22 results about "PINK1" patented technology

The invention belongs to the technical field of medicines, and particularly relates to application of dioscin combined with chidamide in diffuse large B-cell lymphoma. Specifically, research finds that the dioscin can significantly inhibit DLBCL cell proliferation and induce cell cycle arrest and apoptosis by up-regulating PINK1 / Parkin mediated mitochondrial autophagy and enhancing H3K27 acetylation mediated epigenetic regulation. When the chidamide and the dioscin are combined for use, a synergistic effect can be generated, and by further increasing the H3K27ac level, the cell apoptosis induction effect is enhanced, and the in-vivo and in-vitro anti-tumor activity on DLBCL is remarkably improved. The invention provides a novel and efficient DLBCL combined treatment scheme, and provides a new pharmaceutical composition and theoretical support for clinical diagnosis and treatment of DLBCL, so that the application has good practical application value.

The invention discloses an application of an RGS1 gene inhibitor in preparation of a medicine for treating obesity-related metabolic diseases, relates to the technical field of biological medicines, and particularly relates to an application of the RGS1 gene inhibitor in preparation of a medicine for treating obesity-related metabolic diseases. The inhibitor of the RGS1 gene is used for preparing a medicine for treating obesity-related metabolic inflammatory diseases, and the medicine is used for activating a PINK1 / Parkin mediated mitochondrial autophagy pathway in macrophages; the inhibitor of the RGS1 gene is a shRNA (short hairpin Ribonucleic Acid) lentiviral expression vector capable of realizing targeted silencing of RGS1 gene expression; the application of the RGS1 gene inhibitor in preparation of drugs for treating obesity-related metabolic diseases has significant beneficial effects; the drug can accurately activate a PINK1 / Parkin mediated mitochondrial autophagy pathway in macrophages, has high targeting property, and improves the safety and effectiveness of the drug.

Disclosed herein are recombinant gene therapy vectors comprising a gene encoding PTEN-induced kinase 1 (PINK1) operably linked to a promoter, and methods of using the recombinant therapy vectors to inhibit, reduce, or delay neuronal degeneration or death in a subject.

The invention discloses an application of PINK1 in regulation and control of ER positive breast cancer tamoxifen drug resistance. The invention relates to application of PINK1 as a biomarker in evaluating the tamoxifen resistance of ER positive breast cancer cells. The drug resistance is evaluated by detecting the expression level of PINK1 in a sample and combining mitochondrial autophagy activity. The expression level of the PINK1 comprises an mRNA level and / or a protein level. According to the invention, the drug resistance formation process is systematically analyzed from the perspective of quality control of an organelle of mitochondrial autophagy, and through public database analysis and experimental verification, the overall up-regulation of the mitochondrial autophagy pathway in drug-resistant cells is clearly revealed, and the drug-resistant phenotype is promoted by maintaining the mitochondrial steady state, thereby opening up a new direction for understanding the drug-resistant mechanism.

The present application relates to a kind of compositions for regulating autophagy of eukaryotic cell, improving mitochondrial dysfunction and its preparation method and application.It includes the following weight parts of raw materials: 10-30 parts of broccoli powder, 10-30 parts of wheat germ microcapsule powder, 20-40 parts of raspberry extract, 20-40 parts of banana powder, 2-6 parts of leucine, 0.1-1 parts of pyrroloquinoline quinone disodium salt.The present application also provides the preparation method of broccoli powder, wheat germ microcapsule powder, raspberry extract and banana powder, and the use of the composition.The composition combines the efficacy of the above 6 ingredients, reasonable compatibility, safe and effective, various components activate mitochondria through regulating protein, PINK1 / Parkin-dependent pathway and PINK1 / Parkin-independent pathway;At the same time, by activating PGC-1 alpha signal pathway, promote mitochondrial DNA replication and new mitochondria generation;Stabilize mitochondrial membrane potential, improve ATP synthesis efficiency;Synergistically activate mitochondrial autophagy, improve mitochondrial dysfunction and then relieve aging.

The invention relates to the technical field of biological medicines, and particularly discloses application of formononin in preparation of a medicine for regulating and controlling BNIP3-mediated excessive mitochondrial autophagy. The invention discloses that ononin can be used as a direct small molecule inhibitor of BNIP3 protein, specific binding of ononin with BNIP3 is verified through molecular docking, surface plasmon resonance and molecular dynamics simulation in multiple dimensions, and in an iron overload induced ovarian granulosa cell injury model, the ononin can be used as an iron overload induced ovarian granulosa cell injury model. The formononin effectively inhibits mitochondrial excessive autophagy mediated by a BNIP3-PINK1 / Parkin axis through targeting BNIP3, remarkably recovers mitochondrial membrane potential, reduces mitochondrial active oxygen level and improves cell oxygen consumption rate (OCR), so that stressful high-flux and low-efficiency breathing states are corrected, cell senescence phenotypes are delayed, and cell apoptosis is inhibited. And a new small molecule drug strategy with a clear structure and a clear action mechanism is provided for iron overload related ovarian function impairment.

