44 results about "Oxidative phosphorylation" patented technology

The invention belongs to the field of biological medicine, and particularly relates to PGK1 K17 site succinylation modification and application. Experiments show that the 17-site lysine of the PGK1 protein has succinylation modification (PGK1 K17su), and the existence of the modification is confirmed through a specific succinylation modified antibody for the first time. Further, it is found that PGK1 K17su can weaken lung cancer cell oxidative phosphorylation and promote glycolysis metabolism by inhibiting lung cancer cell mitochondrial generation, and functional experiments prove that PGK1 K17 succinylation modification promotes proliferation and migration of lung cancer cells.

The invention belongs to the technical field of biological medicine, and relates to pharmaceutical application of an oxidative phosphorylation inhibitor, in particular to application of the oxidative phosphorylation inhibitor in preparation of an immunomodulatory drug, and the immunomodulatory drug has the advantages that the function damage of newborn myeloid-derived suppressor cells caused by antagonism BCG (bacillus calmette guerin) vaccination is inhibited, and the immunomodulatory effect is improved. The compound is used for preventing or treating neonatal immune-related diseases caused by bacillus calmette guerin vaccine inoculation. The invention finds that the BCG can cause damage to the immunosuppression function of the MDSC of the suckling mouse through up-regulation oxidative phosphorylation, and the negative effect caused by inoculation of the BCG can be reversed by using the OXPHOS inhibitor, so that the immunosuppression function of the MDSC of the suckling mouse is successfully recovered in an in-vivo and in-vitro model, and the immune-related adverse reaction caused by inoculation of the BCG is expected to be improved.

The invention discloses an application of a pyruvate dehydrogenase kinase (PDKS) inhibitor in preparation of a composition for treating Alzheimer's disease (AD), and particularly discloses an application of the PDKs inhibitor in preparation of the composition for treating the AD. According to the invention, the level of oxidative phosphorylation (OXPHOS) of microglial cells is obviously enhanced, the inflammatory response of the microglial cells is effectively reduced, the migration and aggregation capabilities of the microglial cells are obviously improved, the capability of the microglial cells to phagocytize and degrade extracellular beta-amyloid protein (A beta) plaque is obviously enhanced, the cognitive function defect of AD model mice is effectively improved, and the application of the microglial cells in the treatment of the AD model mice is promoted. The preparation is simple, and the application is wide.

A device for activating the mitochondrion, wherein negative charge and reactive oxygen are delivered from outside to the mitochondrion via a negative charge and reactive oxygen delivery unit to serve as material for the mitochondrial redox reaction; and, wherein a calcium ion channel stimulation unit can stimulate an in vivo calcium ion to transport a protein across a calcium ion on an inner membrane of the mitochondrion into a matrix space of the mitochondrion, whereby an influx of the calcium ion promotes the depolarization of the mitochondrion and increases the activity of mitochondrial oxidative phosphorylation.

The invention discloses a polyphosphate-metal nano-composite as well as a preparation method and application thereof, and belongs to the technical field of biological medicines and nano-materials. The polyphosphate-metal nano-composite is formed by self-assembly of polyphosphate and metal ions under the coordination action; wherein the chain length of the polyphosphate is 20 to 75. According to the invention, divalent metal ions are introduced, so that polyphosphate and metal ions form a spherical nano-composite through coordination self-assembly, the composite can be absorbed by tumor cells and degraded under an acidic condition, released polyphosphoric acid is separated through unique Ca < 2 + > phase, Ca < 2 + > is enriched around mitochondria, and the function of tumor treatment is realized. And tumor cell metabolism reprogramming is caused to be dominated by oxidative phosphorylation, so that copper death and immunoregulation are induced, and a triple synergistic anti-tumor effect is realized.

The invention discloses a novel application of total glucosides of paeony in preparation of a medicine for treating triple negative breast cancer. In-vitro and in-vivo experiments prove that the total glucosides of paeony can remarkably inhibit proliferation, migration and invasion of triple negative breast cancer cells (MDA-MB-231 and MDA-MB-468), reverse an epithelial-mesenchymal transition process and induce cell apoptosis by inducing mitochondrial injury, inhibiting oxidative phosphorylation and activating a mitochondrial apoptosis pathway. In an MDA-MB-231 cell xenotransplantation tumor nude mouse model, the total glucosides of paeony can effectively inhibit tumor growth. Therefore, the total glucosides of paeony can be used for preparing the medicine for treating the triple negative breast cancer, and a new treatment choice is provided for clinic.

