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  1. Article: [Mechanism of famous classical formula Huaihua Powder in treatment of ulcerative colitis based on metabonomics].

    Han, Li-Ying / Yu, Hao / Li, Tian-Jiao / Wang, Shuai / Bao, Yong-Rui / Meng, Xian-Sheng

    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

    2023  Volume 48, Issue 5, Page(s) 1300–1309

    Abstract: Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the ... ...

    Abstract Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.
    MeSH term(s) Mice ; Animals ; Colitis, Ulcerative/chemically induced ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/metabolism ; Powders ; Tumor Necrosis Factor-alpha/metabolism ; Interleukin-6/metabolism ; Metabolomics ; Colon ; Disease Models, Animal ; Biomarkers ; Dextran Sulfate/metabolism ; Dextran Sulfate/pharmacology ; Dextran Sulfate/therapeutic use
    Chemical Substances Powders ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Biomarkers ; Dextran Sulfate (9042-14-2)
    Language Chinese
    Publishing date 2023-04-01
    Publishing country China
    Document type English Abstract ; Journal Article
    ZDB-ID 1004649-5
    ISSN 1001-5302 ; 0254-0029
    ISSN 1001-5302 ; 0254-0029
    DOI 10.19540/j.cnki.cjcmm.20221025.401
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma.

    Wang, Shuai / Yang, Xin-Xin / Li, Tian-Jiao / Zhao, Lin / Bao, Yong-Rui / Meng, Xian-Sheng

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 999935

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-08-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.999935
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effect of Oroxylum indicum on hepatocellular carcinoma via the P53 and VEGF pathways based on microfluidic chips.

    Luo, Xi / Zhao, Miao / Liu, Sicong / Zheng, Yi / Zhang, Qiang / Bao, Yong-Rui / Wang, Shuai / Li, Tian-Jiao / Meng, Xian-Sheng

    BMC complementary medicine and therapies

    2023  Volume 23, Issue 1, Page(s) 400

    Abstract: Background: Hepatocellular carcinoma (HCC), abbreviated as liver cancer, is one of the most common cancers in clinics. HCC has a wider spread and higher incidence due to its high malignancy and metastasis. In HCC, effective strategies to block cancer ... ...

    Abstract Background: Hepatocellular carcinoma (HCC), abbreviated as liver cancer, is one of the most common cancers in clinics. HCC has a wider spread and higher incidence due to its high malignancy and metastasis. In HCC, effective strategies to block cancer cell migration, invasion, and neovascularization need to be further studied. Consumption of flavonoid-rich Oroxylum indicum (OI) has been associated with multiple beneficial effects, including anti-inflammatory and anticancer properties, but the potential effects on HCC have not been thoroughly investigated.
    Objective: In this study, we aimed to reveal the effect of OI on HCC and its potential mechanism through microfluidic technology.
    Methods: We designed microfluidic chips for cell migration, invasion, and neovascularization to evaluate the effect of OI on HepG2 cells. To further explore the mechanism of its anti-liver cancer action, the relevant signaling pathways were studied by microfluidic chips, RT‒qPCR and immunofluorescence techniques. Compared to the control group, cell migration, invasion, and angiogenesis were significantly reduced in each administration group. According to the P53 and VEGF pathways predicted by network pharmacology, RT‒qPCR and immunofluorescence staining experiments were conducted.
    Results: The results showed that OI upregulated the expression of Bax, P53 and Caspase-3 and downregulated the expression of Bcl-2 and MDM2. It has been speculated that OI may directly or indirectly induce apoptosis of HepG2 cells by regulating apoptosis-related genes. OI blocks the VEGF signaling pathway by downregulating the expression levels of VEGF, HIF-1α and EGFR and inhibits the migration and invasion of HepG2 cells and the formation of new blood vessels.
    Conclusion: Our findings suggest that OI may inhibit the migration, invasion, and neovascularization of HepG2 cells, and its regulatory mechanism may be related to the regulation of the P53 and VEGF pathways.
    MeSH term(s) Humans ; Carcinoma, Hepatocellular/genetics ; Liver Neoplasms/genetics ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Microfluidics
    Chemical Substances Tumor Suppressor Protein p53 ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2023-11-07
    Publishing country England
    Document type Journal Article
    ISSN 2662-7671
    ISSN (online) 2662-7671
    DOI 10.1186/s12906-023-04217-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Patrinia villosa treat colorectal cancer by activating PI3K/Akt signaling pathway.

