53 results about "Hepatic toxicity" patented technology

The invention belongs to the technical field of biological medicine, and particularly relates to application of magnoflorine in preparation of a product for preventing / treating liver injury. The invention discusses the protective effect and mechanism of magnoflorine on MTX hepatotoxicity for the first time, and magnoflorine regulates ROS accumulation and mPTP permeability through targeting GSK3beta to inhibit pyroptosis of hepatocytes so as to reduce MTX hepatotoxicity. A new target and a new choice are provided for the prevention and treatment of MTX hepatotoxicity, and a research foundation is laid for the research of a new magnoflorine component liver-protecting drug.

The invention discloses application of polydatin in preparation of a medicine for relieving hepatotoxicity caused by zearalenone, and belongs to the technical field of biological medicine. The invention reveals that polydatin inhibits hepatotoxicity caused by zearalenone through targeted xanthine oxidase for the first time, so that the toxicity of zearalenone to an organism is relieved. Polydatin can be directly combined with xanthine oxidase to inhibit the catalytic activity of xanthine oxidase, so that the oxidative stress injury of the liver after ZEA exposure is reduced, meanwhile, the content of malondialdehyde (MDA) in the liver can be remarkably reduced, the activity of superoxide dismutase (SOD) is improved, the liver oxidation-antioxidant balance is recovered, and liver cells are protected from oxidative injury of ZEA. The invention provides a new scientific basis and development direction for application of polydatin in the fields of mycotoxin detoxification, oxidation resistance, liver protection and the like.

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 present application relates to a method for constructing a human acute liver injury and chemotaxis model based on a normal liver organoid and application thereof. Specifically, the present application provides a method for constructing a human liver organoid; further, contacting the liver organoid with a hepatotoxic drug can construct a human acute liver injury model; co-culturing the organoid or the injury model with immune cells can construct an in vitro immune cell chemotaxis model. The present application also provides reversible immunoaffinity magnetic beads for isolating VSIG4-positive macrophages and a method for isolating the same. The human liver organoid, acute liver injury model and chemotaxis model of the present application can be used for screening drugs for treating acute liver injury, evaluating the hepatotoxicity of compounds, researching the pathogenesis of acute liver injury and evaluating the effect of immunomodulatory drugs.

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 a medicine for preventing or treating liver toxic and side effects of osimertinib, and belongs to the technical field of medicines. Aiming at liver toxic and side effects caused by osimertinib, the invention provides an effective therapeutic drug, and the autophagy inhibitor relieves death caused by excessive activation of an autophagy pathway in hepatocytes by inhibiting autophagy activated by osimertinib, so that hepatotoxicity caused by osimertinib is relieved. The autophagy inhibitor and osimertinib are combined, so that the survival rate of hepatocytes can be remarkably improved, and liver injury caused in the osimertinib treatment process is reduced. The invention further provides novel application of the hydroxychloroquine or the S-adenosylmethionine in preparation of the medicine for preventing or treating the liver toxic and side effects of the osimertinib, the hydroxychloroquine or the S-adenosylmethionine has a remarkable treatment effect on liver injuries caused by the osimertinib, the medication safety of the hydroxychloroquine or the S-adenosylmethionine is high, and the hydroxychloroquine or the S-adenosylmethionine can be used for preparing the medicine for preventing or treating the liver toxic and side effects of the osimertinib. Good development prospects are realized.

The invention provides application of bacteroides fragilis 839 in preparation of health food, food composition or medicine for improving hepatotoxicity caused by antituberculosis medicine. The bacteroides fragilis BF839 is adopted for the first time in the world to improve the mouse hepatotoxicity caused by the antituberculous drug, and it is found that the bacteroides fragilis BF839 can reduce or relieve the mouse hepatotoxicity caused by the antituberculous drug and has the advantages of being efficient and safe.

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.

Systems and methods consistent with the present invention generally relate to microorganospheres (MOSs), and methods and apparatuses for forming and using MOSs. More particularly, in some embodiments, systems and methods consistent with the invention relate to the methods and apparatuses for forming and using MOSs generated from hepatocytes. MOPSs that are generated from hepatocytes are suitable for testing liver toxicity and drug induced liver injury effects of various agents.

