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https://www.readbyqxmd.com/read/29150291/ruxolitinib-conjugated-gold-nanoparticles-for-topical-administration-an-alternative-for-treating-alopecia
#1
Sanda Boca, Cristian Berce, Ancuta Jurj, Bobe Petrushev, Laura Pop, Grigore-Aristide Gafencu, Sonia Selicean, Vlad Moisoiu, Daiana Temian, Wilhelm-Thomas Micu, Simion Astilean, Cornelia Braicu, Ciprian Tomuleasa, Ioana Berindan-Neagoe
Alopecia is a dermatological condition for which Janus kinase (JAK) inhibitors have recently emerged as potential therapy options, but with limited practical use because of the systemic side effects. The topical use of Ruxolitinib in alopecia universalis has been demonstrated, but little is known about the pharmacodynamics and pharmacokinetics of this way of administration. Nanomedicine provides improved therapeutics. In the current paper we present preliminary data regarding the potential use of Ruxolitinib-conjugated gold nanoparticles (GNPs) in dermatological conditions, as GNPs have been proven to have a reduced absorption rate into the systemic blood flow for cutaneous administration...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29143896/modulation-of-stimulator-of-interferon-genes-sting-expression-by-interferon-%C3%AE-in-human-keratinocytes
#2
Yohei Nishikawa, Yasushi Matsuzaki, Kazuyuki Kimura, Akiko Rokunohe, Hajime Nakano, Daisuke Sawamura
Infection of microbial pathogen triggers the innate immune system, and the induction of interferons (IFNs) play a vital role in host antiviral response. Stimulator of interferon genes (STING) was identified as a crucial regulator of the DNA sensing pathway, and activates both nuclear factor-κB and interferon regulatory factor 3 transcription pathways to evoke IFNs production. In this study, we studied the upregulation of STING mRNA expression, induced by IFN-γ in human keratinocytes (HaCaT). STING promoter assays clarified that a gamma-activated sequence (GAS), located at - 7 to - 15-bp, is required for IFN-γ-upregulated promoter activity...
November 16, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/29142473/genetic-associations-with-adverse-events-from-anti-tumor-necrosis-factor-therapy-in-inflammatory-bowel-disease-patients
#3
Daniel Lew, Soon Man Yoon, Xiaofei Yan, Lori Robbins, Talin Haritunians, Zhenqiu Liu, Dalin Li, Dermot Pb McGovern
AIM: To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. METHODS: This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol...
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29140406/smad3-stat3-crosstalk-in-pathophysiological-contexts
#4
Yuka Itoh, Masao Saitoh, Keiji Miyazawa
Smad3 and STAT3 are intracellular molecules that transmit signals from plasma membrane receptors to the nucleus. Smad3 operates downstream of growth/differentiation factors that utilize activin receptor-like kinase (ALK)-4, 5, or 7, such as transforming growth factor-β (TGF-β), activin, and myostatin. STAT3 principally functions downstream of cytokines that exert their effects via gp130 and Janus family kinases, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M. Accumulating evidence indicates that Smad3 and STAT3 engage in crosstalk in a highly context-dependent fashion, cooperating in some conditions while acting antagonistically each other in others...
November 13, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29139090/tofacitinib-a-review-in-rheumatoid-arthritis
#5
Sohita Dhillon
Tofacitinib (Xeljanz(®)) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3. In the EU, oral tofacitinib 5 mg twice daily is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant of, one or more DMARDs. Several clinical studies of ≤ 24 months' duration showed that tofacitinib monotherapy (as first- or second-line treatment) and combination therapy with a conventional synthetic DMARD (csDMARD; as second- or third-line treatment) was effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL), with benefits sustained during long-term therapy (≤ 96 months)...