The invention discloses a PINK1 inducible expression cell line of a porcine umbilical vein endothelial cell and a construction method and application thereof, a stable cell line with controllable PINK1 expression level is constructed by introducing a porcine PINK1 gene into the porcine umbilical vein endothelial cell and combining with an inducible expression system taking doxycycline as an inducer. The cell line is in a low-expression or non-expression state under the condition that an inducer is not added, and dose-dependent induced expression can be realized after doxycycline is added. Experimental results show that the induced expression of PINK1 can regulate and control the expression of angiogenesis related genes, activate mitochondrial autophagy related pathways under oxidative stress conditions, and influence the expression of cell proliferation and apoptosis related proteins at the same time. The cell line is clear in construction method and good in stability, can be used as an in-vitro model for researching angiogenesis, oxidative stress and related regulation and control mechanisms of porcine vascular endothelial cells, and has good practical value.

The application belongs to the field of biological medicine, and discloses application of echinocystic acid in preparation of a medicine for preventing and treating liver ischemia-reperfusion injury. The application proves that the echinocystic acid significantly improves liver tissue injury, reduces serum ALT and AST levels, and reduces cell apoptosis through a mouse liver IRI model. It is found that the echinocystic acid activates the p38 MAPK signal pathway by inhibiting PTPN1, thereby activating Nrf2 and enhancing PINK1 / Parkin-mediated mitochondrial autophagy. In addition, the echinocystic acid promotes DRP1 phosphorylation and enhances the transfer of DRP1 to mitochondria, thereby reducing oxidative stress and inflammatory response. It is shown that the echinocystic acid regulates mitochondrial autophagy through the PTPN1 / p38 MAPK / Nrf2 pathway, has a significant liver protection effect, and provides a new idea for the treatment of IRI.

The invention provides application of rosmarinic acid in treatment of cervical spondylotic myelopathy. Specifically, animal experiments and in-vitro cell experiments are carried out by constructing a rat cervical spondylotic myelopathy model, and it is verified that rosmarinic acid has a neuroprotective effect and can inhibit neuronal apoptosis under the conditions of ischemia and hypoxia. Experiments show that the rosmarinic acid can enhance mitochondrial autophagy by activating AMPK-TFEB and PINK1-PRKN signal pathways, so that neurons are protected from ischemia and hypoxia, and neuronal cell apoptosis is inhibited. Based on the invention, the rosmarinic acid or the derivative thereof can be used for preparing the medicine for treating cervical spondylotic myelopathy.

The invention relates to the technical field of modeling, and provides an ischemia-reperfusion injury myocardial autophagy model based on paeoniflorin regulation, which is characterized in that a virtual compound library containing a plurality of analogues is programmatically generated according to a preset chemical modification rule on the basis of a chemical structure of a paeoniflorin parent nucleus; then, carrying out molecular docking calculation on each analogue in the library and the target protein PINK1 to obtain a binding energy value of the target protein PINK1; and predicting the oral bioavailability value of each analogue and whether the analogue is in the state of a P-gp substrate. And finally, integrating all the calculated data by the model, performing screening by using a Pareto optimal algorithm and taking binding energy and oral bioavailability as optimization targets, and outputting a group of candidate molecules which achieve balance between the two targets.

Disclosed herein are recombinant gene therapy vectors comprising a PTEN-induced kinase 1 (PINK1) encoding gene operably linked to a promoter, and methods of inhibiting, reducing, or delaying degeneration or death of neurons in a subject using the recombinant therapy vectors.

This invention discloses the application of the PINK1 gene in porcine trophoblast cells and a method for constructing cell lines. This invention regulates the proliferation, differentiation, and autophagy of porcine trophoblast cells by controlling the expression level of the PINK1 gene, thereby enhancing placental function and efficiency. Induced expression of the PINK1 gene activates the Parkin-P62-LC3B pathway, promotes mitophagy, increases the expression of Mgst1, CTBP2, and IGFBP3 genes, promotes cell proliferation, inhibits apoptosis, and enhances cellular antioxidant capacity. Knockout of the PINK1 gene produces the opposite effect. This invention provides methods for constructing PINK1-induced expression and knockout cell lines. Stable porcine trophoblast cell lines offer new technical means for studying porcine placental development mechanisms, improving placental efficiency, and enhancing sow reproductive performance, which is of great significance to the development of the pig industry.

