65 results about "Podocyte" patented technology

The invention discloses application of oligopeptide in preparation of a medicine for treating and / or preventing diabetic nephropathy. The oligopeptides comprise oligopeptides with the amino acid sequence of SEQ ID NO: 1: LNLYP and derivative sequences or conservative substitution variants of the oligopeptides. The oligopeptide can significantly improve renal function indexes of mice with diabetic nephropathy, such as UACR, serum creatinine, urea nitrogen and the like, enhance podocyte barrier integrity and inhibit accumulation of advanced glycosylation end products AGEs in kidney tissues, and provides a basis for development of novel drugs for treating diabetic nephropathy.

The invention relates to the technical field of preparation of organoids, and discloses a method for regulating and controlling human induced pluripotent stem cells to differentiate into kidney organoids, which comprises the following steps: resuspending a cell cluster formed by human induced pluripotent stem cells by using a basic differentiation culture solution containing a GSK-3beta inhibitor, inoculating the cell cluster into an ultralow adsorption cell culture plate, and starting to culture, marking the time as the 0th hour of differentiation; and after culturing for 70-76 hours, replacing the basic differentiation culture solution containing the GSK-3beta inhibitor with a basic differentiation culture solution containing a Knockout TM serum substitute (KSR), and continuing to carry out differentiation culture. By adopting the method disclosed by the invention, the human induced pluripotent stem cells can be efficiently, quickly, simply, conveniently and stably subjected to directional induced differentiation into kidney organs containing podocytes, renal tubules and other structures, and the time for constructing a kidney in-vitro model can be shortened, so that the research on kidney diseases, kidney development and the like can be greatly assisted; and a powerful platform is provided for kidney toxicity assessment.

The invention provides a traditional Chinese medicine composition for treating diabetic nephropathy and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition provided by the invention is prepared from the following raw materials in parts by weight: 30 to 120 parts of raw radix astragali seu hedysari, 10 to 20 parts of radix pseudostellariae, 5 to 15 parts of herba dendrobii, 5 to 15 parts of radix trichosanthis, 10 to 20 parts of radix rehmanniae recen, 10 to 20 parts of raw radix puerariae, 25 to 35 parts of herba agrimoniae, 5 to 15 parts of rhizoma discoreae, 10 to 20 parts of fructus corni, 10 to 20 parts of ramuli euonymi, 10 to 20 parts of serissa serissoide, 25 to 35 parts of chinaroot greenbrier, 4 to 8 parts of fructus schisandrae chinensis, 10 to 20 parts of herba pyrolae and 10 to 20 parts of corn stigma. The traditional Chinese medicine composition disclosed by the invention can be used for improving the clinical curative effect, improving symptoms, repairing podocyte damage and relieving oxidative stress by virtue of unique traditional Chinese medicine composition and aiming at pathogenesis treatment of the DN with the syndrome of deficiency of both qi and yin, and a new thought and a new method are provided for traditional Chinese medicine treatment of the DN.

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 discloses a diabetic nephropathy marker PARP1, a primer combination and application, and relates to the technical field of biology. The sequence of the primer combination is PARP1-F, and is as shown in SEQ ID NO. 1; 1, PARP1-R as shown in SEQ ID NO. 2; an internal reference primer beta-actin-F, which is as shown in SEQ ID NO. 17; an internal reference primer beta-actin-R is as shown in SEQ ID NO. 18. The invention finds that the expression of PARP1 in the kidney tissue of a patient with diabetic nephropathy is increased and is positively correlated with ACR (Activated Receptor). The invention also finds that PARP1 is related to podocyte damage, and knocking down PARP1 can relieve podocyte endoplasmic reticulum stress and apoptosis, and can reflect the progress of DKD to a certain extent.

The application belongs to the field of biological medicine, and provides application of miR-152 as a target in preparation of a drug for treating podocytopathy and the drug. Specifically, the application relates to application of miR-152 as a therapeutic target and / or a drug screening target in preparation of a drug for treating podocytopathy and a drug for treating FSGS nephropathy. The miR-152 inhibitor can inhibit high expression of miR-152 in kidney tissues of podocytopathy or FSGS nephropathy, inhibit down-regulation of synaptopodin protein, RhoA protein and 14-3-3 beta protein expression, protect stability of a cytoskeleton of a podocyte in kidney tissues, and delay progressive development of FSGS disease. The application provides a new therapeutic target for treatment of FSGS disease, and has important social and economic significance.

