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https://www.readbyqxmd.com/read/28547797/vitamin-d-receptor-agonists-regulate-ocular-developmental-angiogenesis-and-modulate-expression-of-dre-mir-21-and-vegf
#1
Stephanie L Merrigan, Breandán N Kennedy
BACKGROUND AND PURPOSE: Pathological growth of ocular vasculature networks can underpin visual impairment in neovascular age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity. Our aim was to uncover novel pharmacological regulators of ocular angiogenesis by phenotype-based screening in zebrafish. EXPERIMENTAL APPROACH: A bioactive chemical library of 465 drugs was screened to identify small molecule inhibitors of ocular hyaloid vasculature (HV) angiogenesis in zebrafish larvae...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#2
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28544467/a-survey-on-the-beliefs-and-knowledge-of-gout-management-in-new-medical-graduates-new-south-wales-australia
#3
Matthew Terrill, John Riordan
AIM: To assess the beliefs and knowledge of gout management in new medical graduates. METHOD: A survey on gout management was sent to new medical graduates during their orientation week, New South Wales, Australia. RESULTS: Of 15 hospital networks, 11 agreed to participate. From these, 168 graduates responded (23.7% response rate). Most (81.1%) felt that gout was a serious disease, 51.2% answered that they had been taught adequately to manage acute gout, only 37...
May 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28542505/alzhcpi-a-knowledge-base-for-predicting-chemical-protein-interactions-towards-alzheimer-s-disease
#4
Jiansong Fang, Ling Wang, Yecheng Li, Wenwen Lian, Xiaocong Pang, Hong Wang, Dongsheng Yuan, Qi Wang, Ai-Lin Liu, Guan-Hua Du
Alzheimer's disease (AD) is a complicated progressive neurodegeneration disorder. To confront AD, scientists are searching for multi-target-directed ligands (MTDLs) to delay disease progression. The in silico prediction of chemical-protein interactions (CPI) can accelerate target identification and drug discovery. Previously, we developed 100 binary classifiers to predict the CPI for 25 key targets against AD using the multi-target quantitative structure-activity relationship (mt-QSAR) method. In this investigation, we aimed to apply the mt-QSAR method to enlarge the model library to predict CPI towards AD...
2017: PloS One
https://www.readbyqxmd.com/read/28540974/neuroendocrine-neoplasms-of-the-small-intestine-and-appendix-management-guidelines-recommended-by-the-polish-network-of-neuroendocrine-tumours
#5
Tomasz Bednarczuk, Marek Bolanowski, Anna Zemczak, Agata Bałdys-Waligórska, Jolanta Blicharz-Dorniak, Agnieszka Boratyn-Nowicka, Małgorzata Borowska, Andrzej Cichocki, Jarosław B Ćwikła, Massimo Falconi, Wanda Foltyn, Daria Handkiewicz-Junak, Alicja Hubalewska-Dydejczyk, Barbara Jarząb, Roman Junik, Dariusz Kajdaniuk, Grzegorz Kamiński, Agnieszka Kolasińska-Ćwikła, Aldona Kowalska, Robert Król, Leszek Królicki, Jolanta Kunikowska, Katarzyna Kuśnierz, Paweł Lampe, Dariusz Lange, Anna Lewczuk-Myślicka, Andrzej Lewiński, Michał Lipiński, Magdalena Londzin-Olesik, Bogdan Marek, Anna Nasierowska-Guttmejer, Ewa Nowakowska-Duława, Jakub Pałucki, Joanna Pilch-Kowalczyk, Violetta Rosiek, Marek Ruchała, Lucyna Siemińska, Anna Sowa-Staszczak, Teresa Starzyńska, Katarzyna Steinhof-Radwańska, Janusz Strzelczyk, Krzysztof Sworczak, Anhelli Syrenicz, Andrzej Szawłowski, Marek Szczepkowski, Ewa Wachuła, Wojciech Zajęcki, Wojciech Zgliczyński, Beata Kos-Kudła
This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28540972/gastroduodenal-neuroendocrine-neoplasms-including-gastrinoma-management-guidelines-recommended-by-the-polish-network-of-neuroendocrine-tumours
#6
Michał Lipiński, Grażyna Rydzewska, Wanda Foltyn, Elżbieta Andrysiak-Mamos, Agata Bałdys-Waligórska, Tomasz Bednarczuk, Jolanta Blicharz-Dorniak, Marek Bolanowski, Agnieszka Boratyn-Nowicka, Małgorzata Borowska, Andrzej Cichocki, Jarosław B Ćwikła, Massimo Falconi, Daria Handkiewicz-Junak, Alicja Hubalewska-Dydejczyk, Barbara Jarząb, Roman Junik, Dariusz Kajdaniuk, Grzegorz Kamiński, Agnieszka Kolasińska-Ćwikła, Aldona Kowalska, Robert Król, Leszek Królicki, Jolanta Kunikowska, Katarzyna Kuśnierz, Paweł Lampe, Dariusz Lange, Anna Lewczuk-Myślicka, Andrzej Lewiński, Magdalena Londzin-Olesik, Bogdan Marek, Anna Nasierowska-Guttmejer, Ewa Nowakowska-Duława, Joanna Pilch-Kowalczyk, Karolina Poczkaj, Violetta Rosiek, Marek Ruchała, Lucyna Siemińska, Anna Sowa-Staszczak, Teresa Starzyńska, Katarzyna Steinhof-Radwańska, Janusz Strzelczyk, Krzysztof Sworczak, Anhelli Syrenicz, Andrzej Szawłowski, Marek Szczepkowski, Ewa Wachuła, Wojciech Zajęcki, Anna Zemczak, Wojciech Zgliczyński, Beata Kos-Kudła
This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28539398/a-balance-of-outward-and-linear-inward-ionic-currents-is-required-for-the-generation-of-slow-wave-oscillations
#7
Jorge Golowasch, Amitabha Bose, Yinzheng Guan, Dalia Salloum, Andrea Roeser, Farzan Nadim
