47 results about "Mitophagy" patented technology

The invention discloses a mitochondrial / lysosome dual-targeting viscosity response AIE probe as well as a preparation method and application thereof. According to the probe, tetraphenylethylene (TPE) is used as an AIE light-emitting framework, and two flexible side chains containing hydrophilic units are introduced by utilizing the excellent structural modifiability of the TPE. The tail end of each side chain is modified with a trimethylamine group, quaternary ammonium salt cations derived from the trimethylamine group have localized positive charges, and combination with water molecules can be enhanced through ion-dipole interaction, so that the water solubility and biocompatibility of the molecules are effectively improved. Based on the design, the invention provides the AIE polymer probe which is constructed by taking TPE as a core and taking an amphiphilic flexible chain as a functional unit. The probe can establish a three-dimensional linear relationship among drug action time-regional viscosity-fluorescence lifetime (t-eta-tau) by capturing fluorescence lifetime signals inside and outside cells, so as to realize visual detection and quantitative analysis of average viscosity change of mitochondria and lysosome in the mitochondrial autophagy process.

A mitochondrial transplantation system includes a mitochondrial and an apoptosis vesicular membrane, the mitochondrial being carried within the apoptosis vesicular membrane. When a system composed of mitochondria and apoptosis vesicles acts on endothelial cells, the targeting and efficiency of mitochondria transplantation are improved, mitochondria autophagy is generated, mitochondria autophagy is reactivated to remove damaged mitochondria of the endothelial cells, the removal of damaged mitochondria is promoted, and the cell functions of the damaged endothelial cells of mitochondria are recovered. The wound healing is favorably promoted. A system composed of mitochondria and apoptosis vesicle membrane is used as an active component to prepare a drug or a medical device for promoting wound healing.

The present invention discloses use of a male flower extract of Eucommia ulmoides Oliver in preparation of a food or a medicament for resisting muscle aging, belonging to the technical field of plant extracts. A main active ingredient of the male flower extract of Eucommia ulmoides Oliver is iridoids, and the composition of the iridoids includes aucubin, geniposide, geniposidic acid and asperuloside. The present invention reports for the first time that the male flower extract of Eucommia ulmoides Oliver and the iridoids contained therein have mitophagy activation activity and maintain normal mitochondrial function by effectively stimulating mitophagy. The extract has a relatively strong ability to prevent or alleviate aging-related muscle hypofunction, and has great application prospects in food, pharmaceutical and other fields.

The present application discloses use of small-molecule compound having naphthalamine structure. In the present invention, it was found for first time that the general formula I compound can be used to treat diseases associated with kidney injury and diseases associated with mitophagy, and is expected to be an effective special drug for treating the diseases associated with mitophagy and kidney-associated diseases, especially chronic kidney disease.

The present disclosure generally relates to methods and in vitro systems for generation of mitochondria-depleted pluripotent stem cells, composite pluripotent stem cells, or non-human, tetraploid, mitochondria-depleted embryos. The disclosure further provides methods for use of cells or non-human embryos in regenerative medicine and drug screening.

The invention belongs to the technical field of bioengineering, and particularly provides application of a JNK inhibitor in preparation of drugs for preventing and / or relieving and / or treating pulmonary tuberculosis aiming at the problem that whether the existing JNK inhibitor SP600125 can inhibit BNIP3-mediated mitochondrial autophagy and further exert the ROS bactericidal effect is unknown. And the JNK inhibitor is an SP600125 JNK inhibitor. The JNK inhibitor is used for inhibiting mitochondrial autophagy in the BCG infected macrophages. The JNK inhibitor reduces the up-regulation of BNIP3 and LC3B caused by BCG infection. It is found through the application that when the concentration of the JNK inhibitor reaches 15 umol / L, remarkable cytotoxicity begins to appear, and compared with a control group, the cell survival rate is remarkably decreased. The SP600125 can be used for inhibiting mitochondrial autophagy and down-regulating the expression of BNIP3 and LC3B. Inhibition of JNK expression can inhibit survival of Mtb in RAW264.7 macrophages, and a new thought and direction are provided for treatment of tuberculosis.

