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https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#1
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28911530/autophagy-inducing-effect-of-pterostilbene-a%C3%A2-prospective-therapeutic-preventive-option-for-skin-diseases
#2
Rong-Jane Chen, Yu-Hsuan Lee, Ya-Ling Yeh, Wun-Syuan Wu, Chi-Tang Ho, Chia-Yi Li, Bour-Jr Wang, Ying-Jan Wang
Pterostilbene is a naturally occurring analog of resveratrol with many health benefits. These health benefits are associated with its antioxidant activity, anti-inflammatory effects, and chemopreventive effects attributed to its unique structure. The skin cancer chemopreventive potential of pterostilbene is supported by a variety of mechanistic studies confirming the anti-inflammatory effects in skin cancer models. Molecular biological studies have identified that pterostilbene targets pleotropic signaling pathways, including those involved in mitogenesis, cell cycle regulation, and apoptosis...
January 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28880939/arf6-mediates-nephrin-tyrosine-phosphorylation-induced-podocyte-cellular-dynamics
#3
Jamie S Lin, Jin Seok Jeon, Qingfeng Fan, Hetty N Wong, Matthew B Palmer, Lawrence B Holzman
ADP-ribosylation factor 6 (ARF6) is a small GTPase necessary for regulating cellular structure, motility, and vesicle trafficking. In several cellular systems, ARF6 was shown to regulate actin dynamics in coordination with Rac1, a Rho small GTPase. We examined the function of ARF6 in the kidney podocyte because Rac1 was implicated in kidney diseases involving this cell. We found that ARF6 expression was enriched in human podocytes and that it modulated podocyte cytoskeletal dynamics through a functional interaction with nephrin, an intercellular junction protein necessary for podocyte injury-induced signaling requiring activation by tyrosine phosphorylation of its cytoplasmic domain...
2017: PloS One
https://www.readbyqxmd.com/read/28869931/a-phase-ii-exploratory-study-of-pxd-101-belinostat-followed-by-zevalin-in-patients-with-relapsed-aggressive-high-risk-lymphoma
#4
Soham D Puvvada, José M Guillén-Rodríguez, Xavier I Rivera, Kara Heard, Lora Inclan, Monika Schmelz, Jonathan H Schatz, Daniel O Persky
OBJECTIVE: Aggressive lymphomas (aNHL) including diffuse large B-cell lymphoma (DLBCL) have poor outcomes in relapsed refractory patients. Prior studies have demonstrated that loss of major histocompatibility complex class II (MHCII) expression in DLBCL is associated with poor survival. The objective of this single-arm phase II study was to evaluate if PXD-101 would increase MHCII expression, synergize with Zevalin, and improve clinical outcomes. METHODS: This was a single-center open-label phase II trial (NCT01686165) geared toward heavily pretreated patients with CD20-positive aNHL...
September 5, 2017: Oncology
https://www.readbyqxmd.com/read/28757913/the-involvement-of-mg-2-in-regulation-of-cellular-and-mitochondrial-functions
#5
REVIEW
Ivana Pilchova, Katarina Klacanova, Zuzana Tatarkova, Peter Kaplan, Peter Racay
Mg(2+) is an essential mineral with pleotropic impacts on cellular physiology and functions. It acts as a cofactor of several important enzymes, as a regulator of ion channels such as voltage-dependent Ca(2+) channels and K(+) channels and on Ca(2+)-binding proteins. In general, Mg(2+) is considered as the main intracellular antagonist of Ca(2+), which is an essential secondary messenger initiating or regulating a great number of cellular functions. This review examines the effects of Mg(2+) on mitochondrial functions with a particular focus on energy metabolism, mitochondrial Ca(2+) handling, and apoptosis...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28747179/new-insights-into-the-roles-of-cucumber-tir1-homologs-and-mir393-in-regulating-fruit-seed-set-development-and-leaf-morphogenesis
#6
Jian Xu, Ji Li, Li Cui, Ting Zhang, Zhe Wu, Pin-Yu Zhu, Yong-Jiao Meng, Kai-Jing Zhang, Xia-Qing Yu, Qun-Feng Lou, Jin-Feng Chen
BACKGROUND: TIR1-like proteins act as auxin receptors and play essential roles in auxin-mediated plant development processes. The number of auxin receptor family members varies among species. While the functions of auxin receptor genes have been widely studied in Arabidopsis, the distinct functions of cucumber (Cucumis sativus L.) auxin receptors remains poorly understood. To further our understanding of their potential role in cucumber development, two TIR1-like genes were identified and designated CsTIR1 and CsAFB2...
