35 results about "Apoptosis pathway" patented technology

The invention discloses a probe BBM for anchoring OPA1 protein and application of the probe BBM, and belongs to the technical field of biological analysis. Based on the characteristic that the OPA1 protein is rich in hydrophobic amino acid residues and polar amino acids, the probe BBM capable of generating multiple interaction forces with the OPA1 protein is designed by reasonably introducing hydrophobic groups and polar groups. Theoretical calculation and experimental results (including OPA1 knock-down and overexpression) show that the probe realizes efficient enrichment in a mitochondrial inner membrane region. By using the unique probe, the hydrogen peroxide induced mitochondrial inner membrane viscosity change is systematically researched, and the myocardial cell oxidative damage is further confirmed to be realized by a p53 protein mediated apoptosis pathway. The method provides a reliable means for accurately evaluating the oxidative stress of the mitochondrial inner membrane, and has important promotion significance for the development of the cardiovascular research field.

The invention discloses an application of Lumacaftor in the treatment of Parkinson's disease. The treatment effect of Lumacaftor on PD is verified through in-vitro cell experiments and in-vivo animal experiments respectively, and it is found that after Lumacaftor is used in a microglial cell-neuron co-culture PD cell model, apoptosis pathway related protein in neurons is remarkably reduced compared with a model group; after Lumacaftor treatment is performed on a PD mouse in an MPTP mouse PD model, dopaminergic neurons of the PD mouse are remarkably increased, and the motor function is improved. The application provides a new thought for effective treatment of PD, and the application prospect is wide.

The application discloses application of NDUFB4 as a target point in preparation of a drug for treating bladder cancer. Single cell analysis results show that NDUFB4 is highly enriched in bladder cancer epithelial cells, and can be used as a key coordinator to participate in the regulation of multiple carcinogenic signal pathways. Through shRNA-mediated gene silencing and CRISPR / Cas9-mediated gene knockout experiments, it is found that NDUFB4 deletion can significantly inhibit the proliferation, migration and invasion ability of bladder cancer cells, and cause a serious bioenergy crisis, and activate the endogenous apoptosis pathway. In a subcutaneous xenotransplant tumor model, it is further verified that NDUFB4 silencing can significantly inhibit tumor growth. The application discloses that NDUFB4 is a key coordinator between mitochondrial high-functionality and carcinogenic signal pathways, and it is suggested that NDUFB4 can become a potential target for bladder cancer treatment.

Provided are biomarkers for predicting the efficacy of an MDM2 inhibitor or a Bcl-2 / Bcl-xL dual inhibitor or a Bcl-2 inhibitor or a Bcl-xL inhibitor in treating a cancer patient. Also provided are compositions, e.g., kits, for assessing gene levels of the biomarkers, and methods of using such gene levels to predict the response of a cancer patient to an MDM2 inhibitor or a Bcl-2 / Bcl-xL dual inhibitor or a Bcl-2 inhibitor or a Bcl-xL inhibitor. Such information can be used to determine the prognosis and treatment selection of a cancer patient.

The invention provides nanoparticles for tumor photodynamic therapy and a preparation method, a pharmaceutical composition and application thereof, and belongs to the technical field of nano biomedicine. The nanoparticle for tumor photodynamic therapy comprises: an up-conversion nanoparticle; the phospholipid layer is used for coating the up-conversion nano-particles; the nucleic acid aptamer and the endoplasmic reticulum targeting peptide are modified on the surface of the phospholipid layer; and a photosensitizer supported on the surface of the nanoparticle. The nucleic acid aptamer and the endoplasmic reticulum targeting peptide are further co-modified on the basis of the surface of the upconversion nano-particle subjected to phospholipidation treatment, so that the nano-particle can actively recognize tumor cells and deliver the tumor cells to the endoplasmic reticulum, and dual targeting on the tumor cells is realized. The loaded photosensitizer can generate reactive oxygen species (ROS) under excitation of near-infrared light, endoplasmic reticulum stress is specifically induced, then a cell apoptosis pathway is activated, and tumor cells are killed.

