30 results about "CYP2E1" patented technology

The invention provides a shRNA lentiviral expression vector for specifically inhibiting hepatic cell CYP2E1 gene expression, comprising basic sequences, resistance gene sequences, multiple cloning site sequences, promoter sequences of PLKO.1-puro expression vector, and shRNA oligonucleotides sequences of target CYP2E1 genes; the shRNA oligonucleotides sequences are inserted into multiple clone sites forwards. shRNA lentiviral expression vector provided by the invention has the advantages of high transfection efficiency, little dosage, sustainability, high efficiency, stability and specificityfor inhibiting hepatic cell CYP2E1 gene expression, and can be used for preparing medicines for treating diseases related to abnormal CYP2E1 gene expression as powerful tools.

Provided is a pharmaceutical or food or drink composition for preventing or treating alcohol-induced fatty liver or steatohepatitis comprising metadoxine (pyridoxol 1-2-pyrrolidone-5-carboxylate) and garlic oil as active ingredients. The concurrent administration of metadoxine and garlic oil according to the present invention exhibits outstandingly superior effects of inhibiting the accumulation of triglyceride and increase of blood AST (aspartate aminotransferase) level in liver el tissue, inhibiting the expression of FAS (fatty acid synthase), CYP2E1 and iNOS (inducible nitric oxide synthase) and inhibiting the deactivation of AMPK (AMP-activated protein kinase), as compared to the administration of metadoxine or garlic oil only.

The invention discloses a kit for genetic detection of colorectal cancer. The kit comprises a specific primer pair and a specific probe pair which are used for detecting the mononucleotide polymorphism loci genotype of a 5,10-methylenetetrahydrofolate reductase gene (MTHFR), a glutathione-s-transferase T1 gene (GSTT1), a glutathione-s-transferase M1 gene (GSTM1), a cytochrome P450 2E1 gene (CYP2E1), and a mismatching repair enzyme gene (hMLH1), a fluorescent quantitative PCR general component, a PCR reaction component and the like. The kit can evaluate the genetic risk of individuals suffered from the colorectal cancer by detecting the polymorphism loci genotype of the genes closely related to the genetic risk of the colorectal cancer at the same time.

The invention discloses a kit for testing the genetic risk of esophageal cancer, which comprises specific premier pairs for testing the single nucleotide polymorphic locus genotypes of a cytochrome P450 1A1 gene (CYP1A1), a cytochrome P450 2E1 gene (CYP2E1), a glutathione-S-transferase M1 gene (GSTM1), a 5,10-methylenetetrahydrofo late reductase gene (MTHFR), a reduction type coenzyme I quinone oxido-reductase gene (NQ01), an oncoprotein 53 gene (P53), an X-ray repair cross-complementing gene 1 (XRCC1) and a xeroderma pigmentosum complementary set A gene (XPA) as well as specific fluorescent probe pairs, fluorescent quantitative PCR regular components, PCR reaction components and the like. The kit of the invention estimates the individual genetic risk of esophageal cancer by synchronously testing the polymorphic locus genotypes of the genes closely related to the genetic risk of esophageal cancer.

The invention discloses a lactic acid bacteria formula for preventing acute and chronic alcoholic liver injury and application thereof. Lactobacillus plantarum KLDS1.0344 and lactobacillus acidophilusKLDS1.0901 have good gastrointestinal fluid tolerance simulating capacity, have certain adhesion capacity to HT-29 cells and have basic probiotic characteristics; the lactobacillus plantarum KLDS1.0344 and the lactobacillus acidophilus KLDS1.0901 can prevent acute alcoholic liver injury; and the lactobacillus plantarum KLDS1.0344 and the lactobacillus acidophilus KLDS1.0901 can prevent chronic alcoholic liver injury. Specifically, the lactobacillus plantarum KLDS1.0344 and the lactobacillus acidophilus KLDS1.0901 have the functions of reducing the liver index, improving the intestinal barrier, improving the liver function, reducing the inflammation level in the liver, increasing the content of short-chain fatty acid in the intestinal tract, reducing protein expression of CYP2E1 in the liver and the like.