Regenerative inward currents help produce slow oscillations through a negative-slope conductance region of their current-voltage relationship that is well approximated by a linear negative conductance. We used dynamic clamp injections of a linear current with such conductance, INL, to explore why some neurons can generate intrinsic slow oscillations whereas others cannot. We addressed this question, in synaptically isolated neurons of the crab Cancer borealis, after blocking action potentials. The pyloric network consists of a distinct pacemaker and follower neurons, all of which express the same complement of ionic currents...
May 24, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28538013/update-on-the-pathogenesis-and-treatment-of-juvenile-idiopathic-arthritis
#8
Gabriella Giancane, Alessandra Alongi, Angelo Ravelli
PURPOSE OF REVIEW: To provide an overview of recently published studies on pathogenesis and management of juvenile idiopathic arthritis (JIA). RECENT FINDINGS: In the past year, the potential role of network analysis in the understanding of the molecular phenotype of individual JIA subgroups has been highlighted. In addition, potential new targets for pharmacologic interventions have been identified through the elucidation of mechanisms that modulate the function of cells involved in the inflammatory process...
May 22, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28533995/crohn-s-disease-and-ulcerative-colitis-show-unique-cytokine-profiles
#9
Zoltan H Nemeth, Dorian A Bogdanovski, Patricia Barratt-Stopper, Samantha R Paglinco, Luca Antonioli, Rolando H Rolandelli
INTRODUCTION: Networks of cytokines have been implicated in both forms of inflammatory bowel disease (IBD): Crohn's disease (CD) and ulcerative colitis (UC). While CD has associated with T-helper type 1 (Th1) immune responses, UC shows Th2 patterns. Recent studies reported that the inflamed intestinal regions in both CD and UC are significantly infiltrated with a newly described set of T helper, the Th17 cells. These cells have unique cytokine responses. These findings prompted us to further explore the cytokine profiles of CD and UC with a special focus on the Th2 and Th17 related mediators...
April 19, 2017: Curēus
https://www.readbyqxmd.com/read/28528728/spontaneous-calcium-waves-in-the-developing-enteric-nervous-system
#10
Marlene M Hao, Annette J Bergner, Caroline S Hirst, Lincon A Stamp, Franca Casagranda, Joel C Bornstein, Werend Boesmans, Pieter Vanden Berghe, Heather M Young
The enteric nervous system (ENS) is an extensive network of neurons in the gut wall that arises from neural crest-derived cells. Like other populations of neural crest cells, it is known that enteric neural crest-derived cells (ENCCs) influence the behaviour of each other and therefore must communicate. However, little is known about how ENCCs communicate with each other. In this study, we used Ca(2+) imaging to examine communication between ENCCs in the embryonic gut, using mice where ENCCs express a genetically-encoded calcium indicator...
May 18, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28526134/molecular-biology-digest-of-cell-mitophagy
#11
I Matic, D Strobbe, F Di Guglielmo, M Campanella
The homeostasis of eukaryotic cells relies on efficient mitochondrial function. The control of mitochondrial quality is framed by the combination of distinct but interdependent mechanisms spanning biogenesis, regulation of dynamic network, and finely tuned degradation either through ubiquitin-proteasome system or autophagy (mitophagy). There is continuous evolution on the pathways orchestrating the mitochondrial response to stress signals and the organelle adaptation to quality control during acute and subtle dysfunctions...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28525889/eugenol-alleviated-breast-precancerous-lesions-through-her2-pi3k-akt-pathway-induced-cell-apoptosis-and-s-phase-arrest
#12
Min Ma, Yi Ma, Gui-Juan Zhang, Rui Liao, Xue-Feng Jiang, Xian-Xin Yan, Feng-Jie Bie, Xiao-Bo Li, Yan-Hong Lv
Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525544/bistability-causality-and-complexity-in-cortical-networks-an-in-vitro-perturbational-study
#13
Mattia D'Andola, Beatriz Rebollo, Adenauer G Casali, Julia F Weinert, Andrea Pigorini, Rosa Villa, Marcello Massimini, Maria V Sanchez-Vives
Measuring the spatiotemporal complexity of cortical responses to direct perturbations provides a reliable index of the brain's capacity for consciousness in humans under both physiological and pathological conditions. Upon loss of consciousness, the complex pattern of causal interactions observed during wakefulness collapses into a stereotypical slow wave, suggesting that cortical bistability may play a role. Bistability is mainly expressed in the form of slow oscillations, a default pattern of activity that emerges from cortical networks in conditions of functional or anatomical disconnection...
