31 results about "Macrophage infiltration" patented technology

The invention relates to the technical field of medicine, in particular to application of an Acp5 inhibitor in cerebral edema after traumatic brain trauma, and the Acp5 inhibitor comprises a medicine with the ACP5 inhibitor as an active component and a prodrug form of the medicine. According to the invention, through an enzyme-substrate key activation mechanism, a drug is coupled by using an ACP5 specific substrate peptide, dual response release is realized in a lesion area, and the targeting property and the safety are remarkably improved. The prodrug is composed of a core inhibitor module, an ACP5 substrate peptide module and a pH response connection module, and can accurately inhibit ACP5 + macrophage infiltration and reduce encephaledema volume and neuroinflammation. The application can effectively treat acute and chronic encephaledema, reduce off-target effect and side effect, and provide a brand new treatment strategy for traumatic brain trauma.

The application belongs to the technical field of biological medicine, and relates to application of a CXCL14 inhibitor in preparation of a drug for preventing or treating abdominal aortic aneurysm of a patient. The inhibitor effectively eliminates the gender difference of abdominal aortic aneurysm by specifically blocking the combination of CXCL14 and its receptor CXCR4, significantly reduces aortic macrophage infiltration and PDGFRA + macrophage accumulation in the progress of abdominal aortic aneurysm, reduces the degree of collagen degradation and elastic fiber damage, and thus inhibits the pathological progress of abdominal aortic aneurysm. The application provides a new target and drug combination for precise treatment of male abdominal aortic aneurysm, and has clear clinical application value.

The invention discloses gamma-aminobutyric acid and application of a pharmaceutical composition thereof in preparation of drugs for preventing or treating aortic dissection and aortic aneurysm. The invention provides the application of gamma-aminobutyric acid in preparation of drugs for preventing or treating aortic dissection for the first time, and verifies the application of gamma-aminobutyric acid in preparation of drugs for preventing and / or treating aortic dissection and aortic aneurysm by inhibiting endothelial cell dysfunction; the application of gamma-aminobutyric acid in preparation of drugs for preventing and / or treating aortic dissection and aortic aneurysm by inhibiting expression of c-FOS to reduce vascular endothelial cell injury is verified; the application of gamma-aminobutyric acid in preparation of drugs for preventing and / or treating aortic dissection and aortic aneurysm by reducing infiltration of macrophages is verified.

This invention belongs to the field of biomedical technology and relates to the application of OSM inhibitors in the preparation of drugs for the prevention or treatment of calcific aortic valve disease. This invention reveals for the first time that OSM drives osteogenic differentiation and calcified nodule formation of valvular interstitial cells through the OSM-OSMR-JAK2 / JAK3-STAT3-RUNX2 signaling axis, which is the core pathogenic mechanism leading to calcific aortic valve disease. This invention utilizes anti-OSM neutralizing antibodies or sulforaphane to effectively block this signaling axis, significantly inhibiting macrophage infiltration, valvular calcification, and improving hemodynamic abnormalities. This invention provides a precise target and a novel strategy for the modification therapy of calcific aortic valve disease, solving the technical problem of the ineffectiveness of traditional broad-spectrum anti-inflammatory therapy in valvular calcification.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an SIRT5 inhibitor MC3482 in preparation of a medicine for treating premature ovarian failure. According to the invention, a mouse POI model is constructed through the induction of cyclophosphamide (CTX), and the MC3482 is proved to be capable of inhibiting the activity of SIRT5, reducing excessive macrophage infiltration of ovary caused by CTX, reducing M1 type macrophage activation and proinflammatory factor release, further inhibiting the apoptosis of ovarian granular cells, protecting follicular reserve and recovering ovarian functions. The invention clarifies the action effect and application scheme of MC3482 for preventing and treating POI, provides a new treatment strategy for chemotherapy-induced iatrogenic POI, and has important clinical transformation value.