The invention provides a detection method and a detection kit for quantifying a rat CYP2E1 enzyme based on a characteristic peptide fragment and belongs to the technical field of biodetection and proteins. The method comprises the following steps: screening a characteristic peptide fragment of the rat CYP2E1 enzyme as a quantifying peptide fragment and artificially synthesizing the peptide fragment as an analytical reference substance, and synthesizing a stable isotope labeled peptide fragment as an interior label; carrying out linear regression by taking a specific value of the quantifying peptide fragment and the interior label peptide fragment as a vertical coordinate and the quantifying peptide of a series of standard blood serum samples as a transverse coordinate to obtain a regression equation; releasing the quantifying peptide fragment through enzymolysis of a to-be-detected sample; adding the labeled peptide fragment for feeding analysis; and obtaining the precise content of the rate CYP2E1 enzyme in the samples according to the linear regression equation. Two quantifying peptide fragments are selected to synthesize corresponding labeled peptide fragments as interior labels, thereby achieving a purpose of mutual verification. The detection kit can simply a sample pre-treatment step, so that the rat CYP2E1 enzyme is detected conveniently.

The invention discloses a kit for detecting the gastric cancer susceptibility, which is used for detecting four genes nearly concerned with gastric cancer as follows: MTHFR gene, CYP2E1 metabolic enzyme gene, XRCC1 and ADPRT repairase gene. The kit can simultaneously detect the following SNP (single nucleotide polymorphism) sites: the rs1801133 site of the MTHFR gene, the rs2031920 site of the CYP2E1, the rs25478 site of the XRCC1 gene and the rs1136410 site of the ADPRT gene. By using the kit disclosed by the invention, a group of genes and sites related to the gastric cancer susceptibility are detected, and whether the subject population carry gastric cancer susceptible genes can be judged clearly by using a specific primer and a specific probe by a mononucleotide extension technology combined with a microarray chip technology, thereby screening out the gastric cancer susceptible population from the subject population, changing unhealthy habits and customs and achieving the purpose of prevention.

The invention relates to a detection of four sites of single nucleotide polymorphism (SNP) which are arranged on two human body xenobiotics metabolismenzyme genes including ABCG2 and CYP2E1 and which are associated with the systemic lupus erythematosus (SLE). The invention also can use four sites of single nucleotide polymorphism (SNP) to forecast the liability of systemic lupus erythematosus and to determine the drug to cure the systemic lupus erythematosus. The information provided by the invention is helpful for preventing systemic lupus erythematosus (SLE) and for developing effective new treatments.

The invention belongs to the field of biological medicine, and particularly relates to a method for improving a detoxification function of hepatocyte-like cells derived from human stem cells and application of the method. The method is characterized in that the stem cells are transfected with miR-142-3p inhibitors during stem cell hepatic differentiation, and the nucleotide sequence of the miR-142-3p inhibitors is shown as SEQ ID No.1. After differentiation of the stem cells, the miR-142-3p inhibitors are transfected, after transfection, differentiation is performed and molecular and functional testing of the hepatocyte-like cells is detected, it is found that on the 8th day of stem cell hepatic differentiation, 10nM of the miR-142-3p inhibitors are transfected, and enzyme activity of CYP2E1 and CYP3A4 is the highest. The method overcomes the disadvantage of low detoxification ability of the hepatocyte-like cells derived from the human stem cells, facilitates the development of an artificial liver and the in-depth study of medical research and development by using the hepatocyte-like cells derived from the human stem cells or the artificial liver.

Present invention provides a method for screening drug-induced toxicity and screening for drug-induced toxicity by using the NAT2, CYP2E1 and Xanthine Oxidase genes, in particular, provides a method for screening TB drug-induced hepatotoxicity. The method of present invention includes providing test specimen, detection of at least one type of SNPs of the NAT2, CYP2E1 and Xanthine Oxidase genes from the DNA of said test specimen; presence of the SNP genotype indicates the test specimen has a risk for developing anti-TB drug-induced toxicity; said SNP genotype is selected from at least one of the following groups or their combinations thereof: rs1041983, rs1112005, rs1495741, rs1799930, rs1799931, rs1801280, rs1961456, rs2087852, rs11996129, rs2031920, rs2249695, rs3813865, rs3813867, rs1884725, rs2295475 and rs17011368. Moreover, the screening method of the invention includes the test specimen, detection of at least one type of SNPs of the Xanthine Oxidase gene from the DNA of said test specimen; presence of the SNP haplotype indicates the test specimen has a risk for developing high uric acid and its related diseases; said SNP genotype is selected from at least one of the following groups or their combinations thereof: rs1884725, rs2295475 and rs17011368.

