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https://www.readbyqxmd.com/read/28109179/quantitative-and-integrative-analysis-of-paracrine-hepatocyte-activation-by-non-parenchymal-cells-upon-lipopolysaccharide-induction
#1
Katharina Beuke, Frank A Schildberg, Federico Pinna, Ute Albrecht, Roman Liebe, Michaela Bissinger, Peter Schirmacher, Steven Dooley, Johannes G Bode, Percy A Knolle, Ursula Kummer, Kai Breuhahn, Sven Sahle
Gut-derived bacterial lipopolysaccharides (LPS) stimulate the secretion of tumor necrosis factor (TNF) from liver macrophages (MCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs), which control the acute phase response in hepatocytes through activation of the NF-κB pathway. The individual and cooperative impact of non-parenchymal cells on this clinically relevant response has not been analysed in detail due to technical limitations. To gain an integrative view on this complex inter- and intracellular communication, we combined a multi-scale mathematical model with quantitative, time-resolved experimental data of different primary murine liver cell types...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107514/karyopherin-alpha-proteins-regulate-oligodendrocyte-differentiation
#2
Benjamin M Laitman, John N Mariani, Chi Zhang, Setsu Sawai, Gareth R John
Proper regulation of the coordinated transcriptional program that drives oligodendrocyte (OL) differentiation is essential for central nervous system myelin formation and repair. Nuclear import, mediated in part by a group of karyopherin alpha (Kpna) proteins, regulates transcription factor access to the genome. Understanding how canonical nuclear import functions to control genomic access in OL differentiation may aid in the creation of novel therapeutics to stimulate myelination and remyelination. Here, we show that members of the Kpna family regulate OL differentiation, and may play distinct roles downstream of different pro-myelinating stimuli...
2017: PloS One
https://www.readbyqxmd.com/read/28106556/an-improved-drugs-screening-system-reveals-that-baicalein-ameliorates-the-a%C3%AE-ampa-nmda-induced-depolarization-of-neurons
#3
Tian-Syuan Lin, Han-Jung Tsai, Chih-Han Lee, Yan-Qing Song, Rih-Sheng Huang, Hsiu-Mei Hsieh-Li, Mei-Chih Liang, Yenshou Lin
The presence of amyloid-β (Aβ) plaque and tau protein hyperphosphorylation in brain tissue is the pathological hallmark of Alzheimer's disease (AD). At least some Aβ neurotoxicity is caused by the presence of excess glutamate that has been induced by Aβ accumulation. Memantine is currently the only NMDA receptor inhibitor approved for treating moderate-to-severe AD patients. We utilized primary cortical neurons and DiBAC4(3), a slow-response voltage sensitive fluorescence dye, to create a novel system for screening herbal medicines that allows the identification of pure compounds able to ameliorate Aβ-induced abnormal depolarization...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28105791/the-future-of-pleiotropic-therapy-in-heart-failure-lessons-from-the-benefits-of-exercise-training-on-endothelial-function
#4
REVIEW
Gilles W De Keulenaer, Vincent F M Segers, Faiez Zannad, Dirk L Brutsaert
A novel generation of drugs is introduced in the treatment of heart failure (HF). These drugs, including phosphodiesterase-5 inhibitors, guanylate cyclase stimulators and activators, share the feature that their action is either endothelial-mediated or substitutes for endothelial pathways, in particular the nitric oxide-cyclic guanosine monophosphate pathway, thereby influencing homeostatic balances in virtually each organ system in a pleiotropic fashion. Unfortunately, recent clinical trials with some of these drugs have shown disappointing results, at least in the setting of HF with a preserved ejection fraction...
January 19, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28105211/diagnostic-and-therapeutic-approaches-to-multiple-myeloma-patients-real-world-data-from-representative-multicentre-treatment-surveys-in-germany-between-2008-and-2011
#5
Thomas M Moehler, Maximilian Merz, Lenka Kellermann, Hartmut Goldschmidt, Wolfgang Knauf
A survey was conducted to investigate the standard of care for multiple myeloma in Germany, in order to clarify the status of implementation of international and national treatment guidelines. In addition, the changes in disease management over time were investigated by comparison with surveys conducted in 2008 and 2009. The survey captured a representative sample of 478 myeloma patients with a mean age of 67.9 years across various stages of the disease. Diagnostic approaches, prognostic aspects and treatment decisions were evaluated based on a survey conducted in 2011 in 58 representative centres in Germany, including university and non-university hospitals and office-based haematologists...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104585/rcad-bip-pathway-is-necessary-for-the-proper-synthesis-of-digestive-enzymes-and-the-secretory-function-of-the-exocrine-pancreas
#6
Camille Miller, Yafei Cai, Tadd Patton, Sarai Graves, Honglin Li, Maria Eugenia Sabbatini
Alcoholism causes an imbalance of endoplasmic reticulum (ER) homeostasis in pancreatic acini. In those cells, the ER is involved in the synthesis and folding of pancreatic enzymes. Ufm1 (Ubiquitin-fold modifier 1) is part of a novel ubiquitin-like modification system involved in maintaining ER homeostasis. Among the components of the Ufm1 system, Regulator of C53 and DDRGK1 (RCAD) has recently been identified as an Ufm1-specific E3 ligase that promotes ufmylation of DDRGK1, a RCAD-interacting protein. We determined the importance of RCAD in the proper synthesis and secretion of pancreatic enzymes using RCAD-deficient mice...
