45 results about "Bleomycin" patented technology

The invention belongs to the technical field of biological medicines, and particularly relates to application of bleomycin or bleomycin analogues in preparation of an immunopotentiator. The invention also provides a pharmaceutical composition and application of the pharmaceutical composition in preparation of drugs for treating and / or preventing cancers. The pharmaceutical composition comprises bleomycin, bleomycin analogues or a combination thereof and an anti-tumor immunotherapeutic agent.

The invention discloses application of dikafen phenolic acid and ester derivatives thereof in preparation of medicines for treating pulmonary fibrosis. On an MRC-5 cell model induced by TGF-beta1, the bikafen phenolic acid and the multiple ester derivatives thereof show the activity of inhibiting alpha-SMA and COL1A1 protein expression; on a bleomycin-induced pulmonary fibrosis mouse model, the dimethyl ester derivative of the dikafen phenolic acid shows a good protective effect on experimental animals. Therefore, the dicafen phenolic acid and the ester derivative thereof have good application in the field of preparation of medicines for treating pulmonary fibrosis diseases.

The invention discloses application of peimisine in preparation of an anti-fibrosis medicine, and belongs to the technical field of biological medicines. According to the application, mouse pulmonary interstitial fibrosis is induced through bleomycin, the treatment effect of peimine on pulmonary fibrosis is observed, and the influence of peimine on the pulmonary fibrosis process is explored. Results show that peimisine can reduce mouse lung index increase caused by bleomycin, improve damage of pulmonary alveolar structures of mice with pulmonary fibrosis, reduce aggregation of inflammatory cells, reduce serum fibrosis factors TGF-beta1 and inflammatory factors IL-2 of the mice with pulmonary fibrosis, and reduce the number of macrophages and neutrophils in BALF of the mice with pulmonary fibrosis. The peimisine has an obvious regulating effect on MRC-5 cell abnormal proliferation induced by TGF-beta1, can improve in-vivo pulmonary fibrosis induced by bleomycin by regulating the process of extracellular matrix and intercellular matrix, has an obvious treatment effect on mouse pulmonary fibrosis induced by bleomycin, is beneficial to development and utilization of peimisine, and has a good application prospect. And an effective method is provided for clinical treatment of pulmonary fibrosis.

The application discloses application of phenyllactic acid or a composition containing phenyllactic acid in preparation of a drug for relieving lung diseases, wherein the lung diseases are preferably pulmonary fibrosis or acute lung injury. In an acute lung injury research model, the phenyllactic acid can effectively intervene in an inflammatory factor cascade reaction and an oxidative stress damage process, and significantly improve symptoms of acute lung injury caused by the above factors. Compared with a traditional treatment method, experiments prove that the phenyllactic acid or the composition containing the phenyllactic acid can significantly relieve symptoms of acute lung injury (ALI) of a mouse induced by lipopolysaccharide (LPS) and pulmonary fibrosis (PF) of the mouse induced by bleomycin, effectively improve pathological changes of the lung, and restore lung function.

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 an endothelial cell knockout Cdc42 gene aggravated bleomycin induced pulmonary fibrosis mouse model, which comprises the following steps of: mating a Cdc42 gene conditional knockout mouse with a mouse (Tie2-CreER) of which the endothelial cell specifically expresses tamoxifen induced Cre recombinase to obtain a double-transgenic mouse (Cdc42fl / fl-Tie2-CreER); the Cdc42 gene is specifically knocked out in vascular endothelial cells under the induction of tamoxifen, and then pulmonary fibrosis is induced by subcutaneous injection of bleomycin. The model shows aggravated pulmonary fibrosis phenotypes, including collagen deposition increase, alveolar structure damage and fibrosis-related protein expression up-regulation, and is high in construction success rate and good in repeatability. The invention also provides an application of the model in research of systemic sclerosis related interstitial lung disease pathogenesis and screening of anti-pulmonary fibrosis drugs, and an application of the Cdc42 gene as a drug target, and provides an accurate and reliable tool for pulmonary fibrosis research.

