44 results about "Hepatocellular necrosis" patented technology

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 provides a medicine for treating acute hepatic failure. The medicine comprises curcumin and extracellular vesicles derived from honey. The invention further provides a preparation method and application of the medicine. According to the invention, the extracellular vesicles are separated from the honey and are proved to have a remarkable anti-inflammatory effect, curcumin is loaded to the extracellular vesicles of the honey, the treatment effect on acute hepatic failure is excellent, and a new effective medicine is provided for clinic.

This invention discloses a virulent strain of type I canine adenovirus and its application in constructing animal infection models, belonging to the field of biotechnology. The virulent strain of type I canine adenovirus is named canine adenovirus type 1 strain 0601, with accession number CCTCC NO: V202604. The virus titer reaches 10. 7.5 TCID 50 / mL. This virus can be used to construct an animal model of canine adenovirus type I infection, which exhibits typical clinical symptoms, such as hepatic hemorrhage, hepatocellular necrosis, and venous and sinusoidal congestion. The constructed animal model can be used for future canine adenovirus vaccine development, immune protection assessment, and efficacy evaluation of preventive and therapeutic drugs, providing excellent biological materials and theoretical basis for further control of canine adenovirus type I.

The invention discloses a preparation method and application of bioactive lipid and lipid nanoparticles thereof. The bioactive lipid molecule is formed by bonding long-chain fatty acid (LCFA) with different chain lengths with two functional small molecules, namely phenylboronic acid pinacol ester (PBAP) and Tempol (Tpl) respectively, so that two types of lipid molecules, namely PBAP-LCFA and Tpl-LCFA, with anti-inflammatory activity are constructed. The lipids are used as functional components, and the anti-inflammatory lipid nanoparticles with good biocompatibility, including PLP, TLP and TPLP, can be prepared through a film dispersion method. The lipidoid and the lipid nanoparticles are simple and convenient in preparation process, controllable in structure and function and easy for large-scale production, and have treatment potential in various acute and chronic inflammatory diseases. In an animal model, the lipid nanoparticles have remarkable curative effects on acute peritonitis, acute lung injury, acute hepatic failure, asthma and other diseases. Besides, the lipid bilayer structure of the TPLP can efficiently entrap hydrophilic / hydrophobic drugs, can synergistically deliver treatment drugs while exerting the anti-inflammatory effect of the TPLP, and realizes a synergistic combined treatment strategy for chronic lung inflammation and other diseases.

The present invention provides, in part, a novel small molecule PHD inhibitor having a structure according to Formula (A) or a sub-formula thereof: or a pharmaceutically acceptable salt thereof. The compounds provided herein are useful in the treatment of diseases, including heart diseases (e.g., ischemic heart disease, congestive heart failure, and valvular heart disease), lung diseases (e.g., acute lung injury, pulmonary arterial hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), liver diseases (e.g., acute liver failure and liver fibrosis, and cirrhosis), and kidney diseases (e.g., acute liver failure, liver fibrosis, and cirrhosis). Acute kidney injury and chronic kidney disease).

The present invention provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (I), and sub-formulas thereof: Formula (I) or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for treatment or prevention of diseases including heart (e.g. ischemic heart disease, congestive heart failure, and valvular heart disease), lung (e.g., lung inflammation, pneumonia, acute lung injury, pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), respiratory (e.g.,respiratory infection, acute respiratory distress syndrome), liver (e.g. acute liver failure and liver fibrosis and cirrhosis), and kidney (e.g. acute kidney injury and chronic kidney disease) disease, inflammatory bowel disease (IBD), ischemic reperfusion injury (e.g., stroke), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and white matter injury (WMI).

This invention discloses a polyethylene glycol-modified magnesium boride nanosheet and its application in treating acute liver failure and hepatic encephalopathy caused by acetaminophen. The nanosheet uses magnesium boride nanosheets as a core, with polyethylene glycol modified on the surface to improve biocompatibility. The nanosheet of this invention exhibits good antioxidant properties and can be used to prepare nanomedicines for treating acute liver failure and / or hepatic encephalopathy caused by acetaminophen. It generates reducing hydrogen gas through a hydrolysis reaction, effectively scavenging reactive oxygen species at the site of liver failure, thereby inhibiting inflammatory responses and effectively alleviating symptoms caused by acute liver failure.

