12 results about "Bleomycin" patented technology

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.

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.

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 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.

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 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 discloses application of Rineterkib combined with a DNA damaging agent in preparation of a SLFN11-deficient tumor treatment drug. Rineterkib can significantly restore the sensitivity of SLFN11-deficient tumor cells to DNA damaging agents (such as 2-fluoroadenine, cisplatin, bleomycin and etoposide). Further research shows that Rineterkib can achieve a synergistic killing effect on SLFN11-deficient tumor cells by blocking DNA damage repair, inducing G2 / M phase arrest and promoting cell apoptosis.

This invention relates to the application of tanshinone A ester derivatives with carbon chain lengths of C1-C2, as shown in Formula I, in the preparation of drugs for treating idiopathic pulmonary fibrosis. This invention systematically investigated the oral absorption behavior of tanshinone A ester derivatives of different carbon chain lengths in rats, and confirmed through in vitro HFL1 cell models and in vivo bleomycin-induced pulmonary fibrosis mouse models that these short-chain ester derivatives (methyl and ethyl esters) can significantly improve oral bioavailability and inhibit TGF-β1-induced α-SMA expression and extracellular collagen deposition, demonstrating significantly superior characteristics compared to the original tanshinone A and its long-chain ester derivatives. Most importantly, cytotoxicity experiments showed a significantly improved safety profile, demonstrating an excellent therapeutic window. This invention overcomes the shortcomings of low bioavailability and well-defined toxicity of tanshinone A in existing technologies, providing a more efficient and safer new drug option for the treatment of idiopathic pulmonary fibrosis.

This invention discloses an extracellular vesicle miRNA novel-10 derived from fresh Polygonatum rhizome and its application in the preparation of anti-cellular senescence compositions, belonging to the field of extracellular vesicle miRNA technology. Using fresh Polygonatum rhizome as the source, this invention prepares extracellular vesicles using a tangential flow filtration system and detects multiple high-abundance miRNAs from the extracellular vesicles. Among them, miRNA novel-10, shown in SEQ ID No. 1, has a high expression abundance and can significantly reduce SA-β-gal positive levels in a bleomycin-induced MRC-5 cell senescence model, and can be used to prepare anti-cellular senescence compositions.

The application discloses application of an RRBPl protein inhibitor in preparation of a product with a protective effect on lung fibrosis, and belongs to the technical field of biological medicines. The product with the protective effect on lung fibrosis refers to a medicine or a recombinant carrier for inhibiting expression of RRBPl protein, and the recombinant carrier contains or carries a polynucleotide for coding RRBPl shRNA. The application further discloses an adeno-associated virus carrier with the protective effect on lung fibrosis and carrying RRBPl shRNA, which is beneficial to protecting lung fibrosis induced by bleomycin, reducing infiltration of myofibroblasts and deposition of extracellular matrix. In-vivo cell experiments find that RRBPl knockdown can inhibit transdifferentiation of human primary lung fibroblasts into myofibroblasts and deposition of extracellular matrix. These results show that RRBPl can be targeted to treat or prevent fibroproliferative diseases. The application provides a new method for treating fibroproliferative diseases.