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https://www.readbyqxmd.com/read/28718641/in-silico-skin-model-a-multiscale-simulation-study-of-drug-transport
#1
Kishore Gajula, Rakesh Gupta, D B Sridhar, Beena Rai
Accurate in-silico models are required to predict the release of drug molecules through skin in order to supplement the in-vivo experiments for faster development/testing of drugs. The upper most layer of the skin, stratum corneum (SC), offers main resistance for permeation of actives. Most of the SC's molecular level models comprise of cholesterol, and phospholipids only, which is far from the reality. In this study we have implemented a multiscale modelling framework to obtain the release profile of three drugs namely Caffeine, Fentanyl and Naphthol through skin SC...
July 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28714882/vitamin-d-supplementation-enhances-c18-dihydro-ceramide-levels-in-type-2-diabetes-patients
#2
Alexander Koch, Georgios Grammatikos, Sandra Trautmann, Yannick Schreiber, Dominique Thomas, Franziska Bruns, Josef Pfeilschifter, Klaus Badenhoop, Marissa Penna-Martinez
Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients. Thus, plasma samples of 59 patients with non-insulin-requiring T2D from a placebo-controlled, randomized, and double-blind study were retrospectively analyzed...
July 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28711498/promotion-of-hair-growth-by-newly-synthesized-ceramide-mimetic-compound
#3
Bu-Mahn Park, Soon-Sun Bak, Kyung-Oh Shin, Minhee Kim, Daehwan Kim, Sang-Hun Jung, Sekyoo Jeong, Young Kwan Sung, Hyunjong Kim
Based on the crucial roles of ceramides in skin barrier function, use of ceramides or their structural mimetic compounds, pseudoceramides, as cosmetic ingredients are getting more popular. While currently used pseudoceramides are intended to substitute the structural roles of ceramides in stratum corneum, development of bioactive pseudoceramides has been repeatedly reported. In this study, based on the potential involvement of sphingolipids in hair cycle regulation, we investigated the effects of newly synthesized pseudoceramide, bis-oleamido isopropyl alcohol (BOI), on hair growth using cultured human hair follicles and animal models...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710138/disruption-of-lipid-uptake-in-astroglia-exacerbates-diet-induced-obesity
#4
Yuanqing Gao, Clarita Layritz, Beata Legutko, Thomas O Eichmann, Elise Laperrousaz, Valentine S Moullé, Celine Cruciani-Guglielmacci, Christophe Magnan, Serge Luquet, Stephen C Woods, Robert H Eckel, Chun-Xia Yi, Cristina Garcia-Caceres, Matthias H Tschöp
Neuronal circuits in the brain help to control feeding behavior and systemic metabolism in response to afferent nutrient and hormonal signals. Although astrocytes have historically been assumed to be less relevant for such neuroendocrine control, we asked whether lipid uptake via lipoprotein lipase (LPL) in astrocytes is required for the central regulation of energy homeostasis. Ex vivo studies with hypothalamic-derived astrocytes showed that LPL expression is up-regulated by oleic acid; whereas it is decreased in response to palmitic acid or triglyceride...
July 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28709768/plasma-sphingosine-1-phosphate-concentrations-are-associated-with-systolic-heart-failure-in-patients-with-ischemic-heart-disease
#5
Amin Polzin, Kerstin Piayda, Petra Keul, Lisa Dannenberg, Annemarie Mohring, Markus Gräler, Tobias Zeus, Malte Kelm, Bodo Levkau
OBJECTIVE: Sphingosine-1-Phosphate (S1P) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. S1P is associated with prevalence and severity of coronary artery disease and myocardial infarction. However, its relevance in ischemic cardiomyopathy is unknown. We aimed to investigate associations of plasma S1P and other sphingolipids with the extent of heart failure in patients with ischemic heart disease. METHODS AND RESULTS: 74 patients with ischemic heart disease were investigated in this observational study...
July 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28709564/current-and-emerging-concepts-in-atopic-dermatitis-pathogenesis
#6
Marguerite Sullivan, Nanette B Silverberg
Atopic dermatitis is a common skin disorder with a complex, evolving pathogenesis. Research on the pathogenesis has shifted from focusing primarily on generalized immune system abnormalities in T helper 1/T helper 2 (Th1/Th2) activity to more targeted immune and skin barrier abnormalities contributing to the overall phenotype. Specific signaling pathways recently implicated in atopic dermatitis include production of interleukin (IL) 4 and IL-13, which promote immunoglobulin E production, Th17 and Th22 cells, and production of cytokines...
