9 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 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 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.