97 results about "Lysosome" patented technology

The present application relates to a kind of hydrolysis targeting chimera based on artificial antibody and its preparation method and application.The hydrolysis targeting chimera is composed of artificial gold antibody and molecule that can activate cell degradation mechanism, the artificial gold antibody is composed of gold nanoparticle and polypeptide coupled on the surface of gold nanoparticle, the molecule that can activate cell degradation mechanism is coupled on the surface of gold nanoparticle.The hydrolysis targeting chimera can simultaneously bind target protein and activate cell degradation mechanism, with the performance of strong specific recognition target protein, and high stability, orientation controllable.At the same time, the hydrolysis targeting chimera can also play the molecule of activation cell degradation mechanism, such as lysosome sorting signal motif, coupled on the surface, induce clathrin-mediated endocytosis, transport the complex of target protein and chimera to lysosome and degrade.The hydrolysis targeting chimera can play multi-mode cancer treatment effect by synergistic inhibition of tumor cell proliferation, invasion pathway and apoptosis activation.

The application discloses a pinacine alkyl tetrahydrocarbazole fluorescent probe capable of detecting cell lysosome polarity and a preparation method and application thereof. 9-(3-(dimethylamino)propyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-2,4-bridged methylene carbazole-6-formaldehyde is used as raw material, and condensation reaction is carried out with 1,3-indan dione to obtain compound 2-(2-(9-(3-(dimethylamino)propyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-2,4-bridged methylene carbazole-6-yl)vinyl)-1-indene-1,3(2H)-dione (TC-AP-ID), and the probe can specifically detect the polarity of cell lysosomes. In a mixed system of 1,4-dioxane and water, with the increase of the polarity of the system, the fluorescence color of the probe gradually changes from orange to red, and the fluorescence intensity significantly decreases. The probe has the advantages of simple synthesis, good selectivity, high sensitivity, good biocompatibility, low toxicity and the like, can be applied to targeted detection of the polarity of cell lysosomes, and has a good application prospect.

This invention discloses an enhanced CAR-T cell (CARTAC) capable of secreting a targeted membrane protein degrader and its applications. While retaining specific killing function, this cell can expand locally in tumors and continuously secrete the bispecific adaptor molecule scTAC. scTAC can recruit E3 ubiquitin ligases, mediate ubiquitination of tumor cell surface membrane proteins (such as PD-L1), and achieve targeted degradation via the lysosomal pathway, effectively reversing the immunosuppressive microenvironment, overcoming antigen heterogeneity, and eliminating antigen-negative tumor cells through the bystander effect. This invention also utilizes the efficient endocytosis properties of EGFR to design scTAC-dual, which can further enhance degradation efficiency. In various lung cancer mouse models, CARTAC-dual exhibited excellent tumor infiltration capacity, low exhaustion levels, and sustained antitumor activity, without systemic toxicity. This invention integrates the targeted killing and protein degradation delivery functions of CAR-T cells, not only enhancing the control effect on solid tumors but also possessing target scalability, making it suitable for the universal upgrading of various CAR-T products.

The application belongs to the technical field of functional polypeptides, and particularly relates to an active peptide for senescent cells and a preparation method thereof, wherein the active peptide is obtained by molecular docking simulation screening and optimization with a helical structure segment in an IL-6R protein combined with a gp130 protein as a polypeptide template; the active peptide after functional optimization contains an FF unit driving nano self-assembly, a GFLG unit capable of being specifically cut by a lysosome protease highly expressed in a microenvironment of senescent cells, and an RYFQKWEKLRNQ unit generating high affinity with an IL-6 / IL-6R / gp130 complex; the designed active peptide itself has anti-aging activity and can also be used for synergistic delivery of drugs, and has a broad application prospect.

The present disclosure provides oligonucleotides, methods, and compositions for degrading RNA via the lysosomal pathway. Also encompassed are oligonucleotides, methods, and compositions for treating, preventing, or ameliorating diseases, disorders, and conditions associated with EXOC2 , Ku80 and Task1 in a subject in need thereof.

The application provides application of dimethyl itaconate in prevention and treatment of chronic stress-induced anxiety. The application finds that dimethyl itaconate can inhibit excessive activation of microglial cells in a stress state, improve mitochondrial structure and function abnormalities of the microglial cells, and reduce expression of a lysosome marker CD68, so as to inhibit central nervous inflammation, maintain central nervous immune homeostasis, prevent and relieve anxiety-like behavior induced by chronic stress, and effectively prevent and relieve occurrence and development of chronic stress-induced anxiety (generalized anxiety disorder).

