index (CDAI). Further experimental verification shows that blocking of B7-H5 can promote polarization of inflammatory macrophages. Based on the discoveries, the invention provides the application of the serum B7-H5 as the molecular marker of the Crohn's disease to development of products for detection, prognosis or treatment of the Crohn's disease. The molecular marker can be in a soluble B7-H5 gene or protein form. The invention also shows that the B7-H5 can be used as a potential target for developing the medicine for preventing and treating the Crohn disease, and has important clinical application value.

The invention relates to the technical field of biological medicines, and particularly relates to a method for researching the influence of silencing or inhibiting a UBE2G1 gene on the growth of abdominal aortic aneurysm by constructing a UBE2G1 gene function deletion mouse model. Results show that silence or inhibition of UBE2G1 gene expression can inhibit growth of abdominal aortic aneurysm, alleviate destruction of elastic fibers of arterial tissues, reduce levels of inflammatory factors such as TNF-alpha, IL-1beta and IL-6 in a body and inhibit polarization of macrophage M1. According to the invention, a certain theoretical basis is provided in the aspect of treatment of abdominal aortic aneurysm by means of biotechnology, and the UBE2G1 gene (or protein) can be used as a drug target for treatment of abdominal aortic aneurysm.

The invention discloses nanoparticles for tumor chemotherapy and immune combined treatment as well as a preparation method and application of the nanoparticles, and belongs to the technical field of biological medicines. The nanoparticles are rHF (at) Cel nanoparticles formed by wrapping tripterine (Cel) with recombinant human heavy chain ferritin (rHF). The preparation method comprises the following steps: obtaining recombinant rHF protein, mixing and assembling Cel and rHF under specific pH and temperature conditions, and purifying to obtain the recombinant rHF protein. The nanoparticles can effectively target tumor cells and release Cel to kill tumors; meanwhile, the rHF carrier can induce polarization of tumor-related macrophages from a tumor-promoting M2 type to an anti-tumor M1 type, reduce the proportion of regulatory T cells (Treg) in a tumor microenvironment and reverse an immunosuppression microenvironment. In-vitro and in-vivo experiments prove that the rHF (at) Cel nanoparticles have a remarkable killing effect on breast cancer cells and can effectively inhibit the growth of transplanted tumors of mice.

The application discloses application of COPG1 protein in preparation of a drug for promoting M2 polarization of macrophages, and belongs to the technical field of biological medicines.The application firstly proposes that COPG1 can promote M2 polarization of macrophages, and that COPG1 in tumor-derived exosomes can inhibit the M2 polarization of macrophages.The strategy of regulating the COPG1 content in macrophages and exosomes and inhibiting the M2 polarization of macrophages to regulate the immune function of macrophages proposed by the application provides a theoretical and practical basis for developing an immune regulator by targeting COPG1.

According to the immune checkpoint molecule and the pharmaceutical application thereof, a kit for detecting ILDR2 comprises an antibody specifically combined with ILDR2 protein or a primer pair for detecting ILDR2 mRNA, and the kit is used for detecting the expression level of ILDR2 in a liver cancer tissue sample in vitro. The invention discloses application of detection of B7 family protein ILDR2 expression quantity in liver cancer diagnosis and treatment. It is found for the first time that ILDR2 is highly expressed in liver cancer, and the highly expressed ILDR2 is poorly related to prognosis of patients. Liver cancer cells express ILDR2 to inhibit the anti-tumor function of CD4 + T cells, promote formation of regulatory T cells and inhibit polarization of the CD4 + T cells to Th1. The ILDR2 is knocked down, so that liver cancer cell proliferation can be obviously inhibited. Detection of ILDR2 expression can better guide treatment of liver cancer patients with high ILDR2 expression, and targeted ILDR2 can screen candidate immune checkpoint drugs for treating liver cancer.

