201 results about "Cellular infiltration" patented technology

The invention discloses bioactive macroporous hydrogel as well as a preparation method and application thereof. The bioactive macroporous hydrogel comprises hydrogel particles and a bioactive load loaded on the hydrogel particles, the hydrogel particles are obtained by mechanically extruding a hydrogel matrix, and the hydrogel matrix is formed by compounding sodium alginate, agarose and methacrylated hyaluronic acid through hydrogen bond crosslinking and photo-crosslinking; the bioactive load comprises: a) small extracellular vesicles of which the surfaces are modified with macrophage targeted CRV peptides; and b) a PLGA (poly (lactic-co-glycolic acid)) microsphere loaded with a cartilage inducer Kartogenin. The bioactive macroporous hydrogel disclosed by the invention has an internally communicated macroporous network, is beneficial to cell infiltration, blood vessel ingrowth and nutrient substance diffusion, and overcomes the defects that the traditional hydrogel is small in pore size and limits cell behaviors. According to the bioactive macroporous hydrogel disclosed by the invention, dual bioactive loads are adopted to synergistically promote tendon-bone healing, so that the treatment effect is better.

The invention belongs to the technical field of biological medicines, and particularly discloses a nano-engineering T cell membrane coated nano-particle as well as a preparation method and application of the nano-engineering T cell membrane coated nano-particle. Nanoparticles of a specific structure are constructed based on a phospholipid bilayer bionic nanometer platform through a membrane fusion technology, immune clearance caused by phagocytosis of the nanoparticles by macrophages can be avoided through disguise of a T cell membrane, and the blood circulation time is prolonged; the functions of T cells are recovered through specific blocking of immune checkpoint molecules loaded on the immune checkpoint molecules on corresponding immune checkpoint ligands on tumor cells; under ultrasonic radiation, the nano-particles are gradually decomposed and release the sound-sensitive agent to generate a large amount of active oxygen, so that immunogenic death of tumor cells is promoted, more cytotoxic T lymphocytes are recruited to infiltrate into tumor parts, and the recovery of T cell mediated immune response function is facilitated. The synergistic effect of the sound-sensitive agent and the immune checkpoint protein can effectively inhibit tumor growth, induce a long-term immune memory effect and prevent tumor metastasis and recurrence.

The invention belongs to the technical field of biological medicines, and discloses a traditional Chinese medicine composition for treating microsatellite stability (MSS) type tumors by a sensitization immune checkpoint inhibitor. The traditional Chinese medicine composition provided by the invention comprises radix scutellariae, rhizoma zingiberis, Chinese herbaceous peony, liquorice root and Chinese date, can increase CD8 + T cell infiltration, promote the CD8 + T cell to secrete cytokines and improve the immunosuppression of MSS type tumors, and further breaks through the conventional range of anti-tumor treatment of immune examination inhibitors; meanwhile, the traditional Chinese medicine composition can also improve adverse reaction of gastrointestinal tracts caused by tumor treatment by an immune examination inhibitor, and the life quality of patients is improved.

The invention belongs to the technical field of microorganisms, and particularly relates to application of bifidobacterium longum in improving immunity and preparing products for preventing, treating and / or assisting in treating rhinitis. The preservation number of the bifidobacterium longum is GDMCC No: 65969, and the bifidobacterium longum can reduce the levels of MDA and NO in serum of mice and improve the activity of SOD and CAT and the content of GSH so as to relieve oxidative stress injury; inflammatory cell infiltration of nasal mucosa is reduced, and lung tissue inflammatory mediator level and inflammation-related gene expression are reduced to inhibit inflammation; th1 / Th2 immune balance is regulated, Th2 type cytokines are reduced, Th1 type cytokines are increased, and the high-dosage effect is close to that of loratadine. The strain has a treatment effect on allergic rhinitis through multiple mechanisms, and a new choice is provided for treatment of the strain.

