62 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 discloses a self-assembled PROTAC nano material based on natural product mitochondria targeting, which is a nano particle prepared from mitochondria targeting molecules, a photosensitizer and PROTAC as raw materials through a nano precipitation method. The mitochondrial targeting molecule is berberine, the photosensitizer is hypericin, and the PROTAC is dBET57; the ratio of the amount of substance of the dBET57 to the amount of substance of the berberine is (1-10): (1-10), and the ratio of the amount of substance of the dBET57 to the amount of substance of the hypericin is (1-10): (1-10). The nano material can be used for blocking multiple energy metabolism pathways of tumor cells, including glycolysis and oxidative phosphorylation, meanwhile, mitochondria is damaged, ferroptosis is induced, and the anti-tumor capacity of pharmacodynamic molecules is improved; bRD4 in tumor cells and downstream carcinogenic protein c-Myc of the BRD4 can be efficiently degraded. The invention also discloses an application of the nano material in preparation of antitumor drugs.

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 present application relates to the technical field of biomimetic materials, in particular to a multiphase biomimetic mineralized collagen scaffold, a preparation method and application thereof.The preparation method is as follows: type I collagen solution is self-assembled with solid copper sulfide nanoparticles, and through the technology of liquid phase mineralization, intracellular mineralization of collagen fibrils occurs, forming a multiphase biomimetic mineralized collagen scaffold similar to the nanostructure and Young's modulus of natural bone.The scaffold can improve the energy metabolism of cells by regulating the oxidative phosphorylation of bone marrow mesenchymal stem cells, thereby promoting the osteogenic differentiation of the cells; in addition, the scaffold releases copper ions to simulate enzyme activity, catalyzing the generation of a large amount of active oxygen in bacteria, leading to the rupture of the bacterial membrane and the overflow of the contents, thereby achieving the effect of antibacterial.The scaffold can treat simple bone defects or infected bone defects by regulating the energy metabolism of cells and simulating enzyme activity, thereby providing more new methods for the preparation of drugs for realizing bone regeneration and anti-infection in clinic.

The invention discloses an NKT cell, a culture medium and a culture method thereof, and relates to the technical field of cell culture, the NKT cell comprises a basal culture medium, a cell factor combination, a plant extract compound, a metabolism regulator and an antioxidant; wherein the plant extract compound is prepared from astragalus polysaccharide, ganoderic acid, tea polyphenol, asiaticoside and notoginsenoside R1, and the mass ratio of the astragalus polysaccharide to the ganoderic acid to the tea polyphenol to the asiaticoside to the notoginsenoside R1 is (3 to 5) to (1 to 2) to 1 to (0.5 to 1) to (0.5 to 1). According to the NKT cell, the culture medium and the culture method of the NKT cell, through the synergistic effect of the six-membered plant extract compound, the expression of cyclin is promoted, the G1 / S phase conversion is accelerated, and the cell amplification amount is remarkably increased; the ratio of plant extracts and high astragalus polysaccharide are dynamically adjusted, so that cell proliferation and induced differentiation of high ganoderic acid are promoted, cells are forced to turn to efficient-productivity oxidative phosphorylation metabolism in cooperation with 2-deoxyglucose, and the cell multiplication time is shortened.

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 discloses a tumor energy depletion nanoassembly and its preparation method and application, which belongs to the technical field of new excipients and new dosage forms for combined treatment of pharmaceutical preparations. The tumor energy depletion nanoassembly is co-assembled by a mitochondrial oxidative phosphorylation inhibitor and a glycolysis inhibitor through intermolecular forces, and modified with a PEG modifier; the molar ratio of the mitochondrial oxidative phosphorylation inhibitor and the glycolysis inhibitor is 10:1 to 1:10, and the mass ratio of the sum of the mitochondrial oxidative phosphorylation inhibitor and the glycolysis inhibitor to the PEG modifier is 10:90 to 90:10. The tumor energy depletion nanoassembly of the present invention has a high drug loading capacity, good stability, and low toxic and side effects, providing a new strategy for the assembly of homologous synergistic drug nanoparticles, and providing an effective nano-platform for the development of carrier-free hybrid nanoassemblies and energy depletion-driven combined tumor treatment.