November 14, 2017: Drugs
https://www.readbyqxmd.com/read/29134817/the-bcr-abl1-negative-myeloproliferative-neoplasms-a-review-of-jak-inhibitors-in-the-therapeutic-armamentarium
#6
Martin Griesshammer, Parvis Sadjadian
The classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) include primary myelofibrosis (PMF), polycythaemia vera (PV) and essential thrombocythaemia (ET). They are characterized by stem cell-derived clonal proliferation, harbour Janus kinase 2 (JAK2), or calreticulin (CALR), or myeloproliferative leukaemia virus oncogene (MPL) driver mutations and exert an over activated JAK-signal transducer and activator of transcription (STAT) pathway. Therefore JAK inhibiting strategies have been successfully investigated in MPN clinical trials...
November 14, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29134648/pharmacokinetics-pharmacodynamics-and-proposed-dosing-of-the-oral-jak1-and-jak2-inhibitor-baricitinib-in-pediatric-and-young-adult-candle-and-savi-patients
#7
Hanna Kim, Kristina M Brooks, Cheng Cai Tang, Paul Wakim, Mary Blake, Stephen R Brooks, Gina A Montealegre Sanchez, Adriana A de Jesus, Yan Huang, Wanxia Li Tsai, Massimo Gadina, Apurva Prakash, Jonathan Marcus Janes, Xin Zhang, William L Macias, Parag Kumar, Raphaela Goldbach-Mansky
Population pharmacokinetic (popPK) modeling was used to characterize the PK profile of the oral janus kinase (JAK)1/JAK2 inhibitor, baricitinib, in 18 patients with Mendelian interferonopathies who are enrolled in a compassionate use program. Patients received doses between 0.1 to 17 mg per day. Covariates of weight and renal function significantly influenced volume-of-distribution and clearance respectively. The half-life of baricitinib in patients less than 40kg was substantially shorter than in adult populations, requiring the need for dosing up to 4 times daily...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29133519/deep-rna-sequencing-uncovers-a-repertoire-of-human-macrophage-long-intergenic-noncoding-rnas-modulated-by-macrophage-activation-and-associated-with-cardiometabolic-diseases
#8
Hanrui Zhang, Chenyi Xue, Ying Wang, Jianting Shi, Xuan Zhang, Wenjun Li, Sara Nunez, Andrea S Foulkes, Jennie Lin, Christine C Hinkle, Wenli Yang, Edward E Morrisey, Daniel J Rader, Mingyao Li, Muredach P Reilly
BACKGROUND: Sustained and dysfunctional macrophage activation promotes inflammatory cardiometabolic disorders, but the role of long intergenic noncoding RNA (lincRNA) in human macrophage activation and cardiometabolic disorders is poorly defined. Through transcriptomics, bioinformatics, and selective functional studies, we sought to elucidate the lincRNA landscape of human macrophages. METHODS AND RESULTS: We used deep RNA sequencing to assemble the lincRNA transcriptome of human monocyte-derived macrophages at rest and following stimulation with lipopolysaccharide and IFN-γ (interferon γ) for M1 activation and IL-4 (interleukin 4) for M2 activation...
November 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29129493/overexpression-of-microrna-495-improves-the-intestinal-mucosal-barrier-function-by-targeting-stat3-via-inhibition-of-the-jak-stat3-signaling-pathway-in-a-mouse-model-of-ulcerative-colitis
#9
Xian-Qun Chu, Jing Wang, Guang-Xiang Chen, Guan-Qi Zhang, De-Yong Zhang, Yong-Yan Cai
We aim to investigate the role of microRNA-495 (miR-495) in the intestinal mucosal barrier by indirectly targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase-signal transducer and activator of transcription (JAK)/STAT3 signaling pathway in a mouse model of ulcerative colitis (UC). BALB/c mice were selected for establishing mice model of UC, and intestinal tissues of normal and UC mice were collected. ELISA was conducted for detecting levels of TNF-α, IL-6, IFN-γ and IL-10...
