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https://www.readbyqxmd.com/read/28231270/correction-htlv-1-bzip-factor-enhances-t-cell-proliferation-by-impeding-the-suppressive-signaling-of-co-inhibitory-receptors
#1
Haruka Kinosada, Jun-Ichirou Yasunaga, Kazuya Shimura, Paola Miyazato, Chiho Onishi, Tomonori Iyoda, Kayo Inaba, Masao Matsuoka
[This corrects the article DOI: 10.1371/journal.ppat.1006120.].
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28230361/10-gingerol-a-phytochemical-derivative-from-tongling-white-ginger-inhibits-cervical-cancer-insights-into-the-molecular-mechanism-and-inhibitory-targets
#2
Fang Zhang, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
With an aim to evaluate anti-cancerous activities of 10-gingerol (10-G) against Hela cells, it was purified and identified from Tongling White Ginger by HSCCC, UPLC-TOF-MS/MS and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity and arrested cell cycle in G0/G1-phase. The most cell cycle related genes and proteins expression significantly decreased, followed by slight decrease in few and without affecting cyclin B1 and cyclin E1 (protein)...
February 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28230186/glycan-independent-binding-and-internalization-of-human-igm-to-fcmr-its-cognate-cellular-receptor
#3
Katy A Lloyd, Jiabin Wang, Britta C Urban, Daniel M Czajkowsky, Richard J Pleass
IgM is the first antibody to be produced in immune responses and plays an important role in the neutralization of bacteria and viruses. Human IgM is heavily glycosylated, featuring five N-linked glycan sites on the μ chain and one on the J-chain. Glycosylation of IgG is known to modulate the effector functions of Fcγ receptors. In contrast, little is known about the effect of glycosylation on IgM binding to the human Fcμ receptor (hFCMR). In this study, we identify the Cμ4 domain of IgM as the target of hFCMR, and show that binding and internalization of IgM by hFCMR is glycan-independent...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229459/differential-serotonergic-modulation-across-the-main-and-accessory-olfactory-bulbs
#4
Zhenbo Huang, Nicolas Thiebaud, Debra Ann Fadool
Mitral cells (MCs) contained in the main (MOB) and accessory (AOB) olfactory bulb have distinct intrinsic membrane properties but a comparison of the extent of neuromodulation across the two systems is not well explored. Herein, we investigated a widely-distributed CNS modulator, serotonin (5-HT), for its ability to modulate the biophysical properties of MCs across the MOB and AOB, using an in vitro, brain slice approach in postnatal 15-30 day mice. In the MOB, 5-HT elicited three types of responses in 93% of 180 cells tested...
February 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28229330/the-involvement-of-the-myelin-associated-inhibitors-and-their-receptors-in-cns-plasticity-and-injury
#5
REVIEW
Anthony G Boghdadi, Leon Teo, James A Bourne
The limited capacity for the central nervous system (CNS) to repair itself was first described over 100 years ago by Spanish neuroscientist Ramon Y. Cajal. However, the exact mechanisms underlying this failure in neuronal regeneration remain unclear and, as such, no effective therapeutics yet exist. Numerous studies have attempted to elucidate the biochemical and molecular mechanisms that inhibit neuronal repair with increasing evidence suggesting that several inhibitory factors and repulsive guidance cues active during development actually persist into adulthood and may be contributing to the inhibition of repair...
February 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28228354/effect-of-tamoxifen-on-spermatogenesis-and-testicular-steroidogenesis
#6
Rachna Verma, Amitabh Krishna
The aim of this study was to evaluate the effects of in vivo and in vitro treatments with selective estrogen receptor modulator (SERM), tamoxifen on testicular functions. The testis treated with tamoxifen, in vivo or in vitro, showed dose-dependent regressive changes in spermatogenesis. This study showed that the decreased estrogenic effect due to tamoxifen may be directly responsible for decreased testicular expression of aromatase, which in turn may be responsible for decreased synthesis of estradiol in the testis...