This invention discloses a reactive oxygen species (ROS)-responsive nanocomposite for targeting and repairing damaged endothelium, its preparation, and its application, belonging to the field of nanomedicine technology. The nanocomposite comprises a physalicylate-copper nanoparticle core and a P-selectin-targeting polypeptide linked to the core surface via thiol-copper affinity. The physalicylate-copper nanoparticle core is prepared by coordination of physalicylate and copper ions to form a primary complex, followed by ascorbic acid reduction. This composite nanosystem can specifically recognize and accumulate in the blood vessels and peritubular regions of the kidney injury area, releasing Cu in response to high concentrations of ROS in an inflammatory environment. 2+ Together with HBT, it simultaneously achieves antioxidant and anti-inflammatory functions, promotes angiogenesis and repair, and inhibits the release of inflammatory factors and macrophage infiltration and activation, effectively blocking the fibrosis process. This system has a well-defined structure and strong targeting, and can effectively rebuild microvessels, reduce inflammation, and block the process of renal fibrosis, providing a highly efficient and precise new nanomedicine strategy for the anti-fibrotic treatment of kidney diseases.

The invention provides sinomenine in preparation of a medicine for treating chronic pain of rheumatoid arthritis and application of the sinomenine in preparation of the medicine for treating the chronic pain of the rheumatoid arthritis, and aims at solving the problems that an existing medicine for resisting the rheumatoid arthritis is limited in action target spot and poor in treatment effect. The sinomenine takes a histamine receptor H1R on a nervous system dorsal root ganglion M1 type macrophage as the action target spot; the target spot is intervened to regulate and control polarization of macrophages, reduce expression of histamine H1R in M1 type macrophages and inhibit infiltration of the macrophages, so that chronic pain, including crymodynia, mechanical pain, heat pain and the like, of rheumatoid arthritis is effectively relieved; the sinomenine combined action target can improve pain and arthritis symptoms of a model mouse, reduce the level of inflammatory factors and inhibit LPS-induced macrophage migration and H1R expression, and the sinomenine pharmaceutical composition has various dosage forms, has unique action target and mechanism, has a remarkable treatment effect, and can be used for preparing medicines for treating chronic infectious diseases. The compound is expected to become a novel non-opioid anti-rheumatoid arthritis chronic pain medicine.

This invention discloses a method for preparing filler particles for targeted adsorption of low-density lipoprotein (LDL) in patients with atherosclerosis. The steps include: 1) washing D101 macroporous resin with ultrapure water and physiological saline; 2) adding fibrin and PBS solution for soaking; adding thrombin factor II; adding zinc gluconate during the reaction; 3) repeating step 2) at least three times and drying the D101 macroporous resin; 4) adding physiological saline and D101 macroporous resin to lyophilized protein ApoB100 and mixing thoroughly; 5) lyophilizing the resin obtained in step 4) while controlling the humidity at 65±5% to obtain the finished product. This application utilizes this adhesion effect to target the adsorption of foam cells in atherosclerosis, adsorbing foam cells through hemoperfusion, removing redundant blood lipid components in the body, reducing macrophage infiltration of organs and blood vessels, and reducing pathological changes in organs and blood vessels.

The invention discloses application of 9 '''-salvianolic acid B monomethyl ester in preparation of a medicine for preventing and / or treating atrial fibrillation, and belongs to the technical field of biological medicine. Experiments prove that the 9 ''-MSB disclosed by the invention can be used for remarkably improving the blood pressure rise and the atrial inner diameter increase of a mouse after Ang II perfusion; the increase of the occurrence rate and the duration time of atrial fibrillation is inhibited; macrophage infiltration, collagen deposition and oxidative stress injury of atrial tissues are reduced, and the protective effect of 9 ''-MSB is obviously superior to that of SalB. Therefore, the 9 ''-MSB can be used for preparing the medicine for preventing and / or treating the atrial fibrillation, and the invention proves that the 9''-MSB can be used as a new medicine for adjuvant treatment of the atrial fibrillation and has important clinical guiding significance.

The invention discloses application of nintedanib in preparation of a medicine for treating plant migration and plant mineralization, and belongs to the technical field of biological medicine. The research shows that the nintedanib has the effects of reducing deposition of extracellular matrix of an allogeneic kidney transplantation model mouse, improving renal tubular atrophy, relieving mouse CD206 + macrophage infiltration and reducing rejection injury degree and immune infiltration degree of kidney grafts after being administered under the administration dosage without generating liver and kidney toxicity and intestinal side effects; the lesion process of mouse chronic transplanted kidney rejection is obviously slowed down, and the damage of excessively activated inflammatory cells to the transplanted kidney is reduced. The results show that nintedanib can delay the progress of chronic transplantation renal fibrosis.

