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Zhenpeng Qiu, Junxuan Zhou, Cong Zhang, Ye Cheng, Junjie Hu, Guohua Zheng
An abnormality in the Lin28/let-7a axis is relevant to the progression of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), which could be a novel therapeutic target for this malignant tumor. The present study aimed to investigate the antiproliferative and anti-invasive effects of urolithin A in a stable full-length HBV gene integrated cell line HepG2.2.15 using CCK-8 and transwell assays. The RNA and protein expressions of targets were assessed by quantitative PCR and western blot, respectively...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Catarina Oliveira, Fernando Cagide, José Teixeira, Ricardo Amorim, Lisa Sequeira, Francesco Mesiti, Tiago Silva, Jorge Garrido, Fernando Remião, Santiago Vilar, Eugenio Uriarte, Paulo J Oliveira, Fernanda Borges
Alzheimer's disease (AD) is a multifactorial age-related disease associated with oxidative stress (OS) and impaired cholinergic transmission. Accordingly, targeting mitochondrial OS and restoring cholinergic transmission can be an effective therapeutic strategy toward AD. Herein, we report for the first time dual-target hydroxybenzoic acid (HBAc) derivatives acting as mitochondriotropic antioxidants and cholinesterase (ChE) inhibitors. The studies were performed with two mitochondriotropic antioxidants AntiOxBEN 1 (catechol derivative), and AntiOxBEN 2 (pyrogallol derivative) and compounds 15-18 , which have longer spacers...
2018: Frontiers in Chemistry
Birendra Nath Karan, Tapan Kumar Maity, Bikash Chandra Pal, Tanushree Singha, Snehasis Jana
Betulinic acid was first time isolated via bioactivity-guided fractionation from ethyl acetate extract of Nyctanthes arbor-tristis leaves. Its structure was established by FTIR, 1 H and 13 C- nuclear magnetic resonance and high-resolution mass spectrometry. It had shown excellent inhibition of anti-inflammatory properties with IC50 of 10.34 μg/mL (COX-1), 12.92 μg/mL (COX-2), 15.53 μg/mL (5-LOX), 15.21 μg/mL (Nitrite), 16.65 μg/mL (TNF-α), and also exhibited potent antioxidant activity with IC50 of 18...
May 3, 2018: Natural Product Research
Yasunori Nio, Yuichi Akahori, Hitomi Okamura, Koichi Watashi, Takaji Wakita, Makoto Hijikata
Fasiglifam is a selective partial agonist of G-protein-coupled receptor 40 (GPR40), which was developed for the treatment of type 2 diabetes mellitus. However, the clinical development of fasiglifam was voluntarily terminated during phase III clinical trials due to adverse liver effects. Fasiglifam showed an inhibitory effect on sodium taurocholate cotransporting polypeptide (NTCP) in human and rat hepatocytes. Recently, NTCP was reported to be a functional receptor for human hepatitis B virus (HBV) infections...
April 30, 2018: Biochemical and Biophysical Research Communications
Shulian Bai, Bangtian Xu, Yongcan Guo, Juhui Qiu, Wen Yu, Guoming Xie
While detection of microRNA with or without signal amplification is highly informative, nanosensors with high specificity for cell-specific RNA detection are rare. Methods: In this study, a tetrahedral DNA nanostructure (TDN) with a specific function was combined with gold nanoparticles (Au-NP) possessing fluorescence quenching effects and a large surface area to fabricate a fluorescence resonance energy transfer based nanosensor (Au-TDNN). The presence of miR-21 (target) can separate the fluorescent dye-labeled detection probe on Au-TDNNs from Au-NPs, which separates the donor and acceptor, thus inducing an intensive fluorescence signal...
2018: Theranostics
Jufeng Xia, Ling Rong, Tatsuo Sawakami, Yoshinori Inagaki, Peipei Song, Kiyoshi Hasegawa, Yoshihiro Sakamoto, Wei Tang
BACKGROUND: Shufeng Jiedu Capsule (SFJDC), a traditional Chinese medicine, has been used widely as antiviral, antibacterial, antitumor, and anti-inflammatory drugs. Previous studies indicated that some active ingredients of Shufeng Jiedu Capsule, such as resveratrol and quercetin, could suppress hepatocellular carcinoma (HCC) cells through various signaling pathways. However, anti-HCC activity of SFJDC as a complementary medicine remains unexplored. Here, we use a combination of Shufeng Jiedu Capsule and doxorubicin to treat HCC cells and investigated the effects and mechanisms of SFJDC and its ingredientsin vitro...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hui Tian, Zhenkun He
BACKGROUND: Hepatitis B virus (HBV) chronic infection is a health problem in the worldwide, with a underlying higher risk of liver cirrhosis and hepaticocellular carcinoma. A number of studies indicate that microRNAs (miRNAs) play vital roles in HBV replication. This study was designed to explore the potential molecular mechanism of miR-200c in HBV replication. METHODS: The expression of miR-200c, nuclear factor IA (NFIA) mRNA, HBV DNA, and HBV RNA (pregenomic RNA (pgRNA), and total RNA) were measured by qRCR...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Dong-Hwan Jung, Eunyoung Tak, Shin Hwang, Gi-Won Song, Chul-Soo Ahn, Ki-Hun Kim, Deok-Bog Moon, Tae-Yong Ha, Gil-Chun Park, Baek-Yeol Ryoo, Kyoung-Jin Lee, Nayoung Kim, Jae-Hyeon Kwon, Eun-Kyoung Jwa, Sung-Gyu Lee
Both sorafenib and mTOR inhibitor (mTORi) have antitumor effects. This study aimed to evaluate their antitumor effects in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) recurrence. We performed a laboratory study using sorafenib and mTORi and subsequently validated their survival benefit at clinical LT setting. In the laboratory study, HepG2.2.15 liver tumor cell line and five patient-derived graft HCC cell lines were used for in vitro cytotoxic studies. After treatment with everolimus and sorafenib, cell viability and apoptosis assays revealed noticeable cytotoxic effects with individual agents and augmented effects by combination therapy...
