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https://www.readbyqxmd.com/read/29045950/leonurine-prevents-atherosclerosis-via-promoting-the-expression-of-abca1-and-abcg1-in-a-ppar%C3%AE-lxr%C3%AE-signaling-pathway-dependent-manner
#1
Ting Jiang, Kun Ren, Qian Chen, Heng Li, Rong Yao, Hu Hu, Yun-Cheng Lv, Guo-Jun Zhao
BACKGROUND/AIMS: Previous studies have demonstrated that leonurine, a unique alkaloid compound of Herba leonuri, can exert anti-oxidative and anti-inflammatory effects on the development of atherosclerosis (AS). This study was designed to investigate the effects of leonurine on cholesterol efflux from THP-1 macrophage-derived foam cells and development of atherosclerotic lesions in apoE-/- mice, and further determine the potential mechanisms. METHODS: Human THP-1 cells were fully differentiated into foam cells by the pre-treatment with phorbol-12-myristate-13-acetate (PMA) and oxidized density lipoproteins (ox-LDL)...
October 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29045935/emodinol-ameliorates-urate-nephropathy-by-regulating-renal-organic-ion-transporters-and-inhibiting-immune-inflammatory-responses-in-rats
#2
Hui Wu, Mengze Zhou, Guo Lu, Zhonglin Yang, Hui Ji, Qinghua Hu
Emodinol, 1β, 3β, 23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our Research Group, was identified with apparent uricosuric and nephroprotective effects in hyperuricemia mice in our previous study. This study aimed to investigate the renal protective effect of emodinol in urate nephropathy rats. Rats were orally administrated by combined adenine and ethambutol to induce urate nephropathy. Emodinol at various doses were administered intragastrically to urate nephropathy rats daily...
October 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29045907/reactive-neutrophil-responses-dependent-on-the-receptor-tyrosine-kinase-c-met-limit-cancer-immunotherapy
#3
Nicole Glodde, Tobias Bald, Debby van den Boorn-Konijnenberg, Kyohei Nakamura, Jake S O'Donnell, Sabrina Szczepanski, Maria Brandes, Sarah Eickhoff, Indrajit Das, Naveen Shridhar, Daniel Hinze, Meri Rogava, Tetje C van der Sluis, Janne J Ruotsalainen, Evelyn Gaffal, Jennifer Landsberg, Kerstin U Ludwig, Christoph Wilhelm, Monika Riek-Burchardt, Andreas J Müller, Christoffer Gebhardt, Richard A Scolyer, Georgina V Long, Viktor Janzen, Michele W L Teng, Wolfgang Kastenmüller, Massimiliano Mazzone, Mark J Smyth, Thomas Tüting, Michael Hölzel
Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic to target oncogenic signaling in tumor cells. We found that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in murine cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045902/epidermal-growth-factor-receptor-expression-licenses-type-2-helper-t-cells-to-function-in-a-t-cell-receptor-independent-fashion
#4
Carlos M Minutti, Sebastian Drube, Natalie Blair, Christian Schwartz, Jame C McCrae, Andrew N McKenzie, Thomas Kamradt, Michal Mokry, Paul J Coffer, Maria Sibilia, Alice J Sijts, Padraic G Fallon, Rick M Maizels, Dietmar M Zaiss
Gastro-intestinal helminth infections trigger the release of interleukin-33 (IL-33), which induces type-2 helper T cells (Th2 cells) at the site of infection to produce IL-13, thereby contributing to host resistance in a T cell receptor (TCR)-independent manner. Here, we show that, as a prerequisite for IL-33-induced IL-13 secretion, Th2 cells required the expression of the epidermal growth factor receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling complex between T1/ST2 (the IL-33R) and EGFR...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045898/peptidoglycan-sensing-receptors-trigger-the-formation-of-functional-amyloids-of-the-adaptor-protein-imd-to-initiate-drosophila-nf-%C3%AE%C2%BAb-signaling
#5
Anni Kleino, Nancy F Ramia, Gunes Bozkurt, Yanfang Shen, Himani Nailwal, Jing Huang, Johanna Napetschnig, Monique Gangloff, Francis Ka-Ming Chan, Hao Wu, Jixi Li, Neal Silverman
In the Drosophila immune response, bacterial derived diaminopimelic acid-type peptidoglycan binds the receptors PGRP-LC and PGRP-LE, which through interaction with the adaptor protein Imd leads to activation of the NF-κB homolog Relish and robust antimicrobial peptide gene expression. PGRP-LC, PGRP-LE, and Imd each contain a motif with some resemblance to the RIP Homotypic Interaction Motif (RHIM), a domain found in mammalian RIPK proteins forming functional amyloids during necroptosis. Here we found that despite sequence divergence, these Drosophila cryptic RHIMs formed amyloid fibrils in vitro and in cells...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045874/dynamic-scaling-analysis-of-molecular-motion-within-the-lat-grb2-sos-protein-network-on%C3%A2-membranes
#6
William Y C Huang, Han-Kuei Chiang, Jay T Groves
