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https://www.readbyqxmd.com/read/28339658/acute-cell-volume-regulation-by-janus-kinase-2-mediated-sodium-hydrogen-exchange-activation-develops-at-the-late-one-cell-stage-in-mouse-preimplantation-embryos%C3%A2
#1
Baozeng Xu, Chenxi Zhou, Megan Meredith, Jay M Baltz
Early preimplantation embryos are extremely sensitive to dysregulation of cell volume, which can lead to developmental arrest. It was previously shown that mouse embryos at the two-cell stage respond to a cell volume decrease by quickly activating Na+/H+ exchange via a signaling mechanism that involves the tyrosine kinase Janus kinase 2 (JAK2). However, it was not known whether this mechanism is active at the one-cell stage, when embryos are most sensitive to perturbed cell volume. Na+/H+ exchanger activity elicited by an induced cell volume decrease was significantly lower at the mid one-cell stage than at the late one-cell stage or during the two-cell stage...
February 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28337870/jak2-tyrosine-kinase-inhibitor-ag490-suppresses-cell-growth-and-invasion-of-gallbladder-cancer-cells-via-inhibition-of-jak2-stat3-signaling
#2
L X Fu, Q W Lian, J D Pan, Z L Xu, T M Zhou, B Ye
The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) have displayed a critical role in tumor development and progression in multiple malignancies. Previous studies showed that inhibition of JAK/STAT signaling blocked cell growth and metastasis in cancer cells, however, the antitumor effects of JAK inhibitor AG490 on gallbladder cancer (GBC) have not been reported. Our present study aimed to investigate the effects and associated mechanisms of JAK inhibitor AG490 on cell growth, invasive potential and apoptosis in GBC cells (GBC-SD and SGC-996) indicated by MTT, cell colony formation, Transwell and flow cytometry...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28336920/xiaoyaosan-exerts-anxiolytic-like-effects-by-down-regulating-the-tnf-%C3%AE-jak2-stat3-pathway-in-the-rat-hippocampus
#3
Xiao-Juan Li, Qing-Yu Ma, You-Ming Jiang, Xiao-Hui Bai, Zhi-Yi Yan, Qun Liu, Qiu-Xia Pan, Yue-Yun Liu, Jia-Xu Chen
Although the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor-α (TNF-α) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF-α/JAK2-STAT3 pathway in the hippocampus...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336526/identification-of-unipotent-megakaryocyte-progenitors-in-human-hematopoiesis
#4
Kohta Miyawaki, Hiromi Iwasaki, Takashi Jiromaru, Hirotake Kusumoto, Ayano Yurino, Takeshi Sugio, Yasufumi Uehara, Jun Odawara, Shinya Daitoku, Yuya Kunisaki, Yasuo Mori, Yojiro Arinobu, Hirofumi Tsuzuki, Yoshikane Kikushige, Tadafumi Iino, Koji Kato, Katsuto Takenaka, Toshihiro Miyamoto, Takahiro Maeda, Koichi Akashi
The developmental pathway for human megakaryocytes remains unclear and the definition of pure unipotent megakaryocyte progenitor is still controversial. Using single-cell transcriptome analysis, we have identified a cluster of cells within immature hematopoietic stem and progenitor cell populations that specifically express genes related to the megakaryocyte lineage. We used CD41 as a positive marker to identify these cells within the CD34(+)CD38(+)IL-3Rα(dim)CD45RA(-) common myeloid progenitor (CMP) population...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#5
Yue Wang, Zhihua Han, Yuqi Fan, Junfeng Zhang, Kan Chen, Lin Gao, Huasu Zeng, Jiatian Cao, Changqian Wang
BACKGROUND/AIMS: MicroRNA-9 (miR-9) is involved in inflammatory reaction in atherosclerosis; however, its function and regulatory mechanisms remain unclear. We aimed to uncover the exact roles of miR-9 and downstream signaling pathways using in vitro human atherosclerosis models. METHODS: We used oxidized low-density lipoprotein (oxLDL)-stimulated human THP-1 derived macrophages, oxLDL-stimulated human primary peripheral blood monocytes and lipopolysaccharides (LPS) or Alum-stimulated human THP-1 derived macrophages as in vitro atherosclerosis inflammation models...
March 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28333291/corrigendum-the-future-of-janus-kinase-inhibitors-in-inflammatory-bowel-disease
#6
(no author information available yet)
No abstract text is available yet for this article.
