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https://www.readbyqxmd.com/read/29156544/endogenous-sphingolipid-signaling-pathway-implicated-in-the-action-of-croton-membranaceus-on-the-prostate-gland-in-bph-patients
#1
George Awuku Asare, Yvonne Anang, Daniel K Afriyie, Brodrick Yeboah Amoah, Bernice Asiedu, Derek Doku, Hannah Serwah Ocansey, Nana Yaw Odei Danso, Prince Tekpor, Sarah Osam
Background: Croton membranaceus extract has apoptotic effects on BPH-1 cells. This study determined if the apoptotic effects were created through the ceramide pathway. Methods: The study was a follow-up to a previous observational study of 30 histologically confirmed patients with benign prostatic hyperplasia (BPH) who were on C. membranaceus ethanolic extract at 20 mg t.i.d orally for 3 mo. Thereafter, total and free prostate-specific antigen (PSA), lipid profile plus Apo lipoprotein A and B, ceramide/Sphingophospho-kinase 1 (SphK1) and 2 (SphK2), sphingosine lyase (SPL), the cytotoxic adducts of oxidative stress 4-hydroxy-2-nonenal (4HNE) and malondialdehyde (MDA), were determined...
November 18, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/29156223/exploring-apoe-genotype-effects-on-ad-risk-and-%C3%AE-amyloid-burden-in-individuals-with-subjective-cognitive-decline-the-facehbi-study-baseline-results
#2
Sonia Moreno-Grau, O Rodríguez-Gomez, A Sanabria, A Perez-Cordon, D Sanchez-Ruiz, C Abdelnour, S Valero, I Hernandez, M Rosende-Roca, A Mauleon, L Vargas, A Lafuente, S Gil, M A Santos-Santos, M Alegret, A Espinosa, G Ortega, M Guitart, A Gailhajanet, I de Rojas, O Sotolongo-Grau, S Ruiz, N Aguilera, J Papasey, E Martin, E Peleja, F Lomeña, F Campos, A Vivas, M Gomez-Chiari, M A Tejero, J Giménez, M Serrano-Ríos, A Orellana, L Tarraga, A Ruiz, M Boada
INTRODUCTION: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. METHODS: We evaluated apolipoprotein E (APOE) Ɛ4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts...
November 17, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29156222/cerebral-small-vessel-disease-in-middle-age-and-genetic-predisposition-to-late-onset-alzheimer-s-disease
#3
James D Stefaniak, Li Su, Elijah Mak, Nasim Sheikh Bahaei, Katie Wells, Karen Ritchie, Adam Waldman, Craig W Ritchie, John T O'Brien
INTRODUCTION: Cerebral small vessel disease (CSVD) is associated with late-onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E ε4 (APOEε4) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD. METHODS: We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross-sectional analysis of cognitively normal subjects aged 40-59 years recruited from the PREVENT Dementia study...
November 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29155887/effects-of-an-a%C3%AE-antibody-fragment-on-a%C3%AE-aggregation-and-astrocytic-uptake-are-modulated-by-apolipoprotein-e-and-j-mimetic-peptides
#4
Laia Montoliu-Gaya, Sandra D Mulder, Robert Veerhuis, Sandra Villegas
Aβ-Immunotherapy has long been studied in the treatment of Alzheimer's disease (AD), but not how other molecules involved in the disease can affect antibody performance. We previously designed an antibody fragment, scFv-h3D6, and showed that it precludes Aβ-induced cytotoxicity by withdrawing Aβ oligomers from the amyloid pathway towards a non-toxic, worm-like pathway. ScFv-h3D6 was effective at the behavioral, cellular, and molecular levels in the 3xTg-AD mouse model. Because scFv-h3D6 treatment restored apolipoprotein E (apoE) and J (apoJ) concentrations to non-pathological values, and Aβ internalization by glial cells was found to be decreased in the presence of these apolipoproteins, we now aimed to test the influence of scFv-h3D6 on Aβ aggregation and cellular uptake by primary human astrocytes in the presence of therapeutic apoE and apoJ mimetic peptides (MPs)...