This invention provides the application of huperzine A in the preparation of drugs for the prevention and / or treatment of pulmonary fibrosis. Using a bleomycin-induced in vitro pulmonary fibrosis model, this invention demonstrates that huperzine A can act as an aryl hydrocarbon receptor agonist, increasing the intracellular expression of aryl hydrocarbon receptors; using a bleomycin-induced mouse pulmonary fibrosis model, this invention demonstrates that huperzine A possesses anti-pulmonary fibrosis pharmacological activity. By studying the in vivo and in vitro bioactivity of huperzine A in the treatment of pulmonary fibrosis, this invention provides new ideas and solutions for the research and development and production of anti-fibrotic drugs.

A method for the precise cellular destruction of an oncogenic non-coding RNA with a RNA-binding small molecule conjugated with bleomycin A5 is described. The method affords reversal of phenotype. Bleomycin A5 was coupled to an RNA-binding molecule that selectively binds the microRNA-96 hairpin precursor (pri-miR-96). By coupling of bleomycin A5's free amine to the RNA-binding molecule, its affinity for binding to pri-miR-96 is >100-fold stronger than to DNA. The conjugate compound selectively cleaves pri-miR-96 in triple negative breast cancer (TNBC) cells. Selective cleavage of pri-miR-96 enhances expression of FOXO1 protein, a pro-apoptotic transcription factor that miR-96 silences, and triggers apoptosis in TNBC cells. No effects were observed in healthy breast epithelial cells. This method provides programmable control for targeting RNA through the selection of an RNA-binding molecule / bleomycin A5 conjugate and provides a facile method of mapping the cellular binding sites of an RNA-binding molecule.

The invention belongs to the field of PD-L1 / PD-1 monoclonal antibody tumor immunotherapy, and aims to provide a new research and development direction of PD-L1 / PD-1 monoclonal antibody tumor immunodetection or immunotherapy adjuvant drugs and a new drug combination mode. Experimental results of the invention verify that the invention discloses an application of a reagent for detecting the expression quantity of USP51 in preparation of a detection kit for preparing a PD-L1 / PD-1 monoclonal antibody tumor immunotherapy drug, and discloses an application of a combination of a USP51 inhibitor and a PD-L1 / PD-1 monoclonal antibody drug in preparation of a drug for treating melanoma. The invention discloses an application of a combination of a CD200 inhibitor and a PD-L1 / PD-1 monoclonal antibody in preparation of a drug for treating melanoma, and further discloses an application of a combination of liposome-coated bleomycin and a PD-L1 / PD-1 monoclonal antibody in preparation of a drug for treating melanoma, so that the adverse reaction of bleomycin can be reduced.

The application belongs to the technical field of biological medicine, and particularly relates to application of SFRP1 in treatment of aortic aging drugs. SFRP1 can induce generation of vascular organoids, significantly antagonize vascular smooth muscle cell senescence induced by angiotensin II and bleomycin, enhance vascular smooth muscle cell activity, improve cell oxidative stress ability, reduce cell beta-galactosidase activity, reduce intracellular calcium deposition level, reduce phenotype conversion and reduce extracellular matrix remodeling. Taxifolin can significantly improve accelerated aortic aging in VSMC-specific Sfrp1 knockout mice. SFRP1 and / or Taxifolin both play an anti-aortic aging role, prevent and / or treat aortic aging related diseases. SFRP1 can be used as a screening target to screen drugs against cell senescence damage.

The present invention concerns antibody-conjugate having general structure (2):wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

The invention discloses a construction method and application of a Nox5 gene knocked-in mouse pulmonary fibrosis animal model, and relates to the field of biomedicine.The construction method comprises the following steps that Cas9mRNA, gRNA and homologous recombinant vectors are constructed and jointly injected into mouse fertilized eggs, and F0-generation mice are obtained; mating the F0-generation mice with the wild type to obtain F1-generation mice, and mating the F1-generation mice with the wild type to obtain F2-generation mice; inbreeding the F2-generation mice to obtain F3-generation mice, and hybridizing the F3-generation mice with CDH5 / cre mice to obtain Nox5 < + > / < + > / cre-CDH5 mice; injecting a bleomycin solution into the trachea to obtain a pulmonary fibrosis animal model; according to the construction method and application of the Nox5 gene knocked-in mouse pulmonary fibrosis animal model, the specificity of genome editing is improved through gRNA, the off-target effect is avoided, the cost is low, the success rate is high, the practicability is high, and convenience is provided for researching the effect of the Nox5 gene.

