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https://www.readbyqxmd.com/read/28441778/gene-expression-analysis-before-and-after-treatment-with-adalimumab-in-patients-with-ankylosing-spondylitis-identifies-molecular-pathways-associated-with-response-to-therapy
#1
Marzia Dolcino, Elisa Tinazzi, Andrea Pelosi, Giuseppe Patuzzo, Francesca Moretta, Claudio Lunardi, Antonio Puccetti
The etiology of Ankylosing spondylitis (AS) is still unknown and the identification of the involved molecular pathogenetic pathways is a current challenge in the study of the disease. Adalimumab (ADA), an anti-tumor necrosis factor (TNF)-alpha agent, is used in the treatment of AS. We aimed at identifying pathogenetic pathways modified by ADA in patients with a good response to the treatment. Gene expression analysis of Peripheral Blood Cells (PBC) from six responders and four not responder patients was performed before and after treatment...
April 24, 2017: Genes
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#2
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441719/suppression-of-oxidative-stress-and-nf%C3%AE%C2%BAb-mapk-signaling-by-lyophilized-black-raspberries-for-esophageal-cancer-prevention-in-rats
#3
Ni Shi, Fang Chen, Xiaoli Zhang, Steven K Clinton, Xiaofei Tang, Zheng Sun, Tong Chen
Research in the laboratory has shown that lyophilized black raspberries (BRB) significantly inhibit N-nitrosomethylbenzylamine (NMBA)-induced esophageal squamous cell carcinogenesis in rats. The objective of the present study is to characterize the underlying mechanism(s) of anti-cancer action of BRB in this preclinical animal model focusing on oxidative stress and its related oncogenic signaling pathways. Esophageal epithelial tissues were collected and assessed for markers of oxidative stress and nuclear factor κB (NFκB) and mitogen-activated protein kinase (MAPK)...
April 22, 2017: Nutrients
https://www.readbyqxmd.com/read/28441717/dexmedetomidine-relieves-formaldehyde-induced-pain-in-rats-through-both-%C3%AE-2-adrenoceptor-and-imidazoline-receptor
#4
Hong Zhang, Xiang Yan, De-Gui Wang, Yu-Fang Leng, Zhan-Hai Wan, Yong-Qiang Liu, Yan Zhang
Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we investigated the analgesic effect and the underlying mechanisms of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley (SD) rats were randomly divided into 5 groups, including control, sham, low dose DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE) staining was used to evaluate the toxicity of DEX on spinal cord neurons...
April 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28441529/mps1-regulates-kinetochore-microtubule-attachment-stability-via-the-ska-complex-to-ensure-error-free-chromosome-segregation
#5
John Maciejowski, Hauke Drechsler, Kathrin Grundner-Culemann, Edward R Ballister, Jose-Antonio Rodriguez-Rodriguez, Veronica Rodriguez-Bravo, Mathew J K Jones, Emily Foley, Michael A Lampson, Henrik Daub, Andrew D McAinsh, Prasad V Jallepalli
The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28441528/phosphorylation-of-neurog3-links-endocrine-differentiation-to-the-cell-cycle-in-pancreatic-progenitors
#6
Nicole A J Krentz, Dennis van Hoof, Zhongmei Li, Akie Watanabe, Mei Tang, Cuilan Nian, Michael S German, Francis C Lynn
During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28441391/apigenin-inhibits-tnf%C3%AE-il-1%C3%AE-induced-ccl2-release-through-ikbk-epsilon-signaling-in-mda-mb-231-human-breast-cancer-cells
#7
David Bauer, Natalie Redmon, Elizabeth Mazzio, Karam F Soliman
Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFα plays a central orchestrating role. TNFα acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2). These proteins direct inward infiltration/migration of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory cells (Tregs), T helper IL-17-producing cells (Th17s), metastasis-associated macrophages (MAMs) and cancer-associated fibroblasts (CAFs)...
2017: PloS One
https://www.readbyqxmd.com/read/28441383/the-oral-vegf-receptor-tyrosine-kinase-inhibitor-pazopanib-in-combination-with-the-mek-inhibitor-trametinib-in-advanced-cholangiocarcinoma
#8
Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Vivek Subbiah, Ralph Zinner, Nilofer S Azad
BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28441348/deoxynucleoside-salvage-in-fission-yeast-allows-rescue-of-ribonucleotide-reductase-deficiency-but-not-spd1-mediated-inhibition-of-replication
#9
Oliver Fleck, Ulrik Fahnøe, Katrine Vyff Løvschal, Marie-Fabrice Uwamahoro Gasasira, Irina N Marinova, Birthe B Kragelund, Antony M Carr, Edgar Hartsuiker, Christian Holmberg, Olaf Nielsen
In fission yeast, the small, intrinsically disordered protein S-phase delaying protein 1 (Spd1) blocks DNA replication and causes checkpoint activation at least in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible for the synthesis of DNA. The CRL4(Cdt2) E3 ubiquitin ligase mediates degradation of Spd1 and the related protein Spd2 at S phase of the cell cycle. We have generated a conditional allele of CRL4(Cdt2), by expressing the highly unstable substrate-recruiting protein Cdt2 from a repressible promoter...
