33 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 relates to a composition for regulating autophagy of eukaryotic cells and improving mitochondrial dysfunction as well as a preparation method and application of the composition. Comprising the following raw materials in parts by weight: 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 and 0.1-1 part of pyrroloquinoline quinone disodium salt. The invention further provides a preparation method of the broccoli powder, the wheat germ micro-capsule powder, the raspberry extract and the banana powder, and application of the composition of the broccoli powder, the wheat germ micro-capsule powder, the raspberry extract and the banana powder. The composition integrates the effects of the six components, is reasonable in compatibility, safe and effective, and various components activate mitochondria by regulating protein and depending on a PINK1 / Parkin dependent pathway and a PINK1 / Parkin non-dependent pathway; meanwhile, by activating a PGC-1alpha signal channel, mitochondrial DNA replication and new mitochondrial generation are promoted; the mitochondrial membrane potential is stabilized, and the ATP synthesis efficiency is improved; mitochondrial autophagy is synergistically activated, mitochondrial dysfunction is improved, and aging is relieved.

To provide compounds and compositions capable of modulating PINK1 kinase activity, and methods for producing and using the same.SOLUTION: A compound has a structure in the figure. (In the formula: Z is O, NH, or CH2; R1a, R1b, R1c and R1d are H, halogen, CN, NH2, or the like; and R2 is -(CH2)nCy1, -O(CH2)nCy1, Cy1, or the like, where Cy1 is C4-C9 cycloalkyl, C3-C9 heterocycle, or the like.)SELECTED DRAWING: Figure 1A

The disclosure is directed to nitrogen-containing heteroaryl analogs, methods of making nitrogen-containing analogs, and methods of treating disorders associated with PINK1 kinase activity including, but not limited to, neurodegenerative diseases, mitochondrial diseases, fibrosis, and / or cardiomyopathy using these analogs. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The invention belongs to the technical field of novel application of nattokinase, and provides application of nattokinase in preparation of a medicine for preventing and / or treating Parkinson's disease. According to the invention, an MPTP / MPP + induced Parkinson's disease (PD) in-vivo and in-vitro model is established, and a neuroprotection mechanism of nattokinase is disclosed by adopting a systematic experiment method. Results show that the nattokinase can significantly improve dyskinesia and intestinal dysfunction of MPTP-induced PD mice; the damage of dopaminergic neurons of the middle brain is effectively relieved, and the density of tyrosine hydroxylase positive neurons is maintained; the expression of TLR4 and NLRP3 inflammasome pathways and related proinflammatory cytokines is inhibited, and the neuroinflammatory response is relieved; pINK1 / Parkin expression is up-regulated, mitochondrial autophagy is activated, and damaged neurons are cleared. Direct association between nattokinase and Parkinson's disease prevention and treatment is established for the first time, an innovative solution is provided for developing a novel anti-Parkinson's disease medicine with dual effects of motor function improvement and neuroprotection, and the application has important development value in the field of treatment of neurodegenerative diseases.

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.

The invention belongs to the field of biochemistry, and particularly relates to a polypeptide with PINK1 kinase agonistic activity and application thereof. According to the technical scheme, the polypeptide or the polypeptide mixture comprises polypeptide 1, and the amino acid sequence of the polypeptide 1 is shown as SEQ ID NO: 1. The novel polypeptide compound is separated and identified from the earthworm extract, has PINK1 agonist activity, has no obvious cytotoxicity, can save MPP + damaged nerve cells, and has the prospect of preparing the anti-Parkinson's disease medicine.

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 application of PINK1 / Parkin in cognitive impairment by adjusting mitochondria, and relates to the technical field of biological medicine, and the technical key points are as follows: the PINK1 / Parkin can mediate the autophagy mechanism of the mitochondria, inhibit excessive mitochondrial autophagy generated by the cognitive impairment caused by aluminum exposure, maintain the steady state balance of the mitochondria in the body of a patient, and inhibit the mitochondrial autophagy caused by aluminum exposure. The excessive formation of ROS is inhibited, and the progress of cognitive impairment of a patient is slowed down.

