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https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#1
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27905512/plant-phenolic-volatiles-inhibit-quorum-sensing-in-pectobacteria-and-reduce-their-virulence-by-potential-binding-to-expi-and-expr-proteins
#2
Janak Raj Joshi, Netaly Khazanov, Hanoch Senderowitz, Saul Burdman, Alexander Lipsky, Iris Yedidia
Quorum sensing (QS) is a population density-dependent regulatory system in bacteria that couples gene expression to cell density through accumulation of diffusible signaling molecules. Pectobacteria are causal agents of soft rot disease in a range of economically important crops. They rely on QS to coordinate their main virulence factor, production of plant cell wall degrading enzymes (PCWDEs). Plants have evolved an array of antimicrobial compounds to anticipate and cope with pathogens, of which essential oils (EOs) are widely recognized...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902739/degenerative-suspensory-ligament-desmitis-dsld-in-peruvian-paso-horses-is-characterized-by-altered-expression-of-tgf%C3%AE-signaling-components-in-adipose-derived-stromal-fibroblasts
#3
Wei Luo, John Sandy, Katie Trella, Daniel Gorski, Shuguang Gao, Jun Li, Sabrina Brounts, Jorge Galante, Anna Plaas
Equine degenerative suspensory ligament desmitis (DSLD) in Peruvian Paso horses typically presents at 7-15 years and is characterized by lameness, focal disorganization of collagen fibrils, and chondroid deposition in the body of the ligament. With the aim of developing a test for disease risk (that can be used to screen horses before breeding) we have quantified the expression of 76 TGFβ-signaling target genes in adipose-derived stromal fibroblasts (ADSCs) from six DSLD-affected and five unaffected Paso horses...
2016: PloS One
https://www.readbyqxmd.com/read/27881681/a-novel-regulatory-mechanism-of-type-ii-collagen-expression-via-a-sox9-dependent-enhancer-in-intron-6
#4
Hideyo Yasuda, Chun-Do Oh, Di Chen, Benoit de Crombrugghe, Jin-Hoi Kim
Type II collagen α1 is specific for cartilaginous tissues, and mutations in its gene are associated with skeletal diseases. Its expression has been shown to be dependent on SOX9, a master transcription factor required for chondrogenesis that binds to an enhancer region in intron 1. However, ChIP-sequencing revealed that SOX9 does not strongly bind to intron 1, but rather it binds to intron 6 and a site 30 kb upstream of the transcription start site. Here, we aimed to determine the role of the novel SOX9-binding site in intron 6...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27867534/nanog-reprograms-prostate-cancer-cells-to-castration-resistance-via-dynamically-repressing-and-engaging-the-ar-foxa1-signaling-axis
#5
Collene R Jeter, Bigang Liu, Yue Lu, Hsueh-Ping Chao, Dingxiao Zhang, Xin Liu, Xin Chen, Qiuhui Li, Kiera Rycaj, Tammy Calhoun-Davis, Li Yan, Qiang Hu, Jianmin Wang, Jianjun Shen, Song Liu, Dean G Tang
The pluripotency transcription factor NANOG has been implicated in tumor development, and NANOG-expressing cancer cells manifest stem cell properties that sustain tumor homeostasis, mediate therapy resistance and fuel tumor progression. However, how NANOG converges on somatic circuitry to trigger oncogenic reprogramming remains obscure. We previously reported that inducible NANOG expression propels the emergence of aggressive castration-resistant prostate cancer phenotypes. Here we first show that endogenous NANOG is required for the growth of castration-resistant prostate cancer xenografts...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27861821/effects-of-c2ta-genetic-polymorphisms-on-mhc-class-ii-expression-and-autoimmune-diseases
#6
Anthony Cy Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the major histocompatibility complex class II (MHC-II) to CD4(+) T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variation in C2ta has been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2(q) ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27846777/development-and-characterization-of-in-vitro-human-oral-mucosal-equivalents-derived-from-immortalized-oral-keratinocytes
#7
Luke R Jennings, Helen E Colley, Jane Ong, Foti Panagakos, James G Masters, Harsh M Trivedi, Craig Murdoch, Simon Whawell
Tissue-engineered oral mucosal equivalents (OME) are being increasingly used to measure toxicity, drug delivery, and to model oral diseases. Current OME mainly comprise normal oral keratinocytes (NOK) cultured on top of a normal oral fibroblasts-containing matrix. However, the commercial supply of NOK is limited, restricting widespread use of these mucosal models. In addition, NOK suffer from poor longevity and donor-to-donor variability. Therefore, we constructed, characterized, and tested the functionality of OME based on commercial TERT2-immortalized oral keratinocytes (FNB6) to produce a more readily available alternative to NOK-based OME...
