100 results about "Cell Aggregations" patented technology

Provided herein are certain compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use.

The invention provides a preparation method and application of a compound protein preparation, and the preparation method comprises the following steps: dissolving a protein matrix in deionized water, adjusting the pH value to 8.0-8.5, firstly adding an antioxidant, and then adding an oxidant and a reducing agent to obtain a protein coupling solution; dissolving the whey protein isolate in deionized water, adding a thickening agent, stirring, and cooling to room temperature to obtain a proteoglycan composite water phase; and mixing the protein coupling solution and the proteoglycan composite water phase according to a preset proportion, adding the oil phase, carrying out homogenization treatment to form a high internal phase emulsion, carrying out freeze drying, and crushing into particles to obtain the powdery protein pre-preparation. The structural stability of protein molecules is remarkably improved, and protein aggregation and sedimentation are reduced, so that the physical and chemical stability of the protein preparation in the storage and use processes is effectively improved, and the problem of insufficient structural stability in the prior art is solved.

Disclosed is a novel class of fusion proteins to recruit the cell's innate chaperone machinery, specifically the Hsp70-mediated system, to specifically reduce TDP-43-mediated protein aggregation and associated protein conformational diseases.

The invention relates to the technical field of neutrophile granulocyte separation, in particular to a mouse neutrophile granulocyte separation method which comprises the following steps: (1) anesthetizing and disinfecting a mouse; (2) tissue sampling; (3) tissue digestion; (4) preparing a cell suspension; (5) purifying cells; (6) cell culture; according to the method disclosed by the invention, isoflurane is adopted in the anesthesia disinfection step, so that central nervous activity of mice can be rapidly inhibited, tissue damage caused by stress reaction is avoided, and chemical stimulation can be reduced while body surface microorganisms are cleared through combination of ethanol disinfection and sterile normal saline flushing, and aortic tissues with intact activity are provided for subsequent material taking. In the compound enzyme digestive juice, collagenase I can specifically degrade aortic wall collagenous fibers, trypsin dissociates adhesion connection between cells, neutral protease assists in decomposing elastic fibers, and DNA enzyme I is supplemented to inhibit cell aggregation, so that the contradiction between incomplete digestion and large cell damage of the traditional enzyme juice is effectively solved.

Provided herein is a method of decreasing a-syn levels and / or decreasing a-syn toxicity in a cell, the method comprising contacting the cell with a charged multivesicular body protein 2B: a-synuclein (CHMP2B:a-syn) inhibitor and a method of inhibiting neural degeneration, the method comprising administering to a subject in need thereof a charged multivesicular body protein 2B: a-synuclein (CHMP2B:a-syn) inhibitor.

The application discloses a preparation method and application of large-size human liver organoids, and belongs to the technical field of cell culture. In the application, 2D culture mature human primary liver parenchymal cells with different cell amounts are resuspended by using a hepatocyte maturation medium HIM, and are added into a U-shaped bottom 96-hole plate for low-oxygen static culture. After the cells are aggregated, the cells are cultured in normal oxygen and are shaken, so that large-size human liver organoids with different cell contents are prepared. The method does not need biological materials, and can induce human primary liver parenchymal cells to self-assemble and construct functional liver organoids with high uniformity in scale through specific culture conditions. The method solves the problems of large batch difference, high heterogeneity and dedifferentiation in the prior art, and can be widely applied to drug hepatotoxicity testing, in-vitro modeling of liver diseases and development of a bioartificial liver system.

Compounds comprising an amide-linked coumarin scaffold, compositions comprising same, and method of using such compounds and compositions to inhibit tubulin-associated unit (tau) protein aggregation or alpha-synuclein ( α-syn) protein aggregation in a subject having, or at risk for, tau protein aggregation or α-syn protein aggregation, respectively.

The present application provides methods, compositions and kits for determining SHD-catalyzed antibody levels in a biological sample and for treating or preventing protein aggregation disease (PAD) in an individual. Catalytic antibodies that specifically recognize amyloid beta (A beta) peptides and methods of using the same are also provided.