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 provides an application of transporter ABCA8 positive cancer related fibroblast as a marker in preparation of a kit for diagnosing SETD2 defect pancreatic cancer. The invention also provides an application of the transporter ABCA8 positive cancer-related fibroblast as a marker for diagnosing pancreatic cancer with a high oxidative phosphorylation metabolism characteristic. The invention also provides application of the transporter ABCA8 as a target spot in preparing and screening medicines for treating the SETD2 defect pancreatic cancer. According to the invention, it is identified for the first time that a new CAF subgroup with an ABCA8 marker and rich in lipid exists in SETD2-deficient pancreatic cancer, and the subgroup CAF provides lipid for tumor cells through ABCA8 transporter protein, so that OXPHOS of tumor cell mitochondria is enhanced, and tumor progression is maintained.

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 present invention discloses a probe combination and application for detecting mitochondrial respiratory chain supercomplexes based on proximity ligation technology and hybridization chain reaction, belonging to the field of probe detection. By identifying two adjacent protein subunits that reflect the structural integrity of the supercomplex as pedestals, and utilizing the principle of antigen-antibody binding, the antigen-antibody that recognizes and binds to the pedestals triggers a proximity ligation reaction (PLA) due to nucleic acid labeling. Based on the principle of hybridization chain reaction (HCR), cascade amplification of the detection signal is achieved, and the activity of the oxidative phosphorylation system is determined by the structural integrity of the supercomplex. This overcomes the shortcomings and limitations of traditional detection methods and enables rapid, highly sensitive, and accurate detection of supercomplex structure. Furthermore, by fixing cells on a 96-well fluorescence plate and using a multifunctional microplate reader to detect the structural integrity of the mitochondrial supercomplex, the system ultimately enables parallel testing of up to 96 samples, achieving digital and high-throughput detection.

The invention relates to the technical field of animal experiment models, and discloses a feed composition capable of prolonging the life of mice and delaying senescence and application, and the feed composition is prepared by the following steps: raw material pretreatment: corn flour, soybean meal and wheat bran are respectively crushed and sieved by a 80-100 mesh sieve, and fish meal is subjected to ultraviolet sterilization treatment for 10-20 min; additive premixing: metformin and a carrier are mixed and ground, the carrier is microcrystalline cellulose or corn starch, and the mass ratio of metformin to the carrier is (1: 50)-(1: 100); and gradient mixing. Metformin in the feed composition activates an AMPK signal channel, enhances the cell energy perception ability, promotes a metabolic mode to be converted to mitochondrial oxidative phosphorylation direction and reduces glycolysis dependence, meanwhile, NAD + precursor substances in the synergistic components promote biosynthesis of nicotinamide adenine dinucleotide and drive the activity of SIRT deacetylase to be continuously improved, and the effect of improving the activity of the SIRT deacetylase is achieved. The cell metabolism homeostasis is jointly reconstructed, and the decline of senescence-related pathways is delayed from the molecular level.

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.

The invention relates to application of a succinate dehydrogenase subunit B (SDHB) in preparation of a medicine for preventing and / or treating renal fibrosis, and belongs to the technical field of medicine and biology. Based on research of the invention, the expression level of SDHB in renal fibrosis tissue is significantly reduced, and enhancement of the expression or activity of SDHB can effectively improve the function of renal tubular epithelial cells and alleviate the fibrosis process. By improving the expression or activity of SDHB, the oxidative phosphorylation ability of mitochondria can be enhanced, the energy metabolism state of cells can be improved, and the generation of active oxygen can be reduced, so that the occurrence and development of renal cell injury and fibrosis can be prevented. According to the application disclosed by the invention, SDHB is determined as a new target spot for resisting renal fibrosis for the first time, and a new direction is provided for prevention and treatment of renal fibrosis.

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 present invention discloses the use of engineered exosomes rich in RHOT1 in the preparation of drugs for improving insulin resistance. The present invention screened and obtained the polypeptide P15 targeting CD81, formed the recombinant protein RHOT1-P15 with P15 and RHOT1, then constructed a recombinant plasmid expressing the recombinant protein, transfected the cells for culture, and extracted the exosomes to obtain the engineered exosomes RHOT1-Exo rich in RHOT1. RHOT1-Exo is used for insulin resistance cell therapy. Studies have shown that RHOT1-Exo can effectively increase mitochondrial ATP content, improve oxidative phosphorylation levels, enhance cellular antioxidant enzyme activity and reduce ROS, ultimately improving the mitochondrial network structure and increasing the expression of proteins related to the insulin signaling pathway, showing obvious mitochondrial function repair potential and improvement of insulin resistance effect. The present invention successfully realizes the use of RHOT1 protein in the form of exosomes for the treatment of insulin resistance, providing a scientific strategy for its application in drugs for the clinical treatment of insulin resistance.