July 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28707656/-regulation-of-heat-shock-gene-expression-in-response-to-stress
#7
D G Garbuz
Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28701774/inhibition-of-%C3%AE-glucocerebrosidase-activity-preserves-motor-unit-integrity-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#8
Alexandre Henriques, Mylene Huebecker, Hélène Blasco, Céline Keime, Christian R Andres, Philippe Corcia, David A Priestman, Frances M Platt, Michael Spedding, Jean-Philippe Loeffler
Recent metabolomic reports connect dysregulation of glycosphingolipids, particularly ceramide and glucosylceramide, to neurodegeneration and to motor unit dismantling in amyotrophic lateral sclerosis at late disease stage. We report here altered levels of gangliosides in the cerebrospinal fluid of amyotrophic lateral sclerosis patients in early disease stage. Conduritol B epoxide is an inhibitor of acid beta-glucosidase, and lowers glucosylceramide degradation. Glucosylceramide is the precursor for all of the more complex glycosphingolipids...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28699686/ablation-of-ceramide-synthase-2-exacerbates-dextran-sodium-sulphate-induced-colitis-in-mice-due-to-increased-intestinal-permeability
#9
Ye-Ryung Kim, Giora Volpert, Kyong-Oh Shin, So-Yeon Kim, Sun-Hye Shin, Younghay Lee, Sun Hee Sung, Yong-Moon Lee, Jung-Hyuck Ahn, Yael Pewzner-Jung, Woo-Jae Park, Anthony H Futerman, Joo-Won Park
Ceramides mediate crucial cellular processes including cell death and inflammation and have recently been implicated in inflammatory bowel disease. Ceramides consist of a sphingoid long-chain base to which fatty acids of various length can be attached. We now investigate the effect of alerting the ceramide acyl chain length on a mouse model of colitis. Ceramide synthase (CerS) 2 null mice, which lack very-long acyl chain ceramides with concomitant increase of long chain bases and C16-ceramides, were more susceptible to dextran sodium sulphate-induced colitis, and their survival rate was markedly decreased compared with that of wild-type littermates...
July 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28697218/a-1-colloidal-oatmeal-cream-alone-is-effective-in-reducing-symptoms-of-mild-to-moderate-atopic-dermatitis-results-from-two-clinical-studies
#10
Toni Anne Lisante, Chris Nunez, Paul Zhang, Barbara M Mathes
<p>BACKGROUND: The epidermal barrier in patients with atopic dermatitis (AD) is deficient in ceramides and cathelicidins. Such epidermal defects may be a trigger for AD, thereby encouraging research toward development of skin-barrier-targeted preventive strategies.</p> <p>METHODS: Two single-center, single-arm clinical trials were conducted (study 1, age greater than equal to 8 years and study 2, greater than equal to 10 years) in patients with mild to moderate AD to evaluate the effects of an over-the-counter 1% colloidal oatmeal cream administered for 14 days...
July 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28696565/the-er-is-the-sorting-core-facility-in-the-golgi-lacking-protozoan-giardia-lamblia
#11
Nahuel Zamponi, Emiliano Zamponi, Gonzalo F Mayol, Adriana Lanfredi-Rangel, Staffan G Svärd, María C Touz
Our understanding of protein and lipid trafficking in eukaryotic cells has been challenged by the finding of different forms of compartmentalization and cargo processing in protozoan parasites. Here, we show that, in the absence of a Golgi compartment in Giardia, proteins destined for secretion are directly sorted and packaged at specialized ER regions enriched in COPII coatomer complexes and ceramide. We also demonstrated that ER-resident proteins are retained at the ER by the action of a KDEL receptor, which, in contrast to other eukaryotic KDEL receptors, showed no interorganellar dynamic but instead acts specifically at the limit of the ER membrane...
