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https://www.readbyqxmd.com/read/28811274/hypoxia-in-combination-with-muscle-contraction-improves-insulin-action-and-glucose-metabolism-in-human-skeletal-muscle-via-the-hif-1%C3%AE-pathway
#1
Sven W Görgens, Tim Benninghoff, Kristin Eckardt, Christian Springer, Alexandra Chadt, Anita Melior, Jakob Wefers, Andrea Cramer, Jørgen Jensen, Kåre I Birkeland, Christian A Drevon, Hadi Al-Hasani, Jürgen Eckel
Skeletal muscle insulin resistance is the hallmark of type 2 diabetes, and develops long before the onset of the disease. It is well accepted that physical activity improves glycemic control but the knowledge on underlying mechanisms mediating the beneficial effects remains incomplete. Exercise is accompanied by a decrease in intramuscular oxygen levels resulting in induction of HIF-1α. HIF-1α is a master regulator of gene expression and might play an important role in skeletal muscle function and metabolism...
August 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28810929/the-impact-of-age-and-gut-microbiota-on-th17-and-tfh-cells-in-k-bxn-autoimmune-arthritis
#2
Fei Teng, Krysta M Felix, C Pierce Bradley, Debdut Naskar, Heqing Ma, Walid A Raslan, Hsin-Jung Joyce Wu
BACKGROUND: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. METHODS: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis...
August 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#3
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28805701/a-pectic-polysaccharide-from-sijunzi-decoction-promotes-the-antioxidant-defenses-of-sw480-cells
#4
Chao Huang, Zhongkai Zhu, Xiyue Cao, Xingfu Chen, Yuping Fu, Zhengli Chen, Lixia Li, Xu Song, Renyong Jia, Zhongqiong Yin, Gang Ye, Bin Feng, Yuanfeng Zou
Sijunzi Decoction (SJZD) is a formula used for the treatment of spleen deficiency and gastrointestinal diseases in Traditional Chinese Medicine. Polysaccharides are reported to be the main components of SJZD responsible for its bio-functions. However, highly purified and clearly characterized polysaccharides from SJZD are not well described. Here we obtained a purified polysaccharide (SJZDP-II-I) from SJZD using ion exchange chromatography and gel filtration. Structure analysis by FT-IR and NMR identified SJZDP-II-I as a typical pectic polysaccharide with homogalacturonan and rhamnogalacturonan type I regions and arabinogalactan type I and II as side chains...
August 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28804598/a-rigorous-method-to-enrich-for-exosomes-from-brain-tissue
#5
Laura J Vella, Benjamin J Scicluna, Lesley Cheng, Emma G Bawden, Colin L Masters, Ching-Seng Ang, Nicholas Willamson, Catriona McLean, Kevin J Barnham, Andrew F Hill
Extracellular vesicles, including exosomes, are released by all cells, including those of the nervous system. Capable of delivering lipid, protein and nucleic acids to both nearby and distal cells, exosomes have been hypothesized to play a role in progression of many diseases of the nervous system. To date, most analyses on the role of these vesicles in the healthy and diseased state have relied on studying vesicles from in vitro sources, such as conditioned cell culture media, or body fluids. Here we have taken a critical approach to the enrichment and characterization of exosomes from human frontal cortex...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28802996/il-33-matured-dendritic-cells-promote-th17-cell-responses-via-il-1%C3%AE-and-il-6
#6
Su-Ho Park, Myun Soo Kim, Hui Xuan Lim, Daeho Cho, Tae Sung Kim
IL-33 is associated with a variety of autoimmune diseases, such as sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Although IL-33 is mainly involved in the induction of Th2 cells, however, the relationship between IL-33 and Th17 cells is still largely unknown. In this study, we investigated the effects of IL-33 on DC-mediated CD4(+) T cell activation and Th17 cell differentiation because DCs are essential cells for presenting self-antigens to CD4(+) T cells in autoimmune disease conditions...
August 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28794504/promoter-hypermethylation-of-bcl11b-gene-correlates-with-downregulation-of-gene-transcription-in-ankylosing-spondylitis-patients
#7
J Karami, M Mahmoudi, A Amirzargar, M Gharshasbi, A Jamshidi, S Aslani, M H Nicknam
Methylation of DNA is one of the important regulatory mechanisms of gene transcription. B-cell chronic lymphocytic leukemia/lymphoma 11B (BCL11B) plays a key role in the development, proliferation, differentiation, and survival of T cells. The aim of this study was to evaluate promoter methylation of BCL11B gene and its mRNA level in peripheral blood mononuclear cells (PBMCs) of ankylosing spondylitis (AS) patients in relation to healthy controls and evaluate their correlation with diseases clinical indices...
