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EBioMedicine

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https://www.readbyqxmd.com/read/28089792/pharmacological-inhibition-of-pkc%C3%AE-counteracts-muscle-disease-in-a-mouse-model-of-duchenne-muscular-dystrophy
#1
V Marrocco, P Fiore, A Benedetti, S Pisu, E Rizzuto, A Musarò, L Madaro, B Lozanoska-Ochser, M Bouché
: Inflammation plays a considerable role in the progression of Duchenne Muscular Dystrophy (DMD), a severe muscle disease caused by a mutation in the dystrophin gene. We previously showed that genetic ablation of Protein Kinase C θ (PKCθ) in mdx, the mouse model of DMD, improves muscle healing and regeneration, preventing massive inflammation. To establish whether pharmacological targeting of PKCθ in DMD can be proposed as a therapeutic option, in this study we treated young mdx mice with the PKCθ inhibitor Compound 20 (C20)...
January 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28089235/targeting-cutaneous-cannabinoid-signaling-in-inflammation-a-high-way-to-heal
#2
Attila Oláh, Tamás Bíró
No abstract text is available yet for this article.
January 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28089234/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#3
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27923560/nia-interventions-testing-program-investigating-putative-aging-intervention-agents-in-a-genetically-heterogeneous-mouse-model
#4
Nancy L Nadon, Randy Strong, Richard A Miller, David E Harrison
No abstract text is available yet for this article.
December 2, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28029601/hypothalamic-amp-activated-protein-kinase-regulates-biphasic-insulin-secretion-from-pancreatic-%C3%AE-cells-during-fasting-and-in-type-2-diabetes
#5
Shinji Kume, Motoyuki Kondo, Shiro Maeda, Yoshihiko Nishio, Tsuyoshi Yanagimachi, Yukihiro Fujita, Masakazu Haneda, Keiko Kondo, Akihiro Sekine, Shin-Ich Araki, Hisazumi Araki, Masami Chin-Kanasaki, Satoshi Ugi, Daisuke Koya, Sawako Kitahara, Kiyosumi Maeda, Atsunori Kashiwagi, Takashi Uzu, Hiroshi Maegawa
Glucose-stimulated insulin secretion (GSIS) by pancreatic β cells is biphasic. However, the physiological significance of biphasic GSIS and its relationship to diabetes are not yet fully understood. This study demonstrated that impaired first-phase GSIS follows fasting, leading to increased blood glucose levels and brain glucose distribution in humans. Animal experiments to determine a possible network between the brain and β cells revealed that fasting-dependent hyperactivation of AMP-activated protein kinase in the hypothalamus inhibited first-phase GSIS by stimulating the α-adrenergic pancreatic nerve...
October 28, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28029600/therapeutic-targeting-of-autophagy
#6
REVIEW
Christina G Towers, Andrew Thorburn
Autophagy is a catabolic process that facilitates nutrient recycling via degradation of damaged organelles and proteins through lysosomal mediated degradation. Alterations in this complex, and tightly regulated process, lead to disease. Autophagy is widely accepted as cytoprotective against neurodegenerative diseases and a variety of clinical interventions are moving forward to increase autophagy as a therapeutic intervention. Autophagy has both positive and negative roles in cancer and this has led to controversy over whether or how autophagy manipulation should be attempted in cancer therapy...
October 23, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28088295/keeping-the-momentum-a-reflection-on-2016-and-a-look-forward-to-2017
#7
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28065665/unbiased-identification-of-blood-based-biomarkers-for-pulmonary-tuberculosis-by-modeling-and-mining-molecular-interaction-networks
#8
Awanti Sambarey, Abhinandan Devaprasad, Abhilash Mohan, Asma Ahmed, Soumya Nayak, Soumya Swaminathan, George D'Souza, Anto Jesuraj, Chirag Dhar, Subash Babu, Annapurna Vyakarnam, Nagasuma Chandra
Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28063778/violet-light-exposure-can-be-a-preventive-strategy-against-myopia-progression
#9
Hidemasa Torii, Toshihide Kurihara, Yuko Seko, Kazuno Negishi, Kazuhiko Ohnuma, Takaaki Inaba, Motoko Kawashima, Xiaoyan Jiang, Shinichiro Kondo, Maki Miyauchi, Yukihiro Miwa, Yusaku Katada, Kiwako Mori, Keiichi Kato, Kinya Tsubota, Hiroshi Goto, Mayumi Oda, Megumi Hatori, Kazuo Tsubota
Prevalence of myopia is increasing worldwide. Outdoor activity is one of the most important environmental factors for myopia control. Here we show that violet light (VL, 360-400nm wavelength) suppresses myopia progression. First, we confirmed that VL suppressed the axial length (AL) elongation in the chick myopia model. Expression microarray analyses revealed that myopia suppressive gene EGR1 was upregulated by VL exposure. VL exposure induced significantly higher upregulation of EGR1 in chick chorioretinal tissues than blue light under the same conditions...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28057438/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#10
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28043812/muscle-weakness-and-fibrosis-due-to-cell-autonomous-and-non-cell-autonomous-events-in-collagen-vi-deficient-congenital-muscular-dystrophy
#11
Satoru Noguchi, Megumu Ogawa, May Christine Malicdan, Ikuya Nonaka, Ichizo Nishino
