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https://www.readbyqxmd.com/read/28647317/associations-of-systemic-sphingolipids-with-measures-of-hepatic-function-in-liver-cirrhosis-are-related-to-cholesterol
#1
Sabrina Krautbauer, Reiner Wiest, Gerhard Liebisch, Christa Buechler
Lipoprotein particles are composed of various lipid classes including cholesterol and sphingolipids, and are low in serum of patients with liver cirrhosis. Hepatic decompensation is associated with a further decline of lipoproteins. Aim of the present work was to evaluate whether ceramide and sphingomyelin species are similarly changed in patients with liver cirrhosis and whether these variations are related to systemic cholesterol levels. In a cohort of 45 patients suffering from liver cirrhosis, cholesteryl ester species and subsequently total cholesterol were identified to be negatively associated with model of end stage liver disease (MELD) score...
June 21, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28643517/a-novel-strategy-for-comprehensive-profiling-and-identification-of-acidic-glycosphingolipids-using-ultra-high-performance-liquid-chromatography-coupled-with-quadrupole-time-of-flight-mass-spectrometry
#2
Ting Hu, Zhixin Jia, Jinlan Zhang
Acidic glycosphingolipids (AGSLs), which mainly consist of ganglioside and sulfatide moieties, are highly concentrated in the central nervous system. Comprehensive profiling of AGSLs has historically been challenging because of their high complexity and the lack of standards. In this paper, a novel strategy was developed to comprehensively profile AGSLs using ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). Ganglioside isomers with different glycan chains such as GD1a/ GD1b were completely separated on a C18 column for the first time to our knowledge, facilitated by the addition of formic acid in the mobile phase...
June 23, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28634575/association-between-plasmatic-ceramides-profile-and-ast-alt-ratio-c14-0-ceramide-as-predictor-of-hepatic-steatosis-in-adolescents-independently-of-obesity
#3
Jorge Maldonado-Hernández, Gabriela E Saldaña-Dávila, Mónica I Piña-Aguero, Benjamín A Núñez-García, Mardia G López-Alarcón
OBJECTIVE: To assess the association between plasma ceramides and hepatic steatosis (HS) in adolescents, independently of obesity. MATERIALS AND METHODS: Ninety-four adolescents from two previous studies conducted and published by our crew were included. Study subjects were stratified in three groups: normal weight (n = 18), obesity (n = 34), and obesity + HS (n = 42). The presence of HS was defined when ALT/AST ratio was <1. Ceramides subspecies (C14:0, C16:0, C18:0, C24:0, and C24:1) were determined by LC/MS...
2017: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28634228/spatial-mapping-and-profiling-of-metabolite-distributions-during-germination
#4
Adam D Feenstra, Liza E Alexander, Zhihong Song, Andrew R Korte, Marna Yandeau-Nelson, Basil J Nikolau, Young-Jin Lee
Germination is a highly complex process by which seeds begin to develop and establish themselves as viable organisms. In this paper, we utilize a combination of GC-MS, LC-fluorescence, and mass spectrometry imaging (MSI) approaches to profile and visualize the metabolic distributions of germinating seeds from two different inbreds of maize seeds, B73 and Mo17. GC and LC analyses demonstrate that the two inbreds are highly differentiated in their metabolite profiles throughout the course of germination, especially with regard to amino acids, sugar alcohols, and small organic acids...
June 20, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#5
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28624380/plasma-phospholipids-and-sphingolipids-identify-stent-restenosis-after-percutaneous-coronary-intervention
#6
Song Cui, Kefeng Li, Lawrence Ang, Jinghua Liu, Liqian Cui, Xiantao Song, Shuzheng Lv, Ehtisham Mahmud
OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of plasma metabolomic biomarkers for in-stent restenosis (ISR). BACKGROUND: ISR remains an issue for patients after percutaneous coronary intervention. Identification of biomarkers to predict ISR could be invaluable for patient care. METHODS: Next-generation metabolomic profiling was performed in the discovery phase from the plasma of 400 patients undergoing percutaneous coronary intervention...