The invention discloses preparation and application of a hepatic targeting polymer nano-vesicle. The hepatic targeting polymer nano-vesicle comprises a water inner shell arginine nonapeptide, a hydrophobic membrane layer polylactic acid-glycolic acid copolymer, a hydrophilic shell polyethylene glycol and zwitterionic groups embedded in the hydrophilic shell, the polymer nano-vesicle has a vesicle structure, and by embedding zwitterionic groups in a hydrophilic shell, the nano-vesicle has an active liver targeting function; the polymer nano vesicles are loaded with natural enzymes, namely catalase and superoxide dismutase. The polymer nano-vesicles can effectively protect antioxidant enzymes, increase removal of ROS by the liver and improve acetaminophen-induced hepatotoxicity and liver injury.

The invention belongs to the field of antitumor drugs, and particularly relates to a targeted 4-1BB aptamer and application of the targeted 4-1BB aptamer in preparation of antitumor drugs. A target 4-1BB nucleic acid aptamer is obtained through screening, the sequence of the target 4-1BB nucleic acid aptamer is shown as SEQ ID No.1, and the target 4-1BB nucleic acid aptamer is specifically 5 '-CACGCATAACATGTATGGACTGCTCGGGATTGCGG ATTTACATTCGTTATGCGTG-3', the sequence of the target 4-1BB nucleic acid aptamer is shown as SEQ ID No.1, and the sequence of the target 4-1BB nucleic acid aptamer is shown as SEQ ID No.1. The nucleic acid aptamer has a good application effect in preparation of anti-tumor drugs. The capacity of the aptamer for inhibiting mouse Hepa1-6 subcutaneous tumor is superior to that of mouse 4-1BB agonist antibody drugs with the same total mass. The obvious hepatotoxicity and visceral toxicity are not found; growth of mouse Hepa1-6 liver in-situ cancer can be inhibited, and the proportion of CD8 + T cells in T cells in the liver can be increased.

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.

The invention discloses a construction method of a three-dimensional liver micro-tissue model and hepatotoxicity assessment application of the three-dimensional liver micro-tissue model, and belongs to the technical field of environmental science and engineering. The 3D liver micro-tissue model constructed by the invention consists of three cell lines, namely HepaRG (parenchymal hepatic cells), THP-1 (kupffer cells) and hTERT-HSC (hepatic stellate cells), so that a real liver environment can be better simulated, and the defects of a traditional model are overcome; particularly, the occurrence of hepatic fibrosis relates to complex interaction among a plurality of cell lines, however, most of the previous models for evaluating the potential of hepatic fibrosis by chemical substances are lack of consideration of interaction among multiple types of cells no matter whether hepatic parenchymal cell lines or hepatic stellate cell lines are used, and the 3D hepatic micro-tissue model takes the factor into account, so that the potential of hepatic fibrosis cannot be evaluated. Key hepatic fibrosis events caused by hepatic fibrosis substances can be copied, and a more suitable test platform is provided for evaluating the potential of chemical substance hepatic fibrosis.

The invention discloses an ovarian anti-aging cell biological agent and a preparation method and application thereof, and belongs to the technical field of biology, ovarian stem cells and mulberry-source specific polypeptides SEQ ID NO.1 and SEQ ID NO.2 are compounded to obtain the biological agent, a cell repair and molecular regulation dual mechanism is formed, animal experiments show that the efficiency of promoting E2 secretion and inhibiting FSH secretion of the biological agent is improved, and the biological agent has a good application prospect. Moreover, the survival rate of follicles under a microscope is remarkably improved, and a relatively good treatment prospect is shown in the aspect of ovarian aging resistance. Meanwhile, mulberry with homology of medicine and food is adopted to replace polygonum multiflorum to extract active ingredients, and the risk of hepatotoxicity is avoided.

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.

Provided is a pharmaceutical composition of a supramolecular complex with low administration dose. The pharmaceutical composition comprises nintedanib or a pharmaceutically acceptable salt thereof, a supramolecular complex, and a targeting directing agent. The composition addresses the poor solubility of nintedanib, reduces the hepatotoxicity and gastrointestinal toxicity caused by first-pass metabolism of existing nintedanib products after oral administration, greatly improves the effective utilization rate of the drug and the enrichment concentration of the drug after oral administration at the target organs treated, improves the safety, and also improves the treatment effect.