Biochemical signaling pathways often involve proteins with multiple, modular interaction domains. Signaling activates binding sites, such as by tyrosine phosphorylation, which enables protein recruitment and growth of networked protein assemblies. Although widely observed, the physical properties of the assemblies, as well as the mechanisms by which they function, remain largely unknown. Here we examine molecular mobility within LAT:Grb2:SOS assemblies on supported membranes by single-molecule tracking. Trajectory analysis reveals a discrete temporal transition to subdiffusive motion below a characteristic timescale, indicating that the LAT:Grb2:SOS assembly has the dynamical structure of a loosely entangled polymer...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29045862/the-two-state-prehensile-tail-of-the-antibacterial-toxin-colicin-n
#7
Christopher L Johnson, Alexandra S Solovyova, Olli Hecht, Colin Macdonald, Helen Waller, J Günter Grossmann, Geoffrey R Moore, Jeremy H Lakey
Intrinsically disordered regions within proteins are critical elements in many biomolecular interactions and signaling pathways. Antibacterial toxins of the colicin family, which could provide new antibiotic functions against resistant bacteria, contain disordered N-terminal translocation domains (T-domains) that are essential for receptor binding and the penetration of the Escherichia coli outer membrane. Here we investigate the conformational behavior of the T-domain of colicin N (ColN-T) to understand why such domains are widespread in toxins that target Gram-negative bacteria...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29045844/a-b-cell-regulome-links-notch-to-downstream-oncogenic-pathways-in-small-b-cell-lymphomas
#8
Russell J H Ryan, Jelena Petrovic, Dylan M Rausch, Yeqiao Zhou, Caleb A Lareau, Michael J Kluk, Amanda L Christie, Winston Y Lee, Daniel R Tarjan, Bingqian Guo, Laura K H Donohue, Shawn M Gillespie, Valentina Nardi, Ephraim P Hochberg, Stephen C Blacklow, David M Weinstock, Robert B Faryabi, Bradley E Bernstein, Jon C Aster, Warren S Pear
Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045841/phosphorylation-of-irhom2-controls-stimulated-proteolytic-shedding-by-the-metalloprotease-adam17-tace
#9
Miguel Cavadas, Ioanna Oikonomidi, Catarina J Gaspar, Emma Burbridge, Marina Badenes, Inês Félix, Alfonso Bolado, Tianyi Hu, Andrea Bileck, Christopher Gerner, Pedro M Domingos, Alex von Kriegsheim, Colin Adrain
Cell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme), is responsible for cleavage ("shedding") of membrane-tethered signaling molecules, including the cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within the secretory pathway requires its binding to iRhom2, which mediates the exit of TACE from the endoplasmic reticulum. An important, but mechanistically unclear, feature of TACE biology is its ability to be stimulated rapidly on the cell surface by numerous inflammatory and growth-promoting agents...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045828/prolonged-ikk%C3%AE-inhibition-improves-ongoing-ctl-antitumor-responses-by-incapacitating-regulatory-t-cells
#10
Christoph Heuser, Janine Gotot, Eveline Christina Piotrowski, Marie-Sophie Philipp, Christina Johanna Felicia Courrèges, Martin Sylvester Otte, Linlin Guo, Jonathan Leo Schmid-Burgk, Veit Hornung, Annkristin Heine, Percy Alexander Knolle, Natalio Garbi, Edgar Serfling, César Evaristo, Friedrich Thaiss, Christian Kurts
Regulatory T cells (Tregs) prevent autoimmunity but limit antitumor immunity. The canonical NF-κB signaling pathway both activates immunity and promotes thymic Treg development. Here, we report that mature Tregs continue to require NF-κB signaling through IκB-kinase β (IKKβ) after thymic egress. Mice lacking IKKβ in mature Tregs developed scurfy-like immunopathology due to death of peripheral FoxP3(+) Tregs. Also, pharmacological IKKβ inhibition reduced Treg numbers in the circulation by ∼50% and downregulated FoxP3 and CD25 expression and STAT5 phosphorylation...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045821/mir-93-5p-promotes-gastric-cancer-cell-progression-via-inactivation-of-the-hippo-signaling-pathway
#11
Li Li, Jun Deng, Shanshan Huang, Yi Wang, Lingling Zhu, Yuan Cao, Jianping Xiong
MiR-93-5p has been previously found to be associated with gastric cancer (GC) tumorigenesis; however, the current understanding of its function in this context remains largely incomplete. In the present study, we showed that miR-93-5p was upregulated in GC tissues. We also demonstrated that miR-93-5p overexpression promoted the proliferation, migration, invasion, and chemoresistance of SGC-7901 cells in vitro, and conversely, that endogenously silencing miR-93-5p expression induced the opposite effects in HGC-27 cells...