April 25, 2017: Genes
https://www.readbyqxmd.com/read/28441042/aberrantly-expressed-long-noncoding-rnas-in-recurrent-implantation-failure-a-microarray-related-study
#10
Li-Juan Fan, Hong-Jing Han, Jing Guan, Xiao-Wei Zhang, Qing-Hua Cui, Huan Shen, Cheng Shi
Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs longer than 200 nucleotides. They were long regarded as transcription noise for their low expression and non-protein coding features. Recent published reports indicate that lncRNAs are involved in virtually every aspect of human biology. We aimed to profile the endometrial lncRNA expression pattern in women with recurrent implantation failure (RIF) and predict the function of the genes of the dysregulated lncRNA transcripts. Endometrial samples (24) were collected during window of implantation (14 RIF women and 10 women who conceived after embryo transfer)...
April 25, 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28441024/stereoselective-synthesis-and-evaluation-of-c6%C3%A2-substituted-5a-carbasugar-analogues-of-sl0101-as-inhibitors-of-rsk1-2
#11
Mingzong Li, Yu Li, Katarzyna A Ludwik, Zachary M Sandusky, Deborah A Lannigan, George A O'Doherty
A convergent synthesis of 5a-carbasugar analogues of the n-Pr-variant of SL0101 is described. The analogues were synthesized in an effort to find compounds with potent in vivo efficacy in the inhibition of p90 ribosomal s6 kinase (RSK1/2). The synthesis derived the desired C-4 L-rhamnose stereochemistry from quinic acid and used a highly selective cuprate addition, NaBH4 reduction, Mitsunobu inversion, and alkene dihydroxylation to install the remaining stereochemistry. A Pd-catalyzed cyclitolization stereoselectively installed the aglycon at the anomeric position...
April 25, 2017: Organic Letters
https://www.readbyqxmd.com/read/28440912/performance-of-in-silico-tools-for-the-evaluation-of-p16ink4a-cdkn2a-variants-in-cagi
#12
Marco Carraro, Giovanni Minervini, Manuel Giollo, Yana Bromberg, Emidio Capriotti, Rita Casadio, Roland Dunbrack, Lisa Elefanti, Pietro Fariselli, Carlo Ferrari, Julian Gough, Panagiotis Katsonis, Emanuela Leonardi, Olivier Lichtarge, Chiara Menin, Pier Luigi Martelli, Abhishek Niroula, Lipika R Pal, Susanna Repo, Maria Chiara Scaini, Mauno Vihinen, Qiong Wei, Qifang Xu, Yuedong Yang, Yizhou Yin, Jan Zaucha, Huiying Zhao, Yaoqi Zhou, Steven E Brenner, John Moult, Silvio C E Tosatto
Correct phenotypic interpretation of variants of unknown significance for cancer-associated genes is a diagnostic challenge as genetic screenings gain in popularity in the next-generation sequencing era. The Critical Assessment of Genome Interpretation (CAGI) experiment aims to test and define the state of the art of genotype-phenotype interpretation. Here, we present the assessment of the CAGI p16INK4a challenge. Participants were asked to predict the effect on cellular proliferation of ten variants for the p16INK4a tumor suppressor, a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene...
April 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28440874/role-of-glycogen-synthase-kinase-3-in-ischemia-induced-blood-brain-barrier-disruption-in-aged-female-rats
#13
Han Xiao, Mingyang Deng, Binbin Yang, Jianguang Tang, Zhiping Hu
Estrogen receptors have protective effects against ischemic brain injury. However, the molecular mechanisms underlying this phenomenon have yet to be well studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors-mediated protective effects against ischemia-induced blood brain barrier (BBB) disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the brain of ovariectomized female rats, and examined the effects of intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB permeability following middle cerebral artery occlusion (MCAO)...