February 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28228280/autocrine-loop-involving-il-6-family-member-lif-lif-receptor-and-stat4-drives-sustained-fibroblast-production-of-inflammatory-mediators
#7
Hung N Nguyen, Erika H Noss, Fumitaka Mizoguchi, Christine Huppertz, Kevin S Wei, Gerald F M Watts, Michael B Brenner
Fibroblasts are major contributors to and regulators of inflammation and dominant producers of interleukin-6 (IL-6) in inflammatory diseases like rheumatoid arthritis. Yet, compared to leukocytes, the regulation of inflammatory pathways in fibroblasts is largely unknown. Here, we report that analyses of genes coordinately upregulated with IL-6 pointed to STAT4 and leukemia inhibitory factor (LIF) as potentially linked. Gene silencing revealed that STAT4 was required for IL-6 transcription. STAT4 was recruited to the IL-6 promoter after fibroblast activation, and LIF receptor (LIFR) and STAT4 formed a molecular complex that, together with JAK1 and TYK2 kinases, controlled STAT4 activation...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228241/neuropeptide-s-reduces-propofol-or-ketamine-induced-slow-wave-states-through-activation-of-cognate-receptors-in-the-rat
#8
Xiang-Pan Kong, Can Wang, Jun-Fan Xie, Peng Zhao, Li-Rong Dai, Yu-Feng Shao, Jian-Sheng Lin, Yi-Ping Hou
Intracerebroventricular injection of NPS reduces the duration of the ketamine- or thiopental-induced loss of the righting reflex in rats. But the specific EEG activities are unknown. We therefore sought to examine the effects of the NPS-NPSR system on anesthetic-induced characteristics of EEG power spectra and sleep-wake profiles. NPS alone or together with an NPSR antagonist was injected intracerebroventricularly, whereas the propofol (50mg/kg) or ketamine (100mg/kg) was administrated intraperitoneally. NPS (1 or 2nmol) significantly reduced the amount of propofol-induced EEG delta activity and slow wave states (SWS)...
February 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28225186/randomised-clinical-trial-the-efficacy-and-safety-of-oltipraz-a-liver-x-receptor-alpha-inhibitory-dithiolethione-in-patients-with-non-alcoholic-fatty-liver-disease
#9
W Kim, B G Kim, J S Lee, C K Lee, J E Yeon, M S Chang, J H Kim, H Kim, S Yi, J Lee, J-Y Cho, S G Kim, J-H Lee, Y J Kim
BACKGROUND: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. AIM: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a multicentre, double-blind, placebo-controlled, phase II study...
February 22, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28223412/identification-of-a-selective-small-molecule-inhibitor-of-type-1-adenylyl-cyclase-activity-with-analgesic-properties
#10
Tarsis F Brust, Doungkamol Alongkronrusmee, Monica Soto-Velasquez, Tanya A Baldwin, Zhishi Ye, Mingji Dai, Carmen W Dessauer, Richard M van Rijn, Val J Watts
Adenylyl cyclase 1 (AC1) belongs to a group of adenylyl cyclases (ACs) that are stimulated by calcium in a calmodulin-dependent manner. Studies with AC1 knockout mice suggest that inhibitors of AC1 may be useful for treating pain and opioid dependence. However, nonselective inhibition of AC isoforms could result in substantial adverse effects. We used chemical library screening to identify a selective AC1 inhibitor with a chromone core structure that may represent a new analgesic agent. After demonstrating that the compound (ST034307) inhibited Ca(2+)-stimulated adenosine 3',5'-monophosphate (cAMP) accumulation in human embryonic kidney (HEK) cells stably transfected with AC1 (HEK-AC1 cells), we confirmed selectivity for AC1 by testing against all isoforms of membrane-bound ACs...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28222855/direct-growth-inhibitory-effects-of-prostaglandin-e2-in%C3%A2-pancreatic-cancer-cells-in%C3%A2-vitro-through-an-ep4-pka-mediated-mechanism
#11
Andrea Schmidt, James Sinnett-Smith, Steven Young, Hui-Hua Chang, O Joe Hines, David W Dawson, Enrique Rozengurt, Guido Eibl
BACKGROUND: There is strong evidence linking inflammation and the development of pancreatic ductal adenocarcinoma. Cyclooxygenase-2 (COX-2) and COX-2-derived PGE2 are overexpressed in human and murine pancreatic ductal adenocarcinoma. Several studies have demonstrated an important role of COX-2-derived PGE2 in tumor-stroma interactions; however, the direct growth effects of prostaglandin E2 (PGE2) on pancreatic ductal adenocarcinoma cells is less well defined. Our aim was to investigate the effects of PGE2 on pancreatic ductal adenocarcinoma cell growth and to characterize the underlying mechanisms...
