31 results about "Renal inflammation" patented technology

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 application provides a preparation of a sema7A monoclonal antibody 8A12 and a treatment effect of the sema7A monoclonal antibody 8A12 on lupus nephritis, wherein the CDR-H1 of the heavy chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 1, the CDR-H2 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 2, and the CDR-H3 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 3; the CDR-L1 of the light chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 4, the CDR-L2 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 5, and the CDR-L3 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 6. The monoclonal antibody 8A12 can effectively inhibit the expression up-regulation of IL-1beta, TNF-alpha and IL-6 caused by Sema7A recombinant protein, can effectively inhibit the macrophage inflammatory response induced by Sema7A, and can continuously and effectively reduce serum anti-double-stranded DNA antibodies and kidney damage of lupus mice. The monoclonal antibody 8A12 can be used for preparing a pharmaceutical composition for preventing and / or treating systemic lupus erythematosus and / or lupus nephritis thereof.

[0366] Compounds of Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the cGAS pathway, such as autoimmune disorders including Aicardi-Goutieres Syndrome (AGS), Systemic Lupus Erythematosus (SLE), Lupus Nephritis, Scleroderma, Sjogren's Syndrome, Inflammatory Myopathies, Hidradenitis Supperativa (HS), Parkinson's Disease, Rheumatoid Arthritis, Ulcerative Colitis and Crohn's Disease, formula (II) wherein Ra, (A), R1 and R2, are defined herein.

An object of the present invention is to provide a method capable of detecting whether a subject has systemic lupus erythematosus (preferably nephrotic syndrome) with high accuracy without performing a renal biopsy, a biomarker for carrying out such detection, and the like. The concentration of 3′,4′-didehydro-3′-deoxycytidine in urine collected from a test subject is measured, and this concentration is compared with a reference concentration for control, which allows to detect whether the above-mentioned test subject has systemic lupus erythematosus (preferably lupus nephritis) with high accuracy.

The present invention relates to: a novel method for preparing a heterocyclic derivative compound of chemical formula I below; a novel intermediate compound used in the preparation method; a composition for treatment or prevention of hyperuricacidemia, gout, nephritis, chronic renal insufficiency, nephrolith, uremia, urolithiasis, or a uric acid-related disease, the composition containing the compound of chemical formula I at a dose of more than 2 mg and equal to or less than 10 mg and being orally administered once a day; and a hydrochloride 1.5 hydrate of the novel compound of chemical formula I.

This invention relates to the field of biomedical technology, and particularly to the application of crotonin A in the preparation of drugs for treating IgA nephropathy. Pharmacodynamic experiments conducted in vivo on a Thy1 rat model showed that crotonin A effectively reduced 24-hour urinary protein and the urinary protein-to-creatinine ratio in an IgA nephropathy model—an anti-Thy1 rat nephritis model—and inhibited the expression of mRNAs of genes related to renal cortical inflammation, proliferation, and fibrosis, including Cyclin E, α-SMA, FN, CCL2, NF-κB, and IL-6, further improving renal pathology. In in vitro cell models, crotonin A inhibited the proliferation of rat mesangial cells and suppressed the expression of mRNAs of TGF-β, Cyclin E, α-SMA, CCL2, NF-κB, and IL-6, indicating that crotonin A has significant anti-inflammatory, anti-cell proliferation, and anti-fibrotic effects. Brucella oleracea has considerable therapeutic potential, providing a potential new drug option for the clinical prevention and treatment of IgA nephropathy, and is of great significance for the development of safe and effective drugs for the treatment of IgA nephropathy.

The invention relates to the technical field of medicines, in particular to application of ginsenoside in preparation of medicines for improving kidney inflammation and enhancing uric acid excretion. It is found for the first time that ginsenoside Rg2 can reduce systematic and kidney inflammatory reactions by reducing expression levels of inflammatory factors LPS, TNF-alpha and IL-1beta; by down-regulating the expression level of fibrosis marker molecules alpha-SMA and Smad3, the effect of improving HUA-related kidney inflammation and fibrosis is achieved; by up-regulating the expression levels of uric acid transporters OAT1, OAT3 and ABCG2, the active transport and excretion ability of the kidney to uric acid is enhanced. The discovery can generate great influence on research and treatment of relieving hyperuricemia, and has clinical practical value.

The invention relates to a method and a kit for diagnosing systemic lupus erythematosus. Specifically, the invention provides a reagent for detecting tryptophan in a blood-derived sample or a reagent for detecting tryptophan in a blood-derived sample and a tryptophan standard substance, and application of the reagent and the tryptophan standard substance in preparation of a kit, the kit is used for diagnosing the systemic lupus erythematosus and / or identifying the disease activity of a patient with the systemic lupus erythematosus and / or identifying the kidney fatigue degree of the patient with the systemic lupus erythematosus and / or judging the prognosis of the lupus nephritis. The method is simple and rapid, results are accurate, the SLE patient can be diagnosed in real time, and the disease activity, kidney fatigue degree and lupus nephritis prognosis of the SLE patient can be judged in an assisted mode.

The invention discloses an application of a CD177 targeted membrane modified liposome in preparation of a medicine for preventing and / or treating systemic lupus erythematosus. The structure of the CD177 targeting membrane modified lipidosome is divided into three layers, and comprises a lipidosome loaded with a PADI4 inhibitor, a targeting recognition layer formed by coupling CD177 targeting peptide on the surface of the lipidosome, and a bionic functional layer formed by coating a natural neutrophile granulocyte membrane on the outermost layer. In an imiquimod (IMQ)-induced lupus model, the medicine treatment shows strong disease remission capability: 1) improving the whole body phenotype: obviously reducing the swollen spleen and lymph node of lupus mice; 2) repairing kidney functions: significantly relieving glomerulonephritis, and reducing inflammatory cell infiltration and IgG and complement C3 deposition in glomerulus, and 3) significantly reducing the level of proinflammatory cytokines in serum and the titer of a lupus marker anti-dsDNA antibody.

The application discloses application of a CK2 inhibitor CX4945 in preparation of a medicine for preventing and / or treating lupus nephritis, and provides the CK2 inhibitor CX4945 which can significantly reduce kidney immune complex and complement C3 deposition of a lupus animal model, effectively reduce a urine protein / cratin ratio, and has no obvious side effect, and can be prepared into a lupus immunotherapy medicine, and simultaneously provides a new combined treatment mode. The medicine can be prepared into an oral medicine, is convenient for treatment, and has high patient compliance.

Provided is use of a complement factor B inhibitor in the preparation of a drug for treating or preventing IgA nephropathy or a disease or condition related thereto. Specifically, provided is use of a compound represented by formula I or a pharmaceutically acceptable salt thereof or a hydrate thereof in the preparation of a drug for treating or preventing IgA nephropathy or a disease or condition related thereto. The drug can effectively reduce creatinine and urea nitrogen levels in patients with IgA nephropathy, reduce renal inflammation and / or fibrosis in patients with IgA nephropathy, and provide a novel, effective and safe option for the treatment of IgA nephropathy.

The present invention relates to: a novel method for preparing a heterocyclic derivative compound of chemical formula I below; a novel intermediate compound used in the preparation method; a composition for treatment or prevention of hyperuricacidemia, gout, nephritis, chronic renal insufficiency, nephrolith, uremia, urolithiasis, or a uric acid-related disease, the composition containing the compound of chemical formula I at a dose of more than 2 mg and equal to or less than 10 mg and being orally administered once a day; and a hydrochloride 1.5 hydrate of the novel compound of chemical formula I.

Provided are compounds of Formula (I):The compounds target the lanthionine synthetase C-like (LANCL) family of proteins, including LANCL2 and LANCL3. The compounds can be used to treat conditions such as inflammatory diseases, metabolic diseases, autoimmune diseases, cancers, and infectious diseases. Exemplary conditions include inflammatory conditions of the liver, such as nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and cirrhosis; inflammatory conditions of the bile duct, such as primary biliary cholangitis, primary sclerosing cholangitis; inflammatory bowel disease, such as Crohn's disease and ulcerative colitis; lupus, such as systemic lupus erythematosus, lupus nephritis, and cutaneous lupus; arthritis, such as rheumatoid arthritis; hyperglycemia, such as type 1 diabetes, type 2 diabetes, and prediabetes and associated conditions such as atherosclerosis and diabetic kidney disease; psoriasis; and multiple sclerosis.

Disclosed are methods for managing a treatment in an adult individual having systemic lupus erythematosus (SLE) undergoing therapy for lupus nephritis. In aspects, the method comprises detecting a level of each of neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), monocyte chemotactic protein 1 (MCP-1), adiponectin, hemopexin, and ceruloplasmin in a urine sample obtained from the individual, the levels of which are used to determine a score at a first time point and a second time point. Whether the individual is responding to the therapy, in particular an induction phase of a therapy, is determined based on a comparison of the first and second score. The therapy may then be continued or adjusted based on that determination.

This disclosure relates to compounds of formula (I-1) or (I-2): This relates to TIFF2026513962000575.tif74102. The compounds of this disclosure can inhibit the activity of tyrosine kinase 2 (TYK2), for example, in inflammation, autoimmune diseases, neuroinflammation, arthritis, rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, lupus nephritis, arthritis, osteoarthritis, gouty arthritis, pain, fever, pulmonary sarcoidosis, silicosis, cardiovascular disease, atherosclerosis, myocardial infarction, thrombosis, congestive heart failure and cardiac reperfusion injury, cardiomyopathy, stroke, ischemia, reperfusion injury, cerebral edema, head trauma, neurodegeneration, liver disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, nephritis, retina It is useful in treating diseases or disorders such as inflammation, retinopathy, macular degeneration, glaucoma, diabetes (type 1 and type 2), diabetic neuropathy, viral and bacterial infections, myalgia, endotoxin shock, toxic shock syndrome, autoimmune diseases, osteoporosis, multiple sclerosis, endometriosis, menstrual pain, vaginitis, candidiasis, cancer, fibrosis, obesity, muscular dystrophy, polymyositis, dermatomyositis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, vitiligo, alopecia, Alzheimer's disease, skin flushing, eczema, psoriasis, atopic dermatitis, and sunburn. This disclosure further provides a method for preparing the compound.

Loss of B cell tolerance and generation of autoreactive anti-nuclear antibodies are hallmarks of systemic lupus erythematosus (SLE) and lupus nephritis. Lupus nephritis is characterized by glomerular and tubulointerstitial inflammation often initiated by the renal glomerular deposition of anti-nuclear immune complexes which trigger subsequent activation of complement, macrophages / monocytes and other innate inflammatory cells. The mechanism of anti-nuclear immunoglobulin accumulation and clearance in lupus nephritis pathogenesis remains largely uncharacterized. Here, we show that innate immune activation in the NZB / W F1 mouse model and in human lupus nephritis biopsies rapidly reduces DNase1 expression in renal cortex proximal tubular cells. To overcome the loss of endogenous DNase1, we treated lupus-prone mice with a hyperactive actin resistant variant of DNase1 with improved catalytic activity against nucleic acid-IgG immune complexes and acceptable in vivo pharmacokinetics. Hyperactive DNase1-Fc fusion protein ameliorates nephritis in a murine model of lupus nephritis and reduces immune complex deposition / complement fixation. Taken together, our data suggest that the loss of renal DNase1 through TLR signaling or other innate immune activation impairs clearance of autoreactive anti-nuclear immune complex deposits in the kidney to promote nephritis progression. Our findings provide a therapeutic rationale for using an engineered DNase1-Fc as a potential therapeutic approach in lupus nephritis.

The application relates to the field of biological medicine, and specifically discloses a high-affinity T cell receptor for recognizing Smith antigen peptide and application thereof. The T cell receptor comprises a TCR alpha chain and a beta chain variable domain with specific sequences, the variable domain contains specific CDR3 sequences for targeting a Smith antigen peptide-RVLGLVLLRGENLVS-HLA-DRB115:01 complex, and a specific site cysteine mutation is introduced into the constant region of the alpha chain and the beta chain, so that the KD value of the target complex can reach the nanomolar level. A bispecific complex and a pharmaceutical composition based on the T cell receptor can be used for preparing a drug for treating systemic lupus erythematosus or lupus nephritis, and have the advantages of high target recognition specificity, high binding affinity and good structural stability; the matching preparation method steps are controllable and reproducible, can be adapted to large-scale production, and provide a new molecular tool for precise treatment of related autoimmune diseases.

The invention provides an application of an euphorbia nigra extract and an active component thereof in preparing a medicine for treating chronic nephropathy, which is characterized in that an adriamycin-induced chronic nephropathy rat model and a lipopolysaccharide (LPS), hydrogen peroxide (H2O2) and transforming growth factor-beta1 (TGF-beta1) induced HK-2 cell model are used as evaluation means; materials capable of remarkably treating kidney inflammation, oxidative stress and fibrosis are separated and identified from a chronic kidney disease treatment extract of beetle. From the aspects of regulating and controlling inflammation homeostasis, oxidative stress and fibrosis, inhibiting PI3K-Akt, MAPK and HIF-1 signal channels and the like, the effect and the action mechanism of the diving beetle extract and the 6-(3, 4-dihydroxyphenyl)-2, 3-naphthalenediol on treating the chronic kidney disease are elaborated, and the diving beetle extract and the 6-(3, 4-dihydroxyphenyl)-2, 3-naphthalenediol can be used as a chronic kidney disease treatment medicine and a related signal channel regulator.

The invention provides a radiolabeled single-stranded DNA probe suitable for early noninvasive diagnosis of lupus nephritis, and belongs to the technical field of detection of systemic lupus erythematosus. The preparation method comprises the following steps: (1) mixing eluted < 68 > GaCl3 and NOTA-A20, reacting, and purifying, so as to obtain < 68 > Ga-A20; and (2) adding the 68Ga-A20 obtained in the step (1) into a buffer solution containing T20 and ssDNA, and carrying out hybridization, so as to obtain the radiolabeled single-stranded DNA probe [68Ga] Ga-NOTA-ssDNA. The radiolabeled single-stranded DNA probe has good kidney targeting and imaging effects in early diagnosis of LN, is expected to provide a safe and accurate non-invasive visual examination means for early diagnosis of LN, and has a good clinical application prospect.

Provided are oligonucleotides, polynucleotide conjugates, and compositions and populations comprising the same, as well as methods and uses thereof for reducing the amount or activity of Rho guanine nucleotide exchange factor 6 (ARHGEF6) RNA in a cell or animal, and in certain instances reducing the amount of ARHGEF6 protein in a cell or animal Such oligonucleotides, polynucleotide conjugates, and compositions and populations, methods and uses are useful to treat kidney diseases or conditions. In particular, such oligonucleotides, polynucleotide conjugates, and compositions and populations, methods and uses are useful to treat chronic kidney disease, such as diabetic nephropathy (DN), focal segmental glomerulosclerosis (FSGS), renal hypertension (HTN), IgA nephropathy / Berger's disease (IgAN), rapidly progressive glomerulonephritis (RPGN) and systemic lupus erythematosus (SLE).

This invention relates to the fields of regenerative medicine, disease models, and drug screening, and particularly to a high-throughput method and application for constructing human kidney organoids that simulate the pathological characteristics of lupus nephritis. The kidney organoids are mixed and cultured with plasma from lupus nephritis patients in low-adsorption multi-well plates. This invention utilizes a standardized process to prepare human kidney organoids in high throughput, and then stimulates them with plasma from lupus nephritis patients, thereby rapidly and in large quantities constructing disease models in vitro that simulate the severity of individual patients' diseases and reproduce key pathological features (such as podocyte damage and inflammatory fibrosis). This platform provides a closed-loop research tool for lupus nephritis research, from "clinical samples" to "in vitro models" and then to "clinical validation."

The present disclosure belongs to the technical field of biological medicine, and particularly relates to the application of finerenone in the preparation of a drug for treating hypertensive renal injury. The present disclosure provides the application of finerenone in the preparation of a drug for preventing and / or treating hypertensive renal injury, specifically, by using a deoxycorticosterone acetate-salt-induced hypertensive mouse model and a primary mouse renal tubular epithelial cell-bone marrow-derived macrophage co-culture model, it is first revealed that aldosterone and salt corticosteroid receptor signals mediate cell-to-cell communication by promoting PANX1-dependent ATP release in renal tubular epithelial cells, and then activate macrophage P2X7, activate NLRP3-mediated macrophage pyroptosis, and aggravate the molecular mechanism of aldosterone-driven renal inflammation and fibrosis. The present disclosure also provides the application of a substance targeting a PANX1 / extracellular ATP / P2X7 signal axis in the preparation of a drug for preventing and / or treating hypertensive renal injury.

The invention discloses application of dehydrocorydaline in preparation of a helper T cell 17 cell differentiation inhibitor and a medicine for treating systemic lupus erythematosus or nephritis, and relates to the field of medicines for treating immune diseases. The research finds that dehydrocorydaline can be directly combined with mTOR and STAT3 so as to inhibit expression of Th17 differentiation key protein RORc in T cells, so that a Th17 related differentiation pathway is inhibited, and systemic lupus erythematosus and lupus nephritis are treated. When the dehydrocorydaline is clinically applied to SLE or LN treatment, after dehydrocorydaline treatment, the proportion and number of Th17 cells in the spleen and kidney can be reduced, kidney injury can be relieved, the kidney function can be recovered, meanwhile, hypertension and thrombus events can be improved and prevented, development of lupus nephritis can be prevented and intervened in the early stage, and the dehydrocorydaline has a good clinical application prospect. A new method is provided for precisely treating lupus kidney injury caused by autoimmunity, and a new treatment means is supplemented for long-term treatment of lupus nephritis in the prior art.

Disclosed are antagonists of PC3-secreted microprotein (PSMP) and use of the antagonists for treatment of liver, lung, or kidney fibrosis, including various diseases or disorders associated with liver, lung, or kidney fibrosis such as, e.g., non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), drug-induced lung injury, acute kidney injury (AKI), chronic kidney disease (CKD), lupus nephritis, IgA nephropathy, and membranous glomerulonephritis. Also disclosed are PSMP antagonists and their use for treatment of graft-versus-host disease (GVHD) and systemic lupus erythematosus (SLE). Suitable PSMP antagonists for use in disease treatment include PSMP-binding proteins such as, for example, neutralizing anti-PSMP antibodies.

The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. The compounds act as antagonists of the toll-like receptors TLR7, TLR8 and / or TLR9 and are thus useful in the treatment of systemic lupus erythematosus (SLE) and lupus nephritis.

Methods for treating systemic lupus erythematosus using compounds or pharmaceutical compositions that modulate the activity of Bcl-2 family proteins are disclosed. In some methods, the patient to be treated is diagnosed with lupus nephritis. In some methods, the compound or pharmaceutical composition is administered to the patient in need thereof at a therapeutically effective dose sufficient to elicit one or more effects selected from: reduced excretion of protein in the urine of the patient, reduced serum anti-dsDNA autoantibody levels in the patient, reduced skin lesion severity in the patient, reduced lymphadenopathy severity in the patient, reduced glomerulonephritis severity in the patient, reduced vasculitis severity in the patient, reduced lymphocyte cell counts in a peripheral blood mononuclear cell (PMBC) panel taken from the patient, reduced lymphocyte cell counts in the spleen of the patient, and reduced lymphocyte infiltration of the kidneys of the patient.

The invention discloses an application of a CK2 inhibitor CX4945 in preparation of a medicine for preventing and / or treating lupus nephritis. The CK2 inhibitor CX4945 provided by the invention can significantly reduce the deposition of immune complex and complement C3 in the kidney of a lupus animal model, and effectively reduce the ratio of urine protein / creatinine. And the medicine has no obvious side effect, can be prepared into a lupus immunotherapy medicine, and provides a new combined treatment mode. The medicine can be prepared into an oral medicine, treatment is convenient, and patient compliance is high.

To provide PSMP antagonists for use in treatment of fibrosis disease in lung, kidney or liver.SOLUTION: Disclosed are antagonists of PC3-secreted microprotein (PSMP) and use of the antagonists for treatment of liver, lung or kidney fibrosis, including various diseases or disorders associated with liver, lung or kidney fibrosis, e.g., non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), drug-induced lung injury, acute kidney injury (AKI), chronic kidney disease (CKD), lupus nephritis, IgA nephropathy, and membranous glomerulonephritis. Also disclosed are PSMP antagonists and use thereof for treatment of graft-versus-host disease (GVHD) and systemic lupus erythematosus (SLE).SELECTED DRAWING: None

Compounds of Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the cGAS pathway, such as autoimmune disorders including Aicardi-Goutieres Syndrome (AGS), Systemic Lupus Erythematosus (SLE), Lupus Nephritis, Scleroderma, Sjogren's Syndrome, Inflammatory Myopathies, Hidradenitis Supperativa (HS), Parkinson's Disease, Rheumatoid Arthritis, Ulcerative Colitis and Crohn's Disease,wherein Ra, {circle around (A)}, R1 and R2, are defined herein.

Provided herein are methods of treating focal segmental glomerulosclerosis (FSGS), comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to a subject in need thereof. Also provided herein are methods of decreasing renal inflammation and / or fibrosis, reducing the rate of decline in eGFR, delaying the onset of ESKD, decreasing proteinuria, and decreasing fatigue in a subject having FSGS, comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to the subject.