95 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.

A method for treating a flavivirus infection includes administering to a subject in need thereof a composition which includes at least one of gentamicin sulfate, netilmicin, tobramycin, paromomycin, amikacin, capreomycin, trifluoperazine, dihydrostreptomycin, hydroxychloroquine, thioridazine HCl, efavirenz, miltefosine, nystatin, micafungin, bleomycin, resminostat, montelukast, norfloxacin, nedaplatin and cephalothin, which can exhibit excellent growth inhibition or killing effects of various species of flavivirus genus.

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 belongs to the field of biological agents, and particularly relates to application of polypeptide HRH and analogues thereof in preparation of drugs for treating pulmonary fibrosis. The amino acid sequence of the polypeptide HRH disclosed by the invention is NH2-His-Arg-His-Thr-Lys-Gln-Arg-His-Thr-Ala-Leu-His-CONH2. An in-vitro experiment proves that the polypeptide HRH can be used for effectively inhibiting pulmonary epithelial cell and fibroblast fibrosis induced by a transforming growth factor and silicosis fibrosis induced by silicon dioxide; in-vivo experiments further prove that the HRH can improve bleomycin-induced pulmonary fibrosis lesion of mice and improve weight loss and death rate of the mice, and meanwhile, the HRH has relatively high safety and no adverse toxic or side effect. The invention also provides an HRH polypeptide analogue which can more effectively inhibit the activation of fibroblasts. The polypeptide HRH prepared by the invention is low in dosage, safe and effective, and provides a potential new medicine for treating pulmonary fibrosis diseases.

The invention belongs to the technical field of application of plant exosomes, and discloses a plant-derived hybrid exosome and application of the plant-derived hybrid exosome in pulmonary fibrosis resistance. After screening a proper proportion, the obtained hybrid exosome has an obvious treatment effect on a mouse with pulmonary fibrosis induced by bleomycin, and the treatment effect is specifically shown as follows: (1) the hybrid exosome can obviously relieve lung inflammatory cell infiltration of the model mouse, protect a pulmonary alveolar structure and relieve the degree of pulmonary fibrosis; (2) the hybrid exosome can effectively reduce the expression levels of TNF-alpha, IL-1beta and IL-6, and can effectively slow down the pulmonary fibrosis process; the lung tissue inflammation is inhibited; and (3) the hybridized exosome inhibits the generation of ECM (extracellular matrix) and inhibits epithelial mesenchymal transition, so that the anti-fibrosis effect is achieved. The plant source hybrid exosome prepared by the invention is wide in plant source, simple in exosome preparation process and low in cost, and provides new possibility for treating pulmonary fibrosis.

The present invention relates to use of CXCL11 for treating pulmonary fibrosis by inducing the repolarization of M2 macrophages. Specifically, a fibrosis treatment effect was confirmed through the injection of M0, M1 and M2 conditioned media (CM) by using a bleomycin-induced pulmonary fibrosis animal model, and a reduction in fibrosis markers such as collagen and a change in the M1 / M2 ratio close to a normal group were confirmed in the lungs of mice into which the M1 macrophage CM was injected. Also, the fibrosis treatment effect was confirmed through the intravenous injection of human recombinant CXCL11 by using a bleomycin-induced pulmonary fibrosis animal model, and a reduction in fibrosis markers such as collagen and a change in the M1 / M2 ratio close to a normal group were confirmed in the lungs of mice to which CXCL11 was administered. That is, the present invention aims to induce the repolarization of M2 macrophages through CXCL11 in the process of developing pulmonary fibrosis, and thus CXCL11 is presented as a potential target factor for the treatment of pulmonary fibrosis.

The invention belongs to the technical field of biological medicines, and particularly relates to an MAF vaccine as well as a preparation method and application thereof. In order to develop a nasal spray type vaccine capable of effectively preventing and treating fibrotic interstitial lung diseases and avoiding risk increase caused by local inflammatory reaction, the invention adopts two modes of taking a synthesized MAF protein as a model antigen, encapsulating the MAF protein by using a TLR7 adjuvant to form a peptide fragment vaccine or constructing an MAF adenovirus vaccine based on an adenovirus vector. Two vaccines based on the MAF target spot are successfully constructed. Animal experiment results prove that the two vaccines based on the MAF target spot have treatment and prevention effects on bleomycin-induced mouse pulmonary fibrosis models during nasal dripping immunization, and also have good safety in vivo. A good candidate vaccine is provided for future fibrotic disease prevention and treatment vaccine transformation research and clinical experiment development.

