62 results about "Liver regeneration" patented technology

Disclosed in the present invention are a biomimetic vascularized iPSC-hep spheroid for liver regeneration, and a preparation method therefor. The biomimetic vascularized iPSC-hep spheroid is a microcapsule with a porous hyaluronic acid methacryloyl as a shell and a human-induced pluripotent stem-cell-derived hepatocyte spheroid as an inner phase, and human umbilical vein endothelial cells adhere to the surface of the shell. The biomimetic vascularized iPSC-hep spheroid of the present invention promotes effective communication between hiPSC-heps and HUVECs, and provides barrier protection for an encapsulated hiPSC-hep spheroid so as to avoid attack by the immune system. Compared with dispersed cells, the cell-to-cell interaction in the cell spheroid improves cell-to-cell communication, helps to simulate the physiological heterogeneous structure and cell microenvironment of the liver, and can more effectively repair an acutely failing liver.

The present invention relates to novel lipid nanoparticles capable of liver-specific delivery of mRNA, a manufacturing method therefor, and a liver disease therapeutic agent capable of regenerating the liver by liver-specific delivery of the bio-reprogramming factor mRNA using same. The lipid nanoparticles according to the present invention allow for liver-specific delivery of mRNA at very high efficiency, and the lipid nanoparticles that encapsulate the mRNA-based bio-reprogramming factor mRNA are specifically delivered to liver tissues of an individual requiring liver regeneration to induce short-term expression, thereby easily setting the dose and expression period of a therapeutic agent, leading to a significant reduction in side effects of a therapeutic agent for liver regeneration using an existing cell reprogramming factor.

The invention relates to compounds of formula (I) which are inhibitors of MKK4 (mitogen-activated protein kinase kinase 4) and their use in promoting liver regeneration or reducing or preventing hepatocyte death. The compounds selectively inhibit protein kinase MKK4 over protein kinases JNK1 and MKK7. In formula (I), especially, Rw is —NR10SO2R12; either a) Rx and Ry are F and Rz and Rzz are H; or b) Rx, Ry and Rzz are independently halogen and Rz is H; R5 is substituted phenyl or pyrimidinyl.

A microfluidic 3D-printed hydrogel based on fish liver decellularized extracellular matrix for liver regeneration and a preparation method. The hydrogel is prepared by means of combining fish liver decellularized extracellular matrix (dECM) and gelatin methacryloyl (GelMA), and loading induced pluripotent stem cell-derived hepatocytes (iPSC-heps) for liver regeneration. The microfluidic 3D-printed hydrogel based on fish liver decellularized extracellular matrix exhibits excellent biocompatibility, retains intact endogenous growth factors, maintains the biological activity of cells, ensures the effective encapsulation of the cells, and facilitates the robust functional expression of the iPSC-heps. After in-vivo transplantation, the survival rate and liver function of mice with acute liver failure are significantly improved, and liver regeneration and repair are promoted.

The invention relates to the technical field of hepatic failure treatment, and particularly discloses application of tsRNA-20 or a simulant thereof in preparation of drugs for treating chronic plus acute hepatic failure and / or promoting liver cell proliferation. Through tsRNA sequencing and qRT-PCR verification, down-regulated expression of the tsRNA-20 in a plasma sample and liver tissue in chronic and acute hepatic failure is determined, and cell experiments find that the tsRNA-20 regulates an ACPH / GRHL1 axis to promote liver cell proliferation. Specifically, it is found that tsRNA-20 is combined with an amidyl peptide hydrolase (ACPH), so that a Ras-ERK pathway is activated, nuclear translocation of a granulocyte-like transcription factor 1 (GRHL1) is promoted, and finally liver cell proliferation is enhanced. Therefore, when the tsRNA-20, the precursor tRNA-GIy-CCC thereof and the regulated objects ACPH and GRHL1 thereof are applied to treatment of the chronic and acute liver failure, the tsRNA-20, the precursor tRNA-GIy-CCC thereof and the regulated objects ACPH and GRHL1 thereof can be used as targets to be regulated to promote liver cell proliferation, so that liver regeneration is promoted, the treatment effect of the chronic and acute liver failure is improved, the lifetime of patients with liver diseases is prolonged, and the tsRNA-20, the precursor tRNA-GIy-CCC and the regulated objects ACPH and GRHL1 possibly become new targets for precise treatment. The clinical application value is relatively high.

