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https://www.readbyqxmd.com/read/27922820/rapamycin-treatment-benefits-glucose-metabolism-in-mouse-models-of-type-2-diabetes
#1
Peter C Reifsnyder, Kevin Flurkey, Austen Te, David E Harrison
Numerous studies suggest that rapamycin treatment promotes insulin resistance, implying that rapamycin could have negative effects on patients with, or at risk for, type 2 diabetes (T2D). New evidence, however, indicates that rapamycin treatment produces some benefits to energy metabolism, even in the context of T2D. Here, we survey 5 mouse models of T2D (KK, KK-Ay, NONcNZO10, BKS-db/db, TALLYHO) to quantify effects of rapamycin on well-recognized markers of glucose homeostasis within a wide range of T2D environments...
November 30, 2016: Aging
https://www.readbyqxmd.com/read/27919712/extracts-from-two-ubiquitous-mediterranean-plants-ameliorate-cellular-and-animal-models-of-neurodegenerative-proteinopathies
#2
Michelle Briffa, Stephanie Ghio, Johanna Neuner, Alison J Gauci, Rebecca Cacciottolo, Christelle Marchal, Mario Caruana, Christophe Cullin, Neville Vassallo, Ruben J Cauchi
A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27919350/identification-and-characterization-of-severe-familial-hypercholesterolemia-in-patients-presenting-for-cardiac-catheterization
#3
Barak Zafrir, Chen Shapira, Gil Lavie, David A Halon, Moshe Y Flugelman
BACKGROUND: Patients with severe familial hypercholesterolemia (FH) are often unrecognized despite typical presentation. The introduction of PCSK9 inhibitors opens new therapeutic options and emphasizes the need for identification of severe FH patients. OBJECTIVES: The objective was identification, characterization, and management of severe FH patients by screening of cardiac catheterization (CC) database. METHODS: Retrospective analysis of CC database from 2002 to mid-2015 was performed for low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL (n = 2383)...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27919227/high-light-stress-triggers-distinct-proteomic-responses-in-the-marine-diatom-thalassiosira-pseudonana
#4
Hong-Po Dong, Yue-Lei Dong, Lei Cui, Srinivasan Balamurugan, Jian Gao, Song-Hui Lu, Tao Jiang
BACKGROUND: Diatoms are able to acclimate to frequent and large light fluctuations in the surface ocean waters. However, the molecular mechanisms underlying these acclimation responses of diaotms remain elusive. RESULTS: In this study, we investigated the mechanism of high light protection in marine diatom Thalassiosira pseudonana using comparative proteomics in combination with biochemical analyses. Cells treated under high light (800 μmol photons m(-2)s(-1)) for 10 h were subjected to proteomic analysis...
December 5, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27916986/pharmacological-modulation-of-lmna-srsf1-dependent-splicing-abrogates-diet-induced-obesity-in-mice
#5
J Santo, C Lopez-Herrera, C Apolit, Y Bareche, L Lapasset, C Chavey, S Capozi, F Mahuteau, R Najman, P Fornarelli, I C Lopez-Mejía, G Béranger, F Casas, E-Z Amri, B Pau, D Scherrer, J Tazi
BAKGROUND/OBJECTIVES: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. Alternative splicing (AS) and/or polyadenylation enable the LMNA gene to express distinct protein isoforms that exert opposing effects on energy metabolism and lifespan. Here we aimed to use the splicing factor SRSF1 that contribute to the production of these different isoforms as a target to uncover new anti-obesity drug. SUBJECTS/METHODS: Small molecules modulating SR protein activity and splicing, were tested for their abilities to interact with SRSF1 and to modulate LMNA (AS)...
December 5, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27915304/invasive-aspergillosis-in-acute-myeloid-leukemia-are-we-making-progress-in-reducing-mortality
#6
Giulia Dragonetti, Marianna Criscuolo, Luana Fianchi, Livio Pagano
The incidence of invasive fungal disease (IFD) has varied during the last decades. However, over the years, we have observed a progressive reduction of mortality, mainly due to wider use of prophylactic antifungal therapy (i.e., new azoles, such as posaconazole), the development of new and more effective antifungal drugs (lipid compounds of amphotericin B, candins, and azoles of the previous generation) and improvement of diagnostic tools. Based on a number of international studies across three decades, the attributable mortality rate for IFD and invasive aspergillosis (IA) among patients with acute myeloid leukemia (AML) has progressively declined...
December 2, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27911102/anti-cd14-antibody-treated-neutrophils-respond-to-lps-possible-involvement-of-cd14-upregulated-by-anti-cd14-antibody-binding
#7
Terukazu Sanui, Masaaki Takeshita, Takao Fukuda, Akira Haraguchi, Yoshitomi Aida, Fusanori Nishimura
CD14 and Toll-like receptor 4/MD2 (TLR4/MD2) mediate the action of LPS on neutrophils. The anti-CD14 antibody and the TLR4/MD2-antagonist, synthetic lipid IVa (LA-14-PP), are known to inhibit the response of neutrophils to LPS. We studied the role of CD14 in LPS-induced priming of neutrophils for enhanced release of the superoxide anion. The anti-CD14 antibody at much higher concentrations than required to saturate CD14 was required to inhibit priming by LPS. The inhibitory effect of the anti-CD14 antibody was overcome by LPS...
