395 results about "Amyloid" patented technology

The invention belongs to the technical field of modern agriculture, and particularly relates to a biocontrol bacillus amyloliquefaciens BA200 and application thereof. A new biological control bacterium BA200 is separated and identified, is named as bacillus amyloliquefaciens by taxonomy, and has a remarkable inhibition capability on two pathogenic bacteria, namely fusarium oxysporum and phytophthora vigna, causing the cowpea fusarium wilt, and the inhibition rate is up to 60% or above; fermentation liquor prepared from the bacillus amyloliquefaciens BA200 can remarkably reduce the morbidity and disease index of cowpea fusarium wilt, is a good biocontrol microorganism and has application and development potential and important significance in control of cowpea fusarium wilt, and the biocontrol bacterium bacillus amyloliquefaciens BA200 has a broad-spectrum biological control effect, can inhibit various phytopathogens and has a good application prospect. And valuable biocontrol bacterium resources are provided for preparation of biological bactericides.

The invention provides an ER targeting self-assembly AIE probe with cascade ROS / RNS generation performance, and belongs to the technical field of material chemistry, the probe is composed of four units: 1) an AIE photosensitizer OTBS used for generating ROS; 2) deriving peptide FFVLK from beta amyloid protein, and promoting the self-assembly of the peptide to form a nanofiber with a beta-sheet structure; (3) an oligomerization arginine unit RRRR which is used as an NO donor; and 4) ER targeting signal peptide KDEL to endow ER with targeting ability. Based on ER targeting and a self-assembly process, the self-assembly AIE probe is subjected to ER in-situ self-assembly in cells to form nanofibers, ROS / RNS is generated in a cascading manner under illumination, and strong ICD is induced. In addition, the tumor residence time of the photosensitizer is prolonged due to the formation of the nanofibers, and the treatment effect is further improved. The invention provides a new thought for the design of a novel light-operated II-type ICD inducer.

Herein are provided bispecific anti-human A-beta / human transferrin receptor antibodies and methods of using the same.

Compositions and methods are provided for the treatment or prophylaxis of amyloid pathologies such as Alzheimer's Disease.

The present invention relates to a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, comprising selexipag or a pharmaceutically acceptable salt thereof as an active ingredient. Selexipag inhibits the expression and production of pro-inflammatory or inflammatory cytokines in brain tissue, inhibits the activity of microglia or astrocytes, inhibits NLRP3 inflammasome activity and CDK6 expression, reduces amyloid plaques, increases the expression of the amyloid beta-degrading enzyme IDE, and inhibits the hyperphosphorylation of tau protein and the expression of tau kinase, and thus can be effectively used as a novel therapeutic agent for the prevention or treatment of degenerative brain diseases, cognitive disorders, learning disabilities, or memory disorders.

Provided is a new and highly toxic amyloid oligomer Aβo*3F. The Aβo*3F is specifically bound by a 3F antibody, is the most important toxic ingredient in a mixture of Aβ oligomers, and has a strong pathogenic effect. Further provided is a binding agent that specifically binds to Aβo*3F, a composition containing Aβo*3F, and a use of Aβo*3F as a target in the prevention and / or treatment and / or diagnosis of MCI and / or AD in subjects.

The invention belongs to the technical field of biological medicine, particularly relates to an Alzheimer's disease protein marker, an antibody diagnostic kit and application of the antibody diagnostic kit, and provides the Alzheimer's disease protein marker A beta (1-42). The invention provides a kit for detecting human amyloid A beta based on sandwich ELISA (enzyme-linked immunosorbent assay) of 2B6 and 3A8 antibodies, and further provides a kit for detecting human amyloid A beta based on 2B6 and 3A8 antibodies by predicting B cell epitopes of a template A beta (1-42) protein through ABCpred to reconstruct an immune antigen enhanced Alzheimer disease combined antigen such as SEQ ID NO: 1, called AD-A beta 2 for short, and monoclonal antibodies 2B6 and 3A8 with strong affinity and high titer based on the antigen. The A beta concentration detection line effect of at least 0.5 ng / mL is realized.

