105 results about "Cellular Autophagy" patented technology

The invention discloses a beta-carboline ruthenium compound. The molecular formula of the beta-carboline ruthenium compound is [Ru (N^N) 2 (Nh) XClY] (A^A)z, wherein N^N is selected from bpy or phen; A^A is selected from PF6 or SO3CF3; X is equal to 1 or 2, Y is equal to 2-X, and Z is equal to 1 or 2; or the molecular formula of the beta-carboline ruthenium compound is [Ru (N^N) 2 (1-Py-betaC)] (PF^)2, wherein N^N is selected from bpy, phen or DIP. On a molecular mechanism, the invention proves that the beta-carboline ruthenium compound can be used for treating cancers and has a better effectthan the effects of that of the traditional metal compound cisplatin with wide application and ruthenium compounds NAMI-A in clinical tests; . Thethe beta-carboline ruthenium compound for treating the cancers as an autophagic cell inducer fills the blank of the prior art and develops a new line for developing a new generation of high-efficiency medicaments for treating malignant tumors.

The invention provides a molecular probe, and a preparation method and application thereof; the molecular probe comprises water-soluble carrier molecules, responsive polypeptides and signal molecules, wherein the responsive polypeptides have a sequence of (Xaa)m(Thr-Phe-Gly-Phe)(Xaa)nLys(Xaa) i, and wherein Xaa refers to any amino acid, and i, n and m are independently 0-4; the water-soluble carrier molecules and the signal molecules are connected with the responsive polypeptides through amido bonds. The molecular probe herein has good specificity and signal stability, provides richer autophagy detection means and has a promising application prospect.

The invention provides a polypeptide polymer nanomaterial and a preparing method and application thereof. The polypeptide polymer nanomaterial comprises chitosan, a polypeptide sequence for recognizing beta-amyloid protein and a polypeptide sequence for activating autophagy, and the polypeptide sequences are connected to the chitosan. A polypeptide polymer prepared through solid-phase synthesis and Michael addition has good biological compatibility and anti-A[beta] neurotoxicity, polypeptide polymer nanospheres obtained from the polypeptide polymer can be co-assembled with A[beta] so as to effectively prevent aggregation of A[beta] and reduce the neurotoxicity of A[beta], meanwhile, a co-assembly can activate autophagy after entering cells, A[beta] can be degraded through autophagy, so that Alzheimer's disease can be treated in a synergic mode, the Alzheimer's disease treatment efficiency of the polypeptide nanomaterial is improved greatly, and application prospects are broad.

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.

The invention relates to the technical field of pH fluorescent probes and particularly relates to a lysosome targeted pH fluorescent probe for monitoring cell autophagy as well as preparation and application of the lysosome targeted pH fluorescent probe. The preparation method comprises the following steps of dissolving 2-(2-aminoethyl)-3',6'-bis(diethylamino) spiro [isoindole-1,9'-xanthan]-3-ketone and 2-(2-methoxyethoxy)4-methyl benzene sulfonic acid ethyl ester in N, N-dimethylformamide, and carrying out heating reflux to obtain a crude product; and removing a solvent from the crude product, and separating through a silica gel column to obtain a pure product. Cytotoxicity tests show that the probe has almost no toxic or side effect on cells, a cell co-localization experiment determinesthat the probe can specifically target a cell lysosome, and a laser confocal microimaging experiment shows that the probe has good cell membrane permeability and can perform high-sensitivity detectionon pH change in the lysosome. The probe provided by the invention can monitor the autophagy process of the cells by detecting the change of pH in the lysosome.

The invention belongs to the field of biological pharmacy, and relates to a screening method for screening candidate combination molecules through cell death caused by combination of a tumor cell autophagy inducer and a micro-molecular compound, screened compound molecules may not have antitumor activity, and have the antitumor activity after the screened compound molecules are combined with the cell autophagy inducer, such as an HDAC inhibitor, so a drug combination scheme can be determined. In the invention, cancer cells cultured in vitro are respectively processed by the tumor cell autophagy inductor and single compounds as an object, the degree of the cultured cell death caused by the compounds and the cell autophagy inducer is determined, and cell autophagy-based antitumor drugs are screened. A result of cell experiments proves that the method can be used to screen the combination drugs in order to prepare antitumor medicine compositions of the HDAC inhibitor and the micro-molecular compound, and the medicinal compositions are suitable for all dosage forms.