June 7, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28623546/targeting-sphingosine-1-phosphate-signaling-for-cancer-therapy
#7
REVIEW
Zuoquan Xie, Hong Liu, Meiyu Geng
Sphingosine-1-phosphate (S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival, cell proliferation, cell migration, angiogenesis and many other cellular processes. S1P either activates S1P receptors (S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1P signaling and its pathogenic roles in diseases as well as in developing modulators of S1P signaling, including S1P agonists, S1P antagonists and sphingosine kinase (SphK) inhibitors...
May 27, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28623042/corneocyte-lipid-envelope-cle-the-key-structure-for-skin-barrier-function-and-ichthyosis-pathogenesis
#8
REVIEW
Masashi Akiyama
Research on the genetic abnormalities and pathogenetic processes of ichthyoses has progressed remarkably, and many causative genes and molecules have been identified in ichthyoses and ichthyosis syndromes. Most of the genes/molecules causative of ichthyosis are associated with the barrier function of the stratum corneum, and defects in the skin barrier play important roles in the pathogenesis of various ichthyosis phenotypes. It has been elucidated that, of the ichthyosis-causative genes, ABCA12, ALOXE3, ALOX12B, CYP4F22, CERS3, ABHD5, PNPLA1 and ELOVL4 work in the formation of the corneocyte lipid envelope (CLE), a structure that is essential to sound skin barrier function...
June 8, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28621523/mussel-inspired-hyaluronic-acid-derivative-nanostructures-for-improved-tumor-targeting-and-penetration
#9
Song Yi Lee, Ju-Hwan Park, Seung-Hak Ko, Jae-Seong Shim, Dae-Duk Kim, Hyun-Jong Cho
An amphiphilic hyaluronic acid-ceramide-dopamine (HACE-d) conjugate was prepared and HACE-d-based nanoparticles (NPs) including phloretin (as an inhibitor of glucose transporter (GLUT1)) were fabricated. Mussel-inspired property of d was introduced to HACE NPs and it may improve tumor targetability and penetration in addition to passive (based on enhanced permeability and retention effect) and active (interaction between HA and CD44 receptor) tumor targeting effects. HACE-d/phloretin NPs with 279 nm mean diameter, ~0...
June 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28621262/a-peptide-antagonist-of-prep1-p160-interaction-improves-ceramide-induced-insulin-resistance-in-skeletal-muscle-cells
#10
Ilaria Cimmino, Virginia Lorenzo, Francesca Fiory, Nunzianna Doti, Serena Ricci, Serena Cabaro, Antonietta Liotti, Luigi Vitagliano, Michele Longo, Claudia Miele, Pietro Formisano, Francesco Beguinot, Menotti Ruvo, Francesco Oriente
Prep1 is a homeodomain transcription factor belonging to the TALE protein family. Its overexpression affects glucose metabolism in several tissues. In particular, in skeletal muscle tissue the interaction of Prep1 with its cofactor p160 impairs GLUT4 expression and glucose uptake.In this study, we show that ceramides (C2cer), a class of lipids antagonizing insulin signalling, increase the levels of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce their association by 80%. We find that C2cer exposure inhibits insulin receptor, IRS1 and Akt phosphorylation and reduces insulin-stimulated glycogen content and glucose uptake by 1...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28616853/comparison-of-the-simple-patient-centric-atopic-dermatitis-scoring-system-pest-with-scorad-in-young-children-using-a-ceramide-dominant-therapeutic-moisturizer
#11
Mark Jean-Ann Koh, Yoke Chin Giam, Hui Min Liew, Alice Yee-Wah Foong, Chong Jin Ho, Sharon Mun Yee Wong, Mark Boon Yang Tang, Madeline Sheun Ling Ho, Lucinda Siyun Tan, James M Mason, Michael J Cork
INTRODUCTION: Patient eczema severity time (PEST) is a new atopic dermatitis (AD) scoring system based on patients' own perception of their disease. Conventional scales such as SCORing of atopic dermatitis (SCORAD) reflect the clinician's observations during the clinic visit. Instead, the PEST score captures eczema severity, relapse and recovery as experienced by the patient or caregiver on a daily basis, promoting patient engagement, compliance with treatment and improved outcomes. This study aims to determine the correlation between carer-assessed PEST and clinician-assessed SCORAD in paediatric AD patients after 12 weeks of treatment using a ceramide-dominant therapeutic moisturizer...
