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https://www.readbyqxmd.com/read/29166560/analytical-challenges-and-recent-advances-in-mass-spectrometry-based-lipidomics
#1
Yepy Hardi Rustam, Gavin Edmund Reid
Although no internationally accepted consensus definition exists, lipids can be broadly defined as "fatty acids and their derivatives, and substances related biosynthetically or functionally to these compounds". Lipids play critical roles as (i) the major structural components of biological membranes, and as functional and regulatory components of membrane protein signaling, (ii) bioactive intra- and inter-cellular signaling molecules, and (iii) energy storage molecules for the maintenance of energy homeostasis...
November 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29165364/the-rosiglitazone-like-effects-of-vitexilactone-a-constituent-from-vitex-trifolia-l-in-3t3-l1-preadipocytes
#2
Atsuyoshi Nishina, Masaya Itagaki, Daisuke Sato, Hirokazu Kimura, Yasuaki Hirai, Nyunt Phay, Makoto Makishima
The increased number of patients with type 2 diabetes (T2D) has become a worldwide problem, and insulin sensitizers such as thiazolidinediones (TZDs) are used as therapeutic agents. We found that extracts of Vitex trifolia L. (V. trifolia), a medicinal plant from Myanmar, induced adipogenesis similar to rosiglitazone (ROS), which is a TZD, in 3T3-L1 preadipocytes. In the present study, we attempted to isolate from V. trifolia those compounds that showed ROS-like effects. Among the extracts of hexane, ethyl acetate, and methanol obtained from V...
November 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29164426/the-impact-of-vascular-disease-treatment-on-platelet-derived-microvesicles
#3
Justyna Rosińska, Maria Łukasik, Wojciech Kozubski
Platelet-derived microvesicles (pMVs) are small, heterogeneous vesicles released from platelet membranes as a result of activation. These microvesicles possess a wide range of properties, including prothrombotic, proatherogenic, proinflammatory, immunomodulatory, and even anticoagulant activity. The elevated release of these microvesicles has been observed in various metabolic, inflammatory, thrombotic, and vascular diseases, including ischemic heart disease, stroke, hypertension, diabetes, and connective tissue disease...
November 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29162828/selenoprotein-p-neutralizing-antibodies-improve-insulin-secretion-and-glucose-sensitivity-in-type-2-diabetes-mouse-models
#4
Yuichiro Mita, Kaho Nakayama, Shogo Inari, Yukina Nishito, Yuya Yoshioka, Naoko Sakai, Kanade Sotani, Takahiro Nagamura, Yuki Kuzuhara, Kumi Inagaki, Miki Iwasaki, Hirofumi Misu, Masaya Ikegawa, Toshinari Takamura, Noriko Noguchi, Yoshiro Saito
Selenoprotein P (SeP) functions as a selenium (Se)-supply protein. SeP is identified as a hepatokine, promoting insulin resistance in type 2 diabetes. Thus, the suppression of Se-supply activity of SeP might improve glucose metabolism. Here, we develop an anti-human SeP monoclonal antibody AE2 as with neutralizing activity against SeP. Administration of AE2 to mice significantly improves glucose intolerance and insulin resistance that are induced by human SeP administration. Furthermore, excess SeP administration significantly decreases pancreas insulin levels and high glucose-induced insulin secretion, which are improved by AE2 administration...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29160110/peroxiredoxin6-a-multitask-antioxidant-enzyme-involved-in-the-pathophysiology-of-chronic-non-communicable-diseases
#5
Francesca Pacifici, David Della-Morte, Barbara Capuani, Donatella Pastore, Alfonso Bellia, Paolo Sbraccia, Nicola Di Daniele, Renato Lauro, Davide Lauro
SIGNIFICANCE: Chronic Non-Communicable Diseases (NCDs) are the leading causes of disability and death worldwide. NCDs mainly comprise diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease (COPD), cancer, and neurological degenerative diseases, which kill more than 80% of population, especially elderlies, worldwide. Recent Advances: Several recent theories established NCDs as multifactorial diseases, where a combination of genetic, epigenetic and environmental factors contributes to their pathogenesis...