The invention discloses a gene combination, a primer and a probe for detecting gastric cancer susceptibility and application. The gene combination comprises a combination of four genes closely related with a gastric cancer, namely an MTHFR gene, a CYP2E1 metabolic enzyme gene, an XRCC1 repairase gene and an ADPRT repairase gene. The gene combination comprises the following SNP sites: rs1801133 site of the MTHFR gene, rs2031920 site of the CYP2E1 gene, rs25478 site of the XRCC1 gene and rs1136410 site of the ADPRT gene. Whether the detected crowds carry 'gastric cancer susceptible genes' are comprehensively detected and analyzed by detecting a group of genes and sites related with the gastric cancer susceptibility, using the specific primer and the probe and combining a mononucleotide extending technique and a micro array chip technique so as to screen the gastric cancer susceptible crowd from the crowds, change unhealthy lifestyles and fulfill the purpose of preventing.

The present invention discloses a reagent kit to detect lung cancer susceptibility, which comprises a specificity tracer and a specificity fluorescence probe to detect No. 176 SNP locus of gene SEQ ID No: 1 of CYP2E1 and a normal assembly for quantitative fluorescence PCR detection. The reagent kit of the present invention forecasts individual lung cancer susceptibility by analyzing individual carrying type of SNP locus gene of on CYP2E1 gene.

The invention discloses novel application of clomethiazole CMZ. Research findings show that the CMZ has the inhibiting effect on human cytochrome P4502E1(CYP2E1) metabolism nitrosamines compounds of dimethylinitrosamine DMN and Diethylinitrosamine DEN, and therefore clomethiazole can be used as a medicine for preventing and treating hepatic diseases such as hepatitis, hepatic fibrosis, cirrhosis and liver cancer and esophageal diseases such as ingluveosis phrenospasm, hiatal hernia, esophageal diverticula, esophagus polypus and papilloma and esophagus cancers.

The invention relates to a pharmaceutical composite which contains isoniazide, tiopronin or sodium salt thereof that are taken as the active constituents, and a pharmaceutical carrier and / or an excipient, wherein, the mass ratio of the isoniazide and the tiopronin is 1-10:1. The tiopronin has specific action on inhibiting hepatic CYP2E1, and can specifically treat liver damage caused by the isoniazide which is an antituberculotic, and purposefully reduces the toxic and side effect of the isoniazide on the liver. The pharmaceutical composite not only further expands the pharmaceutical value of the tiopronin which is an inhibitor of the hepatic CYP2E1, but also contributes to the safe clinical application of the related pharmaceutical (isoniazide). Therefore, the pharmaceutical composite has important medical value and social and economic benefits.

The invention discloses an application of a compound as a CYP2E1 inhibitor, which is characterized in that the compound or a salt thereof as an inhibitor takes CYP2E1 as a target spot and is combined with the CYP2E1, and the CYP2E1 inhibitor has an inhibition effect on CYP2E1. The inhibitor can be used for preventing and treating tumors such as liver cancer, glioma, ovarian cancer, bladder cancer and gallbladder cancer. Similarly, the inhibitor can also be used for preventing and treating other inflammation-related diseases such as liver injury, fatty liver, hepatitis, hepatic fibrosis, rheumatic and rheumatoid arthritis, sepsis, Alzheimer's disease, ischemic cerebral apoplexy, Parkinson's disease, hyperlipidemia, atherosclerosis, coronary heart disease, diabetes mellitus and the like.

The invention provides a characteristic peptide fragment for detecting a rat CYP2E1 enzyme and a screening method and an application thereof and belongs to the technical field of biodetection and proteins. The characteristic peptide fragment for detecting the rat CYP2E1 enzyme is high in timeliness, can detect the CYP2E1 enzyme specifically and is relatively high in specificity. The peptide fragment can be better prevented from being interfered, the characteristic peptide fragment is applied to detecting the rat CYP2E1 enzyme, and the effect is obvious; the specific fragment can be obtained bymeans of the screening method for the characteristic peptide fragment for detecting the rat CYP2E1 enzyme.

The invention provides construction and application of a vitamin E nano-carrier capable of reversing alcoholic liver diseases. The nano preparation is loaded with chloromethylthiazole CMZ and vitamin E, the nano system is modified by small molecules or polypeptide with endoplasmic reticulum tropism to realize endoplasmic reticulum targeting of a carrier, CMZ is delivered to the endoplasmic reticulum of liver cells for site specific inhibition of CYP2E1 to limit generation of reactive oxygen species (ROS), and vitamin E neutralizes existing ROS, so that the CMZ / vitamin E nano preparation is prepared. Therefore, oxidative stress injury of the liver under alcohol stimulation is relieved, and alcoholic liver diseases are reversed. The nano-carrier disclosed by the invention can be a drug loading system such as nano-emulsion, liposome or lipid nanoparticles, the CMZ can be replaced by other CYP2E1 inhibitors, and the vitamin E can be replaced by other antioxidant components. The nano preparation is used by intravenous injection or oral administration, and can play a role in protecting the liver in related diseases caused by abnormal CYP2E1 expression.

