55 results about "Apolipoprotein e4" patented technology

Provided are an apolipoprotein E detection reagent and the use thereof. The reagent comprises at least one of an ApoE2 protein detection reagent, an ApoE3 protein detection reagent and an ApoE4 protein detection reagent. One of a capture antibody and a detection antibody used for detecting ApoE2 protein or ApoE4 protein is a specific monoclonal antibody, and the capture antibody and the detection antibody used for detecting ApoE3 are both specific monoclonal antibodies. Genotyping of ApoE and quantitative detection of different genotypes of proteins are performed on the basis of an immunological detection method. The detection method has the advantages of being simple, easy to operate, short in time and cheap. A genotype detection result is highly consistent with a fluorescence PCR result. Genotyping of ApoE (6 types) can be performed, which is used to replace the nucleic acid detection and guide medication, and clarify the correlation of the ApoE4 genotype homozygosity / heterozygosity and the protein concentration of ApoE4 with AD.

The present invention relates to a treatment of CCHFV infection, in particular CCFHV infection. Here, the inventors showed that antibody blocking LDL-R family at the surface of human cells could reduce CCHFV infection by 80%, such inhibition only occurred when blocking was performed prior to or at the time of infection though not at later time points. Furthermore, they found that incubation of viral particles with a soluble form of LDL-R could impair CCHFV infection. They found that ApoE antibodies could block CCHFV infectivity by up to 10-fold only when the viral particles were produced in cells that express ApoE. Thus, the present invention relates to an LDL-R family and / or an ApoE inhibitor for use in the prevention and / or the treatment of CCHFV infection in subjects in need thereof.

The invention relates to the technical field of in-vitro diagnostic kits, and provides an apolipoprotein E4 detection kit and application thereof. The immunochromatography test paper comprises detection immunochromatography test paper, the detection immunochromatography test paper comprises a bottom plate, a sample pad, a combination pad, an NC membrane and a water absorption pad, the combination pad and the sample pad are sequentially arranged on one side of the NC membrane, and the water absorption pad is arranged on the other side of the NC membrane; the combination pad is marked with gold manganese oxide nanometer developing particles and an apolipoprotein APOE4 monoclonal antibody. According to the technical scheme, the problems of complicated operation, high cost, low detection sensitivity and weak specificity of apolipoprotein E4 detection in related technologies are solved.

The invention provides application of ancient-Chinese health-preserving essence in preparation of a protein regulating agent, and belongs to the technical field of biological medicines. The invention provides application of an ancient-Chinese health-preserving essence or an ancient-Chinese health-preserving essence extract in preparation of a reagent for regulating protein functions. Protein comprises at least one of NCAM2, NCAM1, MAP2, VGLUT1, CDK5, DCLK1, TUBB3 and apolipoprotein E. The invention also provides an application of the ancient-Chinese health-preserving essence or the ancient-Chinese health-preserving essence extract in preparation of a reagent for regulating protein functions. In ancient and Chinese health preserving essence positive feedback regulation proteins, an important nerve synaptic function network exists and comprises proteins such as NCAM2, NCAM1, MAP2 and the like, and the proteins play an important role in biological processes such as neural development, synaptic shaping, neural signal transmission and the like. In addition, the ancient-Chinese health-preserving essence can regulate the expression of APOE. The application of the invention not only helps to deepen the scientific understanding of the pharmacodynamic effect of the ancient-Chinese health-preserving essence, but also provides a theoretical basis for the modern and precise application of traditional Chinese medicine compounds.

The invention discloses an antibody for resisting apolipoprotein E4 (ApoE4) and application of the antibody, and relates to the field of antibodies. The anti-apolipoprotein E4 antibody disclosed by the invention comprises a heavy chain complementarity determining region and a light chain complementarity determining region, provides an important raw material source for detection of apolipoprotein E4, and has good affinity or activity.

