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Luise Fuhr, Rukeia El-Athman, Rosella Scrima, Olga Cela, Annalucia Carbone, Henning Knoop, Yin Li, Karen Hoffmann, Mikko O Laukkanen, Francesco Corcione, Ralf Steuer, Thomas F Meyer, Gianluigi Mazzoccoli, Nazzareno Capitanio, Angela Relógio
An endogenous molecular clockwork drives various cellular pathways including metabolism and the cell cycle. Its dysregulation is able to prompt pathological phenotypes including cancer. Besides dramatic metabolic alterations, cancer cells display severe changes in the clock phenotype with likely consequences in tumor progression and treatment response. In this study, we use a comprehensive systems-driven approach to investigate the effect of clock disruption on metabolic pathways and its impact on drug response in a cellular model of colon cancer progression...
July 10, 2018: EBioMedicine
Yoshihiro Asano
No abstract text is available yet for this article.
July 10, 2018: EBioMedicine
Yun Zhang, Hongmei Tang, Xiefang Yuan, Qin Ran, Xiaoyun Wang, Qi Song, Lei Zhang, Yuhuan Qiu, Xing Wang
Mucus secretion accumulation in the airways may act as a contributing factor for the development of airflow limitation in severe fetal asthma patients. Accumulated evidences showed that transforming growth factor beta (TGF-β) plays a regulatory role in airway remodeling including mucus hyper-secretion in asthma. However, the detailed molecular mechanisms of TGF-β3 induced MUC5AC hyper-expression in airway epithelium remains unclear. Here, we demonstrated the pivotal roles of autophagy in regulation of MUC5AC hyper-production induced by TGF-β3 in airway epithelium...
July 8, 2018: EBioMedicine
Nathalia Araujo, Nikhil Hebbar, Vivek M Rangnekar
No abstract text is available yet for this article.
July 8, 2018: EBioMedicine
Jagdeep Nanchahal, Catherine Ball, Dominique Davidson, Lynn Williams, William Sones, Fiona E McCann, Marisa Cabrita, Jennifer Swettenham, Neil J Cahoon, Bethan Copsey, E Anne Francis, Peter C Taylor, Joanna Black, Vicki S Barber, Susan Dutton, Marc Feldmann, Sarah E Lamb
BACKGROUND: Dupuytren's disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytren's disease with a TNF inhibitor. METHODS: Patients were randomised to receive adalimumab on one occasion in dose cohorts of 15 mg in 0...
July 5, 2018: EBioMedicine
Dongying Gu, Rui Zheng, Junyi Xin, Shuwei Li, Haiyan Chu, Weida Gong, Fulin Qiang, Zhengdong Zhang, Meilin Wang, Mulong Du, Jinfei Chen
BACKGROUNDS: Genome-wide association studies (GWASs) have identified several gastric cancer (GC) susceptibility loci in Asians, but their effects on disease outcome are still unknown. This study aimed to investigate whether these GWAS-identified genetic variants could serve as robust prognostic biomarkers for GC. METHODS: A multistage clinical cohort, including a total of 2432 GC patients in the Chinese population, was used to identify the association between GWAS-identified risk variants and overall survival of GC...
July 5, 2018: EBioMedicine
Dorien Kiers, Ben Wielockx, Esther Peters, Lucas T van Eijk, Jelle Gerretsen, Aaron John, Emmy Janssen, Rianne Groeneveld, Mara Peters, Lars Damen, Ana M Meneses, Anja Krüger, Jeroen D Langereis, Aldert L Zomer, Michael R Blackburn, Leo A Joosten, Mihai G Netea, Niels P Riksen, Johannes G van der Hoeven, Gert-Jan Scheffer, Holger K Eltzschig, Peter Pickkers, Matthijs Kox
Hypoxia and inflammation are closely intertwined phenomena. Critically ill patients often suffer from systemic inflammatory conditions and concurrently experience short-lived hypoxia. We evaluated the effects of short-term hypoxia on systemic inflammation, and show that it potently attenuates pro-inflammatory cytokine responses during murine endotoxemia. These effects are independent of hypoxia-inducible factors (HIFs), but involve augmented adenosine levels, in turn resulting in an adenosine 2B receptor-mediated post-transcriptional increase of interleukin (IL)-10 production...