February 17, 2017: Surgery
https://www.readbyqxmd.com/read/28222663/mir-29a-suppresses-mcf-7-cell-growth-by-downregulating-tumor-necrosis-factor-receptor-1
#12
Yiling Zhao, Fenghua Yang, Wenyuan Li, Chunyan Xu, Li Li, Lifei Chen, Yancui Liu, Ping Sun
Tumor necrosis factor receptor 1 is the main receptor mediating many tumor necrosis factor-alpha-induced cellular events. Some studies have shown that tumor necrosis factor receptor 1 promotes tumorigenesis by activating nuclear factor-kappa B signaling pathway, while other studies have confirmed that tumor necrosis factor receptor 1 plays an inhibitory role in tumors growth by inducing apoptosis in breast cancer. Therefore, the function of tumor necrosis factor receptor 1 in breast cancer requires clarification...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28222489/characterization-of-a-novel-signal-transducer-element-intrinsic-to-class-iiia-b-adenylate-cyclases-and-guanylate-cyclases
#13
Miriam Ziegler, Jens Bassler, Stephanie Beltz, Anita Schultz, Andrei N Lupas, Joachim E Schultz
Adenylate cyclases (ACs) are signalling proteins that produce the second messenger cAMP. Class III ACs comprises four groups (class IIIa-d); of these, class IIIa and IIIb ACs have been identified in bacteria and eukaryotes. Many class IIIa ACs are anchored to membranes via hexahelical domains. In eukaryotic ACs, membrane anchors are well conserved, suggesting that this region possesses important functional characteristics that are as yet unknown. To address this question, we replaced the hexahelical membrane anchor of the mycobacterial AC Rv1625c by the hexahelical quorum-sensing receptor from Legionella, LqsS...
February 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28221164/positive-and-negative-cues-for-modulating-neurite-dynamics-and-receptor-expression
#14
Melissa Wrobel, Harini Gayathari Sundararaghavan
Many current peripheral nerve repair strategies focus on delivering positive, growth promoting cues (e.g. extracellular matrix, ECM) while eliminating negative, growth inhibiting cues (e.g. chondroitin sulfate proteoglycans, CSPGs) at the injury site. We hypothesized that recapitulating the positive and negative cues of the peripheral nerve injury microenvironment would improve regeneration. First, we tested the effects of a characteristic CSPG, Chondroitin Sulfate A (CSA) on neurite dynamics of dissociated chick embryo dorsal root ganglion (DRG) neurons using time lapse video microscopy...
