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https://www.readbyqxmd.com/read/28231567/innate-lung-defense-during-invasive-aspergillosis-new-mechanisms
#1
Jaleesa M Garth, Chad Steele
Invasive aspergillosis (IA) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. Continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for IA. However, IA is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. The innate immune response to Aspergillus fumigatus, the primary agent in IA, plays a pivotal role in the recognition and elimination of organisms from the pulmonary system...
February 24, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28231550/short-term-particulate-matter-exposure-induces-extracellular-vesicle-release-in-overweight-subjects
#2
Matteo Bonzini, Laura Pergoli, Laura Cantone, Mirjam Hoxha, Andrea Spinazzè, Luca Del Buono, Chiara Favero, Michele Carugno, Laura Angelici, Lucia Broggi, Andrea Cattaneo, Angela C Pesatori, Valentina Bollati
BACKGROUND: Extracellular vesicles (EVs) represent a plausible molecular mechanism linking particulate matter (PM) inhalation to its systemic effects. Microvesicles (MVs) are released from many cell types in response to various stimuli. Increased body mass index (BMI) could modify the response to PM exposure due to enhanced PM uptake and/or an underlying pro-oxidative state. We investigated the relationship between EV release and PM10/PM2.5 exposure in a cohort of 51 volunteers. Subjects were stratified based on their BMI to evaluate whether overweight BMI is a determinant of hypersusceptibility to PM effects...
February 20, 2017: Environmental Research
https://www.readbyqxmd.com/read/28231513/increasing-ascorbate-levels-in-crops-to-enhance-human-nutrition-and-plant-abiotic-stress-tolerance
#3
REVIEW
Richard C Macknight, William A Laing, Sean M Bulley, Ronan C Broad, Alexander At Johnson, Roger P Hellens
Ascorbate (or vitamin C) is an essential human micronutrient predominantly obtained from plants. In addition to preventing scurvy, it is now known to have broader roles in human health, for example as a cofactor for enzymes involved in epigenetic programming and as regulator of cellular iron uptake. Furthermore, ascorbate is the major antioxidant in plants and underpins many environmentally induced abiotic stress responses. Biotechnological approaches to enhance the ascorbate content of crops therefore have potential to improve both human health and abiotic stress tolerance of crops...
February 20, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28231500/silver-nanoparticle-embedded-graphene-oxide-methotrexate-for-targeted-cancer-treatment
#4
Raj Kumar Thapa, Jae Hee Kim, Jee-Heon Jeong, Beom Soo Shin, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Combination therapies are widely investigated cancer treatment modalities. Carbon based systems such as graphene oxide (GO), plasmonic nanoparticles such as silver nanoparticles (AgNPs), and the folate analog, methotrexate (MTX), have been separately studied for their potential anticancer effects. In this study, we combined these systems to develop AgNPs-embedded GO with conjugated MTX (MTX-GO/AgNPs) and studied their folate receptor-targeted anticancer effects. Results revealed successful formation of AgNPs on GO along with MTX conjugation as suggested by UV/visible, TEM, AFM, FTIR, and XRD analysis...
February 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28231483/a-novel-redox-regulator-mntnbuoe-2-pyp-5-enhances-normal-hematopoietic-stem-progenitor-cell-function
#5
Y Zhao, D W Carroll, Y You, L Chaiswing, R Wen, I Batinic-Haberle, S Bondada, Y Liang, D K St Clair
The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP(5+)(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs...
February 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28231452/proteome-scale-identification-classification-and-structural-analysis-of-iron-binding-proteins-in-bread-wheat
#6
Shailender Kumar Verma, Ankita Sharma, Padmani Sandhu, Neha Choudhary, Shailaja Sharma, Vishal Acharya, Yusuf Akhter
Bread wheat is one of the major staple foods of worldwide population and iron plays a significant role in growth and development of the plant. In this report, we are presenting the genome wide identification of iron-binding proteins in bread wheat. The wheat genome derived putative proteome was screened for identification of iron-binding sequence motifs. Out of 602 putative iron-binding proteins, 130 were able to produce reliable structural models by homology techniques and further analyzed for the presence of iron-binding structural motifs...