The present disclosure relates to a method for two-dimensionally culturing an intestinal stem cell population in a chemically defined medium and a use thereof, and also relates to a method for differentiating the intestinal stem cell population into 2.5-dimensional intestinal epithelial cells and a use thereof.

The invention discloses a method for sterilizing a vegetable protein beverage, which comprises the following steps of: adding a composite antibacterial microsphere preparation into a vegetable protein beverage to be treated, uniformly mixing, and performing high-density CO2 treatment and magnetic induction electric field sterilization to obtain a vegetable protein beverage finished product, the composite antibacterial microsphere preparation is prepared by taking fucoidan and a gallic acid acylated quercetin-phospholipid conjugate as a substrate and loading lysozyme and hydroxytyrosol. High-density CO2 and a magnetic induction electric field are adopted for synergistic sterilization, so that the structure of a microbial film can be changed, metabolism is disturbed, a good matrix is provided for electric field sterilization, and the sterilization efficiency is further improved through electric breakdown, magnetic field refining of water molecular groups and heat effect; the composite microspheres are sensitive to an electric field, so that lysozyme and hydroxytyrosol can be triggered to be accurately and quickly released under the action of a magnetic induction electric field, stubborn spores can be efficiently killed, and the killing effect is improved by destroying cell wall structures and disulfide bonds of the spores; meanwhile, protein aggregation and flocculation in the beverage can be effectively prevented, and the stability of a beverage system is guaranteed.

The application provides a screening device and method and application of small molecules for inducing or inhibiting protein polymerization, adopts a solid-state quartz nanopore as a core detection device, drives target proteins or complexes of the target proteins and small molecules to pass through a nanoscale pore, records ion current changes caused by each time of perforation event in real time, analyzes peak current and residence time characteristic values of each event, and can identify whether the proteins are in monomer, oligomer, aggregation or LLPS state. Meanwhile, the nanopore sensing is combined with small molecule processing, a mapping relationship between current signal changes and aggregation state regulation is established, and screening of small molecules for inducing or destroying protein aggregation behavior is realized. The technology has multiple advantages of label-free, single molecule, real-time monitoring and adaptation to multiple protein aggregation states, and breaks through the bottleneck of throughput and resolution capacity of existing methods.

An object of the present invention is to provide a cell aggregate-inducing peptide, a cell aggregate-forming agent containing the same, and a method for forming a cell aggregate using the same.SOLUTION: A cell aggregate-inducing peptide represented by General Formula (1), having hydroxypipecolic acid and lysine as constituent repeating units. (HPA-Lys) n. (1) [In the general formula (1), HPA represents hydroxypipecolic acid, Lys represents lysine, and n is an integer of 4 or more and 30 or less.]. ] SELECTED DRAWING: None

Disclosed herein are small molecule drugs that reduce protein aggregation and their methods of use. One aspect of the invention provides for a method reducing aggregate protein abundance in a protein aggregate, the method comprising administering an effective amount of a compound that stably binds a Glial Fibrillary Acidic Protein (GFAP) to a subject, wherein the aggregate protein comprises BSN, SYN1, MAP2, PLEC, RAB10, MAP1A, DCTN, TUBA4A, SPARE, PRKDC, or any combination thereof.

The invention discloses a sequential enzymatic-ionic synergistic soybean protein isolate modification method, which comprises the following steps: dispersing soybean protein isolate in water to prepare a protein solution, adding glutamine transaminase, carrying out heating reaction to inactivate enzyme to obtain an enzyme cross-linked protein solution, adding MgCl2 into the enzyme cross-linked protein solution, and carrying out heating reaction to induce protein aggregation to obtain a modified soybean protein isolate solution; and cooling to room temperature after the reaction is finished. The invention also discloses an application of the soybean protein product obtained by the sequential enzymatic-ionic synergistic soybean protein isolate modification method as a food additive. According to the method, the sensitization of the soybean protein can be remarkably reduced, meanwhile, the unique stomach resistance-intestinal efficient release dynamic characteristic is shown, and the small intestine peptide fragment release amount is promoted to be increased.