December 2, 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27845762/recent-progress-in-the-molecular-recognition-and-therapeutic-importance-of-interleukin-1-receptor-associated-kinase-4
#8
REVIEW
Mahesh Chandra Patra, Sangdun Choi
Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the cell, which detect pathogen associated molecular patterns and initiate signal transduction, culminating in the transcription of pro-inflammatory cytokines and antiviral interferon. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key mediator in TLR (except for TLR3) and interleukin-1 receptor signaling pathways. The loss of kinase function of IRAK4 is associated with increased susceptibility to various pathogens, while its over-activation causes autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and cancer...
November 13, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27824159/oncometabolite-d-2-hydroxyglurate-directly-induces-epithelial-mesenchymal-transition-and-is-associated-with-distant-metastasis-in-colorectal-cancer
#9
Hugh Colvin, Naohiro Nishida, Masamitsu Konno, Naotsugu Haraguchi, Hidekazu Takahashi, Junichi Nishimura, Taishi Hata, Koichi Kawamoto, Ayumu Asai, Kenta Tsunekuni, Jun Koseki, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Deranged metabolism is a hallmark of cancer, playing a significant role in driving the disease process. One such example is the induction of carcinogenesis by the oncometabolite D-2 hydroxyglutarate (D-2HG), which is produced by the mutated enzyme isocitrate dehydrogenase (IDH) occurring in subsets of leukaemias and brain tumours. The oncogenic property of D-2HG appears to stem from its ability to interfere with the activities of α-ketoglutarate-dependent dioxygenases, including the Jumonji family histone demethylases...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27823936/myod-phosphorylation-on-multiple-c-terminal-sites-regulates-myogenic-conversion-activity
#10
Laura J A Hardwick, John D Davies, Anna Philpott
MyoD is a master regulator of myogenesis with a potent ability to redirect the cell fate of even terminally differentiated cells. Hence, enhancing the activity of MyoD is an important step to maximising its potential utility for in vitro disease modelling and cell replacement therapies. We have previously shown that the reprogramming activity of several neurogenic bHLH proteins can be substantially enhanced by inhibiting their multi-site phosphorylation by proline-directed kinases. Here we have used Xenopus embryos as an in vivo developmental and reprogramming system to investigate the multi-site phospho-regulation of MyoD during muscle differentiation...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27814651/mitochondria-in-the-pathophysiology-of-alzheimer-s-and-parkinson-s-diseases
#11
Isaac G Onyango, Shaharyar M Khan, James P Bennett
Mitochondria are responsible for the majority of energy production in energy-intensive tissues like brain, modulate Ca(+2) signaling and control initiation of cell death. Because of their extensive use of oxygen and lack of protective histone proteins, mitochondria are vulnerable to oxidative stress (ROS)-induced damage to their genome (mtDNA), respiratory chain proteins and ROS repair enzymes. Animal and cell models of PD use toxins that impair mitochondrial complex I activity. Maintenance of mitochondrial mass, mitochondrial biogenesis (mitobiogenesis), particularly in high-energy brain, occurs through complex signaling pathways involving the upstream "master regulator" PGC-1alpha that is transcriptionally and post-translationally regulated...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27812980/ampk-in-neurodegenerative-diseases
#12
Manon Domise, Valérie Vingtdeux
Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are neurodegenerative disorders that are characterized by a progressive degeneration of nerve cells eventually leading to dementia. While these diseases affect different neuronal populations and present distinct clinical features, they share in common several features and signaling pathways. In particular, energy metabolism defects, oxidative stress, and excitotoxicity are commonly described and might be correlated with AMP-activated protein kinase (AMPK) deregulation...
2016: EXS
https://www.readbyqxmd.com/read/27798153/t-cell-independent-mechanisms-associated-with-neutrophil-extracellular-trap-formation-and-selective-autophagy-in-il-17a-mediated-epidermal-hyperplasia
#13
Erika Suzuki, Emanual Maverakis, Ritu Sarin, Laura Bouchareychas, Vijay K Kuchroo, Frank O Nestle, Iannis E Adamopoulos
IL-17A has been strongly associated with epidermal hyperplasia in many cutaneous disorders. However, because IL-17A is mainly produced by αβ and γδT cells in response to IL-23, the role of T cells and IL-23 has overshadowed any IL-17A-independent actions. In this article, we report that IL-17A gene transfer induces epidermal hyperplasia in Il23r(-/-)Rag1(-/-)- and Tcrδ-deficient mice, which can be prevented by neutrophil depletion. Moreover, adoptive transfer of CD11b(+)Gr-1(hi) cells, after IL-17A gene transfer, was sufficient to phenocopy the disease...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27797344/objective-basis-for-chronic-pain-in-patients-with-adult-sickle-cell-disease
#14
Samip Master, Abhishek Patel, Glenn Mills, Richard Mansour
Sickle Cell Disease (SCD) affects approximately 100,000 Americans and due to lack of an organized treatment approach, patients with SCD pose a high economic burden on medical services. The patients with SCD have chronic bone damage from bone marrow infraction and vaso-occulsive events. These bone damages lead to chronic pain in patients with SCD. The inadwquate treatment of chronic pain in adult patients with SCD can lead to pseudo-addictive behavior and also affect their psycho-social life. There are certain barriers to adequate pain management in adult patients with SCD, namely, limited knowledge among the clinicians, inadequate assessment, concerns about addiction, and biases against opioid use...