February 14, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28231341/identification-of-the-er-resident-e3-ubiquitin-ligase-rnf145-as-a-novel-lxr-regulated-gene
#7
Emma C L Cook, Jessica K Nelson, Vincenzo Sorrentino, Duco Koenis, Martina Moeton, Saskia Scheij, Roelof Ottenhoff, Boris Bleijlevens, Anke Loregger, Noam Zelcer
Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol load. In this context, identifying the full set of LXR-regulated genes will contribute to our understanding of their role in cholesterol metabolism. Using global transcriptional analysis we report here the identification of RNF145 as an LXR-regulated target gene...
2017: PloS One
https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#8
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28231262/oleanolic-acid-induces-migration-in-mv1lu-and-mda-mb-231-epithelial-cells-involving-egf-receptor-and-map-kinases-activation
#9
Ángel Bernabé-García, David Armero-Barranco, Sergio Liarte, María Ruzafa-Martínez, Antonio Jesús Ramos-Morcillo, Francisco José Nicolás
During wound healing, skin function is restored by the action of several cell types that undergo differentiation, migration, proliferation and/or apoptosis. These dynamics are tightly regulated by the evolution of the extra cellular matrix (ECM) contents along the process. Pharmacologically active flavonoids have shown to exhibit useful physiological properties interesting in pathological states. Among them, oleanolic acid (OA), a pentacyclic triterpene, shows promising properties over wound healing, as increased cell migration in vitro and improved wound resolution in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28231239/surveillance-for-health-care-access-and-health-services-use-adults-aged-18-64-years-behavioral-risk-factor-surveillance-system-united-states-2014
#10
Catherine A Okoro, Guixiang Zhao, Jared B Fox, Paul I Eke, Kurt J Greenlund, Machell Town
PROBLEM/CONDITION: As a result of the 2010 Patient Protection and Affordable Care Act, millions of U.S. adults attained health insurance coverage. However, millions of adults remain uninsured or underinsured. Compared with adults without barriers to health care, adults who lack health insurance coverage, have coverage gaps, or skip or delay care because of limited personal finances might face increased risk for poor physical and mental health and premature mortality. PERIOD COVERED: 2014...
February 24, 2017: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/28231055/the-role-of-extracellular-vesicle-micrornas-in-cancer-biology
#11
Ryou-U Takahashi, Marta Prieto-Vila, Ai Hironaka, Takahiro Ochiya
MicroRNAs (miRNAs) constitute a large family of small, approximately 20-22 nucleotide non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Multiple studies report that miRNAs are involved in homeostatic maintenance and that aberrant expression of miRNAs is often observed in various types of diseases, including cancer. In cancer biology, miRNAs exert functional roles in tumor initiation, drug resistance, and metastasis. MiRNAs are also secreted through small vesicles called exosomes, which are endosome-derived vesicles derived from various cell types including immune and tumor cells...
February 23, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28231034/upscaling-of-hips-cell-derived-neurons-for-high-throughput-screening
#12
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Ralf Heilker
The advent of human-induced pluripotent stem (hiPS) cell-derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor-driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons...
March 2017: SLAS Discov
https://www.readbyqxmd.com/read/28230989/development-of-the-first-generation-of-disulfide-based-subtype-selective-and-potent-covalent-pyruvate-dehydrogenase-kinase-1-pdk1-inhibitors
#13
Yifu Liu, Zuoquan Xie, Dan Zhao, Jin Zhu, Fei Mao, Shuai Tang, Hui Xu, Cheng Luo, Mei-Yu Geng, Min Huang, Jian Li
Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described Bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, based on the scaffold of 16, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analog, 3a, effectively inhibits PDK1 both at the molecular (kinact/Ki = 4.17×103M-1s-1) and the cellular level (down to 0.1 μM). In contrast to 16, 3a is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2-4...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#14
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230977/extracellular-self-assembly-of-functional-and-tunable-protein-conjugates-from-bacillus-subtilis
#15
Charlie Gilbert, Mark Howarth, Colin R Harwood, Tom Ellis
The ability to stably and specifically conjugate recombinant proteins to one another is a powerful approach for engineering multifunctional enzymes, protein therapeutics and novel biological materials. While many of these applications have been illustrated through in vitro and in vivo intracellular protein conjugation methods, extracellular self-assembly of protein conjugates offers unique advantages: simplifying purification, reducing toxicity and burden, and enabling tunability. Exploiting the recently described SpyTag-SpyCatcher system, we describe here how enzymes and structural proteins can be genetically-encoded to covalently conjugate in culture media following programmable secretion from Bacillus subtilis...
