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https://www.readbyqxmd.com/read/28436280/persistent-foot-ulcer-due-to-ruxolitinib-therapy-for-primary-myelofibrosis
#1
Michael Del Rosario, Henry Tsai, Constantin A Dasanu
Primary myelofibrosis is characterized by bone marrow fibrosis, splenomegaly and presence of JAK-2 V617F mutation in more than 90% of patients. Ruxolitinib is a Janus kinase inhibitor used for the treatment of primary myelofibrosis. We describe herein a persistent foot ulcer development attributed to ruxolitinib therapy. We are unaware of any previous reports of this phenomenon in the scientific literature. A thorough examination of the lower extremities is perhaps necessary before initiating this oral agent...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28436114/all-trans-retinoic-acid-stimulates-overexpression-of-tumor-protein-d52-tpd52-isoform-3-and-neuronal-differentiation-of-imr-32-cells
#2
Sudha Sravanti Kotapalli, Chandrashekhar Dasari, Divya Duscharla, Karthik Reddy Kami Reddy, Manjula Kasula, Ramesh Ummanni
Tumor protein D52 (TPD52), a proto-oncogene is overexpressed in a variety of epithelial carcinomas and plays an important role in cell proliferation, migration and cell death. In the present study we found that the treatment of IMR-32 neuroblastoma (NB) cells with retinoic acid (RA) stimulates an increase in expression of TPD52. TPD52 expression is detectable after 72 h, can be maintained till differentiation of NB cells suggesting that TPD52 is involved in differentiation. Here, we demonstrate that TPD52 is essential for RA to promote differentiation of NB cells...
April 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28433851/dna-methylation-regulates-gene-expression-in-intracranial-aneurysms
#3
Lanbing Yu, Jia Wang, Shuo Wang, Dong Zhang, Yuanli Zhao, Rong Wang, Jizong Zhao
OBJECTIVE: Different gene expression profiles are observed in intracranial aneurysm tissue. Understanding these genes and what regulates their expression will help us understand intracranial aneurysm pathogenesis. We investigated whether differences in DNA methylation regulate gene expression in intracranial aneurysms. METHODS: Twenty intracranial aneurysm tissues were compared with 20 matched samples from the superficial temporal artery as controls. We detected the gene expression profiles in these samples using Human U133 Plus 2...
April 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28433687/steroid-resistance-of-airway-type-2-innate-lymphoid-cells-ilc2s-from-severe-asthma-the-role-of-thymic-stromal-cell-lymphopoietin-tslp
#4
Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M Gorska, Richard J Martin, Rafeul Alam
BACKGROUND: ILC2s represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown. OBJECTIVE: To assess steroid resistance of human blood and airway ILC2s from asthmatic patients and examine its mechanism of induction. METHODS: We studied human blood and lung ILC2s from asthmatic and control subjects by flow cytometry and ELISA. RESULTS: Dexamethasone (Dex) inhibited (P=0.04) CRTH2 and type 2 cytokine expression by blood ILC2s stimulated with IL25 and IL33...
April 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28427244/whole-genome-expression-analyses-of-type-2-diabetes-in-human-skin-reveal-altered-immune-function-and-burden-of-infection
#5
Chun Wu, Xiaopan Chen, Jing Shu, Chun-Ting Lee
Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424262/magnesium-reduces-hepatic-lipid-accumulation-in-yellow-catfish-pelteobagrus-fulvidraco-and-modulates-lipogenesis-and-lipolysis-via-ppara-jak-stat-and-ampk-pathways-in-hepatocytes
#6
Chuan-Chuan Wei, Kun Wu, Yan Gao, Li-Han Zhang, Dan-Dan Li, Zhi Luo
Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C)...
April 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28415825/recombinant-human-erythropoietin-stimulates-melanoma-tumor-growth-through-activation-of-initiation-factor-eif4e
#7
Annabelle Julius, Anjali Desai, Raymond L Yung
Recombinant human erythropoietin (EPO) is standard treatment for anemia in cancer patients. Recent clinical trials suggest that EPO may accelerate tumor progression and increase mortality. However, the evidence supporting a growth-promoting effect of EPO has remained controversial. Employing an in vivo model of B16 murine melanoma, we observed that administration of EPO to tumor bearing C57BL/6 mice resulted in pronounced acceleration of melanoma growth. Our in vitro studies demonstrate that B16 murine melanoma cells express EPOR, both at the protein and mRNA levels...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413047/a-homolog-of-teleostean-signal-transducer-and-activator-of-transcription-3-stat3-from-rock-bream-oplegnathus-fasciatus-structural-insights-transcriptional-modulation-and-subcellular-localization
#8
S D N K Bathige, William Shanthakumar Thulasitha, Navaneethaiyer Umasuthan, J D H E Jayasinghe, Qiang Wan, Bo-Hye Nam, Jehee Lee
Signal transducer and activator of transcription 3 (STAT3) is one of the crucial transcription factors in the Janus kinase (JAK)/STAT signaling pathway, and it was previously considered as acute phase response factor. A number of interleukins (ILs) such as IL-5, IL-6, IL-9, IL-10, IL-12, and IL-22 are known to be involved in activation of STAT3. In addition, various growth factors and pathogenic or oxidative stresses mediate the activation of a wide range of functions via STAT3. In this study, a STAT3 homolog was identified and functionally characterized from rock bream (RbSTAT3), Oplegnathus fasciatus...