The inventors have prepared a novel anti-Cath-D antibody (F1M1) that can reduce tumor growth in a Cath-D secreting basal-like TNBC cell line with strong immune infiltration, without significant toxicity. The F1M1 antibody prevents recruitment of immunosuppressive M2 polarized tumor-associated macrophages (TAMs) and induces activation of natural killer cells in the tumor, and the F1M1 also enhances activation of antitumor M1 polarized TAM, recruitment and maturation of conventional cDC1 dendritic cells in the tumor to promote antigen presentation and reduce depletion marker expression of CD4 + and CD8 + T cells in the tumor and drainage lymph nodes. It is worthy of noting that the affinity of the antibody F1M1 to Cath-D is better than that of the antibody F1 prepared by the inventor in advance. The inventors also have prepared a novel Fc-optimized F1M1-Fc + human antibody which can promote ADCC induction of cancer cells and CAF, improve anti-tumor efficacy, and trigger recruitment, activation and cytotoxic activity of NK cells in tumors. The F1M1-Fc + F1M1-Fc + can inhibit the growth of MDA-MB-231 and SUM159 TNBC cell xenografts and two TNBC-PDX (one of the TNBC-PDX is resistant to neoadjuvant chemotherapy), and has no obvious toxicity. In addition, the F1M1-Fc < + > improves the treatment effect of the paclitaxel and enzalutamide combined medicine. Thus, the present invention relates to anti-cathepsin-D antibodies and their use in the treatment of cancer, in particular triple negative breast cancer.

Provided herein are methods for generating extracellular vesicles (EVs) from massively cultured polarized DCs, as well as additional operations of separating CTLA-4 + EV and CTLA-4-EV from each other and recovering the two EV populations in a physically and functionally intact state; also provided is a composition comprising the EV obtained by the method. In addition, the use of CTLA-4-EV in the treatment of cancer, as well as the use of CTLA-4 + EV in the treatment of GVHD and other T cell mediated autoimmune conditions, is also provided.

The invention discloses an engineered exosome of LTH peptide modified miR-146a-5p and application, the core component of the medicine is the engineered exosome, and the engineered exosome is constructed by the following method: miR-146a-5p mimic infected human renal tubular epithelium HK2 cells with nucleotide sequences shown as SEQ ID NO.1-SEQ ID NO.2 are cultured and screened, the exosome rich in miR-146a-5p is separated from the culture supernatant of the cells, and the exosome rich in miR-146a-5p is obtained. Then, the kidney targeting peptide LTH is modified on the surface of the exosome. The invention reveals that HNRNP M protein is a key molecule for regulating and controlling miR-146a-5p to be sorted and enter the exosome for the first time, and verifies that the engineered exosome can be efficiently enriched in kidney, and by delivering miR-146a-5p to target IRAK1 gene in macrophage and inhibiting TRAF6 / IKK / NF-kappa B inflammation signal pathway, the macrophage is promoted to be polarized to a repairable M2 phenotype, so as to realize the purpose of improving the activity of the miR-146a-5p. And finally, the kidney injury induced by the calcium oxalate crystal is effectively relieved. The medicine has the advantages of clear mechanism, strong targeting property, good biocompatibility and the like, provides a brand new immunoregulation treatment strategy for renal injury, and has a wide clinical application prospect.

The present invention relates to a use of a substance comprising point-mutated FoxM1 protein and peptide for inhibiting growth, migration and invasion of cancer cells. In addition, it relates to a use of a substance comprising point-mutated FoxM1 protein and peptide for inhibiting malignancy in a tumor microenvironment by inhibiting polarization into tumor-associated macrophages in a tumor microenvironment. It relates to a use as an apoptotic inducer using the action of sensitively inhibiting cancer cell death in metastatic cancer cells as well as general solid cancers.

The invention belongs to the field of biological medicine, and particularly relates to a medicine for promoting microglial cell M2 type polarization and application of the medicine. The drug provided by the invention contains Densiflorol B. The drug provided by the invention has the advantages that the drug effect is good; the medicine can promote M2 type polarization of microglial cells, and has protection and repair effects on damaged nerves.