The invention provides an application and a method of GSH in promoting mature differentiation of hiPSC-CMs, and the method is characterized in that in the process of directionally differentiating the hiPSC-CMs into the hiPSC-CMs, an effective dose of GSH is added into a differential medium, and the optimal concentration is 20-100 [mu] M. According to the invention, through simple and economical exogenous supplement of GSH, maturation of hiPSC-CMs is systematically promoted from multiple dimensions, including enhancement of intracellular anti-oxidation defense capability; energy metabolism is promoted to be converted from glycolysis to oxidative phosphorylation; up-regulating expression of cardiac muscle cell specific structural protein and calcium ion channel related genes; mitochondrial biological generation and functions are promoted; and the cell morphological structure is induced to develop to a mature phenotype. The method is simple and convenient to operate and high in biocompatibility, the hiPSC-CMs with mature functions can be stably obtained, and a high-quality cell source is provided for application of the hiPSC-CMs in the fields of heart disease modeling, drug cardiotoxicity screening and the like.

The invention discloses application of a membrane-bound O-acyltransferase structural domain 7 (Mboat7) in preparation of a medicine for treating myocardial infarction, and belongs to the technical field of biology. A research result shows that in a mouse myocardial infarction model, compared with a control group mouse, the death rate of a myocardial cell specific Mboat7 gene overexpressed mouse is reduced, the infarction area is remarkably reduced, and the cardiac function is remarkably improved; the overexpressed Mboat7 gene can relieve mitochondrial damage of myocardial cells under the hypoxia condition and improve the mitochondrial oxidative phosphorylation function. Particularly, overexpression of the Mboat7 gene can improve damage of mitochondria in myocardial tissues of mice suffering from myocardial infarction. The results show that Mboat7 gene overexpression can relieve myocardial damage after myocardial infarction so as to delay the progress of heart failure, and Mboat7 or an expression promoter thereof can be used for preparing the medicine for preventing, relieving and / or treating myocardial infarction.

The invention belongs to the technical field of medicines, and particularly relates to application of arginine in repairing skeletal muscle injury caused by monensin poisoning. It is found for the first time that arginine can remarkably recover the normal function of skeletal muscle mitochondria and the normal polymerization capacity of microtubules by up-regulating the expression level of mitochondrial oxidative phosphorylation (OXPHOS) protein complex and regulating microtubule polymerization kinetics and reversing monensin-induced skeletal muscle mitochondrial dysfunction and microtubule network disintegration; the method provides a theoretical basis for clinical transformation, and has good practical application value.

The present application relates to the technical field of biological medicine, and particularly relates to application of a nucleic acid vector encoding a macrophage monocarboxylate transporter MCT1 in preparation of a pharmaceutical composition for promoting corneal nerve regeneration and recovery of corneal sensitivity after corneal nerve injury. The present application finds that after corneal nerve injury, increasing the level of macrophage MCT1 can drive the change of the metabolic mode of macrophages to the direction of enhanced oxidative phosphorylation and reduced glycolysis, reduce the expression of local pro-inflammatory related factors, and increase the level of pro-regeneration factors and neurotrophic factors, thereby improving the regeneration of corneal nerve structure and the recovery of sensory function. Therefore, a macrophage-targeted or macrophage-biased expression vector containing a nucleic acid sequence encoding MCT1 can be used for preparation of a pharmaceutical composition for treating corneal nerve injury.

The present invention relates to a method for activating the mitochondrion, wherein mainly negative charges and reactive oxygen species are supplied to the mitochondrion from the outside via a negative charge and reactive oxygen species delivery unit to serve as material for the mitochondrial redox reaction. A calcium ion channel stimulation unit stimulates an in vivo calcium ion to transport the protein across the calcium on the inner mitochondrial membrane into a mitochondrial matrix space, such that the influx of calcium ions promotes mitochondrial depolarization and increases the activity of mitochondrial oxidative phosphorylation. This enhances mitochondrial activation and ATP production.