January 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28103946/epcr-promotes-breast-cancer-progression-by-altering-spock1-testican-1-mediated-3d-growth
#7
Naiara Perurena, Carolina Zandueta, Susana Martínez-Canarias, Haritz Moreno, Silvestre Vicent, Ana S Almeida, Elisabet Guruceaga, Roger R Gomis, Marta Santisteban, Mikala Egeblad, José Hermida, Fernando Lecanda
BACKGROUND: Activated protein C/endothelial protein C receptor (APC/EPCR) axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated. METHODS: Transcriptomic status of EPCR was examined in a cohort of 286 breast cancer patients. Cell growth kinetics was evaluated in control and EPCR and SPARC/osteonectin, Cwcv, and kazal-like domains proteoglycan (SPOCK1/testican 1) silenced breast cancer cells in 2D, 3D, and in co-culture conditions...
January 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28103679/histone-ketoamide-adduction-by-4-oxo-2-nonenal-is-a-reversible-posttranslational-modification-regulated-by-sirt2
#8
Yiwen Cui, Xin Li, Jianwei Lin, Quan Hao, Xiang David Li
Lipid-derived electrophiles (LDEs) directly modify proteins to modulate cellular signaling pathways in response to oxidative stress. One such LDE, 4-oxo-2-nonenal (4-ONE), has recently been found to target histones and interfere with histone assembly into nucleosomes. Unlike other LDEs that preferentially modify cysteine via nucleophilic Michael addition, 4-ONE reacts with histone lysine residues to form a new histone modification, gamma-oxononanoylation (Kgon). However, it remains unclear whether Kgon can cause irreversible damage or be regulated by enzymes "erasing" this nonenzymatic modification...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28103509/3-5-dihydroxy-3-4-7-trimethoxyflavone-induces-er-stress-associated-hct-116-programmed-cell-death-via-redox-signaling
#9
Mahendra Pal Singh, Jaehong Han, Sun Chul Kang
Quercetin, a well cognized bioactive flavone possessing great medicinal value, has limited usage. The rapid gastrointestinal digestion of quercetin is also a major obstacle for its clinical implementation due to low bioavailability and poor aqueous solubility. 3',5-dihydroxy-3,4',7-trimethoxyflavone (DTMF), a novel semi-synthetic derivative of quercetin, is known to modulate several biological activities. Therefore, in the present study we examined the cytotoxic mechanism of DTMF in concentration-dependent manner (25, 50, and 100μM; 24h) against HCT-116 human colon carcinoma cells...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28103322/htlv-1-tax-induces-formation-of-the-active-macromolecular-ikk-complex-by-generating-lys63-and-met1-linked-hybrid-polyubiquitin-chains
#10
Yuri Shibata, Fuminori Tokunaga, Eiji Goto, Ginga Komatsu, Jin Gohda, Yasushi Saeki, Keiji Tanaka, Hirotaka Takahashi, Tatsuya Sawasaki, Satoshi Inoue, Hiroyuki Oshiumi, Tsukasa Seya, Hiroyasu Nakano, Yuetsu Tanaka, Kazuhiro Iwai, Jun-Ichiro Inoue
The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains...
January 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28103159/the-effects-of-stimulant-medication-and-training-on-sports-competence-among-children-with-adhd
#11
Amy R Altszuler, Anne S Morrow, Brittany M Merrill, Shannon Bressler, Fiona L Macphee, Elizabeth M Gnagy, Andrew R Greiner, Stefany Coxe, Joseph S Raiker, Erika Coles, William E Pelham
The current study examined the relative efficacy of behavioral sports training, medication, and their combination in improving sports competence among youth with attention deficit/hyperactivity disorder (ADHD). Participants were 73 youth (74% male; 81% Hispanic) between the ages of 5 and 12 diagnosed with Diagnostic and Statistical Manual of Mental Disorders (4th ed.) ADHD enrolled in a Summer Treatment Program (STP). The study consisted of a 2 (medication: methylphenidate, placebo) × 2 (sports training: instruction and practice, recreational play) between-groups design and was conducted over a 3-week period during the STP...
January 19, 2017: Journal of Clinical Child and Adolescent Psychology
https://www.readbyqxmd.com/read/28103022/discovery-of-a-novel-series-of-orally-bioavailable-and-cns-penetrant-glucagon-like-peptide-1-receptor-glp-1r-non-competitive-antagonists-based-on-a-1-3-disubstituted-7-aryl-5-5-bis-trifluoromethyl-5-8-dihydropyrimido-4-5-d-pyrimidine-2-4-1h-3h-dione-core
#12
Kellie D Nance, Emily L Days, C David Weaver, Anastasia Coldren, Tiffany D Farmer, Hyekyung P Cho, Colleen M Niswender, Anna L Blobaum, Kevin D Niswender, Craig W Lindsley
A duplexed, functional multi-addition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) non-competitive antagonist. Antagonist 5d not only blocked Exendin-4-stimulated insulin release in islets, but also lowered insulin levels while increasing blood glucose in vivo.
