14 results about "Apoptosis resistance" patented technology

The invention belongs to the technical field of gene engineering and cell transformation, and discloses a gene engineering construction method and application of anti-apoptosis human mesenchymal stem cells. Through HDAC1 K412 site specific lactic acid mutation, breakthrough improvements are realized: for example, CRISPR-Cas9-mediated accurate gene editing is utilized, only a single amino acid site is changed, that is, K412R mutation simulates persistent lactic acid, and whole genome apparent modification disturbance can be avoided; the modification does not depend on an exogenous metabolic substrate, and the negative feedback effect of traditional metabolic intervention is overcome; the mutant continuously inhibits a P53 apoptosis pathway, so that the oxidative stress mediated apoptosis resistance of the MSC is remarkably improved. According to the design concept of one target spot and one regulation, the core contradiction that long-term effectiveness and specificity cannot be considered in the prior art is fundamentally solved, and a brand new normal form is provided for stem cell treatment.

The present invention relates to the stratification and treatment of patients suffering of cancer. Due to the fact that anti-PD1 therapy targets lymphocytes and the efficiency of anti-cancer therapy is measured by the impact on the tumor cells, the inventors postulated that studying the molecular mechanisms of resistance of anti-PD1 therapy should take into consideration existing intercellular communication between lymphocytes and tumor cells. As exosomes are the carriers for the intercellular transfer of the miRNA responsible of chemoresistance, they herein investigated whether exposure of T cells to anti-PD1 therapy might promote the expression of exosomal miRNA (exomiR) causing the chemoresistance of cancer cells. Surprisingly, they found that anti-PD1 exposure of T-cell promotes an enrichment of exosomal miRNA-4315. They also noted that exosomal miRNA-4315 induced a phenomenon of apopto-resistance to conventional chemotherapies in cancer cells receiving exosomal miRNA-4315. At molecular level, they discern that the apopto-resistance phenomenon was associated with the miRNA-4315-mediated down-regulation of Bim, a pro-apoptotic protein. In cellular and mice models, they observed that the BH3 mimetic agent ABT263 circumvented this resistance. Thus, the invention relates to methods of stratification using exosomal miRNA-4315 and method of treatment of patients suffering of cancer using BH3 mimetic agent.

The invention relates to a 5-[1, 2, 4-oxadiazole]-6-oxygen-pyrazolopyridine derivative as well as a preparation method and application thereof, the 5-[1, 2, 4-oxadiazole]-6-oxygen-pyrazolopyridine derivative and pharmaceutically available salt thereof have a general formula as shown in a formula (II): # imgabs0 #, and the definition of substituent groups is shown in the specification. The 5-[1, 2, 4-oxadiazole]-6-oxygen-pyrazolopyridine derivative and the pharmaceutically available salt thereof have the effects of inhibiting the interaction of Hsp110-STAT3, so that the levels of p-STAT3 and c-Myc are reduced, and the proliferation, migration and apoptosis resistance of pulmonary artery endothelial cells are inhibited; the pulmonary arterial pressure is reduced, and the pulmonary vascular reconstruction degree is improved, so that the effect of resisting pulmonary arterial hypertension is achieved.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tripterine-platinum (IV) complex with antitumor activity as well as a preparation method and application of the tripterine-platinum (IV) complex. The tripterine-platinum (IV) complex takes tripterine as an axial ligand, and a platinum center skeleton structure is cis-platinum, carboplatin or oxaliplatin. The tetravalent platinum complex can induce para-apoptosis of cancer cells, so that the common problem of drug resistance caused by apoptosis resistance of the cancer cells in tumor chemotherapy is solved. Besides, the tetravalent platinum complex has the characteristics of high efficiency and low toxicity, the in-vitro cytotoxicity of the tetravalent platinum complex to tumor cells such as non-small cell lung cancer A549 cells and cisplatin-resistant strains A549cisR thereof is higher than that of clinically applied metal anti-cancer drug cisplatin, and the tetravalent platinum complex has low toxicity to normal cells MRC-5, so that the tetravalent platinum complex has a good application prospect. Good selectivity and relatively high medicinal value are shown in the aspect of inhibiting the growth of tumor cells.