The invention provides a preparation method of a composite artificial flap with a bionic structure and function induction activity. The preparation method comprises the following steps: S1, preparing an epidermis induction layer; s2, preparing a dermis functional remodeling layer; s3, preparation of a vascularization integration substrate layer; and S4, three-layer compounding and sterilization. Through an epidermis-basilar membrane-dermis three-layer integrated structure, a micron-nano multistage gradient pore and basilar membrane belt adhesion structure of natural skin is accurately simulated, and the problems of epidermis-dermis layering and non-uniform cell infiltration of an existing skin flap are solved.

The invention belongs to the technical field of biological medicine, and particularly discloses nano composite particles based on a metal organic framework and a preparation method and application of the nano composite particles. The nano-composite particles are constructed through electron adsorption and coordination based on a nano-scale metal organic framework, and under the acidic microenvironment and ultrasonic irradiation of tumors, the nano-composite particles can be decomposed and released in a responsive manner, play a role of a sound-sensitive agent, generate a large amount of active oxygen and induce tumor cells to generate immunogenic death, so that the tumor cell immunogenicity is improved, and the tumor cell immunogenicity is improved. Further, more cytotoxic T lymphocytes are promoted to infiltrate a tumor microenvironment, T cell mediated anti-tumor immune response is recovered, and tumor metastasis is effectively prevented. The carrier metal organic framework ZIF8 of the nano-composite particles can serve as a sound-sensitive agent to generate active oxygen, the function of ultrasonic imaging of tumor tissue can be achieved, the effect of diagnosis is achieved while treatment is conducted, tumor diagnosis and treatment monitoring can be achieved at the same time through one-time drug administration, and a new strategy is provided for precise medical treatment.

The invention discloses an anti-tumor pharmaceutical composition based on NBDHEX and application of the anti-tumor pharmaceutical composition in treatment of immunosuppressive malignant tumors. The pharmaceutical composition comprises NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and a PD-1 (programmed death-1) inhibitor, and is characterized in that the NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and the PD-1 inhibitor are used as raw materials. The NBDHEX can induce tumor cells to generate immunogenic death and promote tumor antigen release, DAMPs signal activation and dendritic cell maturation, so that an immunosuppressive tumor microenvironment is remodeled, and CD8 + T cell infiltration and effector functions are enhanced. The pharmaceutical composition can significantly improve the anti-tumor immune response intensity and the treatment response rate. Animal experiments and cell experiments verify the synergistic anti-tumor effect of the composition in a lymphoma model. The immunosuppressive malignant tumors are suitable for treatment of various immunosuppressive malignant tumors including lymphoma, and are especially suitable for patients with poor single-drug reaction or drug resistance to immune checkpoint inhibitors, and a new way is provided for clinical treatment of tumors.

The invention relates to the technical field of biological medicines, and discloses application of methionine adenosine transferase 2A and related substances thereof in preparation of wound repair products. According to the application disclosed by the invention, a metabolic regulation network in a diabetic wound surface is researched, so that MAT2A expression down-regulated in pericytes is found to be remarkably and negatively correlated with M1 type macrophage infiltration, and the situation that the wound healing is delayed, the wound surface blood perfusion is reduced and the inflammation macrophage infiltration is increased due to MAT2A specific deletion of the pericytes in the wound is observed; and after saMAT2A-loaded pericellular membrane coated lipid nanoparticles (PMCNPs) are further adopted for treatment, the regeneration process of the wound surface can be remarkably enhanced, continuous inflammatory macrophage infiltration in the diabetic wound surface is relieved, microcirculation recovery is promoted, the safety is high, and good application prospects are achieved in the aspect of promoting wound surface repair.

The invention provides a novel medicine for treating psoriasis by recovering keratinocyte Pp6 and application of the novel medicine. The novel medicine has the structural formula shown in the formula (I), has the remarkable effects of inhibiting epidermal hyperplasia, reducing the infiltration number of dermal inflammatory cells and the like on a psoriasis focus area, and has the very excellent relieving or treating effect on psoriasis.