The invention belongs to the field of small molecule polypeptides, and particularly relates to a scallop polypeptide with a protein aggregation resisting function and application of the scallop polypeptide. The pure natural scallop polypeptide is extracted, separated and identified by taking scallops as raw materials through the steps of enzymolysis separation, ultrafiltration purification, LC-MS / MS identification and the like, the amino acid sequence of the scallop polypeptide is TMYWTDVSNGQIHR, the molecular formula is C74H110N22O23S, the average relative molecular mass is about 1707.88 Da, the theoretical isoelectric point is pH = 6.41, and the scallop polypeptide is hydrophilic polypeptide. The scallop polypeptide has the functions of oxidation resistance, protein aggregation resistance and neuroprotection, can be further applied to development of products such as food, medicines and health care products, and has a wide application prospect.

To provide technology that can be used to inhibit aggregation of β-amyloid protein (Aβ) and microtubule-binding protein Tau, which bring about senile plaque (senile plaque: AP) and neurofibrillary tangle (Neurofibrillary Tangle: NFT).SOLUTION: The present invention provides a protein aggregation inhibitor containing mesostructured particles of calcium hydrogen carbonate as an active ingredient.SELECTED DRAWING: Figure 2

The embodiment of the invention discloses a composite freeze-drying protective agent based on CRISPR-Cas13a, a microsphere molecular diagnostic reagent and a preparation method. The composite freeze-drying protective agent comprises a vitrification matrix component, a structure support component, a protein aggregation inhibitor and a surfactant, the vitrification matrix component comprises mannitol and trehalose, and the mass ratio of mannitol to trehalose is (3-7): (3-7); the structural support component comprises any one of PEG8000, PEG6000 and PEG4000 and any one of glucan 10000, glucan 8000 and glucan 20000, and the mass ratio of the PEG8000 to the PEG6000 to the glucan 8000 to the glucan 20000 is (1-5): (1-5); the protein aggregation inhibitor is bovine serum albumin, and the surfactant is polyoxyethylene sorbitan monolaurate; the mass ratio of the structure supporting component to the vitrification matrix component is (1-5): (3-7), the mass ratio of the protein inhibitor to the structure supporting component is (0.01-1): (2-10), and the mass ratio of the surfactant to the structure supporting component is (0.001-0.1): (2-10).

The present invention relates to a method and system (140) for determining the presence and / or quantity of protein aggregates in a liquid sample comprising a protein. The method comprises: a) measuring ultraviolet-visible spectroscopy (UV- Vis) absorbance of the sample to obtain a UV-Vis absorbance measurement; b) measuring index of refraction (IoR) of the sample to obtain an IoR measurement; c) determining a value for the UV-Vis absorbance measurement; d) determining a value for the IoR measurement; and e) determining the presence and / or quantity of protein aggregates in the sample based on a ratio between the value for the UV-Vis absorbance measurement and the value for the IoR measurement.

The invention discloses a modular combined vaccine soluble microneedle patch based on a mechanical interlocking tenon-and-mortise structure as well as a preparation method and application of the modular combined vaccine soluble microneedle patch. According to the combined and spliced micro-needle vaccine patch designed by the invention, synchronous delivery of various vaccines is realized by virtue of a micro-needle technology through fragmented loading and mechanical interlocking'mortise and tenon 'structural design, mutual interference among different vaccines is reduced at the same time, efficient protection can be provided for groups needing multi-vaccine protection by virtue of one-time inoculation, the number of inoculants is reduced, and the immune procedure is simplified; vaccine hesitation is reduced, and inoculation rate is increased; meanwhile, the biosoluble material of the microneedle structure can quickly release antigens in the skin to stimulate immune cells to aggregate so as to enhance the immune effect; the micron-sized needle array (lt; 500 m) acts on the superficial layer of the skin, is painless and can be designed into a self-adhesive patch, so that the inoculation compliance is improved; single-dose inoculation can also reduce medical cost, is suitable for resource-deficient regions, improves accessibility and burdenability, and accelerates establishment of a population immune barrier.

