116 results about "Th polarization" patented technology

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 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 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.

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 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 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 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.

The invention discloses a method for regulating polarization of microglial cells through a Chuk / NF-kB pathway in electroshock treatment, and relates to the field of biomedicine. According to the method, by simulating an anti-inflammatory mechanism of electroshock treatment, expression of a Chuk gene in the microglial cells is knocked down by adopting specific siRNA, so that activation of an NF-kB signal channel is inhibited, conversion of the microglial cells from an M1 type pro-inflammatory polarization state to an M2 type anti-inflammatory polarization state is regulated, and the method specifically comprises the following steps: culturing and grouping the microglial cells; carrying out siRNA transfection; lPS-induced inflammation; detecting indexes; according to the invention, after an electroshock treatment mechanism is simulated and the Chuk gene is knocked down, LPS-induced NF-kB pathway activation is significantly inhibited, the expression of proinflammatory factors is reduced, and the level of anti-inflammatory factors is improved at the same time.

The invention discloses a combined application of a PARP7 inhibitor or a pharmaceutically acceptable salt thereof and temozolomide, which is characterized in that the PARP7 inhibitor is used for recovering an I-type interferon signal channel and promoting T cell-mediated immune response and polarization of TAMs to M1 type, so that the side effect of temozolomide is reduced, the sensitivity of temozolomide is enhanced, and an excellent synergistic anti-tumor effect is achieved; the traditional Chinese medicine composition especially has a remarkable curative effect on brain glioma with high malignant degree, and is safe and effective.

The invention belongs to the technical field of biological medicine and molecular biology, and particularly relates to a Cu-SAs / C2N nano-enzyme material as well as a preparation method and application thereof. Specifically, a dispersed Cu monatomic catalyst (Cu-SAs / C2N) with a Cu-N2 coordination structure is prepared on a C2N substrate by adopting a two-step pyrolysis process. The unsaturated Cu-N2 loci not only have efficient OXD sample and POD sample characteristics, but also can enhance the affinity to O2 and H2O2 in tumors, so that efficient chemical dynamic therapy (CDT) is realized. Further research shows that the Cu-SAs / C2N nano-enzyme promotes apoptosis of tumor cells, enhances polarization of macrophage M1, further promotes infiltration of NK cells and T cells, and effectively inhibits depletion of the NK cells and the T cells, so that anti-tumor immune response is enhanced. Meanwhile, the combined use of the nano-enzyme and PD-1 immunotherapy synergistically enhances the anti-tumor effect of PD-1, and a new effective scheme is provided for tumor immunotherapy, so that the nano-enzyme has good practical application value.

The present disclosure provides complexes and compositions comprising particles, microparticles or nanoparticles, for delivery of payloads into a cell or across a polarized epithelial cell. The compositions can comprise a payload in a pill or tablet for delivery of the payload into or across a polarized epithelial cell.

This invention relates to the field of biomedical technology, specifically disclosing a biomimetic exosome derived from tumor cell membranes, its preparation method, and its applications. The preparation method of the biomimetic exosomes derived from tumor cell membranes provided by this invention includes the following steps: mixing LLC-derived cell membranes with doxorubicin and resveratrol solutions, and preparing biomimetic exosomes derived from tumor cell membranes by extrusion. The preparation method provided by this invention has advantages such as wide availability of raw materials, simple and controllable process, low technical threshold, and suitability for industrial-scale production. The biomimetic exosomes provided by this invention can effectively induce a specific immune response against tumor cells, achieving the purpose of inhibiting the progression of primary tumors and prolonging the survival of tumor-bearing mice. It can also promote the polarization of macrophages from a pro-tumor M2 phenotype to an anti-tumor M1 phenotype, laying a favorable foundation for the efficient implementation of subsequent immunotherapy and possessing broad application prospects.

