11 results about "Hepatocyte function" patented technology

The invention discloses a perfusion-free parallel double-cell intestine-liver chip system and application thereof in drug uptake evaluation, and belongs to the field of biomedical engineering and organ chips. The chip disclosed by the invention is simple in structure, free of an external pump and a complex pipeline, capable of realizing fluid circulation through swinging, convenient to operate, low in cost and small in pollution risk, and also capable of promoting cell differentiation and optimizing hepatocyte functions. The chip integrates a parallel intestinal cell and a liver cell which are communicated through a shared channel, can continuously simulate intestinal absorption and liver first-pass metabolism, and is closer to an in-vivo physiological state. The device adopts a detachable transparent modular design, can be repeatedly used, supports multi-group parallel operation, can improve experimental flux and result repeatability, and is suitable for in-vitro verification of drug absorption, permeability and metabolism evaluation.

This invention discloses a gRNA combination and its application in the preparation of drugs for the prevention of metabolic-associated fatty liver disease (MASLD). The gRNA combination, when mixed with Cas9 protein, yields an RNP complex, which, when microinjected into mouse zygotes, can breed a stable and heritable mouse strain with TMEM68 gene knockout. Combining lipidomics, transcriptomics, and primary hepatocyte functional verification, the core regulatory role of TMEM68 in hepatic lipid metabolism is revealed for the first time systematically. Experiments demonstrate that TMEM68 deficiency significantly reduces the storage of triglycerides (TAG) in the liver and hepatocytes, decreases lipid droplet formation, and reshapes the metabolic homeostasis of various lipids such as glycerophospholipids, cholesterol esters, and bile acids. Therefore, the gRNA combination of this invention, or the RNP complex obtained by mixing the gRNA combination with Cas9 protein, can be used to prepare drugs for the prevention of MASLD, providing a novel intervention strategy for MASLD prevention with broad application prospects.

The invention provides a combined bioartificial liver system for drivingly enhancing a hepatocyte function. The combined bioartificial liver system comprises a plasma separator, an artery pipeline, a vein pipeline and a first circulating pipeline, the first circulation pipeline is provided with a power part and a circulation purification unit, the circulation purification unit comprises a biological purifier, a hepatocyte carrier area and a perfusate channel are arranged in the biological purifier, the hepatocyte carrier area is filled with hepatocyte carriers, and the hepatocyte carrier area and the perfusate channel are physically isolated through a hollow fiber membrane; an elastic membrane covering the hepatocyte carrier area is arranged in the biological purifier, and the elastic membrane is connected with a pneumatic device for driving the elastic membrane to generate other periodic fluctuations. According to the application, the mechanical stress of the in-vivo respiratory movement to the liver cells is simulated, and the elastic membrane is arranged to simulate the mechanical stress of the in-vivo diaphragm muscle to the liver cells under the respiratory movement, so that the life cycle of the in-vitro liver cells is prolonged, and the detoxification efficiency and the biosynthesis capability of the liver cells are enhanced.

The application discloses application of hsa_circ_0003258 in prevention and / or treatment of liver ischemia-reperfusion injury. The application is found by detection that the expression of hsa_circ_0003258 is significantly decreased in liver ischemia-reperfusion patients; overexpression of hsa_circ_0003258 can significantly inhibit macrophage inflammation and the apoptosis level of hepatocytes after hypoxia-reoxygenation treatment, and improve the function of hepatocytes; hsa_circ_0003258 has a protective effect on relieving liver ischemia-reperfusion injury, and has potential to become a drug for treating liver ischemia-reperfusion injury.

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 provides a < 68 > Ga-labeled small molecule compound as well as a preparation method and application thereof, and belongs to the technical field of radiopharmaceuticals and nuclear medicine. The [68Ga] Ga-DTPA-EOB probe marked by 68Ga is suitable for positron emission tomography, has better temporal-spatial resolution and dynamic imaging capability, and can quantify tracer distribution. Under the condition that the pH value of the < 68 > Ga is 3.8-4.0, < 68 > Ga labeling can be completed only within 5-10 minutes at room temperature, the labeling efficiency is high (the labeling rate is greater than or equal to 95%), and the amount of EOB-DTPA required for labeling is extremely small. The radioactive activity needed by PET imaging is low, the radiation burden on a patient is small, and the gadolinium deposition risk is avoided. The [68Ga] Ga-DTPA-EOB probe is particularly suited for scenes requiring rapid diagnosis, avoiding MRI contraindications, or requiring multi-modal imaging.