The invention discloses application of alpha-ketoglutaric acid in preparation of a medicine for preventing and / or treating antibody-mediated rejection reaction, and belongs to the technical field of biological medicine. According to the application, an acute antibody-mediated rejection reaction model of mouse skin pre-sensitization combined with kidney transplantation is constructed, and alpha-KG is applied for intervention. Results show that the alpha-KG can significantly improve renal functions (serum creatinine and urea nitrogen are reduced), prolong survival time of the transplanted kidney, relieve histological injury of the transplanted kidney (Banff score is reduced), inhibit deposition of complement C3d, reduce the level of a specific antibody (DSA) of a peripheral blood donor, down-regulate expression of kidney local inflammatory factors (Tnf, Il-6, Il-1beta and Nos2), regulate immune cell infiltration in the transplanted kidney, and improve the survival rate of the transplanted kidney. Comprising the steps of reducing transplantation kidney mononuclear / macrophage infiltration, reducing the proportion of transplantation kidney pro-inflammatory macrophages and increasing the proportion of repair macrophages. The application provides a new drug choice for treating the acute antibody-mediated rejection of the transplanted kidney, and has an important clinical application prospect.

This invention discloses the application of the small molecule compound Z2114502286 in the preparation of drugs for the prevention and treatment of liver-related diseases. This invention reveals for the first time that Z2114502286 is a THBS2-specific small molecule inhibitor and verifies its feasibility in preventing and treating liver fibrosis by targeting and inhibiting the THBS2 protein. Through virtual screening and molecular docking, this compound can directly bind to the THBS2 protein. In vitro and in vivo studies show that this compound inhibits THBS2-mediated HSC activation in a concentration- and time-dependent manner, inhibits ECM deposition in a mouse model of liver fibrosis, downregulates the expression of fibrosis-related genes, and alleviates liver inflammation and macrophage infiltration. Simultaneously, the targeted efficacy was verified in a transgenic mouse model specifically expressing human THBS2, demonstrating significant clinical translational value. Furthermore, it exhibits bioavailability and safety at effective dosages, showing broad clinical application prospects.

This invention provides the use of a reagent overexpressing Parp7 in the preparation of drugs for treating septic cardiomyopathy, belonging to the field of biomedical technology. This invention involves constructing a recombinant adeno-associated virus vector AAV9-F4 / 80- that specifically overexpresses PARP7 on macrophages. Parp7 The drug was intravenously injected into mice, and a septic cardiomyopathy model was established using lipopolysaccharide induction. Experimental results showed that macrophage-specific overexpression of PARP7 significantly reduced serum levels of myocardial injury markers CK-MB and cTnT, improved cardiac function indicators such as ejection fraction and fractional shortening, alleviated myocardial tissue pathological damage, and inhibited macrophage infiltration and inflammatory factors. Ifn-beta , Tnf- α , Il‑6 and Il‑1β The expression of PARP7. This invention reveals the protective role of PARP7 in septic cardiomyopathy, providing a new target and strategy for the treatment of septic cardiomyopathy.

The invention discloses an application of TRAF7 in screening of anti-lung injury drugs. In an LPS-induced A549 cell acute lung injury model, TRAF7 gene knock-down significantly aggravates cell apoptosis and inflammatory response, which shows that inflammatory factor release is increased, and cell injury is aggravated; and TRAF7 overexpression can obviously inhibit the pathological change. The result shows that the TRAF7 has a protection effect on alveolar epithelial cells, the expression level of the TRAF7 is in negative correlation with the in-vitro lung injury degree, and it is proved that the TRAF7 has a negative regulation effect in acute lung injury. In a mouse ALI model, TRAF7 overexpression can significantly reduce the total number of cells, the total protein content and the wet / dry weight ratio of lung tissue in bronchoalveolar lavage fluid (BALF), relieve the pathological injury score of the lung and inhibit LY6Gneutrophil and CD68 macrophage infiltration. The TRAF7 can effectively relieve LPS-induced pulmonary edema, vascular permeability increase and tissue inflammation, and the anti-inflammatory and tissue protection functions of the TRAF7 in an in-vivo model are verified.

