65 results about "GDF15" patented technology

The invention provides application of a reagent for detecting GDF15 protein in preparation of a product for evaluating the myocardial infarction risk of a subject in the future, and belongs to the technical field of biomedical detection. By detecting the concentration level of the GDF15 protein in peripheral blood, the risk of myocardial infarction of a subject in the future can be accurately predicted in the early stage, so that early risk guidance is provided for crowds needing intervention, and the application is non-invasive, simple, convenient and low in cost. In order to achieve the maximum economic benefit, only the GDF15 level in the peripheral trace blood of the subject needs to be detected, the clinical index level needed in a traditional model is not needed, the prediction level of a traditional method is exceeded, and meanwhile the economic cost is greatly reduced.

The invention relates to a human recombinant GDF15 protein and application thereof in preparation of drugs for preventing and treating sepsis acute kidney injury, and belongs to the technical field of biological medicines. In order to solve the problem that an effective prevention and treatment scheme for improving SA-AKI by inhibiting oxygen death is lacked in existing clinical and research, the invention provides a human recombinant GDF15 protein of which the coding gene nucleotide sequence is shown as SEQ ID No: 1. Animal experiment results show that by intraperitoneal injection of the human recombinant GDF15 protein, kidney inflammation of sepsis mice can be relieved, and expression of PGAM5 can be down-regulated. Cell experiment results show that when the human recombinant GDF15 protein is given, LPS-induced USF2 increase can be inhibited. The human recombinant GDF15 protein provided by the invention can improve SA-AKI by inhibiting oxygen death and inflammation, provides a new idea and an intervention target for prevention and treatment of SA-AKI, and shows a good clinical application prospect.

The invention provides application of GDF15 in preparation of a medicine for treating or preventing hematopoietic dysfunction caused by DON poisoning. The research finds that the GDF15 has the effects of treating or preventing bone marrow total cell reduction, hematopoietic stem progenitor cell damage, erythroid progenitor cell damage, erythroid end developmental stage damage, reticulocyte number reduction and peripheral blood mature erythrocyte damage caused by DON poisoning, and the exogenous GDF15 can relieve inhibition of DON poisoning on cell growth and development through research. And a GDF15-beta-catenin-Myc signal channel is activated, so that the downstream Myc, p27 and p21 are normally expressed. The invention discloses a new application of GDF15 in treatment of DON poisoning.

The invention belongs to the technical field of in-vitro diagnostic reagents, and particularly relates to application of a detection reagent for GDF15 protein in extracellular vesicles in preparation of a prostate cancer diagnosis and / or staging kit. According to the invention, enrichment and proteomics detection are carried out on plasma EVs of patients with prostatic cancer (PCa) and benign prostatic hyperplasia (BPH), and through bioinformatics analysis, a potential EV protein marker GDF15 which can be used for early diagnosis of PCa is screened for the first time. The GDF15 protein is verified in a plurality of groups of new clinical queues by further adopting an immunological technology and a targeted quantitative mass spectrometry technology, and the distinguishing ability of the GDF15 protein to PCa and BPH and the distinguishing ability of the GDF15 protein to different PCa stages are determined. The method is expected to promote noninvasive precise diagnosis of clinical PCa, and has a good application prospect.

The present invention concerns the field of diagnostics. Specifically, it relates to a method for assessing a subject with suspected infection comprising the steps of determining the amount of a first biomarker in a sample of the subject, said first biomarker being MR-proADM, determining the amount of a second biomarker in a sample of the subject, wherein said second biomarker is selected from the group consisting of: sFlt-1, GDF15 and ESM1, comparing the amounts of the biomarkers to references for said biomarkers and / or calculating a score for assessing the subject with suspected infection based on the amounts of the biomarkers, and assessing said subject based on the comparison and / or the calculation. The invention also relates to the use of a first biomarker being MR-proADM and a second biomarker selected from the group consisting of: sFlt-1, GDF15 and ESM1, or a detection agent specifically binding to said first biomarker and a detection agent specifically binding to said second biomarker for assessing a subject with suspected infection. Moreover, the invention further relates to a computer-implemented method for assessing a subject with suspected infection and a device and a kit for assessing a subject with suspected infection.

