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https://www.readbyqxmd.com/read/28535426/new-role-of-pcsk9-in-atherosclerotic-inflammation-promotion-involving-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#1
Zhi-Han Tang, Juan Peng, Zhong Ren, Jing Yang, Ting-Ting Li, Tao-Hua Li, Zuo Wang, Dang-Heng Wei, Lu-Shan Liu, Xi-Long Zheng, Zhi-Sheng Jiang
BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression...
April 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28535009/microrna-let-7g-alleviates-atherosclerosis-via-the-targeting-of-lox-1-in-vitro-and-in-vivo
#2
Mingxin Liu, Guizhou Tao, Qifeng Liu, Kun Liu, Xinchun Yang
Atherosclerosis is a chronic arterial disease and the leading cause of stroke and myocardial infarction. Micro-RNAs (miRNAs or miRs) have been reported to act as essential modulators during the progression of atherosclerosis. Although miR-let-7g has been demonstrated to contribute to maintaining endothelial function and vascular homeostasis, it is not known whether miR-let-7g exerts a therapeutic effect on experimental atherosclerosis. The aim of this study was to investigate the effects of miR-let-7g on atherosclerosis in vivo and in vitro and to explore its underlying mechanisms...
May 18, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534560/re-configurable-multi-mode-contained-electrospray-ionization-for-protein-folding-and-unfolding-on-the-millisecond-time-scale
#3
Colbert F Miller, Dmytro S Kulyk, Jongin W Kim, Abraham K Badu-Tawiah
A new reconfigurable contained-electrospray (ES) ion source is described that can be operated in three unique modes (Types I, II and III) and was applied to control the charge state of proteins for subsequent online characterization by mass spectrometry. Using this device, proteins prepared in 100% water were highly charged after exposure to hydrochloric acid vapor. For myoglobin, the shift to a higher charge state occurred faster than the heme cofactor could escape the unfolding protein. This effect reflected in the detection of highly charged holo-myoglobin intermediates (+26), which suggests the modification process occurred on a millisecond time scale (Type I mode)...
May 23, 2017: Analyst
https://www.readbyqxmd.com/read/28534408/modulation-of-the-conformational-dynamics-of-apo-adenylate-kinase-through-a-%C3%AF-cation-interaction
#4
Ritaban Halder, Rabindra Nath Manna, Sandipan Chakraborty, Biman Jana
Large scale conformational transition from open to closed state of adenylate kinase (ADK) is essential for its catalytic cycle. Apo-ADK undergoes conformational transition in such a way that closely resembles open to closed conformational transition. Here, equilibrium simulations, free energy simulations, QM/MM calculations in combination with several bioinformatics approaches have been used to explore the molecular origin of this conformational transition in apo-ADK. Apart from its conventional open state, E...
May 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28534127/genetics-of-triglycerides-and-the-risk-of-atherosclerosis
#5
REVIEW
Jacqueline S Dron, Robert A Hegele
PURPOSE OF REVIEW: Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality...
July 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28533891/nuclear-uptake-of-an-amino-terminal-fragment-of-apolipoprotein-e4-promotes-cell-death-and-localizes-within-microglia-of-the-alzheimer-s-disease-brain
#6
Julia E Love, Ryan J Day, Justin W Gause, Raquel J Brown, Xinzhu Pu, Dustin I Theis, Chad A Caraway, Wayne W Poon, Abir A Rahman, Brad E Morrison, Troy T Rohn
Although harboring the apolipoprotein E4 (APOE4) allele is a well known risk factor in Alzheimer's disease (AD), the mechanism by which it contributes to disease risk remains elusive. To investigate the role of proteolysis of apoE4 as a potential mechanism, we designed and characterized a site-directed cleavage antibody directed at position D151 of the mature form of apoE4 and E3. Characterization of this antibody indicated a high specificity for detecting synthesized recombinant proteins corresponding to the amino acid sequences 1-151 of apoE3 and E4 that would generate the 17 kDa (p17) fragment...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/28532220/the-adipokine-tartrate-resistant-acid-phosphatase-5a-in-serum-correlates-to-adipose-tissue-expansion-in-obesity
#7
Christina Patlaka, Laia Mira Pascual, Staffan Paulie, Anni-Frid Henriksson, Peter Arner, Pernilla Lång, Göran Andersson
PURPOSE: Tartrate resistant acid phosphatase (TRAP) exists as two isoforms, 5a and 5b. TRAP 5a is elevated in adipose tissue of obese women, interacts with pre-adipocytes and is linked to insulin-sensitive hyperplastic obesity when overexpressed in mice. The aim of this study was to investigate the relation between serum TRAP 5a, adiposity indices and metabolic syndrome risk markers in lean and obese women, using a newly developed TRAP 5a-specific ELISA. MATERIALS AND METHODS: A TRAP 5a sandwich ELISA was optimized using TRAP 5a-specific monoclonal antibodies and tested in sera of healthy males...
