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https://www.readbyqxmd.com/read/28821164/cape-gooseberry-physalis-peruviana-juice-as-a-modulator-agent-for-hepatocellular-carcinoma-linked-apoptosis-and-cell-cycle-arrest
#1
Hanaa A Hassan, Hanaa M Serag, Makwan S Qadir, Mohamed Fawzy Ramadan
BACKGROUND: Cape gooseberry (Physalis peruviana) fruit is highly nutritious with high content of health-promoting compounds including minerals, phenolic compounds, as well as vitamins A and C. Physalis peruviana fruits were used as mutagenic, antispasmodic, anticoagulant, and antileucemis agents. OBJECTIVE: The objective of the present work was to study the role of cape gooseberry juice (CG) as a natural modulator agent for adverse aspects associated with hepatocellular carcinoma (HCC)...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28818686/methyleugenol-and-selected-oxidative-metabolites-affect-dna-damage-signalling-pathways-and-induce-apoptosis-in-human-colon-tumour-ht29-cells
#2
Isabel Anna Maria Groh, Melanie Esselen
Previously the food carcinogen methyleugenol was found to be cytotoxic and genotoxic in multiple cell lines and in primary hepatocytes. In this study, the question addressed was whether methyleugenol and the selected oxidative metabolites, 1'-hydroxymethyleugenol, methyleugenol-2',3'-epoxide, and 3'-oxomethylisoeugenol trigger a DNA damage response in the human colon carcinoma HT29 cell line. Most notably investigations by flow cytometry revealed that the metabolites induce an accumulation of HT29 cells in the G2 phase of the cell cycle...
August 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#3
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800488/benzo-a-pyrene-induced-a-mitochondria-independent-apoptosis-of-liver-in-juvenile-chinese-rare-minnows-gobiocypris-rarus
#4
Jinmiao Zha, Xiangsheng Hong, Haiou Rao, Lilai Yuan, Zijian Wang, Satyanarayanan Senthil Kumaran
To examine the effects of BaP on tissue apoptosis, laboratory studies were conducted using juvenile Chinese rare minnows (Gobiocypris rarus) exposed to 1, 5, 20, and 80 μg/L of BaP for 28 days. The post-treatment pathological findings in the liver were associated with hepatocyte swelling, karyopyknosis, and karyorrhexis. Moreover, an increase in the goblet cells in the intestine, epithelial hyperplasia of the gills and fusion of gill lamellae were observed. Significant increases in hepatocyte apoptosis using the TUNEL stain were observed in the liver tissue but not in the intestine and gills...
August 8, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28796747/morphologic-and-immunohistochemical-study-of-clear-cell-carcinoma-of-the-uterine-endometrium-and-cervix-in-comparison-to-ovarian-clear-cell-carcinoma
#5
Baohui Ju, Jianmei Wang, Bo Yang, Lin Sun, Yuhong Guo, Quan Hao, Jianghua Wu
Endometrial clear cell carcinoma (ECCC) and clear cell adenocarcinoma of the cervix (CCAC) are uncommon gynecologic cancers that have morphologic and phenotypic features similar to ovarian clear cell carcinoma (OCCC), but the 3 entities may not be completely identical. This study identified the morphologic and phenotypic characteristics and the differences between ECCC and CCAC in Comparison to OCCC. The morphologic features of 16 ECCCs, 7 CCACs, and 22 OCCCs are described. The immunoprofiles of hepatocyte nuclear factor (HNF) 1β, napsin A, estrogen, progesterone, p53, and Ki-67 were assessed...
