82 results about "Immune cell infiltration" patented technology

The invention relates to the technical field of tumor prognosis prediction, in particular to a chest tumor prognosis prediction method and system based on data analysis, and the method comprises the following steps: S1, data collection: collecting multi-modal data of a chest tumor patient; s2, data preprocessing: preprocessing the collected multi-modal data; s3, prediction of tumor immune cell infiltration: predicting the infiltration degree of tumor immune cells, and evaluating the influence of the infiltration degree on patient prognosis; and S4, prognosis analysis and prediction: performing comprehensive analysis through a multi-layer perceptron algorithm to generate prognosis prediction results of the tumor patient, including tumor metastasis risk, recurrence probability and immunotherapy response. According to the invention, the complexity of the tumor immune microenvironment can be better captured, so that more accurate prognosis evaluation is provided, and clinical doctors are helped to understand the potential influence of immune response on tumor metastasis, recurrence and immunotherapy response.

The invention discloses a screening method of sicca syndrome markers based on conjunctival blotting, and relates to the technical field of biomedicine, and the screening method comprises the following steps: S1, conjunctival noninvasive sampling; s2, RNA (Ribonucleic Acid) sequencing and pathway screening; s3, machine learning modeling is carried out; s4, clinical verification. According to the invention, biomarker screening is realized, and similar biomarker screening can also be realized through tear sample analysis or other ophthalmic samples; however, the alternative schemes have the defects of relatively strong invasiveness, complex operation and the like; sampling is carried out through the conjunctival imprinting technology, invasive operation such as biopsy and blood drawing is avoided, and pain and discomfort are reduced; differential expression genes can be accurately identified, and the sensitivity and the accuracy are relatively high; through immune cell infiltration analysis, the relationship between the immune cell subpopulation and the sicca syndrome related gene is disclosed, a new perspective is provided for a disease mechanism, and a theoretical basis is provided for a future immune regulation strategy.

The present application relates to a kind of pH / H2O2 dual-response drug-loaded hydrogel and its preparation method and application, by ε-polylysine derivative as antitumor active ingredient, with oxidized dextran through Schiff base reaction crosslinking rapid gelation. While using 2-formylphenyl boronic acid covalently package CD73 small molecule inhibitor APCP. ε-polylysine derivative has oncolytic activity, can induce ICD and promote the infiltration of immune cells in tumor cells. CD73 small molecule inhibitor APCP can block extracellular CD39-CD73-adenosine pathway, reduce the level of immunosuppressive metabolite adenosine in tumor tissue, so as to activate the infiltrated immune cells, restore its anti-tumor function. The hydrogel of ε-polylysine derivative and APCP co-delivery synergistically inhibits the effect of tumor growth, and its curative effect is greater than the treatment effect of single drug, and is superior to positive control drug oxaliplatin (OXA). The pH / H2O2 dual-response hydrogel is rapidly gelled, and has good biological safety under mild reaction conditions.

The invention discloses a myocardial ischemia reperfusion injury animal model construction method and application thereof in the technical field of model animal preparation. The method comprises the steps of hypertension and hyperlipidemia pretreatment, standardized ischemia-reperfusion operation, immune microenvironment regulation and control and model evaluation and verification. According to the invention, model construction is carried out on an integrated model operation table, so that a standardized ischemia-reperfusion process is realized, reproducibility of a myocardial injury degree and an immune cell infiltration rule of the model is realized, and suitability of the model and nano-drug research is enhanced; and a reliable tool is provided for research and development of targeted drugs such as immune cell membrane coated nanoparticles.

The invention discloses a brain glioma animal model construction method based on an AAV mediated immune microenvironment. The method comprises the following steps: selecting an immunodeficient mouse at the right age; human CD34 + hematopoietic stem cells are injected for immune system reconstruction; human CD45 + immune cells in the peripheral blood PBMC are detected; the method comprises the following steps: selecting tumor tissues with high-expression brain glioma marker genes, carrying out rapid qPCR (quantitative polymerase chain reaction) or targeted RNA-seq immunohistochemical multiple verification, and screening consistent tumor tissues; the method comprises the following steps: physically dicing tumor tissues, treating the tumor tissues with pretreatment liquid, digesting the tumor tissues into single-cell suspension, and inoculating the single-cell suspension into a mouse cranium; an AAV vector carrying a specific immune regulation gene is injected into the tail vein of the mouse, and the brain glioma immune microenvironment is regulated; when it is observed that the tumor tissue grows stably and has immune cell infiltration characteristics, construction of the brain glioma animal model is completed. Compared with an existing model, the brain glioma model which is more stable, more scientific and closer to the human immune background is provided, and the brain glioma model is suitable for related immunotherapy drug screening and mechanism research.