The invention provides application of a preparation for activating RIPKs / MLKL mediated necroptosis signal transduction in preparation of a medicine for reversing taxol drug resistance of ovarian cancer, and belongs to the technical field of biological medicine. It is found for the first time that disulfiram (DSF) can reverse ovarian cancer paclitaxel drug resistance and enhance sensitivity of ovarian cancer paclitaxel drug-resistant cells to paclitaxel. A further research discovers that the DSF is used for enhancing RIPKs / MLKL mediated necroptosis signal transduction by combining an apoptosis-inducing factor (AIF), and finally, the chemosensitivity of the paclitaxel drug-resistant ovarian cancer cells is enhanced through a caspase-dependent apoptosis pathway. The invention deeply studies an ovarian cancer paclitaxel drug resistance mechanism, discovers a new application of DSF in reversing ovarian cancer paclitaxel drug resistance, and provides a new choice for treating paclitaxel drug-resistant ovarian cancer.

The invention discloses application of salvianolic acid C in preparation of a medicine for preventing and / or treating retinal ischemia hypoxic nerve injury diseases, and relates to the technical field of biological medicines. The invention proposes and verifies for the first time that salvianolic acid C can significantly promote the formation of stress particles in photoreceptor cells under retinal ischemia and hypoxia conditions, and drives the salvianolic acid C to be assembled into a stress particle-mitochondrial micro-region in a mitochondrial adjacent region. The microcell is enriched in DDX3X, LARP1 and other key RNA binding proteins and multiple mitochondrial related proteins to cooperatively maintain mitochondrial membrane potential, inhibit mPTP opening and reduce ROS generation, so that an endogenous apoptosis pathway is inhibited, and the neuroprotective effect on a photoreceptor is achieved. On the basis, the salvianolic acid C is used for preparing the medicine for preventing and / or treating the retinal ischemia hypoxia nerve injury disease, can be used as a nerve protection supplement for existing anti-VEGF treatment, and has innovativeness and application value.

The invention discloses application of TAB2 in diagnosis and treatment of Parkinson's disease. According to the present invention, the PD patient midbrain single cell data set analysis results show that the microglial cells are significantly increased, and the Bulk transcriptome data is combined to screen the microglial cell differential gene TAB2; after TAB2 is knocked down in PD animal and cell models, apoptosis pathway related proteins in neurons are significantly reduced compared with a model group, and the motor function of PD mice is improved. Therefore, the TAB2 has a good effect of blocking the progress of the PD, and a new direction is provided for effective diagnosis and timely treatment of the Parkinson's disease.

The application provides a semi-florin chemotherapy drug and a synthesis method thereof, relates to the technical field of drug synthesis, and the semi-florin derivative exhibits significant selective anti-tumor activity, and the mechanism of action is that after entering tumor cells, the semi-florin derivative can induce the increase of the level of reactive oxygen species (ROS) in the cells, causes the collapse of the mitochondrial membrane potential, and finally triggers the late apoptosis pathway of the cells.

Compositions and methods are provided for isolating, manipulating and using for therapeutic and other purposes, mammalian, MHC Class I restricted, antigen-specific regulatory T cells. The regulatory T cells can be characterized as CD8+ cells that specifically suppress the responses of self-reactive and / or pathogenic CD4+ T cells by cytotoxic mechanisms including, without limitation, perforin, other components of the perforin / granzyme apoptosis pathway, etc. The regulatory T cells are antigen-specific, but are not activated by the same antigen as the self-reactive and / or pathogenic CD4+ T cells. In humans the regulatory T cells express inhibitory KIR proteins, e.g. one or more of KIR2DL2, KIR2DL3, and KIR3DL1.

The present application relates to the application of Necrostatin-1 in the preparation of a drug for preventing and / or treating acute aristolochic acid nephropathy. The typical pathological change of acute aristolochic acid nephropathy is the necrosis of renal tubular epithelial cells, and Necrostatin-1 can target this change to prevent and / or treat acute aristolochic acid nephropathy. Necrostatin-1 can significantly inhibit the kinase activity of RIPK1, block the endogenous and exogenous apoptosis pathways dependent on RIPK1, delay the apoptosis and GSDME-dependent pyroptosis of renal tubular epithelial cells, effectively improve the damage of renal tubular epithelial cells, and achieve the purpose of treating acute aristolochic acid nephropathy. The present application can provide a new strategy for the treatment of acute aristolochic acid nephropathy. Necrostatin-1 can be widely used in the preparation of drugs for treating acute aristolochic acid nephropathy.