The present disclosure relates to treating mitochondrial diseases, cancer and other conditions as a result of reduced oxidative phosphorylation (OXPHOS) activity by overexpressing the METTL17 gene, encoding methyltransferase-like 17. Currently, overexpression of METTL17 to increase its copy number and / or intra-mitochondrial activity has not been indicated as a possible therapeutic for treating mitochondrial disease or other diseases such as cancer or aging related to a decline in OXPHOS activity. A variety of gene therapy approaches are presented for overexpression of METTL17 including, but not limited to, AAV, adenovirus and lentiviral vector expression.

The invention discloses application of dendrobium officinale polysaccharide in preparation of a PGC-1alpha signal channel inhibitor, and research shows that dendrobium officinale can regulate and control metabolic gene expression of macrophages in a tumor microenvironment, promote polarization of macrophages M1 and effectively inhibit occurrence and development of tumors; meanwhile, the dendrobium candidum polysaccharide can also promote glycolysis metabolism of tumor-related macrophages, remarkably promote expression of macrophage glycolysis-related genes, inhibit expression of oxidative phosphorylation genes and PGC-1alpha genes, effectively reduce the volume and size of tumors, inhibit PGC-1alpha signal channels in the macrophages and inhibit the growth of tumor cells. In addition, the dendrobium officinale polysaccharide can be used as a PGC-1alpha signal channel inhibitor for preparing antitumor drugs, and a new way is provided for improving the metabolic state in a tumor microenvironment and tumor immunotherapy.

The invention belongs to the technical field of medicines, and particularly relates to application of arginine in repairing skeletal muscle injury caused by monensin poisoning. It is found for the first time that arginine can remarkably recover the normal function of skeletal muscle mitochondria and the normal polymerization capacity of microtubules by up-regulating the expression level of mitochondrial oxidative phosphorylation (OXPHOS) protein complex and regulating microtubule polymerization kinetics and reversing monensin-induced skeletal muscle mitochondrial dysfunction and microtubule network disintegration; the method provides a theoretical basis for clinical transformation, and has good practical application value.

This invention discloses a method for constructing a lupus susceptibility animal model and its application. This application is the first to propose using MTCH2 knockout to construct a lupus animal model, building the model at multiple tissue levels (systemic knockout and B cell-specific knockout). Using this model, a series of functions of lupus B cells, including apoptosis, activation, mitochondrial membrane potential difference, oxidative stress, oxidative phosphorylation, and antibody production, are investigated in depth. This verifies the important role of the MTCH2 molecule in the progression of lupus disease and provides new insights for the study of the disease mechanism of lupus and the screening of therapeutic drugs.

The invention provides a method for improving the sensitivity of an esophageal squamous carcinoma (ESCC) patient to neoadjuvant chemoradiotherapy. Specifically, by reducing the levels of CEBPB, AREG and / or EREG proteins, mitochondrial oxidative phosphorylation (OXPHOS) is inhibited, TCA circulation is inhibited, and / or ERBB signal pathways are inhibited, so that the sensitivity of ESCC patients to neoadjuvant radiotherapy and chemotherapy is improved. In addition, the invention also provides a method for predicting the sensitivity of an ESCC patient to neoadjuvant chemoradiotherapy, and a biomarker for predicting the sensitivity of the ESCC patient.

The application discloses a mycotoxin attenuant for improving mitochondrial function and application, and has the following components: 10-20 parts by weight of L-malic acid, 3-5 parts by weight of alpha-ketoglutaric acid (salt), 15-25 parts by weight of itaconic acid and 1-3 parts by weight of 5-norwongenin. In mycotoxin contaminated feed, the addition of L-malic acid, alpha-ketoglutaric acid (salt), itaconic acid or 5-norwongenin alone cannot improve mitochondrial function or relieve mycotoxin toxicity. Compared with the combination of any one of the four components, the complete addition of the four components can significantly enhance mitochondrial oxidative phosphorylation, weaken glycolysis, obviously improve mitochondrial energy metabolism, effectively relieve mycotoxin-induced mitochondrial damage in the intestines and liver of livestock and poultry, and thus improve the production performance and health status of livestock and poultry. The application can significantly reduce the toxic effect of mycotoxin on livestock and poultry through the synergistic effect of the components.