Methods and uses of increasing or accelerating liver regeneration in a subject in need thereof are provided. In some aspects, such methods and uses comprise administering an effective amount of an androgen receptor inhibitor to a subject in need thereof, including, but not limited to, a subject suffering from one or more risk factors of post-hepatectomy liver failure. Any androgen receptor is contemplated for use in the methods described herein including, but not limited to, enzalutamide, apalutamide, bicalutamide, darolutamide, flutamide, nilutamide, or proxalutamide.

The present invention relates to the field of biomedicine technology, and provides the use of an upregulator of ACOT2 in promoting liver regeneration and liver function recovery after partial hepatectomy. Specifically, it provides the use of an ACOT2 expression promoter in the preparation of a drug for promoting liver regeneration and liver function recovery after partial hepatectomy, as well as a pharmaceutical composition comprising the ACOT2 expression promoter. The present invention has developed new discoveries about the function of the ACOT2 gene. The increased expression of ACOT2 after hepatectomy has a certain protective effect on liver regeneration, or can serve as a potential marker for warning the degree of postoperative liver function damage and liver regeneration capacity, and a therapeutic target for promoting postoperative liver regeneration. By using the intervention method of the present invention, the decomposition and consumption of lipid droplets in the liver lipid metabolism process are targeted, thereby promoting the recovery of liver function and liver-to-body ratio.

The invention relates to a stem cell pretreatment technology in the field of biomedicine, which is characterized in that stem cells are pretreated in a specific parameter window (10-80mu g / mL, 5-60min and 36-38 DEG C) by establishing an ozone concentration-time-temperature cooperative control model, so that the anti-apoptosis ability, homing efficiency and paracrine function of the stem cells are remarkably enhanced. The method breaks through the technical bottleneck of low survival rate of traditional stem cell transplantation, and avoids the carcinogenic risk of gene modification. The application covers the three fields of myocardial repair, liver regeneration and nerve injury, and the special culture medium and the kit developed in a matched manner realize standardized operation. The survival rate of the pretreated stem cells after transplantation is increased by more than two times, the VEGF secretion amount is increased by 150%, and a safe and efficient new treatment strategy is provided for clinic.

The present invention belongs to the technical field of biomedicine, and particularly relates to the use of licochalcone B. Licochalcone B promotes the proliferation of hepatocytes and significantly increases the liver / body weight ratio by inhibiting the activity of 15-PGDH protein, reducing the degradation of PGE2, increasing the level of endogenous PGE2, thereby promoting the regeneration and repair of the liver. The present invention discloses for the first time that licochalcone B is an effective small molecule inhibitor of 15-PGDH with the effect of promoting liver regeneration, and can be used to prepare drugs for promoting liver regeneration.

The invention discloses application of phloretin in preparation of a medicine for promoting liver cell proliferation, and belongs to the technical field of medicine. A specific cell proliferation tracing system of the hepatocytes is utilized, the proliferation activity of the hepatocytes in an animal body can be continuously recorded, animal experiments find that in the physiological homeostasis maintaining process of a mouse, phloretin can effectively promote the proliferation activity of the hepatocytes in the animal body without affecting the morphological structure of liver tissue, and it is found through hepatic lobule zoning analysis that phloretin can effectively promote the proliferation activity of the hepatocytes in the animal body without affecting the morphological structure of the liver tissue. The phloretin can effectively promote proliferation of hepatic cells in the first, second and third regions of the hepatic lobule. Therefore, phloretin is a potential medicine for liver regeneration.

The present invention discloses a biomimetic vascularized iPSC-hepatocyte sphere for liver regeneration and a preparation method thereof. The biomimetic vascularized iPSC-hepatocyte sphere is a microcapsule with porous methacryloylated hyaluronic acid as an outer shell and human induced pluripotent stem cell-derived hepatocyte spheroid as an inner phase, and human umbilical vein endothelial cells are adhered to the surface of the outer shell. The biomimetic vascularized iPSC-hepatocyte sphere of the present invention promotes effective communication between hiPSC-heps and HUVECs, and provides barrier protection for the encapsulated hiPSC-hep sphere to avoid the attack of the immune system. Compared with dispersed cells, the cell-to-cell interaction in the cell sphere improves the communication between cells, helps to simulate the physiological heterogeneous structure and cell microenvironment of the liver, and can more effectively repair the acute failure liver.