The invention provides an application of an ASPL-TFE3 fusion gene in preparation of a medicine for enhancing the curative effect of an immune checkpoint inhibitor. The nucleotide sequence of the fusion gene is as shown in SEQ ID NO: 1 or SEQ ID NO: 2. The invention relates to the field of tumor immunotherapy, in particular to a method for regulating and controlling expression and activity of TFE3 through ASPL-TFE3 fusion protein to enhance tumor cell autophagy and immune cell permeation, and the tumor treatment effect of an immune checkpoint inhibitor can be improved.

The invention provides a pharmaceutical composition for treating gastric cancer. The pharmaceutical composition comprises an NAT10 inhibitor and a PD-1 inhibitor. The gastric cancer is treated by combining the NAT10 inhibitor Remodelin with the PD-1 inhibitor, so that the problems of tumor angiogenesis and immunosuppression in existing treatment are solved, and the clinical curative effect of immunotherapy is improved. Research finds that when the Remodelin or the PD-1 inhibitor is independently used, a certain tumor inhibition effect is achieved, but the tumor volume of a combined treatment group is remarkably reduced, and immune cell infiltration is remarkably increased.

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.

The invention discloses mizoribine for treating cerebral arterial thrombosis. It is found for the first time that mizoribine can reduce the cerebral apoplexy infarction area, inhibit immune cell infiltration of the brain, relieve inflammation of the cerebral parenchyma stroke part, improve damage to the nervous system of the stroke part and promote recovery of the damaged nerve function.

The invention discloses preparation and application of a PD-L1 nano-inhibitor capable of enhancing the immunotherapy effect of cervical cancer, and belongs to the field of nano-drugs. According to the invention, PDA-coated double-high-Z metal nanoparticles, GdPt-coated PDA for short, are synthesized by using a solvothermal method and a solution oxidation method. Compared with the prior art, the GdPt-coated PDA has an excellent immunotherapy effect and good biological safety. The GdPt (at) PDA not only can realize immunotherapy by down-regulating the expression level of PD-L1, but also can improve the tumor immunosuppression microenvironment and promote immune cell infiltration in tumors through combined radiotherapy, and cooperates with alphaCTLA-4 to realize dual-immune checkpoint blocking therapy, thereby successfully inhibiting the growth of primary tumors and distant tumors.

The present invention relates to the field of medicine, and specifically to the use of taraxasterol or its salts in the preparation of drugs for preventing or treating traumatic brain injury. Animal experiments have confirmed that the taraxasterol of the present invention can improve the motor ability of the balance beam experiment in the neurological function score of mice with brain trauma, improve the neurological function scores including motor tests and sensory tests; reduce the permeability of the blood-brain barrier, reduce brain edema, improve the short-term lesion volume after traumatic brain injury, and inhibit microglial activation and immune cell infiltration. Cytological experiments have confirmed that taraxasterol can reduce microglia-mediated neuroinflammation, reduce the expression of inflammatory factors such as TNF-α, IL-6, and IL-1β, and reduce neuronal damage.

Described herein are gene panel compositions and methods of use thereof for spatial omic analysis in biological samples. The gene panels may be organized into distinct modules that target various aspects of immune response, tumor biology, and intercellular communication within the microenvironment. These methods involve spatial omic techniques, such as spatial transcriptomics, to localize gene expression across tissue sections, providing detailed insights into immune cell infiltration, immune checkpoint activation, and tumor-immune interactions. The disclosed compositions and methods are applicable for diagnostics, monitoring therapeutic responses, and guiding personalized treatment strategies. The modular design of the gene panels allows for customization based on specific research or clinical objectives.

The invention specifically discloses a composition for immunotherapy of bile duct cancer and application thereof, and relates to the technical field of biological medicines. The invention provides a pharmaceutical composition. The pharmaceutical composition comprises: (1) a therapeutically effective amount of an immune checkpoint inhibitor and a CD151 antibody; and (2) a pharmaceutically or immunologically acceptable carrier or excipient. By targeting the membrane protein CD151 of tumor-associated fibroblasts, the cGAS-sting mediated I-type IFN reaction is activated, the innate immunity of the cells is enhanced, and more CD8 + T cells are activated and recruited. The combined use of the CD 151 targeted inhibitor and the PD-1 immune checkpoint inhibitor can enhance the problems of less immune cell infiltration, low function and the like of immunotherapy in bile duct cancer, solves the problems of poor effect, immune escape and insufficient immune cell function of existing immunotherapy, and finally improves the treatment effect of bile duct cancer and patient prognosis.

