86 results about "Mitochondrion membrane" patented technology

The present invention provides, among other things, compositions and methods for treatment of Friedrich's Ataxia based on effective targeting of a therapeutic moiety to mitochondria that can substitute for natural FXN protein activity or rescue one or more phenotypes or symptoms associated with frataxin-deficiency. In some embodiments, the present invention provides a targeted therapeutic comprising a therapeutic moiety, which is a polypeptide having an N-terminus and a C-terminus, a mitochondrial targeting sequence associated with the therapeutic moiety at the N-terminus, and a mitochondrial membrane-penetrating peptide associated with the therapeutic moiety at the C-terminus, wherein the therapeutic moiety is targeted to mitochondria upon cellular entry.

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 full-automatic spermatid detector. A seminal fluid sample enters a liquid flow system after being subjected to sample suction, reagent adding and mixed reaction dyeing, the liquid flow system is used for conveying the seminal fluid sample subjected to reaction dyeing to a reaction detection chamber, the seminal fluid sample is subjected to excitation detection by a laseremitted from a laser optical system, a light signal obtained after excitation is collected by a photoelectric detecting system, statistic analysis of data is carried out after the light signal is converted to a digital signal by a control system, and according to data features and a cluster analysis algorithm, semen quality parameter results such as the total quantity of semen, density, core wholeness, mitochondrion membrane potential and acrosomal reaction of the to-be-detected seminal fluid sample are worked out. Full-automatic high-flux rapid detection and analysis of the seminal fluid sample are achieved, full-automatic operation can be carried out after a user places the seminal fluid sample in a sample pond, detection and analysis results are automatically output, the full-automaticspermatid detector can be directly connected to a Lis / His system of a hospital to achieve seamless connection of data management, and the full-automatic spermatid detector is easy and convenient to operate, capable of achieving one-key intelligence, low in cost and wide in adaptability.

The invention provides a novel application of a biflavone compound. A biflavone compound (particularly ginkgetin) has a function of preventing and treating lung cancer (especially non-small cell lung cancer). Experiment results show that the ginkgetin has a high cytotoxic effect on A549 non-small cell lung cancer, is capable of obviously increasing the reduction rate of mitochondrial membrane potential and generation of reactive oxygen species, increasing expression of apoptosis-related protein and autophagy critical protein, inducing apoptosis of the A549 non-small cell lung cancer, and obviously inhibiting tumor growth of an A549 nude mouse bearing the tumor, has good antitumor activity for the A549 nude mouse bearing the tumor and is free of obvious toxicity, and through combined application of the ginkgetin and cisplatin that is a common clinical lung cancer treating medicine, anticancer effects of the cisplatin and the ginkgetin during single using are increased and toxicity of the cisplatin is reduced. The biflavone compound (particularly the ginkgetin) can be used for preparing medicines or healthcare products preventing and treating the lung cancer (especially the non-small cell lung cancer).

The invention belongs to the technical field of molecular biology, and relates to a method for screening traditional Chinese medicine monomers, specifically relating to a method for screening monomer ingredients which have protective effect for oxidative damages to liver cells from Chinese traditional medicines by using mitochondrion index technique. In the invention, mitochondrial function detection is used as the core technology and methods of cell proliferation detection, mitochondrial reactive oxygen species generation detection, mitochondrial membrane potential detection, energy substance ATP in mitochondria detection and mitochondrial cytochrome C detection are adopted. Mitochondrial function changes are detected after H7702 cells, which are subject to oxidative damages induced by H2O2, are treated by the traditional Chinese medicine monomers of SalB, protocatechualdehyde, sodium danshensu, cordyceps polysaccharose, cordycepin and cordycepic acid, and the traditional Chinese medicine monomers, which have protective effect for oxidative damages to liver cells, are screened. The invention further provides applications of the traditional Chinese medicine monomers screened in preparing drugs for preventing and treating liver diseases such as fatty liver, viral hepatic diseases and liver fibrosis.

The invention discloses a novel application of mulgedium tataricum. A water extraction product of the asteraceae mulgedium plant mulgedium tataricum which can both be adopted as a medicine and as a food can strongly inhibit the growth of lung cancer cell H1299 and A549. With the plant, cancer cell mitochondrial membrane potential is reduced, intracellular reactive oxygen level is increased, and a series of physiological responses such as apoptosis is further caused. The discovery of the anticancer effect of the edible herb provides good basis for clinical medicines and the developments of novel medicines or health-care products.