The invention belongs to the technical field of analytical chemistry and the field of early screening of Alzheimer's disease, and particularly relates to an array sensor based on zirconium-based MOF nano-enzyme and application of the array sensor to detection of amyloid protein. The zirconium-based MOF nano-enzyme for detecting amyloid protein comprises UiO-66 (at) Pt, UiO-66 (at) Pd and UiO-66 (at) PtPd, and the array sensor based on the zirconium-based MOF nano-enzyme is constructed by sensing units which are respectively added with the UiO-66 (at) Pt, the UiO-66 (at) Pd and the UiO-66 (at) PtPd. According to the amyloid protein detection method based on the zirconium-based MOF nano-enzyme, rapid and sensitive detection of amyloid protein can be realized, the cost is low, the repeatability is good, and a new idea is provided for detection of amyloid protein related diseases.

The invention provides a multispecific antibody or an antigen-binding fragment thereof. The multispecific antibody or the antigen-binding fragment thereof comprises at least one first antigen-binding region capable of specifically binding to pyroglutamate amyloid-beta and a second antigen-binding region capable of specifically binding to transferrin receptor (TfR). Methods of treating or detecting nervous system disorders and / or delivering therapeutic or diagnostic agents across the blood-brain barrier are also provided. Nucleic acids encoding the antibodies, vectors comprising the nucleic acids, recombinant host cells comprising the nucleic acids and / or vectors, and methods of producing the multispecific antibodies or antigen-binding fragments thereof are also described.

The present application identifies a dose of an active ingredient in therapy provided or considered to be provided to a subject. The level of localized amyloid beta is predicted based on the dose of the active ingredient. The severity of amyloid related imaging anomalies (ARIA) (ARIA-E) exhibiting high signal strength on T2 weighted liquid decay inversion recovery (FLAIR) images is predicted based on the predicted removal of local beta amyloid, wherein predicting the severity of ARIA-E includes predicting the degree of vascular wall disorder. And outputting a result corresponding to the predicted ARIA-E severity degree.

The invention discloses an Alzheimer's disease plasma diagnosis marker based on plasma pTau217 and application of the Alzheimer's disease plasma diagnosis marker. The plasma biomarker provided by the invention is pTau217, pTau217 / A beta 1-40 or pTau217 / A beta 1-42, and the detection of the plasma biomarker not only belongs to a reliable, simple and convenient non-invasive means, but also can efficiently evaluate the disease risk of the Alzheimer's disease. The method can replace the traditional Alzheimer disease detection method, such as cerebrospinal fluid amyloid protein detection and PET imaging, and is easy to clinically and widely apply. The method has an important application value.

A method of pre-screening a human subject for a clinical trial for treatment of tauopathy or an amyloidogenic disease. The method comprises obtaining a plasma sample from the subject and determining a concentration of p217+tau present in the plasma sample. The method further comprises indicating the subject for further screening for the clinical trial when the concentration of p217+tau present in the plasma sample is greater than or equal to a minimum threshold and less than or equal to a maximum threshold. The minimum threshold corresponds to an amount of p217+tau in plasma over which subjects present with mild cognitive impairment (MCI) and an increased accumulation of tau tangles in the brain as compared to a cognitively normal patient. The maximum threshold corresponds to an amount of p217+tau present in plasma over which subjects present with pathology of widespread accumulation of tau tangles in multiple regions of the brain.

A multispecific antibody or antigen binding fragment thereof is provided, the multispecific antibody or antigen-binding fragment thereof comprises at least one first antigen-binding region capable of specifically binding to pyroglutamate amyloid-beta, a second antigen-binding region capable of specifically binding to transferrin receptor (TfR), and a third antigen-binding region capable of specifically binding to paired spiral filaments (PHF)-tau. Methods of treating or detecting nervous system disorders and / or delivering therapeutic or diagnostic agents across the blood-brain barrier are also provided. Nucleic acids encoding the antibodies, vectors comprising the nucleic acids, recombinant host cells comprising the nucleic acids and / or vectors, and methods of producing the multispecific antibodies or antigen-binding fragments thereof are also described.

