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https://www.readbyqxmd.com/read/28108260/triple-negative-metastatic-breast-cancer-is-dependent-on-sphks-s1p-signaling-for-growth-and-survival
#1
Aparna Maiti, Kazuaki Takabe, Nitai C Hait
About 40,000 American women die from metastatic breast cancer each year despite advancements in treatment. Approximately, 15% of breast cancers are triple-negative for estrogen receptor, progesterone receptor, and HER2. Triple-negative cancer is characterized by more aggressive, harder to treat with conventional approaches and having a greater possibility of recurrence. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid signaling mediator has emerged as a key regulatory molecule in breast cancer progression...
January 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28107502/rnai-based-functional-genomics-identifies-new-virulence-determinants-in-mucormycosis
#2
Trung Anh Trieu, María Isabel Navarro-Mendoza, Carlos Pérez-Arques, Marta Sanchis, Javier Capilla, Patricia Navarro-Rodriguez, Loida Lopez-Fernandez, Santiago Torres-Martínez, Victoriano Garre, Rosa María Ruiz-Vázquez, Francisco E Nicolás
Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28106228/expression-of-long-non-coding-rna-pandar-and-its-prognostic-value-in-colorectal-cancer-patients
#3
Xiangke Li, Feng Wang, Yan Sun, Qingxia Fan, Guangfei Cui
BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as key molecules in human cancer. In the present study, we explored the role of the lncRNA PANDAR in colorectal cancer (CRC). METHODS: The relative expression level of lncRNA PANDAR in CRC tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The associations between PANDAR expression and clinicopathological features of CRC patients were further analyzed. Kaplan-Meier survival analysis was performed to evaluate the value of PANDAR in the prognosis of CRC patients...
January 20, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28106124/effect-of-myocyte-fibroblast-coupling-on-the-onset-of-pathological-dynamics-in-a-model-of-ventricular-tissue
#4
S Sridhar, Nele Vandersickel, Alexander V Panfilov
Managing lethal cardiac arrhythmias is one of the biggest challenges in modern cardiology, and hence it is very important to understand the factors underlying such arrhythmias. While early afterdepolarizations (EAD) of cardiac cells is known to be one such arrhythmogenic factor, the mechanisms underlying the emergence of tissue level arrhythmias from cellular level EADs is not fully understood. Another known arrhythmogenic condition is fibrosis of cardiac tissue that occurs both due to aging and in many types of heart diseases...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105287/systematic-study-of-effects-of-structural-modifications-on-the-aqueous-solubility-of-drug-like-molecules
#5
José A Cisneros, Michael J Robertson, Brandon Q Mercado, William L Jorgensen
Aqueous solubilities and activities have been measured for 17 members of the quinolinyltriazole series of inhibitors of human macrophage migration inhibitory factor (MIF). Systematic variation of a solvent-exposed substituent provided increases in solubility from 2 μg/mL for the parent compound 3a up to 867 μg/mL. The low solubility of 3a results from its near-planar structure and an intermolecular hydrogen bond, as revealed in a small-molecule X-ray structure. Removal of the hydrogen bond yields a 3-fold increase in solubility, but a 7-fold drop in activity...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28105244/her2-overexpression-reverses-the-relative-resistance-of-egfr-mutant-h1975-cell-line-to-gefitinib
#6
Jing Xu, Li Shen, Bi-Cheng Zhang, Wen-Hong Xu, Shu-Qin Ruan, Chi Pan, Qi-Chun Wei
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104833/idiosyncratic-drug-induced-liver-injury-is-drug-cytokine-interaction-the-linchpin
#7
Robert A Roth, Ashley R Maiuri, Patricia E Ganey
Idiosyncratic drug-induced liver injury continues to be a human health problem in part because drugs that cause these reactions are not identified in current preclinical testing and because progress in prevention is hampered by incomplete knowledge of mechanisms that underlie these adverse responses. Several hypotheses involving adaptive immune responses, inflammatory stress, inability to adapt to stress, and multiple, concurrent factors have been proposed. Yet much remains unknown about how drugs interact with the liver to effect death of hepatocytes...