The present invention relates to a mitochondrial function protecting agent shown in formula (I), a preparation method therefor and applications thereof to the treatment of Parkinson disease and Alzheimer disease, wherein R1, R2, R3, R4 are independently selected from -NO2, -OH, -F, -CL, -Br, -H, -OCH3 and -CH3; and n=1-9. The mitochondrial function protecting agent provided by the present invention uses triphenyl phosphine cationic as a structural unit, is bound to an antioxidant component (nitroxyl radical unit) by covalent bonds, and drives an entire molecule to be rapidly enriched in the mitochondrion in a potential-dependent manner under the driving of cell membrane potential and mitochondrial membrane potential, thereby realizing mitochondrial targeting of new drug molecules .

The invention belongs to the fields of biochemistry and biomedicines, in particular to application of ciona intestinalis linnaeus peptides in preparation of antineoplastic medicaments. In vitro methods such as MTT assay, scanning electron microscopy, nucleus staining, mitochondrial membrane potential changing and the like prove that the ciona intestinalis linnaeus peptides have a significant antineoplastic effect and can induce apoptosis of tumor cells. The induction mechanism of the ciona intestinalis linnaeus peptides is based on apoptosis, which indicates novel functions and means of cionaintestinalis linnaeus peptides in prevention and treatment of tumors.

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.

The invention relates to preparation of a mitochondrion-targeting radioprotectant and an application of the mitochondrion-targeting radioprotectant in radiation damage protection and belongs to the technical field of medicine. The medicine combines free radicals of nitroxide and triphenylphosphine cations through covalent bonds, and the whole molecule is driven to be quickly enriched on mitochondrion in a potential dependence manner under the joint drive of cell membrane potential and mitochondrion membrane potential, so that the mitochondrion targeting of the compound is realized, and the synthesis method is simple; meanwhile, the radioprotectant has higher free radical scavenging capacity, has the protection degree for anti-oxidative damage of mitochondrion multiple times higher than that of traditional nonselective antioxidants, has better inhibition functions on radiation damage and has the effects equivalent to those of a positive control drug WR2721.

The invention discloses a non-reactive mitochondrial tracking fluorescent probe containing a C12 lalkyl chain, and applications of the probe in labeling or displaying of the distribution of mitochondria in cells, and in mitochondrial autophagy observation, wherein the fluorescent probe is a carbazole pyridine salt compound having a structure represented by a formula (I). According to the present invention, the probe can stain mitochondria in normal living cells, and especially can be fixed on mitochondria when the mitochondrial membrane potential is reduced or disappears, such that the resultsshow that the probe can track the dynamic changes of mitochondria; the probe further has good two-photon properties, and can be used for deep tissue imaging; and the probe has low toxicity, can real-timely track the dynamic process of mitochondrial autophagy, and has broad application prospect in the field of fluorescent biomarkers.

A method of treating patients in need of treatment for a cardiac disorder has been found which comprises administering to the patient a seven carbon fatty acid compound or derivative thereof, wherein the compound or derivative thereof is able to readily enter the mitochondrion without special transport enzymes. A dietary formulation suitable for treatment of heart tissue in cardiac or surgical patients has been found which comprises a seven-carbon fatty acid chain, wherein the seven-carbon fatty acid chain is characterized by the ability to transverse the inner mitochondrial membrane by a transport mechanism which does not require carnitine palmitoyltransferase I, carnitine palmitoyltransferase II, or carnitine / acylcarnitine translocase and the ability to undergo mitochondrial β-oxidation, and wherein the compound is selected from the group consisting of n-heptanoic acid or a derivative thereof, a triglyceride comprising n-heptanoic acid or a derivative thereof, and triheptanoin or a derivative thereof.

The invention relates to a mitochondria-targeting BODIPY compound and a preparation method and application of liposome-coated nanoparticles of the BODIPY compound. The BODIPY compound contains a cationic group which is easily combined with a mitochondrial membrane with negative electricity in cells, so that the BODIPY compound is targeted to mitochondrial organelles of the cells. The BODIPY compound is wrapped by liposome, and liposome nanoparticles with uniform particle size are prepared in an aqueous solution. The nanoparticles have high stability and good biocompatibility in an aqueous solution. After the nanoparticles are taken by tumor cells, the liposome structure is destroyed, and the released BODIPY compound is targeted to cell mitochondria. Besides, under the 665nm illumination condition, active oxygen generated by the BODIPY compound causes oxidative damage to active molecules in mitochondria, so that tumor cells are killed. The liposome nanoparticles can be applied to tumorphotodynamic therapy as a drug for delivering various photosensitizers.