The invention discloses an application of ARN2966 in the treatment of UMOD (Urban Molecular Orthodontic Disease) gene mutant autosomal dominant hereditary renal tubular interstitial nephropathy (ADTKD), and belongs to the field of biomedicine. The ARN2966 has the advantages that the ARN2966 can be used for the treatment of UMOD gene mutant autosomal dominant hereditary ADTKD, and the ARN2966 can be used for the treatment of UMOD gene mutant autosomal dominant hereditary ADTKD; the application comprises the application of the amyloid precursor protein (APP)-CD74 signal axis blocking agent in the preparation of the medicine for treating the hereditary tubulointerstitial nephropathy, and the application comprises the application of the amyloid precursor protein (APP)-CD74 signal axis blocking agent in the preparation of the medicine for treating the hereditary tubulointerstitial nephropathy. Compared with the prior art, the key effect of an APP-CD74 signal axis in ADTKD-Umod pathogenesis is disclosed for the first time, and ARN2966 provides a brand new intervention strategy for treatment of ADTKD-Umod through targeted regulation and control of the pathway. Compared with a broad-spectrum anti-inflammatory drug, the ARN2966 has high targeting specificity, and side effects caused by non-specific immunosuppression can be avoided. Although the ARN2966 does not enter a clinical research stage at present, due to the unique action mechanism and verified safety characteristics of the ARN2966, the ARN2966 has remarkable transformation medical value and clinical application prospect in the aspect of developing ADTKD-Umod targeted therapeutic drugs.

One aspect relates to a method for providing information for predicting a risk group for developing Alzheimer's disease dementia or a risk group for early onset of Alzheimer's symptoms, or a risk group for developing amnestic mild cognitive impairment and / or a positron emission tomography (PET)-positive risk group for amyloid β deposition, based on a European population-East Asian data. According to one aspect, the method makes it possible to accurately predict a risk group for developing Alzheimer's disease dementia or a risk group for early onset of Alzheimer's symptoms, or a risk group for developing amnestic mild cognitive impairment and / or a positron emission tomography (PET)-positive risk group for amyloid β deposition by using only at least 12 single-nucleotide polymorphisms, and the ability to predict the risk groups is further enhanced when up to and at most 80 additional single-nucleotide polymorphisms are used. In addition, the method further includes identifying age, sex, years of education, and APOE genotype as indicators, and thus the ability to predict the risk groups is further enhanced, and the risk groups can be predicted at an early stage with high accuracy.

The present invention relates to methods of measuring the presence and / or levels of a combination of five biomarkers in a sample, said biomarkers being neurofilament light (NfL) polypeptide, glial fibrillary acidic protein (GFAP), β-Amyloid 1-42 (Aβ1-42), β-Amyloid 1-40 (Aβ1-40), and phosphorylated Tau (p-Tau181, pTau-231 and / or p-Tau217). The methods can be used to predict the subject's risk or likelihood of having and / or developing Alzheimer's disease, thus also provided is a method of predicting a subject's risk or likelihood of having and / or developing Alzheimer's disease, said method comprising measuring the presence of and / or the levels of the combination of five biomarkers. Further provided is a method of prognosing or diagnosing Alzheimer's disease in a subject comprising the methods of measuring the presence of and / or the levels of the combination of five biomarkers, and a method of treating Alzheimer's disease comprising predicting a subject's risk or likelihood of developing or having Alzheimer's disease using the methods of measuring the presence and / or levels of the combination of five biomarkers and administering a treatment if the risk or likelihood exceeds a threshold value.

Aspects of the disclosure relate to compositions and methods for modulating levels, transcription, splicing, and / or translation of one or more RNA transcripts (e.g., mRNA transcripts) in a cell or subject. The disclosure is based, in part, on isolated nucleic acids that bind to mRNA transcripts of genes involved in neurodegenerative diseases and disorders, for example an apolipoprotein E gene (APOE), which encodes a protein involved in lipid homeostasis and amyloid plaque formation in the CNS. In some embodiments, compositions of the disclosure are useful for treating neurodegenerative diseases or disorders, such as Alzheimer's disease (AD) or dementia with Lewy Bodies.

The invention relates to the technical field of electrochemical analysis and detection, in particular to an electrochemical biosensor based on CRISPR / Cas12a as well as a preparation method, a detection method and application of the electrochemical biosensor. An electrochemical biosensor based on CRISPR / Cas12a comprises a Cas12a-crRNA detection system, an APT-ActDNA adaptation system and an electrochemical aptamer sensor, and when a target analyte exists, the Cas12a-crRNA detection system and the APT-ActDNA adaptation system are matched with each other to react with the target analyte, so that the electrochemical aptamer sensor generates an electrochemical signal. According to the technical scheme, the problems of specific recognition and detection of amyloid beta peptide (Abeta) in a complex biological sample are solved, the preparation method is simple, the cost is low, and the detection method is high in sensitivity and accuracy.

