122 results about "Oxidative phosphorylation" patented technology

Biological macromolecules are synthesized in vitro under conditions and in a reaction composition wherein oxidative phosphorylation is activated and protein folding is improved.

This invention discloses a method and formulation for treatment / prevention of human and animal cancers. The invention is designed to exploit the vulnerability of cancer with regards to its anaerobic requirement for non-oxidative phosphorylation of glucose to derive energy, which is opposite to the host. The composition is comprised of a combination of one or more of (A) 2,3-dimethoxy-5-methyl-1,4-benzoquinone, ubiquinones (5-45) (B) compound(s) capable of augmenting oxidative phosphorylation such as a riboflavin containing compound and / or ubiquinone (50) (C) 2′,3,4′5,7-pentahydroxyflavone or a lactic acid dehydrogenase inhibitor and (D) compounds (s) that antagonize gluconeogenesis from non-glucose carbon based substrates. The combination of these substances should favor oxidative loss of carbon through decarboxylation reactions, suppress gluconeogenesis and initiate collapse of glycolysis in tumor tissue, a chemical manipulation that should be non-toxic or perhaps even beneficial to normal respiring host tissue. Pilot studies indicate the treatment to be effective without side effects.

Provided herein is a library of monoclonal antibodies specific for native proteins and native protein complexes of the oxidative phosphorylation (OXPHOS) system (for example, Complex I, II, III, IV, or V, or any protein subunit of any of such complexes). Hybridomas expressing such antibodies and antibodies that competitively inhibit the binding of any such antibody (e.g., antibodies that bind the same or a sterically overlapping epitope) are also contemplated. Methods of using, and kits including, the disclosed antibodies are also provided. Antibodies, methods and kits described herein address a need in the art by providing immunological reagents and assays useful, at least, for detecting mitochondrial diseases associated with deficiencies or alterations in OXPHOS Complexes I, II, III, IV and / or V.

The present disclosure describes methods and systems for improving the expression of a properly folded, biologically active protein of interest in a cell free synthesis system. The methods and systems use a bacterial cell free extract having an active oxidative phosphorylation system, and include an exogenous protein chaperone. The exogenous protein chaperone can be expressed by the bacteria used to prepare the cell free extract. The exogenous protein chaperone can be a protein disulfide isomerase and / or a peptidyl-prolyl cis-trans isomerase. The inventors discovered that the combination of a protein disulfide isomerase and a peptidyl-prolyl cis-trans isomerase produces a synergistic increase in the amount of properly folded, biologically active protein of interest.

The invention relates to a composition that includes a first agent selected from the group consisting of an oxidative phosphorylation inhibitor, an ionophore, and an adenosine 5′-monophosphate-activated protein kinase (AMPK) activator; a second agent that possesses anti-inflammatory activity; and a third agent that possesses serotonin activity.

The present invention belongs to the field of insecticides, and relates to a pest-killing and mite-killing composition, which contains an active component A and an active component B, a weight part ratio of the component A to the component B is 1:99-99:1, the active component A is selected from a compound I represented by the following structural formula, the active component B is selected from an organic phosphorus pest / mite killing agent, a nicotine type acetylcholine receptor (nAChR) agonist pest / mite killing agent, an apastia pest / mite killing agent, a proton gradient interference and oxidative phosphorylation affecting uncoupling pest / mite killing agent, a nereistoxin analog pest / mite killing agent, a Ryania receptor regulating pest / mite killing agent, a voltage-dependent sodium ion channel blocking pest / mite killing agent, an ecdysone receptor stimulating pest / mite killing agent, an amino butyric acid (GABA) gated chloride channel antagonism pest / mite killing agent, a microorganism pest / mite killing agent or other pest / mite killing agents, and the active component A has the following structure. The composition of the present invention has advantages of significant synergy, resistance delaying and the like, and can be used for prevention and control of a variety of pests. The compound I is defined in the instruction.

This disclosure relates to a pharmaceutical composition that includes a first agent selected from the group consisting of an oxidative phosphorylation inhibitor, an ionophore, and an adenosine 5′-monophosphate-activated protein kinase (AMPK) activator; a second agent that possesses anti-inflammatory activity; and a third agent that is a serotonin metabolite.

The present invention relates to a culture medium suitable for mammalian cell, tissue or embryo growth in vitro in which enhancers of oxidative phosphorylation are included. These enhancers include coenzyme Q, alpha.lipoic acid, acetyl-L-carnitine, alpha.tocopherol, These products are introduced into the medium in a soluble form through the use of either a polysorbate surfactant such as Tween ™ or a preparation containing lecithin and surfactant.

