18 results about "Hepatic toxicity" patented technology

The application provides a method for analyzing the synergistic mechanism of hepatotoxicity and nephrotoxicity of non-steroidal anti-inflammatory drugs. The method comprises the following steps: preliminary toxicity prediction of NSAIDs and collection of toxicity target points, collection of liver and kidney disease target points, then cross and screening of the target points to obtain core target points and common core target points of NSAIDs induced liver and kidney diseases, and then constructing a protein interaction network of the common core target points; enrichment analysis of the common core target points to obtain the common action pathway of NSAIDs induced liver and kidney diseases; finally, further screening of the common core target points to obtain the key target points of NSAIDs induced liver and kidney diseases, and verification by using molecular docking technology. Compared with the traditional method, the advantages of the method are: first, the method does not depend on large-scale patient clinical data and a large number of animal or cell experiments, avoiding the ethical controversy in animal experiments and human experiments; second, the method can identify the potential cross-pathway and synergistic toxicity mechanism when a compound triggers multiple diseases, which is helpful for more comprehensive evaluation of the toxicity risk of NSAIDs.

The application provides a drug hepatotoxicity prediction method, device, system and medium, the method comprising: sequencing human liver cells after being contacted with a drug to be predicted to obtain a genome expression profile of the human liver cells after being contacted with the drug to be predicted; calculating the sum of the absolute values of the fold changes of the genes in the current gene pathway as the toxicity score of the current gene pathway according to the expression profile; calculating the Z value of the current gene pathway according to the toxicity score of the current gene pathway, the average value and the standard deviation value of the toxicity scores of the gene pathways calculated multiple times by a plurality of preset gene pathways; and predicting that the drug to be predicted has hepatotoxicity when the Z value is greater than 1.5. Therefore, the application can accurately, timely, effectively and sensitively predict drug hepatotoxicity without a large number of living animals as an experimental basis, and has good advantages in safety, environmental protection and animal protection. The application has the advantages of short experimental period and low cost.

The invention discloses application of physcion in preparation of a medicine for reducing liver cell lipid deposition, and particularly relates to application of physcion in preparation of a medicine for preventing and treating lipid deposition fatty liver. In-vitro cell experiments prove that the physcion shows low toxicity and a wide safety range in a human normal hepatocyte line THLE3, a human hepatoma cell line HepG2 and a mouse normal hepatocyte line AML12, and can obviously reduce the level of oleic acid-induced intracellular triglyceride in a dose-dependent manner, so that the physcion can be used for preparing a medicine for treating liver cancer. Oil red O staining results also visually show that lipid droplet accumulation in cells can be effectively reduced; according to the invention, the technical prejudice that the emodin monomethyl ether is regarded as a potential hepatotoxic component in the prior art is overcome, a safe and effective new choice is provided for the treatment of the lipid deposition fatty liver, and the pharmaceutical composition has a wide clinical application prospect.

The present invention discloses the use of a short-term embolic agent in reducing drug accumulation in the liver, hepatic clearance and / or liver toxicity. The present invention provides the use of a short-term embolic agent in the manufacture of a medical composition for: (a) temporarily embolizing blood vessels supplying the liver; and (b) reducing the accumulation of a drug subsequently or concurrently administered intravenously in the liver. The strategy aims to minimize the exposure of a drug (such as LNP) to the liver by temporarily blocking the blood supply to the liver via the portal vein and / or arteries. The present invention significantly reduces the non-specific accumulation of a drug in the liver by temporarily blocking the portal vein, arterial and / or their branch blood flow, thereby greatly reducing the opportunity for the drug to enter the liver from a hemodynamic root.

This invention relates to the field of livestock and poultry breeding and food safety testing technology, and in particular to a method for assessing copper exposure hepatotoxicity based on the endoplasmic reticulum stress-endoplasmic reticulum autophagy axis and its application. This method obtains liver tissue samples or in vitro cultured hepatocyte samples from copper-exposed subjects, and jointly detects the expression levels of key markers of the endoplasmic reticulum stress pathway and characteristic markers of the endoplasmic reticulum autophagy pathway. Combined with two-way pharmacological validation, a grading assessment standard for copper exposure hepatotoxicity is established. This invention overcomes the shortcomings of traditional liver enzyme indicators, such as low sensitivity and strong lag, and has the advantages of early warning, high specificity, and reliable results. It can be widely applied to scenarios such as determining the copper safety threshold in livestock and poultry feed, early screening for copper exposure hepatotoxicity, assessment of copper pollution ecological risks, and screening of copper toxicity protectants, providing technical support for ensuring animal health and the safety of animal-derived food.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tripterine prodrug compound as well as a preparation method and application thereof. The tripterine prodrug compound provided by the invention has a structure as shown in a formula I. The tripterine prodrug compound designed by utilizing the unique high expression characteristic of nitrate reductase in a tumor microenvironment can be specifically activated by the nitrate reductase at a tumor part, so that accurate release of tripterine at the tumor part is realized; the tripterine prodrug compound is kept relatively stable in normal tissues, so that the toxic effect on tissues such as normal livers is greatly reduced, and an innovative and potential solution is provided for solving the hepatotoxicity problem of the tripterine and improving the anti-tumor treatment effect of the tripterine; and breakthrough is hopefully brought to tumor treatment and the clinical application value is improved. Formula I.

