125 results about "Abnormal expression" patented technology

The invention discloses a kit and method for detecting leukemia and lymphoma based on full-spectrum flow cytometry, the kit comprises 25 antibodies, the antibodies are specifically bound with fluorescein respectively, and leukemia and lymphoma are detected through full-spectrum flow cytometry; the 25 kinds of antibodies comprise HLA-DR (human leukocyte antigen-DR), CD38, CD7, CD34, Lambda, CD19, CD64, CD14, CD5, CD123, CD16, CD20, Kappa, CD117, CD13, CD45, CD11b, CD2, CD10, CD8, CD15, CD4, CD3, CD56 and CD33. The kit comprehensively covers development stages of various lines of bone marrow cells, and common abnormal expressions of various leukemia, myelodysplastic syndromes and lymphoma, and can preliminarily screen various leukemia and lymphoma.

The invention relates to the technical field of biological medicines, and discloses a blocking antibody targeting CXCL6 and an application of the blocking antibody in preparation of antitumor drugs. The antibody or antigen-binding fragment thereof is capable of binding specifically to human CXCL6 protein with high affinity (e.g., Kd < = 1 nM). According to the invention, the specificity and high affinity of the antibody are verified by Western Blot, immunofluorescence, immunohistochemistry and surface plasmon resonance (SPR) technologies. Functional experiments show that the antibody can effectively block CXCL6-induced neutrophil chemotaxis, including in Transwell, a three-dimensional gel model and a zebra fish living body model. Besides, in a mouse MC38 colon cancer model, the antibody shows remarkable anti-tumor activity and can inhibit tumor growth driven by CXCL6. The invention also provides a pharmaceutical composition containing the antibody, and application of the antibody in preparation of drugs for preventing or treating diseases (such as inflammatory diseases, autoimmune diseases and cancers) related to abnormal expression or activity of CXCL6.

The invention belongs to the technical field of bioactive peptides, and particularly relates to a phycocyanin peptide and application thereof in preparation of a product with functions of inhibiting PTGS2 expression and regulating an Akt / GSK3beta signal channel. According to the invention, phycocyanin is taken as a raw material, active polypeptides with specific sequences are obtained through an enzymolysis separation technology, and the amino acid sequences of the active polypeptides are respectively Leuu-Ala-Ser and Leuu-Gly-Leu. Experiments prove that the phycocyanin peptide prepared by the invention can significantly inhibit the expression of PTGS2, and can play a related regulation role by activating an Akt / GSK3beta signal channel, so that the technical blank of plant active peptide targeting PTGS2 and Akt / GSK3beta signal channels is filled, and the phycocyanin peptide can be widely applied to the development of related products for regulating the abnormal expression of PTGS2 and Akt / GSK3beta signal channels.

The application provides a personalized cancer driver gene identification method based on network propagation, and the implementation steps are as follows: obtaining related data of cancer driver gene identification; performing data fusion on abnormal genomics data; constructing a cancer gene regulation network of a group; constructing a personalized cancer gene regulation network; calculating influence score of a node pair; and obtaining a personalized cancer driver gene identification result through a network propagation process. In the process of constructing the personalized cancer gene regulation network, statistical analysis is performed on the interaction between each pair of genes of each patient, so that the deviation of the network model caused by abnormal expression of a single gene in the prior art is avoided; and in the process of network propagation, various genomics data and topological information in the network are integrated, the information abundance in the network model is improved, and the accuracy of identifying personalized driver genes is effectively improved.

The invention provides an application of a pair of immune costimulatory factors TNFSF9 / TNFRSF9 as markers in preparation of a product for early prediction of preeclampsia, and the immune costimulatory factors comprise a tumor necrosis factor superfamily member 9 (TNFSF9) and a tumor necrosis factor receptor superfamily member 9 (TNFRSF9). The product is used for carrying out early warning on the preeclampsia occurrence risk 20 weeks before pregnancy. The product is used for detecting the immune costimulatory factor through at least one of serum, plasma, whole blood and placental tissue. The invention aims to improve the early prediction efficiency of preeclampsia by detecting the abnormal expression level of the pair of markers.