The invention discloses a multi-parameter water quality analyzer. The multi-parameter water quality analyzer comprises a hand-held controller and at least one intelligent sensor, wherein the hand-held controller comprises a battery, a battery management module, a display module, a first DC / DC (Direct Current) module, a second DC / DC module, a first central processing unit, a keyboard and a first analogue-to-digital interface; each intelligent sensor comprises a second central processing unit, a third DC / DC module, a second analogue-to-digital interface, a reference voltage source, a signal acquisition module and a sensor. The multi-parameter water quality analyzer is provided with a plurality of sensors, thus being capable of detecting parameters such as PH (potential of hydrogen), OPR (Oxidative Phosphorylation), electrical conductivity and dissolved oxygen content in water, comprehensively detecting the water quality and accurately judging the water quality; meanwhile, the detection part is separated from the observation part so that a user can observe the detected water quality parameters by use of the hand-held controller in the finite range without being restricted to a water quality detection site; the multi-parameter water quality analyzer is provided with the rechargeable battery, thus being capable of working normally without external power source; therefore, the analyzer can be applied to remote water quality detection sites conveniently.

Methods of selecting a subject with cancer for treatment with an active agent that modifies pyruvate metabolism, the TCA cycle, or oxidative phosphorylation, as well as methods of treating the subject, determining the efficacy of the treatment, and adjusting the treatment dosage and frequency are provided. Methods of selecting and treating as subject typically include, (a) detecting the level of one or more biomarkers selected from the group consisting of one or more Mitochondrial Pyruvate Carriers (MPC), one or more components of the Pyruvate Dehydrogenase Complex (PDC), or mitochondrial glutamine transporter in diseased or disordered cells obtained from the subject; and (b) selecting the subject for treatment if the subject meets certain criteria and (c) administering the subject an effective amount of an active agent that modifies pyruvate metabolism, the TCA cycle, a related metabolic pathway, or oxidative phosphorylation to treat the disease or disorder.

The use of compositions which include one or more inhibitors of the citric acid, TCA, cycle and / or one or more inhibitors of oxidative phosphorylation for the treatment of cellular proliferation is disclosed. The composition is administered to or in the region of the proliferating cells or in a resection scar or cavity.

A mitochondria targeted gold nanoparticle (T-3-BP-AuNP) decorated with 3-bromopyruvate (3-BP) and delocalized lipophilic triphenylphosphonium (TPP) cations to target the mitochondrial membrane potential (Δψm) was developed for delivery of 3-BP to cancer cell mitochondria by taking advantage of higher Δψm in cancer cell compared to normal cells. This construct showed remarkable anticancer activity in prostate cancer cells compared to non-targeted construct NT-3-BP-AuNP and free 3-BP. Anticancer activity of T-3-BP-AuNP was further enhanced upon laser irradiation by exciting the surface plasmon resonance band of AuNP and thereby utilizing a combination of 3-BP chemotherapeutic and AuNP photothermal effects. T-3-BP-AuNPs showed markedly enhanced ability to alter cancer cell metabolism by inhibiting glycolysis and demolishing mitochondrial oxidative phosphorylation in prostate cancer cells. Our findings demonstrated that mitochondria targeted and concerted chemo-photothermal treatment of glycolytic cancer cells with a single NP may have promise as a new anticancer therapy.

The invention discloses a composition for regulating the sub-health status of the crowd suffering from lipodystrophy. The composition mainly has the effects of reducing the expression of the hypothalamic neuropeptide gamma by influencing human leptin, improving the energy metabolism efficiency, increasing the energy consumption and inhibiting fat synthesis. The other components with fat decomposing effects are combined, so that the metabolism of human adipose tissues is promoted, and the intracellular oxidative phosphorylation effect and synthesis of cell endogenous cholesterol are inhibited. The composition can be used for achieving the effects of effectively infiltrating into the human skin, inhibiting the activity of lipase and reducing the synthesis of fat. By combining the traditional Chinese medicine naprapathy, the absorption and intracellular transport of the composition can be further promoted, the metabolism is promoted, the triglyceride in the fat is decomposed, the excretion of steroid and gallic acid is increased, the excretion of cholesterol and other metabolites can be accelerated, a local shaping effect is achieved, and the contents of glycerin and cholesterol in serum are reduced in an assisted mode. The pharmacological action of the cardiovascular system is improved, and the blood circulation is improved.

