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jak 2

Kirstin Harling, Ernest Adankwah, Alptekin Güler, Anthony Afum-Adjei Awuah, Louis Adu-Amoah, Ertan Mayatepek, Ellis Owusu-Dabo, Norman Nausch, Marc Jacobsen
T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases...
March 19, 2018: Cellular & Molecular Immunology
Hans Michael Kvasnicka, Jürgen Thiele, Carlos E Bueso-Ramos, William Sun, Jorge Cortes, Hagop M Kantarjian, Srdan Verstovsek
BACKGROUND: Myelofibrosis (MF) is a life-shortening complication of myeloproliferative neoplasms associated with ineffective hematopoiesis, splenomegaly, and progressive bone marrow (BM) fibrosis. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has been shown to improve splenomegaly, symptom burden, and overall survival in patients with intermediate-2 or high-risk MF compared with placebo or best available therapy (BAT). METHODS: The effects of ruxolitinib therapy for up to 66 months on BM morphology in 68 patients with advanced MF with variable BM fibrosis grade were compared with those in 192 matching patients treated with BAT...
March 15, 2018: Journal of Hematology & Oncology
Q N Yu, Y B Guo, X Li, C L Li, W P Tan, X L Fan, Z L Qin, D Chen, W P Wen, S G Zheng, Q L Fu
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. METHODS: The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated...
March 15, 2018: Allergy
Luchao Chen, Zhongxia Lu, Yongle Yang, Lijun Du, Xiaofang Zhou, Yitao Chen
Gastric cancer is one of the most common cancers globally with high rates of morbidity and mortality. Purified Omphalia lapidescens protein (pPe O p) is a protein extracted from the sclerotium of Omphalia lapidescens . The present study aimed to investigate the effects of pPe O p on the viability, migration, cell cycle progression and apoptosis of SGC-7901 cells. The expression of numerous proteins, namely matrix metallopeptidase (MMP)2, MMP9, p53, caspase-3, B-cell lymphoma (Bcl)-2, cyclin A2, cyclin B1, cyclin D1, cyclin dependent kinase (CDK)1, CDK2 and CDK4, were investigated using western blot analysis and reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Yasutaka Mitamura, Satoshi Nunomura, Yasuhiro Nanri, Masahiro Ogawa, Tomohito Yoshihara, Miho Masuoka, Gaku Tsuji, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Simon J Conway, Masutaka Furue, Kenji Izuhara
BACKGROUND: Barrier dysfunction is an important feature of atopic dermatitis (AD) in which IL-4 and IL-13, signature type 2 cytokines, are involved. Periostin, a matricellular protein induced by IL-4 or IL-13, plays a crucial role in the onset of allergic skin inflammation, including barrier dysfunction. However, it remains elusive how periostin causes barrier dysfunction downstream of the IL-13 signal. METHODS: We systematically identified periostin-dependent expression profile using DNA microarrays...
March 12, 2018: Allergy
Xiaoxu Chen, Xiaoke Nie, Jiamin Mao, Yan Zhang, Kaizhi Yin, Shengyang Jiang
Perfluorooctanesulfonate (PFOS)-containing compounds are widely used in all aspects of industrial and consumer products. Recent studies indicated that PFOS is ubiquitous in environments and is considered to be a new type of persistent organic pollutant (POP). This has raised concerns regarding its adverse effects on human health. The nervous system is regarded as a sensitive target of environmental contaminants, including PFOS. Previous findings showed that PFOS can induce neurobehavioral deficits. However, the molecular mechanism underlying PFOS neurotoxicity remains obscure...
March 8, 2018: Neurotoxicology
John Mascarenhas, Ronald Hoffman, Moshe Talpaz, Aaron T Gerds, Brady Stein, Vikas Gupta, Anita Szoke, Mark Drummond, Alexander Pristupa, Tanya Granston, Robert Daly, Suliman Al-Fayoumi, Jennifer A Callahan, Jack W Singer, Jason Gotlib, Catriona Jamieson, Claire Harrison, Ruben Mesa, Srdan Verstovsek
Importance: Myelofibrosis is a hematologic malignancy characterized by splenomegaly and debilitating symptoms. Thrombocytopenia is a poor prognostic feature and limits use of Janus kinase 1 (JAK1)/Janus kinase 2 (JAK2) inhibitor ruxolitinib. Objective: To compare the efficacy and safety of JAK2 inhibitor pacritinib with that of best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis and thrombocytopenia. Design, Setting, and Participants: For this phase 3 randomized international multicenter study-the PERSIST-2 study-of pacritinib vs BAT, 311 patients with myelofibrosis and platelet count 100 × 109/L or less were recruited for analysis...
March 8, 2018: JAMA Oncology
Yu Shuang Tian, Di Zhong, Qing Qing Liu, Xiu Li Zhao, Hong Xue Sun, Jing Jin, Hai Ning Wang, Guo Zhong Li
OBJECTIVE Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke-related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke...