June 14, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/28614356/anticancer-actions-of-lysosomally-targeted-inhibitor-lcl521-of-acid-ceramidase
#12
Aiping Bai, Cungui Mao, Russell W Jenkins, Zdzislaw M Szulc, Alicja Bielawska, Yusuf A Hannun
Acid ceramidase, which catalyzes ceramide hydrolysis to sphingosine and free fatty acid mainly in the lysosome, is being recognized as a potential therapeutic target for cancer. B13 is an effective and selective acid ceramidase inhibitor in vitro, but not as effective in cells due to poor access to the lysosomal compartment. In order to achieve targeting of B13 to the lysosome, we designed lysosomotropic N, N-dimethyl glycine (DMG)-conjugated B13 prodrug LCL521 (1,3-di-DMG-B13). Our previous results indicated the efficient delivery of B13 to the lysosome resulted in augmented effects of LCL521 on cellular acid ceramidase as evaluated by effects on substrate/product levels...
2017: PloS One
https://www.readbyqxmd.com/read/28610718/echinacea-purpurea-derived-alkylamides-exhibit-potent-anti-inflammatory-effects-and-alleviate-clinical-symptoms-of-atopic-eczema
#13
Attila Oláh, Judit Szabó-Papp, Michael Soeberdt, Ulrich Knie, Stephan Dähnhardt-Pfeiffer, Christoph Abels, Tamás Bíró
BACKGROUND: Atopic eczema (AE) is a chronic inflammatory and pruritic skin disease. There is still an unmet need for topical anti-inflammatory and anti-pruritic substances exhibiting an excellent safety profile. The endocannabinoid system is known to regulate various aspects of cutaneous barrier and immune functions, thus targeting it may be a valid approach for alleviating the symptoms of AE. OBJECTIVE: To assess the putative efficacy of Echinacea purpurea-derived alkylamides (Ec...
May 27, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28607453/specific-skeletal-muscle-sphingolipid-compounds-in-energy-expenditure-regulation-and-weight-gain-in-native-americans-of-southwestern-heritage
#14
S Heinitz, P Piaggi, K L Vinales, A Basolo, J Spranger, D Piomelli, J Krakoff, S R Jumpertz von
BACKGROUND/OBJECTIVES: In animal models, a role in the regulation of energy expenditure (EE) has been ascribed to sphingolipids, active components of cell membranes participating in cellular signaling. In humans, it is unknown whether sphingolipids play a role in the modulation of EE and, consequently, influence weight gain. The present study investigated the putative association of EE and weight gain with sphingolipid levels in human skeletal muscle, a component of fat-free mass (the strongest determinant of EE) in adipose tissue and in plasma...