December 2, 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#8
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910283/feeding-behaviors-during-home-based-treatment-of-moderate-acute-malnutrition-using-corn-soy-blends-or-lipid-based-nutrient-supplements
#9
Ann-Sophie Iuel-Brockdorf, Albertine Ouedraogo, Christian Ritz, Tania Aase Draebel, Per Ashorn, Suzanne Filteau, Kim F Michaelsen
Feeding behaviors have an important impact on children's nutritional status and are essential to consider when implementing nutrition programs. The objective of this study was to explore and compare feeding behaviors related to supplementary feeding with corn-soy blends (CSB) and lipid-based nutrient supplements (LNS) based on best practice feeding behaviors. The study was conducted as part of a randomized controlled trial assessing the effectiveness of new formulations of CSB and LNS and comprised 1,546 children from 6 to 23 months...
December 2, 2016: Maternal & Child Nutrition
https://www.readbyqxmd.com/read/27905124/assessment-of-early-atherosclerosis-and-left-ventricular-dysfunction-in-children-with-21-hydroxylase-deficiency
#10
Rahmi Özdemir, Hüseyin Anil Korkmaz, Mehmet Küçük, Cem Karadeniz, Timur Meşe, Behzat Özkan
AIM: We analysed 25 children with 21-hydroxylase deficiency who received glucocorticoid and/or mineralocorticoid treatment for at least 12 months to determine the effects of the disease and its treatment on vascular structures and ventricular function. METHODS: Twenty-five patients with 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH) and 25 control subjects were enrolled into this observational, cross-sectional study. The patients were investigated in terms of fasting blood glucose and insulin; fasting serum lipid profile; serum 17-hydroxyprogesterone; dehydroepiandrosterone sulphate; androstenedione; and adrenocorticotropic hormone...
November 7, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/27900284/effect-of-pantethine-on-ovarian-tumor-progression-and-choline-metabolism
#11
Marie-France Penet, Balaji Krishnamachary, Flonne Wildes, Yelena Mironchik, Delia Mezzanzanica, Franca Podo, Max de Reggi, Bouchra Gharib, Zaver M Bhujwalla
Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27899885/interacting-cannabinoid-and-opioid-receptors-in-the-nucleus-accumbens-core-control-adolescent-social-play
#12
Antonia Manduca, Olivier Lassalle, Marja Sepers, Patrizia Campolongo, Vincenzo Cuomo, Giovanni Marsicano, Brigitte Kieffer, Louk J M J Vanderschuren, Viviana Trezza, Olivier J J Manzoni
Social play behavior is a highly rewarding, developmentally important form of social interaction in young mammals. However, its neurobiological underpinnings remain incompletely understood. Previous work has suggested that opioid and endocannabinoid neurotransmission interact in the modulation of social play. Therefore, we combined behavioral, pharmacological, electrophysiological, and genetic approaches to elucidate the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) in social play, and how cannabinoid and opioid neurotransmission interact to control social behavior in adolescent rodents...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27899853/four-statin-benefit-groups-defined-by-the-2013-acc-aha-new-cholesterol-guideline-are-characterized-by-increased-plasma-level-of-electronegative-low-density-lipoprotein
#13
Chih-Sheng Chu, Liang-Yin Ke, Hua-Chen Chan, Hsiu-Chua Chan, Chih-Chieh Chen, Kai-Hung Cheng, Hsiang-Chun Lee, Hsuan-Fu Kuo, Ching-Tang Chang, Kuan-Cheng Chang, Sheng-Hsiung Sheu, Chu-Huang Chen, Wen-Ter Lai
BACKGROUND: Significantly higher cytotoxic and thrombogenic human electronegative low-density lipoprotein (LDL), or L5, has been found in patients with stable coronary artery disease and acute coronary syndrome. We hypothesized that the statin-benefit groups (SBGs) defined by the new cholesterol guideline were of higher electronegative L5. METHODS: In total, 62 hyperlipidemia patients (mean age 59.4 ± 10.5, M/F 40/22) were retrospectively divided into SBGs (n = 44) and N-SBGs (n = 18)...
November 2016: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/27896589/lipid-nanoparticles-loaded-with-an-antisense-oligonucleotide-gapmer-against-bcl-2-for-treatment-of-lung-cancer
#14
Xinwei Cheng, Qibing Liu, Hong Li, Chen Kang, Yang Liu, Tianqi Guo, Ke Shang, Chengyun Yan, Guang Cheng, Robert J Lee
PURPOSE: Bcl-2 is an anti-apoptotic gene that is frequently overexpressed in human cancers. G3139 is an antisense oligonucleotide against bcl-2 that has shown limited efficacy in clinical trials. Here, we report the synthesis of a new antisense oligonucleotide containing additional chemical modifications and its delivery using nanoparticles. METHODS: An oligonucleotide G3139-GAP was synthesized, which has 2'-O-methyl nucleotides at the 5' and 3' ends based on a "gapmer" design...
