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https://www.readbyqxmd.com/read/29353059/ask-family-kinases-are-required-for-optimal-nlrp3-inflammasome-priming
#1
David E Place, Parimal Samir, Rajendra Karki, Benoit Briard, Peter Vogel, Thirumala-Devi Kanneganti
Activation of the multimeric inflammasome complex leads to inflammatory responses to biotic and abiotic triggers. The inflammasome sensor, Nod-like receptor family Pyrin domain containing 3 (NLRP3), is activated by a range of stimuli and is tightly regulated to restrict excessive inflammation. Because NLRP3 responds broadly to cellular insults and regulates cell death similar to the stress-activated apoptosis signal-regulating kinases 1 and 2 (ASK1/2), we hypothesized that ASK1/2 may regulate NLRP3 activity...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29351847/phosphorylation-of-ezh2-by-ampk-suppresses-prc2-methyltransferase-activity-and-oncogenic-function
#2
Lixin Wan, Kexin Xu, Yongkun Wei, Jinfang Zhang, Tao Han, Christopher Fry, Zhao Zhang, Yao Vickie Wang, Liyu Huang, Min Yuan, Weiya Xia, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Jinsong Liu, Yun Wu, Victor X Jin, Xiangpeng Dai, Jianfeng Guo, Jia Liu, Shulong Jiang, Jin Li, John M Asara, Myles Brown, Mien-Chie Hung, Wenyi Wei
Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351723/mitochondrial-uncoupling-proteins-subtle-regulators-of-cellular-redox-signaling
#3
Petr Jezek, Blanka Holendová, Keith D Garlid, Martin Jaburek
SIGNIFICANCE: Mitochondria are the energetic, metabolic, redox and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1-5) play an eminent role in the regulation of each of the above aspects, being involved in numerous physiological events including redox signaling...
January 19, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29351413/mitochondrial-content-is-preserved-throughout-disease-progression-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-regardless-of-taurine-supplementation
#4
Robert G Barker, Victoria L Wyckelsma, Hongyang Xu, Robyn M Murphy
Mitochondrial dysfunction is a pathological feature of Duchenne muscular Dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterised by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP and involved in Ca2+ regulation and apoptotic signalling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28d which stabilises after 8 weeks. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351412/expression-of-ctgf-ccn2-in-response-to-lpa-is-stimulated-by-fibrotic-extracellular-matrix-via-the-integrin-fak-axis
#5
Camilo Riquelme-Guzman, Osvaldo Contreras, Enrique Brandan
Fibrosis is a common feature of several chronic diseases, and is characterized by exacerbated accumulation of extracellular matrix (ECM). Understanding the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong pro-fibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA)...
December 27, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351204/mtor-cross-talk-in-cancer-and-potential-for-combination-therapy
#6
REVIEW
Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer...
January 19, 2018: Cancers
https://www.readbyqxmd.com/read/29350183/integrated-biocircuits-engineering-functional-multicellular-circuits-and-devices
#7
Jordan Prox, Tory Smith, Chad Holl, Nick Chehade, Liang Guo
Novel in vitro platforms are currently revolutionizing the study and reconstruction of cellular circuitry to bypass the pertaining obstacles of data retrieval in vivo. While earlier approaches have provided great insights into culturing circuits in planar dissociated cell culture systems, the lack of full control over network activity and formation limits our understanding of their functionality. Thus, integrating various controllable parameters are required in creating a suitable microenvironment including cell patterning, highly-specified electrical and chemical stimuli, and rational circuit formation via logic functions...
January 19, 2018: Journal of Neural Engineering
https://www.readbyqxmd.com/read/29349553/differential-jnk-p38-and-erk-response-to-renal-injury-in-a-rat-model-of-acute-pancreatitis-in-pregnancy
#8
Fangchao Mei, Teng Zuo, Liang Zhao, Qiao Shi, Mingwei Xiang, Yupu Hong, Man Li, Weixing Wang
OBJECTIVE: The objective of this study was to determine the mechanism of acute renal injury (ARI) in acute necrotizing pancreatitis in late pregnancy (ANPIP). METHODS: Pregnant Sprague-Dawley rats in the third trimester were used for this study, and an ANPIP model was induced by injecting 5% sodium taurocholate into the biliary pancreatic duct. The rats were randomly divided into three groups: the normal, sham-operated (SO) and acute necrotizing pancreatitis (ANP) groups...