August 10, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28793267/epigenomic-landscapes-of-hesc-derived-neural-rosettes-modeling-neural-tube-formation-and-diseases
#8
Cristina Valensisi, Colin Andrus, Sam Buckberry, Naresh Doni Jayavelu, Riikka J Lund, Ryan Lister, R David Hawkins
We currently lack a comprehensive understanding of the mechanisms underlying neural tube formation and their contributions to neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process, especially one that models human-specific aspects, is critical. Three-dimensional, human embryonic stem cell (hESC)-derived neural rosettes (NRs) provide a powerful resource for in vitro modeling of human neural tube formation. Epigenomic maps reveal enhancer elements unique to NRs relative to 2D systems...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28790933/mechanisms-of-smooth-muscle-cell-differentiation-are-distinctly-altered-in-thoracic-aortic-aneurysms-associated-with-bicuspid-or-tricuspid-aortic-valves
#9
Elena Ignatieva, Daria Kostina, Olga Irtyuga, Vladimir Uspensky, Alexey Golovkin, Natalia Gavriliuk, Olga Moiseeva, Anna Kostareva, Anna Malashicheva
Cellular and molecular mechanisms of thoracic aortic aneurysm are not clear and therapeutic approaches are mostly absent. Thoracic aortic aneurysm is associated with defective differentiation of smooth muscle cells (SMC) of aortic wall. Bicuspid aortic valve (BAV) comparing to tricuspid aortic valve (TAV) significantly predisposes to a risk of thoracic aortic aneurysms. It has been suggested recently that BAV-associated aortopathies represent a separate pathology comparing to TAV-associated dilations. The only proven candidate gene that has been associated with BAV remains NOTCH1...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28782832/aav-delivery-of-grp78-bip-promotes-adaptation-of-human-rpe-cell-to-er-stress
#10
Shima Ghaderi, Shahin Ahmadian, Zahra-Soheila Soheili, Hamid Ahmadieh, Shahram Samiei, Samira Kheitan, Ehsan Ranaei Pirmardan
Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration...
August 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28771724/aberrantly-mirna-promoter-methylation-and-emt-involving-mirnas-in-breast-cancer-metastasis-diagnosis-and-therapeutic-implications
#11
REVIEW
Maryam Zare, Milad Bastami, Saeed Solali, MohammadReza Alivand
Breast cancer (BC) is the most prevalent cancer in women worldwide. Although extensive studies are ongoing concerning its intricate molecular mechanisms, development of novel therapies and more accurate diagnostic and prognostic approaches is still a challenge. Epithelial-mesenchymal transition (EMT) enables the invasion of metastatic cancer cells and has recently been highlighted in a cancer stem cell model of BC. Epigenetic events as well as miRNA expression are the master regulators of tumorigenesis and add a further layer to the complexity of BC pathogenesis...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28769785/amyloid-%C3%AE-induced-redistribution-of-transcriptional-factor-eb-and-lysosomal-dysfunction-in-primary-microglial-cells
#12
Xingzhi Guo, Peng Tang, Li Chen, Peng Liu, Chen Hou, Xin Zhang, Yue Liu, Li Chong, Xiaoqing Li, Rui Li
Impaired clearance of Amyloid β (Aβ) by microglia in the brain may be associated with the senile plaque formation, a pathological hallmark relevant to Alzheimer's disease. Microglial cells in the brain are not able to efficiently degrade Aβ, suggesting that microglial lysosome impairment may occur. However, the mechanism of Aβ-induced impairment of microglia remains poorly understood. We observed the effects of Aβ on the trafficking of nuclear transcriptional factor EB (TFEB), a master regulator of lysosome biogenesis, and the expression of a downstream osteoporosis-associated transmembrane protein 1 (OSTM1), a vital molecule involved in lysosome acidification in primary microglial cells...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28768172/sweet-sixteenth-for-chrebp-established-roles-and-future-goals
#13
REVIEW
Aya Abdul-Wahed, Sandra Guilmeau, Catherine Postic
With the identification of ChREBP in 2001, our interest in understanding the molecular control of carbohydrate sensing has surged. While ChREBP was initially studied as a master regulator of lipogenesis in liver and fat tissue, it is now clear that ChREBP functions as a central metabolic coordinator in a variety of cell types in response to environmental and hormonal signals, with wide implications in health and disease. Celebrating its sweet sixteenth birthday, we review here the current knowledge about the function and regulation of ChREBP throughout usual and less explored tissues, to recapitulate ChREBP's role as a whole-body glucose sensor...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28760435/nutrigenomics-of-%C3%AF-3-fatty-acids-regulators-of-the-master-transcription-factors
#14
REVIEW
Maricela Rodríguez-Cruz, Donovan Solís Serna
It is well known that ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) control some key molecular cell mechanisms, resulting in a beneficial role in inflammatory diseases. Such mechanisms are complex and reflect the diversity of their functions, mainly as modulators of the dynamic properties of membranes, regulators of gene expression, and precursors of active mediators. The aim of this review is to summarize the state of the art of the effects and mechanisms by which ω-3 LC-PUFAs such as eicosapentaenoic acid (EPA, C22:5 ω-3) and docosahexaenoic acid (DHA, C22:6 ω-3) regulate different metabolic processes to maintain homeostasis...