Methods and uses are disclosed for treating a subject suffering from a disorder selected from a liver disorder, Cushing's syndrome, or Cushing's Disease, cancer, an infection, an inflammatory condition, a cardiovascular, endocrine, or kidney disease, and combinations thereof, or other disorder for which they may be administered a drug which may cause liver toxicity, without adverse effects on the liver. Such liver disorders include fatty liver diseases are effective for reducing high levels of liver enzymes with a favorable safety profile. The methods and uses comprise administering to the subject an effective amount of a selective nonsteroidal glucocorticoid receptor modulator such as relacorilant, including methods and uses in combination with another drug, without adverse effects on liver enzyme levels, or on liver function. In embodiments, the other drug may be a drug that may cause liver toxicity, such as drugs that inhibit CYP3A enzymes, e.g., itraconazole or ketoconazole.

This disclosure relates to a method for establishing a HepaRG-based differentiated liver 3D microsphere model and its applications. Specifically, this disclosure provides a chemically defined differentiation medium formulation that does not require DMSO and contains hepatocyte growth factor, dexamethasone, and hepatoprotectin M. Using this medium, HepaRG cells can be efficiently induced to form compact, long-lived 3D microspheres in ultra-low adsorption 96-well plates or in conjunction with high-throughput 3D printing technology. After differentiation and maturation, the model can stably express hepatocyte markers, key drug-metabolizing enzymes, and nuclear receptors at high levels. The liver 3D microsphere model established by this disclosure can effectively simulate hepatocyte function in vivo and is suitable for high-throughput drug hepatotoxicity screening. The results show a high degree of consistency with clinical hepatotoxicity data, and it has important application value in the field of drug safety evaluation.

The invention discloses a medicine for treating hepatotoxicity of bosutinib by taking a CAMK2G gene or protein as a target spot, and belongs to the technical field of medicines. According to the medicine, the hepatotoxicity of bosutinib is relieved by down-regulating the expression of the CAMK2G gene or restoring the phosphorylation of the CAMK2G protein. The invention reveals that the CAMK2G gene is a key gene of liver injury and abnormal glucose metabolism caused by bosutinib, and provides a new prevention and treatment target for intervening hepatotoxicity caused by bosutinib. According to the invention, the CAMK2G phosphorylation activator is utilized to recover CAMK2G phosphorylation to relieve liver injury and abnormal glucose metabolism, a new direction is provided for finding an intervention strategy for causing hepatotoxicity by drugs, and the current situation that few intervention drugs can be used clinically and the mechanism is single is solved to a certain extent.

The invention discloses RNAi for reducing the hepatotoxicity of triptolide and application of the RNAi, and belongs to the technical field of biological medicine. According to the invention, siRNA of a targeted Cyp2e1 gene is subjected to 2 '-O methyl modification and dTsdT 3' phosphorothioate connection modification, and then is delivered through lipid nanoparticles (LNPs). After intravenous injection administration, mouse liver Cyp2e1 protein expression can be reduced by 70% or above within 24 h, and subacute liver injury induced by triptolide can be remarkably relieved by reducing the level of serum glutamic-pyruvic transaminase / aspartate transaminase, inhibiting liver oxidative stress and reducing release of inflammatory factors such as TNF-alpha / IL-1beta / IL-6. According to the invention, the defect that the drug effect is reduced or the targeting property is poor in the existing toxicity attenuation scheme is overcome, a clinical auxiliary toxicity attenuation technical scheme with remarkable targeting regulation effect and high safety is provided, and a new path is provided for safe clinical application of triptolide.

The application discloses an ovarian anti-aging cell biological preparation and a preparation method and application thereof, and belongs to the technical field of biotechnology. The biological preparation is obtained by compounding ovarian stem cells and mulberry source specific polypeptides SEQ ID NO. 1 and SEQ ID NO. 2, a double mechanism of cell repair and molecular regulation is formed, animal experiments show that the efficiency of promoting E2 secretion and inhibiting FSH secretion is improved, and the follicle survival rate under a microscope is significantly improved, and the ovarian anti-aging aspect embodies a good treatment prospect. Meanwhile, the application adopts the medicinal and edible mulberry to replace the active ingredients extracted from radix falcaliae polygoni multiflori, and avoids the hepatotoxicity risk.

