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https://www.readbyqxmd.com/read/29031222/apolipoproteins-adsorption-and-brain-targeting-evaluation-of-baicalin-nanocrystals-modified-by-combination-of-tween80-and-tpgs
#1
Yang Liu, Yueqin Ma, Junnan Xu, Yingchong Chen, Jin Xie, Pengfei Yue, Qin Zheng, Ming Yang
To help baicalin pass across BBB and improve its targeting in brain, we designed a novel formulation strategy of baicalin nanocrystals that preferentially adsorbing apolipoprotein E (ApoE) and repelling protein adsorption of opsonins. Intravenous baicalin nanocrystals suspensions (BCL-NS) modified by different surfactant were prepared by high-pressure homogenization. The targeting potential of surface-modified BCL-NS with mean particles size of about 250nm was assessed by in vitro protein adsorption studies using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and further evaluated in vivo pharmacokinetics...
October 5, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29029165/depicting-new-pharmacological-strategies-for-familial-hypercholesterolaemia-involving-lipoprotein-a
#2
Alpo Vuorio, Gerald F Watts, Petri T Kovanen
Approximately 35 million people worldwide suffer from heterozygous familial hypercholesterolaemia (HeFH), a condition characterized by genetically determined life-long elevation of plasma low-density lipoprotein cholesterol (LDL-C). One in three of these patients also inherit an elevated plasma concentration of lipoprotein (a) [Lp(a)], a lipoprotein particle with atherogenic, inflammatory and prothrombotic properties. Accordingly, the combination of high plasma LDL-C and Lp(a) can markedly accelerate premature atherosclerotic cardiovascular disease (ASCVD)...
October 3, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29028546/enzymatic-characterization-and-crystal-structure-analysis-of-chlamydomonas-reinhardtii-dehydroascorbate-reductase-and-their-implications-for-oxidative-stress
#3
Hsin-Yang Chang, Shu-Tseng Lin, Tzu-Ping Ko, Shu-Mei Wu, Tsen-Hung Lin, Yu-Ching Chang, Kai-Fa Huang, Tse-Min Lee
Dehydroascorbate reductase (DHAR) is a key enzyme for glutathione (GSH)-dependent reduction of dehydroascorbate (DHA) to recycled ascorbate (AsA) in plants, and plays a major role against the toxicity of reactive oxygen species (ROS). Previously, we proposed that the increase of AsA regeneration via enhanced DHAR activity modulates the ascorbate-glutathione cycle activity against photooxidative stress in Chlamydomonas reinhardtii. In the present work, we use site-directed mutagenesis and crystal structure analysis to elucidate the molecular basis of how C...
October 3, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29028340/probing-the-binding-pathway-of-braco19-to-a-parallel-stranded-human-telomeric-g-quadruplex-using-molecular-dynamics-binding-simulation-with-amber-dna-ol15-and-ligand-gaff2-force-fields
#4
Babitha Machireddy, Gurmannat Kalra, Subash Chandra Jonnalagadda, Kandalam V Ramanujachary, Chun Wu
Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex specific ligands that stabilize the G-quadruplex, have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its holo form in complex with BRACO19, a potent G-quadruple ligand) have been solved, yet the binding mechanism and pathway remains to be elusive. In this study, we simulated the binding of a free BRACO19 molecule to the apo form of the G-quadruplex using the latest AMBER DNA (OL15) and ligand GAFF2 force field...
October 13, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29025558/glycated-apolipoprotein-a-iv-induces-atherogenesis-in-patients-with-cad-in%C3%A2-type-2-diabetes
#5
Yang Dai, Ying Shen, Qing Run Li, Feng Hua Ding, Xiao Qun Wang, Hong Juan Liu, Xiao Xiang Yan, Ling Jie Wang, Ke Yang, Hai Bo Wang, Qiu Jing Chen, Wei Feng Shen, Rui Yan Zhang, Lin Lu
BACKGROUND: Nonenzymatic glycation of apolipoproteins plays a role in the pathogenesis of the vascular complications of diabetes. OBJECTIVES: This study investigated whether apolipoprotein (apo) A-IV was glycated in patients with type 2 diabetes mellitus (T2DM) and whether apoA-IV glycation was related to coronary artery disease (CAD). The study also determined the biological effects of glycated apoA-IV. METHODS: The authors consecutively enrolled 204 patients with T2DM without CAD (Group I), 515 patients with T2DM with CAD (Group II), and 176 healthy subjects (control group) in this study...
