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SCIENCE OF THE TOTAL ENVIRONMENT · 2023 · IF 9.8

Integration approach of transcriptomics and metabolomics reveals the toxicity of Anthracene and its chlorinated derivatives on human hepatic cells

Yun Luo,Ningbo Geng,Shuai Sun,Lin Cheng,Shuangshuang Chen,Haijun Zhang,Jiping Chen

Polycyclic aromatic hydrocarbons (PAHs) and Chlorinated PAHs (Cl-PAHs) are ubiquitous environmental contaminants. The toxicological information of anthracene (Ant) and its chlorinated derivatives is quite limited. In this study, an integrated metabolomic and transcriptomic analysis approach was adopted to assess the toxic effects triggered by Ant and its chlorinated derivatives, 2-chloroanthracene (2-ClAnt) and 9,10-dichloroanthracen (9,10-Cl 2 Ant), at human-relevant levels on human normal hepatocyte L02 cells. The cell viability test showed no significant effects on the viability of L02 cells exposed to Ant, 2-ClAnt and 9,10-Cl 2 Ant at doses of 5–500 nM for 24 h. However, based on transcriptomic analysis, Ant, 2-ClAnt and 9,10-Cl 2 Ant exposure at human-relevant levels obviously perturbed global gene expression in L02 cells and induced the differential expression of several genes related to cancer development. As the number of genes related to cancer development altered by 9,10-Cl 2 Ant is the largest, 9,10-Cl 2 Ant posed greater risks of tumor development than Ant and 2-ClAnt did. Metabolomics analysis demonstrated that Ant, 2-ClAnt and 9,10-Cl 2 Ant caused significant metabolic perturbation in L02 cells. Pathway enrichment analysis indicated that Ant, 2-ClAnt and 9,10-Cl 2 Ant mainly perturbed the lipid metabolism and nucleotide metabolism pathway. However, 9,10-Cl 2 Ant caused a wider perturbation to metabolic pathways than Ant and 2-ClAnt did. In addition, dysregulation of nucleotide metabolism perturbed by Ant, 2-ClAnt and 9,10-Cl 2 Ant may be associated with the genomic instability and further carcinogenesis.

研究领域: 环境毒理学 · 分子生物学 · 基因组学 · 代谢组学
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BIOORGANIC CHEMISTRY · 2019 · IF 3.926

Synthesis, anticancer activity and molecular docking studies on 1,2-diarylbenzimidazole analogues as anti-tubulin agents

Ya-Liang Zhang,Rong Yang,Lin-Ying Xia,Ruo-Jun Man,Yi-Chun Chu,Ai-Qin Jiang,Zhong-Chang Wang,Hai-Liang Zhu

Twenty-four 1,2-diarylbenzimidazole derivatives were designed, synthesized and biologically evaluated. It turned out that most of them were potential anticancer drugs. Among them, compound c24 showed the highest anti-tumor activity (GI 50  = 0.71–2.41 μM against HeLa, HepG2, A549 and MCF-7 cells), and low toxicity to normal cells (CC 50  > 100 μM against L02 cells). In the microtubule binding assay, c24 showed the most potent inhibition of microtubule polymerization (IC 50  = 8.47 μM). The binding ability of compound c24 to tubulin crystal was verified by molecular docking simulation experiment. Further studies on HepG2 and HeLa cells showed that compound c24 could cause mitotic arrest of tumor cells to G2/M phase then inducing apoptosis. To sum up, compound c24 is a promising microtubule assembly inhibitor.