July 4, 2018: EBioMedicine
Lei Sun, Caralina Marin de Evsikova, Ka Bian, Alexandra Achille, Elphine Telles, Huadong Pei, Edward Seto
Histone deacetylases (HDACs) are enzymes that regulate protein functions by catalyzing the removal of acetyl and acyl groups from lysine residues. They play pivotal roles in governing cell behaviors and are indispensable in numerous biological processes. HDAC11, the last identified and sole member of class IV HDACs, was reported over a decade ago. However, its physiological function remains poorly understood. Here, we report that HDAC11 knockout mice are resistant to high-fat diet-induced obesity and metabolic syndrome, suggesting that HDAC11 functions as a crucial metabolic regulator...
June 27, 2018: EBioMedicine
Hua Tan
No abstract text is available yet for this article.
June 25, 2018: EBioMedicine
Zhao Yang, Ruiyun Zhang, Yunxia Ge, Xuying Qin, Xing Kang, Yue Wang, Xu Zhang, Chengli Song, Xiaofang Quan, Haifeng Wang, Haige Chen, Chong Li
The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy benefits overall survival for patients with muscle-invasive bladder cancer (MIBC). However, the relationship between the genetic profiling of MIBC and NAC response remains unclear. Here, a mutation panel of six cancer-associated genes (TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC) panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin α3β1 (AG) and CK5/6) were developed...
June 22, 2018: EBioMedicine
Matthew Salter, Emily Corfield, Aroul Ramadass, Francis Grand, Jayne Green, Jurjen Westra, Chun Ren Lim, Lucy Farrimond, Emily Feneberg, Jakub Scaber, Alexander Thompson, Lynn Ossher, Martin Turner, Kevin Talbot, Merit Cudkowicz, James Berry, Ewan Hunter, Alexandre Akoulitchev
BACKGROUND: The identification of blood-based biomarkers specific to the diagnosis of amyotrophic lateral sclerosis (ALS) is an active field of academic and clinical research. While inheritance studies have advanced the field, a majority of patients do not have a known genetic link to the disease, making direct sequence-based genetic testing for ALS difficult. The ability to detect biofluid-based epigenetic changes in ALS would expand the relevance of using genomic information for disease diagnosis...
June 22, 2018: EBioMedicine
Monika M Skubisz, Stephen Tong, Ann Doust, Jill Mollison, Terrance G Johns, Peter Neil, Miranda Robinson, Siladitya Bhattacharya, Euan Wallace, Nicole Krzys, W Colin Duncan, Andrew W Horne
BACKGROUND: Ectopic pregnancies are a leading cause of maternal mortality. Most are treated surgically. We evaluated the efficacy and safety of combining oral gefitinib (epidermal growth factor receptor inhibitor) with methotrexate to treat larger ectopic pregnancies. METHODS: We performed a phase II, single arm, open label study across four hospitals in Edinburgh and Melbourne. We recruited women with a stable tubal ectopic pregnancy and a pre-treatment serum hCG between 1000 and 10,000 IU/L...
June 22, 2018: EBioMedicine
Xin Sun, Lijia Song, Shuang Feng, Li Li, Hongzhi Yu, Qiaoxing Wang, Xing Wang, Zhili Hou, Xue Li, Yu Li, Qiuyang Zhang, Kuan Li, Chao Cui, Junping Wu, Zhonghua Qin, Qi Wu, Huaiyong Chen
BACKGROUND: Human infections with the H7N9 virus could lead to lung damage and even multiple organ failure, which is closely associated with a high mortality rate. However, the metabolic basis of such systemic alterations remains unknown. METHODS: This study included hospitalized patients (n = 4) with laboratory-confirmed H7N9 infection, healthy controls (n = 9), and two disease control groups comprising patients with pneumonia (n = 9) and patients with pneumonia who received steroid treatment (n = 10)...