The invention belongs to the technical field of biomedicine, and particularly relates to CCL25 and application of the CCL25 combined with CD8 + T cells and M1 macrophages to evaluation of a liver cancer immune microenvironment and prediction of a liver cancer immunotherapy curative effect. Based on TCGA liver cancer tissue transcriptome data, liver cancer tissue slice multiple immunohistochemistry, liver cancer tissue MRS score calculation and ROC curve multiple verification, it is proved that the chemotactic factor CCL25 expression level can serve as a biomarker for evaluating the liver cancer immune microenvironment. Furthermore, by analyzing data of liver cancer patients receiving anti-PD-1 treatment, a combined prediction model containing the CCL25 expression level, the CD8 + T cell infiltration level and the M1 macrophage infiltration level is established, and the prediction effect of the combined prediction model is better than that of independent use of immune checkpoint indexes. The technical scheme of the invention provides a potential new method for predicting the curative effect of immunotherapy of clinical liver cancer patients, and has a certain clinical application prospect.

The invention provides development and application of a mouse model for simulating pneumonia mononuclear-derived macrophage recruitment, and belongs to the technical field of biological medicine. A mouse expressing human ACE2 in the lung is constructed through an adeno-associated virus (AAV) carrier, then 2-3 mg / kg of spike protein is atomized to the lung through aerosolization, the modeling time is 3 days, and the process of novel coronavirus infection diseases can be better simulated. By focusing the index that mononuclear macrophages are infiltrated into the lung in quantity, the phenotype that mononuclear macrophages recruitment from the lung in pneumonia is successfully simulated on a mouse. The method is low in operation difficulty and simple in steps. The method has a good application prospect in the development of drugs for regulating / targeting mononuclear macrophage recruitment.

The invention discloses an application of a glycosylated lysosomal membrane protein (GLMP) in preparation of a reagent for gastric cancer diagnosis, prognosis evaluation and treatment. Tissue microarray (TMA) immunohistochemical detection, cancer genome map (TCGA) data verification and clinical pathological characteristic and survival analysis prove that the GLMP is remarkably and highly expressed in GC tissues, and the high expression of the GLMP is related to the M stage and the TNM stage of a GC patient and can be used as an independent prognosis risk factor for predicting the adverse overall survival rate of the patient. Functional enrichment analysis shows that GLMP participates in immune related processes and extracellular matrix tissues, and is closely related to M2 type macrophage infiltration in an immunosuppressive tumor microenvironment. In-vitro experiments prove that the proliferation, migration and invasion ability of GC cells can be inhibited by knocking out the GLMP, and meanwhile, the polarization direction and chemotactic ability of macrophages are regulated and controlled. The molecular mechanism of the GLMP in GC is defined, a novel gastric cancer prognosis biomarker is provided, a novel target spot and strategy are provided for diagnosis, prognosis evaluation and targeted therapy of gastric cancer, and important clinical application value is achieved.

The present invention relates to a novel Lactobacillus plantarum IMB19 strain, polysaccharides derived from the strain and uses thereof. The novel Lactobacillus plantarum IMB19 strain and polysaccharides derived from the strain of the present invention exhibit superior CD8+ T cell activity stimulating capacity and Treg cell inhibitory activity and stimulate and improve anti-tumor immune responses through various mechanisms such as increasing macrophage infiltration in CPS tumors as well as macrophage differentiation and reprogramming into inflammatory phenotype (M1). Thus, the strain and polysaccharides derived from the strain of the present invention can be effectively used for immunomodulation, especially immune boosting, in a subject and can inhibit tumor growth by inducing and enhancing anti-tumor immune responses. The novel strain and polysaccharides derived from the strain of the present invention are useful for preventing, ameliorating or treating various immunological diseases such as tumors, infectious diseases and various immunological diseases caused by or as symptoms of immune dysfunction.