The present invention relates to a formulation in particular an oral formulation for the prophylaxis and treatment of TG2-related disorders like fibrosis in particular diabetic nephropathy and / or diabetic associated non-alcoholic steatohepatitis (NASH) and / or non-alcoholic steatohepatitis, and its use in the prophylaxis and / or treatment of fibrosis in particular nephropathy, NASH, idiopathic pulmonary fibrosis, and cystic fibrosis. Further, the present application relates also to the use of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate as hepatoprotectant, i.e. as hepatoprotective agent. In addition the present invention relates to a pharmaceutical composition comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate for use as hepatoprotective agent and for use in the protection of the liver against liver toxicity, the improvement of liver function, and / or in the prophylaxis or treatment of a liver disease or liver disorder.

The invention discloses an in-vitro hepatotoxic drug screening method based on a high-throughput plug-in chip, and belongs to the technical field of plug-in chip drug toxicity screening. According to the method, a high-throughput plug-in chip is composed of a pore plate layer, a channel layer and a plug-in; every three holes form a chip unit, separation and material exchange between the pore plate layer and the channel layer are carried out through the porous membrane on the plug-in, and gravity flow is provided through the swing table; the chip hole pitch accords with the specification of a commercial pore plate, and is compatible with various analytical instruments. Through liver chip model construction, drug incubation testing and data processing analysis, efficient hepatotoxicity drug screening is realized. According to the invention, the human adult stem cell-derived liver organs are used for establishing the chip model, and the physiological correlation of the cells is strong; compared with a mouse model, human physiological liver parenchyma characteristics can be better simulated; the operation is simple and the consumed time is short. The method realizes high-efficiency and high-reproducibility drug screening, and plays a great role in the fields of basic research, transformation application and the like of preclinical tests of drugs.

The invention belongs to the field of biological medicines, and provides an application of acetoacetic acid and derivatives thereof in preparation of medicines for treating or relieving hepatotoxicity caused by antituberculosis medicines. The hepatocytes formed by differentiation of human induced pluripotent stem cells are verified, and hydrazine is a metabolite with the strongest toxicity, so that the content of acetoacetic acid in the metabolite in the cells is reduced. Acetoacetic acid is one of main ketone metabolites in the ketone metabolism process, and cells can convert acetoacetic acid into acetoacetyl coenzyme A through succinyl coenzyme A: 3-oxo acid coenzyme A transferase. According to the invention, the OXCT1 gene in the human induced pluripotent stem cell is knocked out through CRISPR-cas9 and the human induced pluripotent stem cell is differentiated into the hepatocyte, so that the knockout of the OXCT1 gene increases the content of acetoacetic acid and reduces hepatic differentiation cell death caused by hydrazine.

The invention belongs to the technical field of medicines, and particularly relates to a construction method and application of a triptolide nano delivery system. The invention constructs a triptolide nano delivery system TN-CP NPs with temperature-sensitive response and free radical scavenging functions, and the effectiveness and safety of the triptolide nano delivery system TN-CP NPs in treatment of rheumatoid arthritis are verified through in-vivo and in-vitro experiments. In a CIA mouse model, the system significantly relieves joint swelling, inhibits inflammatory factor expression, improves joint tissue pathological damage, effectively reduces hepatotoxicity and testicular toxicity caused by TN, and does not show obvious hematological or systemic toxicity. Therefore, the TN-CP NPs provides a safe and effective novel nano strategy for realizing high-efficiency and low-toxicity delivery of TN and precise treatment of RA through the synergistic effect of temperature-sensitive controlled release and oxidation resistance, and also provides a reference thought for clinical conversion of other natural medicines with strong activity but high toxicity.

The application discloses application of Lachnospiraceae bacteria in preparation of a medicine for reducing hepatotoxicity of saikosaponin D, and relates to the field of medicines. The application identifies and applies an intestinal bacteria which has specific antagonism to hepatotoxicity of saikosaponin D for the first time. This breaks the limitation of traditional non-specific regulation through broad-spectrum probiotics or complex compounds, and realizes a leap from'macroscopic flora regulation' to 'key strain targeting'. The strategy directly aims at a key link of SSd toxicity, can effectively protect the liver while retaining the core efficacy of SSd to the greatest extent, and truly achieves the final goal of 'attenuation and efficacy reservation'.

The present application relates to the use of platelet factor 4 in the preparation of a drug for treating or preventing Candida albicans infection, platelet factor 4 acts on macrophage CXCR3 receptor, antagonizes Candida albicans induced macrophage PANoptosis, thereby reducing the damage of Candida albicans to macrophages, maintaining the survival and normal function of macrophages, enhancing the clearance ability of the body to Candida albicans, reducing the inflammatory response caused by infection, reducing pathological damage, and different from the treatment mechanism of traditional antifungal drugs, the present application does not directly act on fungi, which helps to reduce the formation of drug-resistant strains and the toxic side effects such as liver toxicity and kidney toxicity caused by antifungal drugs, and can provide a more optimal new treatment mode for clinical Candida albicans infection.