September 2017: Nutrition
https://www.readbyqxmd.com/read/28758577/translational-shift-of-hsp90-as-a-novel-therapeutic-target-from-cancer-to-neurodegenerative-disorders-an-emerging-trend-in-the-cure-of-alzheimer-s-and-parkinson-s-diseases
#15
Qamre Alam, Mohammad Zubair Alam, Khalid Hussain Wali Sait, Nisreen Anfinan, Abdul Wahab Noorwali, Mohd Sajjad Ahmad Khan, Mohammad A Kamal, Absarul Haque
Parkinson's disease (PD) is considered as the second most common neurodegenerative disorder after Alzheimer's disease (AD). Despite having extensive research, the apparent pathogenic mechanism of these neurodegenerative disorders has not yet been fully understood. Recently, a ubiquitous molecular chaperone known as Heat Shock Protein 90 (HSP90) has been shown to play a key role in averting protein mis-folding and involves in assisting immature protein aggregation through inhibition of apoptotic activity in neuro-inflammatory disease...
July 28, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28755990/nf-%C3%AE%C2%BAb-mediated-mir-130a-modulation-in-lung-microvascular-cell-remodeling-implication-in-pulmonary-hypertension
#16
Li Li, Il-Kwon Kim, Valorie Chiasson, Piyali Chatterjee, Sudhiranjan Gupta
Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease which is associated with pulmonary arterial endothelial cells (PAEC) dysfunction and pulmonary arterial smooth muscle cells proliferation. Moreover, inflammation is contributing a critical role in EC dysfunction and remains elusive. Nuclear factor-kappa B (NF-κB) is a master transcriptional regulator in various cardiovascular pathologies; but, NF-κB's role in EC dysfunction in unknown. Our previous study using cardiac and lung specific IκBα mutant mice (3M and IKBM) showed that PAH induced right ventricular hypertrophy (RVH) was prevented in monocrotaline (MCT) treated 3M and IKBM mice, compared to the wild-type mice...
July 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28754707/repression-of-salmonella-host-cell-invasion-by-aromatic-small-molecules-from-the-human-fecal-metabolome
#17
Rafael J M Peixoto, Eduardo S Alves, Melody Wang, Rosana B R Ferreira, Alessandra Granato, Jun Han, Hira Gill, Kevan Jacobson, Leandro A Lobo, Regina M C P Domingues, Christoph H Borchers, Julian E Davies, B Brett Finlay, L Caetano M Antunes
The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions such as the production of vitamins, maturation of the immune system and protection against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on Salmonella enterica serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process...
July 28, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28738792/functional-study-of-dand5-variant-in-patients-with-congenital-heart-disease-and-laterality-defects
#18
Fernando Cristo, José M Inácio, Salomé de Almeida, Patrícia Mendes, Duarte Saraiva Martins, José Maio, Rui Anjos, José A Belo
BACKGROUND: Perturbations on the Left-Right axis establishment lead to laterality defects, with frequently associated Congenital Heart Diseases (CHDs). Indeed, in the last decade, it has been reported that the etiology of isolated cases of CHDs or cases of laterality defects with associated CHDs is linked with variants of genes involved in the Nodal signaling pathway. METHODS: With this in mind, we analyzed a cohort of 38 unrelated patients with Congenital Heart Defects that can arise from initial perturbations in the formation of the Left-Right axis and 40 unrelated ethnically matched healthy individuals as a control population...
July 24, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28738171/emerging-roles-for-tfeb-in-the-immune-response-and-inflammation
#19
Owen A Brady, José A Martina, Rosa Puertollano
Inflammation is a central feature of an effective immune response, which functions to eliminate pathogens and other foreign material, and promote recovery; however, dysregulation of the inflammatory response is associated with a wide variety of disease states. The autophagy-lysosome pathway is one of 2 major degradative pathways used by the cell and serves to eliminate long-lived and dysfunctional proteins and organelles to maintain homeostasis. Mounting evidence implicates the autophagy-lysosome pathway as a key player in regulating the inflammatory response; hence many inflammatory diseases may fundamentally be diseases of autophagy-lysosome pathway dysfunction...
July 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28737171/brg1-swi-snf-dependent-regulation-of-the-wt1-transcriptional-landscape-mediates-epicardial-activity-during-heart-development-and-disease
#20
Joaquim Miguel Vieira, Sara Howard, Cristina Villa Del Campo, Sveva Bollini, Karina N Dubé, Megan Masters, Damien N Barnette, Mala Rohling, Xin Sun, Laura E Hankins, Daria Gavriouchkina, Ruth Williams, Daniel Metzger, Pierre Chambon, Tatjana Sauka-Spengler, Benjamin Davies, Paul R Riley
Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin β4 (Tβ4) and myocardial infarction (MI) by reactivating a fetal gene programme to promote neovascularization and cardiomyogenesis. The mechanism for epicardial gene (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of the SWI/SNF chromatin-remodelling complex, is required for expression of Wilms' tumour 1 (Wt1), fetal EPDC activation and subsequent differentiation into coronary smooth muscle, and restores Wt1 activity upon MI...
July 24, 2017: Nature Communications
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