The present invention relates to the field of liver disease, and more particularly to a method for determining the presence of chronic plus acute liver failure or for determining the risk of developing ACLF in a patient suffering from cirrhosis or a delayed early stage of ACLF. The invention also relates to a method for distinguishing patients suffering from decompensated liver cirrhosis, acute decompensated liver cirrhosis (ADC) or delayed ACLF from patients suffering from early ACLF or ACLF 1, 2, 3, a method for determining the degree of systemic inflammation and a method for determining the presence of a bacterial infection with sepsis.

The invention belongs to the technical field of biological medicines, and relates to an application of Lindenamarin in medicines for preventing, relieving or / and treating acetaminophen-induced liver injury or / and acute hepatic failure. According to the application disclosed by the invention, it is found for the first time that Linocinnamarin can be used for preventing, relieving or / and treating APAP-induced liver injury or / and acute liver failure; in addition, the invention also finds that the Linocinnamarin can improve liver cell apoptosis, inflammatory response and oxidative stress reaction caused by APAP-induced liver injury or / and acute liver failure, and also finds that the Linocinnamarin can improve the liver cell apoptosis, inflammatory response and oxidative stress reaction caused by APAP-induced liver injury. Therefore, the invention provides a new treatment thought for clinically treating the APAP-induced liver injury or / and acute liver failure.

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.

Compositions comprising 5-cholesten-3, 25-diol, 3-sulfate (25HC3S) or pharmaceutically acceptable salt thereof and at least one cyclic oligosaccharide, e.g., a cyclodextrin (CD), are provided. The compositions may be used to prevent and / or treat a variety of diseases and conditions, including organ failure (e.g. acute liver failure), high cholesterol / high lipids, and various inflammatory diseases and conditions.

The invention discloses application of induced pluripotent stem cell-derived mesenchymal stem cells in preparation of a medicine for treating acute hepatic failure, belongs to the technical field of biomedicine, and solves the problem of unsatisfactory treatment effect caused by immunological rejection when the mesenchymal stem cells are used for treating the acute hepatic failure in the prior art. The induced pluripotent stem cell-derived mesenchymal stem cell provided by the invention has a protective effect on acute liver injury, can improve the levels of aspartate aminotransferase and alanine aminotransferase, remarkably improves the liver function of the injured liver, reduces the level of inflammatory factor TNF-alpha, reduces the necrotic focus area, reduces inflammatory cell infiltration, and has the effects of preventing and treating acute liver injury. The apoptosis level of liver cells is reduced, and the level of CD4 + T cells is reduced.

The present application relates to a kind of VSIG4 based on reversible immunological affinity magnetic bead separation + The present application provides a method for isolating VSIG4-positive macrophages, which uses reversible immunological affinity magnetic beads coupled with anti-VSIG4 antibodies to contact with a sample, and enriches VSIG4-positive macrophages by magnetic separation + The present application provides a method for isolating VSIG4-positive macrophages, which uses reversible immunological affinity magnetic beads coupled with anti-VSIG4 antibodies to contact with a sample, and enriches VSIG4-positive macrophages by magnetic separation + The present application provides a method for isolating VSIG4-positive macrophages, which uses reversible immunological affinity magnetic beads coupled with anti-VSIG4 antibodies to contact with a sample, and enriches VSIG4-positive macrophages by magnetic separation + The present application provides a method for isolating VSIG4-positive macrophages, which uses reversible immunological affinity magnetic beads coupled with anti-VSIG4 antibodies to contact with a sample, and enriches VSIG4-positive macrophages by magnetic separation The isolated cells of the present application can reduce liver inflammation and injury, and effectively treat acute liver injury and acute liver failure. The isolation method of the present application is fast, mild and efficient, and the obtained cells are functional and suitable for adoptive cell therapy, which has a broad clinical application prospect.