The invention belongs to the field of biomedicine, and specifically relates to a method for improving the detoxification function of hepatic-like cells derived from human stem cells and an application thereof. It is characterized in that the miR-142-3p inhibitor is transfected during the hepatic differentiation of stem cells, and the nucleotide sequence of the miR-142-3p inhibitor is shown in SEQ ID No.1. After differentiation of stem cells, transfection of miR-142-3p inhibitor, after transfection differentiation and molecular and functional detection of liver-like cells, it was found that 10nM miR-142-3p inhibitor was transfected on the 8th day of stem cell hepatic differentiation , the enzyme activities of CYP2E1 and CYP3A4 are the highest. The method overcomes the disadvantage of low detoxification ability of hepatic cells derived from human stem cells, and is beneficial to the development of artificial livers and the in-depth research of pharmaceutical research and development using hepatic cells derived from human stem cells or artificial livers.

The invention relates to tiopronin or medical new use of the sodium salt thereof, in particular to the application of the tiopronin or the sodium salt thereof in the preparation of medicine for treating liver functional damage caused by cerebral ischemia, diabetes and obesity. The tiopronin has the function of specifically inhibiting liver cytochrome P450 2E1 (CYP2E1), there protecting the liver function from being damaged caused by cerebral ischemia, diabetes and obesity, so as to be a new clinical use having direction. The new use further expands the medical value of the tiopronin, which istaken as an inhibitor of liver CYP2E1 for protecting the function of liver, thus having important medical value, social and economic benefits.

The invention provides a gene detection chip for a lung-cancer-risk-related cytochrome P450 of smokers. The gene detection chip comprises a solid-phase support and oligonucleotide probes sequentially fixed on the solid-phase support, wherein each oligonucleotide probe comprises 14-20 continuous nucleotides at mutant sites in sequences or complementary sequences, including CYP1A13798T>C, CYP1A12454A>G, CYP1A21545T>C, CYP2A6479T>A, CYP2A61436G>T, CYP2A133375C>T, CYP2E1-1053C>T. The genotypes of CYP1A1, CYP1A2, CYP2A6, CYP2A13 and CYP2E1 are detected by using a gene chip, so that the chip detection sensitivity is more than 96 percent, the specificity rate is more than 98 percent, and the characteristics of easiness for operation, accurate result and the like of gene chip detection can be brought into play. The gene detection chip plays an important realistic role in research and development units and clinical relevant applications.

The invention discloses an application of apigenin in preparing medicines or health care foods for preventing and / or treating alcoholic liver injury. On the basis of in vitro and in vivo pharmacological experiments, the apigenin (chemical name:5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) has an obvious protective effect on liver / hepatocyte injury induced by alcohol, and the main action mechanism of the apigenin is related to inhibition of CYP2E1 expression in liver / hepatocytes; and the apigenin, as a CYP2E1 inhibitor, can be used for preparing the medicines or the health care foods for preventing and / or treating the alcoholic liver injury; therefore, the apigenin has important scientific research and economic values.

The invention discloses a lactic acid bacteria formula for preventing acute and chronic alcoholic liver injury and application thereof. Lactobacillus plantarum KLDS1.0344 and lactobacillus acidophilusKLDS1.0901 have good gastrointestinal fluid tolerance simulating capacity, have certain adhesion capacity to HT-29 cells and have basic probiotic characteristics; the lactobacillus plantarum KLDS1.0344 and the lactobacillus acidophilus KLDS1.0901 can prevent acute alcoholic liver injury; and the lactobacillus plantarum KLDS1.0344 and the lactobacillus acidophilus KLDS1.0901 can prevent chronic alcoholic liver injury. Specifically, the lactobacillus plantarum KLDS1.0344 and the lactobacillus acidophilus KLDS1.0901 have the functions of reducing the liver index, improving the intestinal barrier, improving the liver function, reducing the inflammation level in the liver, increasing the content of short-chain fatty acid in the intestinal tract, reducing protein expression of CYP2E1 in the liver and the like.

Genetic markers are disclosed with a useful association with boar taint that can be used for screening and selection of pigs for those with more favorable boar taint characteristics associated with androstenone / skatole metabolism. Specific polymorphic alleles of the 3αHSD, 3βHSD, CYP17A1, CYP2A, CYP2E1, CYTB5, BAC-CT and / or SULT1A1 genes are disclosed for tests to screen pigs to determine those more likely to produce desired boar taint traits.