Embodiments of the present disclosure relate generally to methods used to perform diagnosis and drug screening because the method includes an algorithm that is able to obtain images of immune cells in 3D tissue cultures, analyze such images to create immune cell infiltration maps, automatically score and identify drugs or agents that can be potentially clinically beneficial.

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.

The invention provides a brain glioma immune microenvironment complexity assessment method and application, and the method comprises the following steps: obtaining m glioma samples, and carrying out transcriptome determination on each cell in each glioma sample to obtain transcriptional expression profile data of the cells; carrying out clustering analysis on transcriptional expression profile data of the single cells through K-means clustering, and preliminarily identifying lymphocytes and myeloid cells according to immune cell classical markers; carrying out clustering analysis on the identified transcription expression profile data of the lymphocytes and myeloid cells, and identifying n cell subgroups; calculating the enrichment score of the characteristic gene set of each cell subset in the glioma transcriptome sample, wherein the higher the score is, the higher the enrichment proportion of the cell subset in the sample is; and evaluating the complexity of immune cell enrichment in the glioma sample based on the enrichment score of the characteristic gene set. The immune cell infiltration complexity can be predicted, and the relationship between immune cell enrichment complexity and brain glioma prognosis can be identified.

The invention belongs to the technical field of medicines, and particularly relates to application of adrenosterone and derivatives thereof in preparation of medicines for inhibiting fibrosis and promoting local tissue regeneration. The medicine for inhibiting fibrosis and / or promoting local tissue regeneration is prepared from the adrenosterone and the derivative thereof, fibrosis induced by biological materials, the immune cell infiltration degree and tissue calcification can be resisted, the wound regeneration healing speed can be increased, and meanwhile the effects of resisting fibrosis and promoting local tissue regeneration are achieved.

The application discloses a double-drug self-enhanced layered double hydroxide nanosystem and application thereof. The iron-ruthenium layered double hydroxide in the nanosystem has double enzyme activity, can efficiently catalyze H2O2 to generate O2 and active oxygen in a tumor microenvironment, significantly relieves hypoxia while inducing oxidative stress, the MCT4 specific inhibitor VB124 in the system creates an acidic microenvironment by blocking lactic acid output, amplifies the catalytic efficiency of FeRu, and establishes a self-enhanced catalytic effect; and the co-loaded epigenetic regulator JQ1 down-regulates the expression of PD-L1 by inhibiting BET protein. The system amplifies the catalytic efficiency of FeRu, significantly induces ferroptosis, reverses the immunosuppressive microenvironment with the help of epigenetic regulation, induces the release of damage-associated molecular patterns, causes the infiltration of immune cells, and finally cooperatively triggers a strong anti-tumor immune response. The self-enhanced catalysis-epigenetic regulation synergistic strategy realized by the system provides an innovative solution for improving the effect of tumor immunotherapy.

The invention belongs to the technical field of biological medicines, and particularly relates to application of NLRC5 in targeted screening of medicines for improving immunotherapy of esophageal squamous carcinoma. NLRC5 expression is inhibited or regulated, and immunotherapy of esophageal squamous cell carcinoma is improved. The NLRC5 is highly methylated, and the expression of the NLRC5 in the ESCC is reduced. The NLRC5 is over-expressed, immune cell infiltration is promoted, meanwhile, immune escape is promoted by intensifying T cell depletion, immune checkpoint expression is up-regulated, and an immunosuppression state is created, so that anti-tumor immune response is potentially weakened. The invention discloses a polyhedral function of the NLRC5 in immune regulation and control from a single cell level, and particularly discloses close association of the NLRC5 with an immune checkpoint pathway and T cell depletion. A theoretical basis is provided for developing a therapy for targeting NLRC5, and a new way is possibly opened up for enhancing anti-tumor immune response. Researches show that NLRC5 is an important regulatory factor of immune response in ESCC, and plays a dual role in immune activation and immunosuppression.

The application provides an application of a hair follicle immune homeostasis regulation strategy in treating alopecia diseases. A group of pathological LAMP3 + CCR7 + IL4I1 + DC3 dendritic cell subpopulation. A DC3 dendritic cell subpopulation marker gene Il4i1 Drive conditionally knockout one of the CGRP receptor complexes Calcrl The constructed spontaneous alopecia areata animal model can well simulate the progressive and active hair loss of alopecia areata patients, form stable hair loss patches, and combine with pathological changes such as hair follicle immune cell infiltration, which indicates that the dendritic cell CGRP signal loss is an important inducement for mediating systemic alopecia areata. The application also discloses a pharmaceutical composition or kit for preparing a drug for relieving / treating hair loss, improving hair follicle homeostasis, or enhancing hair growth / black coloration (reducing white hair), which comprises: (a) a JAK kinase inhibitor, and (b) a neuropeptide CGRP or a receptor agonist thereof.

