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https://www.readbyqxmd.com/read/29683002/short-term-evaluation-of-hepatic-toxicity-of-titanium-dioxide-nanofiber-tdnf
#1
Leah K Bartel, Daniel A Hunter, Kayla B Anderson, W Yau, Ji Wu, Worlanyo E Gato
Various in vitro and in vivo studies have shown titanium dioxide nanoparticles (TDNPs) increase the production of reactive oxygen species and change the expression of genes and proteins involved in the inflammatory response and cell division. Although, the cytotoxicity of TDNPs has been shown to be largely dependent on the characteristics of the particles including shape and surface area. This present study investigates the effects of titanium dioxide nanofibers (TDNFs) with a diameter of 300-800 nm, on the histopathology of liver tissue, changes in feed efficiency and liver weights, changes in hepatic gene expression, and serum biochemical parameters in male Sprague-Dawley rats...
April 23, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29665381/a-refined-developability-classification-system-rdcs
#2
J Rosenberger, J Butler, J Dressman
In 2010, the Developability Classification System (DCS) was proposed. The DCS was deigned to close the gap between the BCS, which is aimed at guiding regulatory decisions about well-characterized drugs, and the need for early evaluation of drug candidates with respect to their suitability for oral delivery. The DCS applied solubility in FaSSIF to estimate intestinal solubility, assessed the compensatory nature of permeability and solubility during oral absorption and provided a way of estimating the critical the particle size at which dissolution becomes rate-limiting to absorption...
April 14, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29663407/ground-beef-high-in-total-fat-and-saturated-fatty-acids-decreases-x-receptor-signaling-targets-in-peripheral-blood-mononuclear-cells-of-men-and-women
#3
Seong H Choi, Ghazal Gharahmany, Rosemary L Walzem, Thomas H Meade, Stephen B Smith
We hypothesized that consumption of saturated fatty acids in the form of high-fat ground beef for 5 weeks would depress liver X receptor signaling targets in peripheral blood mononuclear cells (PBMC) and that changes in gene expression would be associated with the corresponding changes in lipoprotein cholesterol (C) concentrations. Older men (n = 5, age 68.0 ± 4.6 years) and postmenopausal women (n = 7, age 60.9 ± 3.1 years) were assigned randomly to consume ground-beef containing 18% total fat (18F) or 25% total fat (25F), five patties per week for 5 weeks with an intervening 4-week washout period...
April 16, 2018: Lipids
https://www.readbyqxmd.com/read/29653119/adenovirus-mediated-overexpression-of-sst2-attenuates-cardiac-injury-in-the-rat-with-severe-acute-pancreatitis
#4
Lei Li, Zhongwei Sun, Caiming Xu, Jun Wu, Geliang Liu, Hongzhang Cui, Hailong Chen
AIMS: Severe acute pancreatitis (SAP) is a serious disease associated with systematic inflammation and multiple organs dysfunction. Soluble ST2 (sST2), a member of the Toll interleukin (IL)-1 receptor (TIR) superfamily, has been demonstrated to exert immune-regulatory and anti-inflammatory properties in several inflammation-related diseases. In this study, we investigated whether transfer of sST2 gene by adenovirus vector could attenuate sodium taurocholate-induced SAP and associated cardiac injury...
April 10, 2018: Life Sciences
https://www.readbyqxmd.com/read/29625982/the-protease-clpxp-and-the-pas-domain-protein-divl-regulate-ctra-and-gene-transfer-agent-production-in-rhodobacter-capsulatus
#5
A B Westbye, L Kater, C Wiesmann, H Ding, C K Yip, J T Beatty
Several members of the Rhodobacterales ( Alphaproteobacteria ) produce a conserved horizontal gene transfer vector, called gene transfer agent (GTA), that appears to have evolved from a bacteriophage. The model system to study GTA biology is the R. capsulatus GTA (RcGTA), a small, tailed bacteriophage-like particle produced by a subset of the cells in a culture. The response regulator CtrA is conserved in the Alphaproteobacteria and is an essential regulator of RcGTA production: it controls production and maturation of the RcGTA particle and RcGTA release from cells...
