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https://www.readbyqxmd.com/read/28394372/maintenance-of-the-marginal-zone-b-cell-compartment-specifically-requires-the-rna-binding-protein-zfp36l1
#1
Rebecca Newman, Helena Ahlfors, Alexander Saveliev, Alison Galloway, Daniel J Hodson, Robert Williams, Gurdyal S Besra, Charlotte N Cook, Adam F Cunningham, Sarah E Bell, Martin Turner
RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype...
April 10, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28381185/the-histone-demethylase-lysine-specific-demethylase-1-mediated-epigenetic-silence-of-klf2-contributes-to-gastric-cancer-cell-proliferation-migration-and-invasion
#2
Ruizhong Fang, Jian Xu, Hai Lin, Xiaoguang Xu, Feng Tian
Gastric cancer is one of the most common malignancies and leading causes of cancer-related death worldwide. An increasing number of evidence has revealed that gastric tumorigenesis is a multistage pathological state, and epigenetic alterations are considered to play critical roles in the etiology of gastric cancer. Lysine-specific demethylase-1, a histone demethylase, has been linked to malignancy in several human cancers and considered to epigenetically regulate many tumor suppressor genes during tumorigenesis and cancer progression...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28373704/noise-processing-by-signaling-networks
#3
Styliani Kontogeorgaki, Rubén J Sánchez-García, Rob M Ewing, Konstantinos C Zygalakis, Ben D MacArthur
Signaling networks mediate environmental information to the cell nucleus. To perform this task effectively they must be able to integrate multiple stimuli and distinguish persistent signals from transient environmental fluctuations. However, the ways in which signaling networks process environmental noise are not well understood. Here we outline a mathematical framework that relates a network's structure to its capacity to process noise, and use this framework to dissect the noise-processing ability of signaling networks...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28351756/oxygenated-hypothermic-machine-perfusion-after-static-cold-storage-improves-endothelial-function-of-extended-criteria-donor-livers
#4
Laura C Burlage, Negin Karimian, Andrie C Westerkamp, Nienke Visser, Alix P M Matton, Rianne van Rijn, Jelle Adelmeijer, Janneke Wiersema-Buist, Annette S H Gouw, Ton Lisman, Robert J Porte
BACKGROUND: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. We investigated the effect of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers. METHODS: Eighteen livers, declined for transplantation, were transported to our center using static cold storage (SCS). After SCS, 6 livers underwent two hours of HMP, and subsequent normothermic machine perfusion (NMP) to assess viability...
March 25, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28348240/endothelial-transcription-factor-klf2-negatively-regulates-liver-regeneration-via-induction-of-activin-a
#5
Yosif Manavski, Tobias Abel, Junhao Hu, Dina Kleinlützum, Christian J Buchholz, Christina Belz, Hellmut G Augustin, Reinier A Boon, Stefanie Dimmeler
Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver damage and augmentation of hepatocyte proliferation after chronic liver injury by treatment with carbon tetrachloride (CCl4). Serum levels of GLDH3 and ALT were significantly reduced in CCl4-treated EC-specific KLF2-deficient mice...
March 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28297625/genomics-of-hairy-cell-leukemia
#6
Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28288718/splenic-marginal-zone-lymphoma
#7
REVIEW
Miguel A Piris, Arantza Onaindía, Manuela Mollejo
Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28263185/laminar-flow-downregulates-notch-activity-to-promote-lymphatic-sprouting
#8
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Jaehyuk Yoo, Esak Lee, Mingu Hong, Sunju Lee, Hiroaki Ishida, James Burford, Janos Peti-Peterdi, Ralf H Adams, Sonal Srikanth, Yousang Gwack, Christopher S Chen, Hans J Vogel, Chester J Koh, Alex K Wong, Young-Kwon Hong
The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28248139/the-flow-dependent-transcription-factor-klf2-protects-lung-vascular-barrier-function-in-acute-respiratory-distress-syndrome
#9
Wolfgang M Kuebler
No abstract text is available yet for this article.
March 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28246014/montelukast-inhibits-oxidized-low-density-lipoproteins-ox-ldl-induced-vascular-endothelial-attachment-an-implication-for-the-treatment-of-atherosclerosis
#10
Xiuhua Di, Xuelu Tang, Xiuting Di
Recruitment of monocytes to endothelial cells is important during early stages of atherosclerosis development, which is activated in response to a number of inflammatory stimuli, including oxidized low-density lipoprotein (ox-LDL). Montelukast is a licensed drug approved by the Food and Drug Administration (FDA) and clinically used for the treatment of asthma by reducing the eosinophilic inflammation in the airway. Little information regarding the effects of Montelukast on endothelial inflammation has been reported before...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28239661/klf2-and-klf4-control-endothelial-identity-and-vascular-integrity
#11
Panjamaporn Sangwung, Guangjin Zhou, Lalitha Nayak, E Ricky Chan, Sandeep Kumar, Dong-Won Kang, Rongli Zhang, Xudong Liao, Yuan Lu, Keiki Sugi, Hisashi Fujioka, Hong Shi, Stephanie D Lapping, Chandra C Ghosh, Sarah J Higgins, Samir M Parikh, Hanjoong Jo, Mukesh K Jain
Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28214253/long-noncoding-rna-linc00673-is-activated-by-sp1-and-exerts-oncogenic-properties-by-interacting-with-lsd1-and-ezh2-in-gastric-cancer
#12
Mingde Huang, Jiakai Hou, Yunfei Wang, Min Xie, Chenchen Wei, Fengqi Nie, Zhaoxia Wang, Ming Sun
Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the biological function of these molecules and the mechanisms responsible for their alteration in gastric cancer (GC) are not fully understood. In this study, we found that lncRNA LINC00673 is significantly upregulated in gastric cancer. Knockdown of LINC00673 inhibited cell proliferation and invasion and induced cell apoptosis, whereas LINC00673 overexpression had the opposite effect...