July 26, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28668359/the-balance-between-induction-and-inhibition-of-mevalonate-pathway-regulates-cancer-suppression-by-statins-a-review-of-molecular-mechanisms
#7
REVIEW
Yasin Ahmadi, Amir Ghorbanihaghjo, Hassan Argani
Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic patients. Statins through inhibition of Hydroxy Methyl Glutaryl-CoA Reductase (HMGCR), the main enzyme of the cholesterol biosynthesis pathway, inhibit mevalonate pathway that provides isoprenoids for prenylation of different proteins such as Ras superfamily which has an essential role in cancer developing. Inhibition of the mevalonate/isoprenoid pathway is the cause of the cholesterol independent effects of statins or pleotropic effects...
June 28, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28652404/current-prospects-of-type-ii-interferon-%C3%AE-signaling-and-autoimmunity
#8
REVIEW
Daniel S Green, Howard A Young, Julio C Valencia
Interferon γ (IFNγ) is a pleiotropic protein secreted by immune cells. IFNγ signals through the IFNγ receptor, a protein complex that mediates downstream signaling events. Studies into IFNγ signaling have provided insight into the general concepts of receptor signaling, receptor internalization, regulation of distinct signaling pathways, and transcriptional regulation. Although IFNγ is the central mediator of the adaptive immune response to pathogens, it has been shown to be involved in several non-infectious physiological processes...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28636814/arsenic-compromises-both-p97-and-proteasome-functions
#9
Joseph Tillotson, Christopher J Zerio, Bryan Harder, Andrew J Ambrose, Kevin S Jung, MinJin Kang, Donna D Zhang, Eli Chapman
Exposure to arsenic is a worldwide problem that affects more than 200 million people. The underlying mechanisms of arsenic toxicity have been difficult to ascertain due to arsenic's pleotropic effects. A number of recent investigations have shown that arsenic can compromise protein quality control through the ubiquitin proteasome system (UPS) or the endoplasmic reticulum associated protein degradation (ERAD) pathway. In this article, a link between arsenic and protein quality control is reported. Biochemical and cellular data demonstrate a misregulation of the ATPase cycle of the ATPase associated with various cellular activities (AAA+) chaperone, p97...
July 7, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28623546/targeting-sphingosine-1-phosphate-signaling-for-cancer-therapy
#10
REVIEW
Zuoquan Xie, Hong Liu, Meiyu Geng
Sphingosine-1-phosphate (S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival, cell proliferation, cell migration, angiogenesis and many other cellular processes. S1P either activates S1P receptors (S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1P signaling and its pathogenic roles in diseases as well as in developing modulators of S1P signaling, including S1P agonists, S1P antagonists and sphingosine kinase (SphK) inhibitors...
May 27, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28621569/down-regulation-of-slcyp1-in-the-phloem-reduces-auxin-response-and-photosynthetic-rate-in-tomato-solanum-lycopersicum-plants
#11
Ziv Spiegelman, Amit Shahar, Shmuel Wolf
The tomato dgt mutant, containing a single mutation in the Cyclophilin1 (SlCyp1) gene, is auxin insensitive and exhibits a pleotropic phenotype that includes lack of lateral roots, malformed xylem structure and reduced root-to-shoot ratio. Recently, we found that the SlCyp1 protein is phloem-mobile and traffic from shoot to root to induce lateral root formation. These processes are achieved through activation of auxin-mediated developmental programs. Inhibition of the trafficked SlCyp1 activity at the target site resulted in inhibition of the auxin response, supporting the hypothesis that this protein is indeed a mobile signal...
June 3, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28620279/interleukin-6-deficiency-attenuates-retinal-ganglion-cell-axonopathy-and-glaucoma-related-vision-loss
#12
Franklin D Echevarria, Cathryn R Formichella, Rebecca M Sappington
The pleotropic cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT) and IL-6 knock-out mice (B6;129S2-IL6(t)(m1kopf)/J; IL-6-/-) after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28559299/the-disulfide-bond-formation-pathway-is-essential-for-anaerobic-growth-of-escherichia-coli
#13
Brian M Meehan, Cristina Landeta, Dana Boyd, Jonathan Beckwith
Disulfide bonds are critical to the stability and function of many bacterial proteins. In the periplasm of Escherichia coli, intramolecular disulfide bond formation is catalyzed by the two-component disulfide bond forming (DSB) system. Inactivation of the DSB pathway has been shown to lead to a number of pleotropic effects, although cells remain viable under standard laboratory conditions. However, we show here that dsb strains of E. coli reversibly filament under aerobic conditions and fail to grow anaerobically unless a strong oxidant is provided in the growth medium...