November 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#6
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/29157806/trigonelline-promotes-auditory-function-through-nerve-growth-factor-signaling-on-diabetic-animal-models
#7
Rodrigo Castañeda, Isabel Rodriguez, Youn Hee Nam, Bin Na Hong, Tong Ho Kang
BACKGROUND: Protection of cochlear function and reconstruction of neuronal networks in damaged auditory sensory structures is crucial for therapeutic treatment of diabetic hearing loss. Nerve growth factor (NGF) has been used as a novel therapeutic target to protect against the neurodegenerative effects of Diabetes Mellitus (DM). PURPOSE: We aimed to evaluate the potential effect of trigonelline (TRG) on reducing auditory damage produced by DM using NGF as a potential marker...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157234/zinc-transporters-and-insulin-resistance-therapeutic-implications-for-type-2-diabetes-and-metabolic-disease
#8
REVIEW
Shaghayegh Norouzi, John Adulcikas, Sukhwinder Singh Sohal, Stephen Myers
BACKGROUND: Zinc is a metal ion that is essential for growth and development, immunity, and metabolism, and therefore vital for life. Recent studies have highlighted zinc's dynamic role as an insulin mimetic and a cellular second messenger that controls many processes associated with insulin signaling and other downstream pathways that are amendable to glycemic control. MAIN BODY: Mechanisms that contribute to the decompartmentalization of zinc and dysfunctional zinc transporter mechanisms, including zinc signaling are associated with metabolic disease, including type 2 diabetes...
November 20, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29155303/therapeutic-vaccine-against-il-1%C3%AE-improved-glucose-control-in-a-mouse-model-of-type-2-diabetes
#9
Yue Zhang, Xiao-Lin Yu, Jun Zha, Li-Zhen Mao, Jia-Qian Chai, Rui-Tian Liu
AIMS: Inflammation is strongly associated with the mechanisms of β-cell failure in type 2 diabetes. Blockade of the key proinflammatory cytokine IL-1β has been implicated as a promising therapeutic strategy for the prevention and treatment of type 2 diabetes. In this study, we developed an IL-1β-targeted therapeutic vaccine consisting of an IL-1β epitope peptide (A1β) and assessed its efficacy on a diabetic KK-A(y) mouse model. MAIN METHODS: KK-A(y) mice were immunized with A1β for three injections at a 2-week interval...
November 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/29155147/selective-and-membrane-permeable-small-molecule-inhibitors-of-nicotinamide-n-methyltransferase-reverse-high-fat-diet-induced-obesity-in-mice
#10
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29153487/endothelial-cell-metabolism-in-health-and-disease
#11
REVIEW
Katerina Rohlenova, Koen Veys, Ines Miranda-Santos, Katrien De Bock, Peter Carmeliet
The metabolism of endothelial cells (ECs) has only recently been recognized as a driving force of angiogenesis. Metabolic pathways, such as glycolysis, fatty acid oxidation, and glutamine metabolism, have distinct, essential roles during vessel formation. Moreover, EC metabolism is markedly perturbed in pathologies such as cancer and diabetes. For instance, because tumor ECs increase glycolysis, lowering hyperglycolysis in tumor ECs induces therapeutic benefits in preclinical tumor models. Expanding our knowledge of how ECs alter their metabolism in disease could pave the way for novel therapeutic opportunities...
November 16, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/29152572/a-null-mutation-in-serpine1-protects-against-biological-aging-in-humans
#12
Sadiya S Khan, Sanjiv J Shah, Ekaterina Klyachko, Abigail S Baldridge, Mesut Eren, Aaron T Place, Abraham Aviv, Eli Puterman, Donald M Lloyd-Jones, Meadow Heiman, Toshio Miyata, Sweta Gupta, Amy D Shapiro, Douglas E Vaughan
Plasminogen activator inhibitor-1 (PAI-1) has been shown to be a key component of the senescence-related secretome and a direct mediator of cellular senescence. In murine models of accelerated aging, genetic deficiency and targeted inhibition of PAI-1 protect against aging-like pathology and prolong life span. However, the role of PAI-1 in human longevity remains unclear. We hypothesized that a rare loss-of-function mutation in SERPINE1 (c.699_700dupTA), which encodes PAI-1, could play a role in longevity and metabolism in humans...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29145743/novel-avenues-for-drug-discovery-in-diabetic-kidney-disease
#13
Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
November 16, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29138836/gata4-protects-against-hyperglycemia%C3%A2-induced-endothelial-dysfunction-by-regulating-nox4-transcription
#14
Hongfei Xu, Zhen Wang, Zewei Sun, Yiming Ni, Liangrong Zheng
Endothelial dysfunction is one of the most common complications associated with diabetes and may lead to atherosclerosis. Conflicting reports indicate that NADPH oxidase 4 (NOX4) induces hydrogen peroxide production and cytotoxicity, but also has a protective effect on endothelial dysfunction. The present study aimed to identify the transcription factor responsible for NOX4 expression using a transcription factor activation profiling plate array and chromatin immunoprecipitation. Data from these analyses indicated that GATA‑binding protein 4 (GATA4) was able to mediate NOX4 transcription and is downregulated in human umbilical vein endothelial cells (HUVECs) that were exposed to hyperglycemic conditions as well as in the endothelial cells of a mouse diabetes model...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29137713/trpv1-a-potential-therapeutic-target-in-type-2-diabetes-and-comorbidities
#15
REVIEW
Dorte X Gram, Jens J Holst, Arpad Szallasi
With an estimated 422 million affected patients worldwide in 2016, type 2 diabetes (T2D) has reached pandemic proportions and represents a major unmet medical need. T2D is a polygenic disease with a chronic, low-grade inflammatory component. Second-generation transient receptor potential vanilloid-1 (TRPV1) antagonists are potent anti-inflammatory agents with proven clinical safety. In rodent models of T2D, TRPV1 blockade was shown to halt disease progression and improve glucose metabolism. Thus, we propose that TRPV1 antagonists merit further study as novel therapeutic approaches to potentially treat T2D and its comorbidities...