The invention discloses an engineered exosome for breaking through a pyroptosis immune starting and maintaining barrier as well as a preparation method and application of the engineered exosome. The exosome is constructed by loading an immune checkpoint inhibitor into a pre-stimulated exosome, and the exosome is derived from immune cells, high-expression interferon gamma and granzyme A. The expression of the tumor cell GSDMB is up-regulated by delivering the interferon gamma through the exosome, and the exogenous granzyme A cuts the GSDMB to trigger pyroptosis; meanwhile, an immune checkpoint inhibitor blocks a PD-1 / PD-L1 pathway in situ, T cell depletion is reversed, and release of endogenous granzyme A is promoted; the pyroptosis cells release antigens to activate the T cells, the activated T cells continuously secrete granzyme A / interferon gamma to form a cascade amplification effect, and the problem of double barriers existing in the pyroptosis immune cycle of granzyme A-GSDMB is solved. The engineered exosome can improve the infiltration degree of CD8 + T cells, and is suitable for treating tumors such as liver cancer and non-small cell lung cancer.

The application discloses application of DUSP4 in preparation of a marker for predicting the curative effect of immunotherapy of hepatocellular carcinoma and a sensitizing drug, and belongs to the technical field of biological medicine.The application finds that high expression of dual specificity phosphatase 4 (DUSP4) is significantly related to high response rate and long survival period of an immunological checkpoint blocking therapy for a hepatocellular carcinoma patient.DUSP4 promotes CD8+ T cell and NK cell infiltration and remodels an immune microenvironment by inhibiting a TGF-beta signal path, down-regulating an immunosuppressive factor and up-regulating an antigen presenting molecule and a chemotactic factor.The application provides a kit and a method for detecting the expression level of DUSP4 to predict an immunotherapy response, and a combined drug composition comprising a DUSP4 activator or a TGF-beta inhibitor and an immunological checkpoint inhibitor.Experiments prove that up-regulation of the expression of DUSP4 can significantly enhance T cell killing function, and produces a synergistic anti-tumor effect with an anti-PD-1 antibody.The application provides a new strategy for precise stratified treatment and overcoming immunological drug resistance of hepatocellular carcinoma.

The application relates to a cell infiltration inference method and system fusing GO function annotation and PPI network information, and the method comprises the following steps: collecting gene expression data, GO function annotation data and PPI network data; constructing a cell-cell function correlation network and a cell-cell physical interaction network respectively; performing weighted fusion processing on the two networks to obtain a comprehensive cell relationship network; calculating a final cell infiltration score through a restart walk algorithm, and inferring the infiltration degree in a tumor microenvironment according to the final cell infiltration score. The application innovatively fuses GO function annotation information and PPI network data, comprehensively considers the functional similarity and physical or signal interaction between cells, enables the model to understand cell synergy from the biological pathway level and analyze cell direct interaction from the protein interaction level, avoids one-sidedness of a single perspective, and provides a more stereoscopic cognitive framework for tumor microenvironment analysis.

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 invention discloses application of NCCRP1 as a lung adenocarcinoma immunotherapy biomarker, and belongs to the field of biological medicine. Bioinformatics analysis finds that the NCCRP1 is remarkably and highly expressed in lung adenocarcinoma tissues, and the expression level of the NCCRP1 is in negative correlation with prognosis of a patient. Secondly, the expression level of lung adenocarcinoma cells NCCRP1 is in negative correlation with infiltration of anti-tumor immune cells such as CD8 + T cells. Experiments show that the knockout of the NCCRP1 can significantly inhibit the growth of mouse lung tumors by increasing the infiltration quantity of CD8 + T cells and NK cells in a lung adenocarcinoma microenvironment. The invention provides a new target spot for immunotherapy of lung adenocarcinoma, including NCCRP1 gene editing (knockout / knockdown) and application of an inhibitor in preparation of antitumor drugs.

