75 results about "Bleomycin" patented technology

The invention discloses a radionuclide labeled molecular probe for detecting collagen structure denaturation and a preparation method and application thereof, and relates to the technical field of biology. The structural general formula of the radionuclide labeled molecular probe disclosed by the invention is as follows: K (chelating agent-nuclide)-K-Linker-CHP, wherein K (chelating agent-nuclide) is a lysine residue labeled by a side chain amino coupling chelating agent and a radionuclide; the Linker is a connection joint; cHP is a collagen hybrid peptide with a polypeptide sequence of (GfO) n or (GPO) n. The probe has excellent definition and signal-to-noise ratio, not only can detect pancreatic ductal adenocarcinoma in a pancreatic cancer model, but also can sensitively detect precancerous lesions (such as pancreatic intraepithelial neoplasia lesions) of the pancreatic ductal adenocarcinoma and pulmonary fibrosis lesions in a bleomycin pulmonary fibrosis model. And the kit has important significance on early detection of pancreatic duct adenocarcinoma and reflection of dynamic change of ECM remodeling.

The invention discloses an application of phenyllactic acid or a composition containing phenyllactic acid in preparation of medicines for relieving lung diseases, and in the application, the lung diseases are preferably pulmonary fibrosis or acute lung injury. In an acute lung injury research model, phenyllactic acid can effectively intervene in the inflammatory factor cascade reaction and oxidative stress injury process, and acute lung injury symptoms caused by the factors are remarkably improved. Compared with the traditional treatment means, the experiment proves that the phenyllactic acid or the composition containing the phenyllactic acid can obviously relieve the symptoms of acute lung injury (ALI) of mice induced by lipopolysaccharide (LPS) and pulmonary fibrosis (PF) of mice induced by bleomycin, the pathological change of the lung is effectively improved, and the lung function is recovered.

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 belongs to the field of pharmacy, and relates to a medicine for treating pulmonary fibrosis, in particular to application of an anti-Gremlin1 antibody to preparation of a medicine for preventing and treating pulmonary fibrosis. The Gremlin1 antibody disclosed by the invention can be applied to prevention and treatment of pulmonary fibrosis, effectively improves bleomycin (BLM)-induced pulmonary fibrosis lesions of mice and improves the survival rate of the mice. Compared with a BLM group, the mouse inspiration capacity (IC) and the lung static compliance (CRS) treated by the Gremlin1 antibody are remarkably improved, the hydroxyproline content in lung tissue is remarkably reduced, and compared with the BLM group, the Ashcroft score, the collagen deposition area in Masson three-color dyeing and the Sirius red dyeing area of an antibody intervention group are remarkably reduced, and the proportion of activated endothelial cells and the proportion of transition-state epithelial cells are remarkably reduced. Therefore, the Gremlin1 antibody can be used for preparing the medicine for preventing and / or treating the pulmonary fibrosis.

The invention belongs to the technical field of biological medicines, and particularly relates to application of small interfering RNA (Ribonucleic Acid) of a targeted Zyx gene. The invention provides siRNA (small interfering Ribonucleic Acid) of a targeted Zyx gene, and further provides application of the siRNA in prevention and treatment of fibrosis interstitial lung diseases. Experimental data prove that in a mouse bleomycin model, siRNA of a targeted Zyx gene can effectively improve the survival rate of a sick mouse, alveolar wall thickening, lung substantive thickening and inflammatory cell infiltration of a Zyx knock-down group are not obvious, and pathological damage caused by bleomycin is effectively relieved through knock-down of the Zyx gene; collagen fiber deposition of a Zyx knock-down group is reduced, and the transcription level of fibrosis-related genes is obviously reduced.

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.

To provide a new hepatic organoid maturation medium for induction or promotion of hepatocyte maturation within a hepatic organoid.SOLUTION: A hepatic organoid maturation medium comprises at least one selected from the group consisting of diethylenetriamine-N',N',N',N'',N''-pentaacetic acid, calcipotriene, and bleomycin.SELECTED DRAWING: Figure 8

The invention discloses an application of an exosome carrying miR-486 in pulmonary interstitial fibrosis, and belongs to the technical field of biological medicines, and the exosome carrying miR-486 is an exosome carrying miR-486 from umbilical cord stem cells; according to the application disclosed by the invention, the umbilical cord stem cell-derived exosome carrying the miR-486 is used for treating the pulmonary interstitial fibrosis for the first time, and the action mechanism of the umbilical cord stem cell-derived exosome carrying the miR-486 is that the umbilical cord stem cell-derived exosome carrying the miR-486 regulates fibroblast MRC-5 cell differentiation and collagen deposition through targeting FGF9; the development process of pulmonary interstitial fibrosis is improved and delayed by improving lung inflammation of mice with pulmonary interstitial fibrosis caused by bleomycin, reducing collagenous fiber deposition, inflammatory response, ECM process and pulmonary vascular structure reconstruction, and a new way is provided for treatment of the disease.

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 provides a liquid gate graphene transistor antibiotic sensor for realizing real-time detection of bleomycin. According to the method, a probe ssDNA is fixed on the surface of a gate electrode of a graphene transistor through an Au-S bond. Wherein coexistence of Fe (II) and bleomycin can cause formation of a binary compound BLMFe (II), oxygen can be reduced into free radicals at recognition sites, and DNA degradation capacity is achieved. A BLMFe (II) complex is added into an electrolyte, ssDNA and BLMFe (II) react at a recognition site, so that part of ssDNA fragments fall off from the surface of a gate electrode, the double-electrode-layer interface characteristic between a transistor and a sample solution is changed, and Dirac point voltage and current in a graphene channel are changed. According to the graphene transistor antibiotic sensor provided by the invention, the drain voltage is fixed, the grid potential is changed, the lowest detection limit of bleomycin can reach 10 <-18 > M, bleomycin solutions with different concentrations are added, the current of the sensor is changed immediately, and the graphene transistor antibiotic sensor has very high sensitivity.