The present invention relates to a traditional Chinese medicine composition for treating diabetic nephropathy and a preparation method thereof, belonging to the technical field of traditional Chinese medicine compositions. To solve the problems of single target for western medicine in treating diabetic nephropathy and high risk of adverse reactions when using a combination of multiple drugs, the present invention provides a traditional Chinese medicine composition for treating diabetic nephropathy. The composition formula includes white ginseng, astragalus membranaceus, stir-fried atractylodes macrocephala, poria cocos, chicken gizzard-membrane, kudzu root, wolfberry fruit, Chinese yam, cornel fruit and oriental waterplantain rhizome. The traditional Chinese medicine composition of the present invention has the advantages of multiple components and multiple targets and small adverse reactions. Animal experiments prove that the traditional Chinese medicine composition provided by the present invention can significantly improve the blood glucose, blood lipid, urine protein, creatinine and blood urea nitrogen levels of rats, can significantly improve the pathological changes of the renal tissue of model rats, and can correct the podocyte metabolic pathway and restore its mitochondrial function by specifically increasing the activities of SIRT1 and PGC-1α. It is an effective medicine for treating diabetic nephropathy and provides a new way for the multi-target treatment of clinical diabetic nephropathy.

The invention belongs to the field of biological medicines, and particularly discloses application of extracellular vesicles EVs carrying CD35 functional molecules in preparation of medicines for treating sepsis-related multi-organ injury, preferably, the EVs are derived from human podocytes or other cells or tool cells capable of naturally or engineered expressing CD35, and the EVs are administrated through caudal vein injection and can be used for preparing medicines for treating sepsis-related multi-organ injury. Normal saline is taken as a carrier, and the dosage of 1 * 10 < 10 > EVs each time is once every 12 hours and twice continuously. It is proved for the first time that EVs carries CD35 to inhibit circulation mononuclear cell complement activation (the EVs are combined with C3b to block downstream complement cascade reaction), migration of mononuclear cells to the kidney, the heart, the liver and the lung is reduced, and therefore multi-organ inflammation damage and cell apoptosis are relieved. In a cecum ligation perforation (CLP) sepsis model, it is proved that the medicine significantly improves the survival rate of mice, improves renal functions (reduces creatinine / urea nitrogen) and kidney pathological tissue damage, and meanwhile relieves pathological damage of multiple organs of the heart, the liver and the lung. The invention provides a new treatment strategy and drug candidate for sepsis-related multi-organ dysfunction.

The invention discloses an application of TMEM106A as a target spot in preparation of a diagnostic kit and a targeted therapeutic drug. Relates to the technical field of immunodiagnosis. Specific applications are provided. The invention discloses a key effect of TMEM106A in podocyte injury related to preeclampsia. TMEM106A is significantly down-regulated in urine of a PE patient, is closely related to podocyte injury and inflammatory response, and can be used as an early noninvasive diagnostic marker; meanwhile, the targeted podocyte up-regulation TMEM106A has remarkable anti-inflammatory and kidney protection effects, and a theoretical basis and practical feasibility are provided for targeted therapy of PE-related podocyte injury. The invention provides a new way for early precise diagnosis and intervention strategy of PE, and has wide clinical application prospect.

According to the application of the PDE4DIP serving as the biomarker in preparation of the reagent kit for adjuvant therapy of the kidney podocyte injury and the podocytosis, the reagent kit comprises a reagent for detecting the PDE4DIP, and in a word, it is confirmed for the first time that the expression of the PDE4DIP can be reduced under the conditions of the kidney podocyte injury and the podocytosis; on one hand, the invention provides the application of the PDE4DIP transcription factor or the functional fragment thereof as a target spot for improving the renal podocyte injury and the podocytosis, and on the other hand, the invention provides the new application of the PDE4DIP as a biomarker (pathological diagnosis) in the diagnosis of the renal podocyte injury and the podocytosis renal injury. The invention solves the blank of no specific targeted treatment tool in the field of kidney diseases, discovers the new application of the PDE4DIP as a biomarker in the treatment of kidney podocyte injury and podocytosis, provides a specific verification method and experimental data, and has very positive significance.