研究领域: 药理学 · 癌症研究 · 分子生物学
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Analytical Methods · 2019 ·Vol. 11 ·期 14 ·1857-1867 · IF 2.378

A turn-on near-infrared fluorescent probe for detection of cysteine over glutathione and homocysteine in vivo

Qing He,Ruixi Li,Zhenwei Yuan,Habtamu Kassaye,Jinrong Zheng,Chen Wei,Fei Wang,Yuxin Yao,Lijuan Gui,Haiyan Chen

Cysteine (Cys) has emerged as a significant sensing target in recent years. Although a lot of biothiol probes have been developed and applied to cellular imaging through thiol-induced disulfide cleavage or Michael addition reactions, relatively few probes assessing Cys with high selectivity over glutathione (GSH) and homocysteine (Hcy) with near-infrared (NIR) fluorescence are capable of in vivo fluorescence imaging in biological systems. Herein, a NIR fluorescent turn-on probe for Cys monitoring in vivo was designed and synthesized. This probe demonstrated a rapid, tremendously selective detection process for Cys with remarkable NIR fluorescence enhancement (Ex: 600 nm, Em: 712 nm, ∼20 fold). In addition, this probe could be utilized to quantitatively detect Cys with a detection limit of 82 nM over a wide linear range (0.01–160 μM), fast response time (5 min) and low toxicity. Moreover, it was further demonstrated that this NIR fluorescent probe could be applied to detect Cys in living cells including L02, A549 and MCF-7 cell lines and different mouse models (tumor-bearing mouse model, hepatitis model and inflammatory model), revealing that this probe possesses great promise for further biological applications.

研究领域: 分析化学 · 生物化学 · 生物医学工程 · 药学
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ANALYST · 2012 ·Vol. 137 ·期 6 ·1389-1395 · IF 4.23

An electrochemical signal ‘off–on’ sensing platform for microRNA detection

Huanshun Yin,Yunlei Zhou,Chuanxia Chen,Lusheng Zhu,Shiyun Ai

The abnormal expression of microRNAs (miRNAs) in many solid tumors makes miRNAs potential biomarkers for disease diagnosis and highlights the need for the sensitive and selective detection of miRNAs. In the present work, an ‘off-on’ signaling genosensor platform for miRNA-21 detection was well developed. This tactic was based on a locked nucleic acid-integrated nucleic acid hairpin probe, a biotin-labeled bridge DNA–AuNPs–bio-barcode signal amplification unit and enzymatic signal amplification. The test is simple, fast and ultrasensitive with a linear range of 0.01–700 pM. The detection limit was estimated to be 6 fM. The overexpression of miRNA-21 was confirmed in total RNA extracted from human hepatocarcinoma cells BEL-7402 and human HeLa cells compared with the control sample extracted from normal human hepatic L02 cells. This method does not need miRNA-21 labeling, isolation, enrichment or PCR amplification. The performance of the assay developed here could satisfy the need for rapid, easy, sensitive and specific early cancer diagnosis in clinical diagnostics.

研究领域: 生物化学 · 分子生物学 · 癌症研究 · 生物技术
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CARBOHYDRATE POLYMERS · 2019 · IF 6.044

Structural characterization and in vitro hepatoprotective activity of polysaccharide from pine nut (Pinus koraiensis Sieb. et Zucc.)

Hang Qu,Xin Gao,Hai-Tian Zhao,Zhen-Yu Wang,Juan-Juan Yi

A new purified polysaccharide (PNP40c-1) with a molecular weight of 2.06 × 10 5 Da was obtained from pine nuts ( Pinus koraiensis Sieb. et Zucc. ). Structural analysis indicated that PNP40c-1 is a homogeneous heteropolysaccharide composed of arabinose, rhamnose and glucose in a molar ratio of 2.98:1.00:0.52. The major backbone consisted of →3,4)- α - l -Ara p (1→, →4)- α - l -Ara p 3Me(1→, →3)- α - l -Rha p (1→ and →6)- β - d -Glc p (1→, and the side chain is β - d -Glc p -(1→ linked at C4-position of →3,4)- α - l -Ara p (1→. In addition, the hepatoprotective effect of PNP40c-1 was investigated by human hepatocyte cell line L02 treated with carbon tetrachloride (CCl 4 ). Results suggested that PNP40c-1 could protect L02 cells from CCl 4 -induced damage by enhancing the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increasing the level of non-enzymatic antioxidant glutathione (GSH), suppressing lipid perioxidation and further reducing the leakage of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hence, PNP40c-1 could be a promising functional food to serve as hepatoprotective agent.