This application discloses the application of PLAC8 as a target in the preparation of tumor therapeutic drugs, involving the field of biomedical technology. This application clarifies that the "sympathetic nervous system-β2-AR-PLAC8-cholesterol metabolism-M2 polarization" pathway is the core driving pathway for stress-related tumor progression and chemotherapy resistance. It reveals the molecular mechanism by which PLAC8 inhibits cholesterol synthesis through phosphorylation at the S67 site, binding to the N-terminal domain of SREBP2, recruiting OGT to mediate SREBP2O-GlcNAc glycosylation. Through strategies such as gene silencing, β2-AR antagonist intervention, and targeted delivery of siPLAC8 via mannose-modified lipid nanoparticles (LNPs), the application achieved the effects of inhibiting M2 macrophage accumulation, inhibiting tumor growth, and reversing chemotherapy resistance in various tumor models, including gallbladder cancer, intrahepatic cholangiocarcinoma, and prostate cancer. Furthermore, the LNPs delivery system showed no significant toxicity. This research provides a novel therapeutic target centered on PLAC8 and a safe and effective targeted intervention strategy for stress-related tumors, highlighting its clinical translational value.

The invention relates to a contrast agent for nuclear spin imaging, comprising a polarizable agent (tracer) having a nuclear spin, tracer molecules being polarizable by polarizing the nuclear spins thereof, and comprising a retarding agent (retarder), a molecular interaction of retarder molecules with tracer molecules resulting in an extension of the T1 relaxation time of the tracer. The invention further relates to a method for producing a hyperpolarized contrast agent, to a retarder for use in a contrast agent for nuclear spin imaging, to a contrast agent for use in an in vivo and / or in vitro diagnostic method, and to the use of a retarder in a contrast agent for nuclear spin imaging in order to extend the T1 relaxation time of the tracer.

The application provides a bicyclic compound with a structure shown in formula (I) or a pharmaceutically acceptable salt, a stereoisomer or a prodrug molecule thereof, a pharmaceutical composition and application. The compound provided by the application can activate CD137, enhance the immune function of cytotoxic T lymphocytes (CTL), enhance the memory function of CD8+ T cells and CD4+ T cells, can make the polarization of CD4+ T cells tilt to a state beneficial to cellular immunity, and can promote the multimerization of CD137, so that T cell immunity can be effectively activated, the volume of a primary tumor can be effectively reduced, and the compound can be used for inhibiting and treating tumors.

The invention relates to the technical field of biological medicine, and particularly discloses a lipidosome targeting SELENOP + macrophages, a preparation method of the lipidosome and application of the lipidosome in lung squamous cell carcinoma treatment. According to the lipidosome, an SELENOP antibody is used as a targeted modification molecule, si-SELENOP and s-ABCA1 / G1 are loaded, and accurate delivery of siRNA in target cells is achieved through specific binding of the antibody and a SELENOP receptor on the surface of a SELENOP + macrophage. The targeting liposome prepared by the invention can specifically inhibit cholesterol efflux pathways of SELENOP + macrophages, reverse tumor phenotypic polarization, remodel a tumor immune microenvironment and recover anti-tumor activity of immune cells such as CD8 + T cells, NK cells and the like. When the liposome is independently used or combined with a PD-1 antibody, the growth and metastasis of the lung squamous cell carcinoma can be remarkably inhibited, the treatment effect is improved, a brand new metabolism-immunity synergistic targeted treatment strategy is provided for the lung squamous cell carcinoma, and the liposome has a good clinical application prospect.

Provided are a novel fluorescent protein, a composition for identifying polarization of macrophages, and a method for identifying polarization of macrophages.　A fluorescent protein is chemically modified with a sugar that binds to a C-type lectin receptor, the fluorescent protein being characterized in that: the sugar that binds to the C-type lectin receptor can bind to C-type lectin receptors expressed in macrophages; and in the fluorescent protein chemically modified with the sugar, the fluorescent protein and the sugar that binds to the C-type lectin receptor are bound directly or via a linker.