The invention relates to a cell infiltration inference method and system fusing GO function annotation and PPI network information. The method comprises the following steps: collecting gene expression data, GO function annotation data and PPI network data; respectively constructing a cell * cell function association network and a cell * cell physical interaction network; carrying out weighted fusion processing on the two to obtain a comprehensive cell relation network; and calculating a final cell infiltration fraction through a restart migration algorithm, and deducing the infiltration degree in the tumor microenvironment according to the final cell infiltration fraction. According to the method, GO function annotation information and PPI network data are creatively fused, functional similarity and physical or signal interaction between cells are comprehensively considered, the model can understand cell synergy from the biological pathway level and can analyze cell direct interaction from the protein interaction level, one-sidedness of a single view angle is avoided, and the method has the advantages of being simple in structure and convenient to operate. And a more three-dimensional cognitive framework is provided for tumor microenvironment analysis.

Provided relates to the field of cytometry, specifically to flow cytometric methods and kits for improved diagnosis, prognosis and monitoring of tumors and other lesions involving immune cell infiltration. Further provided are embodiments of the subject matter which relate to compositions and methods providing high resolution quantitative means for immunophenotyping and immune modeling, and for identification of disease prognostic and therapy predictive biomarkers.

This invention relates to the field of traditional Chinese medicine and natural medicines, and discloses a traditional Chinese medicine composition for treating thyroiditis, nodular goiter, and thyroid nodules, as well as its preparation method and application. The traditional Chinese medicine composition is made from raw materials in parts by weight of 1-30 parts of Prunella vulgaris, 1-30 parts of Taraxacum mongolicum, 1-30 parts of Hordeum vulgare malt, 1-20 parts of Citrus reticulata peel, 1-24 parts of Crataegus pinnatifida, and 1-24 parts of Raphanus sativus seed. It can not only significantly reduce serum TgAb and TPOAb antibody levels, inhibiting the attack of autoimmune response on the thyroid gland from the source, but also effectively reduce lymphocyte infiltration, repair damaged thyroid follicular structure and restore colloid content, thereby reversing immune damage and tissue destruction of the thyroid gland, reducing thyroid nodules, and solving the problems of existing treatments for thyroiditis, nodular goiter, and thyroid nodules that cannot reverse immune damage to the thyroid gland, destruction of follicular structure, and tissue fibrosis.

The invention discloses application of a nerve injury induction protein 1 in preparation of a gastric cancer diagnosis and treatment product. The invention finds that the overexpression of NINJ1 not only can enhance the sensitivity of gastric cancer cells to ferroptosis by down-regulating the expression of aldehyde ketoreductase AKR1C1 / 2 / 3, but also can up-regulate the expression of MHC-I molecules on the surfaces of tumor cells, promote the presentation of tumor antigens and increase the infiltration of CD8 + T cells, so that the dual anti-tumor function is exerted; therefore, NINJ1 overexpression and an immune checkpoint inhibitor (such as a PD-L1 antibody) or a ferroptosis inducer are combined for use, so that the immunotherapy effect can be synergistically improved. The invention provides a brand new targeting strategy for overcoming the immune drug resistance of gastric cancer and improving the treatment effect, and has important clinical transformation value.

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.

This invention provides the application of type IV collagen and its encoding gene in the prognostic assessment and treatment of nasopharyngeal carcinoma (NPC). Research has shown that high expression of type IV collagen and its encoding gene COL4A1 is significantly associated with lower T-cell infiltration in patients with recurrent NPC; compared to NPC patients with low expression of type IV collagen, those with high expression have worse LRRFS and OS; and the expression level of the type IV collagen encoding gene COL4A1 is significantly associated with worse PFS in NPC patients. Therefore, type IV collagen and its encoding gene COL4A1 can serve as specific prognostic biomarkers for assessing the prognosis of NPC patients. Furthermore, inhibiting the expression of type IV collagen can effectively inhibit the growth of NPC; therefore, agents that inhibit type IV collagen expression can be used as drugs to inhibit immune escape in NPC and for the treatment of NPC.