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.

The invention discloses a multi-modal hepatotoxicity prediction model determination method, and belongs to the technical field of big data processing. The method comprises the following steps: acquiring a drug-determination matrix of N rows and M columns, wherein the N rows comprise drug data of N drugs; the M column comprises measurement data of whether the medicine has a biological activity label or not under each target of the M targets; mapping K candidate determination data related to hepatotoxicity and F basic hepatotoxicity mechanism frameworks in the drug-determination matrix to obtain a biological fingerprint; determining heterogeneous data corresponding to each drug according to the chemical structure chart and the biological fingerprint of each drug in the N drugs; according to the drug data and the heterogeneous data of each drug, training the neural network prediction model until a preset training condition is met, and obtaining a multi-modal hepatotoxicity prediction model. Therefore, the cost of determining the hepatotoxicity of the compound can be effectively reduced without depending on experimental animals and manual operation, and the efficiency and accuracy of determining the hepatotoxicity of the compound are improved.

The invention discloses an application of a hispiraceae bacterium in preparation of a medicine for relieving the hepatotoxicity of saikoside D, and relates to the field of medicines. According to the invention, an intestinal bacterium with a specific antagonistic effect on the hepatotoxicity of saikoside D is identified and applied for the first time. The limitation that non-specific regulation is carried out through broad-spectrum probiotics or complex compounds traditionally is broken through, and the crossing from'macroscopic flora regulation 'to'key strain targeting' is realized. The strategy directly aims at a key link of SSd toxicity generation, the liver can be effectively protected, meanwhile, the core drug effect of SSd can be reserved to the maximum extent, and the final goal of toxicity reduction and effect storage is really achieved.

The present invention discloses a method and application for the aquatic ecological toxicity and risk assessment of gatifloxacin based on zebrafish. The steps of the method include: S1 establishing a zebrafish experimental model, selecting zebrafish larvae 3 days after fertilization, according to a standardized breeding procedure; S2, toxicity assessment, calculating the maximum non-lethal concentration (MNLC) and 10% lethal concentration (LC 10 ); S3, assessment of hepatotoxicity indicators; S4, histopathological analysis; S5, detection of the oxidative stress response status; S6, exploring the molecular mechanism by detecting the relative expression levels of PPAR-γ , CYP1A1 and CYP1B1 genes by qPCR; S7, data analysis. The method of the present invention combines morphological, histological, oxidative stress response and molecular mechanism studies, provides a multi-scale evaluation system for the toxicity monitoring of trace drugs in the water environment, and helps to better protect the water ecological environment and public health safety.

The application discloses a vortioxetine impurity, a preparation method and application thereof, and adopts vortioxetine or a pharmaceutically acceptable salt form thereof as raw material, the raw material is easy to obtain and simple to operate, and the reaction condition is mild. The synthesized impurity is characterized by nuclear magnetic resonance, high-resolution mass spectrometry and X-ray single crystal diffraction, and liver toxicity research shows that the compound disclosed by the application has important significance for researching adverse reactions of vortioxetine. The control sample obtained by the method provided by the application can be used for qualitative and quantitative analysis of the vortioxetine impurity, so that the drug safety of vortioxetine is improved.

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 relates to medical application of tea polyphenol, in particular to a tea polyphenol-based aflatoxin (AFB1) liver injury prevention and treatment method. Aiming at the problem that serious economic loss is often caused by AFB1 in livestock and poultry breeding, the invention firstly proposes that pure natural tea polyphenol is taken as a unique active component, and AFB1 poisoning is intervened by oral administration of a preparation. The invention shows that the tea polyphenol can effectively relieve the hepatotoxicity induced by the AFB1, provides a new strategy for application of natural components in prevention and treatment of the hepatotoxicity of the AFB1, and has the characteristics of safety, high efficiency and easiness in industrialization.