The invention discloses application of virus macrophage inflammatory protein vMIP-II for inducing dephosphorylation of CD8<+> T cells to form Tcm. The vMIP-II for inducing dephosphorylation of the CD8<+> T cells to form the Tcm is developed in a laboratory and is verified by the National Institute for Control of Pharmaceutical and Biological Products. According to the invention, the CD8<+> T cellsare researched through a rhesus SIV infection model. The research finds that: the vMIP-II can enable Tcm to be proliferated depending on the dosage of the vMIP-II, and the differential gene of the proliferative cell is mainly enriched in a chemokine receptor and a phosphorylation pathway. The research further finds that: the proliferation is as follows: the vMIP-II closes a CD8<+> T chemokine receptor, promotes low expression of G protein, reduces the concentration of intracellular Ca<2+> and mitochondrial membrane potential, inhibits phosphorylation related genes, and promotes low expressionof phosphorylated proteins ERK1 / 2 and Akt, so that a CD8<+> T phosphorylation signal is weakened, metabolic reprogramming is carried out, and the CD8<+> T is converted into the Tcm. Therefore, the discovery of the vMIP-II action mechanism provides a brand-new strategy for drug research and development of HIV / SIV infected AIDS, provides a new means for adoptive immunotherapy of virus resistance and tumor resistance, and has important clinical application value.

The invention discloses a target ZIP7 related to diagnosis, treatment, prevention and treatment of cardiovascular diseases and application of the target ZIP7. The application of a substance for inhibiting or silencing ZIP7 gene expression or inhibiting ZIP7 protein activity in any one of the following conditions that a medicine for increasing the concentration of zinc ions in mitochondria is prepared; a medicine for reducing the mitochondrial membrane potential is prepared; a medicine for increasing aggregation of PINK1 in mitochondria is prepared; a medicine for increasing the aggregation of Parkin in mitochondria is prepared; a medicine for inducing mitochondrial autophagy is prepared; a medicine for reducing the release level of active oxygen in myocardial tissues is prepared; a medicine for reducing the myocardial infarction risk is prepared; a medicine for treating or adjunctively treating myocardial infarction is prepared; a medicine for improving the cardiac function after myocardial infarction is prepared; a medicine for inhibiting the enlargement of the infarction area after myocardial infarction is prepared; a medicine for inhibiting ventricular negative remodeling after myocardial infarction is prepared; a medicine for reducing damage of myocardial cells and myocardial tissues in the myocardial infarction process is prepared; and a medicine for reducing the death quantity of myocardial cells in a non-infarction region after myocardial infarction is prepared.

The invention discloses a novel cryoprotective liquid, which comprises: 200mL / L of yolk, 13.536g / L of sodium citrate, 24.224g / L of trihydroxymethyl aminomethane, 11g / L of glucose, 1g / L of 1 million unit streptomycin sulfate, 0.8g / L of 1.6 million unit penicillin, 30mL / L of glycerin and 0.05moL / L-0.15moL / L of trehalose. According to the cryoprotective liquid, the toxicity of the protectant is reduced, and the freeze-thawing effect is improved; when sperms are frozen, the vitality, plasma membrane integrity, acrosome integrity, tyrosine phosphorylation level, protamine deficiency level, motilityrate and mitochondrial membrane potential of the sperms can be remarkably improved, and the quality of the frozen and thawed sperms is improved.

The present invention relates to a recombinant inner mitochondrial membrane polypeptide, and its use in methods for treating mitochondrial disorders.

The invention discloses a mitochondrial targeting compound with aggregation-induced emission property, according to the compound, fluorescent small molecules with aggregation-induced emission property are combined with mitochondrial targeting groups to obtain a product with high anticancer activity and low toxic and side effects; the compound has good cell uptake capability and capability of targeting mitochondria in tumor cells; secondly, the compound realizes good anti-tumor activity by inhibiting proliferation of human-derived tumor cells, inducing generation of active oxygen in cancer cells, reducing mitochondrial membrane potential, changing mitochondrial morphology, damaging mitochondrial functions and inducing autophagy of tumor cells (mitochondria); the action mechanism of the compound is different from the action mechanism of a metal anti-tumor drug, so that the problem of drug resistance cannot be generated in the anti-tumor process by using the compound, and a continuous and good anti-tumor effect is ensured; finally, the compound can effectively inhibit the proliferation of tumor cells which have drug resistance to the metal antitumor drug (cisplatin), so that the problem that the existing chemotherapeutic drug cannot effectively overcome the drug resistance of the tumor cells (cisplatin) is solved.