August 7, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28741793/telomerase-enzyme-deficiency-promotes-metabolic-dysfunction-in-murine-hepatocytes-upon-dietary-stress
#6
Raquel M Alves-Paiva, Sachiko Kajigaya, Xingmin Feng, Jichun Chen, Marie Desierto, Susan Wong, Danielle M Townsley, Flávia S Donaires, Adeline Bertola, Bin Gao, Neal S Young, Rodrigo T Calado
Short telomeres and genetic telomerase defects are risk factors for some human liver diseases, ranging from non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) to cirrhosis. In murine models, telomere dysfunction has been shown to metabolically compromise hematopoietic cells, liver, and heart via the activation of the p53-PGC axis METHODS: Tert- and Terc-deficient mice were challenged with liquid high fat diet (HFD). Liver metabolic contents were analyzed by CE-TOFMS and liver fat content was confirmed by confocal and electronic microscopy RESULTS: Tert-deficient but not Terc-deficient mice develop hepatocyte injury and frank steatosis when challenged with liquid HFD...
July 25, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28739727/mir-141-inhibits-proliferation-and-migration-of-colorectal-cancer-sw480-cells
#7
Zhi H Long, Zhi G Bai, Jian N Song, Zhi Zheng, Jun Li, Jun Zhang, Jun Cai, Hong W Yao, Jin Wang, Ying C Yang, Jie Yin, Zhong T Zhang
BACKGROUND: This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). MATERIALS AND METHODS: SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28713991/pien-tze-huang-gan-bao-attenuates-carbon-tetrachloride%C3%A2-induced-hepatocyte-apoptosis-in-rats-associated-with-suppression-of-p53-activation-and-oxidative-stress
#8
Jinyan Zhao, Yuchen Zhang, Yun Wan, Haixia Hu, Zhenfeng Hong
Pien Tze Huang Gan Bao (PZH‑GB), a traditional Chinese medicine, has been used for thousands of years as a protective remedy effective against liver injury induced by excessive alcohol and smoking. The present study aimed to evaluate the protective effects and potential mechanisms of PZH‑GB against carbon tetrachloride (CCl4)‑induced hepatic injury. Rats were pre‑treated with silymarin (50 mg/kg) or different doses of PZH‑GB (150, 300 or 600 mg/kg) orally administered for 7 days. At the end of treatment, the rats were intraperitoneally injected with CCl4, or control rats received a corn oil injection...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28687018/vitamin-d-deficiency-causes-insulin-resistance-by-provoking-oxidative-stress-in-hepatocytes
#9
Sha Tao, Qi Yuan, Li Mao, Feng-Li Chen, Feng Ji, Zhao-Hui Cui
Vitamin D deficiency could cause insulin resistance. However, the underlying mechanisms are unclear. The 1α-Hydroxylase ["1α(OH)ase"] is a key enzyme for activate vitamin D3 synthesis. Here, we show that 1α(OH)ase stable knockdown by targeted shRNA led to vitamin D3 depletion in L02 hepatocytes. 1α(OH)ase silence also inhibited insulin-induced downstream signaling (IRS-1, ERK and AKT) transduction and glucose transporter 4 expression. Further, 1α(OH)ase shRNA in L02 hepatocytes led to significant reactive oxygen species production, p53-p21 activation and DNA damages...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609656/kupffer-cell-derived-tnf-triggers-cholangiocellular-tumorigenesis-through-jnk-due-to-chronic-mitochondrial-dysfunction-and-ros
#10
Detian Yuan, Shan Huang, Emanuel Berger, Lei Liu, Nina Gross, Florian Heinzmann, Marc Ringelhan, Tracy O Connor, Mira Stadler, Michael Meister, Julia Weber, Rupert Öllinger, Nicole Simonavicius, Florian Reisinger, Daniel Hartmann, Rüdiger Meyer, Maria Reich, Marco Seehawer, Valentina Leone, Bastian Höchst, Dirk Wohlleber, Simone Jörs, Marco Prinz, Duncan Spalding, Ulrike Protzer, Tom Luedde, Luigi Terracciano, Matthias Matter, Thomas Longerich, Percy Knolle, Thomas Ried, Verena Keitel, Fabian Geisler, Kristian Unger, Einat Cinnamon, Eli Pikarsky, Norbert Hüser, Roger J Davis, Darjus F Tschaharganeh, Roland Rad, Achim Weber, Lars Zender, Dirk Haller, Mathias Heikenwalder
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28581892/radiation-exposure-enhances-hepatocyte-proliferation-in-neonatal-mice-but-not-in-adult-mice
#11
Yi Shang, Yurika Sawa, Benjamin J Blyth, Chizuru Tsuruoka, Hiroyuki Nogawa, Yoshiya Shimada, Shizuko Kakinuma
There is a natural tendency to expect that irradiation of an infant organ prior to development-related expansion will result in a higher risk of developing cancer than that of fully-developed adult tissue, and this has generally been observed. However, if tissues also vary in their initial responses to radiation depending on age, the interplay between tissue- and age-dependent risk would potentially be quite complex. We have previously shown opposing age-dependent induction of apoptosis for the intestinal epithelium and hematopoietic cells in mice, but such data are not yet available for the liver...