The invention relates to application of a curcumin derivative Ca 37 in preparation of a drug for treating a prostate cancer disease, and relates to the field of biology and pharmacy. The object is to provide a use of the curcumin derivative in treatment of the prostate cancer disease. The application provided by the invention is mainly characterized in that the proliferation of prostate cancer cells PC(Prostate Cancer)-3 which are independent of male hormones is inhibited by the curcumin derivative, and the effect is obviously better than that of curcumin itself, the decrease of the capacity function of the PC-3 cells, i.e., oxygen glycolysis and oxidative phosphorylation, apoptosis starting and autophagy defects are induced, and the growth inhibition function mainly depends on the generation of reactive oxygen species.

The present disclosure describes methods and systems for improving the expression of a properly folded, biologically active protein of interest in a cell free synthesis system. The methods and systems use a bacterial cell free extract having an active oxidative phosphorylation system, and include an exogenous protein chaperone. The exogenous protein chaperone can be expressed by the bacteria used to prepare the cell free extract. The exogenous protein chaperone can be a protein disulfide isomerase and / or a peptidyl-prolyl cis-trans isomerase. The inventors discovered that the combination of a protein disulfide isomerase and a peptidyl-prolyl cis-trans isomerase produces a synergistic increase in the amount of properly folded, biologically active protein of interest.

The invention relates to a method for combating disorders affecting the mitochondrial oxidative phosphorylation system by allotopic expression of the cyanide-insensitive alternative oxidase (AOX) in human cells. The successful expression of AOX in human cells and in Drosophila has been shown to confer spectacular cyanide-resistance to mitochondrial substrate oxidation, alleviate oxidative stress, apoptosis susceptibility and metabolic acidosis. AOX is well tolerated when expressed ubiquitously in the whole organism. AOX expression is a valuable tool to limit the deleterious consequences of respiratory chain deficiency.

The invention provides application of a composition containing fructose-1,6-bisphosphate (FBP) in preparation of antitumor drugs. A proportion of the FBP to metabolic regulators are determined according to respective efficacy doses; the metabolic regulators are different in doses, so that the proportion of the FBP to one metabolic regulator is determined according to the effective dose of the specific metabolic regulator. The composition prevents and cures tumors by damaging activity of a tumor metabolic network. The drugs with the composition as an active ingredient have stronger anticancer efficacy compared with FBP and other metabolic regulators in exclusive use. The composition can completely reverse tumor metabolic characteristics and destroy the tumor metabolic network, prominently featured by blocking glycolysis and an intermediate product of a tricarboxylic acid cycle from biosynthesis while promoting nutriments to enter the tricarboxylic acid cycle and oxidative phosphorylation so as to damage an oxidation-reduction system. The composition is highly safe, and further improves the anticancer efficacy of the FBP.

A system and methods for calculating at least one unknown metabolic flux of a plurality of cells. In one embodiment, the method includes the steps of constructing a metabolic network having a plurality of reaction components, the reaction components representing at least glycolysis, reduction of pyruvate to lactate, TCA cycle, and oxidative phosphorylation, measuring at least two metabolic rates of a plurality of cells corresponding to at least two of the metabolic network reactions, and calculating metabolic fluxes of a plurality of cells for the rest of the metabolic network reactions from at least two measured metabolic rates of a plurality of cells corresponding to at least two of the reactions.

A composition for reducing damage associated with oxidative phosphorylation. The composition comprises an upregulating compound mixture configured to upregulate an endogenous antioxidant system, an exogenous antioxidant mixture configured to inhibit oxidation of biomolecules by reactive oxygen species, and a mineral mixture configured to provide one or more cofactors to a endogenous antioxidant enzyme. The endogenous antioxidant system includes a Nrf2 transcription factors that promotes transcription of antioxidant genes.

The invention discloses a diluent for in-vitro low temperature preservation of boar semen and a preparation method thereof. The diluent comprises following components: broad-spectrum antibiotic bacteriostatic agents of D-fructose, 2-amino-2-hydroxymethyl-1,3-propanediol, trisodium citrate, sodium bicarbonate, citric acid, disodium ethylene diamine tetraacetate, N-acetyl-cysteine, skim milk powder, yolk freeze-dried powder, amikacini sulfatis and the like. The diluent for the in-vitro low temperature preservation of the boar semen is suitable for preserving the fresh boar semen at low temperature (4-5 DEG C). The diluent significantly inhibits injury caused to sperm structure during the low temperature preservation process, maintains glucose metabolism and oxidative phosphorylation metabolism processes of boar sperm, effectively prolongs survival time of the boar sperm in the low temperature preservation, and significantly improves use efficiency of the high quality breeding boar semen and economic benefit of breeding.