October 12, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29128809/icariin-induces-apoptosis-in-acute-promyelocytic-leukemia-by-targeting-pim1
#10
Hong Zhang, Ping Li, Jing Li, Tongguo Song, Lin Wang, Enze Li, Jiao Wang, Luning Wang, Na Wei, Zhi Wang
BACKGROUND: Acute promyelocytic leukemia (APL) is one type of acute myeloid leukemia (AML) featured by abnormal, heavily granulated promyelocytes. This study aimed to investigate the antitumor activity of icariin in APL cells. METHODS: APL cell lines (HL-60 and NB4) were used to investigate the effect of icariin in vitro. Cell viability was determined by WST-8 proliferation assay, while cell apoptosis was assessed by flow cytometry. The mRNA and protein expression was determined by quantitative real-time polymerase chain reaction and Western blot, respectively...
June 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127727/diversity-in-peptide-recognition-by-the-sh2-domain-of-sh2b1
#11
Marissa A McKercher, Xiaoyang Guan, Zhongping Tan, Deborah S Wuttke
SH2B1 is a multidomain protein that serves as a key adapter to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY...
November 11, 2017: Proteins
https://www.readbyqxmd.com/read/29127481/expression-of-janus-kinase-1-in-vitiligo-psoriasis-before-and-after-narrow-band-uvb-a-case-control-study
#12
Hanan Rabea Nada, Dina Ahmed El Sharkawy, Maha Fathy Elmasry, Laila Ahmed Rashed, Sally Mamdouh
Janus kinases (JAKs) are non-receptor protein tyrosine kinases that are expressed in many tissues. Once the JAKs are activated, a cascade of further signaling events is triggered involving phosphorylation of selected receptor chain tyrosines, binding of signal transducer and activator of transcription (STAT) proteins and phosphorylation of these STATs. Due to their ability to selectively modulate immune function, targeted JAK inhibitors are promising candidates for some skin diseases such as psoriasis and atopic dermatitis...
November 10, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29126764/stat5a-and-stat6-gene-expression-levels-in-multiple-sclerosis-patients
#13
Mahsa Hatami, Tayyebali Salmani, Shahram Arsang-Jang, Mir Davood Omrani, Mehrdokht Mazdeh, Soudeh Ghafouri-Fard, Arezou Sayad, Mohammad Taheri
Multiple sclerosis (MS) is a complex inflammatory, autoimmune disease of the central nervous system (CNS). The disease pathogenesis is not well defined yet. Cytokines have an important role in inflammation as characteristic feature of the disease. Janus kinase/signal transducers and activators of transcriptions (JAK/STAT) family promote cytokine-mediated cell activation. Failure in the JAK/STAT signaling pathway is associated with the pathological outcome in MS. In this study, we compared the expression levels of STAT5a and STAT6 genes in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by Taqman Quantitative Real-Time PCR in patients and healthy control group...
November 7, 2017: Cytokine
https://www.readbyqxmd.com/read/29123956/mutations-in-jak2-and-calreticulin-genes-are-associated-with-specific-alterations-of-the-immune-system-in-myelofibrosis
#14
Marco Romano, Daria Sollazzo, Sara Trabanelli, Martina Barone, Nicola Polverelli, Margherita Perricone, Dorian Forte, Simona Luatti, Michele Cavo, Nicola Vianelli, Camilla Jandus, Francesca Palandri, Lucia Catani
Myelofibrosis (MF) is a clonal neoplasia associated with chronic inflammation due to aberrant cytokine production. Mutations in Janus Kinase-2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia protein (MPL) genes have been recently associated to MF and they all activate the JAK/STAT signaling pathway. Since this pathway is essential in shaping the immune response, we investigated the role of circulating immune subsets and cytokines in 38 patients (20 carrying JAK2((V617F)),13 exon-9 CALR mutation and 5 triple negative)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29119628/stat3-expression-and-activity-are-up-regulated-in-diffuse-large-b-cell-lymphoma-of-dogs
#15
A L F V Assumpção, P C Jark, C C Hong, Z Lu, H M Ruetten, C M Heaton, M E Pinkerton, X Pan
BACKGROUND: The Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways play important roles in the pathogenesis of diffuse large B cell lymphoma (DLBCL) in humans, and up-regulated STAT3 expression and activity are associated with worse clinical outcome in humans. No studies have evaluated the JAK-STAT signaling pathway in DLBCL of dogs. HYPOTHESIS: STAT3 pathway is deregulated in DLBCL in dogs. We aim to assess the expression, activation, and cellular localization of STAT3 and mitogen-activated protein kinase ERK1/2 in DLBCL of dogs...
