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https://www.readbyqxmd.com/read/28098861/triptolide-inhibits-viability-and-induces-apoptosis-in-liver-cancer-cells-through-activation-of-the-tumor-suppressor-gene-p53
#1
Yan-Yan Sun, Lei Xiao, Dong Wang, Yan-Chao Ji, Yu-Peng Yang, Rong Ma, Xi-Hai Chen
The present study investigated the effect of triptolide on viability and apoptosis along with underlying mechanism in liver cancer cells. CCK-8 assay showed that triptolide treatment for 48 h significantly reduced the viability of HepG2 and QSG7701 cells at 50 µM concentration. Annexin V-FITC and propidium iodide staining showed that triptolide treatment of HepG2 cells at 50 µM concentrations induced apoptosis in 56.45% cells compared to only 2.36% cells in the control cultures. Western blot assay showed that treatment of HepG2 cells with 50 µM concentration of triptolide significantly induced phosphorylation of p53 in a 2 h-treatment...
January 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28096407/development-of-chronic-allergic-responses-by-dampening-bcl6-mediated-suppressor-activity-in-memory-t-helper-2-cells
#2
Takashi Ogasawara, Masahiko Hatano, Hisae Satake, Jun Ikari, Toshibumi Taniguchi, Nobuhide Tsuruoka, Haruko Watanabe-Takano, Lisa Fujimura, Akemi Sakamoto, Hirokuni Hirata, Kumiya Sugiyama, Yasutsugu Fukushima, Susumu Nakae, Kenji Matsumoto, Hirohisa Saito, Takeshi Fukuda, Kazuhiro Kurasawa, Koichiro Tatsumi, Takeshi Tokuhisa, Masafumi Arima
Mice deficient in the transcriptional repressor B-cell CLL/lymphoma 6 (Bcl6) exhibit similar T helper 2 (TH2) immune responses as patients with allergic diseases. However, the molecular mechanisms underlying Bcl6-directed regulation of TH2 cytokine genes remain unclear. We identified multiple Bcl6/STAT binding sites (BSs) in TH2 cytokine gene loci. We found that Bcl6 is modestly associated with the BSs, and it had no significant effect on cytokine production in newly differentiated TH2 cells. Contrarily, in memory TH2 (mTH2) cells derived from adaptively transferred TH2 effectors, Bcl6 outcompeted STAT5 for binding to TH2 cytokine gene loci, particularly Interleukin4 (Il4) loci, and attenuated GATA binding protein 3 (GATA3) binding to highly conserved intron enhancer regions in mTH2 cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096401/ornithine-decarboxylase-regulates-m1-macrophage-activation-and-mucosal-inflammation-via-histone-modifications
#3
Dana M Hardbower, Mohammad Asim, Paula B Luis, Kshipra Singh, Daniel P Barry, Chunying Yang, Meredith A Steeves, John L Cleveland, Claus Schneider, M Blanca Piazuelo, Alain P Gobert, Keith T Wilson
Macrophage activation is a critical step in host responses during bacterial infections. Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine metabolism, has been well studied in epithelial cells and is known to have essential roles in many different cellular functions. However, its role in regulating macrophage function during bacterial infections is not well characterized. We demonstrate that macrophage-derived ODC is a critical regulator of M1 macrophage activation during both Helicobacter pylori and Citrobacter rodentium infection...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094841/phase-2-randomized-double-blind-study-of-pracinostat-in-combination-with-azacitidine-in-patients-with-untreated-higher-risk-myelodysplastic-syndromes
#4
Guillermo Garcia-Manero, Guillermo Montalban-Bravo, Jesus G Berdeja, Yasmin Abaza, Elias Jabbour, James Essell, Roger M Lyons, Farhad Ravandi, Michael Maris, Brian Heller, Amy E DeZern, Sunil Babu, David Wright, Bertrand Anz, Ralph Boccia, Rami S Komrokji, Philip Kuriakose, James Reeves, Mikkael A Sekeres, Hagop M Kantarjian, Richard Ghalie, Gail J Roboz
BACKGROUND: The prognosis of patients with higher risk myelodysplastic syndromes (MDS) remains poor despite available therapies. Histone deacetylase inhibitors have demonstrated activity in patients with MDS and in vitro synergy with azacitidine. METHODS: A phase 2 randomized, placebo-controlled clinical trial of azacitidine and pracinostat was conducted in patients who had International Prognostic Scoring System intermediate-2-risk or high-risk MDS. The primary endpoint was the complete response (CR) rate by cycle 6 of therapy...