The invention discloses application of PYGL as an auxiliary diagnosis marker for hepatitis E related acute hepatic failure, and belongs to the technical field of biomedical detection. By detecting the expression level of PYGL in serum of a subject, hepatitis E related acute hepatic failure patients (HEV-ALF), acute hepatitis E patients (AHE) and healthy control people (HCs) can be effectively distinguished. The result shows that the serum PYGL expression level of HEV-ALF patients is obviously higher than that of acute hepatitis E patients and healthy control people; the serum PYGL expression level has significant correlation with the clinical outcome of patients with hepatitis E related acute hepatic failure, and the serum PYGL expression level of patients in a death group is significantly higher than that of patients in a survival group; the expression level of the serum PYGL is also associated with the number of organ failure of the patient, and can reflect the dynamic change of the condition of the patient. Therefore, the serum PYGL can be used as an effective biomarker for auxiliary diagnosis of the hepatitis E related acute hepatic failure and prognosis evaluation of the hepatitis E related acute hepatic failure.

This invention relates to the field of biomedical materials technology, providing a heparinized dual-growth factor recellularized adipose tissue decellularized scaffold material, its preparation method, and its applications. The preparation method includes: decellularizing adipose tissue to obtain adipose tissue decellularized scaffold; heparinizing the scaffold to obtain a heparinized adipose tissue decellularized scaffold; loading hepatocyte growth factor and vascular endothelial cell growth factor onto the scaffold to obtain a heparinized dual-growth factor adipose tissue decellularized scaffold; seeding induced pluripotent stem cell-derived hepatocytes onto the scaffold, and culturing to obtain a heparinized dual-growth factor recellularized adipose tissue decellularized scaffold (RAT). This invention uses rat inguinal adipose tissue to prepare RAT material, which is low-cost, readily available, has a simple preparation process, and is easy to scale up. The RAT material of this invention can achieve liver tissue damage repair and hepatocyte regeneration, providing a new treatment strategy for acute liver failure.

Provided herein are methods and compositions related to at least partially recellularizing human organs. Various methods of decellularizing organs of a non-human animal and re-cellularizing extracellular matrix of a non-human animal with a cellular composition. Compositions and methods for treating liver or other diseases, such as acute liver failure, using ex vivo bioengineered liver or other organs are also provided.

The invention discloses a novel TNF-alpha targeted protein degradation agent for treating acute hepatic failure, the TNF-alpha targeted protein degradation agent can accurately remove excessive TNF-alpha to block a liver injury signal, and the defects that a traditional TNF-alpha inhibitor interferes tissue repair due to an overlong half-life period and an Fc fragment triggers an ADCC / CDC effect to cause drug-related hepatotoxicity are overcome. The pharmaceutical safety is improved while the treatment effectiveness is ensured, a better treatment choice is provided for acute hepatic failure and other TNF-alpha related diseases, and the pharmaceutical composition has a good clinical application prospect and an important conversion value.

Disclosed is a kaempferol mesenchymal stem cell membrane biomimetic material capable of more accurately targeting a damaged tissue. The biomimetic nanomaterial is simple to prepare, high in universality, and suitable for large-scale production. The present invention uses mesenchymal stem cell membranes to improve the biocompatibility and targeting property of the carrier and prolong the circulation time of the drug in vivo. The biomimetic nanomaterial prepared by the present invention enables targeted delivery of kaempferol to the liver, providing a novel treatment method for acute liver failure ALF.

Part of this invention provides novel small molecule PHD inhibitors having structures according to formula (I) and its derivatives: or pharmaceutically acceptable salts thereof. The compounds provided herein may be used to treat the following diseases: including heart diseases (e.g., ischemic heart disease, congestive heart failure, and valvular heart disease), lung diseases (e.g., lung inflammation, pneumonia, acute lung injury, pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), respiratory diseases (e.g., respiratory infections, acute respiratory distress syndrome), liver diseases (e.g., acute liver failure, liver fibrosis, and cirrhosis), and kidney diseases (e.g., acute kidney injury and chronic kidney disease), inflammatory bowel disease (IBD), ischemic-reperfusion injury (e.g., stroke), and retinopathy of prematurity (ROP).