The invention relates to the technical field of AKI treatment, in particular to a preparation method and application of nanoparticles, hyaluronic acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine are taken and dissolved in a dimethyl sulfoxide solution, stirring is performed to form carboxyl of HA, and a reaction system is prepared; adding urolithin A into a reaction system, stirring, adding citric acid and cerium nitrate hexahydrate, pouring an ammonia water solution, and stirring overnight; transferring the solution obtained by stirring overnight into a dialysis bag, and dialyzing to remove water-soluble by-products; centrifuging the dialyzed solution so as to remove water insoluble by-products; and then freeze-drying is carried out, such that the nanoparticles HUCNPs are obtained. The HUCNPs nanoparticles disclosed by the invention can be targeted to damaged kidneys, and compared with the existing urolithin A, the HUCNPs nanoparticles disclosed by the invention have the effects of stronger ROS (reactive oxygen species) removal capability, more effective reduction of inflammatory response of HK-2 cells under stimulation, better apoptosis resistance, better mitochondrial protection effect and the like, and have an unexpected AKI treatment effect.

The present invention relates to a method for producing stem cells with increased engraftability and various uses thereof. Stem cells introduced with the exon 2-deleted AIMP2 variant of the present invention showed excellent engraftability as engraftment protein expression, cell number, cell viability, and apoptosis resistance increased. Therefore, the stem cells of the present invention can be activated in a form suitable for transplantation and administration with excellent human-body compatibility and economically manufactured in large quantities. Therefore, they are appropriate as cell therapy products and can be used in related industries.

The present application relates to 5-[1,2,4-oxadiazole]-6-oxygen-pyrazolopyridine derivatives and preparation method and application thereof, and the 5-[1,2,4-oxadiazole]-6-oxygen-pyrazolopyridine derivatives and pharmaceutically acceptable salts thereof, the general formula is as shown in formula (II): wherein, the definition of substituent group is described in the specification. The 5-[1,2,4-oxadiazole]-6-oxygen-pyrazolopyridine derivatives and pharmaceutically acceptable salts thereof of the present application have the functions of inhibiting Hsp110-STAT3 interaction, thereby down-regulating p-STAT3 and c-Myc levels, inhibiting pulmonary arterial endothelial cell proliferation, migration and apoptosis resistance, reducing pulmonary arterial pressure and improving the degree of pulmonary vascular remodeling, and further playing the role of anti-pulmonary arterial hypertension.

The present application discloses a method and device for intelligent identification of third-generation EGFR-TKIs-resistant lung adenocarcinoma organoids, relating to the technical field of lung adenocarcinoma organoid identification. The method includes: obtaining a training set; obtaining an OncoAGMS-U-Net++ model; training the OncoAGMS-U-Net++ model with the training set to obtain a trained OncoAGMS-U-Net++ model; obtaining image data of a sample to be identified, where the image data of the sample to be identified includes bright-field image data to be identified, fluorescence image data to be identified, and spatial probability map data of gene mutations to be identified; inputting the image data of the sample to be identified into the OncoAGMS-U-Net++ model to obtain a drug resistance region probability map, a volume change rate, an apoptosis resistance intensity, and a drug resistance type probability output by the OncoAGMS-U-Net++ model. The OncoAGMS-U-Net++ model created in the present application focuses on the drug resistance of lung adenocarcinoma organoids from four dimensions, and can more accurately model the complex phenotypes of third-generation EGFR-TKIs-resistant lung adenocarcinoma through multi-modal data fusion and drug resistance feature enhancement strategies.

The invention relates to the technical field of biological medicines, in particular to an AAV virus vector carrying a VEGFB (vascular endothelial growth factor B) gene and application of the AAV virus vector in preparation of a medicine for treating retinitis pigmentosa. The invention provides an AAV virus vector carrying a VEGFB gene and application of the vector in preparation of a medicine for treating retinitis pigmentosa. A VEGFB gene is combined with an AAV virus vector to construct a recombinant virus vector capable of effectively transfecting retinal cells and expressing VEGFB protein, and effective treatment on retinitis pigmentosa is realized by utilizing biological functions of oxidation resistance, apoptosis resistance, angiogenesis inhibition and the like of the VEGFB protein.

The invention relates to the technical field of biological medicines and nano preparations, in particular to a preparation method and application of a ginseng-sourced nano-like particle loaded medicine. The method comprises the following steps: S1, extracting a ginseng exosome; s2, purifying the ginseng exosome; and S3, preparing the drug-loaded nanoparticles. According to the invention, GENs is taken as an oral carrier, the problem of low bioavailability of free drugs is solved, the drug stability is enhanced by a natural phospholipid double-layer structure, and intestinal absorption and liver targeting accumulation are facilitated. The dual effects of the active ingredient of the GENs and the loaded drug are obviously better than that of a single drug; and oxidation resistance, inflammation resistance, fibrosis resistance and apoptosis resistance are synchronously realized. By repairing ZO-1 / Occludin, an intestinal barrier is reconstructed, intestinal toxin entering the liver is reduced, and meanwhile, liver injury and fibrosis disappearance are improved; a new strategy is provided for high-valued transformation of ginseng resources, and the safety of the plant exosome is far higher than that of a synthetic vector.