June 13, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28607088/skin-specific-regulation-of-srebp-processing-and-lipid-biosynthesis-by-glycerol-kinase-5
#15
Duanwu Zhang, Wataru Tomisato, Lijing Su, Lei Sun, Jin Huk Choi, Zhao Zhang, Kuan-Wen Wang, Xiaoming Zhan, Mihwa Choi, Xiaohong Li, Miao Tang, Jose M Castro-Perez, Sara Hildebrand, Anne R Murray, Eva Marie Y Moresco, Bruce Beutler
The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands. GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28606997/hpv-e7-induces-chemotherapy-mediated-tumor-suppression-by-ceramide-dependent-mitophagy
#16
Raquela J Thomas, Natalia Oleinik, Shanmugam Panneer Selvam, Silvia G Vaena, Mohammed Dany, Rose N Nganga, Ryan Depalma, Kyla D Baron, Jisun Kim, Zdzislaw M Szulc, Besim Ogretmen
Human papillomavirus (HPV) infection is linked to improved survival in response to chemo-radiotherapy for patients with oropharynx head and neck squamous cell carcinoma (HNSCC). However, mechanisms involved in increased HNSCC cell death by HPV signaling in response to therapy are largely unknown. Here, using molecular, pharmacologic and genetic tools, we show that HPV early protein 7 (E7) enhances ceramide-mediated lethal mitophagy in response to chemotherapy-induced cellular stress in HPV-positive HNSCC cells by selectively targeting retinoblastoma protein (RB)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28603987/pharmacophore-identification-and-scaffold-exploration-to-discover-novel-potent-and-chemically-stable-inhibitors-of-acid-ceramidase-in-melanoma-cells
#17
Jose Antonio Ortega, Jose M Arencibia, Giuseppina La Sala, Marco Borgogno, Inga Bauer, Luca Bono, Clarissa Braccia, Andrea Armirotti, Stefania Girotto, Anand Ganesan, Marco De Vivo
Acid ceramidase (AC) hydrolyses ceramides, which are central lipid messengers for metabolism and signaling of sphingolipids. A growing body of evidence links deregulation of sphingolipids to several diseases, including cancer. Indeed, AC expression is abnormally high in melanoma cells. AC inhibition may thus be key to treating malignant melanoma. Here, we have used a systematic scaffold exploration to design a general pharmacophore for AC inhibition. This pharmacophore comprises a 6+5 fused ring heterocycle linked to an aliphatic substituent via a urea moiety...
June 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28600081/a-daily-skincare-regimen-with-a-unique-ceramide-and-filaggrin-formulation-rapidly-improves-chronic-xerosis-pruritus-and-quality-of-life-in-older-adults
#18
Anne Lynn S Chang, Suephy C Chen, Lars Osterberg, Staci Brandt, Erika C von Grote, Matthew H Meckfessel
A skin care regimen which significantly improved atopic dermatitis and pruritus was evaluated for its efficacy and acceptability in senior subjects diagnosed with xerosis who also suffer from pruritus. This was an open-label, single-center study, designed to evaluate the daily use of a skin care regimen for 15 days. Assessments were made at baseline, day 8 and day 15 for visual skin dryness, transepidermal water loss (TEWL), hydration, desquamation, subject-perceived itch and quality of life (QoL). Twenty-five subjects, ages 60-73 years, had significantly improved skin visual dryness, hydration, desquamation, itch and QoL at days 8 and 15, relative to baseline (P < ...
June 6, 2017: Geriatric Nursing
https://www.readbyqxmd.com/read/28598843/a-lipidomics-approach-to-assess-the%C3%A2-association-between-plasma-sphingolipids-and-verbal-memory-performance-in-coronary-artery-disease-patients-undertaking-cardiac-rehabilitation-a-c18-0-signature-for%C3%A2-cognitive-response-to-exercise
#19
Mahwesh Saleem, Nathan Herrmann, Adam Dinoff, Michelle M Mielke, Paul I Oh, Prathiba Shammi, Xingshan Cao, Swarajya Lakshmi Vattem Venkata, Norman J Haughey, Krista L Lanctôt
BACKGROUND: Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. OBJECTIVE: In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28597878/incorporation-studies-of-clickable-ceramides-in-jurkat-cell-plasma-membranes
#20
T Walter, J Schlegel, A Burgert, A Kurz, J Seibel, M Sauer
The incorporation properties of ceramide analogues for click chemistry in Jurkat T cells were investigated. The analogues varied in the acyl chain length and the position of the functional group for click chemistry. Fluorescence microscopy studies including anisotropy and quenching experiments showed significant differences in the accessibility of the functional group indicating different incorporation properties into the plasma membrane.
June 9, 2017: Chemical Communications: Chem Comm
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