109 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.

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.

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.

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 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.

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 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 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.

The present invention relates to use of an aromatic biological antagonist in preparing a medicament for treating or preventing a kidney disease. Specifically, the present invention provides use of 4'-((2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl-d2)-N-(4-chloro-5-methylisoxazol-3-yl)-2'-(ethoxymethyl)-[1,1'- biphenyl]-2-sulfonamide compound or a pharmaceutically acceptable salt thereof in preparing a medicament for treating or preventing a kidney disease, especially in preparing a medicament for treating or preventing focal segmental glomerulosclerosis and immunoglobulin A nephropathy. The compound or the pharmaceutically acceptable salt thereof shows excellent therapeutic effects on focal segmental glomerulosclerosis and immunoglobulin A nephropathy, and has great clinical application prospects.

The present disclosure relates to methods related to the treatment of B-cell responsive autoimmune glomerulopathies.

This disclosure provides compositions comprising engineered vascularized kidney tissues and methods of making vascularized glomerular kidney tissues. Also provided herein are in vitro kidneys comprising vascularized kidney tissues. Methods of making the compositions and in vitro kidneys and uses thereof are disclosed 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.

The invention discloses application of an SHIP1 agonist AQX-1125 in preparation of a medicine for treating focal segmental glomerulosclerosis, and belongs to the technical field of medicines.The endogenous regulatory factor SHIP1 agonist is used for conducting precise speed limiting on a PI3K / Akt pathway, so that a new effective means is provided for FSGS treatment, and the application form of the SHIP1 agonist AQX-1125 can be an oral preparation and the like; tests prove that the AQX-1125 can remarkably repair renal functions, reduce pathological proteinuria, improve pathological damage of kidney tissues, maintain phenotypic homeostasis and ultrastructural integrity of podocyte and accurately regulate and control pathogenic signal pathways and metabolic homeostasis, so that the AQX-1125 shows remarkable technical progress and clinical application potential in the aspect of FSGS treatment.

The invention discloses a medicinal moxa composition for preventing and treating codiseases of beriberi and chronic glomerulonephritis. The medicinal moxa composition is prepared from radix aconiti carmichaeli, cortex cinnamomi, cornu cervi pantotrichum, rhizoma alismatis, radix achyranthis bidentatae and moxa. The medicinal moxa composition disclosed by the invention has remarkable external antibacterial and warming effects, consists of five yang warming medicines and one warming medicine, releases volatile components through combustion, and stimulates acupuncture points in combination with heating power, so that the dual effects of treating beriberi and chronic glomerulonephritis are achieved. The radix aconiti carmichaeli, cinnamon, cornu cervi pantotrichum, rhizoma alismatis, radix achyranthis bidentatae and wormwood in the formula form a unique synergistic effect mechanism in the external use process, so that the medicinal components directly reach the focus through skin penetration, and meanwhile, the qi and blood of the whole body are regulated. Through infrared radiation, volatile antibacterial components and a warming effect generated by combustion of the medicinal moxa, the dual treatment effects of external warming and dredging and internal qi and blood regulation are achieved, and a new thought is provided for treatment of foot fungal infection and kidney meridian dysfunction.

The invention provides a diabetic nephropathy glomerular basilar membrane thickness measuring method based on artificial intelligence, and relates to the technical field of basilar membrane thickness measurement, and the method comprises the steps: cutting a diabetic nephropathy glomerular basilar membrane to obtain an input set; utilizing instance feature extraction and attention aggregation to construct a multi-instance learning network; training the multi-instance learning network by using the input set to obtain a trained multi-instance learning network; and analyzing the diabetic nephropathy glomerular basilar membrane by using the trained multi-instance learning network to obtain a basilar membrane thickness measurement result, thereby completing the measurement of the diabetic nephropathy glomerular basilar membrane thickness. The problems that in the prior art, equipment is expensive, operation is complex, and universality is poor are solved.