The present disclosure relates to a nucleoside analogue and a use thereof. The nucleoside analogue is a compound shown in formula (Ia) or a prodrug thereof. The nucleoside analogue can enhance targeted delivery of oligonucleotide drugs to nervous system cells, thereby increasing the inhibition rate of the oligonucleotide drugs delivered in a targeted manner on expression of specific genes in the nervous system cells, or enabling the oligonucleotide drugs delivered in a targeted manner to achieve the purpose of preventing and / or treating pathological conditions or diseases caused by abnormal expression of the specific genes in the nervous system cells. The present disclosure also relates to a nucleotide analogue-containing double-stranded oligonucleotide and a use thereof. The double-stranded oligonucleotide comprises a sense strand and an antisense strand, each strand has 17-25 modified and / or unmodified nucleotides, and the antisense strand and the sense strand are complementary to form a duplex region; the sense strand and / or the antisense strand contains at least one nucleotide analogue represented by the structure of formula (100), or a tautomer, or stereoisomer, or pharmaceutically acceptable salt thereof; the double-stranded oligonucleotide can effectively treat and / or prevent pathological conditions or diseases caused by abnormal expression of specific genes in nervous system cells.

Provided are an antibody targeting Trop2, an antibody-drug conjugate, and use thereof. The provided antibody targeting Trop2 is capable of specifically binding to a target cell expressing human Trop2, has high affinity with same, is capable of entering the cell by means of endocytosis and inhibiting tumor growth or progression, and can be used for treating, preventing, and ameliorating conditions in a subject associated with abnormal expression of Trop2 (e.g., breast cancer, urothelial carcinoma, and non-small cell lung cancer).

The present disclosure provides a double-stranded oligonucleotide comprising a lipid-modified monomer and use thereof and pertains to the technical field of oligonucleotide drugs. In the present disclosure, a lipid group is introduced into a nucleotide monomer to prepare a modified nucleotide monomer, and the lipid-modified nucleotide monomer is utilized to prepare a double-stranded oligonucleotide, a double-stranded oligonucleotide conjugate, or a pharmaceutical composition. The modified double-stranded oligonucleotide, the double-stranded oligonucleotide conjugate, or the pharmaceutical composition can effectively treat and / or prevent pathological conditions or diseases caused by abnormal expression of a specific gene in target tissue-related cells.

Provided herein are compounds recognized as inhibitors of ADAR1 activity, such as compounds having the following formula (I) or (II), or pharmaceutically acceptable salts or tautomers thereof, which are useful in the treatment of cancer and other conditions, including those associated with aberrant ADAR1 expression.

The application provides an arginine methyltransferase 6 inhibitor and a preparation method, a pharmaceutical composition and a use thereof, relates to the technical field of biological medicine. The arginine methyltransferase 6 inhibitor provided by the application is a new compound obtained on the basis of a large number of design, synthesis and screening. The arginine methyltransferase 6 inhibitor is different from existing PRMTs inhibitors. The arginine methyltransferase 6 inhibitor can selectively degrade arginine methyltransferase 6, thereby regulating the protein level of arginine methyltransferase 6, has antitumor cell activity, can be used for preventing or treating diseases related to abnormal expression of PRMT6, and provides a new choice for development and application of antitumor drugs. The preparation method of the arginine methyltransferase 6 inhibitor provided by the application adopts raw materials which are easy to obtain, has the advantages of simple synthesis method, safety, easy realization and high yield, and can be used for industrial production.

The invention discloses a compound for targeted ubiquitination degradation of USP7 protein, and a medicinal composition and application thereof. The structural formula of the E3 ubiquitin ligase complex is as shown in formula I. A is a specific protein ligand in the E3 ubiquitin ligase complex; l is a bivalent linking group between a USP7 protein small molecule ligand and a specific protein ligand in an E3 ubiquitin ligase complex. The protein degradation chimera has the activity of inhibiting USP7 protein and the activity of degrading USP7 protein, and can effectively inhibit malignant proliferation of acute lymphatic leukemia cells, so that the protein degradation chimera can be used for related diseases with abnormal expression of USP7 protein.

The invention belongs to the technical field of immunology, and discloses an anti-human CD19 receptor single-domain antibody, and the amino acid sequence of the single-domain antibody is as shown in SEQ ID No.1. The antibody has good reaction activity with human CD19, can be used for detecting or diagnosing CD19 and treating related diseases with abnormal CD19 expression, and has wide application prospects in the fields of drug application, clinical detection and diagnosis and the like.

Disclosed are a compound having a PTPN2 inhibitory effect and a use thereof. Specifically, the invention discloses a compound with a protein tyrosine phosphatase inhibition effect or a pharmaceutically acceptable salt thereof, and application of the compound or the pharmaceutically acceptable salt in treating and / or preventing diseases or symptoms related to abnormal expression of protein tyrosine phosphatase. The compound is represented by formula (I):

Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we have developed an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.