May 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28522735/d3-receptors-regulate-excitability-in-a-unique-class-of-prefrontal-pyramidal-cell
#14
Rebecca L Clarkson, Alayna T Liptak, Steven M Gee, Vikaas S Sohal, Kevin J Bender
The D3 dopamine receptor, a member of the Gi-coupled D2-family of dopamine receptors, is expressed throughout limbic circuits affected in neuropsychiatric disorders, including prefrontal cortex. These receptors are important for prefrontal executive function, as pharmacological and genetic manipulations that affect prefrontal D3 receptors alter anxiety, social interaction, and reversal learning. And yet, the mechanisms by which D3 receptors regulate prefrontal circuits, and whether D3 receptors regulate specific prefrontal subnetworks, remain unknown...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28522678/cigarette-smoking-associated-alterations-in-serotonin-adrenalin-signaling-pathways-of-platelets
#15
Curtis Lee Lowery, Clay Elliott, Anthonya Cooper, Coedy Hadden, Roberto N Sonon, Parastoo Azadi, D Keith Williams, James D Marsh, Donna S Woulfe, Fusun Kilic
BACKGROUND: Cigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system-mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5-HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated...
May 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28522244/low-molecular-weight-heparin-and-the-relative-risk-of-surgical-site-bleeding-complications-results-of-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials-of-venous-thromboprophylaxis-in-patients-after-total-joint-arthroplasty
#16
REVIEW
Kary Suen, Roger N Westh, Leonid Churilov, Andrew J Hardidge
BACKGROUND: Venous thromboembolism causes significant morbidity and mortality in patients after total joint arthroplasty. Although network meta-analyses have demonstrated a benefit of various thromboprophylactic agents, there remains a concern in the surgical community regarding the resulting wound complications. There is currently no systematic review of the surgical site bleeding complications of thromboprophylactic agents. The aim of this study was to systematically review the surgical site bleeding outcomes of venous thromboembolism prophylaxis in this population...
April 14, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28515692/wu-tou-decoction-in-rheumatoid-arthritis-integrating-network-pharmacology-and-in-vivo-pharmacological-evaluation
#17
Qingqing Guo, Kang Zheng, Danping Fan, Yukun Zhao, Li Li, Yanqin Bian, Xuemei Qiu, Xue Liu, Ge Zhang, Chaoying Ma, Xiaojuan He, Aiping Lu
Purpose: This study aimed to explore underlying action mechanism of Wu-Tou decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology prediction and experimental verification. Methods: Chemical compounds and human target proteins of WTD as well as RA-related human genes were obtained from TCM Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular networks and canonical pathways presumably involved in the treatment of WTD on RA were generated by ingenuity pathway analysis (IPA) software...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28515341/bet-bromodomain-inhibition-suppresses-innate-inflammatory-and-profibrotic-transcriptional-networks-in-heart-failure
#18
Qiming Duan, Sarah McMahon, Priti Anand, Hirsh Shah, Sean Thomas, Hazel T Salunga, Yu Huang, Rongli Zhang, Aarathi Sahadevan, Madeleine E Lemieux, Jonathan D Brown, Deepak Srivastava, James E Bradner, Timothy A McKinsey, Saptarsi M Haldar
Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28514737/integration-of-phytochemicals-and-phytotherapy-into-cancer-precision-medicine
#19
REVIEW
Thomas Efferth, Mohamed E M Saeed, Elhaj Mirghani, Awadh Alim, Zahir Yassin, Elfatih Saeed, Hassan E Khalid, Salah Daak
Concepts of individualized therapy in the 1970s and 1980s attempted to develop predictive in vitro tests for individual drug responsiveness without reaching clinical routine. Precision medicine attempts to device novel individual cancer therapy strategies. Using bioinformatics, relevant knowledge is extracted from huge data amounts. However, tumor heterogeneity challenges chemotherapy due to genetically and phenotypically different cell subpopulations, which may lead to refractory tumors. Natural products always served as vital resources for cancer therapy (e...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28510271/application-of-combination-high-throughput-phenotypic-screening-and-target-identification-methods-for-the-discovery-of-natural-product-based-combination-drugs
#20
REVIEW
Monica Isgut, Mukkavilli Rao, Chunhua Yang, Vangala Subrahmanyam, Padmashree C G Rida, Ritu Aneja
Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple targets and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural products in drug discovery...
May 16, 2017: Medicinal Research Reviews
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