The invention relates to an apolipoprotein E detection reagent and application thereof, and belongs to the technical field of biomedicine. The invention provides application of a plant derivative in preparation of an APOE epitope exposure agent. The plant derivative is selected from at least one of curcumin, emodin, EF24 and FLLL-32. The invention also provides an APOE epitope exposure agent which comprises a surfactant, salts, a reducing agent and plant derivatives. According to the present invention, the sample and the protein are pre-treated by using the epitope exposure agent containing the plant derivative to improve the sufficiency of the ApoE protein epitope exposure so as to achieve the accurate typing of the ApoE gene based on the immunological detection method and the accurate quantification of the proteins with different genotypes. Genetic typing of ApoE and quantitative detection of proteins with different genotypes are carried out based on an immunological detection method, and the genotype detection result is highly consistent with a fluorescent PCR (Polymerase Chain Reaction) result.

The invention belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody combination for detecting apolipoprotein E4 and application of the monoclonal antibody combination. The combination comprises a monoclonal antibody 4E10 and a monoclonal antibody 3H7, and complementary determining region (CDR) sequences of the monoclonal antibody 4E10 and the monoclonal antibody 3H7 are shown as SEQ ID NO.1 to SEQ ID NO.12. In double-antibody sandwich ELISA, 4E10 is used as a coating antibody, 3H7 is used as a labeled antibody, APOE4 subtypes can be effectively recognized, high-specificity and high-sensitivity detection of APOE4 can be achieved, the detection limit reaches 100 pg / mL, and the kit is suitable for quantitative detection of APOE4 in samples such as serum and cerebrospinal fluid. The method provides a reliable immunological tool for early risk assessment of the Alzheimer's disease, and has important clinical application value.

The invention discloses liposome nanoparticles as well as a preparation method and application thereof, and relates to the field of biological medicines. The liposome nanoparticle comprises a lipid compound modified with a fusion protein, the fusion protein comprises apolipoprotein E or polypeptide thereof and an antibody, the modification of the fusion protein not only can actively target cells, tissues or organs of corresponding ligands, but also can effectively improve the transfection efficiency and the targeting delivery capability of the liposome nanoparticle to the cells, and the targeting delivery capability of the liposome nanoparticle to the cells can be effectively improved. The nucleic acid delivery system can be applied to preparation of anti-tumor drugs.

The present invention relates to an anti-apolipoprotein E4 (ApoE4) antibody and use thereof and, more specifically, to: an anti-ApoE4 antibody or an antigen-binding fragment thereof; a fusion in which the anti-ApoE4 antibody or an antigen-binding fragment thereof and one or more blood-brain barrier (BBB) receptor-binding peptides are bound; a method for preparing the fusion; and a composition for preventing or treating neurodegenerative diseases or metabolic diseases, comprising the anti-ApoE4 antibody or an antigen-binding fragment thereof, or the fusion.

The invention relates to an APOE typing and quantitative analysis method, and belongs to the technical field of molecular diagnosis. The invention provides a method for detecting the subtype and expression quantity of apolipoprotein E (APOE) in a simply treated plasma or tissue sample by using mass spectrometry. According to the method, a plurality of APOE protein subtype common polypeptides are used as quality control anchor points, each subtype characteristic polypeptide is calibrated, the detection stability and reliability of the characteristic polypeptides can be effectively analyzed, and the APOE subtypes can be accurately qualitative and quantitative at the same time. The method has the advantages of high efficiency, accuracy, stability and the like, and has a wide clinical application prospect.

The invention provides an apolipoprotein E determination kit and a preparation method thereof, the apolipoprotein E determination kit comprises a reagent 1, a reagent 2 and a calibrator / quality control product, the reagent 1 comprises the following components: a PIPES buffer solution, an ionic electrolyte, a polymer accelerator, a reaction accelerator, a surfactant, a stabilizer and a preservative; and the reagent 2 comprises the following components: an anti-ApoE antibody solution, a PIPES buffer solution, glycerol, an ionic electrolyte, a polymer accelerator, a reaction accelerator, a surfactant, a stabilizer and a preservative. The kit is optimized by adding EDTA2Na and mannitol, so that the opening test is more stable. And the preparation process of the reagent 2 and the PEG 6000 sample adding amount are adjusted. The kit is quick in reaction, high in accuracy and lower in blank absorbance.

