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https://www.readbyqxmd.com/read/27876564/rncr3-a-regulator-of-diabetes-mellitus-related-retinal-microvascular-dysfunction
#1
Kun Shan, Chao-Peng Li, Chang Liu, Xin Liu, Biao Yan
Retinal microvascular abnormality is an important pathological feature of diabetic retinopathy. Herein, we report the role of lncRNA-RNCR3 in diabetes mellitus-induced retinal microvascular abnormalities. We show that RNCR3 is significantly up-regulated upon high glucose stress in vivo and in vitro. RNCR3 knockdown alleviates retinal vascular dysfunction in vivo, as shown by decreased retinal acellular capillaries, decreased vascular leakage, and reduced inflammatory response. RNCR3 knockdown decreases retinal endothelial cell proliferation, and reduces cell migration and tube formation in vitro...
November 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27869747/the-vitamin-e-analog-gamma-tocotrienol-gt3-and-statins-synergistically-up-regulate-endothelial-thrombomodulin-tm
#2
Rupak Pathak, Sanchita P Ghosh, Daohong Zhou, Martin Hauer-Jensen
Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) and strongly induce endothelial thrombomodulin (TM); which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3) also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations...
November 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27855271/experimental-lung-injury-reduces-klf2-to-increase-endothelial-permeability-via-regulation-of-rapgef3-rac1-signaling
#3
Ru-Ting Huang, David Wu, Angelo Meliton, Myung-Jin Oh, Matthew Krause, Joyce A Lloyd, Recep Nigdelioglu, Robert B Hamanaka, Mukesh K Jain, Anna Birukova, John P Kress, Konstantin G Birukov, Gökhan M Mutlu, Yun Fang
RATIONALE: The acute respiratory distress syndrome (ARDS) is caused by widespread endothelial barrier disruption and uncontrolled cytokine storm. Genome-wide association studies (GWAS) have linked multiple genes to ARDS. Although mechano-sensitive transcription factor Krüppel-like factor 2 (KLF2) is a major regulator of endothelial function, its role in regulating pulmonary vascular integrity in lung injury and ARDS-associated GWAS genes remains poorly understood. OBJECTIVES: To examine KLF2 expression in multiple animal models of acute lung injury and further elucidate the KLF2-mediated pathways involved in endothelial barrier disruption and cytokine storm in experimental lung injury...
November 17, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27837103/dendritic-cell-klf2-expression-regulates-t-cell-activation-and-proatherogenic-immune-responses
#4
Noah Alberts-Grill, Daniel Engelbertsen, Dexiu Bu, Amanda Foks, Nir Grabie, Jan M Herter, Felicia Kuperwaser, Tao Chen, Gina Destefano, Petr Jarolim, Andrew H Lichtman
Dendritic cells (DCs) have been implicated as important regulators of innate and adaptive inflammation in many diseases, including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies have shown an important anti-inflammatory role for the transcription factor Krüppel-like factor 2 (KLF2) in regulating activation of various cell types that participate in atherosclerotic lesion development, including endothelial cells, macrophages, and T cells...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27791035/mirna92a-targets-klf2-and-the-phosphatase-pten-signaling-to-promote-human-t-follicular-helper-precursors-in-t1d-islet-autoimmunity
#5
Isabelle Serr, Rainer W Fürst, Verena B Ott, Martin G Scherm, Alexei Nikolaev, Füsun Gökmen, Stefanie Kälin, Stephanie Zillmer, Melanie Bunk, Benno Weigmann, Nicole Kunschke, Brigitta Loretz, Claus-Michael Lehr, Benedikt Kirchner, Bettina Haase, Michael Pfaffl, Ari Waisman, Richard A Willis, Anette-G Ziegler, Carolin Daniel
Aberrant immune activation mediated by T effector cell populations is pivotal in the onset of autoimmunity in type 1 diabetes (T1D). T follicular helper (TFH) cells are essential in the induction of high-affinity antibodies, and their precursor memory compartment circulates in the blood. The role of TFH precursors in the onset of islet autoimmunity and signaling pathways regulating their differentiation is incompletely understood. Here, we provide direct evidence that during onset of islet autoimmunity, the insulin-specific target T-cell population is enriched with a C-X-C chemokine receptor type 5 (CXCR5)(+)CD4(+) TFH precursor phenotype...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27756792/a-microrna302-367-erk1-2-klf2-s1pr1-pathway-prevents-tumor-growth-via-restricting-angiogenesis-and-improving-vascular-stability
#6
Jingjiang Pi, Ting Tao, Tao Zhuang, Huimin Sun, Xiaoli Chen, Jie Liu, Yu Cheng, Zuoren Yu, Helen H Zhu, Wei-Qiang Gao, Yuanzhen Suo, Xunbin Wei, Paul Chan, Xiangjian Zheng, Ying Tian, Edward Morrisey, Lin Zhang, Yuzhen Zhang
RATIONALE: Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367cluster in angiogenesis and tumors has not yet been fully evaluated. OBJECTIVE: To investigate the functions of miR302-367 in developmental angiogenesis and tumor angiogenesis and explore the molecular mechanisms of microRNA for the treatment of pathological neovascularization-related diseases...
