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Hongli Hu, Wenwei Zhu, Jun Qin, Min Chen, Liyan Gong, Long Li, Xiangyuan Liu, Yongzhen Tao, Huiyong Yin, Hu Zhou, Lisha Zhou, Dan Ye, Qinghai Ye, Daming Gao
: Phosphoglycerate kinase 1(PGK1) is an important enzyme in metabolic glycolysis pathway. In this study, we observed a significant over-expression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patients survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified the acetylation at K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Toshiaki Tanaka, Kaoru Goto, Mitsuyoshi Iino
Sec8 is one of the subunits of the exocyst, which is an evolutionarily conserved complex of eight proteins, comprising Sec3 (EXOC1), Sec5 (EXOC2), Sec6 (EXOC3), Sec8 (EXOC4), Sec10 (EXOC5), Sec15 (EXOC6), Exo70 (EXOC7), and Exo84 (EXOC8) subunits. Sec8 knockout mice embryos initiate gastrulation but are unable to progress beyond the primitive streak stage and die shortly. During embryonic development, the first epithelial-mesenchymal transition (EMT) event occurs at gastrulation. Sec8 may be involved in the early embryonic development through EMT...
October 18, 2016: Cellular Signalling
Steven Z Josefowicz, Miho Shimada, Anja Armache, Charles H Li, Rand M Miller, Shu Lin, Aerin Yang, Brian D Dill, Henrik Molina, Hee-Sung Park, Benjamin A Garcia, Jack Taunton, Robert G Roeder, C David Allis
The inflammatory response requires coordinated activation of both transcription factors and chromatin to induce transcription for defense against pathogens and environmental insults. We sought to elucidate the connections between inflammatory signaling pathways and chromatin through genomic footprinting of kinase activity and unbiased identification of prominent histone phosphorylation events. We identified H3 serine 28 phosphorylation (H3S28ph) as the principal stimulation-dependent histone modification and observed its enrichment at induced genes in mouse macrophages stimulated with bacterial lipopolysaccharide...
October 20, 2016: Molecular Cell
Yuki Kawarada, Yasumichi Inoue, Fumihiro Kawasaki, Keishi Fukuura, Koichi Sato, Takahito Tanaka, Yuka Itoh, Hidetoshi Hayashi
Transforming growth factor β (TGF-β) signaling facilitates tumor development during the advanced stages of tumorigenesis, but induces cell-cycle arrest for tumor suppression during the early stages. However, the mechanism of functional switching of TGF-β is still unknown, and it is unclear whether inhibition of TGF-β signaling results amelioration or exacerbation of cancers. Here we show that the tumor suppressor p53 cooperates with Smad proteins, which are TGF-β signal transducers, to selectively activate plasminogen activator inhibitor type-1 (PAI-1) transcription...
October 19, 2016: Scientific Reports
Margarida Mendes, Julie Dubourg, Anne Blanchard, Damien Bergerot, Pierre-Yves Courand, Valentina Forni, Michael Frank, Guillaume Bobrie, Joel Menard, Michel Azizi
OBJECTIVES: The participation of vasopressin in the mechanisms of resistant hypertension is unclear. We compared plasma copeptin concentration, a surrogate marker for vasopressin secretion, between patients with resistant hypertension and those with controlled blood pressure (CBP), in a post hoc analysis of the Prise en charge de l'Hypertension Artérielle RESistante au traitement trial. METHODS: After 4-week treatment with irbesartan 300 mg/day, hydrochlorothiazide 12...
October 15, 2016: Journal of Hypertension
Peng Wang, Suling Zhao, Zheng Xu, Bo Qiao, Zhijuan Long, Qingyu Huang
High efficiency, solution-processed, organic light emitting devices (OLEDs), using a thermally-activated delayed fluorescent (TADF) emitter, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), are fabricated, and the transient electroluminescence (EL) decay of the device with a structure of [ITO/PEDOT: PSS/4CzIPN 5 wt % doped 4,40-N,N0-dicarbazolylbiphenyl(CBP)/bis-4,6-(3,5-di-4-pyridylphenyl)-2-methylpyrimidine (B4PyMPM)/lithium fluoride (LiF)/Al], is systematically studied. The results shed light on the dominant operating mechanism in TADF-based OLEDs...
