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Particle disease

Sweet Ping Ng, Joseph M Herman
Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies commonly utilize conventional radiotherapy treatment fractionation and technique (typically 3-D conformal radiotherapy or intensity modulated radiotherapy). Although no clear benefit in overall survival was demonstrated in those studies, those who received radiotherapy did have a clear benefit in terms of local control...
March 16, 2018: Cancers
Johan G Schnitzler, Geesje M Dallinga-Thie, Jeffrey Kroon
Over the last century, many studies have demonstrated that low-density lipoprotein (LDL) is a key risk factor of cardiovascular diseases (CVD) related to atherosclerosis. Thus, for these CVD patients, LDL lowering agents are commonly used in the clinic to reduce the risk for CVD. LDL, upon modification, will develop distinct inflammatory and pro-atherogenic potential, leading to impaired endothelial behavior and subsequent increased foam cell formation. LDL can also directly affect circulating monocyte composition, rendering them in a more favorable position to migrate and accumulate in the subendothelial space...
March 16, 2018: Current Medicinal Chemistry
Tiffany A Thibaudeau, Raymond T Anderson, David M Smith
Protein accumulation and aggregation with a concomitant loss of proteostasis often contribute to neurodegenerative diseases, and the ubiquitin-proteasome system plays a major role in protein degradation and proteostasis. Here, we show that three different proteins from Alzheimer's, Parkinson's, and Huntington's disease that misfold and oligomerize into a shared three-dimensional structure potently impair the proteasome. This study indicates that the shared conformation allows these oligomers to bind and inhibit the proteasome with low nanomolar affinity, impairing ubiquitin-dependent and ubiquitin-independent proteasome function in brain lysates...
March 15, 2018: Nature Communications
Sebhat Erqou, Jane E Clougherty, Oladipupo Olafiranye, Jared W Magnani, Aryan Aiyer, Sheila Tripathy, Ellen Kinnee, Kevin E Kip, Steven E Reis
OBJECTIVE: We aimed to assess racial differences in air pollution exposures to ambient fine particulate matter (particles with median aerodynamic diameter <2.5 µm [PM2.5 ]) and black carbon (BC) and their association with cardiovascular disease (CVD) risk factors, arterial endothelial function, incident CVD events, and all-cause mortality. APPROACH AND RESULTS: Data from the HeartSCORE study (Heart Strategies Concentrating on Risk Evaluation) were used to estimate 1-year average air pollution exposure to PM2...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Minghua Zheng, Jie Jiang, Xiao Zhang, Nan Wang, Kaihang Wang, Qiong Li, Tingting Li, Qingshan Lin, Yingbin Wang, Hai Yu, Ying Gu, Jun Zhang, Shaowei Li, Ningshao Xia
Hepatitis E virus (HEV) is associated with acute hepatitis disease. Numerous truncated HEV capsid proteins have been successfully expressed using different expression systems. Among these, p495, a protein truncated at its N- and C-termini by 111 and 54 amino acids (aa), respectively (HEV ORF2 aa 112-606) can self-assemble into T = 1 virus-like particles (VLPs) when expressed by insect cells. A shorter p239 (aa 368-606) protein is a particulate antigen that we have previously used in our commercialized HEV vaccine, Hecolin...
March 12, 2018: Vaccine
Alexander L Luryi, David Wright, Juliana Lawrence, Seilesh Babu, Michael LaRouere, Dennis I Bojrab, Eric W Sargent, John Zappia, Christopher A Schutt
PURPOSE: Benign paroxysmal positional vertigo (BPPV) involving the horizontal and superior semicircular canals is difficult to study due to variability in diagnosis. We aim to compare disease, treatment, and outcome characteristics between patients with BPPV of non-posterior semicircular canals (NP-BPPV) and BPPV involving the posterior canal only (P-BPPV) using the particle repositioning chair as a diagnostic and therapeutic tool. METHODS: Retrospective review of patients diagnosed with and treated for BPPV at a high volume otology institution using the particle repositioning chair...
