123 results about "Mitophagy" patented technology

The present invention relates to novel isoquinoline derivatives. The derivative has the effect of promoting mitochondrial autophagy activity, so that mitochondria with damaged structure and / or function is reduced. Specifically, the novel isoquinoline derivative according to the present invention does not induce mitochondrial dysfunction and has been determined as a safe compound that is non-toxic to cells, and thus it can be used to prevent, ameliorate and / or treat various diseases that may be caused by mitochondrial abnormality.

The invention provides a traceable mitochondrial targeting nano system as well as a preparation method and application thereof, and belongs to the field of medicines. The traceable mitochondrial targeting nano system constructed by the invention can continuously release resveratrol and maintain the photochemical stability of resveratrol. The nano system shows efficient cellular uptake and accurate mitochondrial targeting ability, and promotes removal of mitochondrial ROS and adjustment of mitochondrial autophagy, so that vascular leakage and angiogenesis are relieved, in-vivo microvascular hyperplasia and retina degeneration are remarkably inhibited, and the curative effect is improved. The distribution of the compound in fundus can be monitored in real time through clinical ophthalmological diagnosis equipment, and the compound has a good application prospect in preparation of drugs for preventing and / or treating diabetic retinopathy.

The invention discloses a preparation method and application of a multifunctional layered nanosheet. The biomimetic hydrogel is prepared through a hydrothermal method, folic acid (FA) is modified on the surface of the biomimetic hydrogel, and the biomimetic hydrogel has the capacity of targeted recognition of pro-inflammatory phenotype macrophages, has the biomimetic activity of multiple enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and can effectively remove ROS; meanwhile, a succinate dehydrogenase (SDH) inhibitor dimethylmalonic acid (DMM) is loaded in an intercalation mode of the nano material, SDH activity is inhibited in a slow release mode, ROS outbreak caused by mitochondrial reverse electron transfer (RET) is blocked from the source, then a mitochondrial autophagy pathway mediated by BNIP3-LC3B is started, and dynamic and steady state recovery of mitochondria is achieved. The system finally realizes macrophage mitochondrial function reconstruction, oxidation environment improvement and transfer of healthy mitochondria to osteoblasts, so that the osteogenic differentiation capability is recovered, and the effect of treating osteoporosis is achieved.

Described herein, inter alia, are compositions comprising and methods of making and using endothelial cells (ECs) comprising one or more mitophagy-inducing agents (e.g., rapamycin, SKF-96365, lithium, carbamazepine, latrepirdine, spermidine, resveratrol, sodium valproate, trehalose, kaempferol, metformin, AICAR, nilotinib, ambroxol, curcumin, and VL-004). Also described herein, inter alia, are methods vascular cell therapy, promoting blood vessel formation, and increasing vascular development, angiogenesis, and cell junction via administration of a population of ECs comprising a mitophagy-inducing agent (MIA-ECs).

The present invention relates to an application and product of mitochondrial DNA G-tetramer in sperm in male infertility detection, and belongs to the field of biomedical technology. The level of mitochondrial DNA G-tetramer in sperm is used as a reference indicator for semen analysis, and is applied to male infertility detection products, providing an effective theoretical reference for male infertility in sperm pathophysiology; then, an adapted TPE-mTO fluorescent probe is used as a relevant detection means to detect the level of mitochondrial DNA G-tetramer in sperm, thereby achieving efficient and convenient clinical detection. In addition, a mitochondrial autophagy inducer is used to restore abnormal fertilization caused by increased sperm mitochondrial DNA G-tetramer levels, and the application and product of the mitochondrial autophagy inducer in abnormal fertilization are proposed, providing a new potential treatment reference and theoretical basis for patients with sperm mitochondrial DNA G-tetramer dysfunction.

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 chimeric molecule for enhancing mitophagy, which, at a low concentration, can effectively enhance mitophagy, repair mitochondrial damage, and thus enhance mitochondrial functions, and has been verified in various cells and in animals. The chimeric molecule has wide application values in the prevention or treatment of diseases of mitochondrial dysfunction.

