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•Theabrownin (TB) inhibits OA-induced lipid accumulation and ROS Overproduction in HepG2 Cells.•TB Regulate OA-induced Circadian Desynchrony in HepG2 Cells•PPAR is a key signaling ...pathway for TB to regulate lipid metabolism disorders.•TB prevent OA-induced lipid metabolism disorder via a bmal1-dependent pathway.
Theabrownin (TB) is the main characteristic component and bioactive substance of Pu-erh tea. Our previous studies have demonstrated interactions among the TB, the circadian rhythm, and obesity, but the underlying mechanism remains unclear. In this study, we focused on the mechanism by which TB ameliorates lipid accumulation caused by oleic acid (OA) by modulating circadian rhythm genes in HepG2 cells. The results showed that TB could reduce triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels, reactive oxygen species (ROS) overproduction and lipid droplet formation. Additionally, TB could regulate OA-mediated circadian desynchrony by regulating the mRNA and protein expression of circadian genes. Furthermore, as revealed by proteomics results, the PPAR pathway is a potential pathway through which TB ameliorates lipid metabolism disorders. After Bmal1 knockdown, the ameliorative effect of TB on OA-induced PPARγ and plin1 protein expression was decreased, which suggested that TB could ameliorate lipid accumulation in HepG2 cells via a Bmal1-dependent pathway.
•A series of novel isoindolinone derivatives synthesized from bioactive Lawsone.•An environmentally benign & efficient protocol developed for the synthesis.•DFT calculations performed at B3LYP level ...of 6-311G basic set.•The compounds exhibits high to moderate activity against HepG2 cell lines.•In vivo studies ascertained that compounds can lead to enhanced tumour regression.
An efficient Mannich type multicomponent reaction approach was developed for the synthesis of a series of novel substituted isoindolinones derived from Lawsone, 2-formyl benzoic acid, and various primary amines. This protocol features direct construction of C-N and C-C bonds via metal-free method at room temperature using an environment-friendly solvent. The synthesized isoindolinone compounds 4a-4m were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and ESI-MS. Computational studies were carried out by the DFT method using B3LYP/6-31G (d,p) basic set as a tool to analyse the chemical reactivity parameters and comprehend the molecular interaction. The molecular electrostatic potential (MEP), dipole moment, chemical reactivity, and stability features of investigated isoindolinones revealed that 4i, 4j, 4l, and 4m could be promising candidates for further biological activity. The cytotoxic activity of selected compounds was evaluated using MTT assay against HepG2 cell lines (Human liver cancer cell line). The data revealed that screened compounds displayed excellent to moderate activity. The docking examination was executed on a promising liver cancer-associated Alpha fetoprotein (AFP). It showed a positive outcome with minimum binding energy and hydrogen bond interaction. Furthermore, In vivo studies ascertained that synthesized isoindolinone derivatives can lead to enhanced cancer cell death and prevention of tumor growth by restoring serum SGOT and SGPT levels near to normal. It further restores matrix metallopeptidase (MMP-2 and MMP-9 levels) near to control confirms the effectiveness of the compound.
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Exosomes are closed-membrane nanovesicles that are secreted by a variety of cells and exist in most body fluids. Recent studies have demonstrated the potential of exosomes as natural vehicles that ...target delivery of functional small RNA and chemotherapeutics to diseased cells.
In this study, we introduce a new approach for the targeted delivery of exosomes loaded with functional miR-26a to scavenger receptor class B type 1-expressing liver cancer cells. The tumor cell-targeting function of these engineered exosomes was introduced by expressing in 293T cell hosts, the gene fusion between the transmembrane protein of CD63 and a sequence from Apo-A1. The exosomes harvested from these 293T cells were loaded with miR-26a via electroporation.
The engineered exosomes were shown to bind selectively to HepG2 cells via the scavenger receptor class B type 1-Apo-A1 complex and then internalized by receptor-mediated endocytosis. The release of miR-26a in exosome-treated HepG2 cells upregulated miR-26a expression and decreased the rates of cell migration and proliferation. We also presented evidence that suggest cell growth was inhibited by miR-26a-mediated decreases in the amounts of key proteins that regulate the cell cycle.
Our gene delivery strategy can be adapted to treat a broad spectrum of cancers by expressing proteins on the surface of miRNA-loaded exosomes that recognize specific biomarkers on the tumor cell.
Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the ...hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.