The invention relates to application of hispidulin or pharmaceutically acceptable salts, esters and solvates thereof in preparation of medicines for treating lupus nephritis. The invention develops a new application of the hispidulin, and proves the treatment effect of the hispidulin on lupus nephritis. Meanwhile, the invention verifies that the hispidulin can obviously improve the renal function indexes (including reducing urine protein, blood urea nitrogen and serum creatinine, increasing serum albumin and improving lipid metabolism) of lupus nephritis, can relieve renal pathological injuries (including reducing glomerular mesangial hyperplasia, basilar membrane thickening, renal tubule dilatation and interstitial inflammation infiltration), and can improve the renal function indexes of lupus nephritis. Kidney immune complex deposition can be reduced (including reduction of deposition of kidney IgG and complement C3), meanwhile, it is found for the first time that angiogenin-like protein 4 (Angptl4) is a key action target for treating lupus nephritis by means of the homospidulin, and the homospidulin plays a kidney protection role by down-regulating Angptl4 expression.

The application discloses a kidney function risk information processing method based on OCTA features and clinical data, and relates to the technical field of artificial intelligence and intelligent medical treatment. Quantitative features such as blood vessel density, perfusion area, retinal thickness and choroidal vascular volume are extracted from multi-scale fundus OCTA images of a subject, and total feature data sets are constructed in combination with clinical biochemical indexes, so as to estimate glomerular filtration rate as an outcome index for binary classification labeling. Elastic network regression is adopted to screen key modeling features, and various machine learning models such as logistic regression, random forest and gradient boosting are simultaneously trained on a training set. After 5-fold cross-validation optimization, the optimal model is selected by comprehensively considering the receiver operating characteristic curve, the calibration curve and the decision curve. A nomogram is constructed based on the optimal model, and individual early kidney function decline risk probability numerical values and auxiliary reference information of the subject are outputted for reference of clinical doctors.

The present disclosure provides a bioengineered kidney construction method based on organoids and acellular scaffolds, which comprises first injecting pro-vascular stem cells into a kidney acellular scaffold material, and then culturing for several days through fluid circulation perfusion, and then injecting kidney organoids (KIO) into the scaffold material for perfusion culture after the kidney acellular scaffold material is recellularized. The bioengineered kidney obtained by the method of the present disclosure can be used as a graft for replacing kidney function. The present disclosure also provides a kidney organoid culture and expansion method, and the organoids obtained by the method contain not only kidney parenchymal cells such as glomerular cells and renal tubular cells, but also blood vessels and immune cells, which provides a good source of kidney parenchymal cells for the preparation of tissue-engineered kidneys.

The utility model discloses a dynamic teaching aid for simulating urine and hematuria forming processes. The dynamic teaching aid comprises a teaching aid bracket, a renal artery model, a globular arteriole model, a glomerulus model, a globular arteriole model, a capillary network model, a renal vein model, a renal capsule model and a bladder model, the renal artery model, the renal vein model, the renal capsule model and the bladder model are sequentially arranged on the teaching aid support; the glomerulus model is mounted in the kidney capsule model; a kidney tubule model is arranged at the bottom of the kidney capsule model, the tail end of the kidney tubule model is communicated with the bladder model, and decoloration cotton is distributed in the kidney capsule model; the capillary network is wound on the renal tubule model of the renal capsule model; one end of the ball-entering arteriole model is communicated with the renal artery model, and the other end is communicated with the glomerular model; one end of the bulbous arteriole model is communicated with the glomerulus model, and the other end is communicated with the capillary network model; and the tail end of the capillary network model is communicated with the renal vein model. The teaching aid has the advantages of being simple in structure, convenient to operate and capable of improving teaching quality.

According to the application of the reagent for detecting the phosphorylation level of the S202 and T205 sites of the MAPT protein in preparation of the renal fibrosis diagnosis product, the function research of the MAPT protein is expanded from the traditional field of glomerular podocytes to renal tubular epithelial cells and the fibrosis pathological process of the renal tubular epithelial cells for the first time, and a brand new direction of the MAPT protein in renal disease research is opened up. Different from the conventional general research means which only depends on overall gene knockout or overexpression, the method provided by the invention realizes accurate analysis of the function of the MAPT key phosphorylation site by using the site-specific mutant. Through a systematic function determination experiment, the invention discloses an anti-intuition biological rule with great theoretical significance: although phosphorylation of the sites S202 and T205 obviously drives the fibrosis process of the renal tubular epithelial cells, the fibrosis phenotype cannot be improved by simulating the dephosphorylation state (S202A / T205A mutant) of the sites.