February 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28104100/pathophysiologic-mechanisms-in-heart-failure-role-of-the-sympathetic-nervous-system
#8
Steve Antoine, Gaurang Vaidya, Haider Imam, Daniel Villarreal
The syndrome of heart failure involves complex pathophysiologic mechanisms and is associated with extremely high-morbidity, mortality and economic costs. This growing global epidemic has diverse etiologies and is fundamentally characterized by dyshomeostasis between heart and kidneys, leading to development and progression of the cardiorenal syndrome. Excessive and sustained sympathoexcitation has emerged as a single prominent factor involved in the structural and functional dysfunction of multiple organ systems during this disease...
January 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28103946/epcr-promotes-breast-cancer-progression-by-altering-spock1-testican-1-mediated-3d-growth
#9
Naiara Perurena, Carolina Zandueta, Susana Martínez-Canarias, Haritz Moreno, Silvestre Vicent, Ana S Almeida, Elisabet Guruceaga, Roger R Gomis, Marta Santisteban, Mikala Egeblad, José Hermida, Fernando Lecanda
BACKGROUND: Activated protein C/endothelial protein C receptor (APC/EPCR) axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated. METHODS: Transcriptomic status of EPCR was examined in a cohort of 286 breast cancer patients. Cell growth kinetics was evaluated in control and EPCR and SPARC/osteonectin, Cwcv, and kazal-like domains proteoglycan (SPOCK1/testican 1) silenced breast cancer cells in 2D, 3D, and in co-culture conditions...
January 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28103925/protocol-for-a-realist-review-of-workplace-learning-in-postgraduate-medical-education-and-training
#10
Anel Wiese, Caroline Kilty, Colm Bergin, Patrick Flood, Na Fu, Mary Horgan, Agnes Higgins, Bridget Maher, Grainne O'Kane, Lucia Prihodova, Dubhfeasa Slattery, Deirdre Bennett
BACKGROUND: Postgraduate medical education and training (PGMET) is a complex social process which happens predominantly during the delivery of patient care. The clinical learning environment (CLE), the context for PGMET, shapes the development of the doctors who learn and work within it, ultimately impacting the quality and safety of patient care. Clinical workplaces are complex, dynamic systems in which learning emerges from non-linear interactions within a network of related factors and activities...
January 19, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28099507/correlations-of-behavioral-deficits-with-brain-pathology-assessed-through-longitudinal-mri-and-histopathology-in-the-hdhq150-q150-mouse-model-of-huntington-s-disease
#11
Ivan Rattray, Edward J Smith, William R Crum, Thomas A Walker, Richard Gale, Gillian P Bates, Michel Modo
A variety of mouse models have been developed that express mutant huntingtin (mHTT) leading to aggregates and inclusions that model the molecular pathology observed in Huntington's disease. Here we show that although homozygous HdhQ150 knock-in mice developed motor impairments (rotarod, locomotor activity, grip strength) by 36 weeks of age, cognitive dysfunction (swimming T maze, fear conditioning, odor discrimination, social interaction) was not evident by 94 weeks. Concomitant to behavioral assessments, T2-weighted MRI volume measurements indicated a slower striatal growth with a significant difference between wild type (WT) and HdhQ150 mice being present even at 15 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28096456/antibody-conjugated-dna-based-nanocarriers-intercalated-with-doxorubicin-eliminate-myofibroblasts-in-explants-of-human-lens-tissue
#12
Jacquelyn Gerhart, Marvin Greenbaum, Lou Casta, Anthony Clemente, Keith Mathers, Robert Getts, Mindy George-Weinstein
Posterior capsule opacification (PCO) occurs in some adults and most children following cataract surgery. The fibrotic form of PCO arises, in part, from migratory, contractile myofibroblasts that deform the lens capsule and impair vision. In short-term cultures of human anterior lens tissue, myofibroblasts emerge from Myo/Nog cells that are identified with the G8 monoclonal antibody and by their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study, we tested the hypothesis that targeted depletion of Myo/Nog cells with the G8 mAb conjugated to three-dimensional DNA nanocarriers intercalated with Doxorubicin (G8:3DNA:Dox) would prevent the accumulation of myofibroblasts in long-term, serum and growth factor free cultures of human lens tissue obtained by capsulorhexis...