October 17, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29024030/melatonin-prevents-endothelial-cell-pyroptosis-via-regulation-of-long-noncoding-rna-meg3-mir-223-nlrp3-axis
#6
Yong Zhang, Xin Liu, Xue Bai, Yuan Lin, Zhange Li, Jiangbo Fu, Mingqi Li, Tong Zhao, Huan Yang, Ranchen Xu, Jiamin Li, Jin Ju, Benzhi Cai, Chaoqian Xu, Baofeng Yang
Atherosclerosis (AS) is an inflammatory disease linked to endothelial dysfunction. Melatonin is reported to possess substantial anti-inflammatory properties, which has proven to be effective in AS. Emerging literature suggests that pyroptosis plays a critical role during AS progression. However, whether pyroptosis contributes to endothelial dysfunction and the underlying molecular mechanisms remained unexploited. This study was designed to investigate the anti-pyroptotic effects of melatonin in atherosclerotic endothelium and to elucidate the potential mechanisms...
October 11, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29023983/age-vascular-health-and-alzheimer-s-disease-biomarkers-in-an-elderly-sample
#7
Prashanthi Vemuri, Timothy G Lesnick, Scott A Przybelski, David S Knopman, Val J Lowe, Jonathan Graff-Radford, Rosebud O Roberts, Michelle M Mielke, Mary M Machulda, Ronald C Petersen, Clifford R Jack
OBJECTIVE: To investigate the associations between age, vascular health, and Alzheimer's disease (AD) imaging biomarkers in an elderly sample. METHODS: We identified 430 individuals along the cognitive continuum aged>60 years with amyloid-PET, Tau-PET, and MRI scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had FDG-PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from healthcare records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac-arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health...
October 10, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29021777/circulating-cholesterol-levels-may-link-to-the-factors-influencing-parkinson-s-risk
#8
Lijun Zhang, Xue Wang, Ming Wang, Nick W Sterling, Guangwei Du, Mechelle M Lewis, Tao Yao, Richard B Mailman, Runze Li, Xuemei Huang
OBJECTIVES: A growing literature suggests that circulating cholesterol levels have been associated with Parkinson's disease (PD). In this study, we investigated a possible causal basis for the cholesterol-PD link. METHODS: Fasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender-matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania State University College of Medicine. Based on the literature, genetic polymorphisms in selected cholesterol management genes (APOE, LDLR, LRP1, and LRPAP1) were chosen as confounding variables because they may influence both cholesterol levels and PD risk...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29020629/differential-regulation-of-lipoprotein-and-hepatitis-c-virus-secretion-by-rab1b
#9
Constantin N Takacs, Ursula Andreo, Viet Loan Dao Thi, Xianfang Wu, Caroline E Gleason, Michelle S Itano, Gabriella S Spitz-Becker, Rachel L Belote, Brenna R Hedin, Margaret A Scull, Charles M Rice, Sanford M Simon
Secretory cells produce diverse cargoes, yet how they regulate concomitant secretory traffic remains insufficiently explored. Rab GTPases control intracellular vesicular transport. To map secretion pathways, we generated a library of lentivirus-expressed dominant-negative Rab mutants and used it in a large-scale screen to identify regulators of hepatic lipoprotein secretion. We identified several candidate pathways, including those mediated by Rab11 and Rab8. Surprisingly, inhibition of Rab1b, the major regulator of transport from the endoplasmic reticulum to the Golgi, differently affected the secretion of the very-low-density lipoprotein components ApoE and ApoB100, despite their final association on mature secreted lipoprotein particles...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29020453/small-angle-neutron-scattering-sans-studies-on-r67-dihydrofolate-reductase-a-tetrameric-protein-with-intrinsically-disordered-n-termini
#10
Purva P Bhojane, Michael R Duff, Khushboo Bafna, Pratul K Agarwal, Christopher B Stanley, Elizabeth E Howell
R67 dihydrofolate reductase (DHFR) is a homo-tetramer with a single active site pore and no sequence or structural homology with chromosomal DHFRs. The R67 enzyme provides resistance to trimethoprim, an active site directed inhibitor of E. coli DHFR. 16-20 N-terminal amino acids are intrinsically disordered in the R67 dimer crystal structure. Chymotrypsin cleavage of 16 N-terminal residues results in an active enzyme with lowered stability. The space sampled by the disordered N-termini of R67 DHFR was investigated using small angle neutron scattering...