June 22, 2018: EBioMedicine
Jinhong Zhu, Wei Jia, Caixia Wu, Wen Fu, Huimin Xia, Guochang Liu, Jing He
Base excision repair (BER) is the main mechanism to repair endogenous DNA lesions caused by reactive oxygen species. BER deficiency is linked with cancer susceptibility and premature aging. Single nucleotide polymorphisms (SNPs) within BER genes have been implicated in various human malignancies. Nevertheless, a comprehensive investigation of their association with Wilms tumor susceptibility is lacking. In this study, 145 cases and 531 sex and age-matched healthy controls were recruited. We systematically genotyped 18 potentially functional SNPs in six core BER pathway genes, using a candidate SNP approach...
June 21, 2018: EBioMedicine
Aki Imai-Matsushima, Laura Martin-Sancho, Alexander Karlas, Seiichiro Imai, Tamara Zoranovic, Andreas C Hocke, Hans-Joachim Mollenkopf, Hilmar Berger, Thomas F Meyer
As the target organ for numerous pathogens, the lung epithelium exerts critical functions in health and disease. However, research in this area has been hampered by the quiescence of the alveolar epithelium under standard culture conditions. Here, we used human distal airway epithelial cells (DAECs) to generate alveolar epithelial cells. Long-term, robust growth of human DAECs was achieved using co-culture with feeder cells and supplementation with epidermal growth factor (EGF), Rho-associated protein kinase inhibitor Y27632, and the Notch pathway inhibitor dibenzazepine (DBZ)...
June 21, 2018: EBioMedicine
Peng-Peng Xu, Chun Sun, Xu Cao, Xia Zhao, Hang-Jun Dai, Shan Lu, Jian-Jun Guo, Shi-Jing Fu, Yu-Xia Liu, Su-Chun Li, Meng Chen, Ron McCord, Jeff Venstrom, Edith Szafer-Glusman, Elizabeth Punnoose, Astrid Kiermaier, Gang Cheng, Wei-Li Zhao
Immunotherapeutic agents have demonstrated encouraging signs of clinical utility in non-Hodgkin lymphoma. The goal of this study is to analyze the immune characteristics of Chinese patients with diffuse large B-cell lymphoma (DLBCL) to inform the development of immunotherapies in this patient population. Tumor samples from 211 DLBCL patients were analyzed for cell of origin (COO) and immune characteristics using the NanoString platform as well as MYC protein expression through immunohistochemistry. Lower incidence of the germinal center B-cell (GCB) subtype (93/211, 44...
June 20, 2018: EBioMedicine
Germaine Cornelissen
No abstract text is available yet for this article.
June 20, 2018: EBioMedicine
Rukeia El-Athman, Luise Fuhr, Angela Relógio
Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively...
June 20, 2018: EBioMedicine
Hiroki Fukuda, Kazuhiro Shindo, Mari Sakamoto, Tomomi Ide, Shintaro Kinugawa, Arata Fukushima, Hiroyuki Tsutsui, Shin Ito, Akira Ishii, Takashi Washio, Masafumi Kitakaze
BACKGROUND: In previous retrospective studies, we identified the 50 most influential clinical predictors of cardiovascular outcomes in patients with heart failure (HF). The present study aimed to use the novel limitless-arity multiple-testing procedure to filter these 50 clinical factors and thus yield combinations of no more than four factors that could potentially predict the onset of cardiovascular events. A Kaplan-Meier analysis was used to investigate the importance of the combinations...
June 20, 2018: EBioMedicine
Heidi Wolfmeier, Sarah C Mansour, Leo T Liu, Daniel Pletzer, Annette Draeger, Eduard B Babiychuk, Robert E W Hancock
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), typified by the pulse-field type USA300, is an emerging endemic pathogen that is spreading rapidly among healthy people. CA-MRSA causes skin and soft tissue infections, life-threatening necrotizing pneumonia and sepsis, and is remarkably resistant to many antibiotics. Here we show that engineered liposomes composed of naturally occurring sphingomyelin were able to sequester cytolytic toxins secreted by USA300 and prevent necrosis of human erythrocytes, peripheral blood mononuclear cells and bronchial epithelial cells...
June 20, 2018: EBioMedicine
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