January 18, 2018: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29348070/rational-approach-to-highly-potent-and-selective-apoptosis-signal-regulating-kinase-1-ask1-inhibitors
#9
Frank Lovering, Paul Morgan, Christophe Allais, Ann Aulabaugh, Joanne Brodfuehrer, Jeanne Chang, Jotham Coe, WeiDong Ding, Heather Dowty, Margaret Fleming, Richard Frisbie, Julia Guzova, David Hepworth, Jayasankar Jasti, Steve Kortum, Ravi Kurumbail, Shashi Mohan, Nikolaos Papaioannou, Joseph W Strohbach, Fabien Vincent, Katherine Lee, Christoph W Zapf
Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases...
December 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29347819/presence-of-rigid-red-blood-cells-in-blood-flow-interfere-with-the-vascular-wall-adhesion-of-leukocytes
#10
Mario Gutierrez, Margaret B Fish, Alexander W Golinski, Omolola Eniola-Adefeso
The symptoms of many blood diseases can often be attributed to irregularities in cellular dynamics produced by abnormalities in blood cells, particularly red blood cells (RBCs). Contingent on the disease and its severity, RBCs can be afflicted with increased membrane rigidity as seen in malaria and sickle cell disease. Despite this understanding, little experimental work has been conducted towards understanding the effect of RBC rigidity on cellular dynamics in physiologic blood flow. Though many have computationally modeled complex blood flow to postulate how RBC rigidity may disrupt normal hemodynamics, to date, there lacks a clear understanding of how rigid RBCs affect the blood cell segregation behavior in blood flow, known as margination, and the resulting change in the adhesion of white blood cells (WBCs)...
January 18, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29347348/consciousness-as-a-global-property-of-brain-dynamic-activity
#11
D M Mateos, R Wennberg, R Guevara, J L Perez Velazquez
We seek general principles of the structure of the cellular collective activity associated with conscious awareness. Can we obtain evidence for features of the optimal brain organization that allows for adequate processing of stimuli and that may guide the emergence of cognition and consciousness? Analyzing brain recordings in conscious and unconscious states, we followed initially the classic approach in physics when it comes to understanding collective behaviours of systems composed of a myriad of units: the assessment of the number of possible configurations (microstates) that the system can adopt, for which we use a global entropic measure associated with the number of connected brain regions...
December 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346132/enzymatic-sources-and-physio-pathological-functions-of-soluble-pro-renin-receptor
#12
Qing Zhu, Tianxin Yang
PURPOSE OF REVIEW: (Pro)renin receptor (PRR) belongs to type I transmembrane receptor family and binds both prorenin and renin, representing a potential regulator of the activity of the renin-angiotensin system. Soluble form of PRR (sPRR) is generated by intracellular protease-mediated cleavage of full-length PRR. The purpose of this review is to highlight recent advances in understanding the mechanisms of action and production of sPRR. RECENT FINDINGS: It has recently been demonstrated that site-1-protease (S1P) plays a dominant role in the generation of sPRR...
January 16, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29346115/mitochondrial-dysfunction-a-key-player-in-the-pathogenesis-of-cardiovascular-diseases-linked-to-air-pollution
#13
REVIEW
Sri Rahavi Boovarahan, Gino A Kurian
Air pollution has become an environmental burden with regard to non-communicable diseases, particularly heart disease. It has been reported that air pollution can accelerate the development of heart failure and atrial fibrillation. Air pollutants encompass various particulate matters (PMs), which change the blood composition and heart rate and eventually leads to cardiac failure by triggering atherosclerotic plaque ruptures or by developing irreversible ischemia. A series of major epidemiological and observational studies have established the noxious effect of air pollutants on cardiovascular diseases (CVD), but the underlying molecular mechanisms of its susceptibility and the pathological disease events remain largely elusive and are predicted to be initiated in the cell organelle...
