363 results about "Systemic lupus" patented technology

Methods and kits are provided for diagnosing of neuropsychiatric syndromes concurrent with SLE (NPSLE) and for determining whether an SLE subject is at risk of developing a neuropsychiatric disease.

The invention discloses a systemic lupus erythematosus assessment method and device based on multi-modal medical map and medical knowledge fusion, terminal equipment and a medium, and relates to the technical field of medical artificial intelligence. The method comprises the following steps: acquiring multi-dimensional medical indexes of a patient, and constructing a multi-modal medical knowledge graph of the patient associated with the indexes; pre-training the self-supervised graph neural network to obtain a patient and medical index embedding vector; grouping and constructing a feature subset combination according to medical knowledge, and training and selecting an optimal sub-model; dynamically weighting and fusing the prediction probabilities of the sub-models to obtain a comprehensive prediction probability; and screening the key indexes based on the embedded vector and quantifying the activity evaluation contribution degree of the key indexes to obtain an activity comprehensive score. The systemic lupus erythematosus evaluation method improves the accuracy and robustness of preliminary evaluation of systemic lupus erythematosus, solves the problems of data missing and sample imbalance, and is explainable in output evaluation, adaptive to primary medical treatment and capable of supporting hierarchical diagnosis and treatment.

The invention discloses a systemic lupus erythematosus interaction management method based on patient sign data modeling, and particularly relates to the field of lupus erythematosus interaction management, which comprises the following steps: collecting basic data and sign data of a patient, generating a standardized basic data set and an integrity sign data set, feature combination, feature correlation detection and factor extraction are executed, a potential feature space representing patient features is constructed, and static health behavior feature modeling is achieved; the method comprises the following steps: acquiring nurse-patient interaction behavior data, generating a preliminary interaction data set, executing interaction feature extraction and activeness judgment, and generating a standardized interaction feature matrix; a multi-dimensional feature vector and dynamic health behavior link is constructed based on patient sign data and interactive behavior features, and time sequence prediction and response feedback closed-loop optimization are combined, so that dynamic management and individualized intervention of active health behaviors of systemic lupus erythematosus patients are realized.

To provide a compound which is a novel proline derivative, and to provide a pharmaceutical composition comprising the compound for the treatment of diseases, for example, systemic lupus erythematosus.SOLUTION: A pharmaceutical composition comprises, as a cGAS inhibitor, a compound which is a novel proline derivative of formula (I) (where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and G are as defined in claim 1), or a prodrug, a pharmaceutically acceptable salt, or a stereoisomer of the compound.SELECTED DRAWING: None

The invention discloses a neutralizing nucleic acid aptamer for targeted inhibition of a B cell activating factor and application of the neutralizing nucleic acid aptamer in treatment of systemic lupus erythematosus. The neutralizing aptamer disclosed by the invention can be used for efficiently inhibiting the combination of BAFF and specific receptors on a B cell membrane, including a BAFF receptor (BAFF-R), a human calcium regulatory cyclophilin ligand interaction molecule (TACI) and a B cell maturation antigen (BCMA), so that the proportion of plasma cells, plasma mother cells and hair growth center B cells is reduced, and finally, the generation and secretion of autoantibodies are reduced; the compound has a targeted therapeutic effect on systemic lupus erythematosus. Compared with an existing biological agent for neutralizing BAFF, the neutralizing nucleic acid aptamer has the advantages of being high in specificity, high in affinity, easy to synthesize, low in immunogenicity, low in cost, capable of being designed and programmed and the like, is a potential novel nucleic acid preparation for SLE targeted therapy, and has a good clinical transformation application prospect.

The invention provides a diagnostic marker for systemic lupus erythematosus and application of the diagnostic marker, and belongs to the technical field of biological medicine. The diagnostic marker is at least one protein of PDGFA (Platelet Derivative Growth Factor Amplification), APOD (Adenosine Polymerase Chain Reaction), CFHR5, AMDHD1 and SCGB3A1; the amino acid sequence of the PDGFA is as shown in SED ID NO. 1; the amino acid sequence of the APOD is as shown in SED ID NO. 2; the amino acid sequence of the CFHR5 is as shown in SED ID NO.3; the amino acid sequence of AMDHD1 is as shown in SED ID NO. 4; and the amino acid sequence of the SCGB3A1 is as shown in SED ID (Sequence of Identification) NO.5. According to the present invention, the five proteins are adopted as the SLE disease diagnosis biomarker independently or in the combination manner, such that advantages of high accuracy, high sensitivity and high specificity are provided, and the new target spot is provided for the diagnosis, the intervention improvement and the like of the SLE patient.