The present application relates to the application of isoquercitrin in the preparation of a drug for treating post-traumatic stress disorder, and belongs to the technical field of natural chemical medicine development. The present application systematically clarifies the whole-chain mechanism of isoquercitrin in treating PTSD through the "GABA A R-PINK1 / Parkin-mitophagy" pathway by means of a variety of technical means such as molecular docking, microthermal swimming, patch clamp, proteomics, cell and animal models. Compared with the clinically commonly used drugs for treating post-traumatic stress disorder, isoquercitrin, as a natural flavonoid compound, can improve the symptoms of PTSD while not damaging the learning and memory function, and has better safety. Moreover, isoquercitrin is widely sourced and has a mature preparation process. The present application provides a theoretical basis and experimental support for the application of isoquercitrin in the development of drugs for treating post-traumatic stress disorder, and has important clinical application value and industrialization prospects.

The invention discloses an application of taurine in treatment of hair growth matrix bleeding of premature infants, and relates to a new application of taurine in preparation of a medicine for preventing or improving white matter injury after the hair growth matrix bleeding (GMH) of the premature infants. The medicine takes taurine as an active ingredient and is administered in manners of intraperitoneal injection and the like, and the preferable dosage is 120 mg / kg / day. In-vivo and in-vitro experiments show that the taurine can remarkably reverse mitochondrial dysfunction of oligodendrocyte precursor cells (OPCs) after GMH, and by activating PINK1 / Parkin mediated mitochondrial autophagy and promoting survival and maturation of the OPCs, myelin sheath formation and tissue structures are improved, and finally sensory movement and cognitive function recovery are promoted. The invention provides a strategy which is novel in mechanism and easy in clinical transformation for preventing and treating secondary white matter injury after GMH.

The invention provides an internal friction network piezoelectric hydrogel microsphere as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. According to the preparation method, supramolecular engineering and a microfluidic strategy are utilized, and a hydrogel microsphere system of an internal friction network is constructed through cooperative assembly of piezoelectric bismuth ferrite nanoparticles (BFs) and slip ring functionalized methacrylated hyaluronic acid (HAMA), so that physiological electroadaptation in degeneration tissues is realized. The BFs convert mechanical stimuli into electrical signals, while a stress-dependent internal friction network modulates energy dissipation. Under low stress, the slip ring moves to generate low friction, so that electric signal generation is enhanced; under high stress, the main chain is straightened, so that friction is increased, excessive signals are inhibited, and physiological electric adaptation is recovered. The microspheres can generate a stable electric field under dynamic loading, mitochondrial autophagy is promoted by activating a PINK1 / Parkin pathway, stable mitochondrial membrane potential is maintained, and nucleus pulposus cell apoptosis is reduced by 75%.

The invention belongs to the technical field of biological medicine, and relates to application of FADS in targeted screening of drugs for treating LUSC or inhibiting LUSC proliferation, migration and invasion. The invention relates to an application of an FADS / PINK1 / Parkin axis in targeted screening of drugs for treating LUSC or inhibiting proliferation, migration and invasion of LUSC. The invention determines that FADS is a new driver gene and a prognosis biomarker of LUSC. The FADS promotes autophagy of mitochondria on which PINK1-Parkin depends by stabilizing PINK1 and enhancing recruitment of Parkin to mitochondria, so that proliferation, invasion and metastasis of LUSC are promoted. The invention discloses a treatment-induced drug-resistant ring for promoting FADS expression through an HIF1alpha / FADS axis by DTX chemotherapy. The invention provides a new combination strategy, HCQ and DTX are used, a direct and convenient-to-transform treatment method is provided to overcome the chemical resistance of LUSC, and important potential clinical influence is achieved.

The invention belongs to the technical field of biological medicines, and particularly relates to an anti-aging mitochondrial preparation as well as a preparation method and application thereof. The mitochondrial preparation is formed by compounding mammalian-derived mitochondria and a pharmaceutically acceptable injection solvent, the membrane potential (delta psi m) of the mammalian-derived mitochondria is kept unchanged or reduced by 50%-90% compared with that before separation, and the outer membrane integrity rate is larger than or equal to 90%. Under the state that the membrane potential is reduced, the outer membrane structure is still kept complete, and the capability of inducing host cell PINK1 / Parkin dependent mitochondrial autophagy and network remodeling is achieved, so that inferior mitochondria is selectively removed, and mitochondrial neogenesis is promoted. The preparation can induce systemic mitochondrial quality remodeling in multiple tissues, significantly improve ATP level, reduce ROS generation, increase mitochondrial DNA copy number, down-regulate aging markers p16 and p21, and improve cognition, movement and organ functions in an old animal model.