The present invention provides for up- and down-regulation of cellular autophagy, e.g., for treating cancer or neurological disease. The invention results, in part, from discovery of two novel proteins, ATG14L (previously called “BISC”) and Rubicon (previously called “BIRC”), which bind to a Class III phophatidylinositol 3′-kinase (PI3K) / Vps34-Beclin 1 autophagic complex. ATG14L and Rubicon each regulate autophagic activity in an opposing manner. ATG14L and Rubicon can be used, for example, to increase / decrease autophagic activity, to increase / decrease PI3K / Vps34 kinase activity, and in so doing, treat diseases and disorders, such as cancer, neurodegenerative disease, stroke, metabolic disease, and age-related disease. ATG14L can increase autophagic activity and PI3K / Vps34 kinase activity; and Rubicon can decrease autophagic activity and PI3K / Vps34 kinase activity.

The invention provides a method and a device for predicting cell autophagy phenotype. The method comprises the following steps of: collecting cell images, preprocessing the cell images, improving image quality and facilitating batch operation to obtain analysis images. According to the position of the cells in the analysis image, the analysis image is divided into a single cell image, so as to realize the accurate recognition of the single cell image. The single cell image is put into a trained convolution neural network model for calculation to obtain autophagy probability, and the cells corresponding to the single cell image whose autophagy probability is greater than a preset classification threshold are determined as autophagy cells, thereby avoiding manual extraction and identification, facilitating batch identification and prediction, and simultaneously realizing cell count.

The invention relates to anti-tumor medicines, and concretely relates to an anti-tumor synergic medicine. The synergic medicine is a medicinal complex consisting of one or a plurality of cell autophagy inhibitors and recombined human argininase. The cell autophagy inhibitor(s) and the recombined human argininase are administrated in a combined administration manner or in a sequential administration manner. By inhibiting autophagy of tumor cells induced by argininase, the antagonistic action, caused by cell autophagy, of tumor on argininase treatment is offset, and therefore the killing effect of recombined human argininase on tumor is enhanced, and the treatment effect of argininase on tumor is substantially enhanced. The synergic medicine is applicable to lymphoma, leukemia, liver cancer, lung cancer, melanoma, breast cancer and myeloma.

The invention belongs to the technical field of medicines and biology, relates to a synergic pharmaceutical composition treating tumors, and especially relates to a compound medicine or a pharmaceutical composition prepared from one or a plurality of cell autophagy inhibitors and beta interferon. The cell autophagy inhibitor(s) and beta interferon of the synergic pharmaceutical composition are administrated in a combined administration manner or in a sequential administration manner. By inhibiting autophagy of tumor cells induced by beta interferon, the antagonistic action, caused by cell autophagy, of tumor on treatment of beta interferon is offset, and therefore the killing effect of individually-used beta interferon on tumors is enhanced, and the treatment effect of beta interferon on tumors is substantially enhanced. The synergic medicine is applicable to glioma, pancreas cancer, lung cancer, liver tumor, vascular cancer and myeloma, and the treatment effect of individually-used beta interferon on tumors is substantially enhanced.

The invention relates to the technical field of medicines and biology, and concretely relates to a pharmaceutical composition treating tumors. The pharmaceutical composition consists of one or a plurality of autophagy adjusting medicines and a monoclonal antibody medicine. The autophagy adjusting medicine(s) and the monoclonal antibody medicine in the pharmaceutical composition are administrated in a combined administration manner or in a sequential administration manner. By adjusting cell autophagy, the curative effect of the monoclonal antibody medicine on various tumors is enhanced. By utilizing the cell autophagy adjusting medicines to activate / inhibit autophagy, the curative effects of a plurality of monoclonal antibody medicines on lymphoma, stomach cancer, breast cancer, lung cancer, ovarian cancer and brain tumor are enhanced, and especially the curative effects on lymphoma, stomach cancer and breast cancer are enhanced.

The invention discloses a chimeric molecule for mediating Tau protein degradation based on an autophagy mechanism, and the amino acid sequence is shown in SEQ ID NO:5 or 7. The invention also discloses a nucleic acid molecule and an expression vector; and the nucleic acid molecule is used for encoding the chimeric molecule for mediating Tau protein degradation based on the autophagy mechanism, andthe expression vector comprises the nucleic acid molecule. The invention also discloses an application of the chimeric molecule for mediating Tau protein degradation based on the autophagy mechanism,the nucleic acid molecule and the expression vector in degradation of Tau protein. The novel targeted chimeric molecule is developed in the invention, and the chimeric molecule is bound to the surface of the aggregate protein Tau, so that the Tau protein is recruited into cell autophagosome and is promoted to be degraded through the cell autophagy pathway. The novel protein targeted degradation technology provided by the invention is expected to be applied to different target proteins, so as to overcome the defect that a current ubiquitin-proteasome pathway-based protein targeted degradationtechnology cannot efficiently degrade intracellular macromolecules.