The invention discloses a fluorescent probe for high-sensitivity monitoring of cell mitochondrial autophagy as well as a preparation method and application thereof. The structure of the fluorescent probe is as shown in formula I in the specification. According to the fluorescent probe provided by the invention, a phenol group is used as an electron donor and a pH response unit, hydroxyl tricyanopyrrole is used as an electron acceptor, triphenylphosphine is used as a mitochondrial targeting group, fluorine atoms are introduced to a benzene ring to improve the response rate and the fluorescence intensity, and meanwhile, a thiophene ring is introduced to further expand the fluorescence emission wavelength. The probe can rapidly target mitochondria and emit corresponding fluorescence signals based on pH differences of different autophagy stages, so that real-time, high-sensitivity and high-selectivity monitoring of the mitochondria autophagy process is realized. In addition, the fluorescent probe is simple in molecular structure, small in molecular weight and easy to synthesize, purify and subsequently modify. Cell experiment results show that the probe can accurately trace the mitochondrial autophagy process in cells, and has good application potential in the field of biological imaging and detection.

This invention discloses a method for constructing carrier-free NADH nanoparticles to restore the function of aging hepatocytes, the product, and its applications, belonging to the pharmaceutical field. The method includes preparing carrier-free nano-coordination polymer NADH-Gd using a reverse microemulsion method, followed by a two-step lipid modification process: first, DOPA modification, then DPPC, cholesterol, and DSPE-PEG. 5k NADH-PEG was synthesized by modification, with DSPE-PEG added during the modification process. 5k NADH-Gal is ultimately synthesized from NADH-Gal. NADH-Gal exhibits excellent hepatocyte targeting and can replenish NAD+ in senescent hepatocytes in the MASH environment. + The content is increased by adjusting... Aldh18a1 The expression of [a specific substance] regulates proline metabolism. Improved proline metabolism can restore mitochondrial function by promoting mitophagy and mitochondrial biosynthesis, thereby alleviating hepatocyte aging. Simultaneously, it reduces monocyte recruitment and hepatic stellate cells (HSCs), ultimately providing an effective treatment for MASH. This invention provides a novel strategy for the treatment of MASH.

The invention is suitable for the technical field of biological medicine, and provides an active composition for relieving fatigue and application of the active composition. The composition is prepared from a silkworm chrysalis-derived mitochondrial repair peptide, a chickpea-derived neuromodulation peptide, a haematococcus pluvialis-derived phagocytosis peptide, a phosphatidylcholine-lipoic acid conjugate, a whey protein-chitosan copolymer and an ergothioneine-selenium compound in a synergistic manner. Through the synergistic effect of four mechanisms of energy metabolism activation, endocrine balance, mitochondrial autophagy repair and oxidative stress removal, physiological fatigue and stress fatigue are effectively and synchronously relieved. After targeted modification, the utilization rate of macamides is remarkably increased, and the composition can remarkably prolong exercise tolerance, reduce cortisol level, promote GABA synthesis, recover mitochondrial function and greatly shorten fatigue recovery time.

The present invention relates to a composition for preventing or treating diabetic cardiomyopathy comprising an MsrB2 activator as an active ingredient. The MsrB2 activator disclosed in the present invention suppresses oxidative damage of ROS, induces autophagy in mitophagy, increases mitochondrial regeneration and biosynthesis in diabetic heart tissue, thereby suppressing overall myocardial function decline, so that it can be effectively used in a pharmaceutical composition or health food composition for preventing or treating diabetic cardiomyopathy, particularly diabetic heart disease in lean diabetes.

The application discloses oleanane triterpene saponin compounds with improved mitochondrial energy anti-aging, a preparation method and application thereof, and belongs to the technical field of medicines and cosmetics. Through systematic chemical component research on Zhejiang Hongshan tea flowers, two new oleanane triterpene saponin compounds CK and CL are separated, and the chemical structures are determined by using high-resolution mass spectrometry and nuclear magnetic technology. In-vitro anti-photoaging activity research shows that the new compounds CK and CL provided in the application have good protection effects on ultraviolet-induced fibroblast photoaging, can significantly improve the content of type I collagen, reduce the expression of matrix metalloproteinases mmp1 and mmp3 , increase the generation of mitochondrial autophagosomes and lysosomes, promote mitochondrial autophagy, relieve mitochondrial damage and improve cell senescence. The preparation method provided in the application is simple, and the activity is significant, so that the application is expected to be developed into a new anti-skin aging medicine or cosmetic.

The invention discloses a composition of a mitochondrial autophagy inhibitor and an immune checkpoint inhibitor and application, and belongs to the technical field of biological medicine. The invention provides a brand-new combined treatment strategy. In-vivo experiments prove that in melanoma, colon cancer and liver cancer models ineffective by single use of the immune checkpoint inhibitor, the curative effect of the immune checkpoint inhibitor can be significantly enhanced by combining the mitochondrial autophagy inhibitor, which is represented by synergistic inhibition of tumor volume and weight and significant increase of CD8 + T cell infiltration in a tumor microenvironment. The invention provides an effective scheme for overcoming the drug resistance of tumor immunotherapy, and the application prospect is wide.