CAS / MDL: 56-23-5 76-05-1
研究领域: 生物化学 · 药理学 · 营养学
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FOOD AND CHEMICAL TOXICOLOGY · 2019 · IF 3.775

In vitro/in vivo hepatoprotective properties of 1-O-(4-hydroxymethylphenyl)-α-L-rhamnopyranoside from Moringa oleifera seeds against carbon tetrachloride-induced hepatic injury

Congyong Sun,Wenjing Li,Yingkun Liu,Wenwen Deng,Michael Adu-Frimpong,Huiyun Zhang,Qilong Wang,Jiangnan Yu,Ximing Xu

1-O-(4-hydroxymethylphenyl)-α-L-rhamnopyranoside (MPG) is a phenolic glycoside that exists in Moringa oleifera seeds with various health benefits, whereas its hepatoprotective effect is lacking clarification. Herein, MPG was isolated from Moringa oleifera seeds, and its hepatoprotection against CCl 4 -induced hepatotoxicity in L02 cells and ICR mice was investigated. Toxicity studies showed that MPG did not induce significant changes in organ coefficients and histological analysis, as well as exhibited no cytotoxicity. In vitro studies indicated that MPG substantially increased cell viability and intracellular SOD activities, and significantly inhibited LDH leakage in CCl 4 -treated cells. In vivo studies demonstrated that MPG significantly alleviated CCl 4 -induced hepatotoxicity in mice, as indicated by diagnostic indicators of hepatic injury, as well as the histopathological analysis. Moreover, MPG reduced the lipid peroxidation levels and regulated the inflammatory cytokines. Notably, MPG substantially suppressed the significant elevation of ROS production in hepatocytes of mice intoxicated with CCl 4 . Moreover, TUNEL assay demonstrated that MPG obviously inhibited hepatic apoptosis induced by CCl 4 . Altogether, these results suggested that MPG has excellent liver-protecting effects against hepatocytotoxicity induced by CCl 4 in mice and L02 cells, which can be further developed as a valuable functional food additive or drug for the treatment of hepatic injury.

研究领域: 药理学 · 毒理学 · 肝脏病学 · 营养保健品
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Food & Nutrition Research · 2020 · IF 3.647

The flavonoid-rich ethanolic extract from the green cocoon shell of silkworm has excellent antioxidation, glucosidase inhibition, and cell protective effects in vitro

Hai-Yan Wang,Jin-Ge Zhao,Yu-Qing Zhang

The green cocoon shell of a novel variety of silkworm, Bombyx mori, is rich in two types of quercetin and kaempferol flavonoids. The aim of this study was to identify these flavonoids in the ethanolic extract (EE) from green cocoons and develop EE applications in healthy foods. The experimental results indicated that the amount of total amino acids in EE was 27.06%. The flavonoids in EE are presented in quercetin and kaempferol glycosides. The total amount of the two aglycones was 33.42 ± 0.08 mg/g. The IC 50 values of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 1,2’-azino-bis (3-ethylbenzthiazoline-6-sulphonicacid) (ABTS), and hydroxyl radical scavenging abilities were 296.95 ± 13.24 μg/mL, 94.31 ± 9.13 μg/mL, and 9.21 ± 0.15 mg/mL, respectively. The IC 50 values of the inhibitory activities of α-amylase and α-glucosidase were 37.57 ± 6.45 μg/mL and 212.69 ± 22.94 μg/mL, respectively. EE also reduced the level of reactive oxygen species (ROS) and oxidative stress in L02 cells induced by high glucose levels. It also effectively decreased the content of 8-hydroxyl deoxyguanosine (8-OHdG), nuclear factor κB (NF-κB), and tumour necrosis factor alpha (TNF-α) in cells with a good dose effect. These results clearly indicated that the flavonoid-rich EE with excellent antioxidant and glucosidase inhibition abilities significantly reduced the damage to cells caused by oxidative stress and inflammatory reactions. It is suggested that EE might serve as useful functional foods for the treatment of related diseases induced by oxidative stress such as diabetes mellitus.

CAS / MDL: 28752-68-3
研究领域: 药理学 · 生物化学 · 营养学 · 食品科学
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