The invention discloses an absolute quantitative detection method for urine exfoliated podocyte, relates to the technical field of biomedical detection, and aims to solve the problem that the urine exfoliated podocyte cannot be accurately and absolutely quantified due to uncertain cell loss in a sample treatment process in the prior art. The method comprises the following steps: before carrying out any physical treatment on a urine sample, adding a known number of internal standard reference substances with physical characteristics similar to those of cells into the urine sample, carrying out co-enrichment treatment on a mixed sample containing target podocytes and the internal standard reference substances, and preparing a cell slide by adopting a standardized slide preparation technology; and carrying out podocyte specific immunofluorescence staining on the slide. Through the design of internal standard preposition and whole-course synchronous calibration, the cell loss error in the operation process is effectively overcome, the traditional semi-quantitative detection is improved into accurate and repeatable absolute quantification, and the reliability and clinical application value of a detection result are remarkably improved.

The invention relates to the technical field of functional foods, and particularly discloses a dietary therapy composition for promoting repair of cranial nerve damaged cells and a preparation method. The composition is prepared from the following raw materials in parts by weight: artichoke peptide, taurine, phosphatidylserine, natural nicotinic acid, guarana extract, collagen peptide, acerola cherry fruit powder, inulin, yak bone marrow powder, vitamin B family, sialic acid and sucralose. The preparation method comprises the following steps: S1, pretreating the raw materials; s2, performing nano crushing; s3, low-temperature drying; s4, embedding the inulin; and S5, mixing and forming. The artichoke peptide and the phosphatidylserine are synergistically matched, and a compound component with liver and brain axis functions is taken into consideration, so that a multi-target synergistic effect is achieved, the requirements of cell repair and neural development are synchronously met, and compared with single-component supplement or neglect of the influence of liver detoxification on brain repair in the prior art, the brain repair effect is greatly improved. The problems of low repairing efficiency and insufficient component utilization rate are solved.

This invention discloses the application of a PDLIM2 gene overexpression viral vector in the preparation of drugs for treating podocyte disease, wherein the nucleotide sequence of the PDLIM2 gene is shown in SEQ ID NO:1. This invention is the first to discover and verify the core role of the PDLIM2 gene in podocyte protection, confirming its significant downregulation in DKD and FSGS disease models, and demonstrating through functional experiments that PDLIM2 overexpression can effectively stabilize the podocyte cytoskeleton, inhibit apoptosis, and reduce proteinuria, thus establishing it as a key target gene for the treatment of podocyte disease. This invention is the first to intervene at the gene level in the core link of podocyte damage—cytoskeleton stability. By specifically upregulating the expression of PDLIM2 in podocytes, it directly enhances their intrinsic cytoskeleton support and anti-damage ability, achieving a fundamental shift in treatment strategy from "symptomatic support" to "causal repair."

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.

A viral vector, wherein the viral vector comprises a COL4A3, COL4A4 or COL4A5 transgene.

The invention belongs to the technical field of biological medicine, and discloses a construction method and application of a podocyte specific S1PR1 gene knockout mouse model. A podocyte specific S1PR1 knockout mouse is constructed through a Cre-LoxP system, and then an FSGS model is constructed through doxorubicin injection. And verifying the model by using urine detection, serum detection, histopathology detection and molecular mechanism detection. Research finds that S1PR1 expression decline causes POLR2A splicing abnormity and expression decline through down-regulation of Xab2, and podocyte senescence and FSGS progress are induced. According to the invention, a related model is constructed for the first time, the regulation effect of the S1PR1-Xab2-POLR2A pathway in podocyte senescence is disclosed, a reliable tool is provided for researching FSGS pathogenesis, the potential of S1PR1 as a therapeutic target is determined, and the S1PR1 can be used for screening drugs for treating FSGS and has important clinical transformation value.

The application provides application of a TAS2R4 agonist in preparation of a drug for treating and preventing diabetic nephropathy, and comprises that a bitter taste receptor 4 subtype (TAS2R4) can be used as a drug target point for treating and preventing diabetic nephropathy, and quinine is used as a TAS2R4 agonist. Specifically, mouse diabetic nephropathy induced by a chemical reagent and mouse podocyte cell line MPC cell damage caused by chronic high glucose are taken as research objects, it is found that mouse TAS2R4 agonist quinine has a prevention and treatment effect on diabetic nephropathy, has a protection effect on podocyte loss caused by high glucose, and has an activation effect on mouse kidney TAS2R4 molecular signal, and a possible molecular mechanism is discussed from the aspects of inhibiting NLRP3 inflammasome activation and NF-kappa B signal activation path, and theoretical basis and technical support are provided for prevention and treatment of diabetic nephropathy, other kidney diseases with inactivation of TAS2R4 molecular signal and other diseases by using TAS2R4 agonists including quinine.