The invention discloses metal-based nanoparticles loaded with traditional Chinese medicine as well as a preparation method and application of the metal-based nanoparticles, and relates to the technical field of nano medical materials. The nano-particle is prepared by taking nickel iron zinc aluminum hydroxide as a multi-metal-based core carrier, carrying out PEG modification and cRGD peptide targeted coupling, and loading a traditional Chinese medicine active ingredient curcumin. The preparation is realized through a multi-step chemical coupling and loading process, and the multi-metal carrier can realize responsive structural disintegration and accurate controlled release of curcumin in a tumor weak acid environment. The nanoparticles have active targeting, multi-metal synergistic killing and immune regulation functions, can specifically recognize a triple negative breast cancer cell surface integrin alpha v beta 3 receptor, inhibit tumor cell proliferation, induce apoptosis, regulate BCR, IL-17 and other immune related signal channels, promote immune cell infiltration and remodel a tumor immune microenvironment. The metal-based nano-particles loaded with the traditional Chinese medicine are simple in preparation process, high in production efficiency and suitable for precise treatment of triple negative breast cancer.

The present invention discloses a method for constructing an animal model of glioma based on AAV-mediated immune microenvironment, comprising: selecting immunodeficient mice of appropriate age; injecting human CD34+ hematopoietic stem cells for immune system reconstruction; detecting human CD45+ immune cells in peripheral blood PBMC; selecting tumor tissues that highly express glioma marker genes, performing rapid qPCR or targeted RNA-seq immunohistochemistry multiple verification, and screening tumor tissues that meet the requirements; physically cutting the tumor tissue and treating it with a pretreatment solution, digesting it into a single cell suspension, and inoculating it into the mouse's skull; injecting an AAV vector carrying a specific immune regulatory gene into the mouse's tail vein to regulate the glioma immune microenvironment; when the tumor tissue is observed to grow stably and have immune cell infiltration characteristics, the construction of the glioma animal model is completed. Compared with existing models, the present invention provides a more stable, more scientific, and more human immune background glioma model, which is suitable for related immunotherapy drug screening and mechanism research.

The application relates to an endometriosis subtype identification method and system, relates to the fields of bioinformatics and medical diagnosis auxiliary technologies, and takes transcriptome expression data as input, constructs a standardized expression matrix, and adopts consistency clustering to perform subtype modeling to obtain a molecular subtype label; expression timing structure of a menstrual cycle phase is introduced to perform dynamic gene identification and discriminant power evaluation, and immune cell infiltration inference and path activity scoring are combined to analyze differences of the subtypes in an immune and inflammation network, then gene-pathway / gene-cell correlation is calculated to form multi-dimensional typing information with mechanism orientation. Based on the above results, an interpretable typing identification model is constructed, which provides a new technical means for accurate diagnosis and target identification of endometriosis.

The invention relates to an application of a soluble epoxide hydrolase inhibitor in the field of transplantation, the soluble epoxide hydrolase inhibitor is TPPU, and the soluble epoxide hydrolase inhibitor is applied in the fields of organ transplantation and tissue transplantation. The TPPU is used for relieving allogeneic mouse heart and skin transplantation immunological rejection, reducing immune cell infiltration in transplantation operation, and inhibiting CD4 + T cell proliferation, CXCR3 chemokine receptor positive and Th1 cell subset proportion. The TPPU inhibits proliferation of primary CD4 + T cells of normal mice and differentiation of Th1 cell subgroups. In organ transplantation and tissue transplantation, the invention provides a single soluble epoxide hydrolase inhibitor TPPU, which can relieve allogeneic mouse heart and skin transplantation immunological rejection, inhibit normal mouse primary CD4 + T cell proliferation and differentiation, and reduce toxic and side effects caused by the use of an immunosuppressant.