October 18, 2016: Circulation Research
https://www.readbyqxmd.com/read/27742373/scutellarin-attenuates-vasospasm-through-the-erk5-klf2-enos-pathway-after-subarachnoid-hemorrhage-in-rats
#7
Qiang Li, Yujie Chen, Xuan Zhang, Shilun Zuo, Hongfei Ge, Yanyan Chen, Xin Liu, John H Zhang, Huaizhen Ruan, Hua Feng
Angiographic vasospasm, especially in the early phases (<72h) of subarachnoid hemorrhage (SAH), is one of the major complications after an aneurysm rupture and is often the cause of delayed neurological deterioration. Scutellarin (SCU), a flavonoid extracted from the traditional Chinese herb Erigeron breviscapus, has been widely accepted as an antioxidant, but the effect of SCU on vasospasm after SAH remains elusive. Endovascular perforation was conducted to induce SAH in Sprague-Dawley rats. Then, the underlying mechanism of the anti-vasospasm effect of SCU was investigated using a modified Garcia scale, India ink angiography, cross-sectional area analysis, immunohistochemistry staining and western blot...
October 11, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27739345/rosuvastatin-inhibits-il-8-and-il-6-production-in-human-coronary-artery-endothelial-cells-stimulated-with-aggregatibacter-actinomycetemcomitans-serotype-b
#8
Diego F Gualtero, Sergio M Viafara-Garcia, Sandra J Morantes, Diana M Buitrago, Octavio A Gonzalez, Gloria I Lafaurie
BACKGROUND: Rosuvastatin exhibits anti-inflammatory effects and reduces periodontal diseases and atherosclerosis; however, its role in regulating periodontopathogen-induced endothelial pro-inflammatory responses remains unclear. The purpose of this study was to determine whether rosuvastatin can reduce the pro-inflammatory response induced by A. actinomycetemcomitans in human coronary artery endothelial cells (HCAECs). METHODS: HCAECs were stimulated with purified A...
October 14, 2016: Journal of Periodontology
https://www.readbyqxmd.com/read/27718235/the-soluble-cytoplasmic-tail-of-cd45-ct-cd45-in-human-plasma-contributes-to-keep-t-cells-in-a-quiescent-state
#9
Alexander Puck, Stefan Hopf, Madhura Modak, Otto Majdic, Petra Cejka, Stephan Blüml, Klaus Schmetterer, Catharina Arnold-Schrauf, Jens G Gerwien, Klaus S Frederiksen, Elisabeth Thell, Judith Leitner, Peter Steinberger, Regina Aigner, Maria Seyerl-Jiresch, Gerhard J Zlabinger, Johannes Stöckl
The cytoplasmic tail of CD45 (ct-CD45) is proteolytically cleaved and released upon activation of human phagocytes. It acts on T cells as an inhibitory, cytokine-like factor in vitro. Here we show, that ct-CD45 is abundant in human peripheral blood plasma from healthy adults compared with plasma derived from umbilical cord blood and plasma from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Plasma depleted of ct-CD45 enhanced T-cell proliferation, while addition of exogenous ct-CD45 protein inhibited proliferation and reduced cytokine production of human T lymphocytes in response to TCR signaling...
October 8, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27644252/long-non-coding-rna-irain-suppresses-apoptosis-and-promotes-proliferation-by-binding-to-lsd1-and-ezh2-in-pancreatic-cancer
#10
Yifan Lian, Juan Wang, Jing Feng, Jie Ding, Zhonghua Ma, Juan Li, Peng Peng, Wei De, Keming Wang
Long non-coding RNA (lncRNA) modulates gene expression, while lncRNA dysregulation is associated with human cancer. Furthermore, while recent studies have shown that lncRNA IRAIN plays an important role in other malignancies, the role of IRAIN in pancreatic cancer (PC) progression remains unclear. In this study, we found that upregulation of lncRNA IRAIN was significantly correlated with tumor size, TNM stage, and lymph node metastasis in a cohort of 37 PC patients. In vitro experiments showed that knockdown of IRAIN by small interfering RNA (siRNA) significantly induced cell apoptosis and inhibited cell proliferation in both BxPC-3 and PANC-1 cells...