August 15, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28497128/innovative-therapeutics-designer-natriuretic-peptides
#14
Laura M G Meems, John C Burnett
Endogenous natriuretic peptides serve as potent activators of particulate guanylyl cyclase receptors and the second messenger cGMP. Natriuretic peptides are essential in maintenance of volume homeostasis, and can be of myocardial, renal and endothelial origin. Advances in peptide engineering have permitted the ability to pursue highly innovative drug discovery strategies. This has resulted in designer natriuretic peptides that go beyond native peptides in efficacy, specificity, and resistance to enzymatic degradation...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28464262/a-tale-of-agriculturalists-and-hunter-gatherers-exploring-the-thrifty-genotype-hypothesis-in-native-south-americans
#15
Guillermo Reales, Diego L Rovaris, Vanessa C Jacovas, Tábita Hünemeier, José R Sandoval, Alcibiades Salazar-Granara, Darío A Demarchi, Eduardo Tarazona-Santos, Aline B Felkl, Michele A Serafini, Francisco M Salzano, Rafael Bisso-Machado, David Comas, Vanessa R Paixão-Côrtes, Maria Cátira Bortolini
OBJECTIVES: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel's thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations. MATERIALS AND METHODS: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701)...
July 2017: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/28448568/inhibitory-effects-of-fenretinide-metabolites-n-4-methoxyphenyl-retinamide-mpr-and-4-oxo-n-4-hydroxyphenyl-retinamide-3-keto-hpr-on-fenretinide-molecular-targets-%C3%AE-carotene-oxygenase-1-stearoyl-coa-desaturase-1-and-dihydroceramide-%C3%AE-4-desaturase-1
#16
Eugenia Poliakov, William Samuel, Todd Duncan, Danielle B Gutierrez, Nathan L Mata, T Michael Redmond
The therapeutic capacity of fenretinide (N-[4-hydroxyphenyl] retinamide; 4-HPR) has been demonstrated for several conditions, including cancer, obesity, diabetes, and ocular disease. Yet, the mechanisms of action for its pleiotropic effects are still undefined. We hypothesized that investigation of two of the major physiological metabolites of fenretinide, N-[4-methoxyphenyl]retinamide (MPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (3-keto-HPR), might begin to resolve the multifaceted effects of this synthetic retinoid...
2017: PloS One
https://www.readbyqxmd.com/read/28445598/dabigatran-enhances-platelet-reactivity-and-platelet-thrombin-receptor-expression-in-patients-with-atrial-fibrillation-reply
#17
LETTER
A Achilles, A Mohring, T Zeus, M Kelm, A Polzin
No abstract text is available yet for this article.
April 26, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28426765/allatotropin-a-pleiotropic-neuropeptide-that-elicits-mosquito-immune-responses
#18
Salvador Hernández-Martínez, Minerva Sánchez-Zavaleta, Kevin Brito, Antonia Herrera-Ortiz, Sheila Ons, Fernando G Noriega
Allatotropins (AT) are neuropeptides with pleotropic functions on a variety of insect tissues. They affect processes such as juvenile hormone biosynthesis, cardiac rhythm, oviduct and hindgut contractions, nutrient absorption and circadian cycle. The present work provides experimental evidence that AT elicits immune responses in two important mosquito disease vectors, Anopheles albimanus and Aedes aegypti. Hemocytes and an immune-competent mosquito cell line responded to AT by showing strong morphological changes and increasing bacterial phagocytic activity...
2017: PloS One
https://www.readbyqxmd.com/read/28423621/epstein-barr-virus-encoded-microrna-bart7-regulates-radiation-sensitivity-of-nasopharyngeal-carcinoma
#19
Wei Gao, Zeng-Hong Li, Siqi Chen, Jimmy Yu-Wai Chan, Min Yin, Min-Juan Zhang, Thian-Sze Wong
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is very sensitive to radiotherapy. To date, the underlying mechanism remains poorly understood. Here, we demonstrated that expression of EBV-encoded microRNA BART7 (ebv-miR-BART7) increases responsiveness of NPC to radiation treatment by targeting GFPT1/TGFβ1 signaling. GFPT1 is the the key rate-limiting enzyme of the hexosamine signaling pathway and governs TGFβ1 production. TGFβ1, a pleotropic cytokine with the potency to trigger self-renewal and damage-repair machinery in somatic cells...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406646/transforming-sphingosine-kinase-1-inhibitors-into-dual-and-sphingosine-kinase-2-selective-inhibitors-design-synthesis-and-in-vivo-activity
#20
Elizabeth S Childress, Yugesh Kharel, Anne M Brown, David R Bevan, Kevin R Lynch, Webster L Santos
Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with its five G-protein coupled receptors (S1P1-5) to regulate cell growth and survival and has been implicated in a variety of diseases including cancer and sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine kinase (SphK) isoforms 1 and 2 have attracted attention as viable targets for pharmaceutical inhibition. In this article, we describe the design, synthesis, and biological evaluation of aminothiazole-based guanidine inhibitors of SphK...
May 11, 2017: Journal of Medicinal Chemistry
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