Aging progresses at different rates among individuals, underscoring the need for better indicators of functional decline. The inventors showed that the T cell energy metabolism in the elderly reveals that high mitochondrial oxidative phosphorylation, especially in CD4 T regulatory cells, is associated with a reduced probability of being frail / prefrail, independent of age, sex, or comorbidities. When mitochondrial respiration drops below a critical threshold, it adversely affects intrinsic capacity. Furthermore, a low level of oxidative phosphorylation in CD4 T helper cells, particularly in central and effector memory subsets, was significantly associated with a faster decline in intrinsic capacity over time, suggesting that T cell mitochondrial bioenergetics represents a key biomarker for managing functional decline in older adults. Accordingly, the present invention relates to a method for determining the risk of age-related functional decline in a subject comprising the step of measuring the mitochondrial dependency in a population of T cells wherein the mitochondrial dependency (MitoDep) correlates with the age-related functional decline.

The invention provides mitochondrial oxidative phosphorylation gene characteristics for prognosis prediction of lung adenocarcinoma, and a risk scoring model and a prognosis prediction model are constructed according to the mitochondrial oxidative phosphorylation gene characteristics. According to the model, survival risk layering can be accurately carried out on the lung adenocarcinoma patient, and reliable reference is provided for clinical treatment strategy formulation and individualized management.

The present application relates to a kind of compound for treating myocardial hypertrophy disease, it is related to the field of biological medicine.The compound can effectively improve the left ventricular systolic function of myocardial hypertrophy mouse, reduce heart weight / body weight, lung weight / body weight, myocardial cell cross-sectional area and fibrosis;Meanwhile, the compound can relieve angiotensin II induced myocardial hypertrophy in vitro.Especially, the compound can improve the damage and dysfunction of mitochondria in myocardial tissue of myocardial hypertrophy mouse, while improving the oxidative phosphorylation level of myocardial cell after angiotensin II stimulation, has the potential of preparation treatment myocardial mitochondrial damage, inhibits myocardial cell hypertrophy, treatment myocardial hypertrophy and heart failure drug.

The invention provides a medicine for targeting early-stage precursor T cell acute lymphocytic leukemia (ETP-ALL) and application of the medicine. Dichloroacetic acid (DCA) is used for regulating mitochondrial oxidative phosphorylation, so that electron transport chain flux can be enhanced, ROS (reactive oxygen species) generation can be promoted, endoplasmic reticulum stress related pathways can be activated, the proliferation states of an ETP-ALL leukemia cell line and a primary patient sample can be influenced, and cell apoptosis can be induced. In cell line-derived and patient-derived xenograft models, DCA treatment can reduce leukemia load in bone marrow, spleen and peripheral blood and affect tumor formation characteristics. DCA shows good tolerance in normal hematopoietic system and other leukemia models. The method provides a treatment strategy based on metabolism targeted regulation, and provides a potential technical route and application reference for ETP-ALL research and drug development.

The application discloses a kind of adipose tissue-derived mitochondrial-derived vesicles and its preparation method and application, belong to the field of biological medicine.The preparation method includes obtaining mouse adipose tissue, including at least one of interscapular brown adipose tissue, epididymal white adipose tissue, beige adipose tissue, in vitro cultured adipocyte;Mouse adipose tissue homogenate is removed by differential centrifugation Unbroken cell, nucleus, mitochondrial and organelle precipitate, the supernatant obtained is treated by trypsin and then ultracentrifuged, the precipitate is collected, washed, to obtain mitochondrial-derived vesicles, which are membrane-coated vesicles, with a particle size of 100-200 nm, enriched in mitochondrial membrane proteins and oxidative phosphorylation-related proteins, and proved by ischemic heart disease model that it can improve heart function, reduce the degree of ventricular remodeling in mice with ischemic heart disease and reduce the fibrosis area, for the preparation of drugs for preventing or treating ischemic heart disease, and has important clinical application value.

The invention belongs to the field of biological medicine, and discloses a pharmaceutical composition combining an aquaporin inhibitor and an oxidative phosphorylation inhibitor for treating brain glioma, and the pharmaceutical composition comprises an AQP4 inhibitor AER-270 and an oxidative phosphorylation inhibitor Gboxin. The invention further discloses a pharmaceutical preparation containing the pharmaceutical composition and application of the pharmaceutical preparation to preparation of drugs for treating brain glioma. According to the composition provided by the invention, through combined administration of the AER270 and the Gboxin, the inhibition effect on the brain glioma is obviously better than that of single AER270 or single Gboxin, the combination of the AER270 and the Gboxin has a synergistic effect on treatment of the brain glioma, and an effective drug combination strategy is provided for treatment of the brain glioma.