2017: PloS One
https://www.readbyqxmd.com/read/29155708/enrichment-of-detergent-insoluble-protein-aggregates-from-human-postmortem-brain
#5
Ian Diner, Tram Nguyen, Nicholas T Seyfried
In this study, we describe an abbreviated single-step fractionation protocol for the enrichment of detergent-insoluble protein aggregates from human postmortem brain. The ionic detergent N-lauryl-sarcosine (sarkosyl) effectively solubilizes natively folded proteins in brain tissue allowing the enrichment of detergent-insoluble protein aggregates from a wide range of neurodegenerative proteinopathies, such as Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis, and prion diseases...
October 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155566/structure-based-insights-into-dynamics-and-function-of-two-domain-slpa-from-escherichia-coli
#6
Anne-Juliane Geitner, Ulrich Weininger, Hauke Paulsen, Jochen Balbach, Michael Kovermann
SlpA (SlyD like protein A) comprises two domains, a FK506 binding domain (FKBP fold) of moderate prolyl cis/trans isomerase activity and an inserted in flap (IF) domain that hosts its chaperone activity. Here we present the NMR solution structure of apo E. coli SlpA determined by NMR which mirrors the structural properties seen for various SlyD homologs. Crucial structural differences in side-chain orientation arise for F37 which points directly into the hydrophobic core of the active site. It forms a prominent aromatic stacking with F15, one of the key residues for PPIase activity, thus giving a possible explanation for the inherently low PPIase activity of SlpA...
November 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/29154926/site-specific-effects-of-apolipoprotein-e-expression-on-diet-induced-obesity-and-white-adipose-tissue-metabolic-activation
#7
Aikaterini Hatziri, Christina Kalogeropoulou, Eva Xepapadaki, Eleni Birli, Eleni A Karavia, Eugenia Papakosta, Serafoula Filou, Caterina Constantinou, Kyriakos E Kypreos
Apolipoprotein E (APOE) has been strongly implicated in the development of diet induced obesity. In the present study, we investigated the contribution of brain and peripherally expressed human apolipoprotein E3 (APOE3), the most common human isoform, to diet induced obesity. In our studies APOE3 knock-in (Apoe3(knock-in)), Apoe-deficient (apoe(-/-)) and brain-specific expressing APOE3 (Apoe3(brain)) mice were fed western-type diet for 12week and biochemical analyses were performed. Moreover, AAV-mediated gene transfer of APOE3 to apoe(-/-) mice was employed, as a means to achieve APOE3 expression selectively in periphery, since peripherally expressed APOE does not cross barrier (BBB) or blood-cerebrospinal fluid barrier (BCSFB)...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154780/the-feedback-loop-of-emmprin-nf-%C3%AE%C2%BAb-worsens-atherosclerotic-plaque-via-suppressing-autophagy-in-macrophage
#8
Xing Liang, Xianhua Hou, Yang Yang, Hong Liu, Ruiwei Guo, Zhihua Yang, Lixia Yang
This study examined the significance of macrophage autophagy in extracellular matrix metalloproteinase inducer (EMMPRIN)-mediated atherosclerosis (AS). Apolipoprotein E-deficient (ApoE-/-) mice were fed a western diet to establish an AS model. EMMPRIN and p62/Sequestosome-1(SQSTM1) expression were evaluated in plaque macrophages from the AS mice using immunofluorescence. The EMMPRIN and p62/SQSTM1 protein expression levels in macrophages increased with the increasing vulnerability of the atherosclerotic plaques...
November 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29154275/association-of-cerebrospinal-fluid-csf-insulin-with-cognitive-performance-and-csf-biomarkers-of-alzheimer-s-disease
#9
Stefan L C Geijselaers, Pauline Aalten, Inez H G B Ramakers, Peter Paul De Deyn, Annemieke C Heijboer, Huiberdina L Koek, Marcel G M OldeRikkert, Janne M Papma, Fransje E Reesink, Lieke L Smits, Coen D A Stehouwer, Charlotte E Teunissen, Frans R J Verhey, Wiesje M van der Flier, Geert Jan Biessels
BACKGROUND: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD). OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype. METHODS: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29152896/trimetazidine-restores-the-positive-adaptation-to-exercise-training-by-mitigating-statin-induced-skeletal-muscle-injury
#10
Ming Song, Fang-Fang Chen, Yi-Hui Li, Lei Zhang, Feng Wang, Ran-Ran Qin, Zhi-Hao Wang, Ming Zhong, Meng-Xiong Tang, Wei Zhang, Lu Han
BACKGROUND: Exercise rehabilitation is demonstrated to improve the prognosis of patients with coronary heart disease (CHD). Statins, as the key medicine to lower cholesterol in CHD, result in skeletal muscle injury and impair exercise training adaptation. Energy metabolism dysfunction is identified as the potential mechanism underlying statin-induced skeletal muscle injury. In this study, we investigated the effects of the metabolic modulator trimetazidine on skeletal muscle energy metabolism and statin-associated exercise intolerance...