April 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28413030/the-role-matrix-metalloproteinases-in-the-production-of-aortic-aneurysm
#9
Simon W Rabkin
Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore, AAA have evidence of inflammation and the cellular elements involved in inflammation such as macrophages can produce and/or activate MMPs This chapter focuses on human aortic aneurysm that are not due to specific known genetic causes because this type of aneurysm is the more common type...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28410228/identification-of-a-novel-functional-jak1-s646p-mutation-in-acute-lymphoblastic-leukemia
#10
Qian Li, Botao Li, Liangding Hu, Hongmei Ning, Min Jiang, Danhong Wang, Tingting Liu, Bin Zhang, Hu Chen
The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching 90%, while the prognosis of adults remains poor due to the limited therapeutic approaches. In order to identify new targets for ALL, we performed whole-exome sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two cases exhibited A639G and P960S mutations separately. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409351/inflammation-and-fibrosis-in-polycystic-kidney-disease
#11
Cheng Jack Song, Kurt A Zimmerman, Scott J Henke, Bradley K Yoder
Polycystic kidney disease (PKD) is a commonly inherited disorder characterized by cyst formation and fibrosis (Wilson, N Engl J Med 350:151-164, 2004) and is caused by mutations in cilia or cilia-related proteins, such as polycystin 1 or 2 (Oh and Katsanis, Development 139:443-448, 2012; Kotsis et al., Nephrol Dial Transplant 28:518-526, 2013). A major pathological feature of PKD is the development of interstitial inflammation and fibrosis with an associated accumulation of inflammatory cells (Grantham, N Engl J Med 359:1477-1485, 2008; Zeier et al...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28409189/daphnetin-reduces-endotoxin-lethality-in-mice-and-decreases-lps-induced-inflammation-in-raw264-7-cells-via-suppressing-jak-stats-activation-and-ros-production
#12
Lei Shen, Ting Zhou, Jing Wang, Xiumei Sang, Lei Lan, Lan Luo, Zhimin Yin
OBJECTIVE: Here, we used various approaches to investigate the suppressive role of daphnetin in LPS-induced inflammatory response, with the goal to understand the underlining molecular mechanism by which daphnetin regulated these processes. METHODS: We examined the survival rate and the lung injury in the mice model of LPS-induced endotoxemia. The production of pro-inflammatory factors including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2) was measured by ELISA and nitrite analysis, respectively...
April 13, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28404878/activation-of-liver-x-receptor-delayed-the-retinal-degeneration-of-rd1-mice-through-modulation-of-the-immunological-function-of-glia
#13
Xiao He, Dayu Sun, Siyu Chen, Haiwei Xu
Retinal degeneration (RD), including retinitis pigmentosa (RP), is an inherited eye disease characterized by progressive degeneration of photoreceptors. Recently, immune cells, including microglia, Müller cells and astrocytes, in degenerative retina are demonstrated to play key roles in the development of RD and can be used as potential therapeutic targets. Liver X receptors (LXRs) are important immuno-inflammatory response transcription factors that have been reported to be a new potential therapeutic drug target for neurodegenerative diseases...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28395559/management-of-myelofibrosis-jak-inhibition-and-beyond
#14
Maximilian Stahl, Amer M Zeidan
Myelofibrosis (MF) is characterized by bone marrow fibrosis with subsequent extramedullary hematopoiesis and abnormal cytokine expression leading to splenomegaly, constitutional symptoms and cytopenias. The discovery of the JAK2 V617F mutation in the majority of MF patients has been followed by significant progress in drug development for MF. Areas covered: In this article, we review advances in the understanding of the underlying disease biology, prognostic assessment and therapeutic modalities for MF. We provide clinical trial evidence behind using the JAK2 inhibitor ruxolitinib, erythropoiesis stimulating agents, androgens, immunomodulatory drugs, interferon, cytoreductive drugs and hypomethylating agents in MF...
April 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28393260/identification-of-biomarkers-for-schistosoma-associated-pulmonary-arterial-hypertension-based-on-rna-seq-data-of-mouse-whole-lung-tissues
#15
Yanbin Sun, Xin Lin, Lei Li
BACKGROUND: Pulmonary arterial hypertension (PAH) is a deadly disease, and the molecular mechanism of PAH has not been clarified clearly. The objective of this study was to identify possible biomarkers and explore the potential mechanisms of Schistosoma-induced PAH. METHODS: GSE49114 RNA-Seq data developed from mouse whole lung tissues were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between control samples and schistosomiasis-induced PAH samples were identified by the edgeR software...
