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https://www.readbyqxmd.com/read/27932944/role-of-homocysteine-in-the-ischemic-stroke-and-development-of-ischemic-tolerance
#1
REVIEW
Ján Lehotský, Barbara Tothová, Maria Kovalská, Dušan Dobrota, Anna Beňová, Dagmar Kalenská, Peter Kaplán
Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27932408/early-responses-of-human-periodontal-ligament-fibroblasts-to-cyclic-and-static-mechanical-stretching
#2
Adamantia Papadopoulou, Anna Iliadi, Theodore Eliades, Dimitris Kletsas
OBJECTIVE: To compare the mechanotransduction caused by cyclic and static mechanical strains in human periodontal ligament fibroblasts (hPDLFs) cultured under identical conditions. MATERIALS AND METHODS: hPDLFs, originating from the same donors, were exposed either to cyclic or to static tensile strain using specially designed devices and under identical culture conditions. Activation of all members of mitogen-activated protein kinases (MAPKs) was monitored by western immunoblot analysis...
December 8, 2016: European Journal of Orthodontics
https://www.readbyqxmd.com/read/27931507/hiv-non-nucleoside-reverse-transcriptase-inhibitor-efavirenz-reduces-neural-stem-cell-proliferation-in-vitro-and-in-vivo
#3
Jingji Jin, Bethany Grimmig, James Izzo, Lecia A M Brown, Charles Hudson, Adam J Smith, Jun Tan, Paula C Bickford, Brian Giunta
The prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite combination antiretroviral therapy (cART). There is evidence that neural stem cells (NSCs) can migrate to sites of brain injury such as those caused by inflammation and oxidative stress, which are pathological features of HAND. Thus, reductions in NSCs may contribute to HAND pathogenesis. Since the HIV non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) has previously been associated with cognitive deficits and promotion of oxidative stress pathways, we examined its effect on NSCs in vitro as well as in C57BL/6J mice...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27929393/xylobiose-an-alternative-sweetener-ameliorates-diabetes-related-metabolic-changes-by-regulating-hepatic-lipogenesis-and-mir-122a-33a-in-db-db-mice
#4
Eunjin Lim, Ji Ye Lim, Eunju Kim, Yoo-Sun Kim, Jae-Ho Shin, Pu Reum Seok, Sangwon Jung, Sang-Ho Yoo, Yuri Kim
Type 2 diabetes is a major public health concern worldwide. Xylobiose (XB) consists of two molecules of d-xylose and is a major disaccharide in xylooligosaccharides that are used as prebiotics. We hypothesized that XB could regulate diabetes-related metabolic and genetic changes via microRNA expression in db/db mice. For six weeks, C57BL/KsJ-db/db mice received 5% XB as part of the total sucrose content of their diet. XB supplementation improved glucose tolerance with reduced levels of OGTT AUC, fasting blood glucose, HbA1c, insulin, and HOMA-IR...
December 5, 2016: Nutrients
https://www.readbyqxmd.com/read/27927748/axl-receptor-signalling-suppresses-p53-in-melanoma-through-stabilization-of-the-mdmx-mdm2-complex
#5
Anna de Polo, Zhongling Luo, Casimiro Gerarduzzi, Xiang Chen, John B Little, Zhi-Min Yuan
Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, but its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the stability of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpression or activation through growth arrest-specific 6 (Gas6) ligand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27927209/coordinated-inhibition-of-c-ebp-by-tribbles-in-multiple-tissues-is-essential-for-caenorhabditis-elegans-development
#6
Kyung Won Kim, Nishant Thakur, Christopher A Piggott, Shizue Omi, Jolanta Polanowska, Yishi Jin, Nathalie Pujol
BACKGROUND: Tribbles proteins are conserved pseudokinases that function to control kinase signalling and transcription in diverse biological processes. Abnormal function in human Tribbles has been implicated in a number of diseases including leukaemia, metabolic syndromes and cardiovascular diseases. Caenorhabditis elegans Tribbles NIPI-3 was previously shown to activate host defense upon infection by promoting the conserved PMK-1/p38 mitogen-activated protein kinase (MAPK) signalling pathway...
December 7, 2016: BMC Biology
https://www.readbyqxmd.com/read/27927200/tribbles-ortholog-nipi-3-and-bzip-transcription-factor-cebp-1-regulate-a-caenorhabditis-elegans-intestinal-immune-surveillance-pathway
#7
Deborah L McEwan, Rhonda L Feinbaum, Nicholas Stroustrup, Wilhelm Haas, Annie L Conery, Anthony Anselmo, Ruslan Sadreyