177 results about "Kidney Glomerulus" patented technology

The invention provides application of AQP1 protein as a target spot in preparation of a diagnostic reagent and a therapeutic drug for hypoglycaemia nephropathy, and belongs to the technical field of biological medicines.The AQP1 protein is used as the target spot, AQP1 protein expression is reduced by adopting an inhibitor, and the hypoglycaemia nephropathy is obtained. According to the present invention, with the application of the kit, the effects of reducing the renal tubule injury markers in the urine, reducing the glomerular filtration rate or relieving the kidney tissue hypoxia can be achieved, the new idea is provided for the early prevention and treatment of the diabetic nephropathy (DKD), and the early recognition and the effective treatment of the kidney injury of the diabetic patient can be well achieved.

The application discloses a fusion protein NGF2 with improved in-vivo half-life and application thereof, and belongs to the technical field of medical biological engineering, and comprises ABD and FGF2, and the gene and protein sequence thereof are respectively composed of the sequences shown in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7, and the complete gene and protein sequence thereof is shown in SEQ ID NO:4 and SEQ ID NO:8. The fusion protein NGF2 can keep activity for more than 7 days in an environment of 37 DEG C, and the half-life of the fusion protein in solution is prolonged. In addition, the ABD is combined with HAS to form a complex, and the total molecular weight reaches 90kDa, which is higher than the cut-off molecular weight of glomerular filtration, so that the in-vivo half-life of the fusion protein is effectively prolonged.

The invention provides a glomerular crescent lesion multi-task semantic segmentation and classification system, which relates to the technical field of medical image processing and comprises an input module, an encoder module, a decoder module, a boundary branch module, a main output module and a processing module. The input module is used for receiving images; the encoder module adopts a symmetric topological structure and is used for carrying out multi-stage down-sampling operation on an input image and outputting feature maps of different scales; the decoder module is used for fusing the feature maps from the corresponding stages of the encoder and carrying out up-sampling step by step; the boundary branch module is connected behind the lowest layer output feature at the tail end of the decoder; the main output module is located at the tail end of the decoder; and the processing module is used for calculating a composite loss function and performing back propagation to update parameters of the encoder module, the decoder module and the boundary branch module, and is used for outputting a final segmentation and classification result of the lesion region of the crescent body. The system provided by the invention can realize accurate segmentation and category prediction of the lesion area of the crescent body.

The present application relates to a kind of pharmaceutical composition for treating type 2 diabetes and its application.The pharmaceutical composition includes icariin, hydroxymethyl coumarin and cinnamaldehyde, by three-component synergistic effect, simultaneously act on insulin resistance, pancreatic beta cell apoptosis and systemic metabolic inflammation three type 2 diabetes core pathological links, auxiliary reduce serum lipid level, and reduce drug-related liver injury risk, good safety.Animal experiment results show that three-drug combination group can effectively reduce blood sugar (decrease about 50%), significantly improve islet structure atrophy, restore hepatocyte index arrangement, reduce glomerular hypertrophy, significantly reduce serum TG and CHOL level (P<0.05) and inflammatory factor IL-6 and TNF-alpha level (P<0.05), and avoid the hepatotoxicity risk (ALT / AST restores to close to normal level) of hydroxymethyl coumarin.The present application is composed of three kinds of natural monomers with clear structure, and has clear components and controllable quality, which provides a more optimal comprehensive treatment strategy for the treatment of type 2 diabetes and its complications.

Disclosed herein is a method for treating immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) with the factor B inhibitor iptacopan or a pharmaceutically acceptable salt thereof (e.g., iptacopan hydrochloride).

This invention relates to the fields of biomedical technology and biological model construction technology, and discloses an ANCA-associated vasculitis glomerular endothelial cell injury model, its construction method and application, and the application of BACH1 inhibitors. The method includes: (1) activating neutrophils sequentially with tumor necrosis factor α and immunoglobulin G to obtain a culture medium containing activated neutrophils; wherein the immunoglobulin G is immunoglobulin G isolated and purified from the plasma of patients with ANCA-associated vasculitis; (2) co-culturing the culture medium containing activated neutrophils with human glomerular endothelial cells to obtain the cell injury model. The cell injury model provided by this invention can verify the role of neutrophil adhesion characteristics in endothelial cell injury, and at the same time, the cell injury model can better simulate the immune microenvironment of ANCA-associated vasculitis glomerular endothelial cells in vivo.

A phosphodiesterase type 5 inhibitor is used in the preparation of a medicament for resisting fibrotic diseases. Experiments in animal models of ischemia-reperfusion (UIRI)-induced renal fibrosis, unilateral ureteral obstruction (UUO)-caused kidney fibrosis and idiopathic pulmonary fibrosis show that a PDE5 inhibitor such as tadalafil, sildenafil and vardenafil can significantly inhibit the expression of multiple fibrosis iconic proteins such as fibronectin, collagen I, renal injury molecule-1, and α-skeletal muscle actin in UIRI and UUO renal fibrosis lesions, improves glomerulopathy, degree of renal tubular distension, renal interstitial collagen fiber deposition and inflammatory cell infiltration, reduces the fibrotic area within the lesion, and significantly inhibits the progression of renal fibrosis; and the PDE5 inhibitor can significantly improve smooth muscle proliferation and inflammatory cell infiltration in bronchioles and pulmonary arterioles of idiopathic pulmonary fibrosis lesion, improve damage condition of alveolar tissue, and significantly inhibit the progression of pulmonary fibrosis.

The application discloses a marker for determining the severity of IgAN kidney tissue lesions and application thereof, and inventors find that ACTN4, ACADS and COL1A1 are significantly differentially expressed proteins in kidney tissues. The significant down-regulation of ACTN4 may cause the change of actin cytoskeleton of IgAN glomerular podocytes; the significant down-regulation of ACAD may indirectly participate in the occurrence process of abnormal structure and function of IgAN renal tubular epithelial cells by affecting fatty acid metabolism in the cells; and the significant up-regulation of COL1A1 may participate in the accumulation of extracellular matrix in the renal interstitium of IgAN, and play a certain role in promoting the renal interstitial fibrosis. The combination of ACTN4, ACADS and COL1A1 has good prediction efficiency for the diagnosis of the severity of IgAN kidney tissue lesions, and the area under the ROC curve is 0.815, P 0.043. In addition, the immunohistochemical results also confirm the expression trend of the three proteins ACTN4, ACADS and COL1A1 in the corresponding kidney tissue substructures in proteomics.

The present disclosure is directed to method of generating human glomeruli endothelial cells (HGECs) from human endothelial cells (ECs), comprising expressing in human ECs an exogenous nucleic acid encoding a T-box transcription factor 3 (Tbx3), alone or in combination with one or more of PR domain zinc finger protein 1 (Prdm1), GATA Binding Protein 5 (Gata5) and Pre-B-Cell Leukemia Transcription Factor 1 (Pbx1). Disclosed also are HGECs produced by the methods of the instant disclosure, as well as methods for using the same.

In an illustrative embodiment, systems and methods for treating kidney disease in a human patient are disclosed. A method includes advancing a collapsible array of RF electrodes through a urinary tract of the patient in collapsed form and into a position in or near a renal pelvis. The effector is deployed to an expanded form to engage at least a portion of an interior wall of the renal pelvis. RF energy delivered through the array of electrodes target afferent nerves proximate the interior wall of the renal pelvis to inhibit or destroy their function. eGFR of the patient can be raised after treatment according to the method.

Described herein are methods of treating immune complex mediated membrane proliferative glomerulonephritis (IC-MPGN) with a factor B inhibitor ipropam or a pharmaceutically acceptable salt thereof, e.g., ipropam hydrochloride.

The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here the inventors show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions. Accordingly, CD9 represents a reliable biomarker and as well as a biotargets in glomerulonephritides.

The present application provides a method for treating a complement-mediated disease in a human individual, the method comprising administering to the individual an effective amount of a fusion protein comprising: i) an antibody portion that specifically binds to human C5; and ii) factor H (FH) or a functional fragment thereof. The complement-mediated disease can be, for example, paroxysmal nocturnal hemoglobinuria (PNH) syndrome, C3 glomerulopathy (C3G), IgA nephropathy (IgAN), and thrombotic microangiopathy secondary to systemic lupus erythematosus (SLE-TMA).

Verdazil derivative compounds and compositions thereof, useful as contrast agents for biomedical imaging, are provided. The compounds and compositions of this disclosure can be used, for example, for quantitative and / or qualitative assessment of glomerular filtration rate (GFR) in subjects, providing a reliable and rapid assessment of renal function.

The present invention relates to an artificial intelligence model and an implementation method therefor, which are capable of selecting and extracting, from CT images of patients with IgA nephropathy, image features significant for prognostic prediction and applying same to a machine learning model to thereby predict, with high accuracy, the likelihood of the patients with IgA nephropathy progressing to end-stage renal failure within five years. The present invention provides a prognostic prediction model that rapidly predicts the prognosis of a patient without an invasive kidney biopsy, overcomes the limitations of conventional pathology diagnosis relying on invasive methods, and enables periodic prognostic evaluation with significantly improved reliability. In addition, the present invention is capable of precisely reflecting characteristics of each item and accurately predicting a clinical course of a patient, by combining various feature selection methods and binary classifiers for each item of mesangial hypercellularity (M), endothelial hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy / interstitial fibrosis (T), which constitute a MEST score.

This disclosure relates to RNAi agents capable of inhibiting complement factor B (CFB) gene expression. Pharmaceutical compositions containing CFB RNAi agents and methods of use thereof are also disclosed. The CFB RNAi agents disclosed herein may be conjugated to a targeted ligand containing an N-acetyl-galactosamine ligand to facilitate in vivo delivery to hepatocytes. RNAi agents can be used in methods of treating diseases, disorders, or conditions partially mediated by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membrane proliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), anti-glomerular basement membrane antibody disease (anti-GBM), ischemia-reperfusion injury and T-cell-mediated rejection in kidney transplantation (TCMR), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD) including early and / or intermediate-stage AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated disorders.

The invention discloses a prediction model of a glomerular filtration rate after cardio-pulmonary resuscitation, a construction method and application thereof. The method comprises the following steps: collecting and preprocessing sample data; determining an independent variable, a dependent variable and an end variable; screening independent influence factors, and evaluating a relationship between the independent influence factors based on a variance expansion factor; constructing a column graph prediction model based on the independent influence factors; performing accuracy evaluation on the prediction model based on the accuracy and the mean absolute error; performing calibration degree analysis on the prediction model through a calibration curve, Bland-Altman consistency evaluation and pairing T test; evaluating the prediction efficiency of the prediction model through an ROC curve and an AUC; and verifying the universality and extrapolation of the prediction model. The early prediction model of the glomerular filtration rate after cardio-pulmonary resuscitation is constructed, so that the probability of chronic kidney diseases can be predicted within 24 hours, early discovery and early intervention are realized, and the disease progress is delayed.

The invention discloses a construction method of a COL4A5-K229X point mutation X-linked Alport syndrome mouse model. The construction method comprises the following steps: aiming at c.685Agt of a No.12 exon of a mouse COL4A5 gene; carrying out T point mutation, and designing and preparing Cas9 mRNA, gRNA and a donor vector; the components are mixed and then microinjected into fertilized eggs of a C57BL / 6J mouse to obtain an F0-generation mouse; identifying the genotype through PCR (Polymerase Chain Reaction) amplification and Sanger sequencing, and screening positive mice; mating the positive F0-generation mice with the wild-type mice, and breeding F1-generation and subsequent generations; the phenotype of the model is further verified through qPCR, biochemical analysis, light microscopic examination, transmission electron microscope and immunofluorescence. The model constructed by the invention shows hematuria, proteinuria, azemia, podocyte loss and irregular thickening and layering of glomerular basement membrane, is consistent with phenotypes of human XLAS patients, and provides an animal model tool for analyzing pathogenesis and developing treatment strategies.