Methods of treating or preventing allergic or pulmonary diseases characterized by endothelial dysfunction with Alda-1 are presented. Treatment of pulmonary endothelial cells subjected to hyperoxia with Alda-1 showed an increase in ALDH2 activity and expression. Treatment with Alda-1 also illustrated a decrease in oxidative stress, a decrease in reactive oxygen species (ROS), a decrease in apoptosis, a decrease in inflammation and an enhancement of mitochondrial membrane potential.

The invention discloses a fluorescent probe for displaying two states (a normal state and a near-zero state) of cell membrane potential by utilizing a fluorescence image. The fluorescent probe is a compound of 4-[2-(9-dodecyl-9H-carbazole-3)vinyl]-1-(2-hydroxyethyl)-pyridine iodate, called CP12 for short. The invention also discloses an application of the fluorescent probe in detection of a normalstate and a near-zero state of cell membrane potential. When the potential of the cell membrane is in a normal state, the probe enables the cell membrane and cytoplasm to be dyed; when the potentialof the cell membrane is in a near-zero state, only the cell membrane is dyed by the probe. Moreover, the probe is not interfered by mitochondrial membrane potential when being used for measuring the cell membrane potential, and shows higher specificity. Compared with a currently used cell membrane potential probe product, the probe having the visual and rapid distinguishing mode has the advantagesthat calibration and standard curve drawing are not needed in the using process, time and labor are saved, and the probe has wide application prospects in the aspects of biological research and medical diagnosis.

The invention provides a composite nanodiamond medicine and a preparation method and application thereof. Nanodiamond (ND) is adopted as a carrier by the medicine, and under the existence of sodium citrate, mitoxantrone (MTO) and doxorubicin (DOX) are sequentially loaded on the surfaces of the NDs by the way of physical adsorption, so that the composite nanomedicine (ND / MTO / DOX) is obtained. The change of cell mitochondrial membrane potential is detected by the JC-1 method, discovering that the degree of mitochondrial membrane potential decreases caused by the composite nanomedicine is greatest; the MTT method proves that the synergistic effect of MTO and DOX increases the ability of killing cancer cells to a great extent, and moreover, the composite nanomedicine has the characteristic ofslow-release medicine; a confocal result indicates that the ND / MTO / DOX composite nanomedicine is mainly located in lysosomes, moreover, as time goes on, the medicine is not migrated to cell nuclei, the system can probably cause an increase in lysosome permeability, so that a great deal of hydrolase can be released, and as a result, apoptosis is promoted. The composite nanodiamond medicine can be applied in the preparation of antitumor medicines.

The invention discloses new polynucleotide coding the human protein with the function of causing mitochondrial membrane potential decrease and polypeptide coded by the polynucleotide and an antibody of the polypeptide. The invention also discloses application of the new polynucleotide in causing mitochondrial membrane potential decrease through exogenous expression in host cells.

The invention provides preparation and application of a mitochondrial targeting type photosensitizer based on BODIPY (boron dipyrromethene). A BODIPY dye (BD) with enhanced photosensitivity is introduced on the basis of heavy atoms, and triphenylphosphine cations (TPP) with mitochondrial targeting, which are widely accepted, are derived at the head of a BODIPY core through esterification reaction to obtain mitoBD. By utilizing the electrostatic adsorption effect and fat solubility of TPP and mitochondrial membrane potential, the mitoBD can selectively and accurately target organelle-mitochondria, so that the photodynamic therapy effect on tumor cells is enhanced, and meanwhile, the mitoBD has the application potential of fluorescence imaging.