The application belongs to the field of biological medicine, and relates to a drug-loaded nanovesicle and a preparation method and application thereof. The drug-loaded nanovesicle comprises: a vesicle core comprising siRNA capable of specifically targeting a silenced NR1D1 gene; and a vesicle membrane fused by red blood cell membranes, macrophage membranes, cardiolipin, cholesterol and lecithin. The drug-loaded nanovesicle can specifically target macrophages in the immune suppression stage of sepsis, and has an intracellular response release function. By inhibiting the expression of NR1D1, the drug-loaded nanovesicle restores the functions of BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axes, reestablishes the phagocytosis function of macrophages and the lysosome-dependent bacterial clearance capacity, significantly improves the survival rate of animals in a sepsis immune suppression model and reduces the bacterial load. Compared with a traditional electroporation method, the preparation method of the application significantly improves the encapsulation rate of siRNA.

The application belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of umbilical cord blood plasma-derived extracellular vesicles and related bioactive molecules thereof in treatment of Alzheimer's disease. Specifically, the application isolates extracellular vesicles (UCBP-sEVs) from umbilical cord blood plasma, which has the effect of improving Alzheimer's disease. Further research finds that high enrichment of miR-16-2-3p therein is a key molecule for mediating treatment of Alzheimer's disease. miR-16-2-3p targets and inhibits expression of ROCK2, reduces phosphorylation level of TFEB and promotes nuclear translocation of the same, activates microglial autophagy-lysosome pathway, and thus promotes phagocytosis and degradation of intracerebral beta amyloid, and therefore has good practical application value.

The application discloses a kind of short peptides simulating RhoE C end, derivative and its pharmaceutical use in treating ventricular remodeling, belong to biological medicine technical field.The short peptide and derivative contain RhoE C end 200-240 linear function domain, can be combined and activated WWP2, remove HGS self-inhibition, start endosome-lysosome degradation pathway.Short peptide sequence is as SEQ ID NO.1, derivative can be coupled with TAT, T7 or RVG membrane penetrating peptide (SEQ ID NO.2-4), and endocytosed to myocardial cell by caveolin high efficiency delivery.The application solves the defects that existing anti-ventricular remodeling drug inhibits protective autophagy flow, and the ability of eliminating toxic protein is limited, can efficiently eliminate damaged mitochondria and misfolded protein, inhibits myocardial hypertrophy, fibrosis, improves cardiac remodeling, provides safe and effective treatment strategy for related diseases.

This invention discloses a method for studying the mechanism by which the mucoprotein channel 1 (TRPML1) regulates the outflow of zinc ions from lysosomes and induces changes in mitochondrial ATP. This method uses 13 nm AuNPs as loading materials to construct a logic-gated sensor for pH and zinc ion regulation within lysosomes and for TRPML1 mRNA in the cytoplasm. It also uses 5 nm AuNPs as loading materials to construct a sensor targeting mitochondrial ATP for cell imaging. This method enables the detection of mRNA and zinc ions in the cytoplasm, lysosomes, and mitochondria. 2+ ATP-associated ATP sensors, Zn 2+ Three sensors—a sensor, an mRNA sensor, and an X-ray sensor—are used simultaneously to image cells, aiming to answer questions about the mechanisms of ATP changes in mitochondria under the regulation of zinc ion efflux from lysosomes by TRPML1.

This invention discloses a glycyrrhizic acid nanomedicine, its preparation method, and its applications, belonging to the field of biomedical nanomaterials technology. The glycyrrhizic acid nanomedicine is prepared by reacting ammonium glycyrrhizate and sodium oleate at a temperature of 15-40 °C. o Glycyrrhizate nanomedicine was prepared via a microemulsion method at temperature C. After entering tumor cells, the glycyrrhizate nanomedicine was rapidly degraded within the acidic lysosomes of the tumor cells, releasing a large amount of sodium. + The presence of glycyrrhizic acid ions and glycyrrhizic acid ions causes a surge in intracellular ion concentration and osmotic pressure, as well as the accumulation of glycyrrhizic acid within tumor cells. This induces pyroptosis in tumor cells and regulates the expression of proliferation-related proteins. Pyroptosis releases a large number of damage-associated molecular patterns (DAMPs) to trigger immune activation, while the regulation of proliferation-related protein expression inhibits tumor cell proliferation. Under the combined effect of these two factors, glycyrrhizic acid nanomedicines can not only activate the systemic anti-tumor immune response but also reduce tumor cell spread, thereby effectively inhibiting tumor growth and metastasis and enhancing the efficacy of tumor immunotherapy.