August 2017: Radiation Research
https://www.readbyqxmd.com/read/28535186/fxr-gankyrin-axis-is-involved-in-development-of-pediatric-liver-cancer
#12
Leila Valanejad, Kyle Lewis, Mary Wright, Yanjun Jiang, Amber D'Souza, Rebekah Karns, Rachel Sheridan, Anita Gupta, Kevin Bove, David Witte, James Geller, Gregory Tiao, David L Nelson, Lubov Timchenko, Nikolai Timchenko
The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28534998/proliferation%C3%A2-inhibiting-pathways-in-liver-regeneration-review
#13
Menggang Liu, Ping Chen
Liver regeneration, an orchestrated process, is the primary compensatory mechanism following liver injury caused by various factors. The process of liver regeneration consists of three stages: Initiation, proliferation and termination. Proliferation‑promoting factors, which stimulate the recovery of mitosis in quiescent hepatocytes, are essential in the initiation and proliferation steps of liver regeneration. Proliferation‑promoting factors act as the 'motor' of liver regeneration, whereas proliferation inhibitors arrest cell proliferation when the remnant liver reaches a suitable size...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28518148/hepatocyte-polyploidization-and-its-association-with-pathophysiological-processes
#14
REVIEW
Min-Jun Wang, Fei Chen, Joseph T Y Lau, Yi-Ping Hu
A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28498799/dietary-luteolin-attenuates-chronic-liver-injury-induced-by-mercuric-chloride-via-the-nrf2-nf-%C3%AE%C2%BAb-p53-signaling-pathway-in-rats
#15
Haili Zhang, Xiao Tan, Daqian Yang, Jingjing Lu, Biying Liu, Ruiqi Baiyun, Zhigang Zhang
Mercury exposure is a common cause of metal poisoning which is biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. Luteolin, a phenolic compound found in many natural products, has multiple biological functions. Our study was aimed to explore the biological effects of luteolin in a liver injury model induced in rats by mercuric chloride (HgCl2). Criteria for injury included liver enzyme, glutathione and malondialdehyde levels, histopathology, TUNEL assay, hepatocyte viability and reactive oxygen species levels...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480888/hepatic-p63-regulates-steatosis-via-ikk%C3%AE-er-stress
#16
Begoña Porteiro, Marcos F Fondevila, Teresa C Delgado, Cristina Iglesias, Monica Imbernon, Paula Iruzubieta, Javier Crespo, Amaia Zabala-Letona, Johan Fernø, Bárbara González-Terán, Nuria Matesanz, Lourdes Hernández-Cosido, Miguel Marcos, Sulay Tovar, Anxo Vidal, Julia Sánchez-Ceinos, Maria M Malagon, Celia Pombo, Juan Zalvide, Arkaitz Carracedo, Xabier Buque, Carlos Dieguez, Guadalupe Sabio, Miguel López, Patricia Aspichueta, María L Martínez-Chantar, Ruben Nogueiras
p53 family members control several metabolic and cellular functions. The p53 ortholog p63 modulates cellular adaptations to stress and has a major role in cell maintenance and proliferation. Here we show that p63 regulates hepatic lipid metabolism. Mice with liver-specific p53 deletion develop steatosis and show increased levels of p63. Down-regulation of p63 attenuates liver steatosis in p53 knockout mice and in diet-induced obese mice, whereas the activation of p63 induces lipid accumulation. Hepatic overexpression of N-terminal transactivation domain TAp63 induces liver steatosis through IKKβ activation and the induction of ER stress, the inhibition of which rescues the liver functions...