The invention relates to the technical field of biomedicine, in particular to a preparation method of sequential targeting mesoporous manganese oxide nano-enzyme and application of the sequential targeting mesoporous manganese oxide nano-enzyme in treatment of ischemia reperfusion induced acute kidney injury. Adding a potassium permanganate solution into the silicon dioxide nanoparticle dispersion liquid under ultrasonic waves, and carrying out alkali etching to obtain mesoporous manganese oxide nanoparticles (HMN); and after surface amination modification, connecting with a mixed PEG spacer layer, and reacting with thiolated SS31 and azidoacyl hyaluronic acid to obtain the nano-enzyme. The preparation can effectively penetrate through a damaged glomerulus filtration barrier and is passively enriched in a damaged kidney, damaged renal tubular epithelial cells over-express CD44 receptor mediated hyaluronic acid modified nano-particle endocytosis is enhanced, SS31 modified nano-particles achieve lysosome escape mitochondrial targeting in cells, the level of active oxygen in mitochondria can be reduced, and the activity of the mitochondria can be improved. The mitochondrial function is recovered, the renal function and tissue pathological injury are improved, and accurate anti-oxidation treatment on the acute kidney injury is realized.

To provide a method for treating a proteinuric kidney disease.SOLUTION: There is provided a method comprising administering a predetermined daily dosage of effective amounts of voclosporin over a projected treatment period of at least 24 weeks. The method further comprises: (a) assessing an estimated Glomerular Filtration Rate (eGFR) of a subject at at least a first time point and a second time point on different days within the treatment period; and (b) (i) when the eGFR of the subject decreases by more than a target % to below a predetermined value between the first and second time points, reducing the daily dosage by units of 7.9 mg BID or discontinuing the administration of voclosporin to the subject; (ii) when the eGFR of the subject decreases by less than the target % between the first and second time points, continuing to administer the same predetermined daily dosage of voclosporin to the subject.SELECTED DRAWING: Figure 1

The application provides application of Trapidil in preparation of a drug for preventing and / or treating doxorubicin-induced organ toxicity, and belongs to the technical field of biological medicines.The application discloses that Trapidil plays an organ protection role by activating a cAMP / PKA / CREB signal axis and driving two parallel downstream effect channels: on the one hand, up-regulating an NRF2-GPX3 positive feedback loop to inhibit doxorubicin-induced myocardial cell pyroptosis and glomerular podocyte pyroptosis; and on the other hand, activating an NRF2 / HO-1 channel to inhibit myocardial cell apoptosis and glomerular podocyte apoptosis.In-vivo and in-vitro experiments prove that Trapidil can improve doxorubicin-induced cardiac dysfunction and kidney function damage, reduce histopathological damage, reduce the level of oxidative stress, inhibit the pyroptosis and apoptosis of myocardial cells and glomerular podocytes, and does not affect the antitumor effect of doxorubicin.The application provides a new drug strategy for doxorubicin chemotherapy-induced multi-organ toxicity.

The utility model relates to the technical field of teaching models, and discloses a renal unit function demonstration model, which comprises a glomerulus model, a renal capsule model and a renal tubule model, the lower end of the glomerulus model is connected with the renal capsule model, and the lower end of the renal capsule model is connected with the renal tubule model; according to the utility model, the structure and the function of the kidney unit are visually displayed through the three-dimensional model, the teaching effect is improved, and the defects that the graphic planarity in a teaching material is relatively abstract, only can be displayed statically, is lack of stereoscopicity and intuitiveness, and cannot dynamically simulate the formation process of urine are overcome; by simulating the movement tracks of blood cells, glucose and urea in the urine forming process, the filter of glomerulus and the reabsorption effect of renal tubules in the urine forming process are visually reflected, and the teaching difficulty is broken through.

The present invention relates to a nanoparticle comprising a nanomaterial and at least a first ligand and a second ligand tethered to the nanoparticle. The present invention also relates to a nanoparticle for use as a medicament or diagnostic agent. The present invention also relates to a nanoparticle for use in a method for preventing or treating a disease selected from the group consisting of diabetic nephropathy, glomerulonephritis, glomerular VEGF A dysregulation, endothelial VEGF A dysregulation, diabetic retinopathy, rheumatoid arthritis, age-related macular degeneration and cancer, such as breast cancer. Furthermore, the present invention relates to a method of preparing a nanoparticle.

Methods for treating primary glomerulonephritis, e.g., focal segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN) or mesangial proliferative glomerulonephritis (MsPGN) are provided.