March 9, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332288/tetrandrine-an-agonist-of-aryl-hydrocarbon-receptor-reciprocally-modulates-the-activities-of-stat3-and-stat5-to-suppress-th17-cell-differentiation
#7
Xusheng Yuan, Yannong Dou, Xin Wu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid constituent of the root of Stephania tetrandra S. Moore, was previously shown to suppress the differentiation of T helper 17 (Th17) cells and consequently ameliorate the collagen-induced arthritis (CIA) in mice by activating the aryl hydrocarbon receptor (AhR), but its underlying mechanism is incompletely understood. Here, we investigated how tetrandrine suppressed Th17 cell differentiation through the AhR pathway. The naïve CD4(+) T cells were stimulated with anti-CD3/CD28 for 72 hrs in the presence or absence of tetrandrine under the Th17-polarizing condition...
March 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28330758/regulation-of-type-i-interferon-signaling-in-immunity-and-inflammation-a-comprehensive-review
#8
REVIEW
Kun Chen, Juan Liu, Xuetao Cao
Type I interferons (IFNs) play essential roles in establishing and modulating host defense against microbial infection via induction of IFN-stimulated genes (ISGs) through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. However, dysregulation of IFNs production and function could also mediate immune pathogenesis such as inflammatory autoimmune diseases and infectious diseases via aberrantly activating inflammatory responses or improperly suppressing microbial controls...
March 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28329404/tofacitinib-in-the-treatment-of-rheumatoid-arthritis-and-chronic-plaque-psoriasis
#9
A K Gupta, M Cernea, C W Lynde
Tofacitinib is an oral immunosuppressant approved for the treatment of rheumatoid arthritis (RA) and is currently undergoing investigation (Phase III trials) for treating chronic plaque psoriasis. Tofacitinib inhibits Janus kinases (JAKs), which are essential for the signaling of multiple inflammatory pathways and have been implicated in the pathogenesis of RA and psoriasis. The efficacy and safety of tofacitinib in the treatment of RA and psoriasis have been demonstrated in Phase III trials. Across all studies, the efficacy of tofacitinib in alleviating symptoms of RA and psoriasis were superior to placebo...
March 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28323260/mechanisms-and-consequences-of-jak-stat-signaling-in-the-immune-system
#10
REVIEW
Alejandro V Villarino, Yuka Kanno, John J O'Shea
Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced breakneck growth in the quarter century since its discovery and has yielded a stream of basic and clinical insights that have profoundly influenced modern understanding of human health and disease, exemplified by the bench-to-bedside success of Jak inhibitors ('jakinibs') and pathway-targeting drugs...
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28317328/evaluating-dosage-optimality-for-tofacitinib-an-oral-janus-kinase-inhibitor-in-plaque-psoriasis-and-the-influence-of-body-weight
#11
M M Hutmacher, K Papp, S Krishnaswami, K Ito, H Tan, R Wolk, H Valdez, C Mebus, S T Rottinghaus, P Gupta
Tofacitinib is an oral Janus kinase inhibitor. An integrated analysis was conducted to evaluate dosage optimality for tofacitinib in patients with moderate-to-severe plaque psoriasis and the impact of body weight on optimality in this patient population. Data were pooled from one phase IIb trial (2, 5, and 15 mg twice daily (b.i.d.)) and four phase III trials (5 and 10 mg b.i.d.). A longitudinal exposure-response model for Psoriasis Area and Severity Index (PASI) improvement (percent change from baseline) was established...
March 20, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28315704/interleukin-6-and-prostate-cancer-current-developments-and-unsolved-questions
#12
Zoran Culig, Martin Puhr
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models...
March 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28301084/the-effect-of-verapamil-a-p-glycoprotein-inhibitor-on-the-pharmacokinetics-of-peficitinib-an-orally-administered-once-daily-jak-inhibitor
#13
Tong Zhu, Corrie Howieson, Tomasz Wojtkowski, Jay P Garg, David Han, Ogert Fisniku, James Keirns
Peficitinib is an orally administered, once-daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P-glycoprotein (P-gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P-gp, on the pharmacokinetic profile of peficitinib were assessed in this open-label, single-center, single-sequence, crossover drug-interaction study. Twenty-four healthy volunteers received a single 150-mg dose of peficitinib on days 1 and 12 of a 14-day treatment period and received verapamil 80 mg 3 times daily on days 5-14...