July 11, 2017: Traffic
https://www.readbyqxmd.com/read/28695226/fenretinide-differentially-modulates-the-levels-of-long-and-very-long-chain-ceramides-by-downregulating-cers5-enzyme-evidence-from-bench-to-bedside
#12
Dušan Garić, Juan B De Sanctis, Gabriella Wojewodka, Daniel Houle, Shanon Cupri, Asmahan Abu-Arish, John W Hanrahan, Marian Hajduch, Elias Matouk, Danuta Radzioch
Cystic fibrosis is the most common genetic disease, in which symptoms may be alleviated but not fully eliminated. Ceramides have long been implicated in the inflammatory etiology of cystic fibrosis, with contradicting reports with regards to their role. Recently, significant biological and biophysical differences have been observed between long- and very long-chain ceramides. This work reveals that long-chain ceramides are upregulated whereas very long-chain ceramides are downregulated in cell lines, mouse animal model, and patients with cystic fibrosis, compared with their controls...
July 10, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28695219/highly-efficient-chemoenzymatic-synthesis-and-facile-purification-of-%C3%AE-gal-pentasaccharyl-ceramide-gal%C3%AE-3nlc4%C3%AE-cer
#13
Abhishek Santra, Yanhong Li, Hai Yu, Teri J Slack, Peng George Wang, Xi Chen
A highly efficient chemoenzymatic method for synthesizing glycosphingolipids using α-Gal pentasaccharyl ceramide as an example is reported here. Enzymatic extension of the chemically synthesized lactosyl sphingosine using efficient sequential one-pot multienzyme (OPME) reactions allowed glycosylation to be carried out in aqueous solutions. Facile C18 cartridge-based quick (<30 minutes) purification protocols were established using minimal amounts of green solvents (CH3CN and H2O). Simple acylation in the last step led to the formation of the target glycosyl ceramide in 4 steps with an overall yield of 57%...
July 11, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28694327/efficacy-of-nutritional-interventions-to-lower-circulating-ceramides-in-young-adults-fruvedomic-pilot-study
#14
Alice T Mathews, Oluremi A Famodu, Melissa D Olfert, Pamela J Murray, Christopher F Cuff, Marianne T Downes, Norman J Haughey, Sarah E Colby, Paul D Chantler, I Mark Olfert, Joseph W McFadden
The 2010 USDA Dietary Guidelines for Americans (DGA) recommends a diet largely composed of fruit and vegetables. Consuming a diet high in fruit and vegetables and low in refined carbohydrates and saturated fat may reduce an individual's risk for type 2 diabetes, nonalcoholic fatty liver disease, low-grade chronic inflammation, and metabolic syndrome (MetS). Several recent studies have implicated the bioactive sphingolipid ceramide as an associative and causative biomarker for the development of these conditions...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28693956/mechanistic-insights-of-the-enhancement-effect-of-sorbitan-monooleate-on-olanzapine-transdermal-patch-both-in-release-and-percutaneous-absorption-processes
#15
Ning Li, Peng Quan, XiaoCao Wan, Chao Liu, Xiaochang Liu, Liang Fang
In this paper, based on the optimized formulation of olanzapine (OLN) transdermal patch, the role of sorbitan monooleate (SP) in OLN release and percutaneous absorption processes was probed in vitro and in vivo. Rheological test, DSC, FT-IR and molecular modeling were conducted to elucidate the effect of SP on the release process of OLN from transdermal patch. Additionally, the action of SP on the percutaneous absorption process was probed using tape stripping transdermal experiment, confocal laser scanning microscopy (CLSM), ATR-FTIR and molecular docking...