November 9, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29119202/-janus-kinase-inhibitor-baricitinib-for-rheumatoid-arthritis-randomized-double-blind-placebo-and-active-controlled-phase%C3%A2-3-study-evaluating-the-efficacy-and-safety-of-baricitinib-in-patients-with-moderately-to-severely-active-rheumatoid-arthritis-who-have
#16
https://www.readbyqxmd.com/read/29118922/il-6-increases-sdcbp-expression-cell-proliferation-and-cell-invasion-by-activating-jak2-stat3-in-human-glioma-cells
#17
Fang Cao, Qiang Zhang, Wei Chen, Chong Han, Yang He, Qishan Ran, Shengtao Yao
Syndecan-binding protein (SDCBP), which is induced by tumor necrosis factor-α and interferon-γ, controls the proliferation and invasion of several different types of cancer cells. Interleukin-6 (IL-6) is known to play an important role in the glioma cell growth and invasion. The present study aimed to investigate the relationship between IL-6 and SDCBP in glioma cells. SDCBP expression was knocked down in two glioma cell lines (T98G and U87) by small interfering RNA (siRNA) transfection. Cell proliferation and invasion were significantly repressed following SDCBP knockdown, and there was a positive correlation between SDCBP and IL-6 expression levels in glioma tissues...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118906/rnai-mediated-silencing-of-nox4-inhibited-the-invasion-of-gastric-cancer-cells-through-jak2-stat3-signaling
#18
Xiang Gao, Jingping Sun, Chunyu Huang, Xiaohua Hu, Ning Jiang, Chenqi Lu
NADPH oxidase 4 (NOX4) is a member of the NADPH oxidase (NOX) family of enzymes and has been found abnormally expressed in human cancers. However, its role in gastric cancer (GC) is still unclear. In the current study, we reported that NOX4 expression levels were significantly up-regulated in GC tissues compared to normal tissues (P<0.0001). Higher NOX4 expression was significantly associated with poorer overall survival in GC patients. Silencing NOX4 in two NOX4 high expression GC cell lines, MGC-803 and BGC-823 cells, did not affect cell proliferation, while inhibited cell adhesion and cell invasion of GC cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29115395/transforming-growth-factor-%C3%AE-1-promotes-migration-and-invasion-in-hepg2-cells-epithelial%C3%A2-to%C3%A2-mesenchymal-transition-via-jak-stat3-signaling
#19
Xiao-Long Lin, Mihua Liu, Yuanbo Liu, Huijun Hu, Yongquan Pan, Weiwen Zou, Xiaojuan Fan, Xuemei Hu
Transforming growth factor β1 (TGFβ1) is a cytokine with multiple functions. TGFβ1 significantly induces migration and invasion of liver cancer cells. However, the molecular mechanisms underlying this effect remain unclear. Epithelial‑to‑mesenchymal transition (EMT) is crucial for the development of invasion and metastasis in human cancers. The aim of the present study was to determine whether TGFβ1‑induced EMT promoted migration and invasion in HepG2 cells. The underlying mechanism and the effect of EMT on HepG2 cells were also investigated...
November 1, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29108908/tofacitinib-2-ointment-a-topical-janus-kinase-inhibitor-for-the-treatment-of-alopecia-areata-a-pilot-study-of-10-patients
#20
Lucy Y Liu, Brittany G Craiglow, Brett A King
No abstract text is available yet for this article.
November 3, 2017: Journal of the American Academy of Dermatology
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