Congenital muscular dystrophies with collagen VI deficiency are inherited muscle disorders with a broad spectrum of clinical presentation and are caused by mutations in one of COL6A1-3 genes. Muscle pathology is characterized by fiber size variation and increased interstitial fibrosis and adipogenesis. In this study, we define critical events that contribute to muscle weakness and fibrosis in a mouse model with collagen VI deficiency. The Col6a1(GT/GT) mice develop non-progressive weakness from younger age, accompanied by stunted muscle growth due to reduced IGF-1 signaling activity...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28041926/chronic-over-expression-of-fibroblast-growth-factor-21-increases-bile-acid-biosynthesis-by-opposing-fgf15-19-action
#12
Jun Zhang, Jamila Gupte, Yan Gong, Jennifer Weiszmann, Yuan Zhang, Ki Jeong Lee, William G Richards, Yang Li
Pharmacological doses of fibroblast growth factor (FGF) 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28040451/regulation-of-xiap-turnover-reveals-a-role-for-usp11-in-promotion-of-tumorigenesis
#13
Zhuan Zhou, Aiping Luo, Indira Shrivastava, Mingjing He, Yi Huang, Ivet Bahar, Zhihua Liu, Yong Wan
The emerging regulatory role of deubiquitinases (DUBs) has been implicated in various fundamental processes and pathogenesis. To determine the pivotal role that DUBs play in mediating tumorigenesis, we have performed a non-biased screen of 67 human DUBs based on a mammary cell transformation assay. This led to the identification of USP11 as a critical determinant of mammary tumor initiation and progression. Using an approach of protein complex purification coupled with mass spectrometry, we further identified XIAP to be a target for USP11...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28024735/metabolic-syndrome-gastric-cancer-mortality-and-competing-risk-survival-analysis
#14
Mohamad Amin Pourhoseingholi, Sara Ashtari, Nastaran Hajizadeh, Mohammad Reza Zali
No abstract text is available yet for this article.
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28024734/lyn-kinase-represses-mucus-hypersecretion-by-regulating-il-13-induced-endoplasmic-reticulum-stress-in-asthma
#15
Xing Wang, Xiaoqiong Yang, Yin Li, Xiaoyun Wang, Yun Zhang, Xi Dai, Bin Niu, Juan Wu, Xiefang Yuan, Anjie Xiong, Zhigang Liu, Nanshan Zhong, Min Wu, Guoping Li
In asthma, mucus hypersecretion is thought to be a prominent pathological feature associated with widespread mucus plugging. However, the current treatments for mucus hypersecretion are often ineffective or temporary. The potential therapeutic targets of mucus hypersecretion in asthma remain unknown. Here, we show that Lyn is a central effector of endoplasmic reticulum stress (ER stress) and mucous hypersecretion in asthma. In Lyn-transgenic mice (Lyn-TG) and wild-type (WT) C57BL/6J mice exposed to ovalbumin (OVA), Lyn overexpression attenuates mucus hypersecretion and ER stress...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28007481/looking-into-the-crystal-ball-predicting-non-response-to-ursodeoxycholic-acid-in-primary-biliary-cholangitis
#16
Vincent Zimmer, Frank Lammert
No abstract text is available yet for this article.
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28007480/paternal-insulin-like-growth-factor-2-igf2-regulates-stem-cell-activity-during-adulthood
#17
Vilma Barroca, Daniel Lewandowski, Agnieszka Jaracz-Ros, Sylvie-Nathalie Hardouin
Insulin-like Growth Factor 2 (IGF2) belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC) successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/27998720/genetics-variants-and-serum-levels-of-mhc-class-i-chain-related-a-in-predicting-hepatocellular-carcinoma-development-in-chronic-hepatitis-c-patients-post-antiviral-treatment
#18
Chung-Feng Huang, Cing-Yi Huang, Ming-Lun Yeh, Shu-Chi Wang, Kuan-Yu Chen, Yu-Min Ko, Ching-Chih Lin, Yi-Shan Tsai, Pei-Chien Tsai, Zu-Yau Lin, Shinn-Cherng Chen, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu
BACKGROUND/AIMS: The genome-wide association study has shown that MHC class I chain-related A (MICA) genetic variants were associated with hepatitis C virus (HCC) related hepatocellular carcinoma. The impact of the genetic variants and its serum levels on post-treatment cohort is elusive. METHODS: MICA rs2596542 genotype and serum MICA (sMICA) levels were evaluated in 705 patients receiving antiviral therapy. RESULTS: Fifty-eight (8·2%) patients developed HCC, with a median follow-up period of 48·2months (range: 6-129months)...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/27993630/low-level-of-pdz-domain-containing-1-pdzk1-predicts-poor-clinical-outcome-in-patients-with-clear-cell-renal-cell-carcinoma
#19
Junfang Zheng, Lei Wang, Zhiqiang Peng, Ying Yang, Duiping Feng, Junqi He
Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In this study, samples from primary ccRCC tumor and their corresponding nontumor adjacent tissues (n=18) were analyzed by quantitative proteomic assay. Proteins downregulated in tumors were studied by GO and KEGG pathways enrichment analyses...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/27988133/lipids-and-their-effects-in-chronic-lymphocytic-leukemia
#20
Daphne R Friedman
No abstract text is available yet for this article.
February 2017: EBioMedicine
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