February 23, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28230967/live-cell-pyrophosphate-imaging-by-in-situ-hot-spot-generation
#16
Mingmin Li, Jin Li, Huixia Di, Huiqiao Liu, Dingbin Liu
Controlling the electromagnetic hot-spot generation is essential for surface-enhanced Raman scattering (SERS) assays. Current hot spot-based SERS assays have been extensively studied in solutions or on substrates. However, probing biospecies by controlling the hot-spot assembly in living systems has not been demonstrated thus far. Herein, we report a background-free SERS probe for imag-ing pyrophosphate (PPi), a biochemically significant anion, in living cells. Intracellular PPi is able to induce the nanoparticle dimeri-zation, thus creating an intense electromagnetic hot spot and dramatically enhancing the signal of the Raman reporters residing in the hot spot...
February 23, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28230922/adipose-derived-aldehyde-dehydrogenase-expressing-cells-promote-dermal-regenerative-potential-with-collagen-glycosaminoglycan-scaffold
#17
Hajime Matsumine, Kazuyuki Numakura, Satoshi Tsunoda, Huan Wang, Rui Matsumine, Mihail Climov, Giorgio Giatsidis, Vikas P Sukhatme, Dennis P Orgill
Aldehyde dehydrogenase (ALDH) is an enzyme that plays an important role in retinoid metabolism and highly expressed in stem cells. This study isolated ALDH-expressing cells from subcutaneous adipose tissue and investigated their potential to enhance healing in a full-thickness skin wound in rats by co-implanting them with collagen-glycosaminoglycan (c-GAG) scaffolds. ALDH-positive cells were isolated by a fluorescence-activated cell sorting technique from Lewis rat's stromal-vascular-fraction (SVF) and transplanted with c-GAG scaffolds in a rat full-thickness skin wound model...
November 7, 2016: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28230857/protein-phosphatase-4-coordinates-glial-membrane-recruitment-and-phagocytic-clearance-of-degenerating-axons-in-drosophila
#18
Lilly M Winfree, Sean D Speese, Mary A Logan
Neuronal damage induced by injury, stroke, or neurodegenerative disease elicits swift immune responses from glial cells, including altered gene expression, directed migration to injury sites, and glial clearance of damaged neurons through phagocytic engulfment. Collectively, these responses hinder further cellular damage, but the mechanisms that underlie these important protective glial reactions are still unclear. Here, we show that the evolutionarily conserved trimeric protein phosphatase 4 (PP4) serine/threonine phosphatase complex is a novel set of factors required for proper glial responses to nerve injury in the adult Drosophila brain...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230856/ginsenoside-rg5-increases-cardiomyocyte-resistance-to-ischemic-injury-through-regulation-of-mitochondrial-hexokinase-ii-and-dynamin-related-protein-1
#19
Yi-Lin Yang, Jia Li, Kang Liu, Lei Zhang, Qun Liu, Baolin Liu, Lian-Wen Qi
Hexokinase-II (HK-II) and dynamin-related protein 1 (Drp1) regulate mitochondrial function differently. This study was designed to investigate the cardioprotective effect of ginsenoside Rg5 (Rg5) with emphasis on the regulation of mitochondrial HK-II and Drp1. Saturated acid palmitate (PA) stimulation increased lactate accumulation and induced cellular acidification by impairing the activity of pyruvate dehydrogenase (PDH) in cardiomyocytes, leading to HK-II dissociation from mitochondria. Rg5 improved PDH activity and prevented cellular acidification by combating fatty-acid oxidation, contributing to protecting mitochondrial HK-II...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230817/common%C3%A2-chemical%C3%A2-inductors%C3%A2-of%C3%A2-replication%C3%A2-stress-%C3%A2-focus%C3%A2-on%C3%A2-cell-based%C3%A2-studies
#20
REVIEW
Eva Vesela, Katarina Chroma, Zsofia Turi, Martin Mistrik
DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS). Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research...
February 21, 2017: Biomolecules
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