This invention belongs to the field of biomedical technology, specifically relating to an anti-tumor nanomaterial, its preparation method, and its application. The anti-tumor nanomaterial is formed by in-situ growth of calcium peroxide on the surface of black phosphorus nanosheets to create hierarchical black phosphorus-calcium peroxide nanosheets, followed by coating the surface of these composite nanosheets with hyaluronic acid. After entering tumor cells, the anti-tumor nanomaterial releases calcium ions and hydrogen peroxide, triggering an abnormal increase in calcium ions and oxidative stress within the cells, thereby causing mitochondrial dysfunction and inducing tumor cell death. Simultaneously, the released calcium ions combine with phosphate ions produced by the degradation of black phosphorus, forming calcium phosphate mineralization deposits within the tumor tissue, inducing tumor biocalcification. Changes in calcium signaling and the oxidative stress process can also promote the infiltration and activation of immune cells, thereby regulating the tumor immune microenvironment and achieving a synergistic effect of cell killing, biocalcification induction, and immune regulation within tumor tissue.

The invention belongs to the technical field of biological medicine and tumor immunotherapy, and discloses application of 3-oxo-valproic acid coenzyme A in preparation of a medicine for inhibiting lung adenocarcinoma. As a specific agonist of GIMAP1, the 3-oxo-valproic acid coenzyme A is used for activating the GIMAP1, enhancing inhibition of lung cancer cell progress and enhancing activation of a tumor immune microenvironment, so that the lung adenocarcinoma is inhibited, and the lung adenocarcinoma is inhibited. The invention has the following beneficial effects: 1, strong targeting property: 3-oxo-valproate coenzyme A is specifically combined with GIMAP1, so that a mediated immunomodulatory pathway is accurately activated, and wide influence on normal cells is avoided; 2, immune microenvironment remodeling: the anti-tumor immune cell infiltration is remarkably improved, the lung adenocarcinoma immunosuppression microenvironment is reversed, and the immunotherapy sensitivity is improved; 3, tumor progression is inhibited, lung cancer cell proliferation is effectively inhibited, and the tumor invasion ability is reduced; 4, the source is natural: as an intestinal microbial metabolite derivative, the safety is high, and the side effect is lower than that of a chemically synthesized medicine.

The invention provides an application of Nr4a3 as a target spot in preparing and screening a medicine for treating a non-alcoholic fatty liver disease. Experiments prove that in the NAFLD pathogenesis process, Nr4a3 expression is increased in the liver. Through knockout of Nr4a3 expression, the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in NAFLD mouse blood can be reduced, the content of triglyceride in liver tissue and the content of collagen in the liver are reduced, and immune cell infiltration in the liver tissue is reduced. The invention provides a new way and exploration direction for the treatment of the non-alcoholic fatty liver disease.

The invention discloses a method and a pharmaceutical composition for regulating and controlling liver cancer fibrosis and immune microenvironment by SRSF3 variable shear. The method comprises the following steps: detecting the expression level of SRSF3 or the variable shear state of SERPINH1 in tumor tissues of a liver cancer patient; for SRSF3 or a short SERPINH1 variant, an effective amount of an inhibitor is administered, said inhibitor being selected from the group consisting of SRSF3-specific shRNA, a SERPINH1 mutant, an antisense oligonucleotide targeting an SRSF3 binding site, or an antibody that blocks the binding of SRSF3 to SERPINH1; by inhibiting the activity of SRSF3 or reducing the generation of short SERPINH1, reducing the fibrosis level of tumor tissues and enhancing immune cell infiltration in a tumor microenvironment, the progress of liver cancer is inhibited, a molecular mechanism of SRSF3 for driving liver cancer fibrosis and immune escape through variable shear SERPINH1 is disclosed, a gene silencing tool of targeted SRSF3 and a SERPINH1 mutant for blocking abnormal shear are developed, and the development of liver cancer is promoted. A pathway inhibitor, an immune checkpoint inhibitor and an anti-fibrosis drug are combined for use, multi-dimensional microenvironment remodeling is achieved, and the SERPINH1 mutant remarkably reduces collagen deposition by retaining exons 4-6.

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.

The invention discloses application of CHPF2 in a glioblastoma prognosis diagnosis reagent, and relates to the technical field of CHPF2 application. The method specifically comprises the following steps: 1, obtaining and treating a glioblastoma sample; step 2, HE and immunohistochemical staining; 3, analyzing expression, prognosis and immune cell infiltration conditions of CHPF2 and mRNA thereof in glioblastoma by a bioinformatics method; and 4, observing the influence of CHPF2 on the proliferation and growth of U251 and A172 cells through an in-vitro experiment. Experimental results prove that CHPF2 is mainly expressed in tumor tissues, the expression of CHPF2 is increased along with the increase of glioma grading, and the expression in primary glioblastoma is the highest; cHPF2mRNA and protein levels thereof of the U251 cell and the A172 cell are higher than those of normal cells; cHPF2 is mainly expressed in a cell nucleus and cytoplasm.