A gene therapy vector comprising an expression cassette coding for a mammalian apolipoprotein E that has a residue other than arginine at at least one of positions 112, 136, or 158, but is not a mammalian apolipoprotein E that has R112, R136 and R158 or a mammalian apolipoprotein E that has C112, R136 and C158, or coding for an antibody that binds to APOE4 or disrupts the binding of APOE to heparan sulfate proteoglycans, and methods of using the vector, are provided.

The invention provides a lipid nanoparticle and application thereof, and particularly provides a cholesterol-free LNP delivery system based on sterol ionizable lipid. According to the system, a sterol group is integrated into an ionizable lipid skeleton as a hydrophobic tail through molecular design to form a novel sterol ionizable lipid, and the novel sterol ionizable lipid is self-assembled with an auxiliary lipid and a PEG-lipid to form a stable three-component LNP. The problem of high liver enrichment caused by the fact that traditional four-component LNP depends on cholesterol is solved, the affinity of core lipid and apolipoprotein E is remarkably reduced, and an ApoE / LDLR-mediated liver cell uptake way is effectively avoided. Under the condition that cholesterol is completely not needed, the LNP achieves high encapsulation efficiency and excellent stability on mRNA at the same time, liver enrichment is greatly reduced, the targeting performance on extrahepatic tissues such as the spleen is improved, high transfection efficiency and good biocompatibility are achieved, and an innovative platform is provided for delivery of extrahepatic disease RNA drugs.

The invention belongs to the technical field of biological medicine, and discloses a brain-targeted nano drug delivery system, a preparation method and application. According to the invention, dipentaerythritol-polycaprolactone-histidine (DPE-PCL-HIS) is used as a basic drug carrier, and drug curcumin (Cur) molecules are entrapped in a physical embedding manner; and modifying bovine serum albumin (BSA) grafted with a bifunctional intermediate connection compound 4-(N-maleimide methyl) cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt (Sulfo-SMCC) on a precoating layer, and finally connecting an apolipoprotein E mimic peptide as a brain-targeting ligand, so as to construct the brain-targeting bionic protein crown nano drug delivery system, wherein the bovine serum albumin (BSA) is grafted with the bifunctional intermediate connection compound 4-(N-maleimide methyl) cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt (Sulfo-SMCC). According to the prepared brain-targeted nano drug delivery system, apolipoprotein E mimic peptide [RLLRKRLK (PEG2000) RLGWC] is used as a ligand and enters the brain under the transendocytosis action of the apolipoprotein E mimic peptide [RLLRKRLK (PEG2000) RLGWC] and a blood-brain barrier (BBB) surface receptor, the blood-brain barrier permeability of a drug is increased, the brain targeting property and bioavailability of drug-loaded nanoparticles are improved, and the brain-targeted nano drug delivery system has wide application prospects in the aspect of treating brain diseases.

The utility model discloses an anti-pollution apolipoprotein E detection kit which comprises a kit body, a supporting cushion block is fixedly connected to the inner wall of a placement groove, a sealing cover is installed at the upper end of the placement groove in an inserted mode, a lifting handle is arranged at the upper end of a kit cover, and positioning buckle blocks are fixedly connected to the two sides of the lower end of the kit cover. Locking knobs are installed on the side faces of the positioning buckle blocks in an inserted mode, the positioning buckle blocks and the positioning buckle grooves are installed in an inserted mode, the positioning buckle grooves are formed in the upper ends of the two sides of the box body, and limiting pad grooves are formed in the lower end of the box cover. According to the anti-pollution apolipoprotein E detection kit, the placing groove can be independently sealed and covered through the sealing cover, the test tube is polluted when being taken comprehensively, the test tube can be bounced through the supporting block and the connecting spring when the sealing cover is opened, taking is convenient, the outer wall can be supported and protected through the protective pad, and when the anti-pollution apolipoprotein E detection kit is used, the test tube is not damaged. Refrigeration can be carried out through the refrigeration groove and the semiconductor refrigerator, cold conduction can be carried out through the heat exchange block, and efficient refrigeration treatment can be achieved.