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 invention belongs to the technical field of preparation and application of natural products, and particularly relates to a perilla frutescens extract product for activating mitochondrial autophagy and resisting aging and application of the perilla frutescens extract product. Perillaldehyde is obtained by purifying perilla leaves, and the purity reaches 99%. The compound has DPPH free radical scavenging capacity and tyrosinase activity inhibition capacity, and the DPPH free radical scavenging capacity is equivalent to that of vitamin E; the service life of the high-concentration perillaldehyde group is prolonged by 8%; the service life of caenorhabditis elegans under the environments of thermal stimulation, ultraviolet stimulation and oxide stimulation is remarkably prolonged, and the adversity service life prolonging rate of a high-concentration perillaldehyde group is at least 20%; sOD (superoxide dismutase) and CAT (catalase) activity of caenorhabditis elegans is remarkably improved, H2O2 accumulation is reduced, and anti-stress capability is improved; the caenorhabditis elegans mitochondrial autophagy is promoted, the mitochondrial autophagy pathway related genes are adjusted, the mitochondrial function is improved, the NAD < + > / NADH ratio is increased, the body metabolism is maintained, and the aging is delayed; the perillaldehyde capable of promoting the mitochondrial autophagy pathway can be applied to development of anti-aging drugs, health care products, food, cosmetics and other products.

The present invention belongs to the field of molecular biology, and particularly relates to a mutant and a mutant plasmid of an FUNDC1 gene, and a construction method therefor and the use thereof. The provided mutant plasmid has an increased FUNDC1 protein expression level, and can increase the protein expression level of mitophagy proteins COXⅣ and TOM20. After the transfection of the mutant plasmid, the cell activity and mitochondrial membrane potential are not significantly changed, indicating that the mutant plasmid can inhibit mitophagy and causes no damage to mitochondria, which provides a feasible solution for the preparation of a mitophagy drug, and has great significance for the research on the pathophysiological mechanism of myocardial I / R injuries.

The present invention belongs to the field of biomedical technologies and discloses the use of arylsulfatase K in the preparation of drugs for preventing, delaying or treating chronic obstructive pulmonary disease. The present invention has for the first time discovered the role of ARSK (arylsulfatase K) in inhibiting mitophagy and delaying the senescence of airway epithelial cells, and further determined the key role of ARSK in the occurrence and development of COPD, which can provide a new target for the prevention and treatment of COPD. The present invention has determined that ARSK can slow down the process of lung senescence by alleviating the process of mitophagy, inhibiting the senescence of airway epithelial cells, thereby providing a new treatment strategy for COPD.

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 invention relates to a chimeric molecule that enhances mitochondrial autophagy. It can effectively enhance mitochondrial autophagy at low concentrations, repair mitochondrial damage, and thus enhance mitochondrial function. The activity has been verified in a variety of cells and animals. The chimeric molecule of the present invention has a wide range of application value in preventing or treating diseases caused by mitochondrial dysfunction.

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 present invention is related to compound of formula (I) or a salt thereof: (I) or a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a compound of formula (I), which are useful for preventing and / or treating Mitophagy related diseases.

The invention provides a compound of formula (I) wherein: A, B, C, D, W, X, Y and Z are each independently selected from H and OH; or a salt thereof; for use in the treatment and / or prophylaxis of a condition, disease or disorder in a subject, wherein the compound or salt is orally administered to a subject in a daily amount of from 1.7 to 2.7 mmol per day, over a period of at least 21 days. Also are provided are the compound of formula (I) for use in increasing mitophagy and / or autophagy, maintaining and / or improving muscle function and administration as a dietary, nutritional and / or health supplement.

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.

The present application relates to the technical field of targeted nanoparticles, and particularly relates to a mitochondria-targeting autophagy-inhibiting polymer and a preparation method thereof, a nano delivery particle and a preparation method and application thereof. A high molecule TPP-PEG-SH (TPS) containing a triphenylphosphonium group (triphenylphosphonium, TPP) is coupled with a mitochondria autophagy inhibitor Mdivi-1 through a disulfide bond to construct a polymer TPSM with mitochondria targeting ability and GSH responsiveness, and further co-assembled with a photosensitizer IT-4Cl to form a nano delivery system TPSM@IT-4Cl. The nano delivery system has mitochondria targeting ability, promotes continuous accumulation of oxidative stress at a tumor site, and can realize responsive drug release in a high-concentration GSH tumor microenvironment.

