208 results about "Autophagic death" patented technology

This invention relates to: a novel use of GST-π and GST-π suppressing agents; an apoptosis-inducing agent containing as active components a drug that suppresses GST-π and a drug that suppresses autophagy; a medical composition containing said agent; and a method using said medical composition for treating diseases associated with abnormal apoptosis.

The disclosed item is a composition comprising catechins and sialic acid to provide an effective prevention and treatment for Helicobacter Pylori infection. This composition inhibits growth of Helicobacter pylori, and can increase the antioxidant activity of gastric mucosal cells through reducing the production of O2.−, H2O2 and NO, and decreasing the expression of inducible nitric oxide synthase (iNOS) in cells. The apoptotic damage of stomach caused by Helicobacter pylori was decreased through up-regulation of autophagy to enhance the defensive ability of gastric epithelial cells toward Helicobacter pylori. Therefore the composition can be used in the treatment or prevention on damages caused by Helicobacter pylori infection.

The present invention relates to a new molecular pathway in which activation of the receptor-interacting protein (RIP, a serine-threonine kinase) and Jun N-terminal kinase induce cell death with the morphology of autophagy. Further, autophagic death is induced by caspase 8 inhibition and expression of the mammalian genes ATG7 and beclin.

The invention belongs to the field of medicine and biotechnology, and relates to a synergistic drug compound for treating tumors and a preparation method thereof. The drug compound is composed of one or more cell autophagy inhibitors and arginase, especially human recombinant Arginase is made into a synergistic drug compound for treating tumors, and the synergistic drug compound can inhibit autophagy by inhibiting autophagy through autophagy inhibitors to increase tumor cells' ability to arginase. sensitivity, and enhance the therapeutic effect of arginase, especially human recombinant arginase, on tumors, especially triple-negative breast cancer cells. The drug compound of the present invention can be used for clinical treatment of breast cancer, melanoma, lung cancer, brain tumor, lymphoma, leukemia and myeloma.

Methods of treating an individual who has been identified as having glycolysis dependent cancer are disclosed. The methods comprise the step of: administering to such an individual a combination of an anti-cancer composition that renders the cancer incapable of glycolysis and an autophagy inhibitor. Pharmaceutical compositions and kits comprising that renders the cancer incapable of glycolysis and an autophagy inhibit are also disclosed. Methods of treating an individual who has a disease characterized b cell degeneration and cell death due to autophagy are disclosed. The methods comprise administering to the individual a permeable form of a metabolic substrate that can be oxidized in the tricarboxylic acid cycle to produce NADH. Methods for identifying an autophagy inhibitor comprising performing a test assay using an apopto sis-resistant cell are disclosed.

The present invention relates to methods of mitigating, preventing or treating weight gain or obesity in patients by administering one or more autophagy inhibitors, thereby, preventing the differentiation process of pre-adipocyte cells into a mature adipocytes. Specifically, the present invention relates to the surprising discovery that autophagy is critical for the cellular remodeling required during pre-adipocyte differentiation into mature adipocyte. By targeting and inhibiting one or more mechanisms in autophagy, adipocyte maturation is also inhibited, thus, providing a novel a pathway to prevent, mitigate and / or treat weight gain, obesity and associated diseases, such as type II diabetes.

This invention relates to a novel use of GST-p and GST-p suppressing agents; an apoptosis-inducing agent containing as active components a drug that suppresses GST-p and a drug that suppresses autophagy; a medical composition containing said agent; and a method using said medical composition for treating diseases associated with abnormal apoptosis.

The invention relates to a drug with autophagia inductivity for treating the diseases caused by the accumulation of misfolded proteins and a screening method thereof. Quantitative analysis is carried out to the changes of the fluorescence marked LC3 in the cells of the known medicine combination and to the changes of the fluorescence marked FYVE in the cells to obtain the candidate compound of an autophagia inductive agent; and then longevous protein degradation and polyQ degradation is carried out to finally determine the drug with the autophagia inductivity for treating the diseases caused by the accumulation of misfolded proteins. The method of the invention is a simple and high effective compound screening method which can affect autophagia.

Compositions and methods of increasing autophagy in a cell, or population of cells are disclosed. The methods generally include contacting the cell or cells with an effective amount of an agent that increases the bioavailability of an active isoform of SDF-1. Exemplary agents include active SDF-1 polypeptides, metformin, and DPP4 inhibitors. The methods can include administering the agent to a subject, or treating cells in vivo, in vitro or ex vivo. In some embodiments, cells are treated ex vivo and then transplanted into a subject. In a preferred embodiment, the cells are mesenchymal stem cells such as those found in bone marrow. The compositions and methods can be utilized in a number of therapeutic applications including increasing the longevity or survival of a graft or transplant, increasing the rate of recovery from an injury, reducing one or more symptoms of a chronic inflammatory disease and reducing effect associated with aging.