Immunoassays to detect the presence of Bcl-2 family heterodimeric complexes are described. The immunoassays are designed to detect one or more of BIM-Bcl-2, BIM-Bcl-xL, BIM-Mcl-1 and BAX BAK heterodimers. The assays can be used, for example, to select a BH3 mimetic, or other drug targeting the apoptosis pathway, that is effective for treating a specific cancer, or to select a subject who is likely to respond to a particular BH3 mimetic.

The invention discloses an application of a vitamin E compound in preparation of a cIAPs protein stabilizer, and particularly, the vitamin E compound or a pharmaceutically acceptable salt thereof is combined with a BIR3 structural domain of cIAPs protein to directly inhibit degradation of cIAPs, so that a caspase-dependent apoptosis pathway and an RIPK1 / RIPK3 / MLKL-mediated programmed necrosis pathway are blocked. The new mechanism not only expands biological function cognition of vitamin E, but also provides a brand new strategy and a compound basis for developing drugs for treating diseases (such as tissue damage, autoimmune diseases and the like) related to cIAPs degradation.

The application discloses application of TAB2 in diagnosis and treatment of Parkinson's disease. Through analysis of a cerebral single cell data set of PD patients, it is shown that microglia cells are significantly increased, and a microglia cell differential gene TAB2 is screened in combination with bulk transcriptome data; after TAB2 is knocked down in a PD animal and cell model, apoptosis pathway related proteins in neurons are significantly reduced compared with a model group, and the motor function of a PD mouse is improved. It is shown that TAB2 has a good effect on blocking the progress of PD, and a new direction is provided for effective diagnosis and timely treatment of Parkinson's disease.

The invention discloses application of TRPV1, NUDT9 and MT-ND5 as targets in preparation and screening of drugs for treating brain glioma, and belongs to the technical field of biology. According to the application disclosed by the invention, experiments prove that the expression of NUDT9 and MT-ND5 in brain glioma cells is knocked down, the proliferation of the brain glioma cells is reduced, TRPV1 in the brain glioma cells is knocked down, the proliferation of the brain glioma cells is promoted, the expression of NUDT9 and MT-ND5 in the brain glioma cells is reduced by beta-elemene, and the beta-elemene has the effect of inhibiting tumor growth; the application prospect of the TRPV1, the NUDT9 and the MT-ND5 serving as the target spot in screening the medicine for treating the brain glioma is shown. According to the application disclosed by the invention, the condition that the beta-elemene and the TMZ are combined to enhance DNA damage accumulation through a synergistic effect, continuously activate a cell apoptosis pathway and increase the sensitivity of glioma cells to the TMZ is determined for the first time, so that the curative effect is improved, and the toxicity is reduced.

This invention relates to a method for extracting compound Alisma alkaloid A from Alisma plantago-aquatica and its application, effectively solving the problem of extracting Alisma alkaloids from Alisma plantago-aquatica and enabling its application in the preparation of drugs for treating lung cancer. This compound, Alisma alkaloid A, significantly reduces cell viability and Bcl2 expression, induces apoptosis and mitochondrial membrane depolarization in A549 lung cancer cells, and significantly increases the expression of Bax, Caspase3, and Caspase9, without affecting normal human lung epithelial cells BEAS-2B. It has the effect of inducing apoptosis in A549 cells through the mitochondrial apoptosis pathway, thus realizing the application of Alisma alkaloid A in the preparation of drugs for treating lung cancer. The method of this invention is scientifically sound, novel, unique, and easy to operate, effectively extracting compound Alisma alkaloid A from Alisma plantago-aquatica. This compound has the effect of inducing apoptosis in A549 cells through the mitochondrial apoptosis pathway, realizing the application of Alisma alkaloid A in the preparation of drugs for treating lung cancer, and expanding the medicinal and commercial value of Alisma plantago-aquatica.