The invention discloses an AKI, CKD and AKI-CKD progress general prediction model based on plasma proteomics and a construction method thereof. The construction method comprises the following steps: selecting a patient which has plasma proteomics data when a baseline which meets the inclusion standard of a research group, has eGFR greater than or equal to 60mL / min / 1.73 m < 2 > when the baseline exists, and has no AKI or CKD medical history; collecting clinical prediction factors and blood proteomics data of the modeling crowd; and randomly dividing the selected modeling crowd data into a training set and a verification set, screening out protein prediction markers such as protein WFDC2 and protein GDF15 shared with the development of the AKI, the CKD and the AKI-CKD, and establishing a general prediction model for the development of the AKI, the CKD and the AKI-CKD. Proteomics is used for predicting AKI-CKD progress for the first time, three renal function outcomes can be predicted at the same time, prediction indexes are simple and easy to obtain, and the model is a universal model with high prediction capacity.

This disclosure generally relates to methods and compositions for functional genetic modifications at selected genomic sites, such as the FGF21 gene or the GDF15 gene. This disclosure further provides compositions and methods for genomic editing of AU-rich elements in the FGF21 and / or GDF15 genes for treating obesity-related diseases and disorders.

In some aspects, the invention teaches pharmaceutical compositions that include a TGF-β ligand trap, and methods of using a TGF-β ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-β ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-β signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-β ligand trap to reduce right ventricular systolic pressure in a subject.

The invention provides a CKD early screening marker based on plasma proteomics. The early screening marker comprises the following five kinds of protein: IGFBP4, GDF15, EDA2R, HAVCR1 and XG. The early screening marker provided by the invention can provide ultra-early warning within 16 years before disease attack, is high in prediction accuracy, and is superior to the conventional model in short-term and long-term prediction aspects; meanwhile, a key proteome pathway is disclosed, and reference can be provided for clinical application and prevention strategies. The invention also provides application of the early screening marker based on the CKD.

In some aspects, the invention teaches pharmaceutical compositions comprising a TGF-beta ligand trapping agent, and methods of using the TGF-beta ligand trapping agent to treat, prevent, or reduce the rate of progression of pulmonary hypertension (PH). The invention also provides methods of using the TGF-beta ligand trapping agents to treat, prevent, or reduce the rate of progression of a variety of disorders, the conditions include, but are not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-beta signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using the TGF-beta ligand trapping agent to reduce right ventricular systolic pressure in a subject.

A GDF15 binding molecule, in particular an antibody and fragments thereof that specifically recognize GDF15. Nucleic acids or host cells comprising such antibodies or fragments thereof, medicaments comprising such antibodies or fragments thereof, and therapeutic and diagnostic methods or uses applying these antibodies and fragments.

In certain embodiments, provided herein are compositions, kits, methods and uses that are useful for preventing or treating a subject suffering from one or more diseases, conditions or disorders associated with chemotherapy such as anthracycline treatment. In some embodiments, provided is a method of treating or preventing a disease, condition or disorder resulting from or exacerbated by chemotherapy treatment in a subject, comprising the step of: administering an effective amount of GDF15 to the subject prior to the chemotherapy. Other example embodiments are described herein. In certain embodiments, the provided novel compositions, kits, methods and uses are highly effective in reducing cardiac cytotoxicity, cheaper, and safer for use.

The objective is to provide a simple and indirect method for estimating the rate of senescent immune cells (the ratio of immune cells with high SAβgal expression levels among T cells whose surface marker is CD8-positive) using a small amount of blood sample. [Solution] This method estimates the rate of senescent immune cells using the relative expression levels of one or more selected from Granzyme K, α-Klotho, GDF15, PAI-1 (SERPIN1), and ferritin in the blood.

Provided herein are method of using GLP1-GDF15 fusion proteins for reducing food intake, preventing, treating or ameliorating diseases and disorders, such as obesity, type 2 diabetes, the metabolic syndrome, insulin resistance, and dyslipidemia, among others, the fusion protein comprising a GLP1 or GLP1 variant peptide, a first linker peptide, a serum albumin protein, a second linker peptide, and a GDF15 protein.