May 22, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/28531594/correlation-between-apoe-alleles-and-obesity-markers-in-adults
#8
Alexandra-Aikaterini Koulouri, Dimitrios Loukovitis, Nikolaos Rodopaios, Eleni Vasara, Tatiana Serafeim, Maria Tsigga, Maria Chasapidou, Antonios Kafatos
No abstract text is available yet for this article.
June 2016: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/28531330/structural-basis-for-substrate-binding-and-catalytic-mechanism-of-a-human-rna-m5c-methyltransferase-nsun6
#9
Ru-Juan Liu, Tao Long, Jing Li, Hao Li, En-Duo Wang
5-methylcytosine (m5C) modifications of RNA are ubiquitous in nature and play important roles in many biological processes such as protein translational regulation, RNA processing and stress response. Aberrant expressions of RNA:m5C methyltransferases are closely associated with various human diseases including cancers. However, no structural information for RNA-bound RNA:m5C methyltransferase was available until now, hindering elucidation of the catalytic mechanism behind RNA:m5C methylation. Here, we have solved the structures of NSun6, a human tRNA:m5C methyltransferase, in the apo form and in complex with a full-length tRNA substrate...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531132/effects-of-%C3%AE-carotene-and-its-cleavage-products-in-primary-pneumocyte-type-ii-cells
#10
Cornelia Haider, Franziska Ferk, Ekramije Bojaxhi, Giuseppe Martano, Hanno Stutz, Nikolaus Bresgen, Siegfried Knasmüller, Avdulla Alija, Peter M Eckl
β-Carotene has been shown to increase the risk of developing lung cancer in smokers and asbestos workers in two large scale trails, the Beta-Carotene and Retinol Efficacy Trial (CARET) and the Alpha-Tocopherol Beta-carotene Cancer Prevention Trial (ATBC). Based on this observation, it was proposed that genotoxic oxidative breakdown products may cause this effect. In support of this assumption, increased levels of sister chromatid exchanges, micronuclei, and chromosomal aberrations were found in primary hepatocyte cultures treated with a mixture of cleavage products (CPs) and the major product apo-8'carotenal...
May 21, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28529649/sak-hv-triggered-a-short-period-lipid-lowering-biotherapy-based-on-the-energy-model-of-liver-proliferation-via-a-novel-pathway
#11
Chao Zhang, Zhiguang Huang, Haoran Jing, Wenliang Fu, Min Yuan, Wenrong Xia, Ling Cai, Xiangdong Gan, Yao Chen, Minji Zou, Minhui Long, Jiaxi Wang, Min Wang, Donggang Xu
The accumulations of excess lipids within liver and serum are defined as non-alcoholic fatty liver disease (NAFLD) and hyperlipemia respectively. Both of them are components of metabolic syndrome that greatly threaten human health. Here, a recombinant fusion protein (SAK-HV) effectively treated NAFLD and hyperlipemia in high-fat-fed ApoE(-/-) mice, quails and rats within just 14 days. Its triglyceride and cholesterol-lowering effects were significantly better than that of atorvastatin during the observation period...
2017: Theranostics
https://www.readbyqxmd.com/read/28528773/apoe-moderates-compensatory-recruitment-of-neuronal-resources-during-working-memory-processing-in-healthy-older-adults
#12
Elisa Scheller, Jessica Peter, Lena V Schumacher, Jacob Lahr, Irina Mader, Christoph P Kaller, Stefan Klöppel
The APOE ε4 allele increases the risk for sporadic Alzheimer's disease and modifies brain activation patterns of numerous cognitive domains. We assessed cognitively intact older adults with a letter n-back task to determine if previously observed increases in ε4 carriers' working-memory-related brain activation are compensatory such that they serve to maintain working memory function. Using multiple regression models, we identified interactions of APOE variant and age in bilateral hippocampus independently from task performance: ε4 carriers only showed a decrease in activation with increasing age, suggesting high sensitivity of fMRI data for detecting changes in Alzheimer's disease-relevant brain areas before cognitive decline...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28528355/increased-retinol-free-rbp4-contributes-to-insulin-resistance-in-gestational-diabetes-mellitus
#13
Yanmin Chen, Ping Lv, Mengkai Du, Zhaoxia Liang, Menglin Zhou, Danqing Chen
PURPOSE: Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. METHODS: Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats...