    Li, Xiao-Chen / Wang, Shuai / Yang, Xin-Xin / Li, Tian-Jiao / Gu, Jia-Xing / Zhao, Lin / Bao, Yong-Rui / Meng, Xian-Sheng

    Journal of ethnopharmacology

    2023  Volume 309, Page(s) 116264

    Abstract: Ethnopharmacological relevance: At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage ... ...

    Abstract Ethnopharmacological relevance: At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage to the body of the patient. Patrinia villosa Juss. (P.V), is a well-known traditional chinese medicine (TCM), and is recorded in the Compendium of Materia Medica as a necessary article for the treatment of intestinal carbuncle. It has been incorporated into traditional cancer treatment prescriptions in modern medicine. While the mechanism of action of P.V in the treatment of CRC remains unclear.
    Aim of the study: To investigate P.V in treating CRC and clarify the underlying mechanism.
    Materials and methods: This study was based on Azoxymethane (AOM) combined with the Dextran Sulfate Sodium Salt (DSS)-induced CRC mouse model to clarify the pharmacological effects of P.V. The mechanism of action was found by metabolites and metabolomics. The rationality of metabolomics results was verified through the clinical target database of network pharmacology, and find the upstream and downstream target information of relevant action pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using quantitative PCR (q-PCR) and Western blot.
    Results: The number and the diameter of tumors were decreased when mice were treated with P.V. P.V group section results showed newly generated cells which improved the degree of colon cell injury. Pathological indicators presented a trend of recovery to normal cells. Compared to the model group, P.V groups had significantly lower levels of the CRC biomarkers CEA, CA19-9, and CA72-4. Through the evaluation of metabolites and metabolomics, it was found that a total of 50 endogenous metabolites had significant changes. Most of these are modulated and recovered after P.V treatment. It alters glycerol phospholipid metabolites, which are closely related to PI3K target, suggesting that P.V can treat CRC though the PI3K target and PI3K/Akt signaling pathway. q-PCR and Western blot results also verified that the expression of VEGF, PI3K, Akt, P38, JNK, ERK1/2, TP53, IL-6, TNF-α and Caspase-3 were significantly decreased, whereas that of Caspase-9 was increased after treatment.
    Conclusion: P.V is dependent on PI3K target and PI3K/Akt signaling pathway for CRC treatment.
    MeSH term(s) Animals ; Mice ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Patrinia ; Colorectal Neoplasms/metabolism ; Signal Transduction
    Chemical Substances Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Language English
    Publishing date 2023-03-01
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.116264
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Metabolic regularity of bioactive compounds in Bufei Jianpi granule in rats using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry analysis technology.

    Wang, Shuai / Yang, Xin Xin / Li, Tian Jiao / Tian, Xiang Mu / Wang, Ying Li / Bai, Gang / Bao, Yong Rui / Meng, Xian Sheng

    Biomedical chromatography : BMC

    2023  Volume 37, Issue 12, Page(s) e5740

    Abstract: Bufei Jianpi granule (BJG) is clinically effective for treating chronic obstructive pulmonary disease (COPD). At present, there is no report regarding the drug metabolism of BJG in vivo. This work developed an ultra-high-performance liquid chromatography ...