Casein-derived antioxidant peptides by using microbial proteases have gained increasing attention. Combination of two microbial proteases, Protin SD-NY10 and Protease A “Amano” 2SD, was employed to ...hydrolyze casein to obtain potential antioxidant peptides that were identified by LC-MS/MS, chemically synthesized and characterized in a oxidatively damaged HepG2 cell model. Four peptides, YQLD, FSDIPNPIGSEN, FSDIPNPIGSE, YFYP were found to possess high 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability. Evaluation with HepG2 cells showed that the 4 peptides at low concentrations (< 1.0 mg/ml) protected the cells against oxidative damage. The 4 peptides exhibited different levels of antioxidant activity by stimulating mRNA and protein expression of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as nuclear factor erythroid-2-related factor 2 (Nrf2), but decreasing the mRNA expression of Kelch-like ECH-associated protein 1 (Keap1). Furthermore, these peptides decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), but increased glutathione (GSH) production in HepG2 cells. Therefore, the 4 casein-derived peptides obtained by using microbial proteases exhibited different antioxidant activity by activating the Keap1-Nrf2 signaling pathway, and they could serve as potential antioxidant agents in functional foods or pharmaceutic preparation.
Acetochlor is one of the most widely used chiral herbicides in the world, and it is usually produced and used as racemic form (Rac). The potential effects of acetochlor in human body are mainly ...induced by its residue in agriculture food. The direct target exposed is the liver in human body. However, the potential toxic and mechanism threat to human liver cells caused by chiral acetochlor has been rarely reported. The purpose of this study is to explore the potential mechanism of the toxicity caused by chiral acetochlor in HepG2 cells. The results revealed that acetochlor and its enantiomers could inhibit cell activity and cause DNA damage in HepG2 cells. The toxicity of Rac was higher than that of the two enantiomers, mainly derived from S configuration. The mechanism is through inducing decreased membrane potential (△Ψ), up-regulated Bax/BcL-2 expression, caused a cascade reaction, activated casepase-3 and casepase-9 and cleaved PARP, which maybe lead to cell death through apoptotic-signaling pathway in the end. These results illuminate that the genotoxic and cytotoxic risks of chiral acetochlor are major coming from S configuration. It provides a theoretical basis for the production of single pesticide to reduce the effects of human health.
•Acetochlor induces HepG2 cells apoptosis by activating BcL/Bax pathway.•Acetochlor promotes ROS generation and causes DNA damage in HepG2 cells.•Acetochlor induces casepase activation and a decrease in mitochondrial membrane potential.•The toxicity of acetochlor enantiomers was stereoselective in HepG2 cells.•S-enantiomer plays a major role than R-enantiomer in toxicity of cells.
The aptamers generated from HepG2 cells Huang, Rongrong; Chen, Zhongsi; Liu, Mei ...
Science China. Chemistry,
06/2017, Letnik:
60, Številka:
6
Journal Article
Recenzirano
Liver cancer, as the second cause of cancer death all around the world, resulted in a series of chronic liver diseases. More than 80%of the patients cannot receive effective treatment because of ...their advanced disease or poor liver function. It is time to improve early clinical diagnosis and find optimal therapeutic treatments. As the tumor cells behave differently from the cell-surface molecules, it is necessary to find a highly specific probe. The aptamers, known as ＂chemical antibodies＂, can bind to their target molecules with high affinity and high specificity. The apatmers were obtained by Cell-SELEX, which was aimed at finding the aptamers against whole living cells. In the article, after 19 selections, the ssDNA pool was cloned and sequenced. After that, six aptamers were obtained, named apt_A to apt_F. By incubating the aptamers with different cells, except apt_E, the other aptamers showed high specificity. As for apt_E, which showed high affinity to several cancer cells, was a potential probe for the common protein presented by several different cancer cells. The equilibrium dissociation constants（Kd） were evaluated by measuring the flow cytometry signal that characterized the binding ability of aptamers to the target cells at a series of concentrations ranging from 46.3（4.5） nM to 199.4（44.2） nM, which exposed the high binding affinities of these aptamers. The research in the confocal fluorescence images further confirmed the specificity of these aptamers and the fact that the aptamers were combined with the targets on the cell-surface.
Ferroptosis is a regulated cell death pathway which depends on iron. Ferroptosis can be induced by limiting intracellular glutathione (GSH) synthesis, or inhibiting the activity of GPX4, or ...increasing intracellular accumulation of PE-AA-OOH, all of which involve NADPH. Therefore, NADPH depletion, excessive PE-AA-OOH, and GPX4 deficiency are generally considered to be the main characteristics of ferroptosis. In this research, the novel self-assembly nanomicelles modified by maltose ligand (Malt-PEG-Abz@RSL3) with superior nano characteristics were designed and fabricated. Malt-PEG-Abz@RSL3 micelles achieved active targeted drug delivery due to the high expression of glucose transporter (GLUT) and high uptake by HepG2 cells. Maltose-polyethylene glycol broke to release RSL3 for inhibiting GPX4 activity when Malt-PEG-Abz@RSL3 micelles entered the cells. Meanwhile, key coenzyme NADPH that participated in synthesis of GSH and Trx(SH)
2
was depleted by azobenzene moiety, resulting in decreasing GSH and Trx(SH)
2
, which dually induced ferroptosis in tumour cells and promoted cell apoptosis.
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