November 19, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29152661/apolipoprotein-status-in-type-2-diabetes-mellitus-and-its-complications-review
#11
Puhong Zhang, Jialin Gao, Chun Pu, Yao Zhang
Dyslipidaemia in type 2 diabetes mellitus (T2DM) is characterized by high plasma triglyceride concentrations, reduced high‑density lipoprotein concentrations and increased small density low‑density lipoprotein concentrations. Dyslipidaemia may lead to cardiovascular disease (CVD) and other complications. Apolipoproteins mainly comprise six species, apolipoprotein (apo)A, apoB, apoC, apoD, apoE and apoM, which are important components of plasma lipoproteins that carry lipids and stabilize the structure of lipoproteins...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29151984/hepatic-and-aortic-arch-expression-and-serum-levels-of-syndecan-1-in-apoe-mice
#12
Elena I Leonova, Elena S Sadovnikova, Elvira R Shaykhutdinova, Oxana V Galzitskaya, Arkady N Murashev, Alexandr S Solonin
Background: Heparan sulfate proteoglycan (HSPG) syndecan-1 (Sdc1) acts as a receptor for triglyceride-rich lipoproteins (TRLs), growth factors, chemokines and enzymes. Due to the disordered structure, its function is as diverse as its ligands. In this paper, we have analyzed hepatic and aortic arch expression of Sdc1 in ApoE(-/-) mice and examined their association with biochemical changes in plasma during the atheroma formation. Methods: ApoE knockout (ApoE(-/-)) mice as a model of atherosclerosis were used...
2017: Open Biochemistry Journal
https://www.readbyqxmd.com/read/29150441/co-ii-and-ni-ii-binding-of-the-escherichia-coli-transcriptional-repressor-rcnr-orders-its-n-terminus-alters-helix-dynamics-and-reduces-dna-affinity
#13
Hsin-Ting Huang, Cedric E Bobst, Jeffrey S Iwig, Peter T Chivers, Igor A Kaltashov, Michael J Maroney
RcnR, a transcriptional regulator in Escherichia coli, derepresses the expression of the export proteins RcnAB upon binding Ni(II) or Co(II). Lack of structural information has precluded elucidation of the allosteric basis for the decreased DNA affinity in RcnR's metal-bound states. Here, using hydrogen-deuterium exchange coupled with MS (HDX-MS), we probed the RcnR structure in the presence of DNA, the cognate metal ions Ni(II) and Co(II), or the noncognate metal ion Zn(II). We found that cognate metal binding altered the flexibility from the N-terminus through helix 1 and modulated the RcnR-DNA interaction...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29149817/high-density-lipoprotein-hdl-dysfunction-and-future-of-hdl
#14
Sibel Ertek
Although high density lipoprotein cholesterol (HDL-C) levels are inversely proportional to cardiovascular risk in many studies, recent pharmacological interventional studies with HDL-C raising strategies did not show a benefit in terms of vascular events. The HDL particle is heterogenous with anti-atherogenic functions and non-vascular effects. Many factors affect HDL components and may either cause compositional changes, post-translational modifications of proteins, or alter lipids and other cargo molecules; generally these factors cause more than one of these changes, resulting in functional differences...