The invention relates to an application of a reagent for detecting SRC expression in preparation of a product for diagnosing and treating lupus nephritis, SRC is highly expressed in a patient with lupus nephritis, when the expression level of SRC is reduced, ferroptosis of podocyte is remarkably relieved, ferroptosis related markers are remarkably reversed, the levels of Fe < 2 + > and MDA are reduced, the level of GSH is increased, and compared with a control group, the SRC expression level is remarkably reduced. The viability of podocyte is increased; the invention relates to application of a reagent for detecting CYBB expression in preparation of a product for diagnosing and treating lupus nephritis, CYBB is highly expressed in a patient suffering from lupus nephritis, when the expression level of CYBB is reduced, ferroptosis in podocytes is remarkably relieved, ferroptosis related markers are remarkably reversed, the levels of ACSL4, Fe < 2 + >, ROS and MDA are reduced, and the levels of GPX4 and GSH are increased, so that the effect of treating lupus nephritis is achieved. The polarization of M2 macrophages is promoted, the ferroptosis phenomenon is further relieved through the polarization of the macrophages, and the viability of podocytes is improved.

The invention discloses a Chinese catalpa fruit-based unilateral preparation for eliminating urine protein and application thereof, and belongs to the technical field of traditional Chinese medicine, the active ingredient of the unilateral preparation is extracted from a single medicinal material of Chinese catalpa fruit, and the unilateral preparation can contain pharmaceutically acceptable auxiliary materials. The single preparation can be prepared into four dosage forms of oral liquid, tablets, dripping pills and granules so as to meet different clinical requirements. Animal experiments prove that the single preparation can effectively eliminate urine protein and improve the renal function through four synergistic mechanisms of anti-inflammation, anti-oxidation, improvement of the renal function, protection of podocyte and immunoregulation and diuresis, and is suitable for treating proteinuria accompanied by nephropathy. The preparation provided by the invention has the characteristics of single formula, easy quality control and various dosage forms, and provides a traditional Chinese medicine scheme with an exact curative effect for clinically treating related diseases.

The present application relates to a kind of tumor infiltrating lymphocyte (TIL) cell expansion culture process. Specifically, the present application provides a kind of TIL cell expansion method, comprising: in expansion culture medium, preliminary culture TIL cell is carried out fast expansion culture. In the TIL cell expansion method of the present application, it is not dependent on activation antibody CD3 antibody, high-dose IL-2 and feeder cell, that is, the TIL cell number hundreds of times expansion can be realized in short time, the demand of TIL cell quantity in TIL cell therapy clinically can be satisfied, and it has broad application prospect in the field of TIL cell treatment.

A low-salt fasting-mimicking diet (LS-FMD) is provided for promoting kidney regeneration and treating kidney disease. The LS-FMD comprises cyclic dietary interventions that reduce caloric and sodium intake to induce fasting-like metabolic effects while maintaining essential nutrition. In animal models of puromycin-induced nephrosis, LS-FMD cycles restore normal proteinuria levels and improve nephron structure and function relative to untreated controls. The diet activates kidney-specific gene expression programs and promotes a quiescent, non-proliferative state in mature podocytes, supporting renal recovery. In human subjects with chronic kidney disease, administration of fasting-mimicking diet cycles for five days per month over three months reduces proteinuria and improves endothelial function. The invention demonstrates that kidney-specific fasting-mimicking dietary cycles have therapeutic potential for slowing or reversing progressive renal disorders.

The invention discloses a monoterpene indole alkaloid compound as well as a preparation method and application thereof, and belongs to the technical field of medicines. The monoterpene indole alkaloid compound disclosed by the invention is separated from ervatamia palmata, has remarkable activity for repairing podocyte injury under the hypoxia condition, and can be used for preparing a medicine for treating chronic renal injury under the hypoxia condition. The traditional Chinese medicine composition has relatively high economic benefits aiming at the current situation of non-hypoxia chronic kidney injury specific medicines.

