115 results about "Podocyte" patented technology

The invention discloses application of ADAM10 or ADAM17 serving as a target spot in preparation of a medicine for preventing / treating membranous nephropathy and application of an ADAM10 or ADAM17 inhibitor in preparation of the medicine for preventing / treating membranous nephropathy. The invention finds that ADAMs mediate the deposition process of immune complexes of autoantigens such as PLA2R1 of membranous nephropathy, and enzyme digestion of podocytes to transmembrane autoantigen proteins such as PLA2R can be inhibited by performing targeted intervention on the activity of ADAMs, especially the activity of ADAM10 and ADAM17, so that immune complexes deposited in glomerulus are reduced, the podocyte damage of membranous nephropathy is improved, and the therapeutic effect is achieved.

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 discloses application of a substance taking an SAA2 gene as a target spot in preparation of a kit for diagnosing DKD and a medicine for treating DKD, relates to the technical field of detection of gene target spots related to diabetic nephropathy and research and development of targeted medicines, discloses an effect of the SAA2 gene in diagnosis of DKD, and meanwhile, finds that expression of the SAA2 gene in DKD kidney tissues is increased, and the expression of the SAA2 gene in the DKD kidney tissues is reduced. The result is negatively correlated with renal function. The invention also finds that the SAA2 gene is related to podocyte injury and inflammatory response, and can reflect the inflammation level of DKD to a certain extent. The effect of the compound in DKD-mediated inflammatory reaction can be verified through further in-vivo and in-vitro experiments subsequently, and a certain theoretical basis is laid for research and development of targeted drugs.

The invention relates to a traditional Chinese medicine composition for treating diabetic nephropathy and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine compositions. In order to solve the problems that the target spot of western medicine for treating diabetic nephropathy is single, and the adverse reaction risk is large when multiple medicines are combined for use, the invention provides a traditional Chinese medicine composition for treating diabetic nephropathy, and the traditional Chinese medicine composition comprises white ginseng, astragalus membranaceus, scorched atractylodes macrocephala, poria cocos, endothelium corneum gigeriae galli, kudzu vine root, medlar, Chinese yam, dogwood and rhizoma alismatis. The traditional Chinese medicine composition has the advantages of multiple components, multiple targets and small adverse reaction, animal experiments prove that the traditional Chinese medicine composition provided by the invention can remarkably improve the levels of blood sugar, blood fat, urine protein, creatinine and urea nitrogen of rats, can remarkably improve pathological changes of renal tissues of model rats, can specifically increase the activity of SIRT1 and PGC-1alpha, and can be used for treating the renal diseases of the rats. The traditional Chinese medicine composition can be used for treating diabetic nephropathy, correcting the metabolic pathway of podocyte and recovering the mitochondrial function, is an effective medicament for treating diabetic nephropathy, and provides a new pathway for clinical multi-target treatment of 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 present invention provides a method for preparing renal podocytes by discontinuous differentiation. Induced pluripotent stem cells are differentiated into the renal podocytes by using a discontinuous method. According to the method, pluripotent stem cells can be subjected to targeted induction of differentiation to obtain renal progenitor cells; renal progenitor cells with a high degree of differentiation are identified and cryopreserved, and then are thawed and subjected to targeted induction of differentiation into podocytes after large-scale preparation. The podocytes obtained by this method have high differentiation efficiency, high consistency, and a high survival rate.

Methods of identifying an enriched heterogeneous renal cell population having therapeutic potential, enriched heterogeneous renal cell populations having therapeutic potential and uses for same. In some embodiments, it includes a method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential. In the method, it is determined whether cells of the enriched heterogeneous renal cell population express at least one: (i) ureteric bud and / or cap mesenchyme (UB / CM) marker; and / or (ii) podocyte marker.

The invention relates to the field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating idiopathic podocytosis, which is prepared from the following raw material medicines in parts by weight: 6 to 12 parts of raw herba ephedrae, 15 to 30 parts of gypsum, 15 to 30 parts of raw radix astragali seu hedysari, 10 to 30 parts of roasted rhizoma atractylodis macrocephalae, 10 to 30 parts of poria cocos, 10 to 30 parts of radix codonopsis, 10 to 15 parts of radix stephaniae tetrandrae, 5 to 15 parts of fresh ginger, 10 to 20 parts of fructus ziziphi jujubae and 5 to 10 parts of liquorice root. Aiming at the symptoms and pathogenesis of the idiopathic podocytosis, the traditional Chinese medicine adopts the treatment principle of opening the Xuanfu, tonifying qi and astringing, is low in raw material cost, simple and convenient to prepare, convenient to use and small in side effect, can be taken for a long time, and has better clinical curative effect and application prospect on the idiopathic podocytosis through clinical application, observation and analysis for many years.