A polytherapy of orally available compounds is disclosed that synergistically modulates and induces the expression of the cathelicidin gene (CAMP), which encodes the host defense peptide LL-37. By providing a number of different CAMP-inducing compounds together at the same time, stronger gene induction is achieved than with just one or two compounds, because the mechanism of induction broadens. Induction also may vary in different parts of the body depending on which compounds are used, and at what levels. We show for the first time that the polytherapy can induce cathelicidin expression in the brain, which may help to treat or prevent Alzheimer's Disease. Systemic cathelicidin gene induction may help treat numerous other conditions including Type 2 Diabetes / Metabolic Syndrome, or chronic bacterial, viral, or fungal infections associated with increased cancer risk or neurodegeneration. By increasing cellular autophagy and macroautophagy and supporting mitochondrial biogenesis and homeostasis, CAMP gene upregulation may reduce the effects of cellular aging and increase longevity.

The invention discloses a PICT-1 (protein interacting with carboxyl terminus 1) protein truncated mutant which has a sequence represented by sites from 181 to 478 in SEQ ID NO: 1. Due to the overexpression of the truncated mutant, the UBF activity can be adjusted, rDNA transcription can be suppressed, and cell autophage can be caused; the PICT-1 protein truncated mutant can be used for preparing an anti-tumor medicament, particularly a medicament for treating glioma. The invention further discloses a nucleic acid for encoding the truncated mutant and application of the nucleic acid, an expression vector of the nucleic acid for encoding the truncated mutant, a host cell comprising the expression vector, and a method and a device for treating the glioma.

The invention provides a pharmaceutical composition for mild photothermal therapy of tumors as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition is composed of a dual-targeting amphiphilic glucan derivative carrier, a material (PTA) with photo-thermal conversion performance and an autophagy inhibitor. The dual-targeting amphiphilic glucan derivative carrier can be self-assembled in water to form nano-micelles, and is physically loaded with PTA and an autophagy inhibitor for tumor photothermal therapy. The preparation is mainly characterized in that: 1) the preparation has active dual-targeting capability of tumor cells and tumor-related fibroblasts, and can efficiently enter the cells through the action of receptor ligands, so that the transfer efficiency of the preparation is improved; 2) under the irradiation of 808nm laser, PTA absorbs light energy and efficiently converts the light energy into heat, and the autophagy inhibitor inhibits the autophagy behavior of tumor cells and sensibilizes photo-thermal, so that an excellent mild photo-thermal treatment effect is realized, and the physical barrier of a tumor matrix can be weakened; tumor photothermal can further induce tumor cells to generate immunogenic cell death, generated tumor fragments can further activate an immune system, and the tumor photothermal treatment effect is greatly improved.

The invention belongs to the technical field of biologics and relates to a preparation method and application of nervous system neoplasm cell autophagosome to preparing a vaccine. Sirolimus and ammonium chloride are adopted to induce and culture nervous tumor cells, autophagosome generation is promoted, and autophagosome is extracted through repeated blowing and beating and high-speed centrifugation at different steps. A great deal of autophagosome can be rapidly prepared by using the method provided by the invention, after the autophagosome is carried by DCs (Dendritic Cells), DC maturation can be effectively promoted, T lymphocyte can be activated, proliferation of the T lymphocyte can be promoted, a remarkable killing function on tumor cells can be achieved, and the killing effect is remarkably better than tumor freeze thawing splitting antigen prepared in the prior art. The autophagosome prepared by using the method can be further adopted to prepare a nervous system tumor vaccine,and the vaccine is a dendritic cell tumor vaccine for nervous system derived tumor cell autophagosome.

The invention relates to a sorafenib drug-resistant marker and application thereof, and belongs to the technical field of biomedicine. The sorafenib drug-resistant marker is CCT6A. Research of the marker finds that on one hand, the relationship between CCT6A / B55 gamma pathway regulation and control of autophagy and liver cancer cell sorafenib drug resistance can be identified through deep research, and a scientific basis is provided for a new approach of targeting the pathway to treat liver caner. On the other hand, sorafenib drug-resistant people can be prompted, and the effects of personalized treatment and precise treatment are achieved in liver cancer treatment or cancer treatment.

