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https://www.readbyqxmd.com/read/27933673/a-biophysical-and-computational-study-unraveling-the-molecular-interaction-mechanism-of-a-new-janus-kinase-inhibitor-tofacitinib-with-bovine-serum-albumin
#1
Ali Saber Abdelhameed, Saima Nusrat, Mohammad Rehan Ajmal, Syed Mohammad Zakariya, Masihuz Zaman, Rizwan Hasan Khan
The interaction of a recently certified kinase inhibitor Tofacitinib (TFB) with bovine serum albumin (BSA) has been studied, by spectroscopic and molecular docking studies. Spectrofluorimetric measurements at 3 different temperatures (288, 298, and 310 K) showed that TFB quench the intrinsic fluorescence of BSA upon forming a nonfluorescent complex. The intrinsic fluorescence data showed that TFB binds to BSA with binding constant (Kb ) of approximately 10(4) M(-1) , affirming a significant affinity of TFB with BSA...
December 9, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27931982/jak-inhibitor-tofacitinib-suppresses-interferon-alfa-production-by-plasmacytoid-dendritic-cells-and-inhibits-arthrogenic-and-antiviral-effects-of-interferon-alfa
#2
Patrick P C Boor, Petra E de Ruiter, Patrick S Asmawidjaja, Erik Lubberts, Luc J W van der Laan, Jaap Kwekkeboom
Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections...
November 20, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27931536/advances-in-atopic-dermatitis-in-2015
#3
REVIEW
Takashi Nomura, Kenji Kabashima
This review aims to highlight recently published articles on atopic dermatitis (AD). Updated are the insights into epidemiology, pathology, diagnostics, and therapy. Epidemiologic studies have revealed a positive correlation between AD and systemic conditions, such as rheumatoid arthritis, inflammatory bowel disease, and neonatal adiposity. Pathologic findings highlight the involvement of novel barrier factors (desmoplakin and claudin), novel immune cell subsets (pathogenic effector TH2 cells and group 2 innate lymphoid cells), and differential skewing of helper T cells (eg, TH17 dominance in Asians with AD)...
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27931295/a-janus-tale-of-the-two-faces-of-corticosteroid-therapy-a-potential-for-adverse-effects-versus-a-steroid-sparing-benefit-of-certain-therapies
#4
Joseph A Bellanti, Russell A Settipane
No abstract text is available yet for this article.
November 2016: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/27931025/ulcerative-colitis
#5
Elena Sonnenberg, Britta Siegmund
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is chronically present in patients throughout their lives. Hence, the chronic nature of the disease invariably requires continuous medical treatment. Advances in medical therapy over the last decades and current developments offer increasing options and are closely associated with a better life quality in patients. SUMMARY: Recent developments in understanding the pathogenesis of UC are discussed...
December 9, 2016: Digestion
https://www.readbyqxmd.com/read/27930318/janus-effect-of-antifreeze-proteins-on-ice-nucleation
#6
Kai Liu, Chunlei Wang, Ji Ma, Guosheng Shi, Xi Yao, Haiping Fang, Yanlin Song, Jianjun Wang
The mechanism of ice nucleation at the molecular level remains largely unknown. Nature endows antifreeze proteins (AFPs) with the unique capability of controlling ice formation. However, the effect of AFPs on ice nucleation has been under debate. Here we report the observation of both depression and promotion effects of AFPs on ice nucleation via selectively binding the ice-binding face (IBF) and the non-ice-binding face (NIBF) of AFPs to solid substrates. Freezing temperature and delay time assays show that ice nucleation is depressed with the NIBF exposed to liquid water, whereas ice nucleation is facilitated with the IBF exposed to liquid water...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929099/stat1-is-essential-for-the-inhibition-of-hepatitis-c-virus-replication-by-interferon-%C3%AE-but-not-by-interferon-%C3%AE
#7
Shota Yamauchi, Kenji Takeuchi, Kazuyasu Chihara, Chisato Honjoh, Yuji Kato, Hatsumi Yoshiki, Hak Hotta, Kiyonao Sada
Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27927913/two-janus-cannabinoids-that-are-both-cb2-agonists-and-cb1-antagonists
#8
Amey Dhopeshwarkar, Natalia Murataeva, Alex Makriyannis, Alex Straiker, Ken P Mackie
The cannabinoid signaling system includes two G protein coupled receptors, CB1 and CB2. These receptors are widely distributed throughout the body and have each been implicated in many physiologically important processes. Though the cannabinoid signaling system has therapeutic potential, a persistent hurdle has remained the development of receptor-selective ligands. Because CB1 and CB2 are involved in diverse processes, it would be advantageous develop ligands that differentially engaging CB1 and CB2. We now report that GW405833 and AM1710, described as selective CB2 agonists, can antagonize CB1 receptor signaling...