February 21, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28220815/cbx3-hp1%C3%AE-deficiency-confers-enhanced-tumor-killing-capacity-on-cd8-t-cells
#15
Michael Sun, Ngoc Ha, Duc-Hung Pham, Megan Frederick, Bandana Sharma, Chie Naruse, Masahide Asano, Matthew E Pipkin, Rani E George, To-Ha Thai
Cbx3/HP1γ is a histone reader whose function in the immune system is not completely understood. Here, we demonstrate that in CD8(+) T cells, Cbx3/HP1γ insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8(+) T cells, there is an increase of CD8(+) effector T cells expressing the stimulatory receptor Klrk1/NKG2D, a decrease in CD4(+) CD25(+) FOXP3(+) regulatory T cells (Treg cells) as well as CD25(+) CD4(+) T cells expressing the inhibitory receptor CTLA4...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220772/tumour-and-host-cell-pd-l1-is-required-to-mediate-suppression-of-anti-tumour-immunity-in-mice
#16
Janet Lau, Jeanne Cheung, Armando Navarro, Steve Lianoglou, Benjamin Haley, Klara Totpal, Laura Sanders, Hartmut Koeppen, Patrick Caplazi, Jacqueline McBride, Henry Chiu, Rebecca Hong, Jane Grogan, Vincent Javinal, Robert Yauch, Bryan Irving, Marcia Belvin, Ira Mellman, Jeong M Kim, Maike Schmidt
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28220078/inhibition-of-vegfr2-activation-and-its-downstream-signaling-to-erk1-2-and-calcium-by-thrombospondin-1-tsp1-in-silico-investigation
#17
Hojjat Bazzazi, Jeffery S Isenberg, Aleksander S Popel
VEGF signaling through VEGFR2 is a central regulator of the angiogenic response. Inhibition of VEGF signaling by the stress-induced matricellular protein TSP1 plays a role in modulating the angiogenic response to VEGF in both health and disease. TSP1 binding to CD47 inhibits VEGFR2 activation. The full implications of this inhibitory interaction are unknown. We developed a detailed rule-based computational model to inquire if TSP1-CD47 signaling through VEGF had downstream effects upon ERK1/2 and calcium. Our Simulations suggest that enhanced degradation of VEGFR2 initiated by the binding of TSP1 to CD47 is sufficient to explain the inhibition of VEGFR2 phosphorylation, calcium elevation, and ERK1/2 activation downstream of VEGF...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28219984/motor-neurons-tune-premotor-activity-in-a-vertebrate-central-pattern-generator
#18
Kristy J Lawton, Wick M Perry, Ayako Yamaguchi, Erik Zornik
Central patterns generators (CPGs) are neural circuits that drive rhythmic motor output without sensory feedback. Vertebrate CPGs are generally believed to operate in a top-down manner in which premotor interneurons activate motor neurons that in turn drive muscles. In contrast, the frog (Xenopus laevis) vocal CPG contains a functionally unexplored neuronal projection from the motor nucleus to the premotor nucleus, indicating a recurrent pathway that may contribute to rhythm generation. In this study we characterized the function of this bottom-up connection...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28219781/adenosine-a2-receptor-activation-ameliorates-mitochondrial-oxidative-stress-upon-reperfusion-through-the-posttranslational-modification-of-ndufv2-subunit-of-complex-i-in-the-heart
#19
Jingman Xu, Xiyun Bian, Yuan Liu, Lan Hong, Tianming Teng, Yuemin Sun, Zhelong Xu
While it is well known that adenosine receptor activation protects the heart from ischemia/reperfusion injury, the precise mitochondrial mechanism responsible for the action remains unknown. This study probed the mitochondrial events associated with the cardioprotective effect of 5'-(N-ethylcarboxamido) adenosine (NECA), an adenosine A2 receptor agonist. Isolated rat hearts were subjected to 30min ischemia followed by 10min of reperfusion, whereas H9c2 cells experienced 20min ischemia and 10min reperfusion...
February 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28219737/membrane-androgen-receptor-characteristics-of-human-zip9-slc39a-zinc-transporter-in-prostate-cancer-cells-androgen-specific-activation-and-involvement-of-an-inhibitory-g-protein-in-zinc-and-map-kinase-signaling
#20
Peter Thomas, Yefei Pang, Jing Dong
Characteristics of novel human membrane androgen receptor (mAR), ZIP9 (SLC39A9), were investigated in ZIP9-transfected PC-3 cells (PC3-ZIP9). Ligand blot analysis showed plasma membrane [(3)H]-T binding corresponds to the position of ZIP9 on Western blots which suggests ZIP9 can bind [(3)H]-T alone, without a protein partner. Progesterone antagonized testosterone actions, blocking increases in zinc, Erk phosphorylation and apoptosis, further evidence that ZIP9 is specifically activated by androgens. Pre-treatment with GTPγS and pertussis toxin decreased plasma membrane [(3)H]-T binding and blocked testosterone-induced increases in Erk phosphorylation and intracellular zinc, indicating ZIP9 is coupled to an inhibitory G protein (Gi) that mediates both MAP kinase and zinc signaling...
February 17, 2017: Molecular and Cellular Endocrinology
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