October 14, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Chen-Huan Chen
Blood pressure (BP) is conventionally measured with a pressure cuff over an upper arm and a cutoff of 140/90 mmHg in the office is the current criteria for diagnosing hypertension. Recently, out of office BP has been suggested as the reference standard for the management of hypertension, due to its better prognostic value over office BP.However, the above BP parameters are all measured at brachial arteries and may be different from the central blood pressure (CBP) measured in the ascending aorta or carotid arteries...
September 2016: Journal of Hypertension
James Sharman
With every cardiac contraction, a pressure wave is generated and propagated within the central large arteries. The characteristic shape of proximal aortic pressure waves (central blood pressure) has been shown to contain prognostic information on cardiovascular risk that is independent from conventional upper arm blood pressure, yet the mechanisms explaining differences in central blood pressure wave shape remain controversial. Uncertainty in this field requires resolution if central blood pressure is to be a target of hypertension management...
September 2016: Journal of Hypertension
Baisuo Zhao, Jie Liu, Craig Frear, Mark Holtzapple, Shulin Chen
This study employed mixed-culture consolidated bioprocessing (CBP) to digest microalgal biomass in an anaerobic sequencing batch reactor (ASBR). The primary objectives are to evaluate the impact of hydraulic residence time (HRT) on the productivity of carboxylic acids and to characterize the bacterial community. HRT affects the production rate and patterns of carboxylic acids. For the 5-L laboratory-scale fermentation, a 12-day HRT was selected because it offered the highest productivity of carboxylic acids and it synthesized longer chains...
October 1, 2016: Bioresource Technology
Zhi Chen, Shaoning Liu, Wenbo Sun, Lei Chen, Dongwan Yoo, Feng Li, Sufang Ren, Lihui Guo, Xiaoyan Cong, Jun Li, Shun Zhou, Jiaqiang Wu, Yijun Du, Jinbao Wang
The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition...
October 5, 2016: Virology
Chun-Jui Weng, Chi-Chuan Wu, Kuo-Fun Feng, I-Chuan Tseng, Po-Cheng Lee, Yu-Chih Huang
BACKGROUND: Treatment of supraintercondylar (AO/OTA 33-C) and supracondylar (AO/OTA 33-A) femur fractures is generally challenging. Standard treatments include open reduction and internal fixation. However, optimal implants are now being well-defined. This study focus on the comparison between clinical and functional outcomes of fractures treated with condylar buttress plates (CBPs). METHODS: We treated 87 patients with supraintercondylar or supracondylar femur fracture from 2004 to 2008, including 30 supraintercondylar and 24 supracondylar fractures treated with CBPs...
October 4, 2016: BMC Musculoskeletal Disorders
Tommaso Cai, Daniele Tiscione, Luca Gallelli, Paolo Verze, Alessandro Palmieri, Vincenzo Mirone, Riccardo Bartoletti, Gianni Malossini
OBJECTIVE: To date, the management of patients with chronic bacterial prostatitis (CBP) is not satisfactory, especially in terms of symptoms relief. Here, we evaluated the efficacy and the safety of a combination of serenoa repens, selenium and lycopene extract + bromelain and methylsulfonylmethane extract associated with levofloxacin in patients with CBP. MATERIALS AND METHODS: All patients with clinical and instrumental diagnosis of CBP, admitted to a single Urological Institution from March to June 2015 were enrolled in this phase III study...
October 5, 2016: Archivio Italiano di Urologia, Andrologia
Yu-Li Jia, Meng Xu, Chang-Wei Dou, Zhi-Kui Liu, Yu-Mo Xue, Bo-Wen Yao, Ling-Long Ding, Kang-Sheng Tu, Xin Zheng, Qing-Guang Liu
Aberrant autophagic processes have been found to have fundamental roles in the pathogenesis of different kinds of tumors, including hepatocellular carcinoma (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), performs its function by acetylating both histone and non-histone proteins. Our previous studies showed that PCAF was downregulated in HCC tissues and its high expression was significantly associated with patient survival after surgery, serving as a prognostic marker. In this study we found that overexpression of PCAF induced autophagy of HCC cells and its knockdown depressed autophagy...
October 6, 2016: Cell Death & Disease
Peter Haberz, Munehito Arai, Maria A Martinez-Yamout, H Jane Dyson, Peter E Wright
Many viruses deregulate the cell and force transcription of viral genes by competing with cellular proteins for binding to the transcriptional co-activators CREB-binding protein (CBP) and p300. Through its interactions with CBP/p300 and the retinoblastoma protein, the adenovirus (AdV) early region 1A (E1A) oncoprotein hijacks the cell cycle and, in rodents, transforms the cell; the mechanistic and structural basis for these effects remain unclear. In this study we compare the affinity of protein constructs from the E1A proteins from two adenovirus serotypes, non-oncogenic AdV5 and highly oncogenic AdV12, for binding to the nuclear receptor coactivator binding domain (NCBD) of CBP...