The invention belongs to the technical field of biomedicine, and particularly relates to application of hydroxytyrosol in liver organ function optimization. The invention discloses a vomitoxin antagonist screening method based on a TGR5 target spot. The vomitoxin antagonist screening method comprises the following steps: constructing a TGR5 / pCREB tool cell; screening a natural product by combining a luciferase luminescence kit; processing the tool cells; if the luminous intensity is obviously increased, the natural product has the function of activating the TGR5, and if the luminous intensity is reduced, the natural product has the activity of inhibiting the TGR5. According to the application disclosed by the invention, the hydroxytyrosol is found to simultaneously improve liver cell functions and liver organ development by activating a TGR5 receptor for the first time, and a new direction is provided for liver health maintenance and regenerative medicine.

The invention relates to the technical field of biological fermentation, in particular to a preparation method and application of a high-activity solid-state fermented ganoderma lucidum compound for repairing hepatocyte functions. According to the method, rice peptide, traditional Chinese medicines with homology of medicine and food and functional precursor substances are taken as substrates, and a three-stage composite process of enzymolysis pretreatment, synergistic pre-fermentation of probiotics and yeast and directional co-fermentation of lucid ganoderma is adopted. Through metabolism synergy and segmented temperature regulation and control of a specific strain, and in combination with an enzymolysis-water extraction-alcohol precipitation-ultrasonic composite post-treatment technology, oriented efficient enrichment of ganoderma lucidum polysaccharides and triterpenoids is realized. The content of active ingredients of the obtained compound is remarkably increased, and the obtained compound has excellent antioxidant, anti-inflammatory and hepatocyte repairing activity and can remarkably reduce ALT and AST levels in acute and chronic liver injury models. The method is good in process stability, low in production cost and suitable for development and production of liver protection drugs, functional foods and liver protection cosmetics.

This invention discloses the application of ornithine aspartate in the preparation of drugs for treating systemic aging. By applying ornithine aspartate to regulate the systemic aging process, this invention can effectively improve hepatocyte dysfunction, restore cell proliferation activity, alleviate cell cycle arrest, and reduce the abnormal expression of aging-related genes and proteins in multiple tissues and organs such as the liver, kidneys, heart, muscles, and fat, thereby delaying the aging process. This technical solution can significantly improve the structural disorder and lipid deposition in aging liver tissue, reduce serum transaminase levels, improve liver function, reduce insulin resistance, inhibit the overexpression of SASP-related inflammatory factors, and maintain metabolic homeostasis. Furthermore, it effectively improves aging phenotypes in multiple tissues and organs. Therefore, this invention has significant technical effects and application potential in delaying systemic aging and improving motor function and metabolic abnormalities.

The application discloses application of ornithine aspartate in preparation of a medicine for treating systematic aging, and the ornithine aspartate is used to regulate the systematic aging process of a body, so that the liver cell dysfunction can be effectively improved, cell proliferation activity can be recovered, cell cycle arrest can be reduced, abnormal expression of aging-related genes and proteins in multiple tissues and organs such as liver, kidney, heart, muscle and fat can be reduced, and the aging process can be delayed. The technical scheme can significantly improve structural disorder and lipid deposition of the aging liver tissue, reduce the serum transaminase level, improve the liver function, reduce insulin resistance, inhibit excessive expression of SASP-related inflammatory factors, and maintain metabolic homeostasis. And the aging phenotype in multiple tissues and organs can be effectively improved. Therefore, the application has significant technical effects and application potential in delaying systematic aging, improving exercise function and metabolic abnormalities.

Provided are compositions for long-term maintenance of functional hepatocytes in culture, a method for improved maintenance of functional hepatocytes in vitro, and functional hepatocytes cultures according to the methods. The culture compositions include at least: one activator of adenylate cyclase, one TGFβinhibitor, one Notch inhibitor, one Wnt inhibitor, and / or one BMP inhibitor. The combinations of compounds are added to any hepatocyte cell culture medium in an effective amount to maintain functional hepatocyte function in vitro, long term. The hepatocytes can be used for in vitro drug research and to model liver disease.