85 results about "Mitophagy" patented technology

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.

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 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 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 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 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 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.

The invention discloses genetically modified neisseria gonorrhoeae and a neisseria gonorrhoeae outer membrane vesicle vaccine, and a gene modification mode is that at least one of a coding gene of PorB1a protein and a coding gene of PorB1b protein is subjected to gene mutation, so that the capability of inducing mitochondrial autophagy is reduced or weakened. According to the present invention, the induction of the mitochondrial autophagy pathway is effectively prevented by precisely mutating the key amino acids (PorB1a-K117Q / K171Q or PorB1b-K117Q / K170Q) at the 117 site and the 171 / 170th site of the PorB protein; the protective efficacy of the neisseria gonorrhoeae OMVs vaccine is improved compared with that of the neisseria gonorrhoeae OMVs vaccine prepared from wild bacteria, and a new treatment means is provided for gonorrhoeae prevention and treatment.

A naphthaleneimide compound, its preparation method, and application. The present invention provides a naphthaleneimide compound, the structure of which is shown in Formula I: R is selected from one of the following: The present invention also provides a method for preparing the naphthaleneimide compound. The compound has the ability to accurately trace mitochondrial autophagy and has the ability to release peroxynitrite (ONOO) ‑ The responsiveness and mitochondrial targeting capabilities of the ELISA can be applied to prepare a kit for tracking oxidative stress-induced mitophagy and / or peroxynitrite activation.

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 belongs to the technical field of biology, and particularly relates to a mitochondrial function evaluation method and application thereof. The invention provides an innovative mitochondrial function evaluation method which comprises the following steps: reporting ATP concentration change and mitochondrial morphology in a mitochondrial matrix in real time, in situ and quantitatively through ATP response fluorescent protein Mito-AT1.03 with a mitochondrial positioning signal, and directly reflecting mitochondrial energy metabolism and mitochondrial fusion / division states; meanwhile, a mitochondrial autophagy key initiation factor Parkin protein is utilized to construct a fusion protein Parkin-mCherry, and the fusion protein Parkin-mCherry is used as an early-stage specific marker for autophagy initiation. The two fluorescent proteins are co-transfected into cells, and the signal levels and positioning conditions of the two fluorescent proteins are observed, so that the mitochondrial function can be accurately evaluated in real time, and a new thought is provided for methodology development of mitochondrial dysfunction mechanism research and mitochondrial function regulator screening.

The invention relates to the technical field of biological medicines, in particular to application of surface-engineered mitochondria for activating mitochondrial autophagy in preparation of a medicine for treating pulmonary fibrosis. According to the present invention, the antibody is covalently coupled to the PLL modified exogenous mitochondrial surface to construct the Ab-mito with characteristics of positive electricity and targeting function, such that the efficient mitochondrial transplantation to the recipient cell is promoted, the problems of poor selectivity and low efficiency confronted by the existing mitochondrial delivery research are overcome, and the new direction is provided for the pulmonary fibrosis treatment. The treatment effect of the traditional Chinese medicine composition on pulmonary fibrosis is equivalent to that of a clinical medicine nintedanib, and the method is simpler and more effective.

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 relates to the application of FUNDC1 inhibitors in the preparation of drugs for preventing and treating photodamage to the skin. Specifically, FUNDC1 inhibitors alleviate, reduce, or prevent photodamage by inhibiting or reducing FUNDC1 expression. This invention establishes a photodamage model using mouse skin and HaCaT cells irradiated with UVB. UVB treatment showed downregulation of FUNDC1 expression. Given that FUNDC1 overexpression exacerbates UVB-induced photodamage, this invention explores whether knocking down FUNDC1 can protect HaCaT cells and the mouse model from UVB-induced photodamage. After FUNDC1 knockdown, cell viability increased to 80%, and compared to the UVB group, ROS levels, apoptosis, and γH2Ax expression were reduced. Following UVB irradiation, FUNDC1 knockdown also alleviated mitochondrial damage, manifested as uniform mitochondrial distribution along the cell nucleus, mitochondrial membrane potential repolarization, and reduced mtROS accumulation. This invention proposes that intervening in FUNDC1-mediated mitophagy, by regulating the mitochondrial apoptosis pathway, can protect against UVB-induced mitochondrial and photodamage, providing a potential target for future mitigation of photodamage to the skin.

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 invention discloses a mitochondrial autophagy enhanced chimeric molecule based on E3 protein ubiquitin ligase ITCH and application of the mitochondrial autophagy enhanced chimeric molecule, and belongs to the field of medicinal chemistry. The structure of the chimeric molecule is I-L-O ', I represents a ligand combined with ITCH, L represents a connecting chain, and O' represents a ligand combined with mitochondrial outer membrane protein. The mitochondrial outer membrane protein comprises a translocation protein and a voltage-dependent anion channel protein. The chimeric molecule can effectively enhance mitochondrial autophagy and repair mitochondrial damage under low concentration (10-100 nanomolar concentration) so as to enhance mitochondrial functions, and verification is carried out in various cells and animal bodies, so that a blank in the field is filled.

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.