33 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.

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.

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 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).

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.

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.

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 provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (I), and sub-formulas thereof: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). 

The invention belongs to the crossing field of nano material preparation and biological medicine, and discloses a polylysine modified tungsten-based heteropolyacid nano-cluster and application thereof. A tungsten-based heteropolyacid nano-cluster is synthesized by simulating a folin phenol detection method, rutin is used as an antioxidant to wrap the surface of the tungsten-based heteropolyacid nano-cluster, and electropositive polylysine is further modified on the surface of the tungsten-based heteropolyacid nano-cluster. The nano-cluster disclosed by the invention has good stability and biocompatibility, can be used for treating acetaminophen-induced acute hepatic failure, and can be used for specifically removing active oxygen at a hepatic failure part in a targeted manner through oxidation reduction and specifically removing extracellular free DNA (Deoxyribonucleic Acid) through an electrostatic adsorption effect, so that inflammatory response is inhibited; the symptoms caused by acute hepatic failure are effectively relieved.

The application belongs to the field of nanometer material preparation and biological medicine, and discloses a polylysine modified tungsten-based heteropoly acid nanocluster and application thereof. The tungsten-based heteropoly acid nanocluster is synthesized by imitating the Folin phenol detection method, rutin is wrapped on the surface of the tungsten-based heteropoly acid nanocluster as an antioxidant, and the polylysine with positive electricity is further modified on the surface of the tungsten-based heteropoly acid nanocluster. The nanocluster has good stability and biocompatibility, and can be used for treating acetaminophen-induced acute liver failure. The nanocluster specifically removes active oxygen at the liver failure site through oxidation and reduction, and specifically removes extracellular free DNA through electrostatic adsorption, so as to inhibit the inflammatory reaction and effectively relieve the symptoms caused by acute liver failure.

The present application relates to the field of medical artificial intelligence and clinical auxiliary decision-making technology, in particular to an abnormal test result combination pattern recognition method and system based on deep learning, comprising: receiving test results output by a hospital test information system to construct a 48-dimensional test index vector; calculating a multi-dimensional joint deviation degree based on a group health joint distribution reference model; constructing a patient individual baseline with stable period test values for baseline drift correction, and inferring an individual baseline and giving a baseline disturbance double-channel representation when the stable period is missing with a meta-learning baseline inference subnetwork output; inputting the individualized joint deviation degree and the baseline disturbance double-channel representation into a multilayer perceptron network classifier to output five types of severe clinical event prediction probabilities of sepsis, acute kidney injury, disseminated intravascular coagulation, acute liver failure and acute exacerbation of chronic diseases, and the training loss contains a pathogenic causal diagram prior constraint term; when the prediction probability exceeds 40%, an orange reminder is pushed to the mobile terminal of the responsible nurse.

This invention relates to a novel use of synephrine in the preparation of drugs for treating cholestatic liver disease, belonging to the field of pharmaceutical technology. Cholestatic liver disease is characterized by jaundice and conjugated bilirubin and / or total bilirubin hyperconjugation caused by impaired bilirubin excretion due to various reasons. Its causes include common bile duct stones, pancreatic duct cancer, common bile duct malignant tumors, pancreatic cancer, biliary parasitic diseases, viral hepatitis cirrhosis, alcoholic liver disease, fatty liver disease, drug-induced liver injury, primary biliary cirrhosis, intrahepatic sclerosing cholangitis, and certain congenital diseases such as Dubin-Johnson syndrome and Rotor syndrome. This invention establishes a mouse cholestasis model using bile duct ligation and administers synephrine by gavage to evaluate its protective effect against liver injury. The results showed that synephrine significantly improved jaundice caused by cholestasis, reduced hepatocellular necrosis and inflammatory infiltration caused by cholestasis, alleviated bile duct dilation, decreased serum total bilirubin (TBIL) and direct bilirubin (DBIL), and reduced the levels of total bile acids (BA) in liver tissue and plasma. Furthermore, the above-mentioned effects of synephrine in improving cholestasis showed a clear dose-dependent effect. This invention reveals for the first time the application of synephrine in cholestatic liver disease, demonstrating good safety and promising clinical development prospects.

The invention provides an application of selenium-rich probiotics in preparation of a preparation for treating fluoxetine-induced liver injury, and relates to the technical field of biological medicine, the application is characterized in that Se-BL is obtained by reducing sodium selenite through ascorbic acid and modifying the surface of bifidobacterium longum, and nano-scale selenium dots are formed. The preparation plays a role through dual mechanisms: active oxygen (ROS) is directly removed, an Nrf2 pathway is activated, and the liver oxidation resistance (GSH, SOD) is improved; the traditional Chinese medicine composition is capable of inhibiting NF-kappa B inflammation signal channels, reducing proinflammatory factors (TNF-alpha and IL-6) and synchronously regulating intestinal flora so as to enhance the intestinal barrier function. Experiments prove that the traditional Chinese medicine composition can remarkably reduce the level of serum transaminase (ALT / AST / ALP) and relieve liver tissue necrosis and lipid peroxidation damage (MDA), the dosage form of the traditional Chinese medicine composition is an oral preparation, and each dose of the traditional Chinese medicine composition contains 1 * 10 <-1 > * 10 <-1 > CFU of Se-BL viable bacteria. The selenium-modified probiotics are used for antagonizing hepatotoxicity of mental drugs for the first time, and an innovative therapy is provided for fluoxetine-induced drug-induced liver injury (DILI) and acute hepatic failure (ALF).

The invention relates to the field of biological diagnosis, in particular to application of a miRNA combination in blood exosome as a biomarker in diagnosis of hepatitis B virus related chronic plus acute liver failure. The invention provides a marker, and the marker comprises one or more of the following components: hsa-miR-548aq-3p, hsa-miR-548j-5p, hsa-miR-185-3p, hsa-miR-455-5p, hsa-miR-6731-3p and hsa-miR-320e. The invention also provides a method for preparing the marker. According to the miRNA biomarker combination and application provided by the invention, HBV-ACLF can be effectively screened without liver biopsy, so that the miRNA biomarker combination has high non-invasive and minimally invasive safety, the accuracy of early diagnosis of HBV-ACLF in China can be improved, the false positive rate of HBV-ACLF diagnosis is reduced, the phenomenon of excessive medical treatment is reduced, and more comprehensive diagnosis information is provided for clinic.

A method of treating a subject with acute liver failure is disclosed. The method involves including an EBDLR system into the subject's blood circuit and passing blood through the EBDLR system, where the blood is continuously taken from the subject. Further, the method includes separating the blood into a plasma component and remainder using a plasma separator of the EBDLR system and then passing the plasma component into a bio purifier having a plurality of layers. Each layer may include hepatocytes on a first side of a membrane in a first channel, and endothelial cells on a second side of the membrane in a second channel. Furthermore, the method includes splitting the plasma component into the first channel and the second channel of the plurality of layers to purify the plasma component, restoring the blood by combining the purified plasma component and the remainder, and continuously returning the restored blood into the subject.

Methods and compositions relating to at least partially recellularized human organs are provided herein. Various methods for decellularizing non-human animal organs and recellularizing the non-human animal extracellular matrix with cellular compositions. Furthermore, compositions and methods for treating liver disease or other diseases (such as acute liver failure) using an extracorporeal bioartificial liver or other organs are provided herein.