The invention discloses a construction method of a spontaneous lupus adipositis animal model, which comprises the following steps: constructing keratinocytes with genotypes of PPAR [gamma] flox / flox- / -Krt5-CreERT < 2 + > / -Adipoq-Cre < + > / -and PPAR [gamma] flox / flox- / -Krt5-CreERT < 2 + > / -Adipoq-CreERT < 2 + > / -and fat cells into a conditional PPAR [gamma]-active receptor gamma gene knockout mouse, so as to construct the animal model with the spontaneous lupus adipositis animal model. Then knocking out PPAR gamma genes in keratinocytes and adipocytes by using a gene knockout activator, so that the mice spontaneously have the phenotypes of lupus septicaemia, including local skin unhairing, lipoatrophy, persistent skin lesion, proteinuria and serum autoantibodies; histological examination finds that lobular adipositis, glomerular volume increase, mesangial cell hyperplasia, inflammatory cell infiltration, glomerular IgG deposition and the like are mainly caused by dermal immune cell infiltration and subcutaneous fat layer lymphocyte infiltration, clinical symptoms of patients with lupus adipositis are simulated, and an important tool is provided for related research of lupus adipositis.

The invention discloses a kidney organoid culture and multifunctional detection integrated micro-fluidic chip, which is characterized in that a first chip (top layer) is provided with six independent cell culture chambers, the bottom is provided with a porous membrane, glomerular cells differentiated by human induced pluripotent stem cells are inoculated, and a blood filtration function is simulated; the second chip (middle layer) is provided with a raw urine-like collecting chamber, and a porous membrane is used for receiving the filtrate and detecting final urine-like components; and the third chip (bottom layer) is inoculated with vascular endothelial cells to simulate renal tubule reabsorption and blood purification processes. According to the invention, glomerular filtration and renal tubule reabsorption full-function chains are coupled, and the limitation of single function simulation is broken through; the parallel culture room supports synchronous drug toxicity testing or disease modeling; a multi-valve dynamic control system can accurately simulate pathological microenvironments such as high glucose and renal toxicity; and in-situ multi-parameter real-time analysis is realized through three paths of detection outlets. The chip provides a highly bionic in-vitro platform for drug screening, diabetic nephropathy mechanism research and kidney injury model construction.

The utility model discloses an acute glomerulonephritis nursing auxiliary device which comprises a fixing frame, a sliding mechanism used for controlling the synchronous sliding direction is arranged in the fixing frame, the sliding mechanism comprises a rotating shaft rotationally connected to the interior of the fixing frame, a worm is fixedly connected to the rotating shaft, and the worm is fixedly connected to the fixing frame. And a fixing plate is fixedly connected to the interior of the fixing frame, a rotating roller is rotationally connected to the side, close to the worm, of the fixing plate, and a worm wheel is fixedly connected to the side, close to the worm, of the rotating roller. By arranging the sliding mechanism, the rotating handle can be rotated to drive the rotating shaft to rotate, the rotating shaft rotates to drive the worm on the rotating shaft to rotate synchronously, the worm rotates to drive the worm gear to rotate, the worm gear rotates to drive the threaded rod to rotate, and the threaded rod rotates to drive the nut on the threaded rod to slide. And finally, the nut can be synchronously pushed to slide through rotation of the rotating handle.

The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and / or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated diseases.

The present application provides a method of treating a complement-mediated disease in a human subject, the method comprising administering to the subject an effective amount of a fusion protein comprising i) an antibody moiety that specifically binds to human C5 and ii) Factor H (FH) or a functional fragment thereof. The complement-mediated diseases may be, for example, paroxysmal sleep hemoglobinuria (PNH) syndrome, C3 glomerulopathy (C3G), IgA nephropathy (IgAN), and thrombotic microangiopathy (SLE-TMA) secondary to systemic lupus erythematosus.

The present invention consists of a digital, always-online computer system designed to optimize perioperative safety through the automated integration of clinical and laboratory parameters. Unlike conventional medical calculators, this system implements a reactive logic engine that simultaneously calculates glomerular filtration rate (CKD-EPI 2021) and scores multiple risk scales (Goldman, LEE, ASA, CHA2DS2-VASc, HAS-BLED) without duplicate data entry. The system includes a drug reconciliation algorithm that cross-references the bleeding risk of the surgical procedure with the patient's renal function, generating accurate recommendations for discontinuing or continuing high-risk medications (anticoagulants, antiplatelet agents, SGLT2 inhibitors) based on current clinical evidence.