This invention relates to the field of traditional Chinese medicine, specifically to the use of a ten-ingredient frankincense powder in the prevention and treatment of kidney diseases. The ten-ingredient frankincense powder exhibits antioxidant effects by reducing ROS and MDA levels and increasing SOD activity. It also inhibits the expression of inflammatory factors IL-1β and TNF-α, as well as pro-apoptotic genes Bax, Caspase-3, and Caspase-9, thus exerting anti-inflammatory and anti-apoptotic effects. It effectively prevents and treats kidney damage, and its mechanism may be related to the upregulation of the Pink1 / Parkin signaling pathway and activation of mitophagy.

The application relates to the field of biological medicine, in particular to pharmaceutical application and a pharmaceutical composition of 1,8-diacetylrhefa. The application of 1.1,8-diacetylrhefa in the preparation of a drug for treating Alzheimer's disease mediated by mitochondrial autophagy; and a pharmaceutical composition, which is composed of a therapeutically effective amount of 1,8-diacetylrhefa and a pharmaceutically acceptable carrier. 1,8-diacetylrhefa can specifically activate the PINK1 / Parkin signal pathway, thereby promoting the removal of damaged mitochondria and restoring the organelle homeostasis in neurons. Experimental results show that in cell and animal models, it can effectively reduce the beta-amyloid level and improve the cognitive dysfunction of model animals, such as increasing the spontaneous alternation rate of Y maze, prolonging the passive avoidance test latency, thereby providing a candidate treatment scheme with disease modification potential for neurodegenerative diseases.

The invention relates to an anti-cancer drug for synergistically regulating and controlling pyroptosis of pancreatic cancer cells based on magnolol and glucose metabolism and application of the anti-cancer drug. The anti-cancer drug is a key enzyme GLUT1 inhibitor for magnolol and glucose metabolism. By combining magnolol with a glucose deprivation / GLUT1 inhibitor (such as BAY-876) and by inhibiting mitochondrial autophagy (PINK1 degradation) and mitochondrial ROS accumulation and triggering a new mechanism of apoptosis-pyroptosis conversion, the limitation that a traditional natural product only depends on an apoptosis pathway is broken through; the immunoregulation of mitochondrial autophagy inhibition and pyroptosis induction is creatively associated; metabolic intervention induced pyroptosis is directly associated with pancreatic cancer'immune cold 'microenvironment remodeling, and an important theoretical basis is provided for natural product combined immunotherapy. Meanwhile, a CDX model (magnolol combined with a GLUT1 inhibitor) and ketogenic diet simulation metabolism intervention are combined, and a closed-loop verification system from a molecular mechanism to in-vivo treatment is established, so that clinical development of metabolism intervention-natural product-immune combined treatment can be promoted.

The invention provides application of an HDAC3 inhibitor in preparation of a medicine for treating demyelination diseases, and belongs to the field of neuroimmunology and neurodegenerative disease treatment. The invention finds that the demyelination pathological characteristics are obviously improved by specifically knocking down the microglial cell HDAC3. According to the present invention, the targeting inhibition microglial cell HDAC3 can promote the acetylation modification of Parkin and enhance the interaction between Parkin and Pink1 so as to activate the mitochondrial autophagy mediated by the HDAC3 / Parkin / LC3 axis, and inhibit the activation of the NLRP3 inflammasome; meanwhile, targeted knock-down of the microglia HDAC3 can also lower the transcriptional level of NLRP3 and further lower the expression of NLRP3, so that polarization of the microglia from M1 type to M2 type is regulated and controlled, and a favorable microenvironment is created for inhibiting demyelination lesion and promoting remyelination.

The invention belongs to the technical field of biological medicines, and relates to application of ramelteon in preparation of a medicine for treating cardiovascular diseases. On the basis of the idea of new use of old drugs, 1912 drugs approved by FDA are used for high-throughput screening, and in combination with an in-vivo mouse model and an in-vitro cell model, it is found that ramelteon can strongly induce expression of Pgc1alpha and Pink1, and the mitochondrial homeostasis and the myocardial cell energy metabolism level are maintained. In-vivo experiments further prove that the ramelteon can relieve the development of cardiomyopathy induced by adriamycin and hypertrophic cardiomyopathy caused by aortic constriction and improve the development of heart failure, so that the ramelteon can improve the prognosis of cardiovascular diseases. The invention provides application of ramelteon as a mitochondrial energizer in preparation of drugs for treating cardiovascular diseases.