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https://www.readbyqxmd.com/read/28733560/mir-122-socs1-jak2-axis-regulates-allergic-inflammation-and-allergic-inflammation-promoted-cellular-interactions
#1
Kyeonga Noh, Misun Kim, Youngmi Kim, Hanearl Kim, Hyuna Kim, Jaehwan Byun, Yeongseo Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Dooil Jeoung
The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733465/the-retinol-binding-protein-receptor-stra6-regulates-diurnal-insulin-responses
#2
Christy M Gliniak, J Mark Brown, Noa Noy
It has long been appreciated that insulin action is closely tied to circadian rhythms. However, mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood. Retinol binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and has become an attractive drug target in type 2 diabetes. RBP4 is synthesized primarily in the liver where it binds retinol and transports it to tissues throughout the body. The retinol-RBP4 complex (holo-RBP) can be recognized by a cell surface receptor known as stimulated by retinoic acid 6 (STRA6) which transports retinol into cells...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28729093/pim-kinases-1-2-and-3-in-intracellular-lif-signalling-proliferation-and-apoptosis-in-trophoblastic-cells
#3
Stella Mary Photini, Wittaya Chaiwangyen, Maja Weber, Boodor Al-Kawlani, Rodolfo R Favaro, Udo Jeschke, Ekkehard Schleussner, Diana M Morales-Prieto, Udo R Markert
Proviral insertion in murine (PIM) lymphoma proteins are mainly regulated by the Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling pathway, which can be activated by members of the Interleukin-6 (IL-6) family, including Leukemia Inhibitory Factor (LIF). Aim of the study was to compare PIM1, PIM2 and PIM3 expression and potential cellular functions in human first and third trimester trophoblast cells, the immortalized first trimester extravillous trophoblast cell line HTR8/SVneo and the choriocarcinoma cell line JEG-3...
July 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28725653/calr-positive-myeloproliferative-disorder-in-a-patient-with-ph-positive-chronic-myeloid-leukemia-in-durable-treatment-free-remission-a-case-report
#4
Irene Dogliotti, Carmen Fava, Anna Serra, Enrico Gottardi, Filomena Daraio, Francesca Carnuccio, Emilia Giugliano, Monica Bocchia, Giuseppe Saglio, Giovanna Rege-Cambrin
Current diagnostic criteria for Philadelphia-negative myeloproliferative neoplasia (MPN) have been redefined by the discovery of Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL) and calreticulin (CALR) genetic alterations. Only few cases of coexistence of CALR-mutated MPN and Philadelphia-positive chronic myeloid leukemia (CML) have been described so far. Here we report the case of a patient with CML diagnosed in 2001, treated with imatinib and pegylated interferon (IFN) frontline. She reached complete molecular remission (CMR) and discontinued imatinib, maintaining treatment free remission...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28722170/activation-of-the-b-cell-receptor-successively-activates-nf-%C3%AE%C2%BAb-and-stat3-in-chronic-lymphocytic-leukemia-cells
#5
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 minutes, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hours. Here we show that this process takes longer because it requires transcriptional activity of NF-κB...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28721333/pulmonary-cryptococcosis-in-a-ruxolitinib-treated-patient-with-primary-myelofibrosis
#6
Anna Hirano, Masahiro Yamasaki, Naomi Saito, Koji Iwato, Wakako Daido, Kunihiko Funaishi, Sayaka Ishiyama, Naoko Deguchi, Masaya Taniwaki, Nobuyuki Ohashi
We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT) after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks) with concomitant ruxolitinib administration, but the pulmonary lesions progressed...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#7
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#8
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28716890/negative-regulation-of-cytokine-signaling-in-immunity
#9
Akihiko Yoshimura, Minako Ito, Shunsuke Chikuma, Takashi Akanuma, Hiroko Nakatsukasa
Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28714416/application-of-kinase-inhibitors-for-anti-aging-intervention
#10
Mercedes Cano, Antonio Ayala, Francesco Marotta, Sandro Argüelles
Protein phosphorylation, mediated by protein kinases, has important physiological and pathological implications in our lives . Targeting kinase is one of the most interesting of the emerging topics in the pharmaceutical industry, especially since there is a focus on cancer therapy. Given that kinases may be involved in the aging process the focus will be on using the kinase inhibitor for anti-aging intervention to enhance healthspan and increase longevity. In this review , we will summarize: (i) the impact of the phosphoproteomic approach to elucidate molecular mechanisms of diseases; (ii) importance of the drug discovery approach for targeting kinases; (iii) the dysregulation of Janus kinase (JAK) / signal-transducing adapter molecules (STAT) and p70 ribosomal protein S6 kinase (S6Ks) pathway in aging and the age-related process; (iv) the epidemiological studies available in order to see whether a correlation between JAK/STAT and S6Ks mRNA expression levels exist in cancer and in patient outcome; (v) finally, we will show selected inhibitors of these kinases approved by the US Food and Drug Administration (FDA)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714180/tofacitinib-for-the-treatment-of-moderate-to-severe-chronic-plaque-psoriasis-in-japanese-patients-subgroup-analyses-from-a-randomized-placebo-controlled-phase-3-trial
#11
Masatoshi Abe, Chikako Nishigori, Hideshi Torii, Hironobu Ihn, Kei Ito, Makoto Nagaoka, Naoki Isogawa, Isao Kawaguchi, Yukiko Tomochika, Mihoko Kobayashi, Anna M Tallman, Kim A Papp
Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16...
July 17, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28713982/protective-effects-of-socs3-overexpression-in-high-glucose%C3%A2-induced-lung-epithelial-cell-injury-through-the-jak2-stat3-pathway
#12
Wei-Na Duan, Zhong-Yuan Xia, Min Liu, Qian Sun, Shao-Qing Lei, Xiao-Jing Wu, Qing-Tao Meng, Yan Leng
Previous studies have suggested that the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is involved in hyperglycemia‑induced lung injury. The present study aimed to investigate the roles of suppressor of cytokine signaling3 (SOCS3) in the regulation of JAK2/STAT3 activation following high glucose (HG) treatment in A549 human pulmonary epithelial cells. Cell viability was evaluated using Cell Counting Kit-8 and lactate dehydrogenase assays. HG‑induced inflammatory injury in A549 cells was assessed through the evaluation of interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α) levels using ELISA...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28711286/novel-therapeutic-targets-for-inflammatory-bowel-disease
#13
REVIEW
Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28711084/herpes-zoster-in-psoriasis-patients-treated-with-tofacitinib
#14
Kevin L Winthrop, Mark Lebwohl, Arnon D Cohen, Jeffrey M Weinberg, Stephen K Tyring, Scott T Rottinghaus, Pankaj Gupta, Kaori Ito, Huaming Tan, Mandeep Kaur, Alexander Egeberg, Lotus Mallbris, Hernan Valdez
BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension (LTE) data from the tofacitinib development program in psoriasis to calculate HZ incidence rates (IR; events per 100 patient-years); potential HZ risk factors were evaluated using Cox-proportional hazard models...
August 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28709568/current-and-emerging-topical-therapies-for-atopic-dermatitis
#15
Jeremy Udkoff, Andrea Waldman, Jusleen Ahluwalia, Jenna Borok, Lawrence F Eichenfield
The pathogenesis of atopic dermatitis (AD) involves epidermal barrier dysfunction and T helper cell type 2 (Th2) lymphocyte-driven inflammation. Cytokines, such as interleukin 4 (IL-4) and IL-13, are important in this reaction. They stimulate B cells to produce immunoglobulin E, causing atopic disease. This process has been well characterized, and new therapies for AD, such as phosphodiesterase 4 (PDE-4) inhibitors, Th2-expressed chemoattractant receptor-homologous molecule antagonists, and Janus kinase inhibitors, work by antagonizing this cellular pathway...
