169 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 provides application of a sperm tRNA (transfer ribonucleic acid) derived fragment 5 'tRF-Glu-CTC in prediction of development potential of assisted reproductive embryos. The expression of a tRNA derived fragment 5 'tRF-Glu-CTC in a sperm sample is detected, the abnormal expression of the sperm specific tRNA derived fragment 5' tRF-Glu-CTC in a DFI increase patient is verified, and the analysis on the correlation with clinical data and reproductive outcome of the patient prompts that the 5 'tRF-Glu-CTC molecular marker has significant correlation with the reproductive outcome, so that the 5' tRF-Glu-CTC molecular marker can be used for detecting the expression of the sperm specific tRNA derived fragment 5 'tRF-Glu-CTC in the DFI increase patient. The embryonic development potential can be effectively predicted, and a biomarker is provided for assisted reproduction treatment. In different experimental groups, the 5 'tRF-Glu-CTC can significantly improve the prediction precision, and shows good prediction performance in different clinical data. The detection method based on the fragment is expected to become a new tool for evaluating the assisted reproduction curative effect, the reproduction treatment scheme is further optimized, and the success rate is improved.

The invention discloses a dual-recognition-framework nucleic acid probe, a preparation method and application, the dual-recognition-framework nucleic acid probe comprises a DNA tetrahedron, and a dual-recognition module and a fuel amplification module which are connected to the vertex of the DNA tetrahedron through complementary pairing of bases, ATP recognition protection and dual-target response are introduced, and the dual-recognition-framework nucleic acid probe is obtained through sequential opening of internal and external locks. The occurrence of false positive conditions can be reduced, and the specificity is effectively improved; signal amplification is realized by virtue of abnormal APE1 expression of tumor cells, so that a fluorescence signal for miRNA detection is increased, and the sensitivity and the imaging signal-to-noise ratio are effectively improved; the preparation is easy; the use is convenient; complicated equipment is not needed. The method can be applied to a target nucleic acid detection reagent or an imaging or positioning reagent of cells, tissues or organs containing target nucleic acid.

The invention discloses an antibody combination and a system for detecting leukemia stem cells. The antibody combination comprises a CD7 antibody, a CD371 antibody, a CD34 antibody, a CD45RA antibody, a CD123 antibody, a CD133 antibody, a CD38 antibody, a CD45 antibody, a CD90 antibody, a CD33 antibody and a CD19 antibody. The antibody combination provided by the invention can accurately identify target cells and distinguish normal HSCs and pluripotent progenitor cells in a CD34 + CD38-cell population, and the specific antibody has abnormal expression or expression intensity change, so that leukemia stem cells can be rapidly, simply and conveniently detected with high accuracy, high sensitivity and high specificity, the sensitivity of MRD evaluation is favorably improved, and the kit has a good application prospect. Therefore, signs of disease recurrence can be found earlier, more information about disease prognosis can be provided, and doctors and patients can be helped to better understand disease prognosis and possible results.

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 present application discloses a method of determining suitability of treating a patient suffering from cancer or metastasis of cancer characterized by aberrant expression of MUC1, with a MUC1* targeting therapeutic.

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 invention provides a bioluminescence probe for detecting norepinephrine, its preparation method and use, belonging to the field of biological detection. The bioluminescence probe of the present invention has high selectivity and high responsiveness to norepinephrine, can specifically recognize norepinephrine, has high sensitivity and low detection limit, and can be used for the precise detection of norepinephrine. In the range of pH 1.0 to 7.4, the bioluminescence probe of the present invention has excellent stability and can meet the application requirements under different physiological environments in vivo. At the same time, the norepinephrine bioluminescence probe of the present invention can also visually track exogenous norepinephrine at the in vivo level, and perform dynamic visual analysis on patients with diseases related to abnormal expression of norepinephrine involving nerves, tumors, blood pressure and heart diseases, which is beneficial to the clinical detection of norepinephrine and has broad application prospects.

The invention relates to the field of detection, in particular to a detection method of an exosome marker combination for monitoring postoperative recurrence of esophageal cancer. The method comprises the following steps: extracting exosomes from a serum sample of a patient, measuring expression levels of biomarkers related to recurrence of esophageal cancer in different exosome subgroups as original signal values, and selecting representative signal values from the original signal values; and performing standardization processing on the representative signal value, calculating a recurrence probability based on the standardized representative signal value of the biomarker, and performing risk classification. The problems that in a traditional exosome marker detection method, an average value or single subgroup data is generally directly taken as a representative signal, and abnormal expression characteristics cannot be highlighted; generally, the recurrence risk is predicted directly based on the expression level of a single time point, and the dynamic change trend of recent signals may be ignored. The technical problems of lack of comprehensive evaluation of the overall deviation trend of all markers and neglecting of the correlation between the distribution disorder degree and the recurrence risk in the prior art are generally solved.