September 19, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27592554/targeting-odc1-inhibits-tumor-growth-through-reduction-of-lipid-metabolism-in-human-hepatocellular-carcinoma
#11
Yunseon Choi, Sang Taek Oh, Min-Ah Won, Kyung Mi Choi, Min Ji Ko, Daekwan Seo, Tae-Won Jeon, In Hye Baik, Sang-Kyu Ye, Keon Uk Park, In-Chul Park, Byeong-Churl Jang, Jun-Young Seo, Yun-Han Lee
Ornithine decarboxylase 1 (ODC1), a metabolic enzyme critically involved in the polyamine biosynthesis, is commonly upregulated in hepatocellular carcinoma (HCC). Despite its altered expression in human HCC tissues, the molecular mechanism by which ODC1 alters the course of HCC progression and functions in HCC cell survival is unknown. Here we identified that silencing of ODC1 expression with small interfering (si) RNA causes inhibition of HCC cell growth through blockade of cell cycle progression and induction of apoptosis...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27554081/braf-v600e-mutation-in-hairy-cell-leukemia-from-bench-to-bedside
#12
Brunangelo Falini, Maria Paola Martelli, Enrico Tiacci
Hairy cell leukemia (HCL) is a distinct clinicopathological entity whose underlying genetic lesion has remained a mystery for over half a century. The BRAF V600E mutation is now recognized as the causal genetic event of HCL because it is somatic, present in the entire tumor clone, detectable in almost all cases at diagnosis (encompassing the whole disease spectrum), and stable at relapse. BRAF V600E leads to the constitutive activation of the RAF-MEK-extracellular signal-regulated kinase (ERK) signaling pathway which represents the key event in the molecular pathogenesis of HCL...
October 13, 2016: Blood
https://www.readbyqxmd.com/read/27545498/cross-talk-between-autophagy-and-klf2-determines-endothelial-cell-phenotype-and-microvascular-function-in-acute-liver-injury
#13
Sergi Guixé-Muntet, Fernanda Cristina de Mesquita, Sergi Vila, Virginia Hernández-Gea, Carmen Peralta, Juan Carlos García-Pagán, Jaime Bosch, Jordi Gracia-Sancho
BACKGROUND & AIMS: The transcription factor Krüppel-like factor 2 (KLF2), inducible by simvastatin, confers endothelial vasoprotection. Considering recent data suggesting activation of autophagy by statins, we aimed to: 1) characterize the relationship between autophagy and KLF2 in the endothelium, 2) assess this relationship in acute liver injury (cold ischemia/reperfusion) and 3) study the effects of modulating KLF2-autophagy in vitro and in vivo. METHODS: Autophagic flux, the vasoprotective KLF2 pathway, cell viability and microvascular function were assessed in endothelial cells and in various pre-clinical models of acute liver injury (cold storage and warm reperfusion)...
August 18, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27540722/compartmentalization-of-total-and-virus-specific-tissue-resident-memory-cd8-t-cells-in-human-lymphoid-organs
#14
Heng Giap Woon, Asolina Braun, Jane Li, Corey Smith, Jarem Edwards, Frederic Sierro, Carl G Feng, Rajiv Khanna, Michael Elliot, Andrew Bell, Andrew D Hislop, Stuart G Tangye, Alan B Rickinson, Thomas Gebhardt, Warwick J Britton, Umaimainthan Palendira
Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27501756/long-noncoding-rna-xist-acts-as-an-oncogene-in-non-small-cell-lung-cancer-by-epigenetically-repressing-klf2-expression
#15
Jing Fang, Cheng-Cao Sun, Cheng Gong
Recently, long noncoding RNAs (lncRNAs) have been identified as critical regulators in numerous types of cancers, including non-small cell lung cancer (NSCLC). X inactivate-specific transcript (XIST) has been found to be up-regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found that XIST is over-expressed in NSCLC, and its increased level is associated with shorter survival and poorer prognosis...