The invention discloses an application of nano-iron carried lncRNACACF in a vascular endothelial cell (VEC). According to the invention, nano-iron-carried lncRNA CACF is taken as a research object, and the application of the nano-iron-carried lncRNA CACF in vascular endothelial cells is researched by adopting a molecular and cell biology method: through EdU, CCK8, flow cytometry, autophagy double-labeled adenovirus and Transwell cell chambers, it is found that nano-iron significantly promotes proliferation, activity, cycle process, autophagy and migration of the vascular endothelial cells and inhibits apoptosis; through qRT-PCR (quantitative real-time polymerase chain reaction), cell proliferation, cycle and expression of autophagy pathway marker genes are promoted, and expression of apoptosis pathway marker genes is inhibited; western Blot finds that cell proliferation and the level of autophagy pathway marker protein are remarkably promoted, and the level of apoptosis pathway marker protein is inhibited. In-vitro angiogenesis of vascular endothelial cells is promoted by simulating an in-vitro angiogenesis environment through matrigel.

The invention relates to the field of treatment of neurodegenerative diseases, and discloses a method for treating ALS through intrathecal targeted drug delivery of an extremely low dose of KN93 after a disease is attacked, and the method comprises the following steps: screening ALS model objects showing disease symptoms; within 24 hours after the ALS model object is confirmed to be diseased, the KN93 pharmaceutical composition is applied to the space in the spinal cord sheath for a single time; and evaluating the curative effect of the ALS model object after the KN93 pharmaceutical composition is applied. In a treatment window period within 24 hours after an ALS model object is attacked, an extremely low dose of KN93 pharmaceutical composition is directly delivered to a spinal cord intrathecal gap in an intrathecal administration manner, so that the medicine can quickly enter cerebrospinal fluid circulation and is enriched in a central lesion target region in a targeted manner without penetrating through a blood brain barrier and a blood-spinal cord barrier; therefore, pathological excessive activation of CaMKII is specifically inhibited, and injury mechanisms such as neuronal excitatory toxicity, calcium overload and pro-apoptosis pathway mediated by CaMKII are blocked.

This invention belongs to the field of pharmaceutical technology, specifically relating to the use of charred astragalus in the preparation of drugs that inhibit aristolochic acid-induced kidney damage. Animal experiments have shown that charred astragalus inhibits aristolochic acid-induced kidney damage through anti-oxidative stress, anti-inflammation, and inhibition of apoptosis pathways.

The application discloses application of Reb B in preparation of a medicine for treating lung ischemia-reperfusion injury. The application screens a natural compound Reb B by establishing an alveolar type II cell A549 ischemia-reperfusion model and combining a high-throughput drug screening mode. The Reb B can significantly enhance the OGD / R tolerance of the A549 cell by inhibiting a mitochondrial apoptosis pathway, and provides a theoretical basis for clinical application of the Reb B in ischemia-reperfusion related diseases.

The invention discloses a fusion protein containing mitochondrial pro-apoptotic protein and a preparation method thereof, and belongs to the technical field of biomedicine. The fusion protein is iRGD-MitoPen-Smac N55 (SEQ ID NO: 4), and a triple mechanism of'tumor targeting-cell / mitochondrial delivery-apoptosis activation 'is constructed by connecting an iRGD targeting peptide, a MitoPen bifunctional peptide and a Smac N55 active fragment in series. The preparation method comprises the steps of gene synthesis and optimization, vector construction, cell transfection expression and affinity purification, and the recombinant protein with the purity larger than or equal to 94% is obtained. The fusion protein can be specifically combined with alpha v integrin highly expressed by tumor cells and NRP-1, targeted delivery and mitochondrial apoptosis pathway activation are achieved, proliferation of tumor cells such as breast cancer and colon cancer is efficiently inhibited, in-vivo and in-vitro experiments prove that the anti-tumor effect of the fusion protein is remarkably superior to that of a Smac simulant LCL161, the fusion protein can be used for preparing anti-tumor drugs, and a new strategy is provided for tumor treatment.