December 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27923824/human-dendritic-cells-mitigate-nk-cell-dysfunction-mediated-by-nonselective-jak1-2-blockade
#9
Shane A Curran, Justin A Shyer, Erin T St Angelo, Lillian R Talbot, Sneh Sharma, David J Chung, Glenn Heller, Katharine C Hsu, Brian C Betts, James W Young
Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-vs-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined...
6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923397/pharmacological-interventions-for-delirium-in-intensive-care-patients-a-protocol-for-an-overview-of-reviews
#10
Marija Barbateskovic, Laura Krone Larsen, Marie Oxenbøll-Collet, Janus Christian Jakobsen, Anders Perner, Jørn Wetterslev
BACKGROUND: The prevalence of delirium in intensive care unit (ICU) patients is high. Delirium has been associated with morbidity and mortality including more ventilator days, longer ICU stay, increased long-term mortality and cognitive impairment. Thus, the burden of delirium for patients, relatives and societies is considerable. Today, reviews of randomised clinical trials are produced in large scales sometimes making it difficult to get an overview of the available evidence. A preliminary search identified several reviews investigating the effects of pharmacological interventions for the management and prevention of delirium in ICU patients...
December 7, 2016: Systematic Reviews
https://www.readbyqxmd.com/read/27921355/catalysis-driven-self-thermophoresis-of-janus-plasmonic-nanomotors
#11
Weiwei Qin, Tianhuan Peng, Yanjing Gao, Fei Wang, Xiaocai Hu, Kun Wang, Jiye Shi, Di Li, Jicun Ren, Chunhai Fan
It is highly demanding to design active nanomotors that can move in response to specific signals with controllable rate and direction. A catalysis-driven nanomotor was constructed by designing catalytically and plasmonically active Janus gold nanoparticles (Au NPs), which generate an asymmetric temperature gradient of local solvent surrounding NPs in catalytic reactions. The self-thermophoresis behavior of the Janus nanomotor is monitored from its inherent plasmonic response. The diffusion coefficient of the self-thermophoresis motion is linearly dependent on chemical reaction rate, as described by a stochastic model...
December 6, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27920773/glucose-metabolism-via-the-entner-doudoroff-pathway-in-campylobacter-a-rare-trait-that-enhances-survival-and-promotes-biofilm-formation-in-some-isolates
#12
Christina S Vegge, Melissa J Jansen van Rensburg, Janus J Rasmussen, Martin C J Maiden, Lea G Johnsen, Morten Danielsen, Sheila MacIntyre, Hanne Ingmer, David J Kelly
Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search for ED pathway genes in a wide range of Campylobacter isolates and in the C. jejuni/coli PubMLST database revealed that 1.7% of >6,000 genomes encoded a complete ED pathway, including both C. jejuni and C. coli from diverse clinical, environmental and animal sources...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27919027/phosphorylation-of-janus-kinase-1-jak1-by-amp-activated-protein-kinase-ampk-links-energy-sensing-to-anti-inflammatory-signaling
#13
Claire Rutherford, Claire Speirs, Jamie J L Williams, Marie-Ann Ewart, Sarah J Mancini, Simon A Hawley, Christian Delles, Benoit Viollet, Ana P Costa-Pereira, George S Baillie, Ian P Salt, Timothy M Palmer
Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser(515) and Ser(518)) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser(515) and Ser(518) and was abolished in cells lacking AMPK catalytic subunits...
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27918450/janus-compounds-5-chloro-n%C3%A2-methyl-n%C3%A2-aryl-9h-pyrimido-4-5-b-indole-2-4-diamines-cause-both-microtubule-depolymerizing-and-stabilizing-effects
#14
Cristina C Rohena, April L Risinger, Ravi Kumar Vyas Devambatla, Nicholas F Dybdal-Hargreaves, Roma Kaul, Shruti Choudhary, Aleem Gangjee, Susan L Mooberry
While evaluating a large library of compounds designed to inhibit microtubule polymerization, we identified four compounds that have unique effects on microtubules. These compounds cause mixed effects reminiscent of both microtubule depolymerizers and stabilizers. Immunofluorescence evaluations showed that each compound initially caused microtubule depolymerization and, surprisingly, with higher concentrations, microtubule bundles were also observed. There were subtle differences in the propensity to cause these competing effects among the compounds with a continuum of stabilizing and destabilizing effects...