July 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28683288/hypothalamic-ampk-er-stress-jnk1-axis-mediates-the-central-actions-of-thyroid-hormones-on-energy-balance
#16
Noelia Martínez-Sánchez, Patricia Seoane-Collazo, Cristina Contreras, Luis Varela, Joan Villarroya, Eva Rial-Pensado, Xabier Buqué, Igor Aurrekoetxea, Teresa C Delgado, Rafael Vázquez-Martínez, Ismael González-García, Juan Roa, Andrew J Whittle, Beatriz Gomez-Santos, Vidya Velagapudi, Y C Loraine Tung, Donald A Morgan, Peter J Voshol, Pablo B Martínez de Morentin, Tania López-González, Laura Liñares-Pose, Francisco Gonzalez, Krishna Chatterjee, Tomás Sobrino, Gema Medina-Gómez, Roger J Davis, Núria Casals, Matej Orešič, Anthony P Coll, Antonio Vidal-Puig, Jens Mittag, Manuel Tena-Sempere, María M Malagón, Carlos Diéguez, María Luz Martínez-Chantar, Patricia Aspichueta, Kamal Rahmouni, Rubén Nogueiras, Guadalupe Sabio, Francesc Villarroya, Miguel López
Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28679588/adipocyte-mtorc1-deficiency-promotes-adipose-tissue-inflammation-and-nlrp3-inflammasome-activation-via-oxidative-stress-and-de-novo-ceramide-synthesis
#17
Patricia Chimin, Maynara L Andrade, Thiago Belchior, Vivian A Paschoal, Juliana Magdalon, Alex S Yamashita, Erique Castro, Angela Castoldi, Adriano B Chaves-Filho, Marcos Y Yoshinaga, Sayuri Miyamoto, Niels O Camara, William T Festuccia
Mechanistic Target of Rapamycin complex 1 (mTORC1) activity is increased in adipose tissue of obese, insulin resistant mice, but its role in the regulation of tissue inflammation is unknown. We investigated herein the effects of adipocyte mTORC1 deficiency on adipose tissue inflammation and glucose homeostasis. For this, mice with adipocyte raptor deletion and controls fed a chow or a high-fat diet were evaluated for body mass, adiposity, glucose homeostasis and adipose tissue inflammation. Despite reducing adiposity, adipocyte mTORC1 deficiency promoted hepatic steatosis, insulin resistance and adipose tissue inflammation (increased infiltration of macrophages, neutrophils and B lymphocytes, crown-like structure density, TNF-α, IL-6 and MCP1 expression, IL-1β protein content, lipid peroxidation and de novo ceramide synthesis)...
July 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28677109/erratum-to-comparison-of-the-simple-patient-centric-atopic-dermatitis-scoring-system-pest-with-scorad-in-young-children-using-a-ceramide-dominant-therapeutic-moisturizer
#18
Mark Jean-Ann Koh, Yoke Chin Giam, Hui Min Liew, Alice Yee-Wah Foong, Jin Ho Chong, Sharon Mun Yee Wong, Mark Boon Yang Tang, Madeline Sheun Ling Ho, Lucinda Siyun Tan, James M Mason, Michael J Cork
No abstract text is available yet for this article.
July 4, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/28674283/neutral-ceramidase-activity-inhibition-is-involved-in-palmitate-induced-apoptosis-in-ins-1-cells
#19
Fen Luo, Yamin Feng, Huimin Ma, Chao Liu, Guofang Chen, Xiao Wei, Xiaodong Mao, Xingjia Li, Yijiao Xu, Shan Tang, Honghua Wen, Junfei Jin, Qun Zhu
Neutral ceramidase (NCDase) is a class of ceramidases, a key enzyme in ceramide degradation. Recently, it was observed that NCDase activity was suppressed by saturated fatty acids to increase ceramide content in rat muscle. However, little is known about its changes in activity and roles in palmitate (Palm)-induced lipotoxicity in pancreatic β cells. Here, we demonstrated that Palm treatment significantly down-regulated NCDase activity, mRNA and protein levels in rat INS-1 cells. In addition, Palm caused a significant accumulation of ceramide, while SPH level remained unchanged, suggesting that inhibition of NCDase activity led to no change of SPH level after treatment with Palm for 24 h...
July 1, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28674269/detection-of-ceramide-a-risk-factor-for-coronary-artery-disease-in-human-coronary-plaques-by-fluorescent-angioscopy
#20
Yasumi Uchida, Yasuto Uchida, Takanobu Kobayashi, Seiichiro Shirai, Nobuyuki Hiruta, Ei Shimoyama, Tsuyoshi Tabata
BACKGROUND: The presence of ceramide in human coronary plaques is a risk factor for ischemic heart disease, but its visualization in the human vessel wall is currently beyond the scope of any available imaging techniques.Methods and Results:Deposition of ceramide was examined by fluorescent angioscopy (FA) and microscopy (FM) using golden fluorescence (Go) as a specific marker of ceramide in yellow plaques, which were obtained from 23 autopsy subjects and classified by conventional angioscopy and histology...
June 30, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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