The present invention provides, in part, a novel small molecule PHD inhibitor having a structure according to Formula (A) or a sub-formula thereof: or a pharmaceutically acceptable salt thereof. The compounds provided herein are useful in the treatment of diseases, including heart diseases (e.g., ischemic heart disease, congestive heart failure, and valvular heart disease), lung diseases (e.g., acute lung injury, pulmonary arterial hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), liver diseases (e.g., acute liver failure and liver fibrosis, and cirrhosis), and kidney diseases (e.g., acute liver failure, liver fibrosis, and cirrhosis). Acute kidney injury and chronic kidney disease).

The present invention provides, in part, novel small molecule PHD inhibitors having a structure according to Formula (A) or its subformulas: or a pharmaceutically acceptable salt thereof. The compounds provided herein are useful for treating diseases including heart disease (e.g., ischemic heart disease, congestive heart failure, and valvular heart disease), lung disease (e.g., acute lung injury, pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), liver disease (e.g., acute liver failure and liver fibrosis and cirrhosis), and kidney disease (e.g., acute kidney injury and chronic kidney disease). #imgabs0#

The invention discloses miR-19b-3p which has a treatment effect on hepatic failure, particularly acute hepatic failure. Therefore, the miR-19b-3p can be prepared into the medicine for treating the hepatic failure, particularly the acute hepatic failure, so that a brand new material basis is laid for the development of the medicine for treating the hepatic failure.

This invention discloses the application of β-1,4-galactosyltransferase 1 and its inhibitors in liver diseases, particularly acute liver injury and liver failure. The application of β-1,4-galactosyltransferase 1 and its inhibitors in acute liver injury and liver failure provides the correlation between β-1,4-galactosyltransferase 1 and acute liver injury and liver failure, confirming that inhibiting the activity of β-1,4-galactosyltransferase 1 can alleviate acute liver injury and liver failure. β-1,4-galactosyltransferase 1 can serve as a drug target for screening acute and chronic hepatitis, liver injury, fatty liver, liver fibrosis, and acute and chronic liver failure. This invention also confirms the alleviating effect of β-1,4-galactosyltransferase 1 inhibitors on acute liver failure. β-1,4-galactosyltransferase 1 inhibitors improve acute liver failure by reducing the enzyme activity or protein expression of β-1,4-galactosyltransferase 1.

The invention discloses application of uridine as a serum marker in prognosis of hepatitis B related chronic-acute hepatic failure, the uridine content is an independent predictive factor of 28-day mortality of patients with hepatitis B related chronic-acute hepatic failure, and when the mortality of the patients is increased, the uridine expression quantity is reduced, so that the content of the uridine in the prognosis of hepatitis B related chronic-acute hepatic failure is reduced. Uridine can be used for constructing a hepatitis B related chronic-acute liver failure prognosis prediction model. The serum marker uridine provided by the invention can be used for identifying high-death-risk patients in the early stage of hepatitis B-related chronic-acute hepatic failure, provides important reference for clinical doctors to accurately judge the severity of illness, and can identify the high-death-risk patients in the early stage and take corresponding positive treatment measures.

The invention relates to the field of medicine application, in particular to application of a fire capsule to treatment and / or prevention of hepatic failure. The fire capsule disclosed by the invention has a good prevention and treatment effect on mouse hepatic failure caused by D-GalN / LPS, can obviously improve the liver function level, has a regulation and control effect on a plurality of inflammation-related signal channels, enhances the oxidative stress resistance of a body, inhibits liver cell apoptosis, obviously relieves hepatic tissue pathological injury caused by D-GalN / LPS, and has an obvious liver protection effect.