The invention discloses a technology for removing viruses from tetanus human immune globulin through a nano film. The process comprises the following steps: pretreating a feed liquid, so that the protein concentration of the feed liquid is 50-60g / L, the pH is 3.8-4.4, and the feed liquid contains 90-110g / L maltose and 50-150mmol / L sodium chloride; then, the feed liquid is subjected to two-stage filtration through a 0.1-micron nylon pre-filtration membrane bag with negative charges and a 20-nm regenerated cellulose (RC) virus removal membrane bag in sequence. According to the process, through optimizing the physical and chemical state of the feed liquid and the synergistic effect of the feed liquid and the functionalized filter membrane, the protein aggregation is effectively inhibited, the membrane pollution is reduced, the virus removal effect is ensured not to be lower than 4log10, the protein load of the RC membrane is remarkably improved to be more than 200L / m, and the product purity is more than or equal to 98%. The invention solves the technical problems of low flux and easy blockage of high-concentration immune globulin in small-aperture virus removal filtration, and is suitable for efficient, safe and large-scale production of blood products.

Provided are: a compound that imparts protein adhesion properties to cells; a method, using the compound, for producing cells having protein adhesion properties; cells adsorbed by the compound; and a cell sheet, a cell aggregation (spheroid, tumor-like body, etc.), an organoid, a three-dimensional tissue, etc. comprising the cells.

The present invention is directed to a protein aggregation assay, and methods of use thereof.

The invention relates to a method for assessing the aggregation propensity of expressed proteins comprising: expressing a protein of interest having a binding tag that upon binding to a detector moiet

Provided is a pre-filled syringe that can inhibit protein aggregation in a protein solution formulation while also reducing the produced amount of a decomposition product of a non-ionic surfactant after long-term storage. The pre-filled syringe includes: a barrel formed of a resin containing a hydrogenated cycloolefin ring-opened polymer and / or a copolymer of a cycloolefin and a chain olefin; a sealing member sealing a nozzle of the barrel; a gasket housed inside the barrel; and a plunger performing a movement operation of the gasket, and contains a protein solution formulation in a space defined by the sealing member, the gasket, and a region that is part of an inner wall surface of the barrel. The protein solution formulation has a non-ionic surfactant concentration of more than 0 mg / mL and less than 0.05 mg / mL.

Stabilized protein formulations and methods of using them are disclosed herein. In some embodiments, the formulations comprise a protein (e.g., insulin, glucagon, GLP-1 analogs, monoclonal antibodies) and a polyzwitterion, or a pharmaceutically acceptable salt thereof. The disclosed formulations promote delayed and reduced amounts of protein aggregation and subsequent protein fibrillation compared to formulations without polyzwitterions. These more stable formulations retain their potency for a longer period of time even at elevated temperatures.

The present invention provides compositions used for the treatment and / or prevention of protein aggregation disorders. [Solution] Proteopathy encompasses a wide range of ailments, including neurodegenerative diseases (e.g., polyglutamine diseases such as huntingtin in Alzheimer's disease, Parkinson's disease, and Huntington's disease, and prion diseases); amyloidosis of other non-neuronal proteins (especially I1-antitrypsin, immunoglobulin light and heavy chains, lactadherin, apolipoprotein, gelzolin, lysozyme, fibrinogen, atrial natriuretic factor, keratin, lactoferrin, and β-2 microglobulin, etc.); sickle cell disease; cataracts; cystic fibrosis; retinitis pigmentosa; and nephrogenic diabetes insipidus. Administration of sulfatase inhibitors is generally suitable for treating and / or preventing protein toxicity associated with proteopathy. Therefore, the present invention provides compositions comprising sulfatase inhibitors for the treatment of proteopathy.

