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https://www.readbyqxmd.com/read/28333239/small-bowel-carcinomas-in-coeliac-or-crohn-s-disease-clinico-pathological-molecular-and-prognostic-features-a-study-from-the-small-bowel-cancer-italian-consortium
#1
Alessandro Vanoli, Antonio Di Sabatino, Daniela Furlan, Catherine Klersy, Federica Grillo, Roberto Fiocca, Claudia Mescoli, Massimo Rugge, Gabriella Nesi, Paolo Fociani, Gianluca Sampietro, Sandro Ardizzone, Ombretta Luinetti, Antonio Calabrò, Francesco Tonelli, Umberto Volta, Donatella Santini, Giacomo Caio, Paolo Giuffrida, Luca Elli, Stefano Ferrero, Giovanni Latella, Antonio Ciardi, Roberto Caronna, Gaspare Solina, Aroldo Rizzo, Carolina Ciacci, Francesco P D'Armiento, Marianna Salemme, Vincenzo Villanacci, Renato Cannizzaro, Vincenzo Canzonieri, Luca Reggiani Bonetti, Livia Biancone, Giovanni Monteleone, Augusto Orlandi, Giuseppe Santeusanio, Maria C Macciomei, Renata D'Incà, Vittorio Perfetti, Giancarlo Sandri, Marco Silano, Ada M Florena, Antonino G Giannone, Claudio Papi, Luigi Coppola, Paolo Usai, Antonio Maccioni, Marco Astegiano, Paola Migliora, Rachele Manca, Michele Martino, Davide Trapani, Roberta Cerutti, Paola Alberizzi, Roberta Riboni, Fausto Sessa, Marco Paulli, Enrico Solcia, Gino R Corazza
Background and Aims.: An increased risk of small bowel carcinoma (SBC) has been reported in coeliac disease (CD) and Crohn's disease (CrD). We explored clinico-pathologic, molecular and prognostic features of CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) in comparison with sporadic SBC (spo-SBC). Methods.: Seventy-six patients undergoing surgical resection for non-familial SBC (26 CD-SBC, 25 CrD-SBC, 25 spo-SBC) were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability (MSI) and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations...
February 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332497/epigenetically-driven-anatomical-diversity-of-synovial-fibroblasts-guides-joint-specific-fibroblast-functions
#2
Mojca Frank-Bertoncelj, Michelle Trenkmann, Kerstin Klein, Emmanuel Karouzakis, Hubert Rehrauer, Anna Bratus, Christoph Kolling, Maria Armaka, Andrew Filer, Beat A Michel, Renate E Gay, Christopher D Buckley, George Kollias, Steffen Gay, Caroline Ospelt
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28325667/early-lung-adenocarcinoma-in-mice-micro-computed-tomography-manifestations-and-correlation-with-pathology
#3
Lin Deng, Shi Man Xiao, Jin Wei Qiang, Yong Ai Li, Yu Zhang
Lung cancer is the most common fatal malignancy for both men and women and adenocarcinoma is the most common histologic type. Early diagnosis of lung cancer can significantly improve the survival rate of patients. This study aimed to investigate the micro-computed tomography (micro-CT) manifestations of early lung adenocarcinoma (LAC) in mice and to provide a new perspective for early clinical diagnosis. Early LAC models in 10 mice were established by subcutaneously injecting 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) solution...
March 15, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28321180/multiple-kinases-involved-in-the-nicotinic-modulation-of-gamma-oscillations-in-the-rat-hippocampal-ca3-area
#4
JianGang Wang, XiaoLong He, Fangli Guo, XiangLin Cheng, Yali Wang, XiaoFang Wang, ZhiWei Feng, Martin Vreugdenhil, ChengBiao Lu
Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28320832/g-csf-receptor-blockade-ameliorates-arthritic-pain-and-disease
#5
Ming-Chin Lee, James A McCubbin, Anne D Christensen, Daniel P Poole, Pradeep Rajasekhar, TinaMarie Lieu, Nigel W Bunnett, Sonia Garcia-Caraballo, Andelain Erickson, Stuart M Brierley, Reem Saleh, Adrian Achuthan, Andrew J Fleetwood, Robin L Anderson, John A Hamilton, Andrew D Cook
G-CSF or CSF-3, originally defined as a regulator of granulocyte lineage development via its cell surface receptor (G-CSFR), can play a role in inflammation, and hence in many pathologies, due to its effects on mature lineage populations. Given this, and because pain is an extremely important arthritis symptom, the efficacy of an anti-G-CSFR mAb for arthritic pain and disease was compared with that of a neutrophil-depleting mAb, anti-Ly6G, in both adaptive and innate immune-mediated murine models. Pain and disease were ameliorated in Ag-induced arthritis, zymosan-induced arthritis, and methylated BSA/IL-1 arthritis by both prophylactic and therapeutic anti-G-CSFR mAb treatment, whereas only prophylactic anti-Ly6G mAb treatment was effective...