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 discloses a kind of detection Tgfβ1 to hepatolenticular degeneration neutrophil polarization method and application, including the following steps: step 1, by immunohistochemistry and immunofluorescence co-localization determine hepatolenticular degeneration mouse liver fibrosis formation process, hepatocyte high expression Tgfβ1;Step 2, by inhibiting the high expression of Tgfβ1 of hepatolenticular degeneration mouse liver fibrosis formation process, determine the mitigation of neutrophil polarization;Step 3, collect mouse bone marrow neutrophil, by real-time fluorescence quantitative PCR, protein electrophoresis and methylation reaction determine the mechanism of Tgfβ1 promote neutrophil polarization.The application can detect the effect of Tgfβ1 in hepatolenticular degeneration neutrophil polarization, facilitate to determine hepatolenticular degeneration liver lesion mechanism.

The invention discloses an application of a POSTN + fibroblast subgroup in screening and preparing a medicine for improving immune checkpoint blocking treatment drug resistance of a patient with head and neck squamous cell carcinoma. The action mechanism of small extracellular vesicles secreted by POSTN < + > fibroblasts in head and neck squamous cell carcinoma is studied, two fibroblast subtypes of POSTN <-> and POSTN < + > are identified through single-cell RNA sequencing, and the POSTN < + > subtype highly expresses FAP and other markers and is related to immune checkpoint blocking treatment drug resistance. Research finds that POSTN is enriched on the surface of sEVs secreted by POSTN + fibroblasts, and macrophages can be driven to be polarized to an M2 type by activating a BMP4 / BMPR2 / Smad signal channel. High expression of POSTN and FAP indicates that ICB treatment response of a patient is poor, and POSTN and FAP can be used as predictive biomarkers. The pathway can be blocked by down-regulating the POSTN, the ICB curative effect is improved, and a new target and a new strategy are provided for treatment of head and neck squamous cell carcinoma.

The invention relates to the technical field of biological medicine, and particularly discloses a chimeric antigen receptor of a targeted NKG2D ligand, a nucleic acid molecule, an expression vector, a macrophage and a preparation method and application of the chimeric antigen receptor, the nucleic acid molecule, the expression vector and the macrophage, and an extracellular antigen binding domain is an NKG2D extracellular structural domain; the hinge region is a CD28 hinge region or a CD8a hinge region; the transmembrane / intracellular signal transduction structural domain is an FCGR1 transmembrane / intracellular signal transduction structural domain or a CD3z transmembrane / intracellular signal transduction structural domain. The chimeric antigen receptor provided by the invention specifically recognizes and is combined with NKG2DLs highly expressed in NKG2DL positive malignant tumors, and macrophages expressing the chimeric antigen receptor can directly swallow tumor cells, promote M1 type polarization, reprogram tumor microenvironment and induce recruitment and activation of T cells, so that effective treatment of the malignant tumors is realized.

The invention relates to the technical field of novel drug application of compounds, in particular to a compound Man-Tz, a biological orthogonal reaction system and application of the compound Man-Tz. The dTRIM24 is accurately released at the atherosclerotic plaque through a biological orthogonal targeting technology, and the problem of non-specific distribution caused by a traditional administration mode is effectively solved by utilizing the specific reaction of an artificial target point Man-Tz and TCO-dTRIM24-TCO. According to the technology, the TRIM24 protein of 117kDa can be specifically degraded, and macrophages are promoted to be polarized to an anti-inflammatory M2 type by inhibiting Stat6 acetylation, so that plaque formation is inhibited. Experiments prove that the system has concentration and time-dependent effects, drug exposure of non-target tissues is remarkably reduced while efficient degradation activity is maintained, and a novel targeted therapy strategy with high specificity and low toxic and side effects is provided for atherosclerosis treatment.

The application provides a method and system for simulating a microtubule self-organizing process in interphase cell polarization, and belongs to the fields of computational biology and physical technology; the method comprises the following steps: abstracting a cell as a two-dimensional circular domain, abstracting a microtubule as a line segment with a fixed direction starting from a point-like centrosome in the circular domain, abstracting a polar factor space distribution as a concentration field in the circular domain, and performing a time-dependent evolution process simulation by coupling centrosome positioning, microtubule length evolution and polar factor space distribution dynamics. The application can comprehensively investigate the feedback regulation mechanism of the microtubule self-organizing process in interphase cell polarization.