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 invention discloses an acid-resistant microalgae construction method based on bicarbonate ion transporter protein, and belongs to the field of biology and molecular biology. The method specifically comprises the following steps: taking Phatr3J33543 with a sequence structure as shown in SEQ ID No.1, Phatr3J50516 with a sequence structure as shown in SEQ ID No.2 or Phatr3Jdraft1806 with a sequence structure as shown in SEQ ID No.3 as a target gene, removing a termination codon of the target gene, and connecting a fluorescent protein gene with an initiation codon removed through a DNA (Deoxyribose Nucleic Acid) sequence for coding glycine to obtain a recombinant gene; inserting the recombinant gene into multiple cloning sites of a pPhaNR plasmid to obtain a vector plasmid; introducing the carrier plasmids into diatom cells through electroporation, and inoculating the diatom cells to an ESAW solid selective culture medium containing bleomycin to grow brown algal colonies; selecting the algal colonies with fluorescent protein signals from the algal colonies, namely the acid-resistant engineering algae. Compared with wild algae, the acid resistance of the engineering algae obtained by the invention is obviously improved. The method has important reference significance on acid-resistant diatom cultivation.

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 relates to the field of medicine and genetic engineering, specifically to guide RNAs and DNA fragments and to cell selection methods, which can be used in CRISPR-Cas9 systems for producing lines of natural killer cells with a PD-1 knockout gene and increased production of TRAIL or Fas-ligand proteins. Methods are disclosed for producing modified lines of NK cells: with a PD-1 knockout gene and constitutive Fas-ligand overexpression, with a PD-1 knockout gene and constitutive TRAIL overexpression, and also a method is described for selecting modified NK cells with a PD-1 knockout gene, which is carried out using a zeocin selection marker. The invention makes it possible to produce a high yield of modified lines of NK cells that are highly active in inhibiting the growth of tumour cells.

The invention provides application of nobiletin and nintedanib combined administration in treatment of pulmonary fibrosis, and belongs to the technical field of combined medication. The invention provides application of nobiletin and nintedanib combined medicine in preparation of medicine for preventing and / or treating pulmonary fibrosis. According to the invention, TGF-beta1 is adopted to induce MRC-5 cells to establish an in-vitro pulmonary fibrosis model, and bleomycin is adopted to induce a C57BL / 6J mouse to establish an in-vivo pulmonary fibrosis model. Researches find that the combination of nobiletin and nintedanib can inhibit MRC-5 cell epithelial-mesenchymal transition and significantly down-regulate the expression of fibrosis marker protein. In-vivo experiments show that nobiletin and nintedanib are combined to obviously improve the pathological state of mouse pulmonary fibrosis. The nobiletin and the nintedanib are combined to play an obvious treatment role in inhibiting the pulmonary fibrosis, so that the nobiletin and the nintedanib can be used as potential medicines for preventing and treating the pulmonary fibrosis, and new clues and ideas are provided for developing medicines for treating the pulmonary fibrosis.

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.

The present invention relates to a pharmaceutical composition for preventing or treating flavivirus infections. The invention provides a pharmaceutical composition. The pharmaceutical composition comprises at least one of gentamicin sulfate, netilmicin, tobramycin, paromomycin, amikacin, capreomycin, triflurazine, dihydrostreptomycin, hydroxychloroquine, thiolidazine hydrochloride, efavirenz, mitefonew, nystatin, micafungin, bleomycin, remistat, montelukast, norfloxacin, nedaplatin and cephalosporin, and the pharmaceutical composition is prepared from the following raw materials in parts by weight. It is possible to exhibit an excellent growth inhibition or inactivation effect on different species of flavivirus.

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 a preparation method and application of a cowpea fat transfer protein microcapsule, and the preparation method comprises the following steps: step 1, connecting a base sequence of a parent to a pGAPZ alpha A carrier to obtain a recombinant plasmid, and transforming the recombinant plasmid into escherichia coli DH5alpha; 2, inoculating the escherichia coli DH5 alpha into an LB culture medium in a monoclonal manner, and extracting plasmids; 3, carrying out enzyme digestion and purification to obtain high-concentration linearized plasmids; 4, electrically transferring the linearized plasmids into pichia pastoris competent cells, and coating the cells on a bleomycin YPD solid plate for culturing; 5, selecting single colonies, and further screening, culturing and purifying to obtain the cowpea fat transfer protein; step 6, mixing the cowpea fat transfer protein with sodium alginate, and wrapping chitosan to obtain cowpea fat transfer protein microcapsules; the preparation method is easy to purify and low in production cost, and can be used for foods, dietary supplements and the like; and the cowpea fat transfer protein microcapsule prepared after modification is relatively high in stability.

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 application belongs to the technical field of medicine, and relates to a 4,5-dihydro-3H-pyrrolo[2,3-c]quinolin-4-one derivative and application thereof in ATX enzyme inhibition and in preparation of a drug for treating and / or preventing a disease caused by an abnormal ATX-LPA function axis, in particular, in preparation of a drug for treating and / or preventing a fibrosis disease and cancer. The derivative is a compound as shown in a general formula (I) and a pharmaceutically acceptable salt thereof. In vitro activity screening shows that the compound has outstanding ATX enzyme inhibition activity and certain anti-tumor cell proliferation activity, and shows better anti-fibrosis activity in a bleomycin-induced pulmonary fibrosis model, and has a good application prospect.