May 20, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#14
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28528308/hyperlipidemia-is-involved-in-apoptosis-in-rat-submandibular-glands
#15
Koichiro Irie, Takaaki Tomofuji, Daisuke Ekuni, Tetsuji Azuma, Toshiki Yoneda, Yoshihiro Shimazaki, Manabu Morita
OBJECTIVE: The aim of the present study was to investigate the effects of hyperlipidemia on histological changes and apoptosis in submandibular glands using apolipoprotein E (apoE)-deficient rats. DESIGN: Histopathological findings related to induced apoptosis in the submandibular glands were compared between apoE-deficient rats (n=6; male; age, 16 weeks) and the corresponding wild-type rats (n=6). RESULTS: ApoE-deficient rats showed significantly higher plasma levels of oxidized low-density lipoprotein (LDL), total cholesterol, very LDL and LDL, and lower plasma levels of high-density lipoprotein when compared to control rats (P<0...
May 17, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28527710/ccn3-regulates-macrophage-foam-cell-formation-and-atherosclerosis
#16
Hong Shi, Chao Zhang, Vinay Pasupuleti, Xingjian Hu, Domenick A Prosdocimo, Wenconghui Wu, Yulan Qing, Shitong Wu, Haneen Mohammad, Stanton L Gerson, Bernard Perbal, Philip A Klenotic, Nianguo Dong, Zhiyong Lin
Recent studies implicate the Cyr61, CTGF, Nov (CCN) matricellular signaling protein family as emerging players in vascular biology, with NOV (alias CCN3) as an important regulator of vascular homeostasis. Herein, we examined the role of CCN3 in the pathogenesis of atherosclerosis. In response to a 15-week high-fat diet feeding, CCN3-deficient mice on the atherosclerosis-prone Apoe(-/-) background developed increased aortic lipid-rich plaques compared to control Apoe(-/-) mice, a result that was observed in the absence of alterations in plasma lipid content...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28527370/atherosclerotic-dyslipidemia-revealed-by-plasma-lipidomics-on-apoe-mice-fed-a-high-fat-diet
#17
Yanyan Chen, Shiyuan Wen, Miaomiao Jiang, Yan Zhu, Liqin Ding, Hong Shi, Pengzhi Dong, Jing Yang, Yue Yang
BACKGROUND AND AIMS: The pathological process of atherosclerosis is closely related to lipid accumulation at arterial wall caused by lipoproteins transporting lipids through blood. In this study, we investigate the lipid composition in the plasma of apolipoprotein E deficient (ApoE(-/-)) mice fed a high-fat diet to reveal atherosclerosis-induced dyslipidemia. METHODS: ApoE(-/-) and corresponding wild-type C57BL/6J mice were used as the pathology model and control, respectively, and were fed a high-fat or normal diet...
May 11, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#18
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28527212/apolipoprotein-e4-gender-body-mass-index-inflammation-insulin-resistance-and-air-pollution-interactions-recipe-for-alzheimer-s-disease-development-in-mexico-city-young-females
#19
Lilian Calderón-Garcidueñas, Suzanne M de la Monte
Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28523739/mechanisms-of-peptide-sex-pheromone-regulation-of-conjugation-in-enterococcus-faecalis
#20
Yuqing Chen, Arpan Bandyopadhyay, Briana K Kozlowicz, Heather A H Haemig, Albert Tai, Wei-Shou Hu, Gary M Dunny
In many gram positive bacteria, horizontal transfer and virulence are regulated by peptide-mediated cell-cell signaling. The heptapeptide cCF10 (C) activates conjugative transfer of the Enterococcus faecalis plasmid pCF10, whereas the iCF10 (I) peptide inhibits transfer. Both peptides bind to the same domain of the master transcription regulator PrgX, a repressor of transcription of the prgQ operon encoding conjugation genes. We show that repression of prgQ by PrgX tetramers requires formation of a pCF10 DNA loop where each of two PrgX DNA-binding sites is occupied by a dimer...
May 19, 2017: MicrobiologyOpen
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