A GDF15 binding molecule, in particular an antibody specifically recognizing GDF15 and a fragment thereof. A nucleic acid or host cell containing the antibody or fragment thereof, a drug containing the antibody or fragment thereof, and a therapeutic and diagnostic method or use applying the antibody and fragment.

To provide constructs comprising GDF15 and mutants thereof.SOLUTION: A fusion protein comprising a GDF15 region and an Fc domain are provided. In various embodiments, constructs comprising GDF15 and mutants thereof can be of use in treating or ameliorating a metabolic disorder. In various embodiments, the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy.SELECTED DRAWING: None

The present invention provides a GDF15-binding nanoantibody, and a use thereof in preparation of a drug for treating tumor cachexia and in detection of GDF15. The nanoantibody provided in the present invention exhibits high affinity for GDF-15 and is capable of blocking the binding of GDF-15 to GFRAL.

The invention discloses a GDF15 detection method based on a homogeneous-phase light-excited chemiluminescence immunoassay technology and a kit. The detection method comprises the following steps: preparing donor microspheres coupled with a GDF15 capture antibody and receptor microspheres coupled with a GDF15 detection antibody, uniformly mixing and incubating a sample to be detected and the coupled donor microspheres and receptor microspheres, and performing fluorescence detection to obtain the GDF15 concentration of the sample to be detected. The kit comprises donor microspheres coupled with a GDF15 capture antibody, receptor microspheres coupled with a GDF15 detection antibody, a GDF15 standard substance solution and an analysis buffer solution. According to the invention, the carboxyl modified microspheres are used, so that the coupling efficiency with the antibody is higher; the GDF15 content in a to-be-detected sample can be rapidly detected by applying a double-antibody sandwich immunoassay and light-activated chemiluminescence characteristics, the detection range is wide, the sensitivity and the accuracy are high, the detection is rapid, simple and convenient, and the GDF15 detection kit can be clinically used for early auxiliary diagnosis of cardiovascular diseases such as HF and MI and has a good application prospect.

Provided herein is a method for treating or preventing a disease or disorder associated with a deregulated NRF2 / KEAP1 pathway, comprising administering a subject in need thereof a therapeutically effective amount of entacapone or nitecapone or a pharmaceutically acceptable salt thereof; and entacapone or nitecapone can reversibly bind to KEAP1, those compounds activated NRF2 in vitro and in vivo by reversibly modifying C151 on KEAP1, and both drugs can enhance the expression of growth differentiation factor 15 (GDF15) and NRF2 downstream antioxidant response elements (ARE) genes.

This invention belongs to the field of biomedical technology, specifically relating to a GDF15 antagonistic peptide and its application. The amino acid sequence of the antagonistic peptide is shown in SEQ ID NO.1. To improve drug stability and blood-brain barrier penetration, GDF15-A-Pep was fused with albumin and transferrin receptor nanobodies. Biological validation results showed that the fusion protein significantly inhibited GDF15-induced MMP1 transcription and protein expression, and exhibited potent antagonistic activity in reporter gene experiments. This invention not only reveals the key structural basis of GDF15 receptor recognition but also provides experimental evidence for the development of novel GDF15 antagonistic drugs with central regulatory potential.

The invention provides a Crohn disease early screening marker based on plasma proteomics. The early screening marker comprises the following nine proteins: CD274, CHI 3L1, REG1B, ITGAV, PRSS8, ITGA11, GDF15, DEFA1DEFA1B and IL6. The early screening marker provided by the invention can accurately and non-invasively predict CD as long as 16 years before diagnosis, which provides an important value for early screening of CD high risk groups and formulation of intervention measures. The invention also provides application of the Crohn disease early screening marker and an early screening kit for Crohn disease prediction.