The invention provides a nano-medicine, a preparation method thereof and an application of the nano-medicine. The nano-medicine comprises a calcium phosphate substrate, a chemotherapy medicine, a photo-thermal agent and an autophagy inhibitor, the chemotherapy medicine is sealed in the calcium phosphate substrate, the surface of the calcium phosphate substrate is modified by the photo-thermal agent, and the autophagy inhibitor is loaded into a pore of the photo-thermal agent. According to the nano-medicine, chemotherapy and thermotherapy are combined, calcium phosphate serves as a rigid substrate, the chemotherapy medicine and the photo-thermal agent are sealed in the rigid substrate of the calcium phosphate, the autophagy inhibitor of a cell is loaded on the rigid substrate, so that chemotherapy and thermotherapy effects can be improved by inhibiting autophagy, and tumor treatment effects are improved.

The invention discloses a 3-hydrogenated pinicolic acid cyanide ethyl ester medicine and application thereof. The medicine comprises a compound with the following structure formula which is as shown in the description. The medicine also comprises pharmaceutically acceptable salts, 3-hydrogenated pinicolic acid cyanide ethyl ester as well as derivatives and pharmaceutically acceptable salts thereof, and pharmaceutically acceptable auxiliary materials or carriers. The 3-hydrogenated pinicolic acid cyanide ethyl ester is a PI3K / mTOR dual inhibitor; the invention also relates to application of the 3-hydrogenated pinicolic acid cyanide ethyl ester medicine to promotion of cell autophagy and application of the 3-hydrogenated pinicolic acid cyanide ethyl ester medicine to preparation of medicines for treating tumors such as gastric cancer, liver cancer, lung cancer, prostatic cancer and nasopharynx cancer and the like, neurodegenerative diseases such as presenile dementia and the like, and diabetes. The 3-hydrogenated pinicolic acid cyanide ethyl ester medicin provides a novel clinical medication choice.

The invention belongs to the field of botany, and relates to a method for creating a wheat seedling drought premature senility physiological phenotype by using a cell autophagy inhibitor. The method inhibits the activity of phosphoinositide 3 phosphokinase (PI3K) necessary for formation of an autophagy vesicle membrane structure by using the cell autophagy inhibitor, and the time for creating thewheat seedling drought premature senility phenotype only needs 3 days. Through the method provided by the invention, the autophagy function of wheat cells under drought stress can be simply and quickly verified, and an important methodological basis is also provided for carrying out autophagy research on other plants under drought stress.

The invention relates to the fields of biotechnology and nano biomaterials, and relates to a preparation method and an application of a quantum dot preparation which is low-toxicity and is applicable to lung cancer diagnosis. A composition or the preparation is prepared by linking conventional quantum dots to lung cancer targeting molecules and then combining an obtained material with an autophagy regulating agent. Especially, the quantum dot preparation is composed of one or more lung cancer targeting quantum dots and one or more autophagy / enhancing agents. The quantum dot preparation prepared by the invention has the characteristics that the quantum dot preparation is lower than general quantum dot preparations in toxicity, the quantum dot preparation is capable of achieving specific targeting of lung cancer and the like. The preparation method of the preparation is simple in process, broad in application scope and applicable to large-scale production. Furthermore, the preparation is mainly used for preparing preparations for diagnosing, treating and detecting the lung cancer and the other cancers. Meanwhile, the preparation is also suitable for preparing preparations for in-vivo cancer cell tracing and localizing.

The invention discloses a method for identifying functional kinase for regulating cell autophagy, and belongs to the technical field of biological information. The method comprises the following steps: carrying out transcriptome, proteome and phosphorylated proteome analysis on a cell sample before and after autophagy inducer treatment to obtain gene expression data, protein expression data and phosphorylation site data of the cell sample before and after autophagy inducer treatment; normalizing the obtained phosphorylation site data to obtain kinase intensity information; according to the obtained kinase intensity information, calculating kinase which is remarkably changed in the cell sample before and after treatment of the autophagy inducer; according to the obtained kinase with significant change, carrying out the significant change analysis on transcriptional expression, protein expression and phosphorylation modification levels of the kinase, and acquiring the functional kinase for regulating and controlling cell autophagy by combining the autophagy regulation and control function of the known kinase. According to the method, the kinase screening range can be effectively reduced, the workload of experimental verification is reduced, and the functional kinase for regulating and controlling cell autophagy is accurately identified.