October 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29019983/human-trpml1-channel-structures-in-open-and-closed-conformations
#11
Philip Schmiege, Michael Fine, Günter Blobel, Xiaochun Li
Transient receptor potential mucolipin 1 (TRPML1) is a Ca(2+)-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes. Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder. Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-Å apo structure at pH 7.0 in the closed state, and a 3.49-Å agonist-bound structure at pH 6.0 in an open state. Several aromatic and hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting a distinct agonist-binding site from that found in TRPV1, a TRP channel from a different subfamily...
October 11, 2017: Nature
https://www.readbyqxmd.com/read/29017909/objectively-measuring-effects-of-electro-acupuncture-in-parkinsonian-rhesus-monkeys
#12
Rui Zhang, Anders H Andersen, Peter A Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M Gash, Richard Grondin, Zhiming Zhang
Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson's disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations...
October 7, 2017: Brain Research
https://www.readbyqxmd.com/read/29016683/the-epigenetic-factor-pcaf-regulates-vascular-inflammation-and-is-essential-for-intimal-hyperplasia-development
#13
Rob C M de Jong, Mark M Ewing, Margreet R de Vries, Jacco C Karper, Antonius J N M Bastiaansen, Hendrika A B Peters, Fabiana Baghana, Peter J van den Elsen, Céline Gongora, J Wouter Jukema, Paul H A Quax
OBJECTIVE: Genetic P300/CBP-associated factor (PCAF) variation affects restenosis-risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear factor kappa-beta (NFκB)-mediated inflammation, which drives post-interventional intimal hyperplasia development. We studied the contributing role of PCAF in post-interventional intimal hyperplasia. METHODS AND RESULTS: PCAF contribution to inflammation and intimal hyperplasia was assessed in leukocytes, macrophages and vascular smooth muscle cells (vSMCs) in vitro and in a mouse model for intimal hyperplasia, in which a cuff is placed around the femoral artery...
2017: PloS One
https://www.readbyqxmd.com/read/29016246/cognitive-dysfunction-and-single-nucleotide-polymorphisms-in-hepatitis-c-virus-infected-persons-a-systematic-review
#14
Tatiana Lins Carvalho, Raul Emídio Lima, Gustavo Henrique Belarmino Góes, Lívio Amaro Pereira, Matheus Santos de Sousa Fernandes, Patrícia Muniz Mendes Freire Moura, Luydson Richardson Silva Vasconcelos, Carolina Cunha Correia
The aim of this study was to realize a systematic review to identify data reported in the literature involving people infected by hepatitis C virus (HCV) with cognitive dysfunctions and single nucleotide polymorphisms (SNPs). The research was realized in six databases and the selection of studies was performed in two stages. Initially, we searched indexed articles from the following electronic databases: SciELO, MEDLINE, PubMed, HighWire, LILACS, and ScienceDirect. Then the articles were completely read and those that did not meet the eligibility criteria were excluded...
October 10, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28994705/role-of-purified-anthocyanins-in-improving-cardiometabolic-risk-factors-in-chinese-men-and-women-with-prediabetes-or-early-untreated-diabetes-a-randomized-controlled-trial
#15
Liping Yang, Wenhua Ling, Yan Yang, Yuming Chen, Zezhong Tian, Zhicheng Du, Jianying Chen, Yuanling Xie, Zhaomin Liu, Lili Yang
Objective: In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia. Research Design and Methods: This was a 12-week randomized, double-blind, placebo-controlled trial...