The invention discloses a method for improving autism behaviors through Npas4 expression and overexpression in a cat chat syndrome model, and belongs to the technical field of animal model construction. Selecting SD wild rats and CdCS model rats, and normally feeding and breeding the rats; the method comprises the following steps: measuring the protein concentration by adopting a BCA method, then carrying out Western Blot, then carrying out brain stereotactic injection, and finally carrying out behavioral testing. According to the invention, a CdCS rat model is established by using a CRISPR-Cas9 technology, and the model shows cognitive and social behavior disorders and medial prefrontal cortex (mPFC) neuron dendritic abnormality; in addition, an abnormally expressed gene is found in the model mouse, the research focuses on Npas4, and a new insight is possibly provided for disease treatment.

This invention discloses a prognostic and therapeutic suitability assessment model for hepatocellular carcinoma (HCC) based on mRNA vaccine antigens, and its construction method. First, the differences in gene expression between normal tissues and HCC tumors are analyzed to understand the mutations and genomic structural changes in HCC patients. Then, genes related to the level of antigen-presenting cell infiltration, as well as genes significantly related to overall survival and disease-free survival, are further selected from anomalously expressed and mutated genes to obtain candidate mRNA vaccine neoantigen targets. Based on the expression levels of these targets, patients are immunophenotyped to assess the patient population suitable for mRNA vaccines. Simultaneously, the relationship between target expression levels and patient prognosis is quantified to predict the probability of HCC patients achieving 3-year and 5-year overall survival. This invention can objectively and accurately assess treatment resistance and tumor immune status in HCC, improving the predictive accuracy of HCC treatment prognosis.

The application discloses a single-domain antibody against CD99 protein and a coding gene and application thereof. The single-domain antibody Nab99-30 against CD99 protein comprises three complementarity determining regions CDR1, CDR2 and CDR3, characterized in that the amino acid sequences are sequentially shown in SEQ ID No. 1, SEQ ID No. 2 and SEQ ID No. 3; the amino acid sequence of the single-domain antibody Nab99-30 is shown in SEQ ID NO. 4, and the nucleotide sequence of the coding gene is shown in SEQ ID NO. 5. The single-domain antibody against CD99 protein screened by the application has the advantages of small volume, good stability, high activity and the like compared to common monoclonal antibodies, has strong binding capacity with CD99 protein, has high specificity and high affinity, and can be applied to preparation of a reagent for detecting CD99 protein or treatment of tumors with extracellular abnormal expression of CD99.

Provided herein are systems, compositions, methods for modulating abnormal expression of a target gene in a cell (e.g., muscle cell) to treat or ameliorate a disease or condition (e.g., muscular dystrophy, such as facial shoulder brachial muscular dystrophy (FSHD)) in a subject.

The application discloses application of SCAMP5 in treatment of autism spectrum disorder. The application research proves that, compared with a CON group, VPA-induced ASD rats have significant neurotransmitter release disorder and synapse signal path abnormality in hippocampus, overexpression of SCAMP5 protein can improve abnormal release of Glu, abnormal expression of scaffold protein Homer1b / c and downstream protein IP3R, and meanwhile, can relieve autism-like behaviors, space working memory and synapse development abnormality of ASD rats. The application provides a new target and a new potential drug for treatment of autism spectrum disorder, and provides a new idea for target treatment of ASD by in-depth exploration of potential path in pathogenesis of autism.

The invention discloses a naphthalene type chalcone compound and a preparation method and application thereof, and relates to the technical field of medicinal chemistry, and the structural formula of the naphthalene type chalcone compound is shown in the specification. Wherein part of the compounds have a good inhibition effect on HDAC6 protein, can obviously inhibit proliferation of tumor cells, and can be used for developing tumor treatment drugs related to abnormal expression of HDAC6 activity.

Antibodies that specifically bind to the human tight junction molecule CLDN18.2 and have functional properties that make them suitable for use in antibody-based immunotherapies of a disease associated with aberrant expression of CLDN18.2 are disclosed.