The invention relates to an application of an energy metabolism-interfering drug in recurrence of pancreatic cancer. Specifically, the invention discloses a pharmaceutical composition which comprisescarboxyamidotriazole or a pharmaceutically acceptable salt thereof and a glycolytic inhibitor. Carboxyamidotriazole and the glycolysis inhibitor are used for blocking from oxidative phosphorylation and glycolysis ways respectively, so the content of ATP in cells can be significantly reduced, the vitality and self renewal of pancreatic cancer stem cells are seriously destroyed, and thus the recurrence of pancreatic cancer after drug treatment can be delayed.

The present invention relates to guanidine compounds for inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and use thereof. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating a OXPHOS-related disease, particularly cancer, by inhibiting mitochondrial oxidative phosphorylation and reprogramming cellular metabolism.

A pharmaceutically-acceptable modulator of the regulation or perturbation of the structure, expression, and / or activity of at least one enzyme and / or enzyme complex, or subunit thereof, such as via the altered mitochondrial energy metabolism of the pyruvate dehydrogenase (PDH) complex of warm-blooded animals, including humans, and methods of use thereof, comprises an effective amount of at least one lipoic acid derivative and at least one pharmaceutically-acceptable carrier thereof to affect the complex's phosphorylation state. By increasing PDH kinase activity and / or decreasing PDH phosphatase activity, the modulator prevents the detoxification anaerobic glycolytic toxic metabolites through inhibition of the activity of the PDH complex's El a subunit, obliging increased mitochondrial oxidative phosphorylation activity. As cells characterized by hyperproliferation, such as tumor cells, cannot also generate acetyl-CoA and NADH because of the modulator's additional action in inhibiting the action of the PDH complex's E2 subunit, the mitochondrial membrane polarization is lost, facilitating cell death.

The invention discloses a nano-drug of a hybrid membrane loaded oxidative phosphorylation inhibitor and a preparation method of the nano-drug, and relates to the technical field of drug carriers. The nano-drug comprises an inner core and a shell; the outer shell covers the periphery of the inner core; the inner core comprises ROS-responsive drug-loaded nano-particles; drugs loaded by the ROS-responsive drug-loaded nano-particles are oxidative phosphorylation inhibitors; and the shell is a mixed membrane of a mitochondrial membrane and a tumor cell membrane. The nano-drug can cross BBB and reach a tumor site by virtue of homologous targeting of the tumor cell membrane, and can perform homologous target and can enter mitochondria by virtue of the mitochondrial membrane, the ROS-responsive drug-loading nano-particle is in a high-level ROS environment of the mitochondria, the core swells and degrades to release the loaded substance oxidation phosphorylation inhibitor, therefore, safe and efficient targeted drug therapy is realized. Through wrapping of the shell, the defect that the half-life period of the loaded medicine in the blood is short is avoided, and long circulation of the medicine in the blood is protected to a great extent.

A method of identifying or evaluating skin-care actives that improve the metabolism of a skin cell. The method includes contacting cells with a stressor and a test agent and determining a response of the cells to the stressor and test agent, based on the change in metabolic indicators associated with glycolysis and / or oxidative phosphylation. The test agent may be identified as a skin-care active when the oxidative phosphorylation and / or glycolysis response corresponds to an improvement in cellular metabolism.

The present invention relates to a succinate prodrug for use in the treatment or prevention of lactic acidosis.

A method of identifying or evaluating skin-care actives that improve the metabolism of a skin cell. The method includes contacting cells with a stressor and a test agent and determining a response of the cells to the stressor and test agent, based on the change in metabolic indicators associated with glycolysis and / or oxidative phosphylation. The test agent may be identified as a skin-care active when the oxidative phosphorylation and / or glycolysis response corresponds to an improvement in cellular metabolism.

A composition for supporting endogenous systems related to life span, inhibiting mTOR, and reducing damage associated with oxidative phosphorylation. The composition comprises an upregulating compound mixture configured to upregulate an endogenous antioxidant system, an exogenous antioxidant mixture configured to inhibit oxidation of biomolecules by reactive oxygen species, and a mineral mixture configured to provide one or more cofactors to a endogenous antioxidant enzyme. The endogenous antioxidant system includes regulation of mitophagy through mTOR mediated regulation, and a Nrf2 transcription factors that promotes transcription of antioxidant genes.