A pharmaceutical composition containing a mitophagy inducer as an active substance. The pharmaceutical composition is conducive to being prepared into a pharmaceutical preparation, can avoid incompatibility caused by the interaction between the active substance and an auxiliary material, and thus can be stored for a long period of time.

A skin care composition that includes bioactive materials, other optional skin ingredients, and a dermatologically acceptable carrier. The materials stimulate mitophagy and prevent or reverse cellular aging to help improve skin health and appearance.

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 discloses a composition with a tumor mitochondrial dual regulation effect, temperature-sensitive hydrogel and application, and belongs to the technical field of biological medicine, the composition is composed of a peroxide initiator and a mitochondrial autophagy inhibitor, the peroxide initiator is used for causing mitochondrial damage, and the mitochondrial autophagy inhibitor is used for causing mitochondrial autophagy. The mitochondrial autophagy inhibitor is used for inhibiting mitochondrial The peroxide initiator is indocyanine green, chlorin, iron oxide nanoparticles or Fe-MOFs (Metal-Organic Frameworks); the mitochondrial autophagy inhibitor is chloroquine, 3-methyladenosine or bajulomycin A1; the tumor is specifically melanoma; the combination of the peroxide initiator and the mitochondrial autophagy inhibitor can better inhibit the energy metabolism of tumor cells and inhibit the occurrence and development of tumors, and after the composition is delivered through the temperature-sensitive hydrogel carrier, the treatment effect of the composition on tumors is further improved.

The invention belongs to the technical field of biology, and discloses siRNA for inhibiting BNIP3L protein expression and application of the siRNA in preparation of a medicine for resisting myocardial cell hypoxia injury. The siRNA for inhibiting BNIP3L protein expression is composed of a positive-sense strand and an antisense strand, the nucleotide sequence of the positive-sense strand is as shown in SEQ ID No. 1, and the nucleotide sequence of the antisense strand is as shown in SEQ ID No. 2. The siRNA for inhibiting the expression of the BNIP3L protein can obviously inhibit the expression of the BNIP3L of myocardial cells H9c2, down-regulate the autophagy level of mitochondria and obviously enhance the cell activity and mitochondrial function of the myocardial cells under hypoxia, and has the effect of resisting hypoxia-induced myocardial injury.

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.

Compositions and methods for modulation by upregulation (up modulation) and / or downregulation (down modulation) of mitophagy are described for the treatment of mitochondrial disorders including OPA-1 related disease and Single Large Scale Mitochondrial DNA Deletion (SLSMD). Also disclosed are a number of screening assays and gene targets having utility for the identification of agents which modulate the phenotype associated with such disorders.

The present application belongs to the field of biomedical technology, and specifically relates to a breast milk-derived polypeptide and its application in preventing and treating childhood obesity. The breast milk-derived polypeptide provided in the present application has an amino acid sequence as shown in SEQ ID NO.1, and the breast milk-derived polypeptide has significant effects in enhancing thermogenesis of brown adipose tissue in lactating mice, reducing the body weight of obese mice mediated by a high-fat diet, improving glucose metabolism, enhancing mitochondrial quality, and reducing mitochondrial autophagy. The breast milk-derived polypeptide and its pharmaceutical composition have good application prospects in the preparation of drugs for preventing and treating childhood obesity.

The invention relates to the technical field of tumor cell metabolism analysis, and discloses a tumor cell metabolism comprehensive evaluation system based on mitochondrial function indexes. Comprising a multi-dimensional detection module used for acquiring detection data of mitochondrial membrane potential, active oxygen and cell ATP energy cycle products of tumor cells; the control module is in communication connection with the multi-dimensional detection module and is configured to receive the detection data and establish a comprehensive analysis model containing energy metabolism, oxidative stress and mitochondrial autophagy related parameters based on the bidirectional regulation and control relationship between the HIF-1alpha and mitochondria so as to perform correlation analysis and weight calculation on the detection data, and the weight of the comprehensive analysis model is calculated; generating a comprehensive evaluation index reflecting the metabolic state of the tumor cells; and outputting a metabolic characteristic analysis report corresponding to the comprehensive evaluation index, wherein the metabolic characteristic analysis report comprises comprehensive evaluation results of the tumor cell mitochondrial oxidation phosphorylation level, mitochondrial autophagy activity and oxidative pressure.