A multi-layered bio purifier includes a plurality of layers. Each layer may include a membrane having a first side and a second side opposite the first side, a first channel formed on the first side, and a second channel formed on the second side. Further, each layer may include a first type of cells formed on the first side in the first channel and a second type of cells formed on the second side in the second channel. The multi-layered bio purifier includes a first manifold assembly to split incoming blood into the first channel and the second channel of the plurality of layers and a second manifold assembly to combine processed blood from the first channel and the second channel of the plurality of layers. The processed blood may include detoxified or purified blood.

An EBDLR system includes a multi-layered bio purifier having a plurality of layers. Each layer includes a membrane, a first type of cells on a first side of the membrane in a first channel, and a second type of cells on a second side of the membrane in a second channel. The EBDLR includes a plasma separator to receive blood from a subject and separate a plasma component from the blood, a first reservoir to collect the plasma component, and a second pump to move the plasma component from the first reservoir to the multi-layered bio purifier. The multi-layered bio purifier distributes the plasma component into the first and second channels of each layer to purify the plasma component. The EBDLR includes a second reservoir to collect the purified plasma component and a third pump to infuse the purified plasma component from the second reservoir into the subject.

An objective of the present invention is to provide a liver disease regulatory formulation, which is beneficial to prevent the occurrence and development of a chronic liver disease by remodeling a liver regeneration microenvironment. The liver disease regulatory formulation, comprises a hepatocyte-derived liver progenitor cell or a secretory supernatant of the hepatocyte-derived liver progenitor cell.

Described herein are compounds that are MST1 inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of MST1 activity, such as diabetes and liver regeneration.

The invention discloses a traditional Chinese medicine compound for reducing the occurrence risk of liver cancer by improving a liver regeneration microenvironment and a preparation method of the traditional Chinese medicine compound. The traditional Chinese medicine compound is prepared by the following steps: adding water into five traditional Chinese medicine decoction pieces such as mistletoe, semen cuscutae, turmeric, oldenlandia diffusa and semen coicis, decocting twice (2 hours each time), combining decoctions, filtering, standing filtrate overnight, taking supernate, concentrating into thick extract, and storing the extract for later use; taking the thick paste, adding a proper amount of starch, uniformly stirring, putting into a drying box, and drying at the temperature of below 80 DEG C; taking out the dried product, weighing, crushing, adding starch until the total weight is 450g, and uniformly mixing for later use; taking the medicinal powder, preparing a soft material by using 80% ethanol, granulating, drying at the temperature of 80 DEG C or below, and finishing granules. And taking the granules, adding 0.3% of magnesium stearate, uniformly mixing, filling into No.0 capsules, preparing 1000 granules (0.45 g per granule), carrying out aluminum-plastic plate pressing, and packaging. The compound traditional Chinese medicine is mainly used for reducing the occurrence risk of liver cancer by improving the liver regeneration microenvironment for chronic liver disease patients.

The invention discloses application of dihydroartemisinin in construction of liver organoid, which is characterized in that by adding dihydroartemisinin into a liver organoid culture medium, the maturity of the liver organoid can be obviously improved, the maturity period is shortened, and the liver function characteristics (such as metabolic function and gene expression maturity) of the organoid are enhanced. The defects of an existing liver organ model in the aspect of simulating primary liver functions are effectively overcome, a more accurate in-vitro model is provided for research of liver related diseases, and a new platform and possibility are provided for development of liver regeneration and treatment methods.

The invention discloses a preparation method and application of a hepatic parenchymal cell targeting gene delivery system, and relates to construction and preparation of a hepatic parenchymal cell targeting lipid material GalNAc-PEG2000-DSPE modified MKK4-siRNA (siMKK4) loaded lipid nanoparticle gene delivery system GalNAc-LNP-siMKK4, and the hepatic parenchymal cell targeting gene delivery system can be used for active targeting gene therapy of hepatic failure. The parenchymal hepatic cell targeted gene delivery system selects siMKK4 as a liver regeneration promoting gene therapy drug, has the advantages of clear target spot and capability of accurately silencing a target gene, and can protect siMKK4 from being degraded by extracellular nuclease as a gene delivery carrier, so that the targeted gene delivery system has a good application prospect. N-acetylgalactosamine (GalNAc) is selected as a target head, so that therapeutic genes can be precisely targeted and delivered to parenchymal hepatic cells, the risk of tumorigenesis of other parts of an organism can be reduced while liver regeneration is promoted, and a new thought and a new method are provided for liver regeneration treatment of hepatic failure patients.