The invention relates to a polypeptide analogue or a derivative thereof as well as a preparation method and application thereof, in particular to an agonistic polypeptide analogue of an insulin amyloid polypeptide receptor or a derivative thereof. The polypeptide analogue or the derivative thereof provided by the invention has good agonism on an insulin amyloid polypeptide receptor, has the characteristics of good stability, high activity and the like, and can be used for treating and preventing diseases related to the insulin amyloid polypeptide receptor, such as abnormal weight, especially obesity and overweight.

A multispecific antibody or antigen binding fragment thereof is provided, the multispecific antibody or antigen-binding fragment thereof comprises at least one first antigen-binding region capable of specifically binding to pyroglutamate amyloid-beta, a second antigen-binding region capable of specifically binding to transferrin receptor (TfR), and a third antigen-binding region capable of specifically binding to paired spiral filaments (PHF)-tau. Methods of treating or detecting nervous system disorders and / or delivering therapeutic or diagnostic agents across the blood-brain barrier are also provided. Nucleic acids encoding the antibodies, vectors comprising the nucleic acids, recombinant host cells comprising the nucleic acids and / or vectors, and methods of producing the multispecific antibodies or antigen-binding fragments thereof are also described.

The present invention provides a combination of superior bacteria for liquefying and degrading food waste and its application. The combination includes Pseudomonas aglycones, Bacillus alcaligenes faecalis, Bacillus amyloliquefaciens, Serratia marcescens, Sphingobacillus suis, Bacillus subtilis, Achromobacter xylosoxidans, Bacillus cereus, Sphingobacillus fusoni, Oligotrophomonas maltophilia, and Sphingobacillus humus. The combination of bacteria can effectively reduce the amount of food waste, and the maximum reduction can be 14.66%, and the COD removal rate can reach 98.19%. The combination of bacteria of the present invention can efficiently degrade and liquefy food waste, and can achieve a high reduction rate and liquefaction effect, which is conducive to the absorption and utilization of nutrients in the subsequent food waste biological resource conversion process.

The invention provides a pharmaceutical composition for treating Alzheimer's disease. The pharmaceutical composition is prepared from the following raw materials in parts by weight: 10-15 parts of ginseng, 10-15 parts of rhizoma acori graminei, 10-15 parts of polygala tenuifolia, 15-20 parts of rhizoma polygonati, 15-20 parts of ginkgo leaves and 5-10 parts of schisandra chinensis. Therefore, the ginseng and the ginkgo leaves jointly regulate a cholinergic system and cerebral blood flow, and the cognitive function is enhanced; the rhizoma acori graminei and the ginkgo leaves cooperate to inhibit aggregation of beta-amyloid protein, improve cerebral circulation and relieve neurotoxicity. Polygonatum sibiricum and Chinese magnoliavine fruit protect nerve cells through anti-oxidation and anti-inflammatory effects and reduce nerve injury. Schizandrin further stabilizes a neurotransmitter system and enhances the synergistic effect of other medicinal materials, a multi-layer treatment network of Abeta deposition inhibition, cholinergic system regulation, anti-inflammation and anti-oxidation and nerve protection is integrally formed, and the core pathological link of the Alzheimer's disease is comprehensively intervened, so that the cognitive function is improved, and the disease progress is delayed.

The invention discloses betulinic acid derivatives containing amide and secondary amine structures and a preparation method and application of the betulinic acid derivatives, and belongs to the technical field of medicines.The betulinic acid derivatives are obtained by conducting structural modification on betulinic acid, and it is proved through an in-vitro thioflavin (Th) T fluorescence experiment that the betulinic acid derivatives have a good application prospect. The compounds can effectively inhibit aggregation of beta-amyloid protein (A beta) 42, can be used as candidate drugs for treating Alzheimer's disease, and have good application prospects in clinic.