The invention discloses application of Tongxinluo in preparation of a medicine capable of activating or enhancing a PERK-eIF2alpha-ATF4 signal channel. The medicine is used for treating or preventing diseases related to endoplasmic reticulum stress-mitochondrial autophagy axis dysfunction. The Tongxinluo regulates PINK1 / Parkin mediated mitochondrial autophagy by activating an eIF2alpha / ATF4 pathway, and can enhance selective elimination of damaged mitochondria while reducing the endoplasmic reticulum stress level of myocardial cells, so that heart remodeling is relieved, the diastolic function of the heart is improved, the symptom of the heart failure is relieved, and the progress of the heart failure is delayed.

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 present disclosure relates generally to compositions and methods for treating, preventing, inhibiting, or delaying central nervous system degeneration. The disclosure relates to a recombinant gene therapy vector comprising a PARK2, PINK1, DJ-1, LRRK2, SCNA, c-Rel, ATG7, VMAT2, or GBA gene, or functional fragment or variant thereof. The disclosure also relates to CRISPR / Cas-based gene editing systems for treating, preventing, inhibiting, or delaying central nervous system degeneration.

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 provides application of a TRIM27 gene as a target spot in screening of drugs for treating mitochondrial autophagy abnormality related diseases, and belongs to the technical field of biomedicine.The research finds that TRIM27 participates in regulation and control of mitochondrial functions; the TRIM27 gene silently weakens mitochondrial functions in cells, reduces mitochondrial membrane potential and activates mitochondrial autophagy, PINK1 protein and Parkin protein levels are up-regulated, a classical autophagy marker LC3B is up-regulated, mitochondrial autophagy can be activated by targeted inhibition of TRIM27 gene expression, and occurrence and development of mitochondrial autophagy abnormality related diseases are further interfered.

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 invention discloses application of 3, 4-dihydroxybenzylidene acetone (DBL) in preparation of a medicine for relieving intestine injury of a Leizhou black duck, and belongs to the technical field of biological medicine. According to the application disclosed by the invention, the DBL can be used for improving the antioxidant enzyme activity, clearing ROS (reactive oxygen species), recovering mitochondrial membrane potential, relieving mitochondrial dysfunction, promoting mitochondrial autophagy and clearing damaged mitochondria by mediating cGAS / STING and Parkin / PINK1 signal channels; in addition, by mediating a Bax / Bcl-2 signal channel, the expression of Bcl-2 can be improved, and the expression of Caspase-3 and Caspase-9 can be reduced, so that the apoptosis can be relieved. The invention discloses an action mechanism of DBL for guaranteeing cell metabolism, relieving inflammatory response and relieving lipopolysaccharide-induced Leizhou black duck intestinal injury through double targets, and provides a candidate medicine for preventing and treating intestinal diseases caused by gram-negative bacteria of livestock.

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 diagnosis and treatment of diabetic complications, and discloses an auxiliary diagnosis and treatment method for cardiovascular complications of gestational diabetes mellitus, which comprises the following steps: S1, collecting an umbilical vein endothelial cell sample of a gestational diabetes mellitus patient; s2, detecting the expression level of miR-584-5p in the umbilical vein endothelial cell sample and the expression levels of the PTEN gene and the downstream PINK1 protein thereof, and detecting related indexes of mitochondrial autophagy at the same time; s3, in combination with clinical indexes, based on the expression level of miR-584-5p, the expression levels of the PTEN gene and the downstream PINK1 protein thereof and related indexes, evaluating the occurrence risk of the cardiovascular complications of the offspring of the gestational diabetes mellitus patient. The application provides molecular evidence for early discovery of endothelial cell dysfunction, and assists in assessment of cardiovascular complication risk of patients.

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.