The invention discloses a gastric cancer genetic susceptible gene screening reagent kit. The gastric cancer genetic susceptible gene screening reagent kit comprises specific primers of rs1801133 loci of MTHFR (methylenetrahydrofolate reductase) genes, rs2031920 loci of CYP2E1 (cytochrome P450 2E1), rs25478 loci of XRCC1 (X-ray repair cross-complementing group 1) genes and res1136410 loci of ADPRT [ADP (adenosine diphosphate)-ribosyltransferase] genes and corresponding extension probes. The gastric cancer genetic susceptible gene screening reagent kit has the advantages that the rs1801133 loci of the multiple MTHFR genes, the rs2031920 loci of the CYP2E1, the rs25478 loci of the XRCC1 genes and the res1136410 loci of the ADPRT genes can be simultaneously detected by the gastric cancer genetic susceptible gene screening reagent kit, and the gastric cancer genetic susceptible gene screening reagent kit is low in detection cost; a plurality of samples can be simultaneously detected at one step, and accordingly the gastric cancer genetic susceptible gene screening reagent kit is high in throughput.

The invention relates to tiopronin or medical new use of the sodium salt thereof, in particular to the application of the tiopronin or the sodium salt thereof in the preparation of medicine for treating liver functional damage caused by cerebral ischemia, diabetes and obesity. The tiopronin has the function of specifically inhibiting liver cytochrome P450 2E1 (CYP2E1), there protecting the liver function from being damaged caused by cerebral ischemia, diabetes and obesity, so as to be a new clinical use having direction. The new use further expands the medical value of the tiopronin, which is taken as an inhibitor of liver CYP2E1 for protecting the function of liver, thus having important medical value, social and economic benefits.

The invention provides a shRNA lentiviral expression vector for specifically inhibiting hepatic cell CYP2E1 gene expression, comprising basic sequences, resistance gene sequences, multiple cloning site sequences, promoter sequences of PLKO.1-puro expression vector, and shRNA oligonucleotides sequences of target CYP2E1 genes; the shRNA oligonucleotides sequences are inserted into multiple clone sites forwards. shRNA lentiviral expression vector provided by the invention has the advantages of high transfection efficiency, little dosage, sustainability, high efficiency, stability and specificityfor inhibiting hepatic cell CYP2E1 gene expression, and can be used for preparing medicines for treating diseases related to abnormal CYP2E1 gene expression as powerful tools.

The invention provides a characteristic peptide segment for detecting rat CYP2E1 enzyme, a screening method and application thereof, and belongs to the technical field of biological detection and protein. The characteristic peptide segment for detection of rat CYP2E1 enzyme provided by the present invention has high timeliness, can specifically detect CYP2E1 enzyme, and has strong specificity; it can better avoid interference, and the characteristic peptide segment can be applied to the detection of rat In the CYP2E1 enzyme, the effect is obvious; the screening method for detecting the characteristic peptide segment of the rat CYP2E1 enzyme can obtain specific fragments through the screening method.

The invention relates to a preparation method, a detection method and application of a probe drug composition for determination of metabolic activity of cytochrome P450. The composition mainly comprises a preparation made with a specific probe with major isoforms of CYP450, i.e. CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, as an active component. Cocktail probe drug solution is prepared, the probe drug composition is injected into an animal or liver microsomes for in vitro co-incubation, and the concentration of each probe drug is determined to assess the metabolic activity of the CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. In the early stage of research and development of new drugs, the effects of the drugs on the activity of each isoform of the cytochrome P450 are screened in a high-throughput way, and the interactions of the drugs can be predicted. In the stage of clinical research, the testing can be performed with the probe drug composition in an in-vivo probe method, and the effects of the drugs on the in-vivo metabolic activity of different isoforms of the human liver CYP450 can be examined.

Provided is a pharmaceutical or food or drink composition for preventing or treating alcohol-induced fatty liver or steatohepatitis comprising metadoxine (pyridoxol 1-2-pyrrolidone-5-carboxylate) and garlic oil as active ingredients. The concurrent administration of metadoxine and garlic oil according to the present invention exhibits outstandingly superior effects of inhibiting the accumulation of triglyceride and increase of blood AST (aspartate aminotransferase) level in liver el tissue, inhibiting the expression of FAS (fatty acid synthase), CYP2E1 and iNOS (inducible nitric oxide synthase) and inhibiting the deactivation of AMPK (AMP-activated protein kinase), as compared to the administration of metadoxine or garlic oil only.