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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
#1
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/28425456/salt-suppresses-ifn%C3%AE-inducible-chemokines-through-the-ifn%C3%AE-jak1-stat1-signaling-pathway-in-proximal-tubular-cells
#2
Yohei Arai, Daiei Takahashi, Kenichi Asano, Masato Tanaka, Mayumi Oda, Shigeru B H Ko, Minoru S H Ko, Shintaro Mandai, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible for salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed...
April 20, 2017: Scientific Reports
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
#3
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/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#4
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28415722/stat3-phosphorylation-is-required-for-embryonic-stem-cells-ground-state-maintenance-in-2i-culture-media
#5
Dan Wang, Hui Sang, Kaiyue Zhang, Yan Nie, Shuang Zhao, Yan Zhang, Ningning He, Yuebing Wang, Yang Xu, Xiaoyan Xie, Zongjin Li, Na Liu
Embryonic stem cells (ES cells) can be maintained its undifferentiated state with feeder cells or LIF, which can activate Jak/Stat3 pathway. Recently, it has been reported a new culture condition comprising serum-free medium with ERK and GSK3β inhibitors (2i) could drive ES cells into a state of pluripotency more like inner cell mass (ICM) in mouse blastocysts called ground state. However, although 2i could sustain ES cells self-renewal, LIF is routinely added. The roles of Stat3 activation are still unclear now...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411130/ifitm1-suppression-blocks-proliferation-and-invasion-of-aromatase-inhibitor-resistant-breast-cancer-in%C3%A2-vivo-by-jak-stat-mediated-induction-of-p21
#6
Asona J Lui, Eric S Geanes, Joshua Ogony, Fariba Behbod, Jordan Marquess, Kelli Valdez, William Jewell, Ossama Tawfik, Joan Lewis-Wambi
Interferon induced transmembrane protein 1 (IFITM1) belongs to a family of interferon stimulated genes (ISGs) that is associated with tumor progression and DNA damage resistance, however, its role in endocrine resistance is not known. Here, we correlate IFITM1 expression with clinical stage and poor response to endocrine therapy in a tissue microarray consisting of 94 estrogen receptor (ER)-positive breast tumors. IFITM1 overexpression is confirmed in the AI-resistant MCF-7:5C cell line and not found in AI-sensitive MCF-7 cells...
April 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28410228/identification-of-a-novel-functional-jak1-s646p-mutation-in-acute-lymphoblastic-leukemia
#7
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/28405527/jak-stat-mediated-chronic-inflammation-impairs-cytotoxic-t-lymphocyte-activation-to-decrease-anti-pd-1-immunotherapy-efficacy-in-pancreatic-cancer
#8
Chunwan Lu, Asif Talukder, Natasha M Savage, Nagendra Singh, Kebin Liu
Human pancreatic cancer does not respond to immune check point blockade immunotherapy. One key feature of pancreatic cancer is the association between its progression and chronic inflammation. Emerging evidence supports a key role for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL activity in pancreatic cancer. We show that human pancreatic carcinomas express high level of PD-L1 and exhibit low level of CTL infiltration...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28402197/minimal-residual-disease-or-cure-in-mpns-rationales-and-perspectives-on-combination-therapy-with-interferon-alpha2-and-ruxolitinib
#9
Mads Emil Bjørn, Hans Carl Hasselbalch
The therapeutic landscape of the Philadelphia-negative myeloproliferative neoplasms (MPNs) is markedly changing consequent to the development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with myelofibrosis (MF) and patients with polycythemia vera (PV) who develop refractoriness or intolerance to hydroxyurea. The use of Interferon-alpha2 (IFN) is rapidly expanding in several countries, based upon favourable safety and efficacy profiles in several single-arm studies during the last 30 years, displaying complete hematological remissions in a large proportion of patients, a reduction in the JAK2V617 F and CALR mutational burden and in a subset of patients with PV with normalisation of the bone marrow after long-term treatment - even being sustained for several years after discontinuation of IFN...
April 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28398275/natural-killer-t-cell-lymphomas-in-pediatric-and-adolescent-patients
#10
REVIEW
Amanda M Termuhlen
Natural killer/T-cell (NK/T-cell) lymphomas are rare in children and adolescents and consist predominantly of nasal-type extranodal NK/T-cell lymphomas. More than half of pediatric/adolescent patients with NK/T-cell lymphomas present with localized nasal/sinus involvement, but the disease may involve many organs. NK/T-cell lymphoma cells are cytotoxic and associated with necrosis and angioinvasion; they express CD56, CD2, cytoplasmic CD3 epsilon, and to a variable degree CD30. The cells contain Epstein-Barr virus (EBV)-encoded RNA...