The present invention provides compositions and methods for treating cancer in a subject by administering to the subject an antibody or fragment thereof that binds to oxidized LDL. In some embodiments, the compositions and methods may reduce the size of the tumor, reduce macrophage infiltration, and / or inhibit metastasis.

The invention relates to hepatic fibrosis intervention, and provides a pharmaceutical composition for treating and / or preventing hepatic fibrosis related to TET2 function deficiency type myeloid cells and application of the pharmaceutical composition. The composition comprises: (a) an inhibitor or antagonist for inhibiting chemotactic signals mediated by CCL2 and / or CCL8 and CCR2 and / or CCR3; and (b) an IL-6 pathway inhibitor. Preferably, (a) is Bindarit or a pharmaceutically acceptable salt thereof, and (b) is an IL-6 neutralizing antibody or an IL-6 receptor antibody. According to the composition, by reducing mononuclear cell recruitment / proinflammatory mononuclear cell source macrophage infiltration and blocking IL-6 mediated hepatic stellate cell activation, collagen deposition is relieved, and fibrosis indexes such as alpha-SMA and Col1a1 are reduced. Animal experiments show that in a CCl4-induced myeloid Tet2 deletion mouse model and an old-age chimeric model, combined administration is superior to single administration.

This invention discloses the application of SB202190 in the preparation of drugs for treating immune checkpoint inhibitor-associated pneumonia (CIP), belonging to the field of pharmaceutical technology. It also discloses related screening methods, model construction methods, and synergistic anti-tumor applications. A CIP mouse model was constructed based on an LLC orthotopic lung cancer model using intraperitoneal injection of a PDL1 monoclonal antibody. Experiments confirmed that SB202190 can inhibit p38 MAPK activity, block abnormal activation of the NF-κB pathway, reduce T cell, neutrophil, and macrophage infiltration, decrease the release of inflammatory factors such as IFN-γ and IL17A, and alleviate pathological damage to lung tissue. When SB202190 is used in combination with anti-tumor drugs, its antitumor activity is not reduced; instead, it synergistically exerts an anti-tumor effect, making it suitable for the treatment of CIP in cancer patients who develop the disease after using immune checkpoint inhibitors. This invention provides a new technical approach and solution for the treatment of CIP.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a CCR1 targeting inhibitor in preparation of a medicine for treating lung cancer and bone metastasis cancer. It is verified for the first time that CCR1 + macrophage infiltration in bone metastasis microenvironments of mice and lung cancer patients is increased, lung cancer bone metastasis development can be inhibited by inhibiting CCR1 + macrophage infiltration, and a small molecule compound BX471 serves as a targeted CCR1 inhibitor and inhibits lung cancer bone metastasis by inhibiting CCR1 + macrophage infiltration and differentiation; a new target spot and a treatment strategy are provided for lung cancer bone metastasis.

The invention discloses an application of ingenol acetate or a derivative thereof and ingenol in preparation of a medicine for preventing or treating non-alcoholic steatohepatitis, and relates to the technical field of biological medicines. Experiments prove that the aromatic phenol acetate has the effect of improving non-alcoholic steatohepatitis (NASH), so that the aromatic phenol acetate can obviously relieve liver tissue damage and inhibit abnormal accumulation of lipid in the liver. The in-vivo anti-inflammatory effect is mainly realized by targeted inhibition of NLRP3 inflammasome signal axes (remarkably down-regulation of Nlrp3, Asc and Caspase-1 expression) and blocking of pannexin-1 inflammatory channels, so that release of downstream proinflammatory factors (TNF alpha, IL-1beta and IL-6) and macrophage infiltration are inhibited. The aromatic phenol acetate can be hydrolyzed and metabolized into deacetylated active product aromatic phenol through esterase in vivo, and the free hydroxyl structure of the aromatic phenol acetate can still retain the binding capacity with NLRP3 inflammasome targets as an active molecule directly acting on organs.