Provided are antibodies that include amino acid sequences of SEQ ID NOs: 2, 4, and 6-12, or amino acid sequences that are about 95% identical thereto, and fragments thereof. Also provided are scFv peptides that include a VH segment having a first amino acid sequence of amino acids 4-113 of any one of SEQ ID NOs: 2 and 8-12, a VL segment having a second amino acid sequence having amino acids 113-237 of SEQ ID NOs. 2 and 8-12, or both; nucleic acids encoding the same; methods for using the same to detect and / or target conformational states of FN in samples; methods for treating diseases and / or disorders and / or for meliorating at least one symptom of consequence of a disease or disorder associated with abnormal expression of a force-induced conformational state of FN in subjects; and methods for screening for compounds having selective binding activities for conformational states of FN.

The invention provides a BRD4 protein degradation agent and application thereof, and particularly provides a compound with a structure as shown in a formula (I) or pharmaceutically acceptable salt thereof, or a stereoisomer or a prodrug molecule thereof. The compound can degrade BRD4 protein in a targeted manner through a ubiquitin-proteasome way, so that the compound can be used for treating indications mediated by abnormal expression of the BRD4 protein. Wherein each group in the formula (I) is defined in the specification.

The application belongs to the field of aquatic molecular breeding and epigenetic marker development, and particularly relates to a group of DNA methylation markers related to loss of Chinese mitten crab in summer extreme high temperature and application thereof in breeding. The methylation markers include 8 differentially methylated cytosine sites located on the reference genome ASM2467909v1, adjacent to LOC126983793 (ADCY9), LOC126997354 (UNC79), LOC126998428 (UBN1), LOC126997943 (IFT52), LOC126991093 (ACO2), LOC126986070, LOC127001126 and LOC126997895 respectively. Among them, the high temperature damage group shows high methylation at part of the sites, low methylation at part of the sites, and abnormal expression of the corresponding adjacent genes. The above markers can be used for molecular detection and assisted selection of heat tolerance, survival rate maintenance ability, large-size crab output stability and high temperature damage risk of Chinese mitten crab.

The invention provides an MITF protein degradation agent and application thereof, and particularly provides a compound or a pharmaceutically acceptable salt thereof, or a stereoisomer or a prodrug thereof, and the compound is shown as a formula (I). The compound can degrade MITF protein in a targeted manner through a ubiquitin-proteasome way, so that the compound can be used for treating indications mediated by abnormal expression of the MITF protein.

The present disclosure provides an oligonucleotide conjugate, which is obtained by covalently linking a kidney-targeting polypeptide as a ligand to an oligonucleotide molecule capable of inhibiting the expression of a target gene via a linker group. The oligonucleotide conjugate has affinity to a cell receptor present on a kidney target cell, and can selectively and effectively reduce or inhibit the expression of a target gene in the kidney of a subject (e.g., a human or an animal). The oligonucleotide conjugate or pharmaceutical composition provided by the present disclosure can effectively treat and / or prevent a pathological condition or disease caused by abnormal expression of a specific gene in kidney tissue cells.

The present invention relates to binding antibodies targeting Mucin 17 (MUC17). The present invention further relates to detection systems comprising such antibodies for the diagnosis of diseases and / or disorders associated with aberrant expression of MUC17.

The invention discloses an antibody CM0735 and application thereof, the antibody CM0735 is an antibody targeting B7-H3 protein, HCDR1-3 in a heavy chain variable region of the antibody CM0735 is respectively as shown in SEQ ID NO: 1-3, LCDR1-3 in a light chain variable region of the antibody CM0735 is respectively as shown in SEQ ID NO: 5-7, and the antibody CM0735 has high binding activity to B7-H3, can be used for detection and treatment of B7-H3 abnormal expression diseases, and has good application prospects. The method has important significance on prevention and control of B7-H3 abnormal expression related diseases.

The present application relates to a kind of 7-difluoromethyl-5-aryl pyrazolopyrimidine compound and preparation and application, the structural general formula of the compound is as shown in formula a, it is a kind of compound with inhibiting HIF-2 alpha activity, can block HIF-2 alpha / ARNT dimerization and play the role of HIF-2 transcription inhibition.The present application is proved by multiple experiments, the synthesized compound all has excellent HIF-2 transcription inhibition effect, in human renal clear cell carcinoma cell strain 786-O, show good VEGF protein inhibitory activity.The compound described in the present application can be applied in the preparation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) inhibitor for treating VHL deletion or / and HIF-2 alpha abnormal expression disease.This kind of compound can inhibit the overexpression and activation of HIF-2 alpha, to achieve the treatment and prevention of target disease, such as VHL deletion or / and HIF-2 alpha abnormal expression disease.