The invention relates to the technical field of biomedical engineering, in particular to a culture medium and a culture method of podocyte fate organoid. Compared with human induced pluripotent stem cells (hiPSCs), cells separated from human adult kidney tissues are taken as objects to induce and culture podocyte fate organoid, so that the podocyte fate organoid has better gene stability and can better reproduce original tissue phenotypes. Compared with a hiPSCs-derived kidney organ, the culture method of the podocyte fate organ provided by the invention has the advantages that a culture system is simplified; the serum-free culture medium component based on a pure compound combination also greatly improves the safety of a culture product possibly used for clinical biological treatment.

The application discloses a method for extracting mitochondria-associated membranes (MAM) and other subcellular components from podocytes, which comprises the following steps: pretreating the podocytes, crushing the podocytes by low-power ultrasonic, separating the crude mitochondrial components by differential centrifugation, and then purifying the high-purity MAM and other subcellular components by density gradient centrifugation and ultracentrifugation. The method replaces the traditional homogenizer grinding with low-power ultrasonic crushing, improves the MAM extraction yield by controlling the ultrasonic parameters, appropriately simplifies the differential centrifugation steps, increases the yield while ensuring the purity, sequentially separates the unbroken cells, the crude mitochondria, the cytoplasm and the endoplasmic reticulum components, and finally obtains the high-purity MAM and other subcellular components by density gradient centrifugation and ultracentrifugation purification. The method effectively improves the yield of the podocyte separation and extraction of the MAM and other subcellular components, reduces the cost, and provides technical support for the research on the podocyte MAM proteomics.

This invention belongs to the field of biomedical technology and discloses a method for constructing and applying a podocyte-specific S1PR1 gene knockout mouse model. Podocyte-specific S1PR1 knockout mice were constructed using the Cre-LoxP system, and then an FSGS model was established via doxorubicin injection. The model was validated using urine, serum, histopathological, and molecular mechanism detection methods. The study found that decreased S1PR1 expression induces podocyte senescence and FSGS progression by downregulating Xab2, leading to abnormal POLR2A splicing and reduced expression. This invention is the first to construct such a model, revealing the regulatory role of the S1PR1-Xab2-POLR2A pathway in podocyte senescence, providing a reliable tool for studying the pathogenesis of FSGS, clarifying the potential of S1PR1 as a therapeutic target, and enabling drug screening for FSGS treatment. It has significant clinical translational value.

Methods are provided for delaying onset or progression of kidney damage, or treating kidney disease, in a subject who has type 1 diabetes or type 2 diabetes or glomerular disease. The methods comprise administering to a subject with type 1 or type 2 diabetes or glomerular disease an effective amount of an agent capable of inhibiting NBL1 activity, and in particular, capable of inhibiting NBL1-mediated toxicity of human podocytes. In some embodiments, the agent is an antibody capable of binding to human NBL1.

The invention relates to application of dendrobium officinale tender shoots and / or extracts thereof, in particular to application of dendrobium officinale tender shoots and / or extracts thereof obtained through differentiation induction of dendrobium officinale stem cells in preparation of drugs for treating and / or preventing glomerular cell fibrosis and / or renal podocyte injury related diseases.

The invention provides a Col4a5 + / -mouse immortalized podocyte line, and the preservation number of the Col4a5 + / -mouse immortalized podocyte line is CGMCC (China General Microbiological Culture Collection Center) NO.46563. The cell line has relatively strong stability guarantee and can be subjected to continuous passage for 30 generations. The Col4a5 < + / -> mouse immortalized podocyte line corresponds to the phenotype of a female XLAS carrier with a light disease degree, can be used for precise pathological modeling, realizes COL4A5 gene dose effect simulation, and can be used as a cell model for screening a treatment drug or a diagnosis drug for hereditary nephropathy. The cell line is subjected to immortalization treatment, can be massively cultured and subcultured, has relatively simple culture requirements, can obtain a large number of experimental cells in a short time, has a short total experimental period, is suitable for popularization, and overcomes the technical problems of difficulty in constructing a single allele mutation (Col4a5 + / -) cell line, low transfection efficiency, allele loss and the like in the prior art.

Provided are dosing regimens for the treatment of Fabry disease in a patient. Certain methods relate to the treatment of ERT-experienced or ERT-naïve Fabry patients. Certain methods comprise administering to the patient about 123 mg free base equivalent of migalastat for improving left ventricular mass and / or improving podocyte globotriaosylceramide.