September 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27462403/adipocyte-nuclei-captured-from-vat-and-sat
#16
Suresh Ambati, Ping Yu, Elizabeth C McKinney, Muthugapatti K Kandasamy, Diane Hartzell, Clifton A Baile, Richard B Meagher
BACKGROUND: Obesity-related comorbidities are thought to result from the reprogramming of the epigenome in numerous tissues and cell types, and in particular, mature adipocytes within visceral and subcutaneous adipose tissue, VAT and SAT. The cell-type specific chromatin remodeling of mature adipocytes within VAT and SAT is poorly understood, in part, because of the difficulties of isolating and manipulating large fragile mature adipocyte cells from adipose tissues. METHODS: We constructed MA-INTACT (Mature Adipocyte-Isolation of Nuclei TAgged in specific Cell Types) mice using the adiponectin (ADIPOQ) promoter (ADNp) to tag the surface of mature adipocyte nuclei with a reporter protein...
2016: BMC Obesity
https://www.readbyqxmd.com/read/27462110/peripheral-tolerance-can-be-modified-by-altering-klf2-regulated-treg-migration
#17
Sudheer K Pabbisetty, Whitney Rabacal, Emmanuel J Volanakis, Vrajesh V Parekh, Danyvid Olivares-Villagómez, Delphine Cendron, Kelli L Boyd, Luc Van Kaer, Eric Sebzda
Tregs are essential for maintaining peripheral tolerance, and thus targeting these cells may aid in the treatment of autoimmunity and cancer by enhancing or reducing suppressive functions, respectively. Before these cells can be harnessed for therapeutic purposes, it is necessary to understand how they maintain tolerance under physiologically relevant conditions. We now report that transcription factor Kruppel-like factor 2 (KLF2) controls naive Treg migration patterns via regulation of homeostatic and inflammatory homing receptors, and that in its absence KLF2-deficient Tregs are unable to migrate efficiently to secondary lymphoid organs (SLOs)...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27411964/inhibition-of-mir-92a-may-protect-endothelial-cells-after-acute-myocardial-infarction-in-rats-role-of-klf2-4
#18
Hongxia Liu, Guofen Li, Wenxue Zhao, Yibo Hu
BACKGROUND This study was designed to investigate the effects of microRNA-92 (miR-92), Kruppel-like factor 2 (KLF2), and Kruppel-like factor 4 (KLF4) on endothelial injury after acute myocardial infarction (AMI). MATERIAL AND METHODS Blood samples were collected from 50 AMI patients for detection of cardiac troponin I (cTnI), heart-type fatty acid-binding protein (H-FABP), and von Willebrand factor (vWF). The Sprague-Dawley rat models of AMI (n=30) were established by ligating their left anterior descending coronary artery...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27402841/novel-roles-and-mechanism-for-kr%C3%A3-ppel-like-factor-16-klf16-regulation-of-neurite-outgrowth-and-ephrin-receptor-a5-epha5-expression-in-retinal-ganglion-cells
#19
Jianbo Wang, Joana Galvao, Krista M Beach, Weijia Luo, Raul A Urrutia, Jeffrey L Goldberg, Deborah C Otteson
Regenerative medicine holds great promise for the treatment of degenerative retinal disorders. Krüppel-like factors (KLFs) are transcription factors that have recently emerged as key tools in regenerative medicine because some of them can function as epigenetic reprogrammers in stem cell biology. Here, we show that KLF16, one of the least understood members of this family, is a POU4F2 independent transcription factor in retinal ganglion cells (RGCs) as early as embryonic day 15. When overexpressed, KLF16 inhibits RGC neurite outgrowth and enhances RGC growth cone collapse in response to exogenous ephrinA5 ligands...
August 26, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27335277/the-genetics-of-nodal-marginal-zone-lymphoma
#20
Valeria Spina, Hossein Khiabanian, Monica Messina, Sara Monti, Luciano Cascione, Alessio Bruscaggin, Elisa Spaccarotella, Antony B Holmes, Luca Arcaini, Marco Lucioni, Fabrizio Tabbò, Sakellarios Zairis, Fary Diop, Michaela Cerri, Sabina Chiaretti, Roberto Marasca, Maurilio Ponzoni, Silvia Deaglio, Antonio Ramponi, Enrico Tiacci, Laura Pasqualucci, Marco Paulli, Brunangelo Falini, Giorgio Inghirami, Francesco Bertoni, Robin Foà, Raul Rabadan, Gianluca Gaidano, Davide Rossi
Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL...
September 8, 2016: Blood
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