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https://www.readbyqxmd.com/read/28103528/topical-vaccination-with-super-stable-ready-to-use-nanovesicles
#1
Ayelen Tatiana Caimi, Federico Parra, Marcelo Alexander de Farias, Rodrigo Villares Portugal, Ana Paula Perez, Eder Lilia Romero, Maria Jose Morilla
Ultradeformable archaeosomes (UDA) are nanovesicles made of total polar archaeolipids (TPA) from the archaea Halorubrum tebenquichense, soybean phosphatidylcholine and sodium cholate (3:3:1w/w). Fresh dispersions of UDA including different type of antigens are acknowledged as efficient topical vaccination agents. UDA dispersions however, if manufactured for pharmaceutical use, have to maintain colloidal stability upon liposomicidal processes such as sterilization and lyophilization (SLRUDA), needed to extend shelf life during storage...
December 26, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28103022/discovery-of-a-novel-series-of-orally-bioavailable-and-cns-penetrant-glucagon-like-peptide-1-receptor-glp-1r-non-competitive-antagonists-based-on-a-1-3-disubstituted-7-aryl-5-5-bis-trifluoromethyl-5-8-dihydropyrimido-4-5-d-pyrimidine-2-4-1h-3h-dione-core
#2
Kellie D Nance, Emily L Days, C David Weaver, Anastasia Coldren, Tiffany D Farmer, Hyekyung P Cho, Colleen M Niswender, Anna L Blobaum, Kevin D Niswender, Craig W Lindsley
A duplexed, functional multi-addition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) non-competitive antagonist. Antagonist 5d not only blocked Exendin-4-stimulated insulin release in islets, but also lowered insulin levels while increasing blood glucose in vivo.
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28102700/aryl-hydrocarbon-receptor-deficient-mice-are-protected-from-high-fat-diet-induced-changes-in-metabolic-rhythms
#3
Cassie Jaeger, Canxin Xu, Mingwei Sun, Stacey Krager, Shelley A Tischkau
High fat diet (HFD) consumption alters the synchronized circadian timing system resulting in harmful loss, gain or shift of transcriptional oscillations. The aryl hydrocarbon receptor (AhR) shares structural homology to clock genes, containing both PAS domains and basic helix-loop helix structural motifs, allowing for interaction with components of the primary circadian feedback loop. Activation of AhR alters circadian rhythmicity, primarily through inhibition of Clock/Bmal1-mediated regulation of Per1. AhR-deficient mice are protected from diet-induced metabolic dysfunction, exhibiting enhanced insulin sensitivity and glucose tolerance...
January 19, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28102587/dietary-%C3%AE-cyclodextrin-reduces-atherosclerosis-and-modifies-gut-flora-in-apolipoprotein-e-deficient-mice
#4
Toshihiro Sakurai, Akiko Sakurai, Ye Chen, Boris L Vaisman, Marcelo J Amar, Milton Pryor, Seth G Thacker, Xue Zhang, Xujing Wang, Yubo Zhang, Jun Zhu, Zhi-Hong Yang, Lita A Freeman, Alan T Remaley
SCOPE: α-Cyclodextrin (α-CD), a cyclic polymer of glucose, has been shown to lower plasma cholesterol in animals and humans; however, its effect on atherosclerosis has not been previously described. METHODS AND RESULTS: apoE-knockout mice were fed either low-fat diet (LFD; 5.2% fat, w/w), or Western high fat diet (21.2% fat) containing either no additions (WD), 1.5% α-CD (WDA); 1.5% β-CD (WDB); or 1.5% oligofructose-enriched inulin (WDI). Although plasma lipids were similar after 11 weeks on the WD vs...
January 19, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28102557/cardiovascular-disease-and-prediabetes-as-complex-illness-people-s-perspectives
#5
Kim van Wissen, Michelle Thunders, Karen Mcbride-Henry, Margaret Ward, Jeremy Krebs, Rachel Page
Cardiovascular disease (CVD) and sustained high blood glucose as prediabetes are an established comorbidity. People's experience in reconciling these long-term conditions requires deeper appreciation if nurses are to more effectively support person-centred care for people who have them. Our analysis explores the initial experience of people admitted to hospital with CVD who then find they also have sustained high blood glucose. Our methodology is informed by the philosophy of Gadamer and applies interpretive description to develop an interpretation of participant experiences...