This invention discloses a method for constructing a PBMC-derived humanized mouse scleroderma model. Human peripheral blood mononuclear cells are transplanted into immunodeficient mice, and a human immune system is reconstructed in the mice. Bleomycin is injected into the local skin of the mice in a round-point manner to induce fibrosis and form a scleroderma model. This application can more comprehensively simulate the complex pathological process of immune abnormalities and tissue fibrosis coexisting in human scleroderma, and provides a more realistic and systematic experimental platform for in-depth exploration of the immune mechanism of this disease.

The invention discloses an application of glutathione peroxidase 3 as a therapeutic target in preparation of a medicine for treating pulmonary fibrosis, and an application of a compound Ebselen in preparation of a medicine for treating pulmonary fibrosis. Through single cell and space transcriptomics analysis, it is found for the first time that expression of GPX3 in pulmonary fibrosis patients and model animal lung tissues is significantly reduced. In-vivo and in-vitro experiments prove that up-regulation of GPX3 expression can effectively inhibit fibroblast activation, migration, proliferation and oxidative stress and block a TGF-beta1 / Smad signal channel, so that collagen deposition and pulmonary fibrosis pathological change are relieved. Furthermore, a GPX3 simulant Ebselen is given by adopting an aerosol inhalation mode, is preferably loaded in liposome, and shows a remarkable anti-fibrosis effect in two mouse pulmonary fibrosis models induced by bleomycin and silicon dioxide. The invention provides a brand-new therapeutic target and a medicine scheme with clinical transformation potential for pulmonary fibrosis.

The present invention relates to compound of Formula 1 for use in treating IPF, by reducing collagen deposition in lungs, attenuating the fibrotic marker's expression (in IPF cell-lines Bleomycin induced rat lungs) and improving the bleomycin induced pathological changes in rat lungs, and ARDS, by reducing the cytokine storm. The invention also relates to compound of Formula 1 for use in treating various fibrotic disorders like lung injuries caused by virus or bacterial infections, cardiac, hepatic and kidney fibrosis.

The application discloses application of gentisic acid and pharmaceutically acceptable salts thereof in preparation of a medicine for treating pulmonary fibrosis. A large number of experiments show that gentisic acid has obvious effects of inhibiting extracellular matrix deposition, and has certain improvement effects on pulmonary fibrosis tissues of a mouse induced by bleomycin, especially can delay alveolar damage and destruction of lung tissue structure of the mouse with pulmonary fibrosis, so that the application has great application prospects in treatment of fibrosis diseases.

The invention belongs to the technical field of medical biology, and particularly relates to Ephrin-B2 recombinant protein as well as a vaccine, a preparation method and application thereof. In order to treat and prevent fibrotic diseases, the Ephrin-B2 recombinant protein is expressed and purified based on an Ephrin-B2 extracellular fragment, and an adjuvant is added to prepare the Ephrin-B2 recombinant protein vaccine which is used for treating and preventing the fibrotic diseases. Animal experiment results show that the Ephrin-B2 recombinant protein vaccine prepared by the invention can initiate obvious cellular immune and humoral immune response in a mouse body, effectively treat and prevent idiopathic pulmonary fibrosis and radiation-induced pulmonary fibrosis, and has an obvious inhibitory effect on bleomycin-induced systemic sclerosis skin fibrosis, which can be seen that the Ephrin-B2 recombinant protein vaccine can be used as a vaccine for treating systemic sclerosis skin fibrosis. The Ephrin-B2 recombinant protein and the vaccine thereof provided by the invention provide a candidate scheme for future research on conversion of preventive and therapeutic vaccines for fibrotic diseases.

The invention belongs to the field of drug activity, and particularly relates to application of dimethyl fumarate in preparation of alveolar cell regeneration drugs. The invention systematically evaluates the effect of dimethyl fumarate in the process of promoting pulmonary alveolar regeneration by constructing a pulmonary alveolar organ model and a bleomycin-induced lung injury mouse model. Research results show that dimethyl fumarate can significantly promote regeneration of alveolar epithelium AT2 cells, so that alveolar epithelium structure repair is accelerated.