The application discloses application of a combination marker in survival time of tumor patients and treatment effect prediction of an immune checkpoint inhibitor, and proposes an ISG15 + macrophages and SPP1 + The macrophage infiltration level is used as the combination marker, the ratio of the two is used as a kit for the survival time of tumor patients and the treatment effect of the immune checkpoint inhibitor, the survival time of tumor objects and the treatment effect of the tumor immune checkpoint inhibitor can be effectively predicted, patients sensitive to the immune checkpoint inhibitor treatment can be effectively screened, the response rate of the tumor immune checkpoint inhibitor treatment is improved, and the combination marker has good clinical transformation and application prospect.

The invention discloses an application of agrimonolide in preparation of a medicine for treating cholestatic liver diseases. It is found for the first time that the agrimonolide promotes bile acid efflux by up-regulating expression and / or functions of bile acid efflux transporter, so that small bile duct hyperplasia is inhibited, hepatic fibrosis is reduced, macrophage infiltration is relieved, a unique liver protection effect is generated, and a new medication strategy is brought to treatment of cholestatic liver diseases.

The present application provides the application, method and drug related to the regulation of tumor or inflammatory disease related macrophage infiltration by CREPT. The present application also provides the application of the inhibition of CREPT positive tumor associated macrophage (TAM) in the preparation of the preparation for regulating the tumor microenvironment, and the application in the preparation of the drug for treating tumor or promoting the action of T lymphocyte. The inhibition of the CREPT positive tumor associated macrophage (TAM) can provide a technical means for controlling tumor proliferation, invasion and metastasis. The CREPT positive tumor associated macrophage (TAM) can also be used as a biomarker for the risk of an individual suffering from tumor, or a biomarker for the development stage of the tumor of an individual, to judge the risk of an individual suffering from tumor or the stage and progress of the tumor of a tumor patient.

The invention provides application of sodium acetoacetate and / or pharmaceutically acceptable salt thereof in preparation of drugs for preventing and treating tumor pulmonary metastasis and improving inflammatory microenvironment, and belongs to the technical field of biological medicine. The invention provides an application of sodium acetoacetate and / or pharmaceutically acceptable salts thereof in preparation of drugs for preventing and / or treating tumor pulmonary metastasis. The embodiment of the invention shows that sodium acetoacetate can effectively inhibit tumor lung metastasis, improve the tumor inflammatory microenvironment and reduce infiltration of tumor-related macrophages in the lung tumor microenvironment. The invention provides a feasible path for improving the inflammatory microenvironment and expanding the prevention and treatment of tumor pulmonary metastasis, and has important significance and application value for improving the clinical treatment level of advanced solid tumors.

The invention discloses application of CLK1 in sepsis, it is determined that an ALKBH5 / m6A / CLK1 signal axis and an ALKBH5 / m6A / CLK1 signal channel targeting macrophages can effectively enhance sepsis immune response, promote macrophage infiltration, reduce bacterial load in abdominal cavity lavage fluid and main organs of lung, spleen, liver and kidney and improve sepsis survival rate, and meanwhile, the ALKBH5 / m6A / CLK1 signal axis and the ALKBH5 / m6A / CLK1 signal channel targeting the macrophages can effectively enhance sepsis immune response, promote macrophage infiltration and improve sepsis survival rate. And pathological changes in main organs such as lung, spleen, liver and kidney are improved. The invention provides a new treatment way for integrating a post-transcriptional modification targeting strategy and an immunotherapy to treat sepsis, and has important significance for treating and preventing sepsis and improving multi-organ dysfunction syndrome caused by sepsis.

The invention belongs to the technical field of biological medicines, and relates to application of a CXCL14 inhibitor in preparation of a medicine for preventing or treating abdominal aortic aneurysm of a patient. The inhibitor effectively eliminates the sex difference of the abdominal aortic aneurysm by specifically blocking the combination of CXCL14 and a receptor CXCR4 thereof, significantly reduces aortic macrophage infiltration and PDGFRA + macrophage accumulation in the progress process of the abdominal aortic aneurysm, and reduces the collagen degradation and elastic fiber destruction degrees, thereby inhibiting the pathological progress of the abdominal aortic aneurysm. The invention provides a new target spot and a medicine composition for precise treatment of male abdominal aortic aneurysm, and has a definite clinical application value.