October 4, 2016: Protein Science: a Publication of the Protein Society
Vittorio Magri, Emanuele Montanari, Emanuela Marras, Gianpaolo Perletti
Although fluoroquinolones are first-line agents for the treatment of National Institutes of Health (NIH) category II chronic bacterial prostatitis (CBP), therapy with these agents is not always feasible due to the increasing worldwide resistance of causative uropathogens. New therapeutic options are urgently required, as drugs such as β-lactam antibiotics distribute poorly to prostatic sites of infection and trimethoprim therapy is often unfeasible due to high resistance rates. The present study aimed to analyze the efficacy of aminoglycosides, administered to a cohort of 78 patients affected by fluoroquinolone-resistant CBP, or excluded from fluoroquinolone therapy due to various contraindications...
October 2016: Experimental and Therapeutic Medicine
Bingbing X Li, Ryan Gardner, Changhui Xue, David Z Qian, Fuchun Xie, George Thomas, Steven C Kazmierczak, Beth A Habecker, Xiangshu Xiao
cAMP-response element binding protein (CREB) is a nuclear transcription factor activated by multiple extracellular signals including growth factors and hormones. These extracellular cues activate CREB through phosphorylation at Ser133 by various protein serine/threonine kinases. Once phosphorylated, it promotes its association with transcription coactivators CREB-binding protein (CBP) and its paralog p300 to activate CREB-dependent gene transcription. Tumor tissues of different origins have been shown to present overexpression and/or overactivation of CREB, indicating CREB as a potential cancer drug target...
October 3, 2016: Scientific Reports
Celine Kempeneers, Claire Seaton, Mark A Chilvers
BACKGROUND: Digital high speed videomicroscopy(DHSV) allows analysis of ciliary beat frequency(CBF) and pattern(CBP) of respiratory cilia in 3 planes. Normal reference data use a sideways edge to evaluate ciliary dyskinesia, and calculate CBF using the time for a cilium to complete 10 beat cycles. Variability in CBF within respiratory epithelium has been described, but data concerning variation of CBP is limited in healthy epithelium. This study aims to document variability of CBP within normal samples, to compare ciliary function in 3 profiles, and CBF calculated over 5 or 10 beat cycles...
September 29, 2016: Chest
Terry D Crawford, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Alexander M Taylor, Gladys de Leon Boenig, Cameron L Noland, Jeremy Murray, Justin Ly, Edna F Choo, Thomas L Hunsaker, Emily W Chan, Mark Merchant, Samir Kharbanda, Karen E Gascoigne, Susan Kaufman, Maureen H Beresini, Jiangpeng Liao, Wenfeng Liu, Kevin X Chen, Zhongguo Chen, Andrew R Conery, Alexandre Côté, Hariharan Jayaram, Ying Jiang, James R Kiefer, Tracy Kleinheinz, Yingjie Li, Jonathan Maher, Eneida Pardo, Florence Poy, Kerry L Spillane, Fei Wang, Jian Wang, Xiaocang Wei, Zhaowu Xu, Zhongya Xu, Ivana Yen, Laura Zawadzke, Xiaoyu Zhu, Steven Bellon, Richard Cummings, Andrea G Cochran, Brian K Albrecht, Steven Magnuson
The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0...
September 28, 2016: Journal of Medicinal Chemistry
Tiina Vilmi-Kerälä, Outi Palomäki, Päivi Kankkunen, Leena Juurinen, Jukka Uotila, Ari Palomäki
INTRODUCTION: Gestational diabetes mellitus (GDM) is an indicator of future cardiovascular disease. We investigated if sensitive biomarkers of increased cardiovascular risk differ between women with and without a history of GDM few years after pregnancy, and whether obesity affects the results. MATERIAL AND METHODS: We studied two cohorts - 120 women with a history of GDM and 120 controls, on average 3.7 years after delivery. Circulating concentrations of oxidized low-density lipoprotein (oxLDL) were determined by ELISA...
September 28, 2016: Acta Obstetricia et Gynecologica Scandinavica
Janet M McNicholl
Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective...
September 28, 2016: Human Vaccines & Immunotherapeutics
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