Disclosed herein are methods for making, culturing, and maintaining engineered podocyte-like cells. The methods comprise growing glomerular cells in in vitro conditions to differentiate the glomerular cells into podocyte-like cells. Also disclosed herein are isolated and purified podocyte-like cells and kits comprising the engineered podocyte-like cells and / or the media used to differentiate the podocyte-like cells. The engineered podocyte-like cells can be used in recellularization of a decellularized extracellular matrix. In some instances, disclosed herein are recellularized isolated organs that can comprise the engineered podocyte-like cells.

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 invention relates to a multiplication culture process of tumor infiltration lymphatic (TIL) cells. Specifically, the invention provides a propagation method of TIL cells, which comprises the step of carrying out rapid propagation culture on preliminarily cultured TIL cells in a propagation culture medium. In the TIL cell expanding culture method, hundreds of times of amplification of the TIL cells can be realized in a short time without depending on an activated antibody CD3, high-dose IL-2 and feeder cells, the requirement of TIL cell therapy on the number of the TIL cells clinically can be met, and the TIL cell expanding culture method has a wide application prospect in the field of TIL cell therapy.

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.

Methods of treating idiopathic nephrotic syndrome in a subject involve reducing urinary and / or blood levels of CD93, reducing or inhibiting CD93-mediated podocyte activation. or reducing or inhibiting CD93 release from glomerular endothelial cells. The methods may include administration of a composition including at least one of an anti-CD93 antibody and an inhibitor of pi integrin.

The invention discloses a device for rapidly detecting podocytosis, and relates to the technical field of biomedical detection. In order to solve the problems that at present, detection of podocytosis mainly depends on kidney biopsy, is traumatic and complex in operation, causes great pain to a patient, and the operation process is complex and needs to be executed by professional medical personnel; however, urine-based podocyte detection avoids biopsy wounds, but generally needs tedious sample treatment steps and professional laboratory equipment, and is not beneficial to rapid screening and diagnosis of diseases. Urine and blood samples are adopted for detection, trauma of kidney biopsy is avoided, the sample treatment and detection process is simplified, the detection time is shortened, the detection efficiency is improved, multiple markers are detected at the same time, the detection accuracy and sensitivity are improved, and by means of marker verification and concentration analysis, the detection accuracy and sensitivity are improved. And a detection report is generated, so that the detection result is more intuitive, and rapid screening and diagnosis of diseases are facilitated.

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 relates to the technical field of medicines. The invention provides application of nilotinib in preparation of a medicine for treating diabetic nephropathy and a medicine for treating podocyte injury. According to the nilotinib disclosed by the invention, through inhibiting ZAK alpha phosphorylation, the expression of P38 phosphorylation and JNK phosphorylation can be down-regulated, the ratio level of urine microalbumin / creatinine is remarkably reduced, the number of WT1 positive cells is remarkably increased, DKD podocyte damage is relieved, and the effect of treating diabetic nephropathy is achieved.

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.

The invention provides application of histone methyltransferase EZH2 as a therapeutic target of diabetic nephropathy podocyte senescence and injury, and relates to the technical field of biological medicine. It is found that the expression level of EZH2 in podocyte under the high glucose condition is remarkably increased, and conditions are provided for taking EZH2 as a biomarker for diagnosing or evaluating diabetic nephropathy podocyte damage and senescence. Subsequently, it is verified that podocyte damage of db / db mice can be remarkably improved, proteinuria of the db / db mice can be reduced, pathological damage of kidneys can be relieved, glomerular senescence of the db / db mice can be delayed, damage and senescence of podocytes under the high-glucose condition can be remarkably improved, the purpose of protecting the kidneys is achieved, the development of diabetic nephropathy is delayed, and the development of diabetic nephropathy is delayed. Therefore, the EZH2 can be used as a potential target for treating diabetic nephropathy.

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.