September 2016: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/27789056/transcription-factor-nrf2-hyperactivation-in-early-phase-renal-ischemia-reperfusion-injury-prevents-tubular-damage-progression
#15
Masahiro Nezu, Tomokazu Souma, Lei Yu, Takafumi Suzuki, Daisuke Saigusa, Sadayoshi Ito, Norio Suzuki, Masayuki Yamamoto
Acute kidney injury is a devastating disease with high morbidity in hospitalized patients and contributes to the pathogenesis of chronic kidney disease. An underlying mechanism of acute kidney injury involves ischemia-reperfusion injury which, in turn, induces oxidative stress and provokes organ damage. Nrf2 is a master transcription factor that regulates the cellular response to oxidative stress. Here, we examined the role of Nrf2 in the progression of ischemia-reperfusion injury-induced kidney damage in mice using genetic and pharmacological approaches...
October 20, 2016: Kidney International
https://www.readbyqxmd.com/read/27780851/microrna-based-therapy-of-gata2-deficient-vascular-disease
#16
Dorothee Hartmann, Jan Fiedler, Kristina Sonnenschein, Annette Just, Angelika Pfanne, Karina Zimmer, Janet Remke, Ariana Foinquinos, Malte Butzlaff, Katharina Schimmel, Lars Maegdefessel, Denise Hilfiker-Kleiner, Nico Lachmann, Andreas Schober, Natali Froese, Joerg Heineke, Johann Bauersachs, Sandor Batkai, Thomas Thum
BACKGROUND: -The transcription factor GATA2 orchestrates the expression of many endothelial-specific genes illustrating its crucial importance for endothelial cell function. The capacity of this transcription factor in orchestrating endothelial important microRNAs (miRNAs/miR) is unknown. METHODS: -Endothelial GATA2 was functionally analyzed in human endothelial cells in vitro. Endogenous siRNA-mediated knockdown and lentiviral-based overexpression were applied to decipher capacity of GATA2 in regulating cell viability and capillary formation...
October 25, 2016: Circulation
https://www.readbyqxmd.com/read/27771930/cddo-and-its-role-in-chronic-diseases
#17
Bryan J Mathis, Taixing Cui
There has been a continued interest in translational research focused on both natural products and manipulation of functional groups on these compounds to create novel derivatives with higher desired activities. Oleanolic acid, a component of traditional Chinese medicine used in hepatitis therapy, was modified by chemical processes to form 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO). This modification increased anti-inflammatory activity significantly and additional functional groups on the CDDO backbone have shown promise in treating conditions ranging from kidney disease to obesity to diabetes...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27771362/transcriptional-control-of-chondrocyte-specification-and-differentiation
#18
Chia-Feng Liu, William E Samsa, Guang Zhou, Véronique Lefebvre
A milestone in the evolutionary emergence of vertebrates was the invention of cartilage, a tissue that has key roles in modeling, protecting and complementing the bony skeleton. Cartilage is elaborated and maintained by chondrocytes. These cells derive from multipotent skeletal progenitors and they perform highly specialized functions as they proceed through sequential lineage commitment and differentiation steps. They form cartilage primordia, the primary skeleton of the embryo. They then transform these primordia either into cartilage growth plates, temporary drivers of skeletal elongation and endochondral ossification, or into permanent tissues, namely articular cartilage...
October 19, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27758118/blockade-of-glutamine-synthetase-enhances-inflammatory-response-in-microglial-cells
#19
Erika M Palmieri, Alessio Menga, Aurore Lebrun, Douglas C Hooper, D Allan Butterfield, Massimiliano Mazzone, Alessandra Castegna
AIMS: Microglial cells are brain resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to LPS-activation in other cell types, which is expressed by microglia...
October 19, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27757418/promiscuous-targeting-of-bromodomains-by-bromosporine-identifies-bet-proteins-as-master-regulators-of-primary-transcription-response-in-leukemia
#20
Sarah Picaud, Katharina Leonards, Jean-Philippe Lambert, Oliver Dovey, Christopher Wells, Oleg Fedorov, Octovia Monteiro, Takao Fujisawa, Chen-Yi Wang, Hannah Lingard, Cynthia Tallant, Nikzad Nikbin, Lucie Guetzoyan, Richard Ingham, Steven V Ley, Paul Brennan, Susanne Muller, Anastasia Samsonova, Anne-Claude Gingras, Juerg Schwaller, George Vassiliou, Stefan Knapp, Panagis Filippakopoulos
Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clinical studies and have motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacological targeting. To address this issue, we developed a promiscuous BRD inhibitor [bromosporine (BSP)] that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function...
October 2016: Science Advances
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