The invention discloses a fluorescent probe for rapidly displaying a normal state and a near-zero state of the potential of a cell membrane. The fluorescent probe is a compound of 4-[2-(9-dodecyl-9H-carbazole-3) vinyl]-1-(2-hydroxyethyl)-quinoline iodate, which is called CQ12 for short. The invention also discloses an application of the fluorescent probe in detection of a normal state and a near-zero state of the potential of a cell membrane. When the potential of a cell membrane is in a normal state, the probe enables the cell membrane and cytoplasm to be dyed; and when the potential of the cell membrane is in a near-zero state, only the cell membrane is dyed by the probe. Moreover, the probe is not interfered by mitochondrial membrane potential when being used for measuring the potentialof the cell membrane, and shows higher specificity. Compared with a currently used cell membrane potential probe product, the visual and rapid distinguishing mode of the probe has the advantages thatcalibration and standard curve drawing are not needed in the using process, and time and labor are saved. The probe has wide application prospects in the aspects of biological research and medical diagnosis.

The invention discloses a preparation method and application of inonotus obliquus polysaccharide. Through water extraction and alcohol precipitation, repeated freeze thawing, deproteinization, dialysis, freeze drying, affinity chromatography and other methods, a polysaccharide component with antioxidant and anti-aging functions is separated and purified from inonotus obliquus; the inonotus obliquus polysaccharide component has strong antioxidant activity; through pretreatment of the inonotus obliquus polysaccharide, etoposide-induced proliferation inhibition and apoptosis of rat aortic smoothmuscle cells can be inhibited, and etoposide-induced cellular senescence beta-galactosidase activity increase, senescence-related heterochromatin aggregation and mitochondrial membrane potential decline can be inhibited; through pretreatment of the inonotus obliquus polysaccharide, etoposide-induced increase in expression levels of p53, p21 and p16 protein and mRNA can be inhibited. The inonotus obliquus polysaccharide components prepared according to the preparation method provided by the invention has good antioxidant and anti-aging activity and has a broad application prospect as a novel anti-aging protective medicine.

The invention provides a pharmaceutical composition and application of the composition in prevention or treatment of neurodegenerative diseases. The pharmaceutical composition comprises sacha inchi oil and / or lipoic acid, and is used for at least one of the following functions: preventing and / or treating neurodegenerative diseases, increasing the survival rate of nerve cells, reducing apoptosis ofnerve cells, increasing the mitochondrial membrane potential of nerve cells, protecting mitochondrial functions and increasing the ATP level in nerve cells. The pharmaceutical composition is good ineffect of preventing and / or treating neurodegenerative diseases, is small in side effect and is capable of effectively increasing the survival rate of nerve cells, effectively protecting mitochondrialmembrane potential of the nerve cells and effectively protecting the energy metabolism level of the nerve cells.

The invention belongs to the technical field of analytical chemistry, and provides a fluorescent probe for detecting mitochondrial membrane potentials as well as a preparation method and application thereof. The fluorescent probe for detecting the mitochondrial membrane potentials has a structural formula shown as: , and can be prepared by allowing reaction between a reaction product of 4-fluorobenzaldehyde and piperazine with 1,2-dimethyl-quinoline iodate. The fluorescent probe for detecting the mitochondrial membrane potentials provided by the invention has the characteristics of being low in biological toxicity, excellent in membrane permeability, simple in synthesis method and convenient in a purification step; and the fluorescent probe can be applied to cell imaging for detecting, labeling or displaying mitochondrial membrane potential changes.

The invention discloses application of a reagent for down-regulating Czib gene expression in preparation of a medicine for treating or improving pulmonary fibrosis, relates to the technical field of biomedicine, and provides that the gene Czib has a remarkable relationship with the occurrence of pulmonary fibrosis for the first time by researching a lung fiber regulation function gene. It is found that the effect of inhibiting pulmonary fibrosis can be achieved by down-regulating the expression level of the Czib gene. In addition, a specific target spot aiming at Czib is screened, the siRNA designed according to the target spot can effectively inhibit bleomycin-induced A549 cell injury, apoptosis, mitochondrial membrane potential drop and cell epithelial-mesenchymal transition, and a new way and research direction are provided for treatment of pulmonary fibrosis and cell injury and inhibition of cell epithelial-mesenchymal transition.

Methods of treating or preventing allergic or pulmonary diseases characterized by endothelial dysfunction with Alda-1 are presented. Treatment of pulmonary endothelial cells subjected to hyperoxia with Alda-1 showed an increase in ALDH2 activity and expression. Treatment with Alda-1 also illustrated a decrease in oxidative stress, a decrease in reactive oxygen species (ROS), a decrease in apoptosis, a decrease in inflammation and an enhancement of mitochondrial membrane potential.