March 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28320414/epidermal-growth-factor-receptor-and-epididymis-invasion-as-prognostic-biomarkers-in-clinical-stage-i-testicular-germ-cell-tumours
#6
Miguel F Sanmamed, E Esteban, E Uriol, R Zarate, M Capelan, C Muriel, G Crespo, J P Berros, P Pardo-Coto, Q Perez, C Alvarez-Fernández, P Jiménez Fonseca, M Luque, A Astudillo
BACKGROUND: Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study...
March 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28320274/brain-mitochondrial-subproteome-of-rpn10-binding-proteins-and-its-changes-induced-by-the-neurotoxin-mptp-and-the-neuroprotector-isatin
#7
A E Medvedev, O A Buneeva, A T Kopylov, O V Tikhonova, M V Medvedeva, L N Nerobkova, I G Kapitsa, V G Zgoda
Mitochondria play an important role in molecular mechanisms of neuroplasticity, adaptive changes of the brain that occur in the structure and function of its cells in response to altered physiological conditions or development of pathological disorders. Mitochondria are a crucial target for actions of neurotoxins, causing symptoms of Parkinson's disease in various experimental animal models, and also neuroprotectors. Good evidence exists in the literature that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria), and neuroprotective effects of certain antiparkinsonian agents (monoamine oxidase inhibitors) may be associated with their effects on UPS...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28315597/discovery-of-n-3-5-3-acrylamido-4-morpholine-4-carbonyl-phenyl-amino-1-methyl-6-oxo-1-6-dihydropyridin-3-yl-2-methylphenyl-4-tert-butyl-benzamide-chmfl-btk-01-as-a-highly-selective-irreversible-bruton-s-tyrosine-kinase-btk-inhibitor
#8
Qianmao Liang, Yongfei Chen, Kailin Yu, Cheng Chen, Shouxiang Zhang, Aoli Wang, Wei Wang, Hong Wu, Xiaochuan Liu, Beilei Wang, Li Wang, Zhenquan Hu, Wenchao Wang, Tao Ren, Shanchun Zhang, Qingsong Liu, Cai-Hong Yun, Jing Liu
Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other kinases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7 nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35) = 0.00) among 468 kinases/mutants at the concentration of 1 μM...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28315268/sigma-1-receptor-antagonists-a-new-class-of-neuromodulatory-analgesics
#9
Cristina Sánchez-Fernández, José Manuel Entrena, José Manuel Baeyens, Enrique José Cobos
The sigma-1 receptor is a unique ligand-operated chaperone present in key areas for pain control, in both the peripheral and central nervous system. Sigma-1 receptors interact with a variety of protein targets to modify their function. These targets include several G-protein-coupled receptors such as the μ-opioid receptor, and ion channels such as the N-methyl-D-aspartate receptor (NMDAR). Sigma-1 antagonists modify the chaperoning activity of sigma-1 receptor by increasing opioid signaling and decreasing NMDAR responses, consequently enhancing opioid antinociception and decreasing the sensory hypersensitivity that characterizes pathological pain conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28306698/oral-application-of-magnesium-l-threonate-attenuates-vincristine-induced-allodynia-and-hyperalgesia-by-normalization-of-tumor-necrosis-factor-%C3%AE-nuclear-factor-%C3%AE%C2%BAb-signaling
#10
Ting Xu, Dai Li, Xin Zhou, Han-Dong Ouyang, Li-Jun Zhou, Hang Zhou, Hong-Mei Zhang, Xu-Hong Wei, Guosong Liu, Xian-Guo Liu
BACKGROUND: Antineoplastic agents, including vincristine, often induce neuropathic pain and magnesium deficiency clinically, but the causal link between them has not been determined. No drug is available for treating this form of neuropathic pain. METHODS: Injection of vincristine (0.1 mg · kg · day, intraperitoneally, for 10 days) was used to induce nociceptive sensitization, which was accessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats...
March 17, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28303940/strain-differences-in-arsenic-induced-oxidative-lesion-via-arsenic-biomethylation-between-c57bl-6j-and-129x1-svj-mice
#11
Ruirui Wu, Xiafang Wu, Huihui Wang, Xin Fang, Yongfang Li, Lanyue Gao, Guifan Sun, Jingbo Pi, Yuanyuan Xu
Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303654/live-cell-imaging-of-bacterial-cells-pyrenoylpyrrole-based-fluorescence-labelling
#12
Arun Divakar Mathiyazhagan, Sivakumar Shanmugam
A novel substituted pyrenoylpyrroles was synthesized by the reaction of pyrenoyl chalcone, TosMIC and methyl iodide under mild condition. All the synthesized compounds were screened for their bioactivity and the MIC was determined, among which few compounds showed moderate antibacterial activity towards gram-positive as well as negative bacteria. Further, cytotoxicity assay ascertained that these compounds were non-toxic to mammalian cells as well. The pyrene chromophore in the synthesized compounds (3a-e) and (5a-e) is responsible for the good photophysical properties which have an absorbance at λ 340 nm and emission at λ 410 nm...