The present invention relates to a composition for preventing, alleviating or treating cognitive disorders or Alzheimer's disease, comprising a Lactobacillus delbrueckii subsp. Lactis strain as an active ingredient. The present invention provides a composition for preventing, alleviating or treating cognitive disorders or Alzheimer's disease (AD), comprising a Lactobacillus delbrueckii subsp. Lactis strain as an active ingredient. The strain of the present invention has excellent effects of reducing amyloid beta protein (A beta) or tau protein (Tau) and improving cognitive function, and thus can be usefully used as a composition for preventing, alleviating or treating cognitive impairment or AD.

A use of a new highly toxic amyloid oligomer Apo*3F as a target for diagnosing Alzheimer's disease (AD) in the early stage and the middle-late stage and mild cognitive impairment (MCI) caused by AD. The Aβo*3F specifically binds to an antibody 3F and is present in cerebrospinal fluid (CSF), blood and / or brain tissue of AD patients and patients with MCI caused by AD, and the levels show highly significant differences in CSF, blood and / or brain tissue of AD patients, MCI patients and healthy elderly persons. In addition, the Apo*3F is an ultra-highly toxic oligomer, is the most important toxic component in an Aβ oligomer mixture, has a strong pathogenic effect, and plays a key role in the occurrence and development of AD.

Herein are provided bispecific anti-human A-beta / human transferrin receptor antibodies and methods of using the same.

Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders. Such biomarker panel might have considerable value in triaging patients with early memory disorders to yet more specific but more invasive and costly approaches such as molecular markers in CSF and on PET imaging in clinical trials and possibly in clinical practice.

The invention discloses a microcapsule structure agricultural chemical based on protein amyloid aggregate. The microcapsule structure agricultural chemical comprises an agricultural chemical, protein, a denaturing agent, plant essential oil, an emulsifier, a pH regulator and water. According to the invention, the denaturing agent is used for inducing protein to form amphiphilic protein amyloid aggregate, and the emulsifier is used for promoting the dissolution of the plant essential oil in water, so that the agricultural chemicals can be dissolved in the plant essential oil; the protein amyloid aggregate is aggregated and assembled on the surface of the plant essential oil through various non-covalent acting forces to form a stable agricultural chemical with a microcapsule structure, and the spreading, permeation and conduction of the agricultural chemical on plant leaves can be enhanced by spraying the agricultural chemical on the plant leaves; meanwhile, the protein amyloid aggregate gathers on the surface of the plant essential oil to form a film, so that the agricultural chemicals are stably adhered to the surface of the plant, the plant is resistant to rain wash, the utilization rate of the agricultural chemicals is increased, the environmental pollution is reduced, and the plant essential oil has a wide application prospect in agricultural production.

The application discloses a kind of cognitive promotion method and system based on multi-modal data.The cognitive promotion method includes: obtaining the first multi-modal data before treatment of patient;Amyloid load grouping is carried out to patient based on the amyloid load in the brain of patient, to obtain the initial cognitive training scheme corresponding;Cognitive training is carried out based on initial cognitive training scheme during the treatment of patient, and the second multi-modal data during treatment is collected;Based on multi-modal data before and after treatment of patient, in combination with brain network group atlas, obtain the multi-modal change data of patient;The multi-modal change data of patient is input into preset model, to output the cognitive promotion scheme that cognitive index of patient is most improved, to push to patient and carry out cognitive training.The method will be integrated by A beta-PET data, functional nuclear magnetic resonance imaging data and event-related potential data, real-time evaluation of the neuroplasticity change of patient, to dynamically generate personalized cognitive promotion scheme.

This invention discloses a method and system for following up on magnetic resonance imaging (MRI) images of amyloid-related radiological abnormalities, belonging to the field of medical image processing. The method includes: acquiring multimodal MRI image data; performing bias field correction and intensity normalization based on a bias field fitting model to generate a first image set; performing global alignment and edge detection on the first image set to extract anatomical physical boundaries, generating brain region mask data; performing branch deformation field registration on the first image set within the brain parenchyma defined by the brain region mask data to generate a spatially aligned second image set; calculating the average intensity of normal brain parenchyma regions in the second image set to obtain a scaling factor, acquiring a three-dimensional residual image; performing anisotropic diffusion filtering denoising on the three-dimensional residual image, and performing differential denoising and morphological screening processing, outputting the detection results. This invention eliminates systematic artifacts caused by insufficient bias field correction.