The invention relates to the technical field of medicines, in particular to a pre-carbon monoxide saturated hemoglobin oxygen carrier preparation as well as a preparation method and application thereof in resisting pulmonary fibrosis. The preparation method of the pre-carbon monoxide saturated hemoglobin oxygen carrier preparation comprises the following steps: carrying out carbon monoxide saturation treatment on the hemoglobin oxygen carrier preparation; the carbon monoxide saturation treatment comprises the step of introducing carbon monoxide for 15-25 minutes at the temperature of 2-6 DEG C and the speed of 0.5-1.5 L / min. The pre-carbon monoxide saturated hemoglobin oxygen carrier preparation can significantly reduce bleomycin induced pulmonary edema and injury, improve the pulmonary hypoxia state and inhibit the pulmonary fibrosis process, and provides a brand new treatment strategy for clinical treatment of pulmonary fibrosis.

The invention belongs to the technical field of biological medicines, and discloses application of AAV-shBmal1 in preparation of a medicine for preventing and treating pulmonary fibrosis. The invention discloses shRNA (short hairpin Ribonucleic Acid) of a targeted Bmal1 gene, which is characterized in that the nucleotide sequence of the shRNA is shown as SEQ ID NO: 1. The invention provides shRNA (short hairpin Ribonucleic Acid) for knocking down Bmal1 in a targeting manner, and further constructs an adeno-associated virus vector containing the shRNA and an adeno-associated virus (AAV-shBmal1). Experiments prove that the AAV-shBmal1 can effectively inhibit formation and development of pulmonary fibrosis induced by bleomycin, can reverse the pulmonary fibrosis induced by bleomycin, and can be used for prevention and treatment of pulmonary fibrosis.

The present application relates to a kind of biomarker associated with pulmonary fibrosis and its application.The biomarker includes interferon regulatory factor 8.The present application utilizes the classic bleomycin induced pulmonary fibrosis model, induces pulmonary fibrosis in experimental animal mouse, carries out transcriptome level analysis, finds that the expression level of bone marrow endothelial rich interferon regulatory factor 8 in pulmonary fibrosis mouse model is reduced, further test finds that the expression level of interferon regulatory factor 8 (such as by agonist regulation etc.) in mouse model can delay the occurrence and development of pulmonary fibrosis, indicates that IRF8 can be used as the new target of pulmonary fibrosis diagnosis, treatment, provides new target, new strategy for the treatment of pulmonary fibrosis.

The invention discloses application of flueggeine B or pharmaceutically acceptable salt thereof in preparation of a medicine for treating pulmonary fibrosis. The chemical structure of the flueggeine B is shown as a formula (I). The flueggemine B shows an improvement effect in a bleomycin-induced pulmonary fibrosis mouse model, improves the weight and lung function parameters of a mouse, relieves the degree of pulmonary fibrosis, has an inhibition effect on lung tissue collagen deposition, can also effectively improve the phenotype of pulmonary epithelial cells and inhibit abnormal activation of myofibroblasts, and can be used for treating pulmonary fibrosis. Therefore, the traditional Chinese medicine composition has a remarkable relieving effect on bleomycin-induced pulmonary fibrosis.

This invention discloses the application of NLRX1 protein inhibitors in the preparation of products with protective effects against pulmonary fibrosis, belonging to the field of biomedical technology. This invention, through the use of an NLRX1 gene knockout mouse model and siRNA silencing technology, demonstrates that inhibiting NLRX1 can significantly alleviate bleomycin-induced pulmonary fibrosis pathological damage. Its protective mechanisms include promoting the proliferation of type II alveolar epithelial cells, inhibiting their damage and apoptosis, and reducing myofibroblast infiltration and extracellular matrix deposition. Based on this, this invention provides for the first time a therapeutic strategy targeting the inhibition of the NLRX1 protein. Related products include recombinant vectors containing RNA molecules encoding NLRX1 expression inhibitors or other drugs capable of inhibiting NLRX1 expression. This invention provides new targets and drug development directions for the treatment of fibrotic diseases, especially pulmonary fibrosis.