May 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28461158/pancreatic-stellate-cells-increase-pancreatic-cancer-cells-invasion-through-the-hepatocyte-growth-factor-c-met-survivin-regulated-by-p53-p21
#17
Xiao-Peng Yang, Shang-Long Liu, Jian-Fei Xu, Shou-Gen Cao, Yu Li, Yan-Bing Zhou
Pancreatic stellate cells (PSCs) are a key cellular component of the pancreatic tumor microenvironment and are considered to contribute to tumor invasion and metastasis. Multiple cytokines and growth factors derived from PSCs are involved in malignant cancer progression, including hepatocyte growth factor (HGF). However, the molecular mechanisms by which HGF regulates cancer invasion and metastasis have not been completely elucidated. Here, we report that two pancreatic cancer (PC) cell lines, Panc-1 and SW1990, displayed different invasive and migratory abilities after treatment with HGF secreted by PSCs...
August 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28421122/potential-antitumor-activity-and-apoptosis-induction-of-glossostemon-bruguieri-root-extract-against-hepatocellular-carcinoma-cells
#18
Mona S Alwhibi, Mahmoud I M Khalil, Mohamed M Ibrahim, Gehan A El-Gaaly, Ahmed S Sultan
Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This study was performed to investigate the antiproliferative effects of moghat root extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC) cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked immunosorbent assay, caspase and apoptotic activation, flow cytometry, and immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 ± 6 μg/ml) and for Hep3B (1510 ± 5 μg/ml) induced significant growth-inhibitory effects against HCC cells, with no cytotoxic effect on normal hepatocytes...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28408319/deriving-and-testing-of-dysplastic-murine-hepatocytes-a-new-platform-in-liver-cancer-research
#19
Sharon Pok, Harpreet Vohra, Charbel Wehbe, Vanessa A Barn, Evi Arfianti, Yock-Young Dan, Geoffrey C Farrell, Narci C Teoh
Dysplastic hepatocytes (DH) represent altered hepatocytes with potential for malignant transformation. To date, most research on pathways to hepatocarcinogenesis has focused on use of "hepatoma" cell lines derived from hepatocellular carcinoma (HCC). We describe a novel technique for deriving/culturing DH and demonstrate their utility for functional studies in vitro, compared to primary hepatocytes (PH) and HCC. PH and DH were prepared by portal vein collagenase perfusion from C57BL/6J mice. DH were subsequently subjected to FACS...
April 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28407767/e167k-polymorphism-of-tm6sf2-gene-affects-cell-cycle-of-hepatocellular-carcinoma-cell-hepa-1-6
#20
Shuixian Du, Linlin Lu, Yingxia Miao, Wenwen Jin, Changfei Li, Yongning Xin, Shiying Xuan
BACKGROUND: Some studties reported that the polymorphism of TM6SF2 gene E167K affects the occurrence and the progression of hepatocytes carcinoma (hepatocellular, HCC). In oeder to investigate the effects of the polymorphism of TM6SF2 gene E167K in the pathogenesis of HCC, we explored its influence on the cell cycle in hepatocellular carcinoma cell HEPA1-6. METHODS: HEPA 1-6 cells which could respectively overexpress TM6SF2 wild type and E167K variant were cultured and HEPA 1-6 cells with zero load plasmids were used as matched control...
April 13, 2017: Lipids in Health and Disease
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