March 7, 2018: American Journal of Otolaryngology
Mark T Corkum, Wei Liu, David A Palma, Glenn S Bauman, Robert E Dinniwell, Andrew Warner, Mark V Mishra, Alexander V Louie
BACKGROUND: Cancer patients frequently search the Internet for treatment options, and hospital websites are seen as reliable sources of knowledge. Guidelines support the use of proton radiotherapy in specific disease sites or on clinical trials. This study aims to evaluate direct-to-consumer advertising content and claims made by proton therapy centre (PTC) websites worldwide. METHODS: Operational PTC websites in English were identified through the Particle Therapy Co-Operative Group website...
March 15, 2018: Radiation Oncology
Kana Ide, Masaya Koshizaka, Hirotake Tokuyama, Takahiko Tokuyama, Takahiro Ishikawa, Yoshiro Maezawa, Minoru Takemoto, Koutaro Yokote
BACKGROUND: Patients with type 2 diabetes are at high risk for cardiovascular disease. Although hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Lipoprotein particle size and fraction changes are thought to contribute to such risks. The purpose of this study was to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid and docosahexaenoic acid, on lipoprotein particle size, concentration, and glycemic control in Japanese patients with type 2 diabetes and hypertriglyceridemia...
March 15, 2018: Lipids in Health and Disease
Fabio Sonvico, Adryana Clementino, Francesca Buttini, Gaia Colombo, Silvia Pescina, Silvia Stanisçuaski Guterres, Adriana Raffin Pohlmann, Sara Nicoli
In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer's disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality...
March 15, 2018: Pharmaceutics
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
Cédric Garcia, Nicolas Montée, Julien Faccini, Jennifer Series, Olivier Meilhac, Anne-Valérie Cantero, Pauline Le Faouder, Meyer Elbaz, Bernard Payrastre, Cécile Vindis
BACKGROUND: While high-density lipoproteins (HDL) have anti-thrombotic effects by reducing platelet activation, the relationship between HDL levels and the risk of acute coronary syndrome (ACS) is unclear since HDL particles are heterogeneous in composition and biological properties OBJECTIVE: We characterized the effects of HDL2 and HDL3 subclasses from ACS patients and non-coronary artery disease (CAD) subjects on platelet activation. METHODS: We measured platelet aggregation and ex vivo thrombus formation, analyzed signaling pathways by flow cytometry and performed a targeted lipidomics analysis on HDL subclasses RESULTS: Analysis of human platelet aggregation in suspension, adhesion on von Willebrand factor and thrombus formation on collagen under arterial shear demonstrated that HDL2 subclass from ACS patients had a higher antiplatelet potency compared to ACS HDL3 particles and HDL subclasses from non-CAD subjects...
March 15, 2018: Journal of Thrombosis and Haemostasis: JTH
Lei Xu, Laura J Braun, Daniel Rönnlund, Jerker Widengren, Pontus Aspenström, Annica K B Gad
Focal adhesions are subcellular regions at the micrometer scale that link the cell to the surrounding microenvironment and control vital cell functions. However, the spatial architecture of focal adhesions remains unclear at the nanometer scale. We used two-color and three-color super-resolution stimulated emission depletion microscopy to determine the spatial distributions and co-localization of endogenous focal adhesion components in fibroblasts. Our data indicate that adhesion proteins inside, but not outside, focal adhesions are organized into nanometer size units of multi-protein assemblies...
March 14, 2018: FEBS Journal
Sudhakar Agnihothram, Vineet D Menachery, Boyd L Yount, Lisa C Lindesmith, Trevor Scobey, Alan Whitmore, Alexandra Schäfer, Mark T Heise, Ralph S Baric
Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this manuscript, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate utility of the VRP 3526 platform in generation of recombinant proteins, production of virus like particles, and in vivo efficacy as a vaccine against emergent viruses...
March 14, 2018: Journal of Virology
María Cecilia Gimenez, Flavia Adriana Zanetti, Mauricio R Terebiznik, María Isabel Colombo, Laura Ruth Delgui
Birnaviruses are unconventional members of the double-stranded RNA (dsRNA) viruses group that are characterized by the lack of a transcriptionally active inner core. Instead, the birnaviral particles organize their genome in ribonucleoprotein complexes (RNPs) composed by dsRNA segments, the dsRNA-binding VP3 protein, and the viral encoded RNA-dependent RNA-polymerase (RdRp). This and other structural features suggests that birnaviruses may follow a completely different replication program from that followed by members of the Reoviridae family, supporting the hypothesis that birnaviruses are the evolutionary link between single-stranded positive RNA (+ssRNA) and dsRNA viruses...