March 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28298607/human-herpesvirus-6b-induces-hypomethylation-on-chromosome-17p13-3-correlating-with-increased-gene-expression-and-virus-integration
#13
Elin Engdahl, Nicky Dunn, Pitt Niehusmann, Sarah Wideman, Peter Wipfler, Albert J Becker, Tomas J Ekström, Malin Almgren, Anna Fogdell-Hahn
Human herpesvirus 6B (HHV-6B) is a neurotropic beta-herpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with Illumina 450K array comparing HHV-6B infected and uninfected Molt-3 T cells three days post infection. Bisulfite pyrosequencing was used to validate Illumina results and investigate methylation over time in vitro Expression of genes was investigated using qPCR, and virus integration was investigated with PCR...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28294537/beyond-histones-the-expanding-roles-of-protein-lysine-methylation
#14
REVIEW
Zhouran Wu, Justin Connolly, Kyle K Biggar
A robust signaling network is essential for cell survival. At the molecular level, this is often mediated by as many as 200 different types of post-translational modifications that are made to proteins. These include well-documented examples such as phosphorylation, ubiquitination, acetylation, and methylation. Of these modifications, non-histone protein lysine methylation has only recently emerged as a prevalent modification occurring on numerous proteins, thus extending its role well beyond the histone code...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28293299/identification-of-epigenetic-signature-associated-with-alpha-thalassemia-mental-retardation-x-linked-syndrome
#15
Laila C Schenkel, Kristin D Kernohan, Arran McBride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic
BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX. The mechanisms involved in the ATR-X pathology are not completely understood, but may involve epigenetic modifications. ATRX has been linked to the regulation of histone H3 and DNA methylation, while mutations in the ATRX gene may lead to the downstream epigenetic and transcriptional effects. Elucidating the underlying epigenetic mechanisms altered in ATR-X will provide a better understanding about the pathobiology of this disease, as well as provide novel diagnostic biomarkers...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28291707/epigenetics-of-atherosclerosis-emerging-mechanisms-and-methods
#16
REVIEW
Nadiya Khyzha, Azad Alizada, Michael D Wilson, Jason E Fish
Atherosclerosis is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls. Vessel occlusion, often occurring after plaque rupture, can result in myocardial and cerebral infarction. Epigenetic changes are increasingly being associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. Emerging genomic approaches that profile DNA methylation, chromatin accessibility, post-translational histone modifications, transcription factor binding, and RNA expression in low or single cell populations are poised to enhance our spatiotemporal understanding of atherogenesis...
March 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28289705/als-patients-regulatory-t-lymphocytes-are-dysfunctional-and-correlate-with-disease-progression-rate-and-severity
#17
David R Beers, Weihua Zhao, Jinghong Wang, Xiujun Zhang, Shixiang Wen, Dan Neal, Jason R Thonhoff, Abdullah S Alsuliman, Elizabeth J Shpall, Katy Rezvani, Stanley H Appel
Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#18
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not appreciably established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28285915/adamantyl-and-other-polycyclic-cage-based-conjugates-of-desferrioxamine-b-dfob-for-treating-iron-mediated-toxicity-in-cell-models-of-parkinson-s-disease
#19
Thomas J Telfer, Jeffrey R Liddell, Clare Duncan, Anthony R White, Rachel Codd
The death of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). Elevated iron within the substantia nigra of the PD brain is thought to catalyze this neuronal death through hydroxyl radical-derived oxidative damage. Removing this excess iron presents a potential therapeutic strategy for PD. Seventeen derivatives of the non-toxic iron chelator desferrioxamine B (DFOB) were prepared by the conjugation of adamantyl- (1-4, 8-12), deconstructed adamantyl units (5-7), norborna(e)ne- (13-16) or bicyclo[2...
March 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28279081/persistent-expression-of-dopamine-synthesizing-enzymes-15-years-after-gene-transfer-in-a-primate-model-of-parkinson-s-disease
#20
Yoshihide Sehara, Ken-Ichi Fujimoto, Kunihiko Ikeguchi, Yuko Katakai, Fumiko Ono, Naomi Takino, Mika Ito, Keiya Ozawa, Shin-Ichi Muramatsu
Restoring dopamine production in the putamen through gene therapy is a straightforward strategy for ameliorating motor symptoms for Parkinson's disease (PD). In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity-based primate model of PD, we previously showed the safety and efficacy of adeno-associated virus (AAV) vector-mediated gene delivery to the putamen of three dopamine-synthesizing enzymes (tyrosine hydroxylase [TH], aromatic l-amino acid decarboxylase [AADC], and guanosine triphosphate cyclohydrolase I [GCH]) up to 10 months post-procedure...
March 9, 2017: Human Gene Therapy. Clinical Development
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