A method for treating a disease or disorder includes administering to a subject an effective amount of an agent that promotes the polarization of macrophages. The macrophages selectively repolarize their phenotype in the microenvironment. The agent can be PKM2 or mutant thereof. Further, wherein administration of the agent reduces inflammation in the subject.

The invention relates to an application of a reagent for detecting SRC expression in preparation of a product for diagnosing and treating lupus nephritis, SRC is highly expressed in a patient with lupus nephritis, when the expression level of SRC is reduced, ferroptosis of podocyte is remarkably relieved, ferroptosis related markers are remarkably reversed, the levels of Fe < 2 + > and MDA are reduced, the level of GSH is increased, and compared with a control group, the SRC expression level is remarkably reduced. The viability of podocyte is increased; the invention relates to application of a reagent for detecting CYBB expression in preparation of a product for diagnosing and treating lupus nephritis, CYBB is highly expressed in a patient suffering from lupus nephritis, when the expression level of CYBB is reduced, ferroptosis in podocytes is remarkably relieved, ferroptosis related markers are remarkably reversed, the levels of ACSL4, Fe < 2 + >, ROS and MDA are reduced, and the levels of GPX4 and GSH are increased, so that the effect of treating lupus nephritis is achieved. The polarization of M2 macrophages is promoted, the ferroptosis phenomenon is further relieved through the polarization of the macrophages, and the viability of podocytes is improved.

The invention discloses an ATM gene knockout THP-1 cell line as well as a construction method and application thereof, and belongs to the technical field of biology. The gRNA for targeted knockout of the ATM gene is provided, the ATM gene of the THP-1 cell line is knocked out in combination with a CRISPR / Cas9 gene editing technology, and the THP-1 cell line with the knocked-out ATM gene is successfully obtained. The cell line stably lacks an ATM gene, can be normally differentiated into macrophages, and can be further polarized into M1 and M2 macrophages. The THP-1 cell line with the ATM gene knocked out, which is constructed by the invention, can be widely applied to research on in-vitro and macrophage physiological and biochemical functions of the ATM gene and immune response drug targets.

The present application relates to the technical field of biological medicine, in particular to a new application of a BTK PROTAC compound NX-5948, especially to a new application of a Bruton's tyrosine kinase protein degradation targeting chimera BTK PROTAC compound NX-5948 in a drug for treating secondary hemophagocytic syndrome (HLH). In the present application, the BTK PROTAC compound NX-5948 inhibits the activation of the macrophage BTK / NF-κB axis signaling pathway through targeting, on the one hand, reduces the number of activated macrophages by inhibiting the proliferation and survival of macrophages, on the other hand, induces the polarization of macrophages from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages through the immunoregulatory effect on macrophages, and then inhibits the release of cytokines and the occurrence and development of HLH, so that the effect of the new application of the present application is that it can inhibit the abnormal activation of macrophages and improve the clinical symptoms or laboratory indexes existing in patients with secondary hemophagocytic syndrome.

The invention relates to the technical field of biology, and particularly discloses application of macrophages in improving immunotherapy stomach cancer. The synergistic effect of CLEC2D + macrophages and a CD161 receptor in gastric cancer immune escape is focused for the first time, the single attention on macrophage M1 / M2 polarization and T cell checkpoint molecules in traditional research is broken through, a new T cell depletion mechanism driven by direct interaction of myeloid cells and lymphocytes is disclosed, and supplement is provided for the tumor immune escape theory; a novel blocking agent (such as a CD161 targeting antibody and a small molecule inhibitor) is developed on the basis of a mechanism of activating and mediating T cell depletion by a CD161 receptor, a basic mechanism research is directly converted into an innovative treatment scheme, and a differentiated strategy is provided for gastric cancer immunotherapy in combination with an existing PD-1 / PD-L1 inhibitor.