The invention discloses a serum-free culture medium for hypoxia culture of mesenchymal stem cells as well as a preparation method and application of the serum-free culture medium. The serum-free culture medium comprises a basic culture medium, ginsenoside Rg1, asiaticoside, sodium pyruvate, recombinant human albumin and recombinant transferrin. The invention further discloses a preparation method of the corresponding serum-free culture medium. The preparation method comprises the steps of weighing and dissolving the components, filtering and sterilizing and the like. The invention also correspondingly discloses application of the serum-free culture medium. The sodium pyruvate, the recombinant human albumin and the recombinant transferrin are added to guarantee nutrition supply and function maintenance of the mesenchymal stem cells in a low-oxygen environment, and the ginsenoside Rg1 and the asiaticoside are added to synergistically promote proliferation, oxidation resistance and apoptosis resistance of the mesenchymal stem cells. The proliferation rate of the cultured mesenchymal stem cells and the expression and differentiation capacity of specific surface markers of the stem cells are improved, the apoptosis rate of the cells is remarkably reduced, and the method has wide application prospects in the fields of cell culture, regenerative medicine and the like.

The invention provides application of an aurora kinase B inhibitor in preparation of a medicine for treating pulmonary arterial hypertension, and relates to the technical field of medicines. The application of the aurora kinase B inhibitor in preparing the medicine for treating the pulmonary arterial hypertension, provided by the invention, can be used for remarkably improving pulmonary vascular remodeling caused by excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells, so that the pulmonary arterial hypertension is effectively relieved; the defect that the occurrence and development of pulmonary vascular remodeling cannot be fundamentally reversed by the conventional targeted therapy is overcome, and the long-term poor prognosis of a patient can be favorably improved. According to the application, a specific inhibitor AZD1152-HQPA of aurora kinase B is adopted to intervene in two representative pulmonary arterial hypertension rat models, and it is found that inhibition of the kinase activity of aurora kinase B has a good curative effect on pulmonary arterial hypertension. The invention clarifies a new application of AZD1152-HQPA in treating pulmonary arterial hypertension, and provides a new medicine for treating pulmonary arterial hypertension by targeting aurora kinase B.

The invention belongs to the crossing field of coordination chemistry and biomedicine, and relates to a pair of chiral iridium (III) complex photosensitizers delta-Ir-Car and lambda-Ir-Car with high singlet oxygen quantum yield, a preparation method of the chiral iridium (III) complex photosensitizers delta-Ir-Car and lambda-Ir-Car and application of the chiral iridium (III) complex photosensitizers in photodynamic therapy. Although the two enantiomers are almost the same in ultraviolet visible absorption and phosphorescence emission properties, the two enantiomers exhibit chiral dependent biological activity. Compared with the lambda-Ir-Car, the delta-Ir-Car has the advantage that the cell uptake efficiency of the delta-Ir-Car is higher. In an aqueous solution, the singlet oxygen generation capacities of the delta-Ir-Car and the delta-Ir-Car are equivalent, but at the cellular level, the delta-Ir-Car shows higher active oxygen generation capacity. More importantly, the two complexes can induce pyroptosis, and have the potential of overcoming apoptosis drug resistance and activating anti-tumor immune response. Due to the dual capabilities, the delta / lambda-Ir-Car becomes a creative drug combining photodynamic therapy and anti-tumor immunity. The preparation method disclosed by the invention is simple and convenient, high in yield and good in repeatability, and the prepared iridium complex is expected to be applied to photodynamic therapy of tumors.

The utility model belongs to the field of medical instruments, particularly relates to a device for screening medicines for resisting colorectal cancer pulmonary metastasis, and provides the following scheme aiming at the problem that a plurality of links of apoptosis resistance, liquid-phase shearing force resistance and the like of cancer cells in blood flow cannot be simulated in the prior art: the device comprises a screening mechanism, the screening mechanism comprises a liquid-phase flowing assembly and a plurality of diversion grooves, the diversion grooves and the liquid-phase flowing assembly form a closed circulating flowing system, the colorectal cell culture medium serving as a flowing liquid phase circularly flows in the system, and colorectal cancer cells circularly flow in the liquid phase and interact with lung organs. The condition is close to the in-vivo condition; a plurality of processes of cancer cell metastasis are simulated in vitro, the drug can be sensitively reflected to a fluorescence intensity result as long as the drug can generate an intervention effect on one of the links, and screening of a plurality of anti-metastasis new drugs is facilitated; the method belongs to an in-vitro screening model and is simple to operate.