A fish liver decellularized extracellular matrix based microfluidic 3D printing hydrogel for liver regeneration, and a preparation method thereof are provided. A fish liver decellularized extracellular matrix (dECM) is combined with gelatin methacryloyl (GelMA), and loaded with hepatic spheroids derived from induced pluripotent stem cells (iPSC-hep) for liver regeneration. The fish liver decellularized extracellular matrix based microfluidic 3D printing hydrogel of the present disclosure has excellent biocompatibility and retains intact endogenous growth factors, maintains the biological activity of cells, ensures effective cell encapsulation, and is conducive to robust functional expression of iPSC-hep. After being transplanted in vivo, the hydrogel significantly improves the survival rate and liver function of mice with acute liver failure, and promotes liver regeneration and repair.

The invention provides a cell surface marker of a subgroup with strong liver differentiation capability and application thereof. The invention discloses that the pluripotent stem cells have NAD < + > and NADH metabolic heterogeneity, and are closely related to the expression of CD157. On the basis, the content of NAD < + > / NADH or the expression of CD157 can be taken as an investigation object, and cells with strong liver differentiation capacity or cells with high self-renewal capacity can be obtained from the pluripotent stem cells. The invention also provides a method for sorting the cells, a method for preparing hepatic differentiation cells by using the cells, and the like. The invention provides a new way for the fields of stem cell differentiation and liver regeneration.

The present invention discloses the use of an acetyl-CoA (Ac‑CoA) promoter in the preparation of a drug for promoting liver regeneration. The present invention utilizes a mouse partial hepatectomy model and administers GS‑0976 before hepatectomy to increase Ac‑CoA in the liver. The results show that increased Ac‑CoA in the liver has the ability to improve liver function after liver injury and promote hepatocyte proliferation. The mechanism involves Ac‑CoA promoting MSL1 phase separation, increased STAT3 and H4K16 acetylation, which manifests as significantly upregulated cell cycle-related genes and increased hepatocyte proliferation. The experimental results show that increasing liver Ac‑CoA levels has the effect of promoting liver regeneration, providing a new solution for the recovery and treatment of hepatectomy and its complications.

This invention discloses a double-sided hydrogel with hemostatic, anti-adhesion, and wound repair properties, as well as its preparation and application, belonging to the field of biomedical materials technology. The double-sided hydrogel comprises a repair layer and an anti-adhesion layer. The repair layer is a hydrogel formed by photocuring with OHA, GelMA, AAc, AAc-NHS, and p(APMA-co-THMA) as core components. p(APMA-co-THMA) is obtained by polymerizing THMA and APMA. The anti-adhesion layer is formed by immersing one side of the repair layer in an aqueous solution containing SBMA, GelMA, and MBAA, followed by a thermal cross-linking reaction. The double-sided hydrogel provided by this invention possesses ideal mechanical properties and wet adhesion ability, and exerts anti-inflammatory and wound-healing effects on liver wounds, which can solve the problems of postoperative bleeding, adhesion, and liver regeneration disorders after partial hepatectomy in clinical practice.

A cryopreservation solution and use thereof in reducing an ischemia-reperfusion injury (IRI) of a cell, a tissue, or an organ, belonging to the technical field of cold storage or cryopreservation. By using innovative exploration mechanisms, it is found that phosphocholine, quinoline-4-carboxylic acid (QCA), and sodium tauroursodeoxycholate (TUDCA) have significant differences during a cryopreservation-rewarming period between hibernating and non-hibernating animals. Based on this, adding the phosphocholine, the QCA, and the TUDCA into a preservation solution to allow cryopreservation of cells, tissues, and / or organs shows a high cell survival rate, can effectively reduce apoptosis caused by cryopreservation-rewarming, reduce mitochondrial reactive oxygen species (ROS), maintain a cell membrane integrity, effectively reduce mitochondrial damage caused by cryopreservation-rewarming, reduce the IRI, and promote liver regeneration. This is of great significance to the advancement of organ transplantation and preservation.

The invention discloses application of NSD2 in promoting liver regeneration and improving liver injury. Specifically, the invention provides application of an NSD2 gene, mRNA, protein or an expression promoting agent thereof, the NSD2 gene, the mRNA, the protein or the expression promoting agent is used for preparing a preparation or a composition, and the preparation or the composition is used for promoting liver regeneration or relieving and / or treating liver injury. Research shows that overexpression of the NSD2 can effectively promote liver regeneration.