    Abstract Bufei Jianpi granule (BJG) is clinically effective for treating chronic obstructive pulmonary disease (COPD). At present, there is no report regarding the drug metabolism of BJG in vivo. This work developed an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method with high accuracy and sensitivity to determine drug metabolism of this compound in vivo. After continuous administration of BJG, the concentrations of 10 components in rat plasma, namely betaine, peimine, peiminine, astragaloside A, sinensetin, nobiletin, naringin, calycosin, formononetin, and magnolol, were determined at different time points. Meanwhile, the pharmacokinetic parameters and metabolic rules of these 10 components were evaluated: C
    MeSH term(s) Rats ; Animals ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid/methods ; Drugs, Chinese Herbal/chemistry ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Pulmonary Disease, Chronic Obstructive/metabolism ; Mass Spectrometry ; Technology
    Chemical Substances bufei jianpi ; Drugs, Chinese Herbal
    Language English
    Publishing date 2023-09-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 632848-9
    ISSN 1099-0801 ; 0269-3879
    ISSN (online) 1099-0801
    ISSN 0269-3879
    DOI 10.1002/bmc.5740
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

    Han, Li-Ying / Yu, Hao / Wang, Shuai / Bao, Yong-Rui / Li, Tian-Jiao / Zheng, Ying / Luo, Xi / Jia, Meng-Nan / Zhang, Qiang / Meng, Xian-Sheng

    Journal of ethnopharmacology

    2024  Volume 325, Page(s) 117805

    Abstract: Ethnopharmacological relevance: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is ... ...

    Abstract Ethnopharmacological relevance: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study.
    Aim of the study: To investigate F.S in treating CRC and clarify the underlying mechanism.
    Materials and methods: This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action.
    Results: In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment.
    Conclusion: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.
    MeSH term(s) Animals ; Mice ; Powders/therapeutic use ; Proto-Oncogene Proteins p21(ras)/metabolism ; Selective Estrogen Receptor Modulators/therapeutic use ; Signal Transduction ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Colorectal Neoplasms/metabolism ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use
    Chemical Substances Powders ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Selective Estrogen Receptor Modulators ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; Drugs, Chinese Herbal
    Language English
    Publishing date 2024-01-24
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2024.117805
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Qualitative, quantitative, and pharmacokinetic study on the absorbed components of Ardisia japonica (Thunb.) Blume in rat plasma based on molecular networking combined with quadrupole time-of-flight LC/MS and triple quadrupole LC/MS.

    Wang, He Chen / Li, Tian Jiao / Bao, Yong Rui / Wang, Shuai / Meng, Xian Sheng

    Biomedical chromatography : BMC

    2021  Volume 35, Issue 7, Page(s) e5099

    Abstract: Isolation and screening of different compounds from plant extracts are always the key for natural drug research, and the absorbed prototype components have been considered as potential active ingredients. UHPLC combined with quadrupole time-of-flight ... ...

    Abstract Isolation and screening of different compounds from plant extracts are always the key for natural drug research, and the absorbed prototype components have been considered as potential active ingredients. UHPLC combined with quadrupole time-of-flight mass spectrometry (Q-TOF-LC/MS) has been widely used in the research of natural drugs; however, we still need a more effective tool to compare and treat from a raw data. In this study, we provided a fast analytical method to measure the absorbed prototype components and their metabolites both qualitatively and quantitatively based on molecular networking (MN). For example, in Ardisia japonica (Thunb.) Blume, a total of eight absorbed prototype components in rat plasma were identified. Furthermore, pharmacokinetic study was also successfully performed on the eight absorbed prototype components in rat plasma. Our findings have provided important information on the investigation of A. japonica in vivo. More importantly, the MS network analysis pattern serves as an integral solution for qualitative and quantitative determination of phytochemical compounds in natural drugs.
    MeSH term(s) Animals ; Ardisia/chemistry ; Chromatography, High Pressure Liquid/methods ; Computational Biology ; Linear Models ; Male ; Phytochemicals/blood ; Phytochemicals/chemistry ; Phytochemicals/pharmacokinetics ; Plant Extracts/blood ; Plant Extracts/chemistry ; Plant Extracts/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry/methods
    Chemical Substances Phytochemicals ; Plant Extracts
    Language English
    Publishing date 2021-04-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 632848-9
    ISSN 1099-0801 ; 0269-3879
    ISSN (online) 1099-0801
    ISSN 0269-3879
    DOI 10.1002/bmc.5099
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Mechanism of total glucosides from Chishao (Radix Paeoniae Rubra) on proliferation and apoptosis of hepatocellular carcinoma cells via phosphatase and tensin homolog deleted on chromosome ten / phosphatidylinositol 3-kinase / protein kinase B signaling pathway.