January 19, 2017: Nursing Inquiry
https://www.readbyqxmd.com/read/28102395/sesamol-ameliorates-high-fat-and-high-fructose-induced-cognitive-defects-via-improving-insulin-signaling-disruption-in-the-central-nervous-system
#6
Zhigang Liu, Yali Sun, Qinglian Qiao, Tong Zhao, Wentong Zhang, Bo Ren, Qian Liu, Xuebo Liu
Sesamol, a nutritional component from sesame, possesses antioxidant, lipid lowering and antidepressant activities. Nonetheless, few studies report its effects on high-energy-dense diet-induced cognitive loss. The present research aimed to elucidate the action of sesamol on high-fat and high-fructose (HFFD) "western"-diet-induced central nervous system insulin resistance and learning and memory impairment, and further determined the possible underlying mechanism. 3 month-old C57BL/6J mice were divided into 3 groups with/without sesamol in the drinking water (0...
January 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28102299/systemic-regulation-of-l-carnitine-in-nutritional-metabolism-in-zebrafish-danio-rerio
#7
Jia-Min Li, Ling-Yu Li, Xun Qin, Li-Jun Ning, Dong-Liang Lu, Dong-Liang Li, Mei-Ling Zhang, Xin Wang, Zhen-Yu Du
Excess fat accumulation has been observed widely in farmed fish; therefore, efficient lipid-lowering factors have obtained high attention in the current fish nutrition studies. Dietary L-carnitine can increase fatty acid β-oxidation in mammals, but has produced contradictory results in different fish species. To date, the mechanisms of metabolic regulation of L-carnitine in fish have not been fully determined. The present study used zebrafish to investigate the systemic regulation of nutrient metabolism by dietary L-carnitine supplementation...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101820/insulin-insulin-like-growth-factor-1-signalling-iis-based-regulation-of-lifespan-across-species
#8
REVIEW
Rebecca Mathew, Manika Pal Bhadra, Utpal Bhadra
An organism's well-being is facilitated by numerous molecular and biochemical pathways that ensure homeostasis within cells and tissues. Aging causes a gradual let-down in the maintenance of homeostasis due to various endogenous and environmental challenges, leading to amassing of damages, functional deterioration of different tissues and vulnerability to ailments. Nutrient sensing pathways that maintain glucose homeostasis in body are involved in regulation of aging. Insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) pathway was the first nutrient sensing pathway discovered to affect the aging process...
January 18, 2017: Biogerontology
https://www.readbyqxmd.com/read/28101792/medical-management-of-diabesity-do-we-have-realistic-targets
#9
REVIEW
Joseph M Pappachan, Ananth K Viswanath
PURPOSE OF REVIEW: The global prevalence of "diabesity"-diabetes related to obesity-is increasing steadily over the past few decades because of the obesity epidemic. Although bariatric surgery is an effective treatment option for patients with diabesity, its limited availability, invasiveness, relatively high costs and the potential for surgical and postsurgical complications restrict its widespread use. Therefore, medical management is the only option for a majority of patients with diabesity...
January 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28101749/twenty-seven-years-of-cerebral-pyruvate-recycling
#10
Sebastián Cerdán
Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates...
January 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28101358/novel-predictive-biomarkers-for-cervical-cancer-prognosis
#11
Pablo Moreno-Acosta, Schyrly Carrillo, Oscar Gamboa, Alfredo Romero-Rojas, Jinneth Acosta, Monica Molano, Joseph Balart-Serra, Martha Cotes, Chloé Rancoule, Nicolas Magné
High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28101343/effect-of-1-25-oh-2d3-on-transdifferentiation-of-rat-renal-tubular-epithelial-cells-induced-by-high-glucose
#12
Hongtao Hu, Shen Xu, Shuang Hu, Yue Gao, Hua Shui
Deficiency in vitamin D and its active metabolite is a characteristic of chronic kidney diseases (CKDs). Previous studies have reported that 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D, can attenuate renal interstitial fibrosis. The present study aimed to explore the effect of 1,25(OH)2D3 on the transdifferentiation of NRK-52E rat renal tubular epithelial cells (RTECs) induced by high glucose, as well as the expression of vitamin D receptor (VDR) and production of angiotensin (Ang) II...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28101192/c-peptide-exhibits-a-late-induction-effect-on-matrix-metallopeptidase-9-in-high-glucose-stimulated-rat-mesangial-cells
#13
Junxia Wang, Yanning Li, Mingzhi Xu, Dandan Li, Yu Wang, Jinsheng Qi, Kunyu He
Insufficient matrix metalloproteinase (MMP)-9 and MMP-2 is considered to be a contributor of extracellular matrix (ECM) accumulation in diabetic nephropathy (DN). C-peptide can reverse fibrosis, thus exerting a beneficial effect on DN. Whether C-peptide induces MMP-9 and MMP-2 to reverse ECM accumulation is not clear. In the present study, in order to determine ECM metabolism, rat mesangial cells were treated with high glucose (HG) and C-peptide intervention, then the early and late effects of C-peptide on HG-affected MMP-9 and MMP-2 were evaluated...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28101143/clinical-aspects-of-pancreatogenic-diabetes-secondary-to-hereditary-pancreatitis
