24 results about "Cell Aggregations" patented technology

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 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.

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.

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.

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.

The present invention is in the field of medicine and provides compositions for the treatment and / or prevention of protein aggregation diseases.

The application belongs to the field of biological medicine, and particularly relates to a homogeneous chemiluminescence kit for detecting platelet-monocyte aggregates and a detection method thereof. The kit comprises: R1 reagent: CD41 antibody-DNA1 conjugate; R2 reagent: CD14 antibody-DNA2 conjugate; R3 reagent: DNA3 labeled with acridinium ester; and R4 reagent: antioxidant combined with graphene oxide. The application realizes direct whole blood detection of platelet-monocyte aggregates in 5-10 minutes through homogeneous chemiluminescence+orthogonal DNA hybridization+special sample stabilizer, greatly simplifies the process, reduces the cost, and enables the sample to be stable at room temperature for 6 hours. The detection result is highly correlated with flow cytometry, and has good diagnostic efficiency for sepsis.

The application belongs to the field of biological medicine, and particularly relates to a homogeneous chemiluminescence kit for detecting platelet-monocyte aggregates and a detection method thereof. The kit comprises: R1 reagent: CD41 antibody-DNA1 conjugate; R2 reagent: CD14 antibody-DNA2 conjugate; R3 reagent: DNA3 labeled with acridinium ester; and R4 reagent: antioxidant combined with graphene oxide. The application realizes direct whole blood detection of platelet-monocyte aggregates in 5-10 minutes through homogeneous chemiluminescence+orthogonal DNA hybridization+special sample stabilizer, greatly simplifies the process, reduces the cost, and enables the sample to be stable at room temperature for 6 hours. The detection result is highly correlated with flow cytometry, and has good diagnostic efficiency for sepsis.

The application discloses an antisense oligonucleotide for inducing skipping of the 11th exon of a NOTCH3 gene, a pharmaceutical composition thereof and application thereof. The application provides six candidate sequences of ASO12, ASO15, ASO16, ASO17, ASO19 and ASO20 for efficiently inducing exon skipping, wherein the half effective concentration (EC50) of ASO17 is as low as 36.53 nM. The application also provides a pharmaceutical composition containing the antisense oligonucleotide and application thereof in preparation of a medicine for treating CADASIL, and is especially suitable for a Chinese CADASIL patient population carrying a mutation of the 11th exon of a NOTCH3 gene. It is verified through experiments that the truncated NOTCH3 protein produced by skipping the 11th exon retains normal expression level, subcellular localization and signal transduction function, and meanwhile, pathogenic protein aggregation is reduced. The application fills the blank of specific treatment of CADASIL for Chinese population, and has clear clinical conversion value.

The present application relates to a kind of protein aggregation state detection method and its detection device.The protein aggregation state detection method described in the present application includes: the solution to be detected is mixed with optical microcavity, obtains the second original WGM spectrum data after the solution to be detected and optical microcavity effect;The optical bar code of the second original WGM spectrum data is obtained;The optical bar code is input into detection classification model, and the protein aggregate class is obtained;Wherein, the detection classification model includes deep learning classification model.The detection method of the present application can automatically, efficiently extract deep features from complex optical bar code, and can learn the nonlinear discrimination boundary between different protein aggregation states, overcome the limitations of traditional methods relying on artificial feature extraction and simple linear judgment, greatly improve the accuracy and robustness of protein aggregation state classification.

Abstract The present invention provides novel methods of identifying, monitoring or determining the risk of developing a protein misfolding neurodegenerative disorder in a subject, particularly an alpha synucleinopathy (including Parkinson’s disease and dementia with Lewy bodies) using extracellular vesicle samples. Corresponding methods for selecting a treatment and assaying for the presence of a pathological prion-like protein (or one or more ceramide species) in an extracellular vesicle sample are also provided. Abstract The present invention provides novel methods of identifying, monitoring or determining the risk of developing a protein misfolding neurodegenerative disorder in a subject, particularly an alpha synucleinopathy (including Parkinson's disease and dementia with Lewy bodies) using extracellular vesicle samples. Corresponding methods for selecting a treatment and assaying for the presence of a pathological prion-like protein (or one or more ceramide species) in an extracellular vesicle sample are also provided. 20 24 27 84 87 17 D ec 2 02 4 A b s t r a c t 2 0 2 4 2 7 8 4 8 7 1 7 D e c 2 0 2 4

A novel class of fusion proteins is disclosed to recruit cellular innate chaperones, particularly the Hsp70-mediated system, to specifically reduce TDP-43-mediated protein aggregation and associated protein conformation disorders.

A serum-free endothelial cell differentiation culture medium including (a) a basal culture medium and (b) an endothelial cell differentiation combination of EGF, FGF and VEGF protein. In the culture medium, the amount of EGF is higher than the amount of FGF protein. A process for the preparation of cellular aggregate suspensions comprising differentiated endothelial cells from dental stem cells using the serum-free medium. The use of the resulting suspension in therapy.