January 17, 2017: Cancer
https://www.readbyqxmd.com/read/28092155/discovery-of-first-in-class-potent-and-orally-bioavailable-eed-inhibitor-with-robust-anti-cancer-efficacy
#5
Ying Huang, Jeff Zhang, Zhengtian Yu, Hailong Zhang, Youzhen Wang, Andreas Lingel, Wei Qi, X Justin Gu, Kehao Zhao, Michael David Shultz, Long Wang, Xingnian Fu, Yongfeng Sun, Qiong Zhang, Xiangqing Jiang, Jiang-Wei Zhang, Chunye Zhang, Ling Li, Jue Zeng, Lijian Feng, Chao Zhang, Yueqin Liu, Man Zhang, Lijun Zhang, Mengxi Zhao, Zhenting Gao, Xianghui Liu, Douglas Fang, Haibing Guo, Yuan Mi, Tobias Gabriel, Michael P Dillon, Peter Atadja, Counde Oyang
Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit Polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (Tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective and orally bioavailable EED inhibitor EED226 (compound 43)...
January 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28089048/identification-of-a-arborescens-a-grandis-and-a-protenta-as-new-members-of-the-european-alternaria-population-on-potato
#6
Sofie Landschoot, Michiel Vandecasteele, Bernard De Baets, Monica Höfte, Kris Audenaert, Geert Haesaert
Alternaria species, primarily the small-spored Alternaria alternata and the large-spored Alternaria solani, are considered a serious threat to potato cultivation. To develop control strategies, it is important to gain insight into the Alternaria population. Based on the sequence analyses of the internal transcribed spacer region (ITS) and the glyceraldehyde-3-phosphate dehydrogenase gene, the small-spored and large-spored Alternaria isolates could be separated from each other. Sequence analyses of the calmodulin gene and the RNA polymerase second largest subunit showed that besides A...
February 2017: Fungal Biology
https://www.readbyqxmd.com/read/28087897/fgfr1-analyses-in-four-patients-with-hypogonadotropic-hypogonadism-with-split-hand-foot-malformation-implications-for-the-promoter-region
#7
Kohnosuke Ohtaka, Yasuko Fujisawa, Fumio Takada, Yukihiro Hasegawa, Tatsuya Miyoshi, Tomonobu Hasegawa, Hideaki Miyoshi, Hiraku Kameda, Misuzu Kurokawa Seo, Maki Fukami, Tsutomu Ogata
Heterozygous loss-of-function mutations of FGFR1 cause various disorders including hypogonadotropic hypogonadism with split-hand/foot malformation (HH-SHFM). We examined FGFR1 in four Japanese patients with HH-SHFM (cases 1-4) and the mother of case 4 with HH only. Cases 1 and 2 had heterozygous loss-of-function mutations with no dominant negative effect [c.289G>A, p.(G97S); and c.2231G>C, p.(R744T)], and case 3 had a splice donor site mutation [c.1663+1G>T]. Notably, case 4 had a maternally inherited 8,312 bp microdeletion that involved non-coding exon 1U and impaired FGFR1 expression...
January 13, 2017: Human Mutation
https://www.readbyqxmd.com/read/28081156/generation-of-a-stable-transgenic-swine-model-expressing-a-porcine-histone-2b-egfp-fusion-protein-for-cell-tracking-and-chromosome-dynamics-studies
#8
Renan B Sper, Sehwon Koh, Xia Zhang, Sean Simpson, Bruce Collins, Jeff Sommer, Robert M Petters, Ignacio Caballero, Jeff L Platt, Jorge A Piedrahita
Transgenic pigs have become an attractive research model in the field of translational research, regenerative medicine, and stem cell therapy due to their anatomic, genetic and physiological similarities with humans. The development of fluorescent proteins as molecular tags has allowed investigators to track cell migration and engraftment levels after transplantation. Here we describe the development of two transgenic pig models via SCNT expressing a fusion protein composed of eGFP and porcine Histone 2B (pH2B)...