April 6, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29624167/proteasome-storage-granules-protect-proteasomes-from-autophagic-degradation-upon-carbon-starvation
#6
Richard Scott Marshall, Richard David Vierstra
26S proteasome abundance is tightly regulated at multiple levels, including the elimination of excess or inactive particles by autophagy. In yeast, this proteaphagy occurs upon nitrogen starvation but not carbon starvation, which instead stimulates the rapid sequestration of proteasomes into cytoplasmic puncta termed proteasome storage granules (PSGs). Here, we show that PSGs help protect proteasomes from autophagic degradation. Both the core protease and regulatory particle sub-complexes are sequestered separately into PSGs via pathways dependent on the accessory proteins Blm10 and Spg5, respectively...
April 6, 2018: ELife
https://www.readbyqxmd.com/read/29620292/nik%C3%A2-and-ikk%C3%AE-%C3%A2-binding-protein-contributes-to-gastric-cancer-chemoresistance-by-promoting-epithelial%C3%A2-mesenchymal-transition-through-the-nf%C3%A2-%C3%AE%C2%BAb-signaling-pathway
#7
Zhen-Hua Fu, Shi-Quan Liu, Meng-Bin Qin, Jie-An Huang, Chun-Yan Xu, Wen-Hong Wu, Li-Ye Zhu, Nan Qin, Ming-Yu Lai
Systematic chemotherapy is indispensable for gastric cancer patients with advanced stage disease, but the occurrence of chemoresistance drastically limits treatment effectiveness. There is a tremendous need for identifying the underlying mechanism of chemoresistance. NIK‑ and IKKβ‑binding protein (NIBP) (also known as TRAPPC9, trafficking protein particle complex 9) is a regulator of the cytokine‑induced NF‑κB signaling pathway which has been proven to play pivotal roles in the progression of various malignancies...
March 30, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29611480/systematic-development-and-optimization-of-in-situ-gelling-system-for-moxifloxacin-ocular-nanosuspension-using-high-pressure-homogenization-with-improved-encapsulation-efficiency
#8
Lalit Kumar Khurana, Romi Singh, Harinder Singh, Manju Sharma
BACKGROUND: The objective of this study was to apply Quality by Design (QbD) principles on process parameter optimization for development of hybrid delivery system (combination of (SLNs) and In-situ gelling system) for hydrophilic drug Moxifloxacin Hydrochloride (MOX) to achieve its controlled delivery, which otherwise may not be possible through single type of technology. METHODS: Risk assessment studies were carried out to identify probable risks influencing CQAs on the product...
April 2, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29593046/host-factor-spcs1-regulates-the-replication-of-japanese-encephalitis-virus-through-interactions-with-transmembrane-domains-of-ns2b
#9
Le Ma, Fang Li, Jing-Wei Zhang, Wei Li, Dong-Ming Zhao, Han Wang, Rong-Hong Hua, Zhi-Gao Bu
Signal peptidase complex subunit 1 (SPCS1) is a newly identified host factor that regulates flavivirus replication, but the molecular mechanism is not fully understood. Herein, using Japanese encephalitis virus (JEV) as a model, we investigated the mechanism through which host factor SPCS1 regulates the replication of flaviviruses. We first validated the regulatory function of SPCS1 in JEV propagation by knocking down and knocking out endogenous SPCS1. Loss of SPCS1 function markedly reduced intracellular virion assembly and production of infectious JEV particles, but did not affect virus cell entry, RNA replication, or translation...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29574228/a-platform-for-preparing-homogeneous-proteinaceous-sub-visible-particles-with-distinct-morphologies
#10
Malthe Møhl Schack, Eva Horn Møller, John F Carpenter, Thomas Rades, Minna Groenning
Regulatory authorities and scientific communities are increasingly attentive to the known and universal presence of small particulates in biological drug products. The underlying concern is that these particulates may cause unwanted formation of anti-drug antibodies in patients Pharmacological studies, however, have to date not succeeded in unambiguously identifying risk-prone particle properties. This lack of success may be partly due to a lack of available, well-defined, homogenous particle material. Protein particles arising from stress of protein drug products are by nature often highly heterogeneous in size, morphology, and structure of the constituent protein in the particles...