April 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28208647/soy-leaf-extract-exerts-atheroprotective-effects-via-modulation-of-kr%C3%A3-ppel-like-factor-2-and-adhesion-molecules
#13
Jong-Min Han, Hua Li, Moon-Hee Cho, Seung-Hwa Baek, Chul-Ho Lee, Ho-Yong Park, Tae-Sook Jeong
Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL) in human umbilical vein endothelial cells (HUVECs) and high-cholesterol diet (HCD)-fed low-density lipoprotein receptor deficient (LDLR-/-) mice. ESL induced the expression of Krüppel-like factor 2 (KLF2), an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS), and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α)-stimulated HUVECs but also in 7-ketocholesterol (7-KC)-stimulated HUVECs...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28188237/first-identification-of-kr%C3%A3-ppel-like-factor-2-mutation-in-heritable-pulmonary-arterial-hypertension
#14
Christina A Eichstaedt, Jie Song, Rebecca Rodríguez Viales, Zixuan Pan, Nicola Benjamin, Christine Fischer, Marius Hoeper, Silvia Ulrich, Katrin Hinderhofer, Ekkehard Grünig
Heritable pulmonary arterial hypertension (HPAH) is an autosomal dominantly inherited disease caused by mutations in the bone morphogenic protein receptor 2 gene and/or genes of its signalling pathway in about 85% of patients. We clinically and genetically analysed a HPAH family without mutations in previously described PAH genes. Clinical assessment included electrocardiogram, lung function, blood gas analysis, chest X-ray, laboratory testing, echocardiography and right heart catheterisation in case of suspected disease...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28167653/orai1-activates-proliferation-of-lymphatic-endothelial-cells-in-response-to-laminar-flow-through-kr%C3%A3-ppel-like-factors-2-and-4
#15
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Mingu Hong, Sunju Lee, James Burford, Georgina Gyarmati, Janos Peti-Peterdi, Sonal Srikanth, Yousang Gwack, Chester J Koh, Evgenii Boriushkin, Anne Hamik, Alex K Wong, Young-Kwon Hong
RATIONALE: Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown. OBJECTIVE: We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation. METHODS AND RESULTS: Primary endothelial cells from dermal blood and lymphatic vessels (BECs and LECs) were exposed to low-rate steady laminar flow...
February 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28130078/molecular-identification-and-functional-analysis-of-klf2-in-plecoglossus-altivelis-ayu-it-s-regulatory-role-in-monocyte-macrophage-activation
#16
Xin-Jiang Lu, Qiang Chen, Jie Chen, Jiong Chen
Monocytes/macrophages (MO/MФ) play an important role in the response to infection in Plecoglossus altivelis (ayu). However, the role of transcription factors in the function of ayu MO/MФ is poorly understood. Here, we cloned the cDNA sequence of the Kruppel-like factor 2 (PaKLF2) gene from ayu. Phylogenetic analysis indicated that PaKLF2 was closest to that of Atlantic salmon (Salmo salar). Real time quantitative PCR (RT-qPCR) revealed that the PaKLF2 mRNA level was highest in the peripheral blood mononuclear cells among all tested tissues...
March 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28130053/vascular-protective-effects-of-klf2-on-a%C3%AE-induced-toxicity-implications-for-alzheimer-s-disease
#17
Xuejun Fang, Xiaoli Zhong, Gang Yu, Si Shao, Qidong Yang
Alzheimer's disease (AD) is characterized by excessive amounts of senile plaques and neurofibrillary tangles in the brain, and cerebrovascular pathologies in AD are attracting increasingly more attention. Krüppel-like factor (KLF) 2, a transcription regulator expressed in the mouse embryonic vasculature and involved in the regulation of vascular gene expression, serves as a protective factor in endothelial cells. However, whether KLF2 is involved in neurodegenerative disease, and especially in AD, remains unknown...
January 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28117095/preconditioning-by-portal-vein-embolization-modulates-hepatic-hemodynamics-and-improves-liver-function-in-pigs-with-extended-hepatectomy
#18
José M Asencio, José L García-Sabrido, José A López-Baena, Luis Olmedilla, Isabel Peligros, Pablo Lozano, Álvaro Morales-Taboada, Carolina Fernández-Mena, Miguel A Steiner, Emma Sola, José M Perez-Peña, Miriam Herrero, Juan Laso, Cristina Lisbona, Rafael Bañares, Javier Casanova, Javier Vaquero
BACKGROUND: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. METHODS: An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group)...
January 20, 2017: Surgery
https://www.readbyqxmd.com/read/28112720/long-noncoding-rna-hoxa-as2-represses-p21-and-klf2-expression-transcription-by-binding-with-ezh2-lsd1-in-colorectal-cancer
#19
J Ding, M Xie, Y Lian, Y Zhu, P Peng, J Wang, L Wang, K Wang
Long noncoding RNAs (lncRNAs) have received increased attention as a new class of functional regulators involved in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2) is a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes in the HOXA cluster that regulates gene expression at a transcription level. HOXA-AS2 is previously found to be overexpressed in gastric cancer (GC) and promotes GC cells proliferation. However, its potential role and molecular mechanism in colorectal cancer (CRC) are not known...
January 23, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28100021/identifying-the-biphasic-role-of-calcineurin-nfat-signaling-enables-replacement-of-sox2-in-somatic-cell-reprogramming
#20
Sherif Khodeer, Takumi Era
Induction of pluripotency with defined factors (Oct4, Sox2, Klf4, c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal-epithelial transition...
January 18, 2017: Stem Cells
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