The invention relates to the technical field of biological medicine, and particularly discloses application of combination of an IGF1R inhibitor and immunotherapy in preparation of a medicine for treating lung cancer, the combination of the IGF1R inhibitor OSI-906 and an immune checkpoint inhibitor can effectively enhance the curative effect of small cell lung cancer immunotherapy, and compared with treatment with a single immune checkpoint inhibitor or the IGF1R inhibitor, the curative effect of the IGF1R inhibitor OSI-906 and the curative effect of the IGF1R inhibitor OSI-906 can be effectively enhanced. The IGF1R inhibitor combined with the immune checkpoint inhibitor can remarkably inhibit the growth level of tumors, the growth level of the tumors is obviously lower than that of the single use of common antibody drugs, because the IGF1R inhibitor can reduce the activity of endothelial cell IGF1 / IGF1R pathways and destroy the vascular structure of small cell lung cancer, the combined immunotherapy of the IGF1R inhibitor can remarkably enhance T cell infiltrating tumors, and the immune checkpoint inhibitor can effectively inhibit the tumor growth. Therefore, growth of small cell lung cancer cells is inhibited, the tumor immunotherapy effect of the immune checkpoint inhibitor is improved, and tumor growth is better inhibited.

The invention discloses a manganese-based layered hydroxide modified by gold nanoparticles and a preparation method thereof, and relates to the technical field of drug synthesis, and the key points of the technical scheme are as follows: the layered morphology of Mn-LDH is observed on the manganese-based layered hydroxide in a transmission electron microscope, and spherical AuNPs dispersed on the surface and edge of a laminate have a uniform particle size and a uniform particle size. EDS energy spectrum analysis finds that gold, manganese, magnesium, aluminum and carbon elements exist, the hydrated particle size is 312 nm, and the dispersity is good. The material can initiate an excellent photo-thermal effect under the irradiation of 808nm near-infrared light to generate active oxygen and hydroxyl radicals to destroy bacterial cell walls and cell membranes, and the antibacterial effect can reach 99%. In addition, the material can stimulate a local active immune function, promote T cell infiltration and realize active immune sterilization. The nano material shows a remarkable anti-infection effect in an in-vitro antibacterial experiment and an in-vivo osteomyelitis animal model experiment, and a new insight is provided for treating osteomyelitis caused by methicillin-resistant staphylococcus aureus.

The present invention discloses a dual-targeted macrophage membrane nanosystem, its preparation method and application, which belongs to the field of biomedicine. MKA is formed by connecting AuNPs with the mitochondrial targeting peptide KLA and then encapsulating it in the macrophage membrane. During preparation, AuNPs are first synthesized and modified, and then encapsulated with the macrophage membrane. During treatment, it can dual-target tumor cells and mitochondria, enhance radiation-induced DNA damage, inhibit DDR, activate immune pathways, promote T cell infiltration, and consume glutathione and amplify oxidative stress to enhance immune effects. The dose enhancement ratio synergistic with 8GyX-rays is 3.1. In addition, MKA has good biocompatibility in the body, a long blood circulation time, high tumor targeting, and can be quickly cleared through the kidneys. This invention provides a new approach for tumor radioimmunotherapy and helps promote progress in clinical tumor treatment.

The present invention relates to a 100% natural product consisting of natural matrices showing emerging properties, which allows to re-establish a correct metabolism in tissues infiltrated by cancer cells, adjuvating cancer treatment and tissue homeostasis. The product of the invention, as demonstrated by the inventors, is itself a natural matrix, representing native natural intelligence, said natural intelligence being the only capable to allow a physiological endogenous interconnection with other entities which are self-assembled in nature, such as the human species. By modulating tumor microenvironment and thus selectively inducing cancer cells mortality, the product achieves reconstitution of conditions favourable to tissue homeostasis in tissues infiltrated by cancer cells. Factually, the invention allows for a shift of paradigm based on the passage from a deterministic validation of properties to a probabilistic one based on functional redundancy logics, that will grant an industrially viable source of innovation for manufacturers in the field of 100% natural therapeutic or beneficial products.