The application belongs to the technical field of target drugs, and particularly relates to application of CASZ1b protein; the amino acid sequence of the CASZ1b protein is shown as SEQ ID NO. 1, and the application of the CASZ1b protein in preparation of a drug for treating diseases mediated by mitochondrial function damage; the drug can activate expression of mitochondrial autophagy proteins Beclin1 and P62, improve a mitochondrial membrane potential, inhibit ROS production, and repair mitochondrial function damage.

The present invention relates to a pharmaceutical composition containing a mitophagy inducer as an active ingredient. The pharmaceutical composition is advantageous for the manufacture of pharmaceutical formulations, avoids the occurrence of incompatibility due to interactions between the active ingredient and auxiliary agents, and allows for long-term storage.

This invention discloses a high-BNIP3-loaded exosome, its preparation method, and its applications, relating to the field of biomedical engineering technology. The high-BNIP3-loaded exosomes are obtained by pre-treating human bone marrow mesenchymal stem cells transfected with a recombinant expression vector carrying the BNIP3 gene, followed by 24 hours of hypoxia at 1% oxygen concentration. The exosomes have a particle size of 40-130 nm and highly express BNIP3 and exosome markers HSP70, CD63, and TSG101. The preparation method includes constructing a pcDNA3.1-BNIP3 recombinant vector, transfecting and screening stable-expressing engineered cells, hypoxia pre-treatment, and purification by gradient centrifugation combined with ultracentrifugation. This invention achieves efficient loading and targeted delivery of BNIP3 through a synergistic strategy of genetic engineering and microenvironment simulation, significantly improving the endocytosis efficiency of nucleus pulposus cells, activating mitophagy, restoring mitochondrial function, and promoting extracellular matrix synthesis. It can be used to prepare drugs for treating intervertebral disc degeneration and has excellent clinical application prospects.

The present application relates to the technical field of Congo red derivative photocatalytic probe application, and particularly relates to a Congo red derivative photocatalytic probe, a preparation method and a use method thereof, comprising a compound I, the compound I is selected from at least one of the Congo red derivative photocatalytic probes, and the Congo red derivative photocatalytic probe comprises two arene, the arene represents an aromatic heterocycle, and the aromatic heterocycle is selected from one of a benzene ring, furan, thiophene and a naphthalene ring. The Congo red derivative photocatalytic probe provided by the present application can specifically label amyloid plaques in AD brain tissue slices, the binding affinity is significantly improved (Kd of Aβ 1‑40 The Congo red derivative photocatalytic probe can reveal the molecular heterogeneity of amyloid deposition and the key regulatory role of the mitochondrial autophagy-lysosome axis, provide a new tool for AD pathological mechanism research, support proteomic analysis and pathological mechanism analysis across brain regions (hippocampus / cortex), and protect the molecular structure and application in the research of neurodegenerative diseases.

The present invention relates to a pharmaceutical composition for the prevention or treatment of Parkinson's disease. Leading to the present invention, an isoquinoline derivative, identified through screening based on mitophagy activation, was found to exhibit an excellent effect in promoting mitophagy and proved to be a fundamental therapeutic agent for Parkinson's disease. Specifically, the isoquinoline derivative according to the present invention not only reduces mitochondrial dysfunction closely associated with Parkinson's disease in a Parkinson' disease animal model but also ameliorates motor function impairment in the Parkinson's disease animal model. Particularly, in the Parkinson's disease animal model treated with the isoquinoline derivative according to the present invention, the demise of dopaminergic neurons, a primary cause of Parkinson's disease, was effectively inhibited. Thus, the isoquinoline derivative according to the present invention is expected to be advantageously utilized as a fundamental therapeutic agent in the field of prevention, alleviation, and / or treatment of Parkinson's disease.

The invention discloses a screening method of action targets of traditional Chinese medicine phellinus linteus and application of the screening method to treatment of HPV positive tumors, and the screening method comprises the following steps: (1) screening potential action targets of phellinus linteus, respectively obtaining pathogenic targets of HPV infected cervical cancer by combining a GeneCards database, an OMIM database and a DisGeNET database, and taking intersection to obtain common targets; (2) obtaining a protein-protein interaction network of the intersection targets by using an STRING database, and constructing a PPI network between the intersection targets; (3) carrying out GO function enrichment and KEGG pathway enrichment analysis on the core target spot; and (4) carrying out molecular docking on the identified potential target spot of the phellinus linteus. The traditional Chinese medicine phellinus linteus ketone screened by the method disclosed by the invention can accurately target HPV virus, promote degradation of key oncoprotein E6 / E7 and play an anti-tumor role by regulating mitochondrial autophagy and reducing growth and metastasis of HPV-induced cervical cancer, and the medicine is identified to be low in cost and small in toxic and side effects and has relatively good treatment potential in HPV positive tumors.