April 30, 2018: Liver Transplantation
Li Bai, Liming Fu, Lu Li, Feng Ren, Qingfen Zheng, Shuang Liu, Yuanping Han, Sujun Zheng, Yu Chen, Zhongping Duan
BACKGROUND Acute liver injury in the setting of hepatic fibrosis is an intriguing and still unsettled issue. We previously have demonstrated the protective effects conferred by M2-like macrophages in the fibrotic liver. In the present work, we further decipher the cellular mechanisms governing this hepatoprotection. MATERIAL AND METHODS Macrophages were isolated from control mice (M0 macrophages), then polarized into M1 or M2 phenotype using IFN-γ or IL-4, respectively. Conditioned media (CM) from M0, M1, and M2 macrophages were harvested and applied to M1 macrophages...
April 30, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Wei Wang, Xiu Feng, Huan-Xiang Liu, Shi-Wu Chen, Ling Hui
A series of 2,4-disubstituted phthalazinones were synthesized and their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects were evaluated. Among them, N-cyclohexyl-4-((4-(1-methyl-1H-pyrazol-4-yl)-1-oxophthalazin-2(1H)-yl) methyl) benzamide (12c) exhibited the most potent antiproliferation against five carcinoma cell lines (HeLa, A549, HepG2, LoVo and HCT116 cells) with IC50 values in range of 2.2-4.6 μM, while the IC50 value of reference compound VX-680 was 8...
April 23, 2018: Bioorganic & Medicinal Chemistry
Krungchanuchat Saowalak, Thongtem Titipun, Thongtem Somchai, Pilapong Chalermchai
Herein, a new molecular nanoparticle based on iron(III)-tannic complexes (Fe-TA NPs) is presented. The Fe-TA NPs were simply obtained by mixing the precursors in a buffered solution at room temperature, and they exhibited good physicochemical properties with capability of inducing autophagy in both hepatocellular carcinoma cells (HepG2.2.15) and normal rat hepatocytes (AML12). The Fe-TA NPs were found to induce HepG2.2.15 cell death via autophagic cell death but have no effect on cell viability in AML12 cells...
April 27, 2018: Scientific Reports
Yan Liu, Weiming Yao, Lanlan Si, Jun Hou, Jiabo Wang, Zhihui Xu, Weijie Li, Jianhong Chen, Ruisheng Li, Penggao Li, Lvping Bo, Xiaohe Xiao, Jinchu Lan, Dongping Xu
The present study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2. A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 μg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42...
April 24, 2018: Antiviral Research
Abdulrahman M Alahdal, Hani Z Asfour, Safwat A Ahmed, Ahmad O Noor, Ahmed M Al-Abd, Mahmoud A Elfaky, Sameh S Elhady
The Red Sea specimen of the marine sponge Hyrtios erectus (order Dictyoceratida) was found to contain scalarane-type sesterterpenes. 12- O -deacetyl-12,19-di- epi -scalarin ( 14 ), a new scalarane sesterterpenoid, along with fourteen previously-reported scalarane-type sesterterpenes ( 1 ⁻ 13 and 15 ) have been isolated. The chemical structures of the isolated compounds were elucidated on the basis of detailed 1D and 2D NMR spectral data and mass spectroscopy, as well as by comparison with reported data. The anti- Helicobacter pylori , antitubercular and cytotoxic activities of all fifteen compounds were evaluated to reveal the potency of Compounds 1 , 2 , 3 , 4 , 6 , 7 and 10 ...
April 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Abdullah A AlKahtane, Saud Alarifi, Ahmed A Al-Qahtani, Daoud Ali, Suliman Y Alomar, Mohammed S Aleissia, Saad Alkahtani
Most of the agricultural workers are potentially exposed to pesticides through different routes. Inhalation exposures may result in numerous diseases that can adversely affect an individual's health and capacity to perform at work. The aim of this study was to determine the cytotoxic potential of cypermethrin pesticide on cultured human hepatocarcinoma (HepG2) cells. The HepG2 cells were exposed to cypermethrin (0, 5, 15, 40 ng/mL) for 24 and 48 hours. We observed that cypermethrin caused cell death of HepG2 cells using 3-(4, 5-dimethylthiozolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase tests...