March 21, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29564630/proteomic-analysis-of-melatonin-mediated-osmotic-tolerance-by-improving-energy-metabolism-and-autophagy-in-wheat-triticum-aestivum-l
#11
Guibin Cui, Fengli Sun, Xinmei Gao, Kunliang Xie, Chao Zhang, Shudong Liu, Yajun Xi
Melatonin-mediated osmotic tolerance was attributed to increased antioxidant capacity, energy metabolism, osmoregulation and autophagy in wheat (Triticum aestivum L.). Melatonin is known to play multiple roles in plant abiotic stress tolerance. However, its role in wheat has been rarely investigated. In this study, 25% polyethylene glycol 6000 (PEG 6000) was used to simulate osmotic stress, and wheat seeds and seedlings were treated with different concentrations of melatonin under PEG stress. Isobaric tag for relative and absolute quantification (iTRAQ)-based proteomic techniques were used to identify the differentially accumulated proteins from melatonin-treated and non-treated seedlings...
March 21, 2018: Planta
https://www.readbyqxmd.com/read/29556699/the-novel-deubiquitinase-inhibitor-b-ap15-induces-direct-and-nk-cell-mediated-antitumor-effects-in-human-mantle-cell-lymphoma
#12
Korbinian N Kropp, Stefanie Maurer, Kathrin Rothfelder, Bastian J Schmied, Kim L Clar, Moritz Schmidt, Benedikt Strunz, Hans-Georg Kopp, Alexander Steinle, Frank Grünebach, Susanne M Rittig, Helmut R Salih, Daniela Dörfel
The first therapeutic proteasome inhibitor bortezomib has clinical efficacy in mantle cell lymphoma (MCL) which resulted in its incorporation in treatment algorithms for this disease. Impairment of proteasomal function by bortezomib is mediated via inhibition of the 20S core particle. However, proteasome function can also be modified by targeting upstream components of the ubiquitin-proteasome system. Recently, b-AP15 has been identified as a small molecule achieving proteasome inhibition by targeting the deubiquitinase (DUB) activity of the 19S regulatory subunit and was found to inhibit cancer cell growth in preclinical analyses...
March 19, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29556352/the-enhanced-antitumor-specific-immune-response-with-mannose-and-cpg-odn-coated-liposomes-delivering-trp2-peptide
#13
Chunhui Lai, Siliang Duan, Fang Ye, Xiaoqiong Hou, Xi Li, Jin Zhao, Xia Yu, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaomei Yang, Xiaoling Lu
PURPOSE: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. METHODS: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine...
2018: Theranostics
https://www.readbyqxmd.com/read/29556036/autophagy-during-viral-infection-a-double-edged-sword
#14
REVIEW
Younho Choi, James W Bowman, Jae U Jung
Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes...
March 19, 2018: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/29553842/assessment-of-the-in-vitro-genotoxicity-of-tio-2-nanoparticles-in-a-regulatory-context
#15
Sandrine Charles, Stéphane Jomini, Valérie Fessard, Emilie Bigorgne-Vizade, Christophe Rousselle, Cécile Michel
A review of in vitro genotoxicity studies on titanium dioxide nanoparticles (TiO2 -NPs) published between 2010 and 2016 was performed by France in the framework of the CLP Regulation 1272/2008/EC. Neither the few in vivo studies of low quality nor the larger number of acceptable in vitro studies available for genotoxicity allowed France to conclude on the genotoxicity of TiO2 -NPs. Based on this work, it was decided to compare the acceptable in vitro studies to understand the reasons for the diverging results observed, such as the materials tested or of the protocols used and their inherent interferences...