The application belongs to the technical field of antitumor drugs, and relates to a Zn-penicillamine nano-chelating agent and a preparation method and application thereof. The nano-chelating agent is a non-water-soluble nanomaterial formed by chelating coordination of zinc ions and D-penicillamine. The preparation method is as follows: D-penicillamine and a divalent zinc salt are uniformly mixed in a solution, the pH is adjusted to neutral or alkaline, and continuous stirring reaction is carried out, and the Zn-penicillamine nano-chelating agent is obtained. The Zn-penicillamine nano-chelating agent provided by the application can interfere with cell ion homeostasis, realize dual inhibition of oxidative phosphorylation (OXPHOS) and glycolysis metabolism in breast cancer, and effectively activate an antitumor immune response.

The invention belongs to the technical field of medicines, and discloses a cationic pyrrole compound with an aggregation-induced emission property as well as a preparation method and application thereof. The structure of the cationic pyrrole compound is shown as a formula I or a formula IV. The invention discloses a preparation method of the compound. The compound can specifically target mitochondria, is combined with SDHAF1 protein with high affinity, and inhibits the activity and oxidative phosphorylation function of a compound II, thereby efficiently killing acute myelogenous leukemia cells. Meanwhile, the compound also shows remarkable inhibitory activity on pathogenic fungi such as candida albicans. The compound provided by the invention is used for preparing SDHAF1 inhibitors, mitochondrial targeting fluorescence imaging agents, drugs for treating oxidative phosphorylation dependent cancers such as acute myelogenous leukemia and / or antifungal drugs. Formula I: Formula IV:

The invention discloses an MFN1 engineered mitochondrial vesicle and an application of the MFN1 engineered mitochondrial vesicle in preparation of an anti-cell aging drug. The MFN1 engineered mitochondrial vesicles are prepared by the following steps: firstly, constructing an overexpression vector of an MFN1 gene, transfecting cells, obtaining a cell line of the overexpressed MFN1 gene, culturing, collecting a culture solution, and separating and extracting mitochondrial vesicles, so as to obtain the MFN1 engineered mitochondrial vesicles MFN1-MDVs rich in mtDNA. The MFN1-MDVs is used for treating senescent cells caused by mitochondrial dysfunction, and the result shows that the MFN1-MDVs can be internalized into the senescent cells, so that the mtDNA and ATP content of senescent cell mitochondria is effectively improved, the oxidative phosphorylation level is improved, the antioxidant enzyme activity of the senescent cells is enhanced, ROS is reduced, the mitochondrial membrane potential is recovered, and finally the mitochondrial network structure is improved. The obvious mitochondrial function repairing potential and the cell senescence improving effect are shown.

The invention discloses a hepatocellular carcinoma prognosis evaluation marker TKFC and application thereof, and belongs to the technical field of prognosis markers. By comparing tumor tissues of patients with different prognosis, the invention discovers that the HCC subtype with relatively strong invasiveness shows a systematic state imbalance, that is, the oxidative metabolism function represented by mitochondrial oxidative phosphorylation and tricarboxylic acid cycle is weakened, and the intracellular proliferation procedure related to chromatin remodeling and cell cycle progress is abnormally active. The state of low oxidative metabolism-high proliferation output may form the metabolism and epigenetic basis of malignant HCC. The low expression of the TKFC is obviously related to high-risk clinical pathological characteristics such as later tumor staging and higher occurrence rate of vascular invasion, and is an independent poor prognosis factor influencing the total lifetime of a patient, which indicates that the TKFC can be used as a prognosis biomarker of HCC.

A collar worn around the neck of an animal delivers non-invasive light energy to free-floating mitochondria flowing through the animal's veins and arteries. The collar comprises a housing which holds at least one light source, a power source, a controller and in some configurations a reflector. The housing has an aperture through which the light energy is emitted towards the animal's tissue. The housing is connected to a band or harness, which positions the housing where the neck broadens out to the shoulder. Preferably the collar is secured around the neck of the animal loosely enough that the housing falls naturally by gravity to where the neck broadens out to the shoulder. The non-invasive light energy impinges the animal's fur or tissue and penetrates to free- floating mitochondria in the blood flowing through the animal's veins and arteries. This results in improved oxidative phosphorylation and mitochondrial function in the treated mitochondria.