The invention provides a method for constructing an animal model with sicca syndrome combined with pulmonary fibrosis, and relates to the technical field of animal model construction.The method comprises the following steps that 8-week-old NOD / Ltj mice qualified in quarantine are purchased and fed for 12 weeks; in 12 weeks, bleomycin (BLM) is injected into the mouse in the trachea, the injection dosage of bleomycin is 3 mg / kg, and construction of the sicca syndrome combined pulmonary fibrosis animal model is completed 21 days after injection. The SS-PF mouse model disclosed by the invention has high repeatability and stability, can be constructed on a large scale, and is suitable for various research requirements. The model is not only suitable for basic research, but also can be applied to drug screening and curative effect evaluation, and has a wide application prospect. Through the model, large-scale drug screening experiments can be carried out, the effectiveness and safety of drugs can be evaluated, a new treatment choice is provided for SS-PF patients, and the clinical treatment effect is improved.

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 present invention discloses a method for constructing acid-resistant engineered algae, belonging to the fields of biology and molecular biology. The specific method is as follows: Using Phatr3_J33543 with the sequence structure shown in SEQ ID No.1, Phatr3_J50516 with the sequence structure shown in SEQ ID No.2, or Phatr3_Jdraft1806 with the sequence structure shown in SEQ ID No.3 as the target gene, removing the stop codon of the target gene, and connecting the fluorescent protein gene without the start codon through the DNA sequence encoding glycine to obtain a recombinant gene; inserting the recombinant gene into the multiple cloning site of the pPhaNR plasmid to obtain a vector plasmid; introducing the vector plasmid into diatom cells by electroporation and then inoculating them onto the ESAW solid selection medium containing bleomycin, and growing brown colonies; selecting the colonies with fluorescent protein signals in the colonies, which are the acid-resistant engineered algae. Compared with the wild algal species, the acid-resistant ability of the engineered algae obtained by the present invention is significantly improved. The present invention has important reference significance for the cultivation of acid-resistant diatoms.

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 invention relates to a method for establishing an idiopathic pulmonary fibrosis model through in-situ injection of bleomycin in unilateral lung tissue. According to the method, lung tissue is directly exposed in a surgical operation mode, and bleomycin solution is introduced into the lung in a direct injection mode. Wherein the difficulty of exposing the lung tissue by the surgical operation is obviously reduced compared with that of exposing the lung tissue by the traditional trachea, so that the applicability of the disease model is greatly improved. And secondly, the bleomycin solution is directly injected into the lung tissue, so that the operability is better than that of a mode of atomizing from a trachea. The death rate of animals with successful modeling is 0, vital signs such as the body weight of the animals are not abnormal, histopathologic examination shows that the bleomycin is more uniformly distributed in lungs after direct injection, and the injury degrees of all areas of the lungs are similar.

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 belongs to the technical field of medicines, and relates to a 4, 5-dihydro-3H-pyrrolo [2, 3-c] quinoline-4-ketone derivative, an application of the 4, 5-dihydro-3H-pyrrolo [2, 3-c] quinoline-4-ketone derivative as an ATX enzyme inhibitor, and an application of the 4, 5-dihydro-3H-pyrrolo [2, 3-c] quinoline-4-ketone derivative in preparation of drugs for treating and / or preventing diseases caused by ATX-LPA functional axis abnormality. The invention particularly relates to application in preparation of drugs for treating and / or preventing fibrosis diseases and cancers. The derivative is a compound as shown in a general formula (I) and pharmaceutically acceptable salt thereof, and in-vitro activity screening shows that the compound has outstanding ATX enzyme inhibitory activity and certain anti-tumor cell proliferation activity, shows better anti-fibrosis activity in a bleomycin-induced pulmonary fibrosis model, and has a good application prospect. # imgabs0 #

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 invention belongs to the field of biomedical animal models, and specifically discloses a method for establishing an adenovirus-induced acute exacerbation of pulmonary fibrosis animal model, which comprises at least the following steps: on the basis of establishing a mouse pulmonary fibrosis model with bleomycin, inducing acute exacerbation symptoms AE by tracheal administration of an adenovirus vector Ad without replication activity, so as to form an adenovirus-induced acute exacerbation of pulmonary fibrosis animal model AE-IPF; the invention adopts intratracheal injection administration under direct vision of a mouse laryngoscope, which can not only ensure the reliability and accuracy of administration, but also reduce damage to mice, improve survival rate and humanitarian protection; the administration time is preferably on the 14th day (mouse pulmonary fibrosis stage), and it is a single administration, which highly simulates clinical practice and relieves the pain of mice; creatively selecting inactivated adenovirus can not only simulate the possible induction of AE in IPF patients after viral infection, but also reduce environmental pollution and toxic side effects, and reduce the risk of infection for experimental personnel.

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.