January 18, 2018: Reviews on Environmental Health
https://www.readbyqxmd.com/read/29344894/systems-biology-approaches-in-cancer-pathology
#14
Aaron DeWard, Rebecca J Critchley-Thorne
The complex network of the tissue system, in both pre-neoplastic tissues and tumors, demonstrates the need for a systems biology approach to cancer pathology, in which quantification of key tissue system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. A systems biology approach to cancer pathology enables integration of key system features that are relevant to diagnoses, patient outcomes, and responses to therapies. Key tissue system features relevant to cancer pathology include molecular and morphologic abnormalities in epithelia, cellular changes in the stroma such as immune infiltrates, and relationships between components of the system, such as interactions and spatial relationships between epithelial and stromal components, and also between specific immune cell subsets...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344431/noncoding-rnas-in-wound-healing-a-new-and-vast-frontier
#15
REVIEW
Anna Luan, Michael S Hu, Tripp Leavitt, Elizabeth A Brett, Kevin C Wang, Michael T Longaker, Derrick C Wan
Significance: Wound healing requires a highly orchestrated coordination of processes that are not yet fully understood. Therefore, available clinical therapies are thus far limited in their efficacy in preventing and treating both chronic wounds and scars. Current gene-based therapeutics is largely based on our understanding of the protein-coding genome and proteins involved in known wound healing pathways. Recent Advances: Noncoding RNAs such as microRNAs and long noncoding RNAs have recently been found to be significant modulators of gene expression in diverse cellular pathways...
January 1, 2018: Advances in Wound Care
https://www.readbyqxmd.com/read/29344413/therapeutic-potential-and-cellular-mechanisms-of-panax-notoginseng-on-prevention-of-aging-and-cell-senescence-associated-diseases
#16
REVIEW
Haiping Zhao, Ziping Han, Guangwen Li, Sijia Zhang, Yumin Luo
Owing to a dramatic increase in average life expectancy, most countries in the world are rapidly entering an aging society. Therefore, extending health span with pharmacological agents targeting aging-related pathological changes, are now in the spotlight of gerosciences. Panax notoginseng (Burk.) F. H. Chen, a species of the genus Panax, has been called the "Miracle Root for the Preservation of Life," and has long been used as a Chinese herb with magical medicinal value. Panax notoginseng has been extensively employed in China to treat microcirculatory disturbances, inflammation, trauma, internal and external bleeding due to injury, and as a tonic...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29343728/oxidation-of-sqstm1-p62-mediates-the-link-between-redox-state-and-protein-homeostasis
#17
Bernadette Carroll, Elsje G Otten, Diego Manni, Rhoda Stefanatos, Fiona M Menzies, Graham R Smith, Diana Jurk, Niall Kenneth, Simon Wilkinson, Joao F Passos, Johannes Attems, Elizabeth A Veal, Elisa Teyssou, Danielle Seilhean, Stéphanie Millecamps, Eeva-Liisa Eskelinen, Agnieszka K Bronowska, David C Rubinsztein, Alberto Sanz, Viktor I Korolchuk
Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343554/biased-generation-and-in-situ-activation-of-lung-tissue-resident-memory-cd4-t-cells-in-the-pathogenesis-of-allergic-asthma
#18
Damian L Turner, Monica Goldklang, Filip Cvetkovski, Daniel Paik, Jordis Trischler, Josselyn Barahona, Minwei Cao, Ronak Dave, Nicole Tanna, Jeanine M D'Armiento, Donna L Farber
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells that promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRMs) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. In this study, we used a mouse model of chronic exposure to intranasal house dust mite (HDM) extract to dissect how lung TRMs are generated and function in the persistence and pathogenesis of allergic airway disease...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29342309/prognostic-power-of-a-tumor-differentiation-gene-signature-for-bladder-urothelial-carcinomas
#19
Qianxing Mo, Fotis Nikolos, Fengju Chen, Zoe Tramel, Yu-Cheng Lee, Kazukuni Hayashi, Jing Xiao, Jianjun Shen, Keith Syson Chan
Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Methods: Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29342222/mechano-electric-feedback-effects-in-a-three-dimensional-3d-model-of-the-contracting-cardiac-ventricle
#20
Ani Amar, Sharon Zlochiver, Ofer Barnea
Mechano-electric feedback affects the electrophysiological and mechanical function of the heart and the cellular, tissue, and organ properties. To determine the main factors that contribute to this effect, this study investigated the changes in the action potential characteristics of the ventricle during contraction. A model of stretch-activated channels was incorporated into a three-dimensional multiscale model of the contracting ventricle to assess the effect of different preload lengths on the electrophysiological behavior...
2018: PloS One
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