The invention belongs to the technical field of disease detection and health examination, and particularly relates to an enzyme-linked immunosorbent assay method of apolipoprotein E and application of the apolipoprotein E in glaucoma diagnosis. A capture antibody used by the kit is 1D4, a heavy chain variable region of the capture antibody comprises HCDR1-3 as shown in SEQ ID NO: 4-6, and a light chain variable region of the capture antibody comprises LCDR1-3 as shown in SEQ ID NO: 1-3; a detection antibody used by the kit is 3A6, a heavy chain variable region of the detection antibody comprises HCDR1-3 as shown in SEQ ID NO: 12-14, and a light chain variable region of the detection antibody comprises LCDR1-3 as shown in SEQ ID NO: 9-11. The double-antibody sandwich ELISA detection kit for detecting ApoE4 provided by the invention has no cross reaction with other subtypes of ApoEs, the used monoclonal antibody has high sensitivity, the kit can be used for screening glaucoma in physical examination and ophthalmic examination of old people, and the screening result is counted and summarized to a health information system and a cloud platform for big data analysis, so that the health condition of a patient can be detected.

The present invention relates to: an apolipoprotein E (APOE) antisense oligonucleotide; and a pharmaceutical composition comprising the same for treating Alzheimer's disease. The antisense oligonucleotide of the present invention can reduce the expression of an APOE4 variant gene, the expression of which contributes to an increased risk and worsening of Alzheimer's disease, and can be used as an RNA therapeutic agent for a disease caused by an abnormal level of APOE protein or APOE variant gene expression.

This invention relates to a novel truncated mutant apolipoprotein E and its calibrators and quality control methods. The amino acid sequence of the truncated mutant apolipoprotein E is shown in SEQ ID. The diluent for the calibrators and quality control methods for detecting the truncated mutant apolipoprotein E includes a preservative, a protein protection composition, a surfactant composition, an ion stabilizer composition, and a buffer solution. The method for preparing the apolipoprotein E mutant includes the following steps: 1. Determining the specific sequence of the truncated mutant; 2. Determining that the mutation site is located at position 78 of wild-type apolipoprotein E; 3. Containing the NdeI site and the mutation sequence; locking the mutation; artificially optimizing the apolipoprotein E nucleotides using E. coli; 4. Extracting the corresponding truncated mutant by electrophoresis; 5. Obtaining the truncated mutant apolipoprotein E through recombination with E. coli. This invention solves the problems of discrepancies between detection results and actual clinical applications, as well as the poor stability of apolipoprotein E calibrators.

Disclosed are synthetic apolipoprotein E-mimicking peptides, derivatives thereof, and related peptides, which are useful as therapeutic agents for reducing plasma cholesterol; synthetic methods of making the peptides; pharmaceutical compositions comprising the peptides, and methods of treating lipid and metabolic disorders using the disclosed synthetic apolipoprotein E-mimicking peptides and compositions thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The present disclosure relates to double-stranded ribonucleic acid (dsRNAi) agents and compositions that target the APOE gene, and methods of using such dsRNAi agents and compositions to inhibit expression of the APOE gene and to treat subjects with APOE-associated neurodegenerative diseases or disorders, such as Alzheimer's disease and Parkinson's disease.

The present invention relates to: an apolipoprotein E (APOE) antisense oligonucleotide; and a pharmaceutical composition for treating Alzheimer's disease comprising same. The antisense oligonucleotide of the present invention can reduce the expression of the APOE4 variant gene that contributes to increased risk and exacerbation of Alzheimer's disease, and can be used as an RNA therapeutic agent for diseases caused by abnormal levels of APOE proteins or APOE variant genome expression.

ApoE mimetic peptides having a length of 8-17 amino acids are provided, comprising an ApoE receptor binding region or a portion thereof, and one or more covalent linkages linking at least two discontinuous amino acids of the peptide. Also provided are methods of treating a dyslipidemia disorder, such as hypertriglyceridemia or hypercholesterolemia, or a viral infection using the peptides.

A method for applying cold atmospheric plasma treatment to target tissue comprising the steps of treating a patient with a pharmaceutical for suppressing apolipoprotein E genes, selecting through a graphical user interface a particular soft tissue sarcoma cell line associated with target tissue, retrieving, with the computing device, settings data associated with the selected soft tissue sarcoma cell line from a database of cell line data and associated settings data in a storage, and applying, with the computing device, the retrieved settings data to a cold atmospheric plasma system.