The invention discloses a two-photon pH (potential of hydrogen) ratio measurement fluorescence probe for monitoring cell autophagy, a preparation method of the fluorescence probe and an application. The structure of the two-photon pH (potential of hydrogen) ratio measurement fluorescence probe for monitoring cell autophagy is as shown in the specification. The fluorescence probe has specific fluorescence signal response to pH. By the aid of a cell co-localization test, the fluorescence probe can be specifically targeted to cell lysosomes, a cell toxicity test indicates that the fluorescence probe has almost no toxic and side effect on cells, a two-photon confocal fluorescence micro-imaging test indicates that the fluorescence probe has good penetrability for MCF-7 cells, pKa of the fluorescence probe is 3.88 through calculation, the fluorescence probe is suitable for monitoring change ranges of the pH of the cell lysosomes, and the cell autophagy process can be monitored in real time by detecting change of the pH of the cell lysosomes.

The embodiment of the invention discloses application of specnuezhenide in preparing an autophagy inducer or a pharmaceutical composition. By means of discovery of the autophagy inducing effect of thespecnuezhenide, the specnuezhenide is expected to the developed into the novel autophagy inducer to be used for disease treatment or auxiliary treatment, such as auxiliary treatment of bacterial infection diseases and auxiliary treatment of tumors.

The invention discloses application of tanshinone I in preparation of tumor cell autophagy inducer drugs. Compared with the prior art, the invention for the first time finds that tanshinone I can induce autophagy of tumor cells and has a remarkable treatment effect on cervical cancer, breast cancer or liver cancer, especially cervical cancer. Research proves that tanshinone I can inhibit cancer cell growth, inhibit cancer cell mitochondrial injury and autophagy, and induce the expression of tumor cell autophagy molecules and cutting of autophagy molecule LC3.

The invention discloses an application of a curcumin analogue CUR5g as an autophagy inhibitor. According to the invention, the influence of 5g of CURR on A549 cell autophagy is detected through a transmission electron microscope experiment, the influence of 5g of CURR on A549 cell autophagy marker protein level is detected through a protein immunoblotting method, and the influence of 5g of CURR on H157, HepG-2 and MCF-7 cell autophagy marker protein levels is detected through the protein immunoblotting method. The effects of cur5g on autophagy marker protein level of A549 cells under autophagy inhibition and activation conditions were detected by Western blotting, and the effects of cur5g on autophagy initiation protein level of A549 cells were detected by Western blotting. It was proved that cur5g can effectively inhibit the fusion of autophagosomes and lysosomes in vitro, so as to inhibit the autophagy. 5g of CUR5 has a remarkable effect as an autophagy inhibitor, and an attractive prospect is provided for development and application of the autophagy inhibitor.

The invention relates to an autophagic inhibiting polypeptide which has an amino acid sequence of LPDISLKDLQFLQSFCPSEVQ. The polypeptide can be prepared by an artificial synthesis or host cell expression method, and can be used for preparing tumor treatment medicines. The autophagic inhibiting polypeptde only has 21 amino acids, can be easily and feasibly prepared by either artificially synthesizing or applying host cell expression, and is beneficial to large-scale popularization and utilization. The polypeptide is derived from inherent protein in a living body, cannot cause immune elimination in an animal experiment, has small toxicity to cells, and is more specific. The inhibiting polypeptide can be used for introducing a gene segment coding the polypeptide into a cell for stable expression through a lentivirus or transfection and other means, is convenient to operate, and is beneficial to researches for cell level and animal level.

The present invention relates to the technical field of biomedicine. According to the present invention, research results show that arginase can significantly induce head and neck neoplasm cells to produce autophagy while the autophagy can partially counteract the anti-tumor effect of the arginase; and with use of the autophagy inhibitor to inhibit the autophagy, and the sensitivity of the head and neck neoplasm cells on the arginase can be increased so as to enhance the treatment effect of the arginase on the head and neck neoplasms. The present invention provides a preparation for combined treatment of head and neck neoplasms, specifically a drug composition comprising the autophagy inhibitor and the arginase. The present invention further provides applications of the drug composition in preparation of drugs for treatment of head and neck neoplasms, especially laryngeal cancer, hypopharyngeal cancer and nasopharyngeal cancer.