The present disclosure provides a Lactobacillus reuteri SJ-47 with a preservation number of CGMCC No. 16416 and an exopolysaccharide secreted by the Lactobacillus reuteri SJ-47 and a preparation method thereof, which comprises: a fermentation culture step: after the Lactobacillus reuteri SJ-47 is inoculated in MRS broth and subjected to fermentation culture treatment, the fermentation broth supernatant is obtained by sterilization and separation; a crude polysaccharide extraction step: the fermentation broth supernatant is concentrated and enriched, and then subjected to first alcohol precipitation, enzymatic deproteinization, second alcohol precipitation, sevage deproteinization, dialysis and freeze-drying treatment to obtain a crude polysaccharide extract. The exopolysaccharide of the Lactobacillus reuteri SJ-47 provided in the present application has high yield and excellent performance, can effectively scavenge DPPH free radicals and hydroxyl free radicals, has good antioxidant capacity, can improve the expression levels of SOD, CAT and GSH, can increase the expression levels of type I collagen and matrix metalloproteinase, and plays a certain regulating role on the cell aging-apoptosis pathway.

The invention discloses application of plantaginin D serving as a PGAM5 inhibitor in preparation of a medicine for treating organ injury and a product, and belongs to the technical field of biological medicine. The plantaginin D is used as the PGAM5 inhibitor, targeted inhibition of key factors in necroptosis pathways is realized, expression of inflammatory factors is inhibited, mitochondrial homeostasis and organ injury are improved, and the plantaginin D has the advantages that defects of existing inhibitors are overcome, multi-organ protection is realized, and clinical transformation potential is high. The problems that an existing inhibitor is insufficient in selectivity, poor in metabolic stability and toxic and side effects are effectively solved, and safe and effective multi-organ injury intervention is achieved.

The application discloses application of a substance for inhibiting FAM111B protein activity and / or expression quantity in prevention of non-small cell lung cancer. The substance for inhibiting FAM111B protein activity and / or expression quantity is z1) or z2): z1) an RNAi molecule shown in SEQ ID NO:1; and z2) an shRNA synthesized by an shRNA expression system and taking the RNAi molecule as a target. Experiments prove that FAM111B is significantly highly expressed in non-small cell lung cancer tissues, and is obviously related to gender, histological type, tumor size, stage, and lymph node metastasis; FAM111B enhances the anti-apoptosis ability of non-small cell lung cancer cells by participating in a p53-regulated mitochondrial apoptosis pathway; and inhibition of the activity and / or expression quantity of FAM111B in non-small cell lung cancer cells can promote apoptosis of the non-small cell lung cancer cells, thereby preventing and / or treating non-small cell lung cancer. The application has important application value.

The application discloses a nucleic acid multicolor fluorescent probe and application thereof in preparation and in-situ real-time observation of sequential activation of a P53-mediated cell apoptosis pathway. A P53 fixed chain, a Bax fixed chain and a Cyt c fixed chain are modified on the surface of S-AuNSs@SiO2 through an amide bond, and a complementary chain modified with different fluorescent groups, an aptamer chain are connected through a complementary pairing rule to construct a multicolor fluorescent probe. In the presence of a target, DNA double strands are forced to be opened, and a fluorescent group is released from the system to restore quenched fluorescence. Due to 20 symmetrical 'hot spots', a stronger local electric field can be generated, and the probe based on S-AuNSs shows better optical performance. The S-AuNSs@SiO2-P of the application has high integration, is easy to obtain, and realizes in-situ real-time observation of sequential activation of a P53-mediated apoptosis pathway in living cells, and has application prospects in mechanism research, drug discovery, dynamic monitoring of an apoptosis process and the like.