March 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28395559/management-of-myelofibrosis-jak-inhibition-and-beyond
#11
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/28394822/janus-kinase-signal-transducer-and-activator-of-transcription-pathways-in-spondyloarthritis
#12
Smriti K Raychaudhuri, Siba P Raychaudhuri
PURPOSE OF REVIEW: Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway represents a group of several intracellular molecules with a key role in signal pathways activated by growth factors and cytokines. These kinase proteins are associated with the signaling process of multiple key cytokines, which regulates various T-cell subpopulations and their effector cytokines...
April 7, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28392989/sevoflurane-postconditioning-protects-the-myocardium-against-ischemia-reperfusion-injury-via-activation-of-the-jak2-stat3-pathway
#13
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
#14
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
#15
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/28389709/-familial-chilblain-lupus-type-1-interferonopathy-with-model-character
#16
REVIEW
C Fiehn
Familial chilblain lupus belongs to the group of type 1 interferonopathies and is particularly characterized by typical skin manifestations and ischemia of the acra. There are various mutations that can lead to this autosomal dominant disease. A mutation in the TREX-1 gene has been most frequently found; however, families with mutations in the SAMHD1 gene and recently in the gene which codes for the stimulator of interferon genes (STING) protein were also described. A common feature of these genetic defects is that they are all involved in the process of detection of intracellular free DNA, which as a result leads to increased production of type 1 interferons and the induced gene products...
April 7, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28382662/successful-targeted-treatment-of-mast-cell-activation-syndrome-with-tofacitinib
#17
Lawrence B Afrin, Roger W Fox, Susan L Zito, Leo Choe, Sarah C Glover
Mast cell (MC) activation syndrome (MCAS) is a collection of illnesses of inappropriate MC activation with little to no neoplastic MC proliferation, distinguishing it from mastocytosis. MCAS presents as chronic, generally inflammatory multisystem polymorbidity likely driven in most by heterogeneous patterns of constitutively activating mutations in MC regulatory elements, posing challenges for identifying optimal mutation-targeted treatment in individual patients. Targeting commonly affected downstream effectors may yield clinical benefit independent of upstream mutational profile...
April 6, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28378336/review-of-treatment-for-alopecia-totalis-and-alopecia-universalis
#18
REVIEW
Sama Kassira, Dorota Z Korta, Lance W Chapman, Francis Dann
Alopecia areata (AA) is an autoimmune disease directed at the hair follicle. Although usually limited to patchy hair loss over the scalp (focalis), AA can present as total loss of scalp hair (totalis; AT) or as total loss of both scalp and body hair (universalis; AU). Management of AT and AU can be challenging, and although multiple treatment modalities have been explored, no therapy is currently FDA-approved. This review focuses on the evidence for current treatment options for AT and AU. The PubMed database was searched from January 1, 2000, to September 1, 2016, for clinical trials, retrospective studies, and case reports of treatments for AT and AU...
April 5, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28371605/microrna-294-promotes-cellular-proliferation-and-motility-through-the-pi3k-akt-and-jak-stat-pathways-by-upregulation-of-nras-in-bladder-cancer
#19
Yongwei Li, Zhengfei Shan, Chu Liu, Diandong Yang, Jitao Wu, Changping Men, Yankai Xu
In our study we examined the role of microRNA-294 (miR-294) in bladder cancer and related mechanisms. Real-time polymerase chain reaction (RT-PCR) was performed to determine the expression level of miR-294. Western blot was used to determine the expression of NRAS, mainly factors in the PI3K/AKT and JAK/STAT pathways. Cell counting kit-8 assay, clonogenic assay, wound-healing assay, transwell and flow cytometry were used to explore, respectively, cell proliferation, survival, migration, invasion, and apoptosis of bladder cancer cell line T24...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28371574/tofacitinib-suppresses-disease-activity-and-febrile-attacks-in-a-patient-with-coexisting-rheumatoid-arthritis-and-familial-mediterranean-fever
#20
Kevser Gök, Gizem Cengiz, Kemal Erol, Salih Ozgocmen
Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA)...
January 2017: Acta Reumatológica Portuguesa
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