2017: PloS One
https://www.readbyqxmd.com/read/28078853/oxidative-stress-in-asthma-a-distinct-clinical-and-pathologic-feature
#9
Y Li, G P Li
Asthma is a type of chronic airway inflammation. Corticosteroids are inadequate for asthma therapy. However, it remains unclear whether oxidative stress is a distinct clinical and pathologic feature in asthma. We reviewed the articles on asthma-associated oxidative stress. The exposures to airborne allergens, such as house dust mite (HDM) and birch pollen, may not only trigger innate and adaptive immune responses but also cause oxidative stress damage in the airways. Allergen-induced reactive oxygen species (ROS) is involved in p38 MAPK, phosphoinositide-3-kinase (PI3K)/Akt and nuclear factor erythroid 2-related factor (Nrf2) kinase pathway signaling...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28078190/loss-of-quiescence-and-self-renewal-capacity-of-hematopoietic-stem-cell-in-an-in-vitro-leukemic-niche
#10
Natalia-Del Pilar Vanegas, Jean-Paul Vernot
BACKGROUND: Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. METHODS: A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28074841/the-mito-damp-cardiolipin-blocks-il-10-production-causing-persistent-inflammation-during-bacterial-pneumonia
#11
Krishnendu Chakraborty, Mahesh Raundhal, Bill B Chen, Christina Morse, Yulia Y Tyurina, Anupriya Khare, Timothy B Oriss, Rachael Huff, Janet S Lee, Claudette M St Croix, Simon Watkins, Rama K Mallampalli, Valerian E Kagan, Anuradha Ray, Prabir Ray
Bacterial pneumonia is a significant healthcare burden worldwide. Failure to resolve inflammation after infection precipitates lung injury and an increase in morbidity and mortality. Gram-negative bacteria are common in pneumonia and increased levels of the mito-damage-associated molecular pattern (DAMP) cardiolipin can be detected in the lungs. Here we show that mice infected with Klebsiella pneumoniae develop lung injury with accumulation of cardiolipin. Cardiolipin inhibits resolution of inflammation by suppressing production of anti-inflammatory IL-10 by lung CD11b(+)Ly6G(int)Ly6C(lo)F4/80(+) cells...
January 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#12
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28072604/epigenetic-upregulation-of-cxcl12-expression-mediates-anti-tubulin-chemotherapeutics-induced-neuropathic-pain
#13
Ting Xu, Xiao-Long Zhang, Han-Dong Ou-Yang, Zhen-Yu Li, Cui-Cui Liu, Zhen-Zhen Huang, Jing Xu, Jia-You Wei, Bi-Lin Nie, Chao Ma, Shao-Ling Wu, Wen-Jun Xin
Clinically, Microtubule-targeted agents-induced neuropathic pain hampers chemotherapeutics for cancer patients. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12, and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation (LTP) of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 by using the transgenic mice (CXCL12) or neutralizing antibody or siRNA ameliorated the mEPSCs enhancement and mechanical allodynia...
January 7, 2017: Pain
https://www.readbyqxmd.com/read/28070584/changes-in-protein-expression-profiles-in-bovine-endometrial-epithelial-cells-exposed-to-e-coli-lps-challenge
#14
Cristian Piras, Yongzhi Guo, Alessio Soggiu, Metasu Chanrot, Viviana Greco, Andrea Urbani, Gilles Charpigny, Luigi Bonizzi, Paola Roncada, Patrice Humblot
E. coli is one of the most frequently involved bacteria in uterine diseases. Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria involved in pathogenic processes leading to post-partum metritis and endometritis in cattle. It also causes inflammation of the endometrium. The increase of cell proliferation by LPS is part of the inflammatory process. The aim of this study was to investigate possible changes in protein expression in relation to the proliferative response of bEECs after challenge with E...