November 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29135673/myocardial-cobalt-levels-are-elevated-in-the-setting-of-total-hip-arthroplasty
#16
Cody C Wyles, T Carson Wright, Melanie C Bois, Md Shahrier Amin, Ahmed Fayyaz, Sarah M Jenkins, Saranya P Wyles, Patrick L Day, David L Murray, Robert T Trousdale, Nandan S Anavekar, William D Edwards, Joseph J Maleszewski
BACKGROUND: Arthroplasty implants commonly contain elemental metal that may undergo wear-related release. Recently, cases of hip implant-associated myocardial injury have been reported. However, we are not aware of any previous study that has systematically measured myocardial metal levels or examined the relationship with total hip arthroplasty (THA). METHODS: Archives of our institution were queried for autopsies of individuals who had undergone THA between 1990 and 2013...
November 15, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/29133386/restoration-of-rostral-ventrolateral-medulla-cystathionine-%C3%AE-lyase-activity-underlies-moxonidine-evoked-neuroprotection-and-sympathoinhibition-in-diabetic-rats
#17
Mohamed A Fouda, Shaimaa S El-Sayed, Abdel A Abdel-Rahman
We recently demonstrated a fundamental role for cystathionine-γ lyase (CSE)-derived hydrogen sulfide (H2S) in the cardioprotective effect of the centrally acting drug moxonidine in diabetic rats. Whether a downregulated CSE/H2S system in the rostral ventrolateral medulla (RVLM) underlies neuronal oxidative stress and sympathoexcitation in diabetes has not been investigated. Along with addressing this question, we tested the hypothesis that moxonidine prevents the diabetes-evoked neurochemical effects by restoring CSE/H2S function within its major site of action, the RVLM...
November 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29130686/thioamide-substitution-selectively-modulates-proteolysis-and-receptor-activity-of-therapeutic-peptide-hormones
#18
Xing Chen, Elizabeth G Mietlicki-Baase, Taylor M Barrett, Lauren E McGrath, Kieran Koch-Laskowski, John J Ferrie, Matthew R Hayes, E James Petersson
Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution...
November 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29129775/connecting-alzheimer-s-disease-to-diabetes-underlying-mechanisms-and-potential-therapeutic-targets
#19
REVIEW
Marcelo N N Vieira, Ricardo A S Lima-Filho, Fernanda G De Felice
Alzheimer's disease (AD) is a risk factor for type 2 diabetes and vice versa, and a growing body of evidence indicates that these diseases are connected both at epidemiological, clinical and molecular levels. Recent studies have begun to reveal common pathogenic mechanisms shared by AD and type 2 diabetes. Impaired neuronal insulin signaling and endoplasmic reticulum (ER) stress are present in animal models of AD, similar to observations in peripheral tissue in T2D. These findings shed light into novel diabetes-related mechanisms leading to brain dysfunction in AD...
November 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29128846/tissue-adhesive-fk506-loaded-polymeric-nanoparticles-for-multi-layered-nano-shielding-of-pancreatic-islets-to-enhance-xenograft-survival-in-a-diabetic-mouse-model
#20
Tung Thanh Pham, Tiep Tien Nguyen, Shiva Pathak, Shobha Regmi, Hanh Thuy Nguyen, Tuan Hiep Tran, Chul Soon Yong, Jong Oh Kim, Pil-Hoon Park, Min Hui Park, Young Kyung Bae, Jeong Uk Choi, Youngro Byun, Cheol-Hee Ahn, Simmyung Yook, Jee-Heon Jeong
This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4-dihydroxyphenethylamine (DOPA) conjugated poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (DOPA-NPs) carrying immunosuppressant FK506 (FK506/DOPA-NPs). The functionalized DOPA-NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co-culture condition with xenogenic lymphocytes for 7 days...
November 1, 2017: Biomaterials
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