The invention provides application of an IP receptor stimulant in preparation of a medicine for treating lung injury, and relates to the technical field of biological medicine. Transdifferentiation of alveolar II-type epithelial cells to I-type epithelial cells after lung injury is realized by utilizing selepag and other IP receptor agonists, and the scheme not only can relieve lung tissue inflammation and fibrosis degree induced by bleomycin and other factors, but also can reduce the death rate of model animals and improve lung function prognosis. Meanwhile, the used IP receptor stimulant part is a clinically mastered drug, so that the safety is higher, the selectivity is good, and a new effective way and a new drug development direction are provided for the treatment of lung injury and related fibrosis diseases.

The invention belongs to the technical field of traditional Chinese medicine, and relates to application of a yin-nourishing and lung-clearing composition in preparation of medicine for preventing and / or treating pulmonary fibrosis, and the yin-nourishing and lung-clearing composition is prepared from the following raw materials: rehmannia, radix scrophulariae, radix ophiopogonis, moutan bark, bulbus fritillariae cirrhosae, radix paeoniae alba, mint and liquorice. The invention provides the application of the yin-nourishing and lung-clearing composition in preparing the medicine for preventing and / or treating the pulmonary fibrosis, bleomycin is injected into the trachea to construct a pulmonary fibrosis mouse model, and the effect of the yin-nourishing and lung-clearing composition on treating the pulmonary fibrosis is determined from the three aspects of the lung coefficient, the pathological change and the hydroxyproline content of a model animal. Basic data support is provided for increasing clinical application of the composition for nourishing yin and clearing away lung-heat.

The application discloses application of 2''-O-galloylgeniposide in preparation of anti-fibrosis drugs. In the application, the 2''-O-galloylgeniposide can inhibit up-regulation of cell alpha-smooth muscle actin (alpha-SMA) and / or fibronectin expression and up-regulation of type I collagen (CO11A1) gene, fibronectin (FN1) gene and / or alpha-smooth muscle actin (ACTA2) gene transcription in a lung epithelial cell interstitial transformation model, a skin fibroblast activation model, a liver stellate cell activation model and a bleomycin-induced mouse lung fibrosis animal model, and the 2''-O-galloylgeniposide shows a significant anti-fibrosis effect and can be used for preparation of anti-fibrosis drugs.

The application relates to the field of biological medicine, and particularly relates to a WDR6 gene and application thereof Wdr6 in preparation of a liver aging delaying product. Wdr6 Low expression can aggravate the liver aging degree, and liver-specific Wdr6 Overexpression can significantly down-regulate the expression of a p21 protein, which is a marker of aging, in liver tissues of naturally aging mice, and the number of cells that are positively colored by aging-related beta-galactosidase staining is significantly reduced, indicating that Wdr6 Overexpression can effectively maintain liver young homeostasis and delay liver aging. Meanwhile, through an in-vitro culture of a liver cell line aging model induced by bleomycin, it is verified that the WDR6 protein can increase the expression of a long-life protein SIRT1 protein, down-regulate the expression of a p21 protein, and reduce beta-galactosidase, so as to realize liver aging delay.

The application provides application of chamaecyparis funebris polysaccharide in preparation of a medicine for preventing and / or treating pulmonary fibrosis, and belongs to the technical field of medicines.The application finds that chamaecyparis funebris polysaccharide can effectively prevent and / or treat pulmonary fibrosis, and can effectively reduce lung injury and inhibit lung inflammation; chamaecyparis funebris polysaccharide inhibits fibrosis and migration of human embryo lung fibroblasts induced by recombinant human transforming growth factor, improves lung function injury and pulmonary fibrosis of a bleomycin-induced pulmonary fibrosis mouse, inhibits inflammatory cell infiltration of bronchial alveoli and expression of NOD-like receptor family pyridine domain-containing protein 3 (NLRP3) in lung tissue of the pulmonary fibrosis mouse, and further inhibits lung inflammation; chamaecyparis funebris polysaccharide can also inhibit the Hedgehog signal pathway in vitro and in vivo, and the improvement of lung function of the bleomycin-induced pulmonary fibrosis mouse and the treatment of pulmonary fibrosis by chamaecyparis funebris polysaccharide are further enhanced when assisted by a Hedgehog pathway inhibitor.