    Fan, Bing-Bing / Li, Tian-Jiao / Meng, Xian-Sheng / Wang, Shuai / Bao, Yong-Rui / Wang, Fei

    Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan

    2021  Volume 41, Issue 5, Page(s) 677–683

    Abstract: Objective: To investigate the possible molecular mechanism of total glycosides of Chishao (Radix Paeoniae Rubra) (TG-RPR) on proliferation and apoptosis of hepatocellular carcinoma cells.: Methods: The proliferation of TG-RPR on HepG2 cells was ... ...

    Abstract Objective: To investigate the possible molecular mechanism of total glycosides of Chishao (Radix Paeoniae Rubra) (TG-RPR) on proliferation and apoptosis of hepatocellular carcinoma cells.
    Methods: The proliferation of TG-RPR on HepG2 cells was detected using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis of HepG2 cells was measured by annexin V-FITC/double staining. The phosphatase and tensin homolog deleted on chromosome ten (PTEN) / phosphatidylinositol 3-kinase (PI3K) / protein kinase B (Akt) signaling pathway was evaluated by Western Blot and reverse transcription-polymerase chain reaction (RT-PCR).
    Results: TG-RPR can up-regulation the expression of pro-apoptotic factors such as PTEN and BCL2-Associated X (Bax), down-regulation the expression of anti-apoptotic factors including B-cell lymphoma-2 (Bcl-2), PI3K, and Akt.
    Conclusion: TG-RPR significantly inhibits the proliferation of HepG2 cells in a dose-dependent manner and promotes apoptosis. These results demonstrated TG-RPR has significant inhibitory effect on HepG2 cells. These results identify a critical role of TG-RPR in proliferation and apoptosis of HepG2 cells via modulating PTEN/PI3K/Akt signaling pathway. TG-RPR may offer a promise as a potential pharmaceutical therapy for hepatocellular carcinoma.
    MeSH term(s) Apoptosis ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Proliferation ; Chromosomes/metabolism ; Drugs, Chinese Herbal/pharmacology ; Glucosides/pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/pathology ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinase/genetics ; Phosphatidylinositol 3-Kinase/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
    Chemical Substances Drugs, Chinese Herbal ; Glucosides ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
    Language English
    Publishing date 2021-10-28
    Publishing country China
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603186-9
    ISSN 2589-451X ; 0254-6272 ; 0255-2922
    ISSN (online) 2589-451X ; 0254-6272
    ISSN 0255-2922
    DOI 10.19852/j.cnki.jtcm.2021.05.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Potential effects of fructus aurantii ethanol extracts against colitis-associated carcinogenesis through coordination of Notch/NF-κB/IL-1 signaling pathways.

    Luo, Xi / Zheng, Yi / Bao, Yong-Rui / Wang, Shuai / Li, Tian-Jiao / Leng, Jia-Peng / Meng, Xian-Sheng

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2022  Volume 152, Page(s) 113278

    Abstract: Colitis-associated cancer (CAC) is the colorectal cancer (CRC) subtype that is difficult to treat, and shows high mortality. The consumption of flavonoid-rich fructus aurantii extracts (FAE) has been associated with multiple beneficial effects including ... ...