March 9, 2018: Journal of Neurosurgery
Ana Paula Toniazzo, Danusa M Arcego, Camilla Lazzaretti, Carine Lampert, Simone N Weis, Rodrigo Proto-Siqueira, Rachel Krolow, Carla Dalmaz
OBJECTIVE: Both stress exposure and high-fat diet (HFD) are contributors to the alarming prevalence of obesity. Leptin is secreted from adipose tissue and regulates appetite and body weight via the JAK-STAT3 pathway in the hypothalamus; it also regulates the hypothalamic-pituitary-thyroid axis, modulating energy homeostasis. Leptin signaling may be impaired by HFD intake, and here we investigate whether social isolation during the prepubertal period, associated with chronic HFD, can exert long-term effects on metabolic parameters in a sex-specific manner...
November 29, 2017: Nutrition
Xian-Tao Zeng, Xiao-Ping Liu, Tong-Zu Liu, Xing-Huan Wang
The present study was aimed to investigate the relationship between the expression of collagen type V alpha 2 chain (COL5A2) and clinical outcomes of patients with bladder cancer.Chi-square test and log-rank-based survival analysis were performed to assess the correlation of COL5A2 expression with clinical characteristics and survivals of patients with bladder cancer using GSE13507. Gene set enrichment analysis was conducted to study the relevant mechanisms.Bladder cancer patients in COL5A2 low expression group were associated with better invasiveness (P < ...
March 2018: Medicine (Baltimore)
Patrick M Harrington, Claire N Harrison
The outlook for patients with myeloproliferative neoplasms, particularly myelofibrosis, has improved in recent years, with greater understanding of the pathogenesis and the subsequent development of a plethora of new agents. Areas covered: This article will discuss some of the advances in the field in recent years and explore in greater detail some of the most advanced emerging agents as well as those with greatest potential. An extensive literature review has been performed to identify recent clinical trials and any relevant pre-clinical work...
March 8, 2018: Expert Review of Hematology
P Zhang, W Zhang, D Zhang, M Wang, R Aprecio, N Ji, O Mohamed, Y Li, Y Ding, Q Wang
BACKGROUND AND OBJECTIVE: Periodontitis is an increasingly prevalent complication of diabetes mellitus (known as diabetes mellitus-associated periodontitis), and 25-hydroxyvitamin D3 (25VD3 ) was recently found to be a critical regulator of innate immunity in this disease, but the underlying mechanisms remain poorly understood. T-cell protein tyrosine phosphatase non-receptor type 2 (PTPN2) is a potential downstream protein of the 25VD3 /vitamin D receptor pathway. The aim of this study was to investigate the regulation of PTPN2 in periodontal inflammation in diabetes mellitus-associated periodontitis...
March 8, 2018: Journal of Periodontal Research
Ling Wang, Zongliang Jiang, Delun Huang, Jingyue Duan, Chang Huang, Shannon Sullivan, Kaneha Vali, Yexuan Yin, Ming Zhang, Jill Wegrzyn, Xiuchun Cindy Tian, Young Tang
BACKGROUND: The generation of induced pluripotent stem cells (iPSCs) has underdefined mechanisms. In addition, leukemia inhibitory factor (LIF) activated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is the master regulator for naïve-state pluripotency achievement and maintenance. However, the regulatory process to attain naïve pluripotent iPSCs is not well understood. RESULTS: We performed transcriptome analysis to dissect the genomic expression during mouse iPSC induction, with or without blocking the JAK/STAT3 activity...
March 6, 2018: BMC Genomics
Thai Hoa Tran, Marian H Harris, Jonathan V Nguyen, Traci M Blonquist, Kristen E Stevenson, Eileen Stonerock, Barbara L Asselin, Uma H Athale, Luis A Clavell, Peter D Cole, Kara M Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A Schorin, Jennifer J G Welch, Shalini C Reshmi, Donna S Neuberg, Stephen E Sallan, Mignon L Loh, Lewis B Silverman
Recurrent chromosomal rearrangements carry prognostic significance in pediatric B-lineage acute lymphoblastic leukemia (B-ALL). Recent genome-wide analyses identified a high-risk B-ALL subtype characterized by a diverse spectrum of genetic alterations activating kinases and cytokine receptor genes. This subtype is associated with a poor prognosis when treated with conventional chemotherapy but has demonstrated sensitivity to the relevant tyrosine kinase inhibitors. We sought to determine the frequency of kinase-activating fusions among National Cancer Institute (NCI) high-risk, Ph-negative, B-ALL patients enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-001 and to describe their associated clinical characteristics and outcomes...