April 9, 2017: Lung
https://www.readbyqxmd.com/read/28392989/sevoflurane-postconditioning-protects-the-myocardium-against-ischemia-reperfusion-injury-via-activation-of-the-jak2-stat3-pathway
#16
Jianjiang Wu, Jin Yu, Peng Xie, Yiliyaer Maimaitili, Jiang Wang, Long Yang, Haiping Ma, Xing Zhang, Yining Yang, Hong Zheng
BACKGROUND: Sevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2-STAT3) plays an important role in cardioprotection. The purpose of this study was to determine whether the cardioprotective effects of S-post are associated with activation of the JAK2-STAT3 signal pathway. METHODS: An adult male Sprague-Dawley (SD) rat model of myocardial ischemia/reperfusion (I/R) injury was established using the Langendorff isolated heart perfusion apparatus...
2017: PeerJ
https://www.readbyqxmd.com/read/28390952/hypothyroidism-decreases-jak-stat-signaling-pathway-in-lactating-rat-mammary-gland
#17
Fiorella Campo Verde Arboccó, Fabio Andres Persia, María Belén Hapon, Graciela A Jahn
Thyroid pathologies have deleterious effects on lactation. Especially hypothyroidism (HypoT) induces premature mammary involution at the end of lactation and decreases milk production and quality in mid lactation. Milk synthesis is controlled by JAK2/STAT5 signaling pathway and prolactin (PRL), which activates the pathway. In this work we analyzed the effect of chronic 6-propyl-2- thiouracil (PTU)-induced HypoT on PRL signaling pathway on mammary glands from rats on lactation (L) days 2, 7 and 14. HypoT decreased prolactin receptor expression, and expression and activation of Stat5a/b protein...
April 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28390197/hdac8-overexpression-in-mesenchymal-stromal-cells-from-jak2-myeloproliferative-neoplasms-a-new-therapeutic-target
#18
Teresa L Ramos, Luis Ignacio Sánchez-Abarca, Alba Redondo, Ángel Hernández-Hernández, Antonio M Almeida, Noemí Puig, Concepción Rodríguez, Rebeca Ortega, Silvia Preciado, Ana Rico, Sandra Muntión, José Ramón González Porras, Consuelo Del Cañizo, Fermín Sánchez-Guijo
Histone deacetylases (HDACs) are involved in epigenetic modulation and their aberrant expression has been demonstrated in myeloproliferative neoplasms (MPN). HDAC8 inhibition has been shown to inhibit JAK2/STAT5 signaling in hematopoietic cells from MPN. Nevertheless, the role of HDAC8 expression in bone marrow-mesenchymal stromal cells (BM-MSC) has not been assessed. In the current work we describe that HDAC8 is significantly over-expressed in MSC from in JAK-2 positive MPN compared to those from healthy-donors (HD-MSC)...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28370306/is-allogeneic-stem-cell-transplantation-for-myelofibrosis-still-indicated-at-the-time-of-molecular-markers-and-jak-inhibitors-era
#19
Elsa Lestang, Pierre Peterlin, Yannick Le Bris, Viviane Dubruille, Jacques Delaunay, Catherine Godon, Olivier Theisen, Nicolas Blin, Beatrice Mahe, Thomas Gastinne, Alice Garnier, Cyrille Touzeau, Maud Voldoire, Marie C Bene, Steven Le Gouill, Noel Milpied, Mohamad Mohty, Philippe Moreau, Thierry Guillaume, Patrice Chevallier
OBJECTIVE: The role of allogenic stem cell transplantation (ASCT) is still debated in myelofibrosis. METHOD: A retrospective analyzed was performed to compare the outcome of 71 patients with intermediate-2 or high-risk Dynamic International Prognosis Scoring System+ (DIPSS+) primary (PMF) or secondary (SMF) myelofibrosis with an indication of ASCT as they ultimately underwent the procedure (n=34) or not (n=37). RESULTS: Five-year overall survival (OS) was not statistically different between both groups (allograft: 52% vs no allograft: 34%, p=0,12)...
March 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28369102/abnormal-repression-of-shp-1-shp-2-and-socs-1-transcription-sustains-the-activation-of-the-jak-stat3-pathway-and-the-progression-of-the-disease-in-multiple-myeloma
#20
Asma Beldi-Ferchiou, Nour Skouri, Cyrine Ben Ali, Ines Safra, Abderrahman Abdelkefi, Saloua Ladeb, Karima Mrad, Tarek Ben Othman, Mélika Ben Ahmed
Sustained activation of JAK/STAT3 signaling pathway is classically described in Multiple Myeloma (MM). One explanation could be the silencing of the JAK/STAT suppressor genes, through the hypermethylation of SHP-1 and SOCS-1, previously demonstrated in MM cell lines or in whole bone marrow aspirates. The link between such suppressor gene silencing and the degree of bone marrow invasion or the treatment response has not been evaluated in depth. Using real-time RT-PCR, we studied the expression profile of three JAK/STAT suppressor genes: SHP-1, SHP-2 and SOCS-1 in plasma cells freshly isolated from the bone marrows of MM patients and healthy controls...
2017: PloS One
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