October 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28994390/clearance-of-beta-amyloid-is-facilitated-by-apolipoprotein-e-and-circulating-high-density-lipoproteins-in-bioengineered-human-vessels
#16
Jerome Robert, Emily B Button, Brian Yuen, Megan Gilmour, Kevin Kang, Arvin Bahrabadi, Sophie Stukas, Wenchen Zhao, Iva Kulic, Cheryl L Wellington
Amyloid plaques, consisting of deposited beta-amyloid (Aβ), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Aβ is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels...
October 10, 2017: ELife
https://www.readbyqxmd.com/read/28992410/product-release-mechanism-associated-with-structural-changes-in-monomeric-l-threonine-3-dehydrogenase
#17
Tomoharu Motoyama, Shogo Nakano, Yuta Yamamoto, Hiroaki Tokiwa, Yasuhisa Asano, Sohei Ito
A short-chain dehydrogenase like L-threonine 3-dehydrogenase (SDR-TDH) from metagenome data (mtTDH) was identified by database mining. Its enzymatic properties suggested that mtTDH has unique characteristics relative to other SDR-TDHs, including two mesophilic and thermophilic SDR-TDHs identified in this study. The activation energy of mtTDH was the lowest (29.6 kJ/mol) among SDR-TDHs, indicating that it is a psychrophilic enzyme. Size-exclusion chromatography analysis revealed mtTDH is monomer. Crystal structures of mtTDH in apo, binary, and two ternary complexes (L-Ser and L-Thr soaked forms) were determined at resolutions of 1...
October 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/28991263/structural-basis-for-gabaa-receptor-potentiation-by-neurosteroids
#18
Paul S Miller, Suzanne Scott, Simonas Masiulis, Luigi De Colibus, Els Pardon, Jan Steyaert, A Radu Aricescu
Type A γ-aminobutyric acid receptors (GABAARs) are the principal mediators of inhibitory neurotransmission in the human brain. Endogenous neurosteroids interact with GABAARs to regulate acute and chronic anxiety and are potent sedative, analgesic, anticonvulsant and anesthetic agents. Their mode of binding and mechanism of receptor potentiation, however, remain unknown. Here we report crystal structures of a chimeric GABAAR construct in apo and pregnanolone-bound states. The neurosteroid-binding site is mechanically coupled to the helices lining the ion channel pore and modulates the desensitization-gate conformation...
October 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28991238/the-structure-energy-landscape-of-nmda-receptor-gating
#19
Drew M Dolino, Sudeshna Chatterjee, David M MacLean, Charlotte Flatebo, Logan D C Bishop, Sana A Shaikh, Christy F Landes, Vasanthi Jayaraman
N-Methyl-D-aspartate (NMDA) receptors are the main calcium-permeable excitatory receptors in the mammalian central nervous system. The NMDA receptor gating is complex, exhibiting multiple closed, open, and desensitized states; however, central questions regarding the conformations and energetics of the transmembrane domains as they relate to the gating states are still unanswered. Here, using single-molecule Förster resonance energy transfer (smFRET), we map the energy landscape of the first transmembrane segment of the Rattus norvegicus NMDA receptor under resting and various liganded conditions...
October 9, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28990402/reassessing-the-structure-and-function-relationship-of-the-o-sub-2-sub-sensing-transcription-factor-fnr
#20
Erin L Mettert, Patricia Kiley
SIGNIFICANCE: The <i>Escherichia coli </i>regulatory protein FNR mediates a global transcriptional response upon O<sub>2</sub>-deprivation. Spanning nearly 40 years of research investigations, our understanding of how FNR senses and responds to O<sub>2</sub> has considerably progressed despite a lack of structural information for most of that period. This knowledge has established the paradigm for how facultative anaerobic bacteria sense changes in O<sub>2</sub> tension...
October 7, 2017: Antioxidants & Redox Signaling
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