January 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28068416/growth-enhanced-transgenic-coho-salmon-oncorhynchus-kisutch-strains-have-varied-success-in-simulated-streams-implications-for-risk-assessment
#15
Rosalind A Leggatt, L Fredrik Sundström, Krista Woodward, Robert H Devlin
Growth hormone (GH) transgenic fish have accelerated growth and could improve production efficiency in aquaculture. However, concern exists regarding potential environmental risks of GH transgenic fish should they escape rearing facilities. While environmental effects have been examined in some GH transgenic models, there is a lack of information on whether effects differ among different constructs or strains of transgenic fish. We compared growth and survival of wild-type coho salmon (Oncorhynchus kisutch) fry, a fast-growing GH transgenic strain containing a metallothionein promoter (TMT), and three lines/strains containing a reportedly weaker histone-3 promoter (TH3) in hatchery conditions and semi-natural stream tanks with varying levels of natural food and predators...
2017: PloS One
https://www.readbyqxmd.com/read/28067802/stabilization-of-nucleosomes-by-histone-tails-and-by-fact-revealed-by-spfret-microscopy
#16
Maria E Valieva, Nadezhda S Gerasimova, Kseniya S Kudryashova, Anastasia L Kozlova, Mikhail P Kirpichnikov, Qi Hu, Maria Victoria Botuyan, Georges Mer, Alexey V Feofanov, Vasily M Studitsky
A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription) is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET) microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers...
January 6, 2017: Cancers
https://www.readbyqxmd.com/read/28067305/gomisin-n-inhibits-adipogenesis-and-prevents-high-fat-diet-induced-obesity
#17
Min-Kyung Jang, Ye-Rang Yun, Ji-Hyun Kim, Mi-Hee Park, Myeong Ho Jung
Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065600/lysyl-oxidase-3-is-a-dual-specificity-enzyme-involved-in-stat3-deacetylation-and-deacetylimination-modulation
#18
Li Ma, Chao Huang, Xiong-Jun Wang, Dazhuan Eric Xin, Li-Shun Wang, Quanli C Zou, Ya-Nan S Zhang, Min-Dian Tan, Yu-Mei Wang, Ting C Zhao, Devasis Chatterjee, Rachel A Altura, Chuangui Wang, Yan S Xu, Jing-Hua Yang, Yong-Sheng Fan, Bao-Hui Han, Jianmin Si, Xiaoren Zhang, Jinke Cheng, Zhijie Chang, Y Eugene Chin
In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity...
December 29, 2016: Molecular Cell
https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#19
REVIEW
Julieann Lee, D A Solomon, Tarik Tihan
Genetic profiling is an increasingly useful tool for sub-classification of gliomas in adults and children. Specific gene mutations, structural rearrangements, DNA methylation patterns, and gene expression profiles are now recognized to define molecular subgroups of gliomas that arise in distinct anatomic locations and patient age groups, and also provide a better prediction of clinical outcomes for glioma patients compared to histologic assessment alone. Understanding the role of these distinctive genetic alterations in gliomagenesis is also important for the development of potential targeted therapeutic interventions...
January 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28063130/glucocorticoids-curtail-stimuli-induced-creb-phosphorylation-in-trh-neurons-through-interaction-of-the-glucocorticoid-receptor-with-the-catalytic-subunit-of-protein-kinase-a
#20
Israim Sotelo-Rivera, Antonieta Cote-Vélez, Rosa-María Uribe, Jean-Louis Charli, Patricia Joseph-Bravo
PURPOSE: Corticosterone prevents cold-induced stimulation of thyrotropin-releasing hormone (Trh) expression in rats, and the stimulatory effect of dibutyryl cyclic-adenosine monophosphate (dB-cAMP) on Trh transcription in hypothalamic cultures. We searched for the mechanism of this interference. METHODS: Immunohistochemical analyses of phosphorylated cAMP-response element binding protein (pCREB) were performed in the paraventricular nucleus (PVN) of Wistar rats, and in cell cultures of 17-day old rat hypothalami, or neuroblastoma SH-SY5Y cells...
January 6, 2017: Endocrine
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