December 2, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27917774/screening-for-calreticulin-mutations-in-a-cohort-of-patients-suspected-of-having-a-myeloproliferative-neoplasm
#15
A De Kock, C Booysen
BACKGROUND: The discovery of calreticulin (CALR) has shown it to be the second most frequent mutation after the Janus Kinase 2 (JAK2) mutation in myeloproliferative neoplasms (MPNs). Its structure indicates various functions, of which two are to ensure calcium homeostasis and proper folding of other target proteins. Over 36 types of CALR mutations have been identified, all causing a recurrent frameshift in the C-terminal domain affecting CALR's localisation and calcium-binding function...
December 1, 2016: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/27917282/ginkgetin-induces-apoptosis-in-786-o-cell-line-via-suppression-of-jak2-stat3-pathway
#16
Yu Ren, Shuang-Shuang Huang, Xue Wang, Zhong-Guan Lou, Xu-Ping Yao, Guo-Bin Weng
OBJECTIVES: Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy. Ginkgetin effectively treats several carcinoma cells. However, little is known about effects of Ginkgetin on RCC. In the present study, using 786-O cells, we evaluate whether Ginkgetin exerts anticancer effects against RCC. MATERIALS AND METHODS: 786-O cells suspended in the medium containing Ginkgetin were cultured for 24 hr to 72 hr, and then MTT assay was used to study cytotoxic effect of Ginkgetin...
November 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27917175/nuclear-localization-of-suppressor-of-cytokine-signaling-1-regulates-local-immunity-in-the-lung
#17
Jana Zimmer, Michael Weitnauer, Sébastien Boutin, Günter Küblbeck, Sabrina Thiele, Patrick Walker, Felix Lasitschka, Lars Lunding, Zane Orinska, Christina Vock, Bernd Arnold, Michael Wegmann, Alexander Dalpke
Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet, the in vivo importance of nuclear translocation is unknown. We generated transgenic mice containing mutated Socs1ΔNLS that fails to translocate in the cell nucleus (MGL(tg) mice). Whereas mice fully deficient for SOCS1 die within the first 3 weeks due to excessive interferon signaling and multiorgan inflammation, mice expressing only non-nuclear Socs1ΔNLS (Socs1(-/-)MGL(tg) mice) were rescued from early lethality...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27916398/ruxolitinib-for-the-treatment-of-inadequately-controlled-polycythaemia-vera-without-splenomegaly-response-2-a-randomised-open-label-phase-3b-study
#18
Francesco Passamonti, Martin Griesshammer, Francesca Palandri, Miklos Egyed, Giulia Benevolo, Timothy Devos, Jeannie Callum, Alessandro M Vannucchi, Serdar Sivgin, Caroline Bensasson, Mahmudul Khan, Nadjat Mounedji, Guray Saydam
BACKGROUND: In the pivotal RESPONSE study, ruxolitinib, a Janus kinase (JAK)1 and JAK2 inhibitor, was superior to best available therapy at controlling haematocrit and improving splenomegaly and symptoms in patients with polycythaemia vera with splenomegaly who were inadequately controlled with hydroxyurea. In this study, we assessed the efficacy and safety of ruxolitinib in controlling disease in patients with polycythaemia vera without splenomegaly who need second-line therapy. METHODS: RESPONSE-2 is a randomised, open-label, phase 3b study assessing ruxolitinib versus best available therapy in patients with polycythaemia vera done in 48 hospitals or clinics across 12 countries in Asia, Australia, Europe, and North America...
December 1, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27916280/novel-targeted-therapies-for-inflammatory-bowel-disease
#19
REVIEW
Mehmet Coskun, Severine Vermeire, Ole Haagen Nielsen
Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easily administered therapeutics that may be viable candidates for the management of IBD, such as antibodies against interleukin 6 (IL-6) and IL-12/23, small molecules including Janus kinase inhibitors, antisense oligonucleotide against SMAD7 mRNA, and inhibitors of leukocyte trafficking to intestinal sites of inflammation (e...
December 1, 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27914346/tuning-particle-geometry-of-chemically-anisotropic-dumbbell-shaped-colloids
#20
Bas G P van Ravensteijn, Willem K Kegel
Chemically anisotropic dumbbell-shaped colloids are prepared starting from cross-linked polymer seed particles coated with a chlorinated outer layer. These chlorinated seeds are swollen with monomer. Subsequently, a liquid protrusion is formed on the surface of the seed particle by phase separation between the monomer and the swollen polymer network. Solidification of these liquid lobes by polymerization leads to the desired dumbbell-shaped colloids. The chlorine groups remain confined on the seed lobe of the particles, ensuring chemical anisotropy of the resulting particles...
November 15, 2016: Journal of Colloid and Interface Science
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