April 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28440734/cholinergic-activation-suppresses-palmitate-induced-macrophage-activation-and-improves-acylation-stimulating-protein-resistance-in-co-cultured-adipocytes
#14
Jing Wu, Zhou-Yang Jiao, Rui-Zhen Li, Hui-Ling Lu, Hao-Hao Zhang, Katherine Cianflone
Acylation-stimulating protein (ASP), produced through activation of the alternative complement immune system, modulates lipid metabolism. Using a trans-well co-culture cell model, the mitigating role of α7-nicotinic acetylcholine receptor (α7nAChR)-mediated cholinergic pathway on ASP resistance was evaluated. ASP signaling in adipocytes via its receptor C5L2 and signaling intermediates Gαq, Gβ, phosphorylated protein kinase C-α, and protein kinase C-ζ were markedly suppressed in the presence of TNFα or medium from palmitate-treated RAW264...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28440712/gelatin-albumin-hybrid-nanoparticles-as-matrix-metalloproteinases-degradable-delivery-systems-for-breast-cancer-therapy
#15
Vahid Heravi Shargh, Hubert Hondermarck, Mingtao Liang
AIM: To develop matrix metalloproteinase-responsive gelatin-albumin hybrid nanoparticles encapsulating a selective tropomyosin receptor kinase A (TrkA) inhibitor GNF-5837 (Gel-Alb-GNF HNPs) and to demonstrate their anticancer effects in breast cancer. METHODS: Gel-Alb-GNF HNPs were prepared using a pH-controlled complexation process from cationic gelatin, dextran sulfate and albumin-bound GNF-5837. The anticancer activities of Gel-Alb-GNF HNPs were tested in a panel of subtype-specific breast cancer cell lines...
April 25, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28440514/silibinin-downregulates-mmp2-expression-via-jak2-stat3-pathway-and-inhibits-the-migration-and-invasive-potential-in-mda-mb-231-cells
#16
Hyo Joo Byun, Pramod Darvin, Dong Young Kang, Nipin Sp, Youn Hee Joung, Jong Hwan Park, Sun Jin Kim, Young Mok Yang
Worldwide, breast cancer (BCa) is the most common cancer in women. Among its subtypes, triple-negative breast cancer (TNBC) is an aggressive form associated with diminished survival. TNBCs are characterized by their absence, or minimal expression, of the estrogen and progesterone receptors, as well as the human epidermal growth factor receptor 2 (i.e. ER-/-, PR-/-, Her2-/Low). Consequently, treatment for this subtype of BCa remains problematic. Silibinin, a derivative of the flavonoid silymarin, is reported to have anticancer activities against hepatic and non-small cell lung cancers...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440510/migration-of-oral-squamous-cell-carcinoma-cells-are-induced-by-hgf-c-met-signalling-via-lamellipodia-and-filopodia-formation
#17
Hiroki Yasui, Yuichi Ohnishi, Masahiro Nakajima, Masami Nozaki
The activation of receptor tyrosine kinases (RTKs) results in cellular effects including cell proliferation, survival, migration and invasion; RTKs also play an important role in tumourigenesis. It has been reported that EGFR signalling controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells but not of HSC4 cells, although the proliferation of HSC4 cells is regulated by EGF/EGFR. In the present study, we investigated the roles of EGFR and the c-Met signalling pathway in cell migration via filopodia and lamellipodia formation, which may be prerequisites for migration...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440493/the-extracellular-signal-regulated-kinase-1-2-pathway-in-neurological-diseases-a-potential-therapeutic-target-review
#18
Jing Sun, Guangxian Nan
Signaling pathways are critical modulators of a variety of physiological and pathological processes, and the abnormal activation of some signaling pathways can contribute to disease progression in various conditions. As a result, signaling pathways have emerged as an important tool through which the occurrence and development of diseases can be studied, which may then lead to the development of novel drugs. Accumulating evidence supports a key role for extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the embryonic development of the central nervous system (CNS) and in the regulation of adult brain function...
April 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28440492/axl-and-gas6-co-expression-in-lung-adenocarcinoma-as-a-prognostic-classifier
#19
Masahiro Seike, Cheol-Hong Kim, Fenfei Zou, Rintaro Noro, Mika Chiba, Arimi Ishikawa, Shinobu Κunugi, Kaoru Kubota, Akihiko Gemma
AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and migration, is also associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated the prognostic significance of the expression of AXL and/or its ligand, growth arrest-specific 6 (GAS6), in completely resected lung AD. We evaluated the relationship between AXL, GAS6, and vimentin expression, as determined by immunohistochemistry (IHC) analysis, with overall survival and disease-free survival in 113 patients with stages I-III lung AD...
April 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440488/dipeptidyl-peptidase%C3%A2-4-inhibitor-sitagliptin-prevents-high-glucose%C3%A2-induced-apoptosis-via-activation-of-amp%C3%A2-activated-protein-kinase-in-endothelial-cells
#20
Chao Wu, Shunying Hu, Nanping Wang, Jianwei Tian
Diabetes mellitus (DM), which is a chronic metabolic disorder, is the primary risk factor of life‑threatening vascular complications. Endothelial apoptosis is important in the development of the initial vascular lesion preceding the diabetic disease. Sitagliptin is a dipeptidyl peptidase‑4 (DPP‑4) inhibitor and extensively used in the clinical treatment of DM. DPP‑4 inhibitors have been demonstrated to be beneficial in the improvement of endothelial homeostasis, however the molecular mechanism by which they exhibit these effects remains to be elucidated...
April 21, 2017: Molecular Medicine Reports
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