128 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 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.

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 present invention relates to the use of an ROR inverse agonist or a pharmaceutically acceptable salt thereof for the preparation of a medicament for modulating ROR in a patient and / or for controlling autoimmune diseases and antibody-mediated rejection in a patient. The ROR-mediated diseases or autoimmune diseases include HIV, cancer, celiac disease, type 1 diabetes, Graves' disease (Graves' disease), inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, asthma, dermatitis, fatty liver disease, Crohn's disease (Crohn's disease), cardiovascular disease, inflammatory disease, nervous system disorders, multiple sclerosis, and the like. Acute respiratory distress syndrome and arteriosclerosis.

The present invention relates to compounds of formula (I), and stereoisomers, tautomers, N- oxides, and pharmaceutically acceptable salts thereof that are useful for modulating, preferably inhibiting three-prime repair exonuclease (TREX1). The present invention further relates to compounds of formula (I) for use as a medicament and to pharmaceutical compositions comprising said compounds. Further, the present invention relates to compounds of formula (I) and pharmaceutical compositions comprising said compounds for use in the treatment of cancer, such as breast, small cell lung cancer and colorectal cancer, in particular cancers with chromosomal instability, TREX1-mediated autoimmune diseases, inflammatory myocarditis, Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus (SLE) and retinal vasculopathy with cerebral leukodystrophy (RVCL).

The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for improving systemic lupus erythematosus and a preparation method thereof. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15-30 parts of dry rehmannia, 12-26 parts of calcined turtle shell, 13-25 parts of chicken tendon ginseng, 11-18 parts of red peony root, 10-20 parts of white flower snake tongue grass, 6-18 parts of small rosmarinus officinalis, 4-15 parts of artemisia annua, 5-10 parts of centella asiatica, 4-12 parts of cimicifuga foetida, 3-10 parts of coix seed, 2-9 parts of bergamot slice, and 3-7 parts of raw licorice. Test results show that the traditional Chinese medicine composition for improving systemic lupus erythematosus prepared by the application can inhibit the expression of IL-10 and IL-17 in serum, reduce anti-dsDNA antibodies in serum, significantly improve the clinical symptoms of systemic lupus erythematosus, and has a wide application prospect.

The application provides a method for constructing an animal model of systemic lupus erythematosus, and the animal model of systemic lupus erythematosus shows high autoantibody, low complement, high inflammatory factor and severe kidney damage. The animal model of systemic lupus erythematosus provided by the application has a clear cause, can cause abnormalities of innate immunity and acquired immunity systems, and has a short experimental cycle, thereby providing a new animal model for drug candidate screening, drug treatment effect evaluation and pathogenesis research of systemic lupus erythematosus.

The application discloses a kind of biomarkers for evaluating systemic lupus erythematosus to lupus nephritis progression, prediction model and application, belong to lupus nephritis prediction technical field.The application provides a kind of for evaluating systemic lupus erythematosus to lupus nephritis progression prediction model, the prediction model is according to the ratio of biomarker CD8 / CD4 and the κ / λ ratio of naive B cell, carries out binary Logistic regression analysis, obtains LogitP value, by comparing the high and low of the LogitP value and critical value 0.66938, predicts systemic lupus erythematosus to lupus nephritis progression situation.The prediction model constructed in the application aims to identify the individuals in lupus patients who may develop into lupus nephritis.This innovative model not only provides important guidance in the diagnosis, prognosis prediction and efficacy evaluation of the disease, but also provides a new perspective for the clinical management of lupus nephritis.

The present invention is directed to the use of antiviral agents, in particular valomaciclovir stearate and its polymorph Form A, as well as H2G (omaciclovir) to treat multiple sclerosis in combination with other agents, as well as the use of these agents to treat diseases and conditions such as chronic mononucleosis, long COVID, chronic fatigue syndrome, fibromyalgia, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, Alzheimer's disease, mesial temporal lobe seizures, Epstein-Barr-virus-linked autism, or an Epstein-Barr-virus-linked cancer.

This invention relates to double-stranded oligonucleotides complementary to JAK1 that result in the regulation of JAK1 expression. Regulation of JAK1 expression is beneficial for a range of medical disorders, including inflammatory bowel disease, organ transplant rejection, graft-versus-host disease, multiple sclerosis, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriasis, dermatitis, diabetic nephropathy, systemic lupus erythematosus (SLE), dry eye disease, cancer, myelofibrosis, and asthma. The invention also includes compositions comprising double-stranded oligonucleotides and therapeutic methods using double-stranded oligonucleotides.

The present invention provides an antibody or a conjugated fragment of a citrulline-containing epitope used for the treatment or prevention of diseases associated with the release of extracellular traps from cells, such as neutrophil extracellular trap (NET)-associated pathology (NET-associated pathology) or eosinophil extracellular trap (EET)-associated pathology (EET-associated pathology), and provides a method comprising administering at least one dose of the antibody at a specific concentration. The present invention also provides the method itself. NET-related pathologies include systemic lupus erythematosus (SLE), lupus, sepsis, vasculitis, inflammatory arthritis, rheumatoid arthritis and osteoarthritis, psoriasis, Alzheimer's disease, autoimmune hepatitis, juvenile idiopathic arthritis, myositis (polymyositis and dermatomyositis), Sjögren's disease, antiphospholipid syndrome, Behçet's disease, spondylitis, spondyloarthritis, multiple system atrophy, Parkinson's disease, Lewy body dementia, asthma, allergic rhinovirus exacerbated asthma, allergic asthma, acute respiratory distress syndrome, cystic fibrosis, fibrosis and idiopathic pulmonary fibrosis, heart failure, atherosclerosis, dry eye disease, uveitis, non-granulomatous uveitis, granulomatous uveitis, dermatitis, atopic dermatitis, COPD, bronchitis, or wound healing in diabetes, cancer, cancer metastasis, or wound healing in diabetes, cancer, cancer metastasis, and in This includes other NET-related pathologies, such as the health of transplanted organs in vivo or ex vivo.The present invention also relates to wound healing in SLE, lupus, sepsis, vasculitis, inflammatory arthritis, rheumatoid arthritis and osteoarthritis, psoriasis, Alzheimer's disease, autoimmune hepatitis, juvenile idiopathic arthritis, myositis (polymyositis and dermatomyositis), Sjögren's disease, antiphospholipid antibody syndrome, Behçet's disease, spondylitis, spondyloarthritis, multiple system atrophy, Parkinson's disease, Lewy body dementia asthma, allergic rhinovirus exacerbating asthma, allergic asthma, acute respiratory distress syndrome, cystic fibrosis, fibrosis and idiopathic pulmonary fibrosis, heart failure, atherosclerosis, dry eye disease, uveitis, non-granulomatous uveitis, granulomatous uveitis, dermatitis, atopic dermatitis, COPD, bronchitis, thrombotic disease, cardiovascular disease, or diabetes, cancer, cancer metastasis, or wound healing in diabetes, cancer, cancer metastasis, and in vivo or ex vivo The present invention provides pharmaceutical compositions and methods for treating and preventing NET-related pathologies, including other NET-related pathologies such as the health of transplanted organs in vivo. NET-related pathologies include eosinophilic diseases or conditions of the skin, respiratory eosinophilic diseases or conditions, gastrointestinal eosinophilic diseases or conditions, allergic diseases or conditions, or eosinophilic diseases or conditions such as helminthic, fungal, viral or bacterial infections.

The application provides a trophoblast organ-on-chip system for simulating a maternal-fetal interface of a systemic lupus erythematosus model based on an organ chip and a construction method thereof, the system taking an organ chip as a carrier and comprising three core parts of a trophoblast organ, an endometrial chip and an SLE disease model. The application completes separation culture and characterization of the trophoblast organ, multi-cell co-culture construction and characterization of the endometrial chip, and then constructs a pathological model, and the three parts cooperatively form a three-dimensional maternal-fetal interface. The system can clearly observe the dynamic process of the trophoblast organ invading the endometrial chip, can detect the continuous secretion of hCG and SLE-related inflammatory factors, and breaks through the defects of the prior art model, such as low authenticity, inability to dynamically observe, single detection dimension and lack of standardization, and has both physiological and pathological adhesion and experimental repeatability, can multi-dimensionally characterize the cell phenotype and function of the maternal-fetal interface, and provides an in-vitro research platform for the pathological mechanism research of the SLE pregnancy-related abnormal maternal-fetal interface.

The application relates to application of a reagent for detecting expression levels of a PSIP1 gene or a coded protein LEDGF / p75 in preparation of a product for evaluating systemic lupus erythematosus disease activity, which makes up for the problems of insufficient sensitivity and specificity of existing evaluation indexes; the application also discloses a key role of the PSIP1 gene in a pathogenesis mechanism of systemic lupus erythematosus, and clearly shows the relationship between the PSIP1 gene in T cells and cell cycle arrest, cell aging and abnormal immune function, so as to provide a theoretical basis for target regulation of the PSIP1 to improve T cell function and delay or block disease progression; the application firstly proposes that the expression levels of the PSIP1 / LEDGF / p75 are detected to be used for evaluating systemic lupus erythematosus disease activity, auxiliary diagnosis, prognosis prediction and treatment effect monitoring, so as to provide a brand-new tool and direction for precise diagnosis, activity evaluation, prognosis judgment and future target treatment development of systemic lupus erythematosus.

To provide a compound in the manufacture of a medicament for treating diseases associated with overexpression or abnormal activation of JAK kinase and SYK kinase, including autoimmune diseases such as immune-mediated skin diseases (especially psoriasis, atopic dermatitis and SLE).SOLUTION: Provided is a compound of formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

A compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof is disclosed. The compound inhibits a toll-like receptor (TLR) signaling pathway. A composition containing the compound and uses thereof are disclosed. The novel compound blocks the TNF-α secretion by inhibiting the expression and activation of NF-κB- and MAPK-related proinflammatory genes, and thus can be utilized as a therapeutic agent for many autoimmune diseases, such as systemic lupus erythematosus, psoriasis and psoriatic arthritis, associated with a hyperactivity of a nucleic acid:

The invention discloses an in-vitro biological efficacy evaluation method suitable for evaluating the efficacy of mesenchymal stem cells for treating systemic lupus erythematosus, and relates to the technical field of mesenchymal stem cell detection. The in-vitro biological efficacy evaluation method suitable for evaluating the efficacy of the mesenchymal stem cells for treating systemic lupus erythematosus comprises the following steps: S1, large-scale production of the mesenchymal stem cells; s2, sorting the B cells; s3, activating the cells B; s4, co-culturing the mesenchymal stem cells and the activated B cells, and taking a co-culture group as an experimental group; s5, detecting, analyzing and evaluating: detecting the regulation of the mesenchymal stem cells on the B cells, and analyzing and evaluating statistical data; b cell proliferation is stimulated through in-vitro sorting, the morbidity state of systemic lupus erythematosus (SLE) is simulated, in-vitro biological efficacy is detected through co-culture with mesenchymal stem cells, the method is rapid and simple, and the curative effect of mesenchymal stem cells of different sources can be evaluated.

The present invention includes a method of characterizing disease activity in a systemic lupus erythematosus patient (SEE), comprising: obtaining a dataset associated with a blood, serum, plasma or urine sample from the patient, wherein the dataset comprises data representing the level of one or more biomarkers in the blood, serum, plasma or urine sample from each of (b) to (g); at least one innate serum or plasma mediator biomarker; at least one adaptive serum or plasma mediator; at least one chemokine / adhesion molecule biomarker; at least one soluble TNF superfamily biomarker; the inflammatory mediator biomarker SCF; at least one SLE-associated autoantibody specificity biomarker; and calculating a Lupus Disease Activity Immune.

The invention relates to the technical field of biological medicine, in particular to application of targeted DBC1 in treatment of systemic lupus erythematosus. The application for knocking out or inhibiting the expression of the DBC1 gene as shown in SEQ ID NO.1, or blocking or inhibiting the active function of the DBC1 protein as shown in SEQ ID NO.2 comprises the following applications: 1) inhibiting the transcription of STAT5 and inhibiting the activation of an STAT5 signal channel; 2) the differentiation of Treg cells is promoted, and the differentiation of Tfh and Th2 cells is inhibited; according to the application, DBC1 in DCs is inhibited or knocked out, STAT5 signal activity is lowered, then Treg differentiation is promoted, Tfh and Th2 differentiation is inhibited, and finally the SLE treatment effect is achieved.

Disclosed is a method for treating autoimmune diseases, wherein a therapeutically effective amount of a proteasome inhibitor or a pharmaceutically acceptable salt or pharmaceutical composition thereof is administered to a patient with autoimmune diseases. This method has a certain therapeutic effect on patients with autoimmune diseases, such as systemic lupus erythematosus, lupus nephritis (LN), and autoimmune hepatitis. The proteasome inhibitor or the pharmaceutically acceptable salt or pharmaceutical composition thereof has low toxicity, thereby showing excellent clinical application prospects.

The present invention relates to the use of chimeric antigen receptors (CARs) that bind to the B lymphocyte antigen CD19 (cluster of differentiation 19) and T cells expressing such CARs for the treatment of autoimmune diseases, such as systemic lupus erythematosus (SLE).

The application provides a biomarker for assisting in diagnosing systemic lupus erythematosus and application thereof, proves that 15(S)-HETE has good diagnostic efficiency for systemic lupus erythematosus, and the diagnostic efficiency is improved after 15(S)-HETE is combined with anti-dsDNA antibody or anti-Smith antibody, has good diagnostic efficiency for systemic lupus erythematosus with negative specific autoantibody, and 15(S)-HETE can also reflect the disease activity of systemic lupus erythematosus.

The application discloses a traditional Chinese medicine composition for treating systemic lupus erythematosus (SLE) related pulmonary arterial hypertension and application, and relates to the technical field of traditional Chinese medicine, wherein the composition is prepared from pueraria, gotukola, salvia miltiorrhiza, chuanxiong, radix scrophulariae, poria cocos, wheat bran-fried atractylodes, dried tangerine or orange peel, prepared pinellia, baked licorice, immature bitter orange fruit and gotukola, and has the functions of activating blood circulation to remove blood stasis and clearing heat and resolving toxins, and is aimed at the pathogenesis of the heat-toxin blood stasis syndrome of SLE-PAH. The application further provides a preparation method of the composition. The composition can effectively reduce the pulmonary arterial pressure of a model animal, relieve right ventricular hypertrophy and pulmonary vascular remodeling, and improve the oxidation stress level in experiments. In combination with western medicine, the composition can significantly improve the exercise endurance of a patient, improve the pulmonary arterial systolic pressure and key serological indexes, and has a better curative effect than simple western medicine and good safety, thereby providing a safe and effective traditional Chinese medicine composition for treating SLE-PAH.

Various embodiments of the present application provide binding molecules for B-lymphocyte antigens (e.g., CD19 and CD20), including antigen recognizing receptors (e.g., CARs) that target B-lymphocyte antigens (e.g., CD19 and CD20). Embodiments of the present application also provide cells expressing such binding molecules, therapeutic compositions comprising such cells, and methods for treating diseases or disorders associated with B-lymphocyte antigens (e.g., CD19 and CD20), including hematological cancers, autoimmune diseases (e.g., multiple sclerosis and systemic lupus erythematosus).

The invention discloses a systemic lupus erythematosus subtype identification method based on adaptive clustering, and the method comprises the steps: collecting related data of a new systemic lupus erythematosus user, and forming an original sample data set; missing value elimination, abnormal value processing and Z-score standardization processing are carried out on the original sample data; performing data enhancement on the minority class sample data by adopting an SMOTE algorithm; saliency features are screened through T test and chi-square test, the weight of each variable is calculated in combination with a logistic regression model, and a key feature set is constructed; calculating the similarity between samples based on a Power distance matrix, and determining an optimal neighborhood parameter by using a DBSCAN algorithm; an adaptive hierarchical clustering algorithm is introduced, an optimal clustering segmentation point is automatically determined by dynamically adjusting a clustering threshold value and maximizing a contour coefficient, and subtype division is carried out; and carrying out dimension reduction visualization on the clustering result by utilizing a principal component analysis method, and carrying out evaluation. According to the invention, the clustering robustness and clinical interpretability are improved through an adaptive algorithm.

Methods for characterizing disease activity in a systemic lupus erythematosus (SLE) patient. Methods include obtaining a blood, serum, plasma, or urine sample from the patient; assessing the sample for expression of a biomarker selected from the group consisting of IFN-α, IL-10, BLyS, IL-7, IFN-γ, TRAIL, IL-15, IP-10 / CXCL10, and IL-4; assessing the sample for expression of an inflammatory mediator selected from the group consisting of TNFRII, Resistin, and Osteopontin (OPN); assessing the sample for an SLE-associated autoantibody specificity biomarker selected from the group consisting of dsDNA, chromatin, RiboP, Ro / SSA, La / SSB, Sm, SmRNP, and RNP; and calculating a Lupus Disease Activity (Immune) Index (LDAII / L-DAI) score. The LDAII / L-DAI score may distinguish between active and low lupus disease activity. Methods of treatment are also provided including administering a treatment prior to reaching clinical disease classification after determining that the patient has the prognosis for transitioning to classified SLE.

The present invention relates to a method for identifying a compound that modulates the C-terminal Src kinase (Csk) by modulating at least one of the following features: the expression, amount, stability, biological activity of the Csk protein, and / or the interaction of the Csk protein with the lymphocyte-specific tyrosine kinase (Lck) protein in a mammalian cell. The identified compound is particularly suitable for use in the prevention or treatment of an autoimmune disease, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), multiple sclerosis (MS), and type 1 diabetes (T1D), or an infection, such as a bacterial or viral infection, cancer, cardiovascular diseases, age-related diseases, and preferably for use in increasing cellular immunity against cancer cells.Further aspects of the invention relate to a screening method for screening for a compound and / or a pharmaceutical composition comprising the compound.

The application discloses an amide compound containing a pyrimidine structure and application thereof in preparation of a TYK2 JH2 kinase inhibitor, and relates to the technical field of compound preparation.The application provides an amide compound containing a pyrimidine structure, which can effectively block IL-12 / IL-23 and type I interferon signaling pathways by inhibiting TYK2 JH2 kinase activity with high selectivity, and significantly improve the pathological process of autoimmune diseases (such as psoriasis, colitis, systemic lupus erythematosus and the like); the compound has the advantages of low toxic side effect and high targeting, can precisely regulate abnormal immune response, and can provide various dosage forms (tablets, capsules, injection agents and the like), support oral or injection administration, and has both curative effect and medication convenience, and therefore provides a safe and efficient novel drug scheme for autoimmune disease treatment.

The invention provides certain tetrahydropyran-imidazotriazine compounds of formula I or II as IL-17A inhibitors, pharmaceutical compositions thereof, and methods of using a compound of formula I or II to treat psoriasis, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, psoriatic arthritis, axial spondyloarthritis, ankylosing spondylitis, hidradenitis suppurativa, systemic lupus erythematosus, palmoplantar pustulosis (PPP), atopic dermatitis, asthma, non-infectious uveitis, or COPD.

Recent studies indicate that sIL7R is involved in the development of autoimmune diseases. The present invention provides methods and compositions for a novel antibody therapeutic against the soluble isoform of the interleukin 7 receptor (sIL7R), a potent driver of self-destructive immune responses that cause autoimmune diseases including multiple sclerosis, lupus nephritis, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, and many other autoimmune diseases. The present invention includes antibodies specific for sIL7R that inhibit SIL7R, a driver of autoimmunity, without inhibiting mIL7R, thereby reducing the severity of or preventing autoimmunity without activating immunosuppressive mechanisms.

The invention relates to application of a reagent for detecting the expression level of a PSIP1 gene or an encoded protein LEDGF / p75 of the PSIP1 gene to preparation of a product for evaluating the activity of systemic lupus erythematosus disease. The problem that an existing evaluation index is insufficient in sensitivity and specificity is solved. The invention also discloses a key effect of the PSIP1 gene in the pathogenesis of systemic lupus erythematosus, the relationship between reduction of the PSIP1 gene in T cells and cell cycle arrest, cell senescence and immune function abnormality is defined, and a theoretical basis is provided for targeted regulation and control of the PSIP1 to improve the functions of the T cells and delay or block disease progression; according to the invention, it is proposed for the first time that detection of the expression level of PSIP1 / LEDGF / p75 is used for evaluating the disease activity of systemic lupus erythematosus, assisting in diagnosis, predicting prognosis and monitoring the treatment effect, and a brand new tool and direction are provided for precise diagnosis, activity evaluation, prognosis judgment and future targeted treatment development of systemic lupus erythematosus.