March 14, 2018: Journal of Virology
Sarah A Aroner, Manja Koch, Kenneth J Mukamal, Jeremy D Furtado, James H Stein, Matthew C Tattersall, Robyn L McClelland, Majken K Jensen
BACKGROUND: Apolipoprotein C-III (apoC-III), a small proinflammatory protein present on 6% to 7% of high-density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi-ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC-III-defined HDL subspecies and subclinical markers of atherosclerotic pathology. METHODS AND RESULTS: We investigated cross-sectional associations between apolipoprotein A-I concentrations of apoC-III-defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi-Ethnic Study of Atherosclerosis) at baseline (2000-2002)...
March 14, 2018: Journal of the American Heart Association
Yanting Yu, Feng Bai, Nan Qin, Wenjin Liu, Qi Sun, Yang Zhou, Junwei Yang
BACKGROUND: Renal fibrosis is a common outcome of nearly all kinds of chronic kidney disease (CKD) and eventually progresses to end-stage renal disease. The identification of an optimal biomarker of renal fibrosis to replace the invasive renal biopsy will have important clinical implications. METHODS: We isolated urinary exosomes from 50 participants and examined the exosomal protein content and particle number in 38 CKD patients with different degrees of renal fibrosis and in 12 normal individuals...
March 14, 2018: Nephron
Marilda Savoia Nascimento, Anna Maria Simonsen Stolf, Heitor Franco de Andrade Junior, Ramendra Pati Pandey, Eufrosina Setsu Umezawa
BACKGROUND: Vimentin is a main structural protein of the cell, a component of intermediate cell filaments and immersed in cytoplasm. Vimentin is mimicked by some bacterial proteins and anti-vimentin antibodies occur in autoimmune cardiac disease, as rheumatic fever. In this work we studied vimentin distribution on LLC-MK2 cells infected with T. cruzi and anti-vimentin antibodies in sera from several clinical pictures of Chagas' disease or American Trypanosomiasis, in order to elucidate any vimentin involvement in the humoral response of this pathology...
March 12, 2018: Arquivos Brasileiros de Cardiologia
Junhua Mai, Xin Li, Guodong Zhang, Yi Huang, Rong Xu, Qi Shen, Ganesh Lakshmana Rao Lokesh, Varatharasa Thiviyanathan, Lingxiao Chen, Haoran Liu, Youli Zu, Xiaojing Ma, David E Volk, David G Gorenstein, Mauro Ferrari, Haifa Shen
Selective drug accumulation in the malignant tissue is a prerequisite for effective cancer treatment. However, most drug molecules and their formulated particles are blocked en route to the destiny tissue due to the existence of multiple biological and physical barriers including the tumor microvessel endothelium. Since the endothelial cells on the surface of the microvessel wall can be modulated by inflammatory cytokines and chemokines secreted by the tumor or stromal cells, an effective drug delivery approach is to enhance interaction between the drug particles and the unique spectrum of surface proteins on the tumor endothelium...
March 14, 2018: Molecular Pharmaceutics
J Breza, Z Durackova, J Payer, A Dukat, J Breza
Asymptomatic atherosclerotic disease is prevalent in the middle-aged group of kidney transplant recipients. In order to improve the estimation of their cardiovascular risk, dyslipidaemia pattern is very important to be evaluated. Knowledge of the lipid particle spectrum in patients undergoing kidney transplantation could help the clinicians to timely start intervention and prevention of atherosclerosis with an early hypolipidemic statin treatment (Tab. 2, Ref. 20).
2018: Bratislavské Lekárske Listy
Rong Wang, Lei Cao, Zhenxing Shen, Yongxiao Cao
Fine particle matters (PM2.5 ) is a well-known risk factor for cardiovascular diseases. However, the underlying molecular mechanisms are largely unknown. Vascular hyper-reactivity plays an important roles in the pathogenesis of cardiovascular diseases. The present study was designed to investigate a hypothesis that PM2.5 up-regulated endothelin receptors in mesenteric artery and the potential underlying mechanisms. Rat mesenteric arteries were cultured with PM2.5 . The artery contractile responses were recorded by a sensitive myograph...
March 13, 2018: Environmental Science and Pollution Research International
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