The invention discloses an E-CAR-NK cell for treating systemic lupus erythematosus and application of the E-CAR-NK cell, and belongs to the technical field of genetic engineering.A CD19 and BCMA double-target E-CAR is adopted for modifying an NK cell, and the E-CAR-NK cell is obtained; the CD19 and BCMA double-target E-CAR is composed of the following modules: a CD8 signal peptide, a CD19 scFv, a Linker, a BCMA scFv, a CD8 Hinge region, an NKG2D transmembrane region, a CD3 epsilon signal transduction region, a DAP12 costimulatory region, a 2B4 costimulatory region, and a CD3 zeta signal transduction region. Compared with a common CAR-NK cell, the E-CAR-NK cell disclosed by the invention has higher antigen sensitivity and better continuous killing ability, so that the treatment effect of SLE is improved, and the E-CAR-NK cell has lower side effects and higher safety.

The invention discloses application of docosapentaenoic acid or medicinal salt thereof in preparation of a medicine for preventing and / or treating systemic lupus erythematosus. The invention aims to provide novel application of docosapentaenoic acid in treatment of systemic lupus erythematosus. In view of various immune abnormalities existing in the systemic lupus erythematosus morbidity process, the docosapentaenoic acid has potential application value in the field of systemic lupus erythematosus treatment due to the effects of regulating immune cell functions and improving immune microenvironment.

The invention provides a biomarker for diagnosing systemic lupus erythematosus and application of the biomarker. According to the application disclosed by the invention, the expression of Ferritin in neutrophil of a systemic lupus erythematosus patient is found to be obviously reduced and is improved after treatment, the neutrophil has disease specificity and cell specificity, and the Ferritin in the neutrophil has important significance on clinical diagnosis or auxiliary diagnosis of systemic lupus erythematosus and disease condition evaluation.

The invention discloses a traditional Chinese medicine composition for preventing / treating systemic lupus erythematosus and application thereof.The traditional Chinese medicine composition is reasonably combined according to etiology and pathogenesis of systemic lupus erythematosus, pseudo-ginseng, ginseng, glossy privet fruit and syngnathus serve as monarch drugs, and the traditional Chinese medicine composition has the effects of promoting blood circulation to remove blood stasis, nourishing the liver and tonifying the kidney and directly tonifying yin deficiency of the liver and the kidney; salvia miltiorrhiza, safflower, peach kernel, American ginseng, codonopsis pilosula, prepared rhizome of rehmannia, wolfberry, mulberry and panax japonicus are taken as ministerial drugs and are matched to assist the monarch drugs and clear stasis heat, cornu cervi pantotrichum, herba epimedii, hippocampus, pericarpium citri reticulatae, polygonum multiflorum, angelica sinensis, radix paeoniae alba, rhizoma polygonati and dog kidney are taken as adjuvant and conductant drugs and assist the monarch and ministerial drugs to harmonize yin and yang, all the drugs are matched and have a synergistic effect, and the effects of nourishing kidney and replenishing essence, reinforcing qi and nourishing yin, promoting blood circulation to remove meridian obstruction, warming yang and removing stasis can be achieved. The traditional Chinese medicine can treat both symptoms and root causes, and can effectively treat systemic lupus erythematosus.

To provide compounds as new proline derivatives, and to provide a pharmaceutical composition comprising the compounds for the treatment of diseases such as systemic lupus erythematosus, systemic sclerosis, non-alcoholic steatohepatitis, interstitial lung disease and idiopathic pulmonary fibrosis.SOLUTION: There are provided new proline derivatives of formula (I) as cGAS inhibitors, or pharmaceutical compositions comprising a prodrug, a pharmaceutically acceptable salt, or a stereoisomer of the compound.SELECTED DRAWING: None

The invention relates to a cyclopeptide inhibitor aiming at human STING (stimulating interferon gene) and application of the cyclopeptide inhibitor. The cyclic peptide can specifically bind to and inhibit activation of human STING. The invention also provides a nanoparticle delivery system for loading the cyclopeptide on a cationic polymer PBAE and an amphiphilic polymer pDMA-pEPEMA, and a preparation method of the nanoparticle delivery system. The cyclic peptide and the nanoparticles thereof can be used for preparing medicines for treating autoimmune diseases (such as systemic lupus erythematosus and the like) caused by excessive activation of the cGAS-STING signal pathway. Compared with the existing small molecule STING inhibitor, the cyclopeptide inhibitor provided by the invention has higher specificity, stability and inhibition effect.

The invention belongs to the field of new application of medicines, and particularly relates to application of SIRT4-IN-1 in preparation of medicines for treating autoimmune diseases. It is found for the first time that SIRT4-IN-1 reduces the activation degree of immune response induced by HSV-1 virus infection by up-regulating acetylation modification of cGAS, inhibits abnormal activation of immune response in Trex1 deficient mouse cells and peripheral blood mononuclear cells of systemic lupus erythematosus patients, and improves abnormal activation of autoimmune response. The invention provides a new candidate drug for clinical treatment of systemic lupus erythematosus.

The present invention relates methods of producing B cell depletion in autoimmune diseases. More specifically, the invention shows the use of CD-19 bispecific targeting molecules to effectively treat autoimmune disorders such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren's disease (SjD).

The present invention provides compounds of formula I for the treatment of diseases such as systemic lupus erythematosus, systemic sclerosis (SSc), interferonosis, nonalcoholic steatohepatitis (NASH), interstitial lung disease (ILD), and idiopathic pulmonary fibrosis (IPF). JPEG2026504613000125.jpg8493 (in the formula, R 1 , R 2 , R 3 , R 4 , A, D, E, G, J, K, and L are as defined in claim 1), and prodrugs, deuterated analogs, and pharmaceutically acceptable salts thereof.

Provided is a circular RNA encoding CARs and the use thereof to create immune cells that target specific diseases, e. g., lymphoma, multiple myeloma and leukemia and auntoimmune diseases, such as systemic lupus erythematousus, lupus nephritis and myasthenia gravis.

The invention relates to a mesenchymal stem cell immunomodulatory function enhancing technology based on gene editing. The invention relates to the field of biomedical engineering and regenerative medicine, and particularly provides a method for enhancing the immune regulation function of mesenchymal stem cells through a CRISPR-Cas9 gene editing technology, and aims at up-regulating IDO1, IL-10 and other key genes in a targeted manner and remarkably improving the excessive immune response inhibition capability of MSCs. The technology can be used for developing high-efficiency and low-toxicity novel cell drugs for treating autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus.

The invention relates to an application of a small molecule medicine STK000311 in a medicine for treating a cGAS-STING pathway abnormal activation disease, and belongs to the technical field of biological medicines. According to the application disclosed by the invention, the small-molecular medicine STK000311 or the pharmaceutically acceptable salt of the small-molecular medicine STK000311 serving as the cGAS-STING signaling pathway inhibitor has an obvious treatment effect on the cGAS-STING pathway abnormal activation diseases for the first time, and verification experiments show that the small-molecular medicine STK000311 can be used for obviously inhibiting the activity of human cGAS protein in a targeted manner and inhibiting cGAS-mediated antiviral immune response; the transcription level of ISGs in PBMCs (peripheral blood mononuclear cells) of an SLE (systemic lupus erythematosus) patient is inhibited, the fact that the small-molecule medicine STK000311 has huge potential of developing cGAS activity related diseases is fully proved, a novel treatment medicine is provided for clinic, and the small-molecule medicine STK000311 has good clinical application value and wide application prospect.

A method for characterizing disease activity in a systemic lupus erythematosus patient (SLE), comprising obtaining a dataset associated with a blood, serum, plasma or urine sample from the patient, assessing the dataset for a presence or an amount of protein expression of at least one innate serum or plasma mediator, assessing the dataset for a presence or an amount of protein expression of at least one adaptive serum or plasma mediator biomarker, assessing the dataset for a presence or an amount of at least one chemokine / adhesion molecule biomarker, assessing the dataset for a presence or an amount of at least one soluble TNF superfamily biomarker, assessing the dataset for a presence or an amount of at least one inflammatory mediator biomarker, assessing the dataset for a presence or an amount at least one SLE-associated autoantibody specificity biomarker and calculating a Lupus Disease Activity Immune Index (LDAII) score.

The invention discloses a biomarker for diagnosing systemic lupus erythematosus and lupus nephritis and application of the biomarker, and relates to the technical field of biological medicines. The biomarker is an ISG15hiCD16 < + > mononuclear cell. According to the application disclosed by the invention, the ISG15hiCD16 + mononuclear cell subpopulation is found to be obviously increased in an SLE (systemic lupus erythematosus) patient. The invention also finds that the expression level of the ISG15hiCD16 + mononuclear cell subpopulation is positively correlated with the disease activity of the SLE patient, and the expression level of the ISG15hiCD16 + mononuclear cell subpopulation of the SLE patient with the kidney enduring expression is obviously higher than that of the SLE patient without the kidney enduring expression. The working characteristic curve analysis of a subject shows that the ISG15hiCD16 + mononuclear cell subset has better sensitivity and specificity for diagnosing the SLE and the LN, and has important significance for clinical auxiliary diagnosis of the SLE and the LN and illness state evaluation.

The invention relates to the technical field of biological medicine, and provides application of TRIM69 in preparation of a kit for auxiliary diagnosis of systemic lupus erythematosus. The kit assists in diagnosing systemic lupus erythematosus by detecting the TRIM69 level. Through the mRNA expression quantity of the TRIM69 and the expression quantity and / or concentration of the protein, the auxiliary diagnosis of the systemic lupus erythematosus is realized, and the TRIM69 as a biomarker has important values in the aspects of auxiliary diagnosis, disease activity monitoring, prognosis evaluation, diagnosis efficiency improvement and the like. Not only can a doctor be helped to recognize a high-risk patient earlier, but also a basis can be provided for individualized treatment, so that the long-term prognosis of the systemic lupus erythematosus patient is improved.

Fusion polypeptides are provided and comprise at least two ligand binding domains and a fragment crystallizable (Fc) region of immunoglobulin G (IgG). The ligand binding domains include an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-25 and / or one of the at least two ligand binding domains binds modulates B cell activity while the other modulates T cell activity. Isolated nucleic acids, vectors, and isolated cells encoding or including the fusion peptides are further provided. Pharmaceutical compositions include the fusion peptides and a pharmaceutically-acceptable vehicle, carrier, or excipient. Methods of treating Sjögren's Syndrome and / or Systemic Lupus Erythematosus are also provided and comprise administering to a subject in need thereof the fusion polypeptide including the two ligand binding domains and the Fc region of IgG.

The invention provides an SNP (Single Nucleotide Polymorphism) marker for targeted identification of systemic lupus erythematosus of children and application of the SNP marker. A new SNP site (RS25671007) is identified in a child systemic lupus erythematosus patient through whole exon sequencing, the site is located at the 734th pair of basic groups of a PABPC3 gene, and mutation from C to T exists at the site, or mutation from threonine to isoleucine exists in coded amino acid. In addition, in-vitro cell model experiments prove that the SNP causes significant up-regulation of the antibody type transformation function, and the SNP can be used as a reference marker for risk stratification or medication guidance of early targeted diagnosis, detection, gene evaluation and the like of systemic lupus erythematosus of children.

The application discloses a kit for diagnosing systemic lupus erythematosus, which is lanosterol lipid metabolite key enzyme CYP51A1, the expression amount of the transcription level of the lanosterol lipid metabolite key enzyme CYP51A1, and the cDNA sequence of the lanosterol lipid metabolite key enzyme CYP51A1 is shown as SEQ ID No. 1. The kit for diagnosing SLE provided by the application comprises CYP51A1 gene primers and primers of a housekeeping gene GAPDH, a standard product and amplification reagents. The application overcomes the defect that SLE gene diagnosis cannot be diagnosed. The application adopts a real-time fluorescent quantitative PCR method, has the characteristics of rapidness, sensitivity, accuracy and the like, the expression of CYP51A1 is detected through real-time fluorescent quantitative PCR, important basis and reference value can be provided for clinical diagnosis of diseases, thus being beneficial to the formulation of a treatment scheme of the disease, and having popularization and application value.

The invention discloses a novel compound and application thereof in preparation of a medicine for treating systemic lupus erythematosus. In-vitro experiments show that the compound provided by the invention can further inhibit the secretion of anti-dsDNA IgG + B cell subtype mediated autoantibody by inhibiting the process that B cells are differentiated into plasmoblasts; in-vivo experiments show that the compound provided by the invention can effectively reduce the content of total IgG and anti-dsDNA-IgG in peripheral blood of a systemic lupus erythematosus model mouse, inhibit splenomegaly and peripheral lymph node hyperplasia of the mouse, slow down urine protein increment of the mouse, inhibit glomerular lesion and renal tubule lesion of the mouse and inhibit IFN-gamma generation of the mouse kidney; differentiation of spleen and peripheral lymph node plasmablasts of mice is inhibited, that is, differentiation and function development (antibody secretion) processes of B cells are directly acted. Therefore, the compound provided by the invention has a prospect of being developed into drugs for treating systemic lupus erythematosus.

The disclosure relates to compounds of the disclosure and pharmaceutically acceptable salts thereof to their use in medicine; to compositions containing them; to processes for their preparation; and to intermediates used in such processes. The compounds of the disclosure may be useful in the treatment, prevention, suppression and amelioration of disease(s) such as atopic dermatitis, eosinophilic gastritis, atopic keratoconjunctivitis, allergy, alopecia, Alzheimer's disease, asthma, atherosclerosis, Bechet's disease, bullous pemphigoid, cancer, chronic obstructive pulmonary disease, chronic pruritis, chronic urticaria, Crohn's disease (CD), dermatitis, diabetic kidney disease, eosinophilic esophagitis, fungal keratitis, gout, idiopathic pulmonary fibrosis (IPF), keloids, non-alcoholic steatohepatitis (NASH), primary biliary cirrhosis, prurigo nodularis, psoriasis, psoriatic arthritis, rhinosinusitis, scleroderma, systemic lupus erythematosus (SLE), systemic sclerosis, ulcerative colitis (UC), vitiligo, or hidradenitis suppurativa. The compounds of the disclosure may be useful in the treatment, prevention, suppression and amelioration of a dermatological condition or a respiratory condition.

The invention discloses a black phosphorus hydrogel microneedle patch loaded with trained mesenchymal stem cells as well as a preparation method and application of the black phosphorus hydrogel microneedle patch, and belongs to the technical field of biological medicines. The micro-needle patch comprises a hydrogel substrate layer loaded with black phosphorus nanosheets and a hydrogel needle tip part for packaging the stem cells. The mesenchymal stem cells are subjected to combined domestication with low oxygen and high active oxygen, so that the anti-oxidative stress, anti-inflammatory and angiogenesis promoting capabilities of the mesenchymal stem cells are remarkably enhanced. After the patch is subcutaneously delivered, the black phosphorus component can efficiently remove bacteria and reduce drug resistance; after being domesticated, the stem cells can adapt to the immune microenvironment of the wound surface, and the immune regulation, inflammation inhibition and tissue regeneration promotion are synergistically realized by continuously releasing anti-inflammatory and angiogenesis promoting factors, so that the refractory wound surface caused by immune disorders such as systemic lupus erythematosus (SLE) and the like is effectively treated. The invention provides an innovative treatment strategy for chronic inflammatory wound healing.

Formulations and dosage regimens of anti-Blood Dendritic Cell Antigen 2 (BDCA2) antibodies are provided. These formulations and dosage regimens find use in the treatment of BDCA2-associated disorders such as systematic lupus erythematosus, cutaneous lupus erythematosus, and discoid lupus erythematosus, and cytokine release syndrome.

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38′ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and / or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

The invention provides an immune regulation type stem cell as well as a preparation method and application thereof in preparation of a medicine for treating lupus erythematosus, and belongs to the technical field of stem cell treatment. According to the preparation method of the immunomodulatory stem cells, the mesenchymal stem cells capable of remarkably improving the secretion capacity of IL-10 are screened by adopting CD106 + / CD274 + double-labeled magnetic beads for sorting, and the immunomodulatory stem cells which are definite in curative effect, small in side effect and high in immunomodulatory efficiency are prepared by performing hypoxia pretreatment, improving the homing capacity of the stem cells and performing induction by using immunomodulatory factors in three stages. The immunoregulation stem cell has a remarkable curative effect on systemic lupus erythematosus.