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

This invention discloses a 3-hydroxypyridinone derivative, its preparation method, and its applications. This 3-hydroxypyridinone derivative, through structural modification of the 3-hydroxypyridinone core, significantly enhances its anti-ferroptosis activity against hippocampal neurons in HT-22 mice. In vitro experiments show that its inhibitory effect on ferroptosis is more than twice that of the positive control deferoxone. Furthermore, the 3-hydroxypyridinone derivative can also chelate Fe... 3+ To alleviate iron-mediated Aβ 1‑42 Protein aggregation and its cytotoxicity. This invention also provides synthetic routes, purification methods, and in vitro activity evaluation systems for 3-hydroxypyridinone derivatives, offering structural optimization strategies and candidate compounds for the development of drugs targeting iron metabolism disorders.

The application discloses a high-loading temperature-sensitive ion chromatography medium and a preparation method and application thereof. The chromatography medium is grafted with copolymer chains on the surface of a matrix. The copolymer chains are formed by double bond addition polymerization of monomer A and monomer B into random copolymers, wherein the molar ratio of monomer A to monomer B is (1-99):(99-1). The chromatography medium obtained by the application can realize ultra-high loading and fast elution under mild conditions through a reversible adjustment mechanism, thereby solving the technical contradiction between high loading and protein aggregation.

The application discloses an injectable hydrogel of islet-like spheroids based on double sequential encapsulation and a preparation and application thereof, and belongs to the technical field of bioengineering medical materials. The preparation method utilizes the positive and negative charges of a polymer material, forms an immune protection film of islet beta cells through electrostatic adsorption layer-by-layer self-assembly, and utilizes the extracellular matrix of a spleen, i.e., the characteristics of a liquid state in vitro and self-assembly into a nanofiber gel structure at a physiological temperature in vivo, to prepare the injectable hydrogel of islet-like spheroids, so as to ensure the stability of the hydrogel structure, self-assembly into a nanofiber three-dimensional gel structure in vivo, provide a natural specific microenvironment for cell self-renewal and differentiation, promote the aggregation of beta cells into islet-like spheroids, and enhance the insulin secretion and vascularization capacity. The immune protection film is formed on the surface of the islet beta cells through layer-by-layer self-assembly of gelatin and alginate, so that the beta cell immune protection encapsulation is realized.

Disclosed is a novel class of fusion proteins to recruit the innate chaperone machinery of cells, in particular the Hsp70-mediated system, to specifically reduce alpha-synuclein-mediated protein aggregation and associated protein conformational diseases.

Described herein, inter alia, are compounds and methods for treating protein aggregation diseases.

Compounds comprising a triazole scaffold, compositions comprising same, and the use of such compounds and compositions to inhibit tubulin-associated unit (tau) protein and alpha-synuclein (α-syn) protein aggregation, including neurofibrillary tangles (NFTs) and Lewy bodies.

The application belongs to the technical field of small-molecule fluorescent materials, and particularly relates to an imine small molecule and application of the imine small molecule as a fluorescent probe in detection of heavy metal ions and A beta peptide. 2+ In order to mine a multifunctional fluorescent material with a simple synthesis method, high sensitivity and a low detection limit, the application provides an imine small-molecule compound. 2+ The small molecule has high sensitivity and selectivity to Zn 2+ , Cu 2+ and Fe 2+ , wherein the small molecule shows a fluorescence 'off' effect to Cu 2+ and Fe 2+ , and shows a fluorescence 'on' effect to Zn 2+ . In addition, the small molecule can selectively combine with A beta peptide to produce a fluorescence 'on' effect, and the fluorescence is continuously enhanced with protein aggregation, so that different aggregation states of amyloid A beta can be distinguished. Therefore, the small molecule as the fluorescent probe can be used for simultaneously detecting Zn 2+ , Cu 2+ 0> , Fe 2+ 1> and amyloid beta aggregates, and has a wide application prospect.

This invention discloses a method for regulating β-amyloid protein aggregation based on circularly polarized light and its application. The method includes electrostatically binding an amino-modified upconversion luminescent nanoparticle to a SiO2-coated chiral optically active nanostructure to obtain an upconversion chiral nanomaterial; coating the surface of the upconversion chiral nanomaterial with a biocompatible coating and a brain-targeting ligand, then mixing it with β-amyloid protein, and targeting the region with 5–100 mW / cm² light. 2 Irradiation with an 800–1400 nm laser for 15–30 min excites upconversion chiral nanomaterials to emit circularly polarized light. This circularly polarized light inhibits the aggregation of β-amyloid protein by interfering with the formation of its β-sheet conformation. This invention utilizes circularly polarized light (CPL) to induce changes in key protein site interactions, thereby altering the conformation of protein aggregation. This process is reversible and highly spatially selective. Animal experiments have verified that this method can effectively block Aβ aggregation and improve cognitive function.

The application relates to the field of artificial intelligence, and specifically discloses an intelligent decision-making method and system for a brine point slurry process, aiming to solve the problem of low precision and poor adaptability caused by the dependence of traditional point slurry on manual experience. The method comprises the following steps: constructing a multi-modal sensing system to collect the conductivity, pH value, turbidity and rheological parameters of soybean milk in real time; generating dynamic high-dimensional features of protein aggregation based on time series data; constructing a transferable process knowledge graph using historical successful cases; fusing the features and graph embedding vectors, and outputting the brine addition rate and stirring speed in real time through deep reinforcement learning; and introducing a gel strength prediction residual before the end of the point slurry to perform closed-loop feedback correction. Through the above technical solution, high-precision end-point control, strong adaptive process transfer, efficient resource utilization and safe and reliable deployment are achieved, and the soybean curd yield, texture consistency and production intelligence level are significantly improved.