    Abstract Colitis-associated cancer (CAC) is the colorectal cancer (CRC) subtype that is difficult to treat, and shows high mortality. The consumption of flavonoid-rich fructus aurantii extracts (FAE) has been associated with multiple beneficial effects including anti-inflammatory and anti-cancer properties, but the potential effects on the colitis-associated carcinogenesis have not been thoroughly investigated. Recent clinical data show that, as yet, few agents clearly inhibited CRC development in long-standing inflammatory bowel diseases. Here, we identified that FAE showed significant efficiency to inhibit HT-29 cell proliferation. The potential of FAE in vivo was further evaluated in an AOM/DSS-induced CAC mouse model. Intriguingly, FAE diminished the number of polyps in mice. Furthermore, FAE inhibited CAC by regulating the gene expression of Notch/ NF-κB/IL-1 signaling pathways. Collectively, these results were indicative of FAE has great potential in CAC prevention and treatment.
    MeSH term(s) Animals ; Carcinogenesis ; Colitis/chemically induced ; Colitis/complications ; Colitis/drug therapy ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Ethanol/adverse effects ; Interleukin-1 ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Plant Extracts/adverse effects ; Signal Transduction
    Chemical Substances Interleukin-1 ; NF-kappa B ; Plant Extracts ; Ethanol (3K9958V90M) ; Dextran Sulfate (9042-14-2)
    Language English
    Publishing date 2022-06-13
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2022.113278
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Design and fabrication of an integrated 3D dynamic multicellular liver-on-a-chip and its application in hepatotoxicity screening

    Zheng, Yi-bo / Ma, Li-dong / Wu, Jian-lin / Wang, Yi-ming / Meng, Xian-sheng / Hu, Ping / Liang, Qiong-lin / Xie, Yuan-yuan / Luo, Guo'an

    Talanta. 2022 May 01, v. 241 p.123262-

    2022  

    Abstract: Nowadays, major methods of in vitro hepatotoxicity research are still based on traditional static two- or three-dimensional cell culture, although these means could investigate some toxic chemicals induced hepatotoxicity, but most of these toxicities ... ...

    Abstract Nowadays, major methods of in vitro hepatotoxicity research are still based on traditional static two- or three-dimensional cell culture, although these means could investigate some toxic chemicals induced hepatotoxicity, but most of these toxicities failed to reappear in human, at least not in similar or calculable dose level. These failures may cause by the monoculture of only hepatocytes, ignored the signal communication to other non-parenchymal cells in liver tissue, also other complex microenvironment such as endothelial barrier, shear stress and other factors which were really existed in vivo but absent here, final leading to a low reliability of experimental results. In this study, a three-dimensional dynamic multi-cellular liver-on-a-chip device (3D-DMLoC) was developed to reproduce the microenvironment of in vivo liver tissue, including the simulation of hepatic sinusoid, perisinusoidal space and continuous liquid perfusion, hepatocytes could gather to some 3D cell spheroids in this chip. The perfusion could bring a real-time exchange of chemicals, nutrients, metabolites, supply suitable oxygen and a weak shear stress. The pressure and oxygen distribution inner the chip were simulated and evaluated by COMSOL Multiphysics software. HepaRG were co-cultured with HUVEC for 7 days in this chip, expression of hepatic polarization protein ZO-1 and MRP2, liver function factors ALB, UREA and CYP450s were almost all higher than in traditional static culture. Several drugs and heavy metal ions induced hepatotoxicity were then investigated, LDH released from hepatocyte spheroids in mostly 3D-DMLoC groups were higher than same-dosed 2D group, indicated the spheroids were more sensibility to the toxins. The hepatoxicity might be induced by acute hepatocytes injury according to the ratios of secreted AST/ALT contents. In conclusion, a liver-on-a-chip device was successfully developed and verified for better reproducing the in vivo physiological microenvironment of liver. It could be applied for easily, efficiently, and accurately screening the potential hepatotoxic chemicals in future.
    Keywords coculture ; computer software ; heavy metals ; hepatocytes ; hepatotoxicity ; humans ; liquids ; liver ; liver function ; metabolites ; organ-on-a-chip ; oxygen ; shear stress ; urea ; Liver-on-a-chip ; Microfluidics ; Hepatocyte spheroids ; Cell co-culture
    Language English
    Dates of publication 2022-0501
    Publishing place Elsevier B.V.
    Document type Article ; Online
    ZDB-ID 1500969-5
    ISSN 1873-3573 ; 0039-9140
    ISSN (online) 1873-3573
    ISSN 0039-9140
    DOI 10.1016/j.talanta.2022.123262
    Database NAL-Catalogue (AGRICOLA)

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