October 15, 2017: Gene
https://www.readbyqxmd.com/read/29045811/top2a-induces-malignant-character-of-pancreatic-cancer-through-activating-%C3%AE-catenin-signaling-pathway
#12
Yao-Fei Pei, Xi-Min Yin, Xi-Qiang Liu
It has been reported that Topoisomerase II alpha (TOP2A) could induce tumor development and progression in many cancer types. Herein, through analysis of different independent cohorts, we found TOP2A was up-regulated in pancreatic cancer as compared with non-tumor tissues. Moreover, the up-regulation of TOP2A was significantly correlated with tumor metastasis and shorter survival in patients with pancreatic cancer. Knockdown of TOP2A in pancreatic cancer cell lines inhibited cell proliferation and migration...
October 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29045789/nano-hydroxyapatite-stimulation-of-gene-expression-requires-fgf-receptor-phosphate-transporter-and-erk1-2-signaling
#13
Shin-Woo Ha, Jonathan Park, Mark M Habib, George R Beck
Hydroxyapatite (HAp) is critical to health both as the main structural material of the skeleton and storage material of calcium and phosphate. Nano-sized HAp (nHAp) is naturally produced by mineralizing cells during bone formation and remodeling and is the main constituent of the skeleton. As such, HAp is currently being investigated as a therapeutic biomaterial for orthopedic and dental purposes. Recent studies have suggested that extracellular nHAp can influence osteoblast lineage commitment and cell function through changes in gene expression, however the mechanisms remain to be elucidated...
October 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29045691/genetic-dissection-of-arabidopsis-map-kinase-phosphatase-1-dependent-pamp-induced-transcriptional-responses
#14
Lingyan Jiang, Ying Wan, Jeffrey C Anderson, Jie Hou, Soliman M Islam, Jianlin Cheng, Scott C Peck, Katherine Denby
Plant immunity is initiated by extracellular detection of pathogen-associated molecular patterns (PAMPs) through surface-localized pattern recognition receptors (PRRs). PRR activation induces many responses including the activation of mitogen-activated protein kinases (MAPKs) that ultimately limit bacterial growth. Previous work identified Arabidopsis MAP kinase phosphatase 1 (MKP1) as a negative regulator of signaling pathways required for some, but not all, of PAMP-initiated responses. Specifically, loss of MAPK MPK6 in an mkp1 background suppressed a subset of the mkp1-dependent biological phenotypes, indicating the requirement for MPK6 in MKP1-dependent signaling...
October 13, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29045593/a-teleost-androgen-promotes-development-of-primary-ovarian-follicles-in-coho-salmon-and-rapidly-alters-the-ovarian-transcriptome
#15
Christopher Monson, Kristy Forsgren, Giles Goetz, Louisa Harding, Penny Swanson, Graham Young
Recent studies using several teleost models have revealed that androgens increase the size of previtellogenic (primary and/or early secondary) ovarian follicles. To explore our hypothesis that androgens drive the development of primary follicles into early secondary follicles, and to determine the mechanisms underlying these androgenic effects, we exposed juvenile coho salmon to near-physiological and relatively sustained levels of the non-aromatizable androgen 11-ketotestosterone (11-KT). This resulted in significant growth of primary ovarian follicles after 10 and 20 days, with follicles after 20 days displaying a morphological phenotype characteristic of early secondary follicles (presence of cortical alveoli)...