The present invention discloses a hepatic progenitor organoid culture medium and culture method, which belong to the field of organoid culture technology. It includes basal culture medium, Jagged‑1, Dexamethasone, TGF‑α, β-mercaptoethanol, BMP4, FGF2, specific additive factors Glutamax, HEPES, Nicotinamide, Penicillin streptomycin, etc. The present invention uses liver tissue to construct hepatic progenitor organoids for the first time, which can promote the continuous growth and efficient proliferation of human hepatic progenitor cells in vitro without gene editing, while maintaining the pluripotency of hepatic progenitor organoids and the consistency of specific marker expression, providing a new batch model for the current evaluation of hepatotoxicity. In the long run, it lays the foundation for the construction of a more advanced hepatic organoid model with multiple types of differentiated cells.

The invention belongs to the field of traditional Chinese medicines, and particularly relates to an anti-tumor traditional Chinese medicine composition. The traditional Chinese medicine composition comprises the pleurotus eryngii mycelium polypeptide and the cistanche polysaccharide, through the synergistic effect, the growth of tumors can be inhibited, the hepatotoxicity can be relieved, and a safer and more effective treatment method is provided for treatment of tumor and hepatotoxic diseases.

The invention relates to a hepatotoxicity three-dimensional cell model as well as a construction method and application thereof, and relates to the field of pharmacology and toxicology. The construction method comprises the following steps: inoculating hepatic cells and hepatic stellate cells into a culture medium containing an extracellular matrix, and carrying out three-dimensional cell co-culture to obtain the three-dimensional cell model. In the early stage of drug research and development, drug compounds with potential hepatotoxicity can be rapidly screened out by using the hepatotoxicity three-dimensional cell model provided by the invention; according to the present invention, whether the drug damages the liver cells or not is determined by observing the changes of the form, the metabolism, the function and the like of the cells under the drug effect, such that the drug candidate possibly having the serious hepatotoxicity can be timely eliminated so as to avoid the problem discovery in the subsequent clinical test, such that the research and development time and the research and development cost can be saved.

The invention discloses an application of a composition containing a semen raphani extract in enhancing the anti-tumor curative effect of paclitaxel (PTX), and particularly discloses a composition containing a semen raphani extract and an application of the composition containing the semen raphani extract in enhancing the anti-tumor curative effect of PTX. Researches show that the composition containing the semen raphani extract can synergistically enhance the anti-lung cancer curative effect of PTX, can significantly inhibit the growth of tumors, reduce the size of the tumors, reduce the expression of a proliferation marker Ki67 in the tumors, promote lung cancer cell apoptosis and also can improve the pathological morphology of tongue tissues after combined medication; the composition has no obvious influence on tumor model animals by singly adopting the composition, and the combined use of the two can not only obviously enhance the curative effect of PTX, but also reduce toxic and side effects caused by PTX, repair taste structural damage and taste disorder caused by PTX, and also relieve hepatotoxicity caused by PTX administration. The combined medication scheme provided by the invention not only can enhance the anti-tumor curative effect of PTX, but also can reduce toxic and side effects caused by PTX, has good safety, and provides a safer and more efficient method and means with lower toxic and side effects for the combined medication scheme of anti-tumor drugs.

The invention relates to the technical field of medical diagnosis, in particular to an antifungal drug hepatotoxicity detection method and system, and the method comprises the following steps: obtaining a blood-derived sample of an individual who is subjected to antifungal drug treatment due to invasive fungal infection, is subjected to bacterial infection and has liver injury; detecting the concentration of a first characteristic component related to fungal lysis under the action of the antifungal drug in a blood-derived sample to obtain a first concentration value; detecting the concentration of a second characteristic component related to the concurrent bacterial infection in the blood-derived sample to obtain a second concentration value; based on the first concentration value and the second concentration value, an attribution index representing the relative strength of the first characteristic component and the second characteristic component is calculated; by detecting the concentration of the characteristic components related to fungal lysis and bacterial infection and calculating the attribution index, the dominant inducements of the liver injury are distinguished, and the method has the advantages that the dominant inducements of the liver injury can be distinguished, and a basis is provided for clinical decision making.

A polyherbal formulation for preparing a pharmaceutical composition for the treatment of a liver disease, hepatic injury, or hepatotoxicity in a subject in need thereof, comprising plant material in the form of Rauwolfia serpentina, Eclipta alba, and Phyllanthus amarus.