March 19, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29545616/apolipoprotein-ai-prevents-regulatory-to-follicular-helper-t-cell-switching-during-atherosclerosis
#16
Dalia E Gaddis, Lindsey E Padgett, Runpei Wu, Chantel McSkimming, Veronica Romines, Angela M Taylor, Coleen A McNamara, Mitchell Kronenberg, Shane Crotty, Michael J Thomas, Mary G Sorci-Thomas, Catherine C Hedrick
Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis. Mechanistically, the conversion of Treg cells to Tfh cells correlates with reduced expression of IL-2Rα and pSTAT5 levels and increased expression of IL-6Rα...
March 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29545515/a-common-mechanism-of-proteasome-impairment-by-neurodegenerative-disease-associated-oligomers
#17
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
https://www.readbyqxmd.com/read/29535732/the-mek1-2-erk-pathway-inhibits-type-i-ifn-production-in-plasmacytoid-dendritic-cells
#18
Vaclav Janovec, Besma Aouar, Albert Font-Haro, Tomas Hofman, Katerina Trejbalova, Jan Weber, Laurence Chaperot, Joel Plumas, Daniel Olive, Patrice Dubreuil, Jacques A Nunès, Ruzena Stranska, Ivan Hirsch
Recent studies have reported that the crosslinking of regulatory receptors (RRs), such as blood dendritic cell antigen 2 (BDCA-2) (CD303) or ILT7 (CD85g), of plasmacytoid dendritic cells (pDCs) efficiently suppresses the production of type I interferons (IFN-I, α/β/ω) and other cytokines in response to toll-like receptor 7 and 9 (TLR7/9) ligands. The exact mechanism of how this B cell receptor (BCR)-like signaling blocks TLR7/9-mediated IFN-I production is unknown. Here, we stimulated BCR-like signaling by ligation of RRs with BDCA-2 and ILT7 mAbs, hepatitis C virus particles, or BST2 expressing cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29519818/proteasome-activity-is-influenced-by-the-hect_2-protein-ipa1-in-budding-yeast
#19
Anne P Lutz, Sarah Schladebeck, Christian Renicke, Roberta Spadaccini, Hans-Ulrich Mösch, Christof Taxis
The ubiquitin-proteasome system (UPS) controls cellular functions by maintenance of a functional proteome and degradation of key regulatory proteins. Central to the UPS is the proteasome that adjusts the abundance of numerous proteins, thereby safeguarding their activity or initiating regulatory events. Here, we demonstrate that the essential Saccharomyces cerevisiae protein Yjr141w/Ipa1 (Important for cleavage and PolyAdenylation) belongs to the HECT_2 (homologous to E6-AP carboxyl terminus_2) family. We found that five cysteine residues within the HECT_2 family signature and the C-terminus are essential for Ipa1 activity...
March 8, 2018: Genetics
https://www.readbyqxmd.com/read/29518358/axon-axon-interactions-regulate-topographic-optic-tract-sorting-via-cyfip2-dependent-wave-complex-function
#20
Jean-Michel Cioni, Hovy Ho-Wai Wong, Dario Bressan, Lay Kodama, William A Harris, Christine E Holt
The axons of retinal ganglion cells (RGCs) are topographically sorted before they arrive at the optic tectum. This pre-target sorting, typical of axon tracts throughout the brain, is poorly understood. Here, we show that cytoplasmic FMR1-interacting proteins (CYFIPs) fulfill non-redundant functions in RGCs, with CYFIP1 mediating axon growth and CYFIP2 specifically involved in axon sorting. We find that CYFIP2 mediates homotypic and heterotypic contact-triggered fasciculation and repulsion responses between dorsal and ventral axons...
March 7, 2018: Neuron
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