The application belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody combination for detecting apolipoprotein E4 and application thereof. The combination comprises monoclonal antibody 4E10 and monoclonal antibody 3H7, and the complementarity determining region (CDR) sequences thereof are shown as SEQ ID NO. 1 to SEQ ID NO. 12. In a double antibody sandwich ELISA, 4E10 is used as a coating antibody, and 3H7 is used as a labeled antibody, so that APOE4 subtypes can be effectively recognized, high specificity and high sensitivity detection of APOE4 can be realized, the detection limit reaches 100 pg / mL, and the method is suitable for quantitative detection of APOE4 in serum, cerebrospinal fluid and the like. The method provides a reliable immunological tool for early risk assessment of Alzheimer's disease, and has important clinical application value.

This invention discloses an antibody for detecting apolipoprotein E4 and its application, specifically involving a detection antibody and kit for detecting ApoE4, a blood marker of Alzheimer's disease. Based on this antibody and kit, the presence of apolipoprotein E4 can be accurately detected.

The invention discloses aromatic acid salt of apolipoprotein E mimetic peptide as well as a preparation method and medical application of the aromatic acid salt. The aromatic acid salt, namely the compound ZYH-76, regulates and controls miR-29a-5p, inhibits an iNOS / HMGB1 / TLR4 / MMP-9 signal channel, reduces polarization of A1 type astrocytes, promotes polarization of A2 type astrocytes and protects the integrity of a blood-brain barrier, so that hemorrhagic transformation (HT) after acute ischemic stroke is inhibited. The compound ZYH-76 has a remarkable drug effect in various HT animal models, excellent pharmacokinetic properties and high safety, can be prepared into a freeze-dried preparation for injection, is suitable for HT risk prevention and treatment, and has a good clinical application prospect.

The present invention discloses an anti-snake venom drug and its application. The drug comprises apolipoprotein E, or can inhibit the hemorrhagic toxicity, myotoxicity, and coagulative toxicity of snake venom by increasing the concentration or expression of apolipoprotein E, and inhibit the activities of snake venom metalloproteinase (SVMP), snake venom phospholipase A2 (PLA2), and snake venom C-type lectin (CTL). The drug has the potential to be used in the medical field as a new broad-spectrum anti-snake venom drug, improving the problem that existing antivenom serum has high specificity and strong limitations.

ApoE mimetic peptides of 8-17 amino acids long including the ApoE receptor binding region or a portion thereof, and one or more covalent linkages joining at least two non-contiguous amino acids of the peptide are provided. Methods of treating dyslipidemic disorders, such as hypertriglyceridemia or hypercholesterolemia, or viral infection using the peptides are also provided.

The present invention relates to a C-terminal fragment (such as ApoE CT) of apolipoprotein E (ApoE) and modified ApoE2 and an application of the fragment in inhibiting γ-secretase activity. In one aspect, the present invention provides an isolated ApoE construct, which contains an ApoE polypeptide, the ApoE polypeptide: (1) contains a fragment from an amino acid sequence as shown by SEQ ID NO: 12, a first amino acid residue at a N-terminal of the fragment being an amino acid residue at any position between positions 215-221 of SEQ ID NO: 12, and a last amino acid residue at a C-terminal of the fragment being an amino acid residue at any position between positions 274-299 of SEQ ID NO: 12; or (2) the amino acid sequence has at least about 70% sequence identity with the fragment of (1), and retains at least about 50% of inhibition of the fragment of (1) against γ-secretase enzymatic digestion activity. The present invention further provides an encoding sequence, nucleic acid construct, host cell, construction method, pharmaceutical composition, and application of a protein portion of the ApoE construct.

The present invention relates to the field of neurodegenerative diseases, in particular Alzheimer's disease. The present invention further relates to fibrillary Apolipoprotein E (ApoE) for use in a method of treatment and / or prevention of a neurodegenerative disease and methods of producing said fibrillary ApoE. Moreover, the present invention relates to an antigen-binding peptide specifically binding to fibrillary ApoE, preferably human ApoE, a method of generating said antigen-binding peptide, and its use in a method of treatment and / or prevention and / or diagnosis of a neurodegenerative disease in a patient in need thereof.