April 2018: Dose-response: a Publication of International Hormesis Society
Dorota Łażewska, Maria Kaleta, Stefanie Hagenow, Szczepan Mogilski, Gniewomir Latacz, Tadeusz Karcz, Annamaria Lubelska, Ewelina Honkisz, Jadwiga Handzlik, David Reiner, Grzegorz Satała, Barbara Filipek, Holger Stark, Katarzyna Kieć-Kononowicz
A series of 1- and 2-naphthyloxy derivatives were synthesized and evaluated for histamine H3 receptor affinity. Most compounds showed high affinities with Ki values below 100 nM. The most potent ligand, 1-(5-(naphthalen-1-yloxy)pentyl)azepane (11) displayed high affinity for the histamine H3 receptor with a Ki value of 21.9 nM. The antagonist behaviour of 11 was confirmed both in vitro in the cAMP assay (IC50  = 312 nM) and in vivo in the rat dipsogenia model (ED50  = 3.68 nM). Moreover, compound 11 showed positive effects on scopolamine induced-memory deficits in mice (at doses of 10 and 15 mg/kg) and an analgesic effect in the formalin test in mice with ED50  = 30...
April 11, 2018: Bioorganic & Medicinal Chemistry
Dongxin Zhang, Haojing Liu, Jusheng Lin, Duyun Ye
Hepatitis B virus (HBV) infection is a leading cause for hepatocellular carcinoma (HCC). Dysregulation of DNA double-strand break (DSB) repair may explain the pathogenesis of HBV-related HCC. Tumor suppressor CtIP plays a critical role in DSB repair. The purpose of present study was to clarify whether HBV affects CtIP expression in DSB repair of hepatoma cell. HepG2.2.15 was selected as the HBV positive hepatoma cell line, while HepG2 as the HBV negative hepatoma cell line. The two cell lines were treated with bleomycin to induce DSB...
2018: Journal of Cancer
Xin Xin Zhou, Long Jin, Rui Qun Qi, Teng Ma
In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(polyethylene glycol)] conjugated poly(β-amino esters) (DSPE- b -PEG- b -PAE- b -PEG- b -DSPE), was designed and successfully synthesized via Michael-type step polymerization. The chemical structure of the pentablock copolymer was confirmed with proton nuclear magnetic resonance (1 H-NMR) and Fourier transform infrared (FT-IR) spectroscopy. The copolymer was able to self-assemble into core/shell polymeric micelles in aqueous solution at low concentrations, and its critical micelle concentration (CMC) value was 4...
March 2018: Royal Society Open Science
Jing-Tao Huang, Ying Yang, Yi-Min Hu, Xing-Hui Liu, Mei-Yan Liao, Roy Morgan, Er-Feng Yuan, Xia Li, Song-Mei Liu
Despite implications of persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the development of hepatocellular carcinoma (HCC), little is known about serum cccDNA in HBV-infected diseases. We developed a cccDNA-selective droplet digital PCR (ddPCR) to assess cccDNA content and dynamics across different stages of HCC development. One hundred forty-seven serum samples and 35 formalin-fixed, paraffin-embedded tumor tissues were derived from patients with HCC or HBV hepatitis/cirrhosis...
May 2018: Journal of Molecular Diagnostics: JMD
Lili Wang, Yongxiang Yi, Wenxiu Jiang, Dandan Yin, Jing Fan, Wei Ye, Wei Zhao
Immune active cells (IACs) have been shown to be an alternative immunotherapy for CHB patients. However, there is a practical problem of different expansion rate and function of HBV inhibition as individual variability exists. Our previous studies have confirmed that the proliferation and cytolysis of IACs were significantly up-regulated by engineered cells for costimulatory enhancement (ECCE) delivering a 4-1BBζ activating signal. In this study, we aimed to investigate the contribution of ECCE to IACs from CHB patients...
April 2, 2018: Cellular Immunology
Yi Liu, Jun Zhang, Ran Wen, Guang-Zhong Tu, Hu-Biao Chen, Hong Liang, Yu-Ying Zhao
Five new prenylated chalcones hedysarumines C-G (1-5), along with eight known chalcones (6-13) all of which were isolated from the genus Hedysarum for the first time, were isolated from the roots of Hedysarum gmelinii by chromatographic methods. Their structures were determined by extensive spectroscopic techniques. The isolated chalcones (2-13) and previously isolated prenylated chalcones (14-16) were evaluated for antiproliferative activity against five human cancer cell lines (HepG2, A549, Du145, BGC823, and HCT116) and in vitro anti-inflammatory activity...
March 28, 2018: Journal of Asian Natural Products Research
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