According to the application of the triple-network hydrogel to preparation of the osteochondral defect repair material, a PRP-coated OSA-GEL three-network composite hydrogel system is provided based on PRP, OSA and gelatin, in the system, a dynamic covalent network of OSA and gelatin, a physical network of fibrin and an egg box model formed between Ca < 2 + > and OSA form an IPN network with enhanced mechanical properties, and the PRP-coated OSA-GEL three-network composite hydrogel system has the advantages that the mechanical properties of the PRP-coated OSA-GEL three-network composite hydrogel system are enhanced; a dynamic cross-linking system of the PRP-coated OSA-GEL hydrogel not only can support cell infiltration and tissue regeneration, but also brings self-repairing capability to the hydrogel, so that a hydrogel network can be quickly recovered after the hydrogel is broken, the vulnerable biological activity of PRP is protected, new cartilage of the PRP-coated OSA-GEL is complete, regenerated cartilage tissue in a defect area is almost completely fused with surrounding normal cartilage, and the defect area of the PRP-coated OSA-GEL is not damaged. It is indicated that the PRP remarkably enhances the cartilage regeneration effect through PRP-coated OSA-GEL, and the PRP has effectiveness in the aspect of promoting and enhancing osteochondral regeneration.

The present invention relates to a 100% natural product consisting of natural matrices showing emerging properties, which allows to re-establish a correct metabolism in tissues infiltrated by cancer cells, adjuvating cancer treatment and tissue homeostasis. The product of the invention, as demonstrated by the inventors, is itself a natural matrix, representing native natural intelligence, said natural intelligence being the only capable to allow a physiological endogenous interconnection with other entities which are self-assembled in nature, such as the human species. By modulating tumor microenvironment and thus selectively inducing cancer cells mortality, the product achieves reconstitution of conditions favourable to tissue homeostasis in tissues infiltrated by cancer cells. Factually, the invention allows for a shift of paradigm based on the passage from a deterministic validation of properties to a probabilistic one based on functional redundancy logics, that will grant an industrially viable source of innovation for manufacturers in the field of 100% natural therapeutic or beneficial products.

The application discloses application of a PRMT3 inhibitor SGC707 in preparation of a drug for treating pulmonary fibrosis, and for the first time verifies that a selective PRMT3 inhibitor SGC707 can dose-dependently inhibit expression of fibrosis markers such as COL1A1 and alpha-SMA in fibroblasts induced by TGF-beta 1 in vitro; in a bleomycin (BLM) induced mouse pulmonary fibrosis model, SGC707 administration can significantly improve lung tissue collagen deposition, reduce inflammatory cell infiltration, repair alveolar structure damage, and effectively down-regulate expression levels of fibrosis related proteins in lung tissues. It is proved that PRMT3 is a functional target with important intervention value in pulmonary fibrosis, SGC707 has definite anti-pulmonary fibrosis activity in vitro and in vivo, and a new drug strategy is provided for treatment of pulmonary fibrosis.

The invention discloses a construction method of a spontaneous lupus adipositis animal model, which comprises the following steps: constructing keratinocytes with genotypes of PPAR [gamma] flox / flox- / -Krt5-CreERT < 2 + > / -Adipoq-Cre < + > / -and PPAR [gamma] flox / flox- / -Krt5-CreERT < 2 + > / -Adipoq-CreERT < 2 + > / -and fat cells into a conditional PPAR [gamma]-active receptor gamma gene knockout mouse, so as to construct the animal model with the spontaneous lupus adipositis animal model. Then knocking out PPAR gamma genes in keratinocytes and adipocytes by using a gene knockout activator, so that the mice spontaneously have the phenotypes of lupus septicaemia, including local skin unhairing, lipoatrophy, persistent skin lesion, proteinuria and serum autoantibodies; histological examination finds that lobular adipositis, glomerular volume increase, mesangial cell hyperplasia, inflammatory cell infiltration, glomerular IgG deposition and the like are mainly caused by dermal immune cell infiltration and subcutaneous fat layer lymphocyte infiltration, clinical symptoms of patients with lupus adipositis are simulated, and an important tool is provided for related research of lupus adipositis.