This invention discloses the application of β-hydroxybutyric acid (BHB) in the preparation of products that promote hepatocyte proliferation and liver regeneration. This invention discovers that β-hydroxybutyric acid can promote liver regeneration and recovery by promoting the proliferation of hepatocytes in the residual liver after partial hepatectomy. Therefore, β-hydroxybutyric acid can be used to prepare products that promote liver regeneration. This invention not only discloses the application of β-hydroxybutyric acid in promoting liver regeneration, providing a drug source for the development of products that promote liver regeneration, but also provides a theoretical basis for subsequent clinical intervention strategies to promote liver regeneration. This helps to improve liver regeneration capacity and avoid poor prognosis and liver failure caused by insufficient liver regeneration capacity after partial hepatectomy or living donor liver transplantation.

The invention relates to the field of biological medicine, and discloses application of a reagent for promoting expression of an LECT2 gene in preparation of a medicine for promoting liver regeneration, application of the reagent for promoting expression of the LECT2 gene in preparation of the medicine for promoting liver regeneration and the medicine for promoting liver regeneration with overexpressed LECT2 as a main active component. According to the present invention, with the application of the virus vector, the liver regeneration after the liver resection can be promoted, the AAV9-Lect2 or the control (AAV9-Ctrl) is injected into the C57BL / 6J mouse body through the overexpression of the virus vector, the molding succeeds after 4 weeks, the 2 / 3 resection operation of the liver is performed on the two groups of mice, and the sample is collected after 48 h; the result shows that in the mouse treated by AAV9-Lect2, the expression of LECT2 in the liver is obviously increased. Compared with a control group, mice subjected to AAV9-Lect2 treatment show more proliferative hepatocytes, the immunohistochemical staining results of Ki67 and PCNA are more remarkable, and LECT2 has potential application value in drugs for promoting liver regeneration and treatment.

The present invention provides application of quinoline-4-carboxylic acid in the preparation of anti-aging products, and liver protection and liver regeneration promotion products, and belongs to the technical field of medicines. The present invention reveals that quinoline-4-carboxylic acid can be used as a novel additive for in vitro expansion culture of mesenchymal stem cells, which breaks through the bottleneck that mesenchymal stem cells are prone to aging in vitro culture, and optimizes the clinical development and application of mesenchymal stem cells; quinoline-4-carboxylic acid can relieve the aging-related phenotype of drosophila and mouse, enhance the movement ability of the drosophila and the muscle strength of the mouse, prolong the life span of the drosophila and the mouse, and thus is expected to become an effective component of anti-aging treatment drugs or health-care products; quinoline-4-carboxylic acid can increase the survival rate of mice after the liver cutting operation, promote liver regeneration after liver cutting injury, and thus is expected to become an effective component of drugs or health-care products to promote the prognosis of patients after the liver cutting operation, to promote liver regeneration, and to relieve or treat liver injury.

The invention provides an application research of nano layered double hydroxides (LDH) for immunoregulation of interleukin-6 (IL-6) to promote liver regeneration, and based on the biomedical potential of the layered double hydroxide nano material, the action mechanism of the layered double hydroxides nano material in liver regeneration is systematically clarified. According to the application, a potential molecular mechanism of promoting liver regeneration by LDH is disclosed for the first time from the perspectives of immunoregulation and signal transduction, and a new theoretical basis and an experimental basis are provided for application of a nano material in tissue regeneration and liver function reconstruction. In the future, physicochemical properties and targeting of LDH can be further optimized, interaction with immune cells, signal transduction network remodeling and long-term safety of LDH can be deeply discussed in combination with a multi-omics technology and an in-vivo imaging means, and a direction is provided for developing novel immunoregulation type nano-drugs.

The present invention relates to pyrazolopyridine compounds which inhibit mitogen-activated protein kinase kinase 4 (MKK4), and in particular selectively inhibit MKK4 relative to protein kinases JNK1 and MKK7. The compounds can be used to promote liver regeneration or reduce or prevent liver cell death. They can also be used to treat osteoarthritis or rheumatoid arthritis or CNS related diseases.

The invention discloses an application of Laminarin in preparation of a medicine for treating cholestatic liver diseases. The invention reveals that the Laminarin can simultaneously inhibit the expression of inflammatory factors and promote liver regeneration for the first time, and fills the blank of the prior art.