March 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28300440/review-of-atopic-dermatitis-and-topical-therapies
#14
Julia N Mayba, Melinda J Gooderham
Atopic dermatitis is one of the most common skin disorders in the developed world, affecting up to 20% of children and 1% to 3% of adults. This review concisely explains the pathophysiology and epidemiology of atopic dermatitis, as well as potential challenges facing its successful treatment. Furthermore, mainstay topical treatment modalities are evaluated, such as emollients, topical corticosteroids, and topical calcineurin inhibitors. The use of topical corticosteroids and topical calcineurin inhibitors in combination is discussed, as studies have indicated encouraging results...
December 1, 2016: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28296539/high-salt-induced-activation-and-expression-of-inflammatory-cytokines-in-cultured-astrocytes
#15
Zhezhi Deng, Yuge Wang, Li Zhou, Yilong Shan, Sha Tan, Wei Cai, Siyuan Liao, Lisheng Peng, Zhengqi Lu
Salt (sodium chloride, NaCl) accumulation in the brain is associated with various diseases of central nervous system (CNS). Activation of astrocytes is an important manifestation of pathophysiological processes in the CNS. However, the direct impact of high salt (HS) environment on astrocytes is unclear. In the current study, we found that high salt treatment can induce activation of astrocytes both in vivo and in vitro, manifested as morphological alteration coupled with increased expression of glial fibrillary acidic protein (GFAP)...
March 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28294642/cost-effectiveness-of-sequenced-treatment-of-rheumatoid-arthritis-with-targeted-immune-modulators
#16
Jeroen P Jansen, Devin Incerti, Alex Mutebi, Desi Peneva, Joanna MacEwan, Bradley Stolshek, Primal Kaur, Mahdi Gharaibeh, Vibeke Strand
AIMS: To determine the cost-effectiveness of treatment sequences of biologic disease-modifying antirheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) versus conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs. MATERIALS AND METHODS: We developed an individual patient simulation model that assesses the impact of treatments on disease based on clinical trial data and real-world evidence...
March 15, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28293189/investigation-into-the-role-of-pi3k-and-jak3-kinase-inhibitors-in-murine-models-of-asthma
#17
Akshaya D Wagh, Manoranjan Sharma, Jogeshwar Mahapatra, Abhijeet Chatterjee, Mukul Jain, Veeranjaneyulu Addepalli
Asthma is a clinical disorder commonly characterized by chronic eosinophilic inflammation, remodeling and hyper responsiveness of the airways. However, the kinases like Phosphoinositide 3 kinase (PI3K) and Janus kinase 3 (JAK3) are involved in mast cell proliferation, activation, recruitment, migration, and prolonged survival of inflammatory cells. The present study was designed to evaluate the in-vivo comparative effects of two kinase inhibitors on airway inflammation and airway remodeling in acute and chronic models of asthma...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28290136/baricitinib-first-global-approval
#18
Anthony Markham
Baricitinib (Olumiant™) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus. JAKs transduce intracellular signals from cell surface receptors for various cytokines and growth factors involved in inflammation and immune function, suggesting JAK inhibitors may be of therapeutic benefit in inflammatory conditions. In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs)...
March 13, 2017: Drugs
https://www.readbyqxmd.com/read/28289331/screening-of-breast-cancer-stem-cell-inhibitors-using-a-protein-kinase-inhibitor-library
#19
Hack Sun Choi, Dal-Ah Kim, Heesung Chung, In Ho Park, Bo Hye Kim, Eok-Soo Oh, Duk-Hee Kang
BACKGROUND: Cancer stem cells (CSCs), a subpopulation in tumors, are known to cause drug resistance, tumor recurrence and metastasis. Based on the characteristic formation of mammospheres in in vitro conditions, the mammosphere formation assay has become an essential tool for quantifying CSC activity in breast cancer research. However, manual counting of mammospheres is a time-consuming process that is not amenable to high-throughput screening, and there are occasional inaccuracies in the process of determining the mammosphere diameter...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28284718/novel-jak3-activating-mutations-in-extranodal-nk-t-cell-lymphoma-nasal-type
#20
Sung H Sim, Soyeon Kim, Tae M Kim, Yoon K Jeon, Soo J Nam, Yong-Oon Ahn, Bhumsuk Keam, Hyun H Park, Dong-Wan Kim, Chul W Kim, Dae S Heo
Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3(A573V), two JAK3(H583Y), and one JAK3(G589D) mutation...
March 8, 2017: American Journal of Pathology
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