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28102847/curcumin-represses-mouse-3t3-l1-cell-adipogenic-differentiation-via-inhibiting-mir-17-5p-and-stimulating-the-wnt-signalling-pathway-effector-tcf7l2
#13
Lili Tian, Zhuolun Song, Weijuan Shao, William W Du, Lisa R Zhao, Kejing Zeng, Burton B Yang, Tianru Jin
Understanding mechanisms underlying adipogenic differentiation may lead to the discovery of novel therapeutic targets for obesity. Wnt signalling pathway activation leads to repressed adipogenic differentiation while certain microRNAs may regulate pre-adipocyte proliferation and differentiation. We show here that in mouse white adipose tissue, miR-17-5p level is elevated after high fat diet consumption. miR-17-5p upregulates adipogenic differentiation, as its over-expression increased while its inhibition repressed 3T3-L1 differentiation...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102225/glucocorticoid-receptor-signalling-activates-yap-in-breast-cancer
#14
Giovanni Sorrentino, Naomi Ruggeri, Alessandro Zannini, Eleonora Ingallina, Rebecca Bertolio, Carolina Marotta, Carmelo Neri, Elisa Cappuzzello, Mattia Forcato, Antonio Rosato, Miguel Mano, Silvio Bicciato, Giannino Del Sal
The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101570/inhibition-of-tlr4-protects-rat-islets-against-lipopolysaccharide-induced-dysfunction
#15
Xiao Wang, Qin Min Ge, Fan Bian, Yan Dong, Chun Mei Huang
Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the importance of the LPS/TLR4 interaction in apoptosis induced by oxidative stress in pancreatic β cells remains to be elucidated. The present study aimed to investigate the importance of TLR4 during LPS‑induced oxidative stress, apoptosis and dysfunction of insulin secretion in isolated islets of rats...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28101410/modulation-of-cardiomyocyte-activity-using-pulsed-laser-irradiated-gold-nanoparticles
#16
Lara Gentemann, Stefan Kalies, Michelle Coffee, Heiko Meyer, Tammo Ripken, Alexander Heisterkamp, Robert Zweigerdt, Dag Heinemann
Can photothermal gold nanoparticle mediated laser manipulation be applied to induce cardiac contraction? Based on our previous work, we present a novel concept of cell stimulation. A 532 nm picosecond laser was employed to heat gold nanoparticles on cardiomyocytes. This leads to calcium oscillations in the HL-1 cardiomyocyte cell line. As calcium is connected to the contractility, we aimed to alter the contraction rate of native and stem cell derived cardiomyocytes. A contraction rate increase was particularly observed in calcium containing buffer with neonatal rat cardiomyocytes...
January 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28101337/adipocyte-lipolysis-links-obesity-to-breast-cancer-growth-adipocyte-derived-fatty-acids-drive-breast-cancer-cell-proliferation-and-migration
#17
Seher Balaban, Robert F Shearer, Lisa S Lee, Michelle van Geldermalsen, Mark Schreuder, Harrison C Shtein, Rose Cairns, Kristen C Thomas, Daniel J Fazakerley, Thomas Grewal, Jeff Holst, Darren N Saunders, Andrew J Hoy
BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28100850/molecular-characteristic-and-physiological-role-of-dopa-decarboxylase
#18
Joanna Guenter, Robert Lenartowski
The enzyme DOPA decarboxylase (aromatic-L-amino-acid decarboxylase, DDC) plays an important role in the dopaminergic system and participates in the uptake and decarboxylation of amine precursors in the peripheral tissues. Apart from catecholamines, DDC catalyses the biosynthesis of serotonin and trace amines. It has been shown that the DDC amino acid sequence is highly evolutionarily conserved across many species. The activity of holoenzyme is regulated by stimulation/blockade of membrane receptors, phosphorylation of serine residues, and DDC interaction with regulatory proteins...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#19
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28099911/bradykinin-regulates-cell-growth-and-migration-in-cultured-human-cardiac-c-kit-progenitor-cells
#20
Gang Li, Yan Wang, Gui-Rong Li
Bradykinin is a well-known endogenous vasoactive peptide. The present study investigated the bradykinin receptor expression in human cardiac c-Kit+ progenitor cells and the potential role of bradykinin in regulating cell cycling progression and mobility. It was found that mRNA and protein of bradykinin type 2 receptors, but not bradykinin type 1 receptors, were abundant in cultured human cardiac c-Kit+ progenitor cells. Bradykinin (1-10 nM) stimulated cell growth and migration in a concentration-dependent manner...
January 12, 2017: Oncotarget
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