Provided herein are compositions and methods using a bicistronic vector for treating or preventing a lysosomal storage disease (LSD) in a subject. The disclosed compositions include a bicistronic vector comprising a promoter, an internal ribosome entry site (IRES), a polynucleotide encoding a lysosomal enzyme, and a polynucleotide encoding a modified GlcNAc-1 phosphotransferase (GlcNAc-1 PTase). The method includes administering to a subject a pharmaceutical composition comprising the bicistronic vector disclosed herein.

The application discloses an application of intervention of stress granule degradation by regulating TM9SF1 expression, and belongs to the technical field of biotechnology.It is found for the first time that TM9SF1 is a key molecule for regulating stress granule degradation, up-regulation of TM9SF1 expression can significantly promote stress granule degradation through an autophagy-lysosome pathway, and down-regulation of TM9SF1 expression will lead to stress granule degradation disorder and abnormal accumulation.The application also provides application of TM9SF1 in preparation of medicines for preventing, relieving or treating diseases (neurodegenerative diseases, malignant tumors, viral infectious diseases and the like) related to abnormal accumulation of stress granules, and a method for intervention of stress granule degradation.The application provides a new target for treatment of stress granule related diseases, has the advantages of strong targeting, wide application range, wide clinical conversion prospect and the like, and fills the blank of specific regulation of stress granule in the prior art.

The application discloses a butyl tin-cycloiridium phenanthroline complex with an aggregation-induced emission (AIE) property, a preparation method of the complex and anticancer application of the complex. The structural formula of the complex is shown as formula (I), and R is one of hydrogen, a phenyl group, a p-tolyl group, a p-bromophenyl group, a p-fluorophenyl group, a biphenyl group, a triphenylamine group, a carbazole group, a tetraphenyl ethene group and a triphenylbenzene group. The growth inhibition rates of the target compound on human alveolar basal epithelial carcinoma cells (A549) and cisplatin-resistant cells (A549 / DDP), cervical cancer cells (Hela) and human lung normal epithelial cells (BEAS-2B) are tested, and it is found through comparison that the target compound shows potential anticancer activity. In addition, the target compound shows unique AIE emission characteristics. The target compound mainly targets the lysosomes of A549 cells, and influences the mitochondria to cause the decline of the mitochondrial membrane potential, thereby showing anticancer activity.

Provided are a composition for preventing and treating an oral disease or condition, a preparation method therefor, and the use thereof. The composition comprises extracellular vesicles derived from oral pathogenic bacteria. The extracellular vesicles are nanoscale vesicles rich in immune activation and defensive factors against pathogenic bacterial infection. Upon administration via the oral mucosa into a body, the vesicles are passively aimed at lymph nodes associated with the oral mucosa to induce the expression of a mucosal immunity-specific antibody, thereby enhancing immune defense against pathogenic bacteria. The extracellular vesicles of oral pathogenic bacteria are coated with a calcium phosphate shell, and the shell is soluble only under acidic conditions and degrades only after the extracellular vesicles are aimed at the lymph nodes and are phagocytosed into lysosomes of dendritic cells, thereby avoiding inflammatory reactions in an administration area. By using a sublingual disintegrating tablet as the form of administration, the bioavailability of a vaccine can be enhanced while achieving the local administration at the mucosa and activating mucosal immunity. Moreover, the composition is convenient to administer, which is conducive to the diagnosis and treatment of oral bacterial infectious diseases.

The present invention provides novel fluorinated cyclic derivatives of sulfonamides and sulfones, compositions thereof, and methods for preparing and using them, which are useful for treating various diseases and disorders related to TRPML activity, such as neurodegenerative diseases, lysosomal storage disorders, muscular dystrophy, common neurodegenerative diseases associated with aging, diseases associated with oxidative stress or reactive oxygen species (ROS), and aging.

This invention belongs to the fields of pharmaceutical application and biomedicine, specifically relating to the application of clofazimine in the preparation of drugs for treating gastric cancer. This invention is the first to discover that clofazimine possesses significant anti-gastric cancer activity, which is confirmed through systematic experiments. This activity stems from its ability to induce mitochondrial damage and simultaneously cause lysosomal dysfunction, leading to lethal inhibition of autophagic flux. In vitro, clofazimine can inhibit gastric cancer cell viability and induce apoptosis in a concentration-dependent manner; in vivo, clofazimine effectively inhibits tumor growth and exhibits good biocompatibility. This represents the development of a novel use for a known drug, providing a potential new treatment option for gastric cancer treatment, particularly overcoming the limitations of existing treatment strategies.