November 16, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29147686/lipoprotein-a-associated-molecules-are-prominent-components-in-plasma-and-valve-leaflets-in-calcific-aortic-valve-stenosis
#15
Michael Torzewski, Amir Ravandi, Calvin Yeang, Andrea Edel, Rahul Bhindi, Stefan Kath, Laura Twardowski, Jens Schmid, Xiaohong Yang, Ulrich F W Franke, Joseph L Witztum, Sotirios Tsimikas
The LPA gene is the only monogenetic risk factor for calcific aortic valve stenosis (CAVS). Oxidized phospholipids (OxPL) and lysophosphatidic acid generated by autotaxin (ATX) from OxPL are pro-inflammatory. Aortic valve leaflets were categorized pathologically from Both ATX-apoB and ATX-apo(a) were measureable in plasma. Lp(a), autotaxin, OxPL and MDA epitopes progressively increased in immunostaining (p<0.001 for all). Six species of OxPL and LysoPA were identified following extraction from valve leaflets...
June 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29146892/intermedin-ameliorates-atherosclerosis-by-increasing-cholesterol-efflux-through-the-camp-pka-pathway-in-macrophage-raw264-7-cell-line
#16
Hang Liao, Shixi Wan, Xin Zhang, Di Shi, Xiaojiang Zhu, Xiaoping Chen
BACKGROUND The aim of this study was to explore the role of intermedin and its mechanism in cholesterol efflux of macrophage THP-1 and RAW264.7 cell lines in atherosclerosis (AS). MATERIAL AND METHODS ApoE-/- mice were fed with a high-fat diet, and the concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. The lipidoses of the aortic sinus were analyzed by hematoxylin and eosin staining, and the cAMP level was detected by enzyme-linked immunosorbent assay (ELISA)...
November 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29146749/statins-promote-cardiac-infarct-healing-by-modulating-endothelial-barrier-function-revealed-by-contrast-enhanced-magnetic-resonance-imaging
#17
Geert J Leenders, Mirjam B Smeets, Maaike van den Boomen, Monique Berben, Miranda Nabben, Dianne van Strijp, Gustav J Strijkers, Jeanine J Prompers, Fatih Arslan, Klaas Nicolay, Katrien Vandoorne
OBJECTIVE: The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging...
November 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29144736/inference-of-calmodulin-s-ca2-dependent-free-energy-landscapes-via-gaussian-mixture-model-validation
#18
Annie M Westerlund, Tyler J Harpole, Christian Blau, Lucie Delemotte
A free energy landscape estimation-method based on the well-known Gaussian mixture model (GMM) is used for comparing the efficiency of thermally enhanced sampling methods with respect to regular molecular dynamics. The simulations are carried out on two binding states of calmodulin and the free energy estimation method is compared to other estimators using a toy model. We show that GMM with cross-validation provides a robust estimate that is not subject to overfitting. The continuous nature of Gaussians provides better estimates on sparse data than canonical histogramming...
November 16, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29143599/epistasis-physical-capacity-related-genes-and-exceptional-longevity-fndc5-gene-interactions-with-candidate-genes-foxoa3-and-apoe
#19
Noriyuki Fuku, Roberto Díaz-Peña, Yasumichi Arai, Yukiko Abe, Hirofumi Zempo, Hisashi Naito, Haruka Murakami, Motohiko Miyachi, Carlos Spuch, José A Serra-Rexach, Enzo Emanuele, Nobuyoshi Hirose, Alejandro Lucia
BACKGROUND: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population...
November 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29143455/understanding-the-functional-role-of-microrna-214-3p-in-atherosclerosis-for-the-identification-of-novel-targeted-therapies-to-prevent-or-reverse-endothelial-cell-dysfunction-and-stimulate-autophagy
#20
EDITORIAL
Adriana Georgescu
The original article by Jing Wang and collaborators, entitled "MicroRNA-214-3p: A Link between Autophagy and Endothelial Cell Dysfunction in Atherosclerosis", brings new data concerning molecular mechanisms linking decreased autophagy to endothelial dysfunction in atherosclerosis. In this issue of Acta Physiologica, the authors concluded that microRNA-214-3p (miR-214-3p) controls oxidized low-density lipoprotein (ox-LDL)-induced autophagy in human umbilical vein endothelial cells (HUVECs) by regulating intracellular levels of autophagy-related protein 5 (ATG5), and may have a relevant role in the pathogenesis of atherosclerosis...
November 16, 2017: Acta Physiologica
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