The invention relates to the field of drug carrier design, in particular to a traditional Chinese medicine nano delivery system with a targeted A beta protein aggregation inhibition function as well as a preparation method and application of the traditional Chinese medicine nano delivery system. The traditional Chinese medicine nano-delivery system is a traditional Chinese medicine nano-carrier which is based on polypeptide A beta 16-21-r9 as shown in the amino acid sequence SEQ ID NO.1 and has the cell barrier penetrating and amyloid protein capturing capacity, and beta amyloid protein aggregation activity can be regulated in a targeted mode through the carrier. According to the traditional Chinese medicine nano delivery system prepared by the preparation method disclosed by the invention, the efficient delivery of a drug carrier can be realized, the blood brain barrier can be quickly penetrated, and the A beta protein can be accurately targeted.

The present invention relates to a buffered protein containing formulation comprising as stabilizing ingredient an amphiphilic surfactant. Said surfactant is formed by polyalkoxylating an a-tocopherol compound. The polyalkoxy residue is either a block copolymer or a statistical or random copolymer composed of a majority of ethylene oxide moieties and a smaller amount of propylene oxide and / or butylene oxide moieties. Said surfactant significantly improves stability, in particular aggregation stability of the protein formulation, while showing low hemolytic activity and good water solubility. Said surfactant is particularly suitable for preparing stabilized formulations of enzymes and immunoglobulin molecules as well as adducts and conjugates comprising such biomolecules. Said formulations may be provided in liquid or dry form and are suitable for the preparation of pharmaceutical compositions. According to another aspect of the invention the use of such formulations in medicine, in particular for diagnostic and / or therapeutic applications is provided. The present invention also relates to a method of preparing such formulations as well as a method for preparing such specific amphiphilic surfactants. According to a further aspect a method for preventing or suppressing protein aggregation of a liquid protein containing formulation in vitro by using an amphiphilic surfactant of the present invention as a stabilizer is provided. A prefilled syringe, comprising a reservoir prefilled with an amount of a formulation of the invention constitutes another aspect of the invention.

The invention belongs to the technical field of protein aggregation detection fluorescent probes, and particularly relates to a protein aggregation detection fluorescent probe containing quaternary ammonium salt and an aggregation-induced emission skeleton as well as a preparation method and application of the protein aggregation detection fluorescent probe. The probe takes a reaction product of 4-bromo-1, 8-naphthalic anhydride and 4-(diphenylamino) phenylboronic acid as the aggregation-induced emission skeleton, and the reaction product is reacted with N, N-dimethylformamide to obtain the protein aggregation detection fluorescent probe containing quaternary ammonium salt and the aggregation-induced emission skeleton. The quaternary ammonium salt group is introduced by sequentially reacting N, N-dimethyl ethylenediamine and diethyleneglycol-2-bromoethyl methyl ether, the quaternary ammonium salt group has the characteristics of water solubility and aggregation-induced emission, and the chemical structure of the quaternary ammonium salt group comprises a naphthalimide mother nucleus, a diphenylamino substituent group and a quaternized side chain.

This invention relates to the field of cardiovascular disease research technology, and particularly to the application of the NOD1 inhibitor ML130 in hypoxia-induced macrophage polarization, including the use of ML130 in the preparation of drugs that regulate hypoxia-induced macrophage polarization. These drugs inhibit the NOD1 / RIP2 signaling axis and can be used to intervene in the formation and progression of atherosclerotic plaques. This invention creatively combines the NOD1 inhibitor ML130 with the hypoxic microenvironment of atherosclerotic plaques, specifically inhibiting the NOD1 / RIP2 signaling pathway and directly regulating macrophage polarization balance; reducing the accumulation of pro-inflammatory cells in unstable plaque areas, inhibiting foam cell formation and necrotic core expansion, significantly improving plaque stability, and reducing the risk of serious cardiovascular events such as acute coronary syndrome; it clarifies that ML130 exerts its effect by blocking the NOD1 / RIP2-NF-κB / MAPK signaling axis, exhibiting high target specificity and avoiding the side effects of broad-spectrum inhibition by traditional anti-inflammatory drugs.