The present application belongs to the field of biopharmaceuticals. Disclosed is the use of a stem cell extract in the preparation of a drug for treating or preventing arthritis by regulating lysosomal and / or mitochondrial functions, wherein a method for preparing the stem cell extract comprises: S1) culturing mesenchymal stem cells and creating stress conditions to stimulate the mesenchymal stem cells; and S2) isolating and purifying a culture supernatant of the mesenchymal stem cells cultured in S1) to obtain a stem cell extract, wherein S2) comprises: S21) filtering the culture supernatant to obtain a filtrate; S22) concentrating the filtrate by means of 3KD ultrafiltration to obtain a crude sample; S23) purifying the crude sample by means of size-exclusion chromatography or reversed-phase chromatography to prepare a purified sample; and S24) preparing the purified sample into a preparation. In the present application, the culture supernatant containing secretions of the stressed stem cells is obtained by means of stress culturing of the stem cells, and in combination with a purification method, the supernatant is prepared into a preparation which can be used for treating arthritis.

The application discloses application of FBXO2 in colorectal cancer and prognosis judgment. Specifically, the application finds the role of FBXO2-FABP5 axis in p53-mediated colorectal cancer ferroptosis resistance: p53-activated FBXO2 promotes lysosomal degradation of FABP5 through the CMA pathway, leading to a decrease in PUFA levels, and ultimately leading to colorectal cancer ferroptosis resistance. Therefore, FBXO2 protein and FABP5 can be used as new colorectal cancer diagnostic markers.

The application discloses application of cathepsin E in preparation of a drug for treating or preventing lung cancer, relates to the technical field of biological medicine, and first proves that CTSE is highly expressed in lung adenocarcinoma tissues and has the biological function of inhibiting lung cancer cell proliferation through clinical sample analysis, cell function experiment and animal experiment. Mechanism research shows that CTSE plays the anticancer role by down-regulating the expression of cathepsin B (CTSB) and promoting the degradation of STING protein through a lysosome pathway and inhibiting the cGAS-STING natural immune pathway. The application clarifies the application value of CTSE as a new target for treating lung adenocarcinoma, provides a theoretical basis and experimental basis for developing a novel lung cancer treatment drug, and has an important clinical application prospect.

The application discloses oleanane triterpene saponin compounds with improved mitochondrial energy anti-aging, a preparation method and application thereof, and belongs to the technical field of medicines and cosmetics. Through systematic chemical component research on Zhejiang Hongshan tea flowers, two new oleanane triterpene saponin compounds CK and CL are separated, and the chemical structures are determined by using high-resolution mass spectrometry and nuclear magnetic technology. In-vitro anti-photoaging activity research shows that the new compounds CK and CL provided in the application have good protection effects on ultraviolet-induced fibroblast photoaging, can significantly improve the content of type I collagen, reduce the expression of matrix metalloproteinases mmp1 and mmp3 , increase the generation of mitochondrial autophagosomes and lysosomes, promote mitochondrial autophagy, relieve mitochondrial damage and improve cell senescence. The preparation method provided in the application is simple, and the activity is significant, so that the application is expected to be developed into a new anti-skin aging medicine or cosmetic.

The application discloses the technical field of carbon dot application, and relates to a luteolin carbon dot for guiding lysosomes and a preparation method and application thereof. The luteolin carbon dot is prepared by using luteolin and 2,5-dihydroxyterephthalic acid as carbon source precursors through a hydrothermal method. The prepared luteolin carbon dot has a particle size of 0.5-4 nm, a fluorescence excitation wavelength of 360-440 nm, a maximum emission wavelength of 540 nm and a Zeta potential of -19 mv. Research shows that the luteolin carbon dot can guide macrophage and adipocyte lysosomes, promote M2 type macrophage polarization, and up-regulate the expression of the heat production and brown colorization marker gene Ucp1 of beige adipocytes. Further, the M2 type macrophage loaded with the luteolin carbon dot can promote the expression of the Ucp1 of the beige adipocyte through the release of the carbon dot and the paracrine effect, thereby increasing heat production and energy consumption. The application lays a foundation for developing an intervention and treatment scheme for obesity and related metabolic diseases based on the carbon dot in the future.