The invention provides a COPD (chronic obstructive pulmonary disease) early screening marker based on plasma proteomics. The early screening marker comprises the following ten proteins: CXCL17, WFDC2, SCGB1A1, GDF15, EDA2R, TNR, AGER, CA14, ODAM and TNFRSF10B. The early screening marker provided by the invention can provide ultra-early warning within 16 years before disease attack, is high in prediction accuracy, and is superior to the conventional model in short-term and long-term prediction aspects; meanwhile, a key proteome pathway is disclosed, and reference can be provided for clinical application and prevention strategies. The invention also provides application of the chronic obstructive pulmonary disease early screening marker and a corresponding early screening kit.

The application discloses application of growth differentiation factor 15 in preparation of products for diagnosis, prognosis and treatment of retinal arterial obstruction, and finds that serum GDF15 level of a patient with RAO is greater than or equal to 442.64 pg / mL, and is significantly positively correlated with the risk of RAO (OR=12.6), and the diagnostic accuracy can be improved by combining glucose, triglyceride and other indexes (AUC=0.922). The recombinant human GDF15 protein can inhibit ischemia and hypoxia RGC apoptosis and protect visual function. The application has important application value in early diagnosis of RAO, visual prognosis evaluation and targeted treatment.

The present invention provides an antibody or a fragment thereof for human growth differentiation factor 15 protein (GDF15). The present invention further provides a use of said antibody or a fragment thereof in the manufacture of a medicament for treating a disease or condition. The antibody or a fragment thereof provided by the present invention can specifically bind to human GDF15 with high affinity, block the interaction of GDF15 with its receptor GFRAL, and has a longer in vivo half-life than its homologous antibody.

The present invention discloses an anti-GDF15 antibody, a preparation method thereof and an application thereof. In the present invention, a prokaryotic host cell is used to recombinantly express human GDF15 in an immunogen. By fusing a thioredoxin tag at the N-terminus, the recombinant GDF15 antigen has stronger immunogenicity and more exposed dominant epitopes, and a monoclonal antibody with higher affinity is prepared. In addition, the present invention uses multiple negative and positive clinical samples for verification, and the results show that the monoclonal antibody screened in the present invention has higher detection sensitivity and stronger specificity for cancer. The antibody of the present invention has broad application prospects in the early diagnosis and prognosis of cancer.

Provided in the present invention is an antibody or fragment thereof against a human growth and differentiation factor 15 protein (GDF15). Further provided in the present invention is the use of the antibody or fragment thereof in the preparation of a drug for treating diseases or conditions. The antibody or fragment thereof provided in the present invention can bind to human GDF15 with high affinity and specificity, blocks the interaction of GDF15 with receptor GFRAL thereof, and has a longer half-life period in vivo in comparison with antibodies of the same kind.

The invention provides a liver cirrhosis complication early screening marker based on plasma proteomics. The liver cirrhosis complication early screening marker comprises the following five proteins: GDF15, NOTCH2, PROC, GGT1 and COL4A1. The early screening marker provided by the invention can provide ultra-early warning within 16 years before disease attack, is high in prediction accuracy, and is superior to the conventional model in short-term and long-term prediction aspects; meanwhile, a key proteome pathway is disclosed, and reference can be provided for clinical application and prevention strategies. The invention also provides application of the liver cirrhosis complication early screening marker and a corresponding early screening kit.

The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to GDF15, as well as methods and uses for the antibodies.

This invention relates to the field of biomedical technology. It provides a cardiac-targeting bispecific antibody protein and its applications. The bispecific antibody protein comprises a targeting conjugate that specifically recognizes NPR1 and a sequence that specifically recognizes GDF15. The amino acid sequence of the bispecific antibody protein is shown in SEQ ID NO.2. This invention cleverly achieves the dual functions of cardiac tissue targeting and effectively mediating endocytosis by utilizing a membrane protein specifically highly expressed in myocardial tissue as an effector molecule. The cardiac-targeting bispecific antibody protein of this invention can target the cardiac tissue surface receptor NPR1 and specifically target and degrade GDF15 within cardiac tissue, showing promising application prospects in the treatment of heart failure.

The present disclosure provides a method of treating cardiometabolic syndrome (CMS) with a GDF15 molecule. Also provided herein is a method of treating a cardiac or heart condition. In some embodiments, the GDF15 molecule is a GDF15-Fc fusion, in which a GDF15 region is fused to an Fc region, optionally via a linker.