November 28, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27896568/how-can-a-good-idea-fail-basal-insulin-peglispro-ly2605541-for-the-treatment-of-type-2-diabetes
#15
REVIEW
Araceli Muñoz-Garach, María Molina-Vega, Francisco J Tinahones
INTRODUCTION: Lack of control in diabetic patients has stimulated the development of new insulin analogues. One of these was basal insulin peglispro (BIL) or LY2605541; it had a large hydrodynamic size, flat pharmacokinetic profile, half life of 2-3 days and acted preferably in the liver. METHODS: We reviewed the recent literature examining the pharmacokinetics, pharmacodynamics, efficacy and safety of BIL treatment in type 2 diabetes patients. RESULTS: The pharmacodynamic and pharmacokinetic outline of BIL seemed to have an advantage over neutral protamine Hagedorn and glargine insulins...
November 28, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27896349/silver-nanoparticles-a-mechanism-of-action-on-moulds
#16
Katarzyna Pietrzak, Sława Glińska, Magdalena Gapińska, Tomasz Ruman, Adriana Nowak, Egemen Aydin, Beata Gutarowska
Silver nanoparticles (AgNPs) are widely used in all branches of industry. However, their mechanisms of action towards moulds have not been studied yet. Thus we conducted this study in which we have used laser desorption/ionization time-of-flight mass spectrometry (LDI-ToF-MS) analysis to determine metabolomic changes, and microscopic analysis (transmission electron microscopy, fluorescent microscopy) to observe changes in mould cells. The AgNP treatment caused the downregulation of 162 (15 ppm) and 284 (62 ppm), and 19 (15 ppm) and 29 (62 ppm) metabolites of Aspergillus niger and Penicillium chrysogenum, respectively...
November 29, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27895698/combinations-of-bio-active-dietary-constituents-affect-human-white-adipocyte-function-in-vitro
#17
Ines Warnke, Johan W E Jocken, Rotraut Schoop, Christine Toepfer, Regina Goralczyk, Joseph Schwager
BACKGROUND: Specific bio-active dietary compounds modulate numerous metabolic processes in adipose tissue (AT), including pre-adipocyte proliferation and differentiation. AT dysfunction, rather than an increased fat mass per se, is strongly associated with the development of insulin resistance and is characterized by impaired adipogenesis, hypertrophic adipocytes, inflammation, and impairments in substrate metabolism. A better understanding of mechanisms underlying AT dysfunction may provide new strategies for the treatment of obesity-associated metabolic diseases...
2016: Nutrition & Metabolism
https://www.readbyqxmd.com/read/27894787/safety-and-efficacy-of-liraglutide-treatment-in-japanese-type-2-diabetes-patients-after-acute-myocardial-infarction-a-non-randomized-interventional-pilot-trial
#18
Masataka Kajiwara, Atsushi Tanaka, Tomohiro Kawasaki, Koichi Nakao, Tomohiro Sakamoto, Shigeru Toyoda, Teruo Inoue, Nobuhiko Koga, Koichi Node
BACKGROUND: Glucagon-like peptide 1 analogs are expected to exert a cardio-protective action due to their effective glucose-lowering action and favorable potency on multifactorial metabolic pathways. However, the safety and tolerability of liraglutide treatment after a recent acute coronary syndrome (ACS) in Japanese patients with type 2 diabetes mellitus (T2DM) have yet to be fully established. METHODS: A total of eight T2DM patients were recruited within 2 weeks after the onset of a ST-elevation myocardial infarction (STEMI) followed by successful percutaneous coronary intervention (PCI)...
November 25, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/27893806/hplc-based-mass-spectrometry-characterizes-the-phospholipid-alterations-in-ether-linked-lipid-deficiency-models-following-oxidative-stress
#19
Robin Drechsler, Shaw-Wen Chen, Blair C R Dancy, Lena Mehrabkhani, Carissa Perez Olsen
Despite the fact that the discovery of ether-linked phospholipids occurred nearly a century ago, many unanswered questions remain concerning these unique lipids. Here, we characterize the ether-linked lipids of the nematode with HPLC-MS/MS and find that more than half of the phosphoethanolamine-containing lipids are ether-linked, a distribution similar to that found in mammalian membranes. To explore the biological role of ether lipids in vivo, we target fatty acyl-CoA reductase (fard-1), an essential enzyme in ether lipid synthesis, with two distinct RNAi strategies...
2016: PloS One
https://www.readbyqxmd.com/read/27889702/statins-and-the-cholesterol-mortality-paradox
#20
José Pedro L Nunes
Large-scale randomised controlled trials, carried out in the context of secondary cardiovascular prevention, have shown that statins are superior to placebo: these drugs were shown to decrease cardiovascular events and total mortality. A further set of clinical trials compared high intensity to low/standard intensity LDL cholesterol lowering in the same setting (using either statins or a statin/ezetimibe association). In this case, a decrease in LDL cholesterol and a concomitant significant reduction in cardiovascular events were seen with intensive therapy, however with no change in total mortality...
November 26, 2016: Scottish Medical Journal
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