Aspects of the invention relate to recombinant adeno-associated viruses (rAAVs). In some aspects, the rAAVs comprise artificial genetic regulatory elements that modulate transgene expression. In some aspects, the disclosure relates to the treatment of lysosomal storage disorders.

The present disclosure provides a method for degrading a target protein, comprising: contacting a T-cell with a multispecific binding protein, wherein the multispecific binding protein comprises: a) a first cell surface binding moiety that specifically binds to membrane- bound CTLA-4 on the surface of the T-cell; and b) a second binding moiety that is operatively linked to the first cell surface binding moiety and that specifically binds to the target protein, wherein binding of the multispecific binding protein to the membrane-bound CTLA-4 on the surface of the T-cell facilitates the internalization of the target protein by the T-cell. After internalization, the multispecific binding protein plus the target protein traffic to a lysosome within the T-cell, enabling degradation of the target protein within the lysosome. The present disclosure also provides multispecific binding protein compositions, host cells for making the multispecific binding protein compositions, and methods of using the multispecific binding protein compositions to treat disease.

The application discloses a tetrazine cyanine compound and a preparation method and application thereof. The skeleton of the tetrazine cyanine compound is directly connected with a BFI part of cyanine, can better affect the overall fluorescence opening multiple of the tetrazine cyanine compound by adjusting an R1 group, can also realize high-resolution imaging of a lysosome, an endoplasmic reticulum and a mitochondrial membrane by selecting a suitable R1 group and cooperating with a predetermined site molecule, can realize high fluorescence opening multiple in a near-infrared region, can significantly enhance a fluorescence emission signal from an extremely low background level after reacting with BCN, and can also have excellent light stability, wherein the fluorescence intensity of a TBCy3P addition product generated in situ is basically maintained unchanged in the whole irradiation period under continuous 100-frame laser scanning excitation, and the cell morphology is normal.

Provided are a targeting vector and a method for targeting same to a host cell. The vector comprises a first molecule that binds to an endocytosis receptor of the target cell and a second molecule that promotes the release of a substance carried by the targeting vector into a cytoplasm. When the targeting vector is a viral vector, the first molecule is not part of a viral envelope protein, and the second molecule promotes endosomal escape or lysosomal escape of the targeting vector. The first molecule is designed according to the endocytosis receptor of the cell to be targeted, different types of cells can be targeted, and after a reasonable mutation is carried out on the vector, infection of cells that do not need to be targeted can be avoided, thereby improving the accuracy of the vector.

The application relates to the technical field of biological medicine, and discloses a preparation method of a liposome with a pH response type membrane fusion effect and application of the liposome. The pyridium betaine-terminated lipid molecule provided by the application can be quickly and reversibly protonated in a weak acid microenvironment of a tumor, the surface charge of the liposome is changed from negative to positive, and the precise switch of the membrane fusion behavior is realized; the self-adaptive fusion liposome constructed based on the pyridium betaine-terminated lipid molecule successfully converts the non-specific toxicity risk of the traditional fusion liposome into a space-limited intelligent response, remains stable and inert in blood circulation (pH=7.4), and specifically activates the membrane fusion at a tumor site, realizes direct cytoplasmic delivery of a drug and avoids lysosome degradation; the STING nano agonist constructed by loading the nano composite of a STING pathway agonist and a divalent metal ion on the platform exhibits a strong pH-dependent anti-tumor immune activation effect in vitro and in vivo, and significantly inhibits tumor growth while the systemic toxicity is extremely low.

This invention relates to the field of pharmaceutical biotechnology, providing the application of aminoquinoline compounds (such as hydroxychloroquine and chloroquine) in the preparation of drugs for treating hyperparathyroidism. These compounds restore the expression of calcium-sensitive receptors (CaSRs) on the cell membrane surface by inhibiting the lysosomal degradation pathway of CaSRs in parathyroid cells. Experiments have confirmed that 4-aminoquinoline compounds, used alone or in combination with calcimimetics (such as cinacalcet), significantly reduce serum PTH and calcium levels in a model of refractory secondary hyperparathyroidism (SHPT) and inhibit glandular hyperplasia. In particular, the combination therapy regimen exhibits a significant synergistic effect, effectively reversing calcimimetics resistance. This invention is the first to discover a novel use for the antimalarial / antirheumatic drug hydroxychloroquine in the treatment of hyperparathyroidism, realizing a new use for an existing drug; and providing a safe and effective new drug treatment strategy for clinically refractory SHPT.