#14
Marcio Garrison Dytz, Pedro Arthur Hamamoto Marcelino, Olga de Castro Santos, Lenita Zajdenverg, Flavia Lucia Conceição, Tânia Maria Ortiga-Carvalho, Melanie Rodacki
BACKGROUND: Hereditary pancreatitis is a rare inherited form of pancreatitis, characterized by recurrent episodes of acute pancreatitis with early onset and/or chronic pancreatitis, and presenting brittle diabetes, composed of episodes of nonketotic hyperglycemia and severe hypoglycemia. The existing literature regarding this form of diabetes is scarce. In this report, clinical features of pancreatogenic diabetes secondary to hereditary pancreatitis are presented along with recommendations for appropriate medical treatment...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28101123/regulatory-landscape-of-age-rage-oxidative-stress-axis-and-its-modulation-by-ppar%C3%AE-activation-in-high-fructose-diet-induced-metabolic-syndrome
#15
Luca Cannizzaro, Giuseppe Rossoni, Federica Savi, Alessandra Altomare, Cristina Marinello, Thammakorn Saethang, Marina Carini, D Michael Payne, Trairak Pisitkun, Giancarlo Aldini, Asada Leelahavanichkul
BACKGROUND: The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ)...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28100772/de-novo-sphingolipid-biosynthesis-is-required-for-adipocyte-survival-and-metabolic-homeostasis
#16
Aikaterini Alexaki, Benjamin A Clarke, Oksana Gavrilova, Yinyan Ma, Hongling Zhu, Xinran Ma, Lingyan Xu, Galina Tuymetova, Bridget C Larman, Maria L Allende, Teresa M Dunn, Richard L Proia
Sphingolipids are a diverse class of essential cellular lipids that function as structural membrane components and as signaling molecules. Cells acquire sphingolipids by both de novo biosynthesis and recycling of exogenous sphingolipids. The individual importance of these pathways for the generation of essential sphingolipids in differentiated cells is not well understood. To investigate the requirement for de novo sphingolipid biosynthesis in adipocytes, a cell type with highly regulated lipid metabolism, we generated mice with an adipocyte-specific deletion of Sptlc1 Sptlc1 is an obligate subunit of serine palmitoyltransferase, the enzyme responsible for the first and rate-limiting step of de novo sphingolipid biosynthesis...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100678/modulation-of-naive-cd8-t-cell-response-features-by-ligand-density-affinity-and-continued-signaling-via-internalized-tcrs
#17
Renu Balyan, Rupali Gund, Chitra Ebenezer, Jasneet Kaur Khalsa, Divya Anna Verghese, Thyagarajan Krishnamurthy, Anna George, Vineeta Bal, Satyajit Rath, Ashutosh Chaudhry
T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific T cells or also alters responses at the single cell level. Using brief (3 h) exposure of TCR-transgenic mouse CD8 T cells in vitro to varying densities of cognate peptide-MHC ligand followed by ligand-free culture in IL-2, we found that ligand density determined the frequencies of responding cells but not the expression levels of the early activation marker molecule, CD69...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100376/-related-factors-for-severe-liver-fibrosis-in-chronic-hepatitis-c-patients-with-remunerated-blood-donation-history-in-jurong-of-jiangsu-province
#18
Y N Yao, P Huang, H B Chen, L Zhang, M Z Chen, R B Yu
Objective: The incidence of liver fibrosis in patients with chronic hepatitis C is high. Without effective treatment, it would lead to liver cirrhosis. This study is to identify the related factors for the incidence of liver fibrosis in patients with chronic hepatitis C in order to make early intervention treatment and reduce the case fatality rate. Methods: This cross-sectional survey was conducted in adults aged ≥50 years with local residence for more than 5 years in Jurong of Jiangsu province from March to May in 2015, the patients infected with hepatitis C virus through remunerated blood donation were screened and included in the analysis...
January 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28100287/characterisation-of-fatty-acid-metabolism-in-different-insulin-resistant-phenotypes-by-means-of-stable-isotopes
#19
Ellen E Blaak
The obese insulin resistant and/or prediabetic state is characterised by systemic lipid overflow, mainly driven by an impaired lipid buffering capacity of adipose tissue, and an impaired capacity of skeletal muscle to increase fat oxidation upon increased supply. This leads to the accumulation of bioactive lipid metabolites in skeletal muscle interfering with insulin sensitivity via various mechanisms. In this review, the contribution of dietary v. endogenous fatty acids to lipid overflow, their extraction or uptake by skeletal muscle as well as the fractional synthetic rate, content and composition of the muscle lipid pools is discussed in relation to the development or presence of insulin resistance and/or an impaired glucose metabolism...
January 19, 2017: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#20
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
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