This invention discloses a mitochondrial micro / nanoreactor system, its preparation method, and its applications. The system comprises mitochondrial-trained apoptotic bodies and a piezoelectric short-fiber scaffold, which are covalently linked via a copper-free click chemical linker. The mitochondrial-trained apoptotic bodies are obtained by inducing apoptosis in macrophages overexpressing Miro1 protein and pretreated with hypoxia, and are rich in functional mitochondria. The piezoelectric short-fiber scaffold is obtained by electrospinning a composite of poly-L-lactic acid and collagen, and can convert external mechanical energy into electrical signals. This invention, through synergistic action, on the one hand, utilizes apoptotic bodies to target and deliver functional mitochondria, enhancing intercellular mitochondrial transfer; on the other hand, it utilizes the piezoelectric effect to generate endogenous electrical stimulation, activating the mitochondrial autophagy pathway, thereby bidirectionally regulating mitochondrial energy metabolism homeostasis in diabetic wounds and significantly promoting wound healing.

The present invention relates to: a pharmaceutical composition for preventing or treating Melas syndrome; and the like, and has been completed by identifying that an isopquinoline derivative, discovered through mitophagy activity-based screening, exhibits an excellent mitophagy promotion effect, and thus can be used as a fundamental therapeutic agent for Melas syndrome. Particularly, an isopquinoline derivative according to the present invention promotes mitophagy activity and remarkably alleviates mitochondria dysfunction in Melas syndrome cell models and in cells derived from Melas syndrome patients. Therefore, the isopquinoline derivative is expected to be effectively used, in the field of prevention, alleviation and treatment of the disease, as a fundamental therapeutic agent capable of inhibiting the cause of Melas syndrome.

This invention relates to the field of biomedical technology, specifically to the application of schisandrin A in the preparation of drugs for treating multiple myeloma. The schisandrin A (SchA) provided by this invention exerts its therapeutic effect on multiple myeloma by synergistically inducing apoptosis and mitophagy in multiple myeloma cells. The structural formula of the schisandrin A is as follows:

The invention discloses a preparation method and application of a light-operated mitochondrial autophagy nano inducer based on thermosensitive liposome, and the preparation method comprises the following steps: (1) dissolving ICG and TPP-Ser in DMSO, carrying out ultrasonic treatment, dropwise adding into ultrapure water, carrying out room temperature stirring reaction, and carrying out centrifugal collection and washing to obtain TSI; (2) dissolving DPPC, DSPC and DSPE-PEG2000-iRGD in a chloroform-methanol mixed solvent, and carrying out rotary evaporation to remove the solvent so as to form a lipid membrane; and (3) adding an aqueous solution of TSI into the lipid membrane, and carrying out hydration and ultrasonic treatment to obtain a suspension. The light-operated mitochondrial autophagy nano inducer prepared by the invention is applied to precise treatment of cancers, and drug release and mitochondrial autophagy regulation are realized through near-infrared laser irradiation. The preparation method has the advantages of strong space-time controllability, high tumor targeting property, multi-mechanism synergistic anti-tumor effect and diagnosis and treatment integration capability, stable preparation process and convenience in clinical transformation.

The application relates to application of an RPL3L overexpression vector in preparation of MIRI treatment drugs and belongs to the technical field of biological medicines. In order to solve the problem that treatment of MIRI lacks effective and precise intervention targets, the application provides application of the RPL3L overexpression vector in preparation of MIRI treatment drugs, through an adeno-associated virus (AAV) mediated RPL3L overexpression system, it is first confirmed that RPL3L is a core value of a precise target point of myocardial ischemia reperfusion injury, overexpression of the RPL3L can realize targeted protection of myocardial ischemia reperfusion injury through three key dimensions of improving ribosome function, inhibiting damage autophagy of mitochondria and improving heart function. The application provides a new strategy taking RPL3L as a precise target point for treatment of myocardial ischemia reperfusion injury, lays a foundation for development of myocardial protection drugs targeting RPL3L, and has outstanding clinical conversion potential.