October 13, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29045588/the-mycotoxin-metabolite-deepoxy-deoxynivalenol-increases-apoptosis-and-decreases-steroidogenesis-in-bovine-ovarian-theca-cells
#16
Hilda M Guerrero-Netro, Anthony Estienne, Younès Chorfi, Christopher A Price
The mycotoxin deoxynivalenol (DON) has been shown to inhibit ovarian granulosa cell function in cattle in vitro, but it is not known whether DON or its metabolite deepoxy-DON (DOM-1) affect theca cell function. The objectives of the present study were to determine the effects of DON and of DOM-1 on theca cell steroidogenesis and apoptosis, and to determine the main pathways through which they act. Bovine theca cells were cultured in a non-luteinizing serum-free culture system, and challenged with DON or DOM-1 for 4 d to measure steroidogenesis and apoptosis, for 1-8 h to measure immediate-early genes, and for 5-60 min to measure phosphorylation of intracellular signaling proteins...
October 13, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29045529/impact-of-genetic-variations-in-the-mapk-signaling-pathway-on-outcome-in-metastatic-colorectal-cancer-patients-treated-with-first-line-folfiri-and-bevacizumab-data-from-fire-3-and-tribe-trials
#17
M D Berger, S Stintzing, V Heinemann, D Yang, S Cao, Y Sunakawa, Y Ning, S Matsusaka, S Okazaki, Y Miyamoto, M Suenaga, M Schirripa, S Soni, W Zhang, A Falcone, F Loupakis, H-J Lenz
Background: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045518/negative-hyper-selection-of-metastatic-colorectal-cancer-patients-for-anti-egfr-monoclonal-antibodies-the-pressing-case-control-study
#18
C Cremolini, F Morano, R Moretto, R Berenato, E Tamborini, F Perrone, D Rossini, A Gloghini, A Busico, G Zucchelli, C Baratelli, E Tamburini, M Tampellini, E Sensi, G Fucà, C Volpi, M Milione, M Di Maio, G Fontanini, F De Braud, A Falcone, F Pietrantonio
Background: Refining the selection of metastatic colorectal cancer (mCRC) patients candidates for anti-EGFR monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signaling pathways, have been suggested by preclinical and retrospective studies. Patients and methods: We conducted this multicenter, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations (PRESSING panel), including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions, and HER2/PI3K/PTEN/AKT1 mutations...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045470/structural-and-functional-analysis-of-smo-1-the-sumo-homolog-in-caenorhabditis-elegans
#19
Parag Surana, Chandrakala M Gowda, Vasvi Tripathi, Limor Broday, Ranabir Das
SUMO proteins are important post-translational modifiers involved in multiple cellular pathways in eukaryotes, especially during the different developmental stages in multicellular organisms. The nematode C. elegans is a well known model system for studying metazoan development and has a single SUMO homolog, SMO-1. Interestingly, SMO-1 modification is linked to embryogenesis and development in the nematode. However, high-resolution information about SMO-1 and the mechanism of its conjugation is lacking. In this work, we report the high-resolution three dimensional structure of SMO-1 solved by NMR spectroscopy...
2017: PloS One
https://www.readbyqxmd.com/read/29045468/cordycepin-promotes-apoptosis-in-renal-carcinoma-cells-by-activating-the-mkk7-jnk-signaling-pathway-through-inhibition-of-c-flipl-expression
#20
In-Hu Hwang, Seung Yoon Oh, Hyun-Jin Jang, Eunbi Jo, Jong Cheon Joo, Kyung-Bok Lee, Hwa-Seung Yoo, Mi Young Lee, Soo Jung Park, Ik-Soon Jang
Cellular FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that associates with the signaling complex downstream of NF-κB, negatively interfering with apoptotic signaling. The role of c-FLIP downregulation by negative regulation of NF-κB signaling during apoptosis is poorly understood. Here, we demonstrate that NF-κB-mediated c-FLIPL negatively regulates the JNK signaling pathway, and that cordycepin treatment of human renal cancer cells leads to apoptosis induction through c-FLIPL inhibition...
2017: PloS One
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