Disclosed herein are extracellular vesicle (EV) composites and their uses in the treatment of liver injury, particularly, acute liver failure (ALF). The EV composite includes an EV derived from a mesenchymal stem cell (MSC), and a recombinant polypeptide conjugated to the EV via a click chemistry reaction. Preferably, the recombinant polypeptide is a single-chain variable fragment (scFv) that recognizes and binds to asialoglycoprotein receptor 1 (ASGR1) or ASGR2. The present disclosure thus also encompasses a method of treating ALF in a subject. The method includes the step of administering an effective amount of the EV composite to the subject to alleviate symptoms associated with the ALF.

This invention discloses a macromolecular JAK inhibitor, its preparation method, and its applications. This macromolecular JAK inhibitor is an anti-inflammatory amphiphilic polymer of hexachlorocyclotriphosphazene or cyanuric chloride coupled with different functional groups. The anti-inflammatory amphiphilic polymer is synthesized with hexachlorocyclotriphosphazene or cyanuric chloride as the backbone structure, linked by a stepwise nucleophilic substitution reaction with different proportions of hydrophilic modules polyethylene glycol and 3-aminobenzoyl hydrazide (i.e., luminol). The preparation method of this type of anti-inflammatory macromolecular drug is simple, its structure and function are controllable, and it is easy to synthesize on a large scale. Furthermore, this type of amphiphilic anti-inflammatory macromolecular drug can self-assemble into nanomicelles in aqueous solution through intermolecular interactions. It can be applied to the treatment of various acute and chronic inflammations or diseases related to the JAK signaling pathway, and can be administered via intravenous injection, subcutaneous injection, nebulized inhalation, intramuscular injection, and any combination of the above methods. This anti-inflammatory macromolecular drug has significant therapeutic effects in acute lung injury, acute kidney injury, acute liver failure, sepsis, and asthma.

There is provided the compound N,N-bis-2-mercaptoethyl isophthalamide (NBMI), or a pharmaceutically-acceptable salt and / or derivative thereof, for use in the treatment or prevention of paracetamol toxicity. Such compounds have particular utility in the treatment or prevention of acute liver failure associated with paracetamol toxicity.

The invention is suitable for the technical field of biomedical materials, and provides a biological mixed decellularized liver cancer para-carcinoma tissue hydrogel as well as a preparation method and application thereof. The prepared decellularized hydrogel is wide in raw material source, clinically available waste such as human liver cancer para-carcinoma tissue blocks is converted into a scaffold material, the problem that scaffold sources are scarce is effectively solved, and resource utilization of clinical waste is achieved; meanwhile, the decellularized hydrogel completely retains a natural extracellular matrix, is low in immunogenicity and excellent in biocompatibility, can provide a highly bionic structural platform for cells (such as hepatocytes derived from human induced pluripotent stem cells), and fully meets the requirements of cell adhesion, growth and proliferation; besides, exogenous regeneration active substances such as mesenchymal stem cell source exosomes can be effectively integrated, the capabilities of regulating inflammation, promoting tissue repair and improving cell survival are remarkably enhanced, and a novel and effective treatment mode is provided for acute hepatic failure treatment.

The present invention discloses ion-specific high-cell-density microcarriers, a bioartificial liver system, and preparation methods and applications. Protein particle microcarriers are produced by shearing between an aqueous phase and an oil phase, wherein the aqueous phase is composed of ions and a photocurable protein hydrogel, and the oil phase is composed of a high-viscosity oil. The protein particles are recrystallized using a quenching-annealing method. The polymer structure network produced during the recrystallization process is retained by freeze-drying to form a biomimetic niche pore structure, thereby obtaining ion-specific high-cell-density microcarriers. The present invention combines protein-based hydrogels with the Hofmeister effect through microfluidic technology to prepare in vitro biomimetic liver microcarriers with high liver cell density. Liver cells can proliferate in large numbers on the microcarriers and express normal metabolites. The microcarriers can be used to prepare bioartificial liver systems for the treatment of acute liver failure.