March 13, 2018: Blood Advances
Huifeng Yue, Wei Yan, Xiaotong Ji, Yingying Zhang, Guangke Li, Nan Sang
Previous studies have indicated that nitrogen dioxide (NO2 ) exposure could increase airway sensitivity to allergens for children. Recently, fetal stress was proposed as a crucial factor for allergic airway response occurring in offspring. Considering that there is inadequate evidence linking maternal NO2 exposure to offspring airway sensitivity to allergens, pregnant Balb/c mice were exposed daily to 2.5 ppm NO2 throughout the gestation period; then, the offspring were challenged to an allergen (ovalbumin, OVA) to evaluate airway sensitivity...
February 21, 2018: Chemosphere
Laura Gómez-Virgilio, Gerardo Bernabé Ramírez-Rodríguez, Carmen Sánchez-Torres, Leonardo Ortiz-López, Marco Antonio Meraz-Ríos
Neurogenesis plays a significant role during adulthood, and the observation that neural stem cells reside in the central nervous system and the olfactory epithelium has attracted attention due to their importance in neuronal regeneration. In addition, soluble factors (SFs) release by neural stem cells may modulate the neurogenic process. Thus, in this study, we identified the SFs released by olfactory human neural stem/progenitor cells (hNS/PCs-OE). These cells express Ki67, nestin, and βIII-tubulin, indicating their neural lineage...
March 1, 2018: Molecular Neurobiology
Min Cheng, Yuqiang Niu, Jingjing Fan, Xiaojing Chi, Xiuying Liu, Wei Yang
Induction of interferons (IFNs) is a central event of antiviral innate immunity. As crucial post-transcriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimulation, the detailed mechanisms of these miRNAs in the antiviral response is underexplored and of great significance. Here, we show that hsa-miR-1225-3p is specifically downregulated by type I IFN through IFN/JAK/STAT signaling pathway...
March 1, 2018: Journal of Biological Chemistry
Noriyoshi Iriyama, Hiromichi Takahashi, Katsuhiro Miura, Yoshihito Uchino, Masaru Nakagawa, Yoshihiro Hatta, Masami Takei
We investigated the effects of dasatinib on natural killer (NK) cell-induced signaling protein and perforin expression as well as plasma cytokine levels by analyzing blood samples from patients with well-controlled chronic myeloid leukemia receiving tyrosine kinase inhibitor (TKI) therapy. Perforin expression and phosphorylation of signal transducer and activator of transcription (STAT) 1, STAT3, Janus kinase (JAK) 1, and JAK2 in NK cells were evaluated by flow cytometry, and the levels of plasma cytokines, including interferon (IFN)-γ and interleukin (IL)-2, were determined by enzyme-linked immunosorbent assays in 40 patients (dasatinib, n = 23; imatinib, n = 11; and nilotinib, n = 6)...
February 24, 2018: Leukemia Research
Sarah Hintermair, Elisabeth Zwickl-Traxler, Martin Pecherstorfer, Josef Singer
Myeloproliferative neoplasms (MPN), classified as polycythemia vera (PV), essential thrombocytosis (ET) and myelofibrosis (MF) are stem-cell derived disorders. Mutations in either the januskinase-2 (JAK-2) or the calreticulin (CALR) gene are characteristic for MPN and may result in enhanced proliferation of red blood cells, white blood cells and platelets, and thus increase the risk for vascular events. This study is a retrospective and descriptive analysis of records of patients, who underwent treatment for myeloproliferative syndromes at the Department of Hemato-Oncology of the University hospital Krems from 2008 to the end of 2015...
February 2, 2018: Oncotarget
Qi Zhang, Ce Shi, Lina Han, Nitin Jain, Kathryn G Roberts, Helen Ma, Tianyu Cai, Antonio Cavazos, Yoko Tabe, Rodrigo O Jacamo, Hong Mu, Yang Zhao, Jing Wang, Shuo-Chieh Wu, Fenglin Cao, Zhihong Zeng, Jin Zhou, Yingchang Mi, Elias J Jabbour, Ross Levine, Sarah K Tasian, Charles G Mullighan, David M Weinstock, David A Fruman, Marina Konopleva
Patients with cytokine receptor-like factor 2 rearranged ( CRLF2 -re) subgroup Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like B-ALL) have a high relapse rate and poor clinical outcomes. CRFL2 -re Ph-like B-ALL is characterized by heightened activation of multiple signaling pathways, including the JAK/STAT and PI3K/AKT/mTOR pathways. We hypothesized that the combined inhibition by JAK2 and mTOR inhibitors would induce an additive antileukemia effect in CRLF2 -re Ph-like B-ALL. In this study, we tested the antileukemia efficacy of the type I JAK inhibitor ruxolitinib and type II JAK inhibitor NVP-BBT594 (hereafter abbreviated BBT594) [1] alone and combined with allosteric mTOR inhibitor rapamycin and a second generation ATP-competitive mTOR kinase inhibitor AZD2014...
January 30, 2018: Oncotarget
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