The invention provides a precise nutrition regulation and control method for promoting intestinal development of young meat breeding chickens and application, belongs to the technical field of livestock and poultry breeding and production, and aims to solve the problem that hatching eggs laid by meat breeding chickens of 50 weeks old or above are insufficient in nutrition reserve, and L-methionine is injected through amniotic cavities when the meat breeding chickens are hatched to 17 embryonic ages. According to the method, the jejunum length, the jejunum weight and the ileum length (Plt: 0.05) of the 21-day-old offspring broiler chicken are remarkably increased, the expression of ileum proinflammatory factors (IL-8 and TNF-alpha) and apoptosis pathway genes (BAX, Caspase-3 and the like) is down-regulated, the expression of anti-apoptosis genes Bcl-2 is up-regulated, and the serum urea nitrogen level is reduced. Meanwhile, the daily average feed intake and the daily weight gain (Plt; 0.05) are improved. Through accurate intervention in the embryonic period, parent nutrition transfer limitation is broken through, the intestinal development and immune functions of offspring are improved, and an effective solution is provided for healthy breeding of offspring of elderly breeding hens.

This invention discloses the application of an oligopeptide derived from *Sipunculus nudus* and 5-FU in the preparation of drugs for treating colorectal cancer, belonging to the field of biomedical technology. This invention isolates an oligopeptide from *Sipunculus nudus*. Experimental verification shows that this small-molecule oligopeptide, when combined with 5-FU at high concentrations, significantly inhibits the proliferation of colon cancer cells, exhibiting a dose-dependent synergistic effect. Oligopeptide 659 and 5-FU synergistically activate the mitochondrial apoptosis pathway; combined administration enhances γ-H2AX focal point formation and exacerbates DNA double-strand breaks, thereby synergistically inhibiting CRC cell proliferation. In vivo analysis of the antitumor effect of peptide 659 using NOD-SCID female mice inoculated with DLD-1 cells further demonstrates the anti-colorectal tumor effect of oligopeptide 659. Analysis of mouse autopsies showed that, compared to the control group, oligopeptide 659 inhibited tumor growth in mice.

This invention belongs to the field of natural product extraction and biomedicine technology, and discloses a carrageenan polysaccharide ATSP-1 derived from Taxus chinensis and its applications. This polysaccharide, obtained through hot water extraction and purification, has a triple helix conformation, is mainly composed of galactose, has a weight-average molecular weight of 725.95 kDa, and its backbone contains specific glycosidic bonds and differentiated sulfation patterns. ATSP-1 can upregulate the expression of MHC-I / II molecules in colonic tissue through the antigen presentation signaling pathway, thereby activating CD4+. + / CD8 + It induces specific immune responses mediated by T cells; simultaneously activates the p53 apoptosis pathway, induces tumor cell apoptosis, achieves a tumor inhibition rate of 43.14%, and has no significant liver toxicity. It can be used to prepare immune-related anti-tumor products and provides natural active polysaccharide resources.

The invention provides a composition for improving an ovarian function as well as a preparation method and application thereof, and relates to the technical field of compositions. The composition is prepared from urolithin and S-equol. The mass ratio of the urolithin to the S-equol in the composition is (1-30): 1. The composition can significantly improve the ovarian function and repair ovarian structure damage, and through the synergistic effect of urolithin and S-equol, the composition can significantly improve the survival rate of zebra fish oocyte, effectively increase the ovary weight index, reverse cisplatin-induced ovarian atrophy, and inhibit activation of apoptosis pathway key molecule Caspase-3. And the composition can improve the fertility, reduce the problem of poor development of the offspring, and realize dual improvement of the fertility and the health of the offspring.

The invention belongs to the technical field of natural product extraction and biological medicine, and discloses carrageenan polysaccharide ATSP-1 derived from sea asparagi and application of the carrageenan polysaccharide ATSP-1. The polysaccharide is obtained through hot water extraction, separation and purification, has triple helix conformation, is mainly composed of galactose and has the weight-average molecular weight of 725.95 kDa, and a framework contains specific glucosidic bond connection and differential sulfation modes. The ATSP-1 can up-regulate the expression of MHC-I / II molecules in colon tissues through an antigen presentation signal channel, so as to activate CD4 < + > / CD8 < + > T cell mediated specific immune response; meanwhile, a p53 apoptosis pathway is activated, tumor cell apoptosis is induced, the tumor inhibition rate reaches 43.14%, no obvious hepatotoxicity exists, the polysaccharide can be used for preparing immune-related anti-tumor products, and a natural active polysaccharide resource is provided.