The invention belongs to the technical field of medicine preparation, and particularly discloses an interference peptide for inhibiting mitochondrial autophagy induced by coronavirus nucleocapsid protein as well as a preparation method and application of the interference peptide. The interference peptide (named as ISQOR beta2) is composed of D-type amino acids, and the structure of the interference peptide comprises a polypeptide sequence as shown in SEQ ID NO: 1; the 5-fluorescein isothiocyanate is covalently connected to the N end of the polypeptide. By competitively blocking the interaction between IBV-N and SARS-CoV-2-N and quinone sulfide oxidoreductase, mitochondrial autophagy activation, H2S accumulation in cells and mitochondrial potential depolarization are effectively inhibited, and the expression of innate immune molecules is recovered, so that virus replication is resisted, and lung injury is relieved. The invention solves the problems of difficulty in blocking protein interaction, poor peptide stability and incapability of effectively recovering immune pathways in the prior art, and has the advantages of high in-vitro and in-vivo stability, small toxic and side effects, large patent medicine potential and the like.

The application discloses a Parkinson's disease targeted application of a pueraria exosome loaded with a mitochondria-activated miRNA, and belongs to the field of biological applications.The miRNA comprises at least one of miRNAs shown in sequences as shown in SEQ ID No, 1 to SEQ ID No, 23.The pueraria exosome and the miRNA delivered thereby in the application show a good treatment effect on Parkinson's disease, and mainly play a role in improving mitochondrial dysfunction, such as promoting mitochondrial autophagy, improving mitochondrial membrane potential, reducing oxidative stress, maintaining the integrity of the mitochondrial inner membrane respiratory chain, and increasing ATP generation.The application further discloses a delivery scheme of the pueraria-derived exosome as the miRNA carrier by using neuron-targeted modification, which can improve the targeting and stability of the miRNA, and overcome the problems of low miRNA drug delivery efficiency and easy degradation.The application is expected to promote the treatment process of Parkinson's disease through the neuron-targeted pueraria exosome and the miRNA delivered thereby.

This invention relates to the field of biomedical technology, disclosing extracellular vesicles derived from Poria cocos and their application in the development and preparation of drugs for the prevention or treatment of metabolic-associated steatohepatitis (MAS). The drugs improve liver tissue morphology and pathological lesions, regulate serum and liver lipid levels and inflammatory factor levels, and regulate mitochondrial structure and function, including alleviating mitochondrial ultrastructural damage, increasing the number of autophagosomes, improving oxidative stress and energy metabolism, promoting the expression of mitochondrial autophagy-related proteins, and reducing the production and efflux of Ox-mtDNA, thereby inhibiting the expression of NLRP3 inflammasome-related proteins. These drugs can improve MAS and provide a new direction for the development and research of drugs for the prevention and treatment of MAS.

The invention discloses application of melatonin in preparation of products for resisting skin aging, promoting collagen regeneration, improving mitochondrial dysfunction and enhancing proline synthesis. A large number of studies show that melatonin intervention can improve mitochondrial dysfunction and up-regulate proline and total collagen content at the same time, so that proline generation can be promoted by adding melatonin to mediate mitochondrial dynamic balance, and the application prospect in collagen content improvement is wide. The melatonin improves the autophagy level of mitochondria, eliminates damaged mitochondria and increases proline synthesis in the mitochondria, so that the collagen content is increased, the elasticity in aged skin can be remarkably improved, and finally the symptom of skin aging is improved. The melatonin is safe, non-toxic, small in dosage and good in stability, and has a wide application prospect in preparation of anti-skin aging products.

The invention discloses an application of isovitexin in preparation of a medicine for treating oral submucosal fibrosis (OSF). Experiments prove that isovitexin improves OSF pathological changes in a dose-dependent manner, and the effect of isovitexin is superior to that of a positive control drug tanshinone II A. The mechanism is to up-regulate Mfn2 and STX17 protein expression, enhance mitochondrial and lysosome co-localization and STX17-VDAC1 combination, down-regulate mitochondrial DNA copy number and ROS generation, and regulate mitochondrial autophagy; meanwhile, the level of p-Smad3 is reduced, the secretion of type I collagen is reduced, the activity of MMP-1 is improved, collagen deposition is reduced, and the mitochondrial membrane potential is improved. The oral coating particle prefabricated tablet (prepared from isovitexin, hydroxypropyl methyl cellulose and the like) and the gel (containing isovitexin, carbomer 940 and the like) provided by the invention are administrated through local smearing or focus injection, the mucous membrane morphology can be effectively recovered, the mouth opening degree can be improved, the safety is good, and a new choice is provided for OSF treatment.