July 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28708884/a-jak1-2-inhibitor-baricitinib-inhibits-osteoclastogenesis-by-suppressing-rankl-expression-in-osteoblasts-in-vitro
#16
Kohei Murakami, Yasuhiro Kobayashi, Shunsuke Uehara, Takako Suzuki, Masanori Koide, Teruhito Yamashita, Midori Nakamura, Naoyuki Takahashi, Hiroyuki Kato, Nobuyuki Udagawa, Yukio Nakamura
The Janus kinases (Jaks) are hubs in the signaling process of more than 50 cytokine or hormone receptors. However, the function of Jak in bone metabolism remains to be elucidated. Here, we showed that the inhibition of Jak1 and/or Jak2 in osteoblast-lineage cells led to impaired osteoclastogenesis due to the reduced expression of receptor activator of nuclear factor-κB ligand (RANKL). Murine calvaria-derived osteoblasts induced differentiation of bone marrow cells into osteoclasts in the presence of 1,25-dihydroxyvitamin D3 (1,25D3) and prostaglandin E2 (PGE2) in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28705811/proprotein-convertase-furin1-expression-in-the-drosophila-fat-body-is-essential-for-a-normal-antimicrobial-peptide-response-and-bacterial-host-defense
#17
Saara Aittomäki, Susanna Valanne, Tapio Lehtinen, Sampsa Matikainen, Tuula A Nyman, Mika Rämet, Marko Pesu
Invading pathogens provoke robust innate immune responses in Dipteran insects, such as Drosophila melanogaster In a systemic bacterial infection, a humoral response is induced in the fat body. Gram-positive bacteria trigger the Toll signaling pathway, whereas gram-negative bacterial infections are signaled via the immune deficiency (IMD) pathway. We show here that the RNA interference-mediated silencing of Furin1-a member of the proprotein convertase enzyme family-specifically in the fat body, results in a reduction in the expression of antimicrobial peptides...
July 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28702412/megakaryocytic-morphology-in-janus-kinase-2-v617f-positive-myeloproliferative-neoplasm
#18
Shuchi Ghai, Sharada Rai
CONTEXT: Alterations in megakaryocyte morphology are the hallmark of myeloproliferative neoplasms (MPNs). These neoplasm are also associated with Janus kinase 2 (JAK2) V617F mutation in nearly 95% patients with polycythemia vera (PV), 40% patients of essential thrombocythemia (ET) and 50% patients of myelofibrosis (MF). The utility of megakaryocyte morphology in these disorders in correlation with JAK2 V617F remains unresolved. AIMS: The aim of the study was to assess the morphology of megakaryocytes in bone marrow aspirates (BMAs) and bone marrow biopsies of patients of BCR-ABL negative MPNs with JAK2 V617F mutation...
April 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28701183/ruxolitinib-found-to-cause-eyelash-growth-a-case-report
#19
Julia Song, Alice Song, Trisa Palmares, Michael Song, Harold Song
BACKGROUND: Hypereosinophilic syndrome is a hematologic disorder in which the eosinophils proliferate. Oral Janus kinase inhibitors are known to be effective treating hypereosinophilic syndrome. Janus kinase inhibitors have also demonstrated efficacy in alopecia. Madarosis is a condition in which the eyelashes are missing or absent and can been seen in alopecia patients. CASE PRESENTATION: We present the case of a 77-year-old Asian man who was diagnosed with hypereosinophilic syndrome, refractive to all medications except ruxolitinib...
July 12, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28696382/phosphoinositide-3-kinase-dependent-signalling-pathways-in-cutaneous-squamous-cell-carcinomas
#20
REVIEW
Joanna M Janus, Ryan F L O'Shaughnessy, Catherine A Harwood, Tania Maffucci
Cutaneous squamous cell carcinoma (cSCC) derives from keratinocytes in the epidermis and accounts for 15-20% of all cutaneous malignancies. Although it is usually curable by surgery, 5% of these tumours metastasise leading to poor prognosis mostly because of a lack of therapies and validated biomarkers. As the incidence rate is rising worldwide it has become increasingly important to better understand the mechanisms involved in cSCC development and progression in order to develop therapeutic strategies. Here we discuss some of the evidence indicating that activation of phosphoinositide 3-kinases (PI3Ks)-dependent signalling pathways (in particular the PI3Ks targets Akt and mTOR) has a key role in cSCC...
July 11, 2017: Cancers
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