Frontiers in Cell and Developmental Biology
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2025
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IF 4.3
Weijie Li,Xi Yang,Wenyan Bi,Liyong Song,Baolin Liu
Developing bioartificial liver and hepatocyte transplantation technology causes increasing hepatocyte cell demand. Effective long-term hepatocyte cell preservation methods are necessary to promote. Progressive cooling is a key preservation technology for cell banks. However, the cell solution needs to be supercooled in a slow freezing process. The high degree of supercooling possibly induces uncontrollable intracellular ice formation. This work designs an ultrasonic ice-seeding system for L-02 hepatocyte cell preservation, reducing supercooling and improving cell survival rate. The effect of ultrasonic intensities on the hepatocyte’s survival rate was investigated and optimized. The results prove the calorimetric method can efficiently measure the ultrasonic intensity dissipated in the hepatocyte cell preservation solution. When the ultrasonic intensity is 0.0329 W/cm 2 ∼ 0.4316 W/cm 2 , the hepatocyte survival rate is over 90%. There is no significant difference between experiment groups (p < 0.05) when the ultrasonic intensity is larger than 0.4316 W/cm 2 . The hepatocyte cell survival rate reduced significantly with the increase of ultrasonic intensity. The 7-day hepatic function indicator experiment results indicate that the ultrasonic ice seeding has the weakest impact on hepatocyte cells in the four groups. The secretion of urea, albumin and glucose proved that ultrasonic ice seeding technology does not affect cell secretion and has an enormous advantage in cryopreservation. It can be widely applied to cell freezing fields.
研究领域:
生物技术
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医学工程
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2018
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IF 3.095
Qin-You Tan,Qian Hu,Sheng-Nan Zhu,Lu-Lu Jia,Juan Xiao,Hua-Zhen Su,Shao-Yuan Huang,Jing Zhang,Junfei Jin
Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury. The aim of this study was to investigate the role of the factor erythroid 2-related factor 2 pathway in the protective effects of LE and MIG against triptolide-induced hepatotoxicity. Hepatotoxicity models were established in L-02 cells and rats using triptolide, and the protective effects of LE and MIG were investigated in vitro and in vivo, respectively. LE and MIG significantly protected against triptolide-induced cytotoxicity. Additionally, triptolide decreased the mRNA and protein levels of Nrf2 and down-regulated Nrf2 target genes, including UGT1A, BSEP, and MRP2, while pretreatment with LE and MIG reversed these effects. Finally, Nrf2-involved antioxidant responses were activated in the presence of LE and MIG.
研究领域:
药理学
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毒理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2019
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IF 4.18
Licong Zhao,Jiaqi Zhang,Lingyun Pan,Long Chen,Yu Wang,Xinhua Liu,Lisha You,Yiqun Jia,Cheng Hu
Background Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Fisetin (FST) is a phenolic compound that has been isolated from many natural products. Purpose Our aim is to study the protection effect and mechanisms of FST on APAP-induced hepatotoxicity in endogenous metabolism and metabolomics in vitro and in vivo . Methods FST was i.g. administered to mice at 10 , 20 and 40 mg/kg for 7 days and a single dose of APAP (400 mg/kg) was given on the last day. Serum and tissue were collected for biochemical analysis . L-02 cells were used to assess cell viability . LC–MS was used to study the metabolic fingerprinting in vivo and vitro . PCA and OPLS-DA were used to search the potential biomarkers (VIP > 1, p < 0.05). The pathway analysis was conducted on Metaboanalyst 4.0. Then liver oxidative stress indices and glutathione markers were examined using PCR and kits. Results ALT , AST, liver histological observation and cell viability results showed that FST could reverse APAP induced toxicology in mice and L-02 cells. In metabolomics study, 26 metabolites in vitro and 60 metabolites in vivo were identified by searching in the library and most of them decreased to normal level in FST treatment . It is observed in pathway analysis that the most significant pathway was glutathione metabolism. Furthermore, the results of mRNA and immunofluorescence showed that FST suppressed ROS formation in liver tissue and L-02 cells, as well as restored the expression of GPX1 , GST and other antioxidative enzymes genes. Conclusion Our results indicate that FST prevented APAP-induced hepatotoxicity by regulating glutathione metabolism and the expression of related antioxidative signals.
研究领域:
药理学
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毒理学
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代谢组学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
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2019
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IF 3.31
Yun Li,Yueqin Li,Nana Wang,Dong Lin,Xiaohui Liu,Yong Yang,Qinwei Gao
Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙− radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7 μM, which showed potent cytotoxic activity over standard drug cisplatin. AbbreviationsA549human lung carcinoma cellBSAbovine serum albuminCCK-8Cell Counting Kit-8DFTdensity functional theoryDNAdeoxyribonucleic acidDPPH˙2,2-diphenyl-1-picrylhydrazylH2L12-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneH2L2N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneHOMOhighest occupied molecular orbitalIC50the 50% activityL-02human normal liver cellLOMOlowest unoccupied molecular orbital (LUMO)MCF-7human breast carcinoma cellNO˙nitric oxideO2˙−superoxide anionSODsuperoxide dismutaseCommunicated by Ramaswamy H. Sarma
研究领域:
无机化学
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生物化学
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药理学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2023
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IF 5.2
Yanping Fan,Meilan Xue,Tianhu Shan,Yixian Bai,Huaqi Zhang,Man Liu,Peng Wang,Xi Liang,Hui Liang
Alcoholic liver fibrosis (ALF) is a reversible pathological change in the liver caused by chronic alcohol consumption and is associated with the activation of hepatic stellate cells . Recent findings suggest that niacin can lower triglyceride levels and exert potent antioxidant effects in liver damage. However, the therapeutic effects and molecular mechanisms of niacin in liver fibrosis remain unclear. Therefore, this study aimed to investigate the effects and mechanisms of niacin in ALF using in vivo and in vitro experiments. To establish a murine model of ALF, male C57BL/6N mice were fed a Lieber–DeCarli liquid diet containing 4 % (vol/vol) ethanol and injected with carbon tetrachloride twice weekly (2 mL/kg) for 8 weeks. L-02 and LX2 cells were treated with 400 μM acetaldehyde for 24 h to establish an in vitro ALF model. Serum parameters were examined to investigate the protective effects of niacin against ALF, and network pharmacology was used to identify potential targets and pathways of niacin. Niacin protects against ALF by suppressing the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase , and alkaline phosphatase . Additionally, niacin treatment ameliorated liver fibrosis by improving the antioxidant system, inhibiting heat shock protein 90 (HSP90) activation, promoting signal transducer and activator of transcription 3 (STAT3) ubiquitination , and suppressing the JAK1/STAT3 signaling pathway . Collectively, this study provides experimental evidence that niacin protects against ALF by downregulating the HSP90/JAK1/STAT3 signaling pathway.
研究领域:
药理学
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肝病学
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分子生物学
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细胞生物学
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产品关联
DOI
高影响因子
Oncotarget
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2016
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IF 5.008
Hui-Yun Zhang,Wen-Qian Xu,Yuan-yuan Zheng,Emmanuel Omari-Siaw,Yuan Zhu,Xia Cao,Shan-Shan Tong,Jiang-nan Yu,Xi-ming Xu
Cardiac glycosides could increase intracellular Ca 2+ ion by inhibiting the Na + /K + ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae . The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H 22 tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H 22 cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy.
研究领域:
药理学
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肿瘤学
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药物递送系统
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药物化学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）