The purpose of the present invention is to provide a compound, a method, and a pharmaceutical composition for normalizing dual homologous frame 4 (DUX4) in an individual in which the DUX4 gene is abnormally expressed, and to provide a modified oligonucleotide comprising 12-30 residues, comprising at least 8 contiguous nucleic acid base sequences, the modified oligonucleotide has a nucleic acid base sequence which is complementary to the isometric portion of the nucleic acid base of the mature mRNA of DUX4 of SEQ ID NO: 1 from the 5'terminal thereof at positions 126th to 147th, positions 232th to 248, positions 1306th to 1325th, or positions 1472nd to 1495th, and the nucleic acid base sequence of the modified oligonucleotide has at least 90% complementarity with the isometric portion of the nucleic acid base sequence of the mature mRNA of DUX4 of SEQ ID NO: 1.

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 method for treating cancers by combined application of Mobosertinib and an anti-PD-1 antibody, researches on the synergistic effect of Mobosertinib on non-EGFR exon 20 insertion mutation diseases and the synergistic effect of Mobosertinib and the anti-PD-1 antibody, and finds that the action mechanism of Mobosertinib is related to abnormal expression of SET. The invention provides a technical scheme of new application and combined application of Mobosertinib, and a new research direction is provided for treatment of cancers related to SET abnormal expression.

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.

The invention discloses a hepatocellular carcinoma prognosis and treatment adaptability evaluation model based on mRNA vaccine antigen and a construction method. The method comprises the following steps: firstly, analyzing gene expression difference between normal tissues and hepatocellular carcinoma tumors, understanding mutation and genome structure change of hepatocellular carcinoma patients, and then further selecting genes related to the infiltration level of antigen presenting cells from abnormally expressed genes and mutant genes, and the genes having a significant relationship with the overall lifetime and disease-free lifetime of the patient, so as to obtain candidate mRNA vaccine neoantigen targets. Based on the expression level of the target, immunotyping is performed on the patient, and the patient population suitable for the mRNA vaccine is evaluated. Meanwhile, the relationship between the expression level of the target spot and the prognosis of the patient is quantified, so that the probability value that the total survival time of the hepatocellular carcinoma patient reaches 3 years and 5 years is predicted. According to the invention, the hepatocellular carcinoma treatment resistance and tumor immune state can be objectively and accurately evaluated, and the prediction accuracy of hepatocellular carcinoma treatment prognosis is improved.

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):

The invention belongs to the technical field of medicines, and particularly relates to a novel method for relieving toxic and side effects of bevacizumab. Based on preclinical research, the combination of glutathione and bevacizumab relieves toxic and side effects on immune cells when bevacizumab is independently used. Experimental data comparison shows that compared with bevacizumab single drug treatment, the combined glutathione can significantly reduce the inhibition effect on immune cell activity, so that the cell proliferation activity is repaired, and meanwhile, the disordered cell cycle and the abnormally expressed cell factor level tend to be normalized. The invention provides a novel treatment scheme and thought for targeted treatment of tumor patients with the VEGF monoclonal antibody bevacizumab, is also beneficial to research on the toxic action mechanism of drugs and optimization of the treatment scheme, and has important potential clinical experimental research value.

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 invention discloses an application of a fusion gene RPL17-C18orf32 as a benzo [g, h, i] perylene acute exposure marker, an in-vitro benzo [g, h, i] perylene acute exposure human lung bronchial epithelial cell model is established, abnormal expression of the fusion gene RPL17-C18orf32 is detected, and RPL17-C18orf32 participates in benzo [g, h, i] perylene acute exposure marker expression. The processes of cell proliferation capacity decline, apoptosis rate increase, cycle disorder, cell DNA damage and the like caused by acute exposure of benzo [g, h, i] perylene, so that the fusion gene RPL17-C18orf32 can be used as a biomarker for acute exposure of benzo [g, h, i] perylene. The invention not only provides a potential biomarker for early diagnosis for evaluating the acute exposure of the benzo [g, h, i] perylene, but also provides a new strategy for developing diseases related to the acute exposure of the benzo [g, h, i] perylene for preventing and treating the acute exposure of the benzo [g, h, i] perylene.