January 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28096332/human-nf-%C3%AE%C2%BAb-repressing-factor-acts-as-a-stress-regulated-switch-for-ribosomal-rna-processing-and-nucleolar-homeostasis-surveillance
#13
Marta Coccia, Antonio Rossi, Anna Riccio, Edoardo Trotta, Maria Gabriella Santoro
The nucleolus, a dynamic nuclear compartment long regarded as the cell ribosome factory, is emerging as an important player in the regulation of cell survival and recovery from stress. In larger eukaryotes, the stress-induced transcriptional response is mediated by a family of heat-shock transcription factors. Among these, HSF1, considered the master regulator of stress-induced transcriptional responses, controls the expression of cytoprotective heat shock proteins (HSPs), molecular chaperones/cochaperones constituting a major component of the cell protein quality control machinery essential to circumvent stress-induced degradation and aggregation of misfolded proteins...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096130/early-life-nutrition-and-neurodevelopment-use-of-the-piglet-as-a-translational-model
#14
REVIEW
Austin T Mudd, Ryan N Dilger
Optimal nutrition early in life is critical to ensure proper structural and functional development of infant organ systems. Although pediatric nutrition historically has emphasized research on the relation between nutrition, growth rates, and gastrointestinal maturation, efforts increasingly have focused on how nutrition influences neurodevelopment. The provision of human milk is considered the gold standard in pediatric nutrition; thus, there is interest in understanding how functional nutrients and bioactive components in milk may modulate developmental processes...
January 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28093994/viral-infection-and-obesity-current-status-and-future-prospective
#15
Sayed Sartaj Sohrab, Mohammad Amjad Kamal, Richard L Atkinson, Maha M Alawi, Esam I Azhar
The association of pathogenic viruses with obesity has now been well-known in both human and animals. Globally, human obesity has become a serious problem leading to the emergence of multiple life-threatening diseases. Adenoviruses contribute a significant role in the induction of obesity by affecting various pathways. Due to impaired immunity, obese individuals are more prone to nosocomial infections leading to complications of obesity. In contrast, several other important factors contributing to human obesity are known...
January 16, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28091579/impact-of-age-and-vaccination-history-on-long-term-serological-responses-after-symptomatic-b-pertussis-infection-a-high-dimensional-data-analysis
#16
Inonge van Twillert, Axel A Bonačić Marinović, Betsy Kuipers, Jacqueline A M van Gaans-van den Brink, Elisabeth A M Sanders, Cécile A C M van Els
Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089917/micrornas-and-dicer1-are-regulated-by-1-25-dihydroxyvitamin-d-in-prostate-stroma
#17
Shweta Dambal, Angeline A Giangreco, Andres M Acosta, Andrew Fairchild, Zachary Richards, Ryan Deaton, Dennis Wagner, Reinhold Vieth, Peter H Gann, Andre Kajdacsy-Balla, Theodorus Van der Kwast, Larisa Nonn
Vitamin D deficiency increases the risk of lethal prostate adenocarcinomas (PCa) and the majority of older men are deficient. Although PCa arises from the epithelium, the surrounding stroma has hormonal regulatory control over the epithelium and contributes to carcinogenesis. Herein, we describe regulation of microRNAs (miRs) by the active hormone dihydroxyvitamin D (1,25(OH)2D) in human prostate stroma. 1,25(OH)2D binds the vitamin D receptor (VDR) transcription factor to regulate gene expression, including miRs, which have emerged as potent regulators of protein expression...
January 12, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28087948/regulation-of-immunity-to-tuberculosis
#18
Susanna Brighenti, Diane J Ordway
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087363/membrane-restructuring-following-in-situ-sialidase-digestion-of-gangliosides-complex-model-bilayers-by-synchrotron-radiation-reflectivity
#19
Valeria Rondelli, Paola Brocca, Giovanna Fragneto, Jean Daillant, Cristina Tringali, Laura Cantu', Elena Del Favero
Synchrotron radiation reflectometry was used to access the transverse structure of model membranes under the action of the human sialidase NEU2, down to the Ångström length scale. Model membranes were designed to mimic the lipid composition of so-called Glycosphingolipids Enriched Microdomains (GEMs), which are membrane platforms specifically enriched in cholesterol and sphingolipids, where also typical signalling molecules are hosted. Gangliosides, glycosphingolipids containing one or more sialic acid residues, are asymmetrically embedded in GEMs, in the outer membrane leaflet...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28086978/correlation-of-cytokine-level-with-the-severity-of-severe-fever-with-thrombocytopenia-syndrome
#20
Miao-Miao Liu, Xiao-Ying Lei, Hao Yu, Jian-Zhi Zhang, Xue-Jie Yu
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. METHODS: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay...
January 13, 2017: Virology Journal
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