The invention relates to a nano-silver combined autophagy inhibitor capable of killing and damaging tumor, and particularly relates to applications of a nano-silver combined autophagy inhibitor and / or a reagent for knocking down / knocking out autophagy related gene expression on preparation of an anti-tumor medicament, and applications of the autophagy inhibitor and / or the reagent for knocking down / knocking out autophagy related gene expression on promotion of nano silver to kill and damage tumor cells.

The present invention relates to methods for inducing or promoting autophagy in a cell, the method comprising exposing to the cell an effective amount of a compound of formula I as described herein. The invention also relates to methods for treating or preventing diseases and disorders by administering to subjects in need thereof an effective amount of a compound of formula I, wherein the compound induces or promotes autophagy in at least one cell of the subject.

The invention belongs to the biomedicine field, and aims at providing an expression vector for stably indicating cell autophagy activities, an establishing method and an application method thereof. By constructing a slow-virus expression plasmid containing an EGFP-LC3 autophagy reporter gene and adopting a four-plasmid system, the invention establishes a slow-virus expression vector capable of enabling cells to stably express an EGFP-LC3 gene. By using the expression vector to infect a host cell, the EGFP-LC3 gene can be stably integrated in a genome of the host cell, and the host cell can stably and efficiently express the EGFP-LC3 and indicate cell autophagy changes. A stable autophagy indicating cell can be established by using the expression vector, and the cell autophagy changes are quickly and quantitatively analyzed by an image analysis method based on Top-hat operators and morphological filtration. The invention has the characteristics of stable and reliable autophagy indication, real-time sensitivity, quick and accurate autophagy quantification, simply and convenient operation and the like, greatly facilitates autophagy observation and analysis, and can be widely used for autophagy-correlated researches.

The invention relates to the novel usage of an antimalarial medicine, in particular to the novel usage of hydroxychloroquine having sensitivity enhancing effect on various chemical anti-multiple myeloma medicaments. The novel usage is characterized in the application of hydroxychloroquine in treatment of multiple myeloma through chemotherapeutic medicaments. The hydroxychloroquine can obviously enhance the killing activity of chemotherapeutic medicines such as doxorubicine, epidoxorubicin, cis-platinum and mitoxantrone to multiple myeloma cells, and the killing activity thereof is realized by inhibiting the myeloma cell autophagy signals by hydroxychloroquine. Hydroxychloroquine can induce the quantity of the autophagy lysosomes of the multiple myeloma cells to be increased and the expression of the autophagy-associated albumen LC3-II to be increased.

The invention provides a plurality of Pichia pastoris strains capable of utilizing non methyl alcohol carbon source induced AOX1 promoter to express outside source protein. PpHXT1 gene in the Pichia pastoris strain mutates, thus protein can not be coded or the coded protein has no activity, and autophagy gene PpATG30 gene also mutates, thus protein can not be coded or the coded protein has no activity; or PpMIG1 gene in the Pichia pastoris strain mutates, thus protein can not be coded or the coded protein has no activity, and PpMIG2 gene in the Pichia pastoris strain mutates, thus protein can not be coded or the coded protein has no activity. The Pichia pastoris strain of the invention not only has the advantages of the existing Pichia pastoris strain but also can utilize non methyl alcohol carbon source induced AOX1 promoter to express outside source protein, is safe and environmentally friendly, has simple operation and lower cost, also can be applied to production of food or additive and is applicable to large-scale popularization and application.

Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.

The invention relates to application of GMFB (glia maturation factor beta) as a biomarker for early diagnosis of diabetic retinopathy and for diabetes progression, application of GMFB as a therapeutic target of diabetic retinopathy, a GMFB disrupter and application of the GMFB disrupter. Compared with the prior art, the invention proves that the GMFB content in vitreous body is significantly improved in early period of diabetes in rats of STZ-induced I type diabetes (TIDM). The invention is the first to prove that GMFB content gradually drops with the development of DR (diabetic retinopathy), therefore the GMFB is applicable to dynamic detection of DR progress; the invention is the first to prove that by interfering GMFB expression in rats of DR, visual function can be protected; and the invention is the first to prove that GMFB mediates retinopathy mechanism, including causing decrease of glutamine synthetase of Muller cell, death of ganglion cells and inducing autophagy of photoreceptor cells.

The present invention relates to novel bisaminoquinoline compounds, pharmaceutical compositions comprising these novel compounds and methods for inhibiting autophagy in biological systems. Methods of treating cancer in patients in need using compounds and / or compositions according to the present invention alone or in combination with at least one additional anticancer agent represent additional aspects of the invention. Methods of treating disease states and / or conditions in which inhibition of autophagy plays a favorable treatment role including rheumatoid arthritis, malaria, antiphospholipid antibody syndrome, lupus, chronic urticaria and Sjogren's disease, with compounds according to the present invention represent additional aspects of the invention.

The invention discloses an expression method of Beclin1 and MAP1-LC3 (microtubule-associated protein 1-light chain 3) in steroid-induced avascular necrosis of femoral head of a rabbit, detection of a bone cell apoptosis index of a femoral head tissue of a rabbit SANFH (steroid-induced avascular necrosis of femoral head) model and the MAP1-LC3 expression shows that autophagy-related gene Beclin1 can regulate autophagy activity and also can selectively combine with family members of Bcl-2 (B-cell lymphoma-2) to regulate the cell apoptosis activity. By detection of the expression of the Beclin1 in the SANFH model, the expression method provides a new molecular target for treatment of SANFH. The expression method is simple and convenient in operation, better solves the problem that no study on cell apoptosis and autophagy expression and mutual relation thereof in the SANFH model is found at home and abroad, and fills the blank of the study on cell apoptosis and autophagy expression and the mutual relation thereof in an ANFH (avascular necrosis of femoral head) model.

The invention discloses a cell autophagy inhibitor taking rubiaceae-type cyclopeptides as effective components. The cell autophagy inhibitor is particularly used for inhibiting KRAS mutation, particularly KRAS dependent tumor cell protective autophagy, and promoting tumor cell apoptosis. The inhibitor is preferably a nano-micelle injection and can be applied to preparation of medicines for treating and preventing KRAS related cancers such as colon cancers, rectal cancers, lung cancers and pancreatic cancers. The cell autophagy inhibitor can effectively inhibit tumor cell protective autophagy, the rubiaceae-type cyclopeptides serving as the effective components are wide in source, the extraction process is mature, dosage forms and pharmacy modes are diversified, and the inhibitor can be applied to treatment and prevention of the KRAS related cancers and has a wide clinical application prospect.

The invention relates to a use of an autophagy (B-cell apoptosis) inhibitor. The inventor finds that the autophagy (B-cell apoptosis) inhibitor can be used for preventing and / or curing bird flu, and particularly has surprising effect on bird flu prevention. The inventor additionally finds that the autophagy (B-cell apoptosis) inhibitor can also be used for preventing and / or curing lung injuries caused or deteriorated by nano materials. The autophagy (B-cell apoptosis) inhibitor comprises 3-methyladenine, SB203580, LY294002 or wortmannin. The effect of the autophagy (B-cell apoptosis) inhibitor is very obvious, the occurrence of autophagy can be obviously inhibited, the cell deaths, especially the deaths of lung epithelial cells of mammals are greatly reduced, the injury degree of organs, especially the injury degree of the lung is reduced, and thereby the bird flu can be prevented and cured; and the autophagy (B-cell apoptosis) inhibitor can prevent and cure the lung injuries caused or deteriorated by the nano materials.

The invention relates to a preparation method of an autophagy-imitated immune cell supported antitumor therapeutic agent. The preparation method comprises steps as follows: an antitumor therapeutic agent, cell membranes and immune cells are taken as raw materials, immune cell membranes are extracted to encapsulate the antitumor therapeutic agent, nano-particles containing apoptosis groups are co-cultured with the immune cells after being formed, the nano-particles are phagocytized by the immune cells, the antitumor therapeutic agent is enabled to be indirectly encapsulated into the immune cells, and the autophagy-imitated immune cell supported antitumor therapeutic agent is prepared. Compared with the prior art, the antitumor therapeutic agent is encapsulated with the cell membranes containing the apoptosis groups, the phagocytosis quantity of the antitumor therapeutic agent by the immune cells is increased, cell carriers meeting various demands are prepared, the problems of irregularrelease and low phagocytosis quantity of the therapeutic agent due to adoption of a traditional supporting method are solved, and meanwhile, toxicity of drugs for the cell carriers is reduced.

The invention provides application of optineurin protein in preparing acute hepatic damage diagnosis and treatment products. Experiments prove that the OPTN (optineurin) protein is increased in protein in acute hepatic damage tissues and relieves polarization of macrophages through autophagy to release acute hepatic damage, and accordingly acute hepatic damage can be relieved by expressing the OPTN protein or applying bavachinin. Therefore, the OPTN protein can serve as a specific marker protein for diagnosis and drug therapy of acute hepatic damage, and through the agonist of the bavachinin and overexpression viruses, effectively treats acute hepatic damage to achieve more accurate and quicker diagnosis and treatment of acute hepatic damage. The optineurin protein provides a new therapeutic target and an effective new drug for treating acute hepatic damage.

The invention belongs to the technical field of biology and relates to a drug composition reducing in-vivo and in-vitro toxicity of a nano drug delivery material and a preparation method thereof. In the invention, biological technologies are employed for reducing the in-vivo and in-vitro toxicity of the nano drug delivery material and the in-vivo and in-vitro toxicity of an autophagy-intervention nano material are controlled through the biological technologies, thereby reducing adverse side effects of the nano materials and improve safety of application of the nano materials. The invention particularly provides an autophagy-intervention composition which is composed of following substances including, but not limited to an autophagy-intervention drug (such as a compound or a polypeptide), an autophagy-related gene, an autophagy-related signal pathway protein blocking agent, with the nano material.

This invention provides compositions and method of diminishing or inhibiting autophagy by administering a FLIP protein that binds to Atg3, interfering with the formation of the LC3-Atg4-Atg7-Atg3 conjugation complex necessary for autophagy induction. This invention also provides FLIP peptide fragments that promote or induce autophagy by interfering with the activity of FLIP.

The invention discloses application of timosaponin AIII in anemarrhena to preparation of antitumor drugs, which belongs to the field of pharmacology. Pharmacological experiments prove that timosaponin AIII has broad-spectrum strong antineoplastic activity, especially strong and stable cytotoxicity on T475-S2 cells; timosaponin AIII has stronger capacity in killing T475-S2 cells compared with 5-Fu and paclitaxel; the IC50 value of timosaponin AIII is 6.97 +- 0.72 mu M after 24 h, the concentration of used timosaponin AIII is 6 mu M, timosaponin AIII can induce apoptosis and autophagy of T475-S2 cells, the effect of apoptosis is dominating, so timosaponin AIII can be used for preparing drugs for preventing and treating tumors.

The invention discloses application of 4-benzothiopheneaminoquinazoline derivative and salt thereof in preparing tumor treatment medicine. The in vitro and in vivo activities of the 4-benzothiopheneaminoquinazoline derivative are evaluated; and the derivative kills tumor cells by means of inducing tumor cell apoptosis and autophagy to inhibit the growth of tumor cells and provide the application in preparing medicaments for treating cancers, especially pancreatic cancer, prostate cancer, lung cancer or breast cancer. In the invention, the action mechanism and the action target of the 4-benzothiopheneaminoquinazoline derivative are studied, and the derivative has stronger inhibitory activity to a plurality of receptortyrosinekinases and provides the application of acting as an inhibitor of receptortyrosinekinase, especially polyreceptortyrosinekinase.

Provided are methods and pharmaceutical combinations utilizing a phospholipase A2 inhibitor for the inhibition of treatment-induced autophagy.

The invention provides application of sinomenine to preparation of a medicament for treating human brain glioma. As proved by experiments, the sinomenine has a function of restraining human-derived glioma U87MG and SF767 cell strains, and the function is improved along with the increase of dose and time. Moreover, the sinomenine can induce the increase of autophagosomes, increase the quantity of autophagic vesicles, prompt the expression increase of human glioma cells LC3B-II, induce autophagic death of human glioma cells, and restrain the growth of U87MG cell xenograft tumors. The sinomenine is a novel and effective glioma-resisting medicament with a great potential, and can be used for preparing a human brain glioma medicament; by adopting the sinomenine, a new way is created for medical treatment of human brain glioma, and the medical application of the sinomenine is expanded.

The invention discloses an application of inhibiting autophagy of mesenchymal stem cells in autoimmune diseases, and in particular, the invention relates to the application of an autophagy inhibitor of the mesenchymal stem cells, wherein the application includes preparation of a composition for enhancing immunosuppression capability of the mesenchymal stem cells and / or preparation of a medicine composition of preventing or treating the autoimmune diseases. The invention also relates to a method of employing the autophagy inhibitor of the mesenchymal stem cells in a safe effective dose as an active component in a drug composition and using the drug composition for treating the autoimmune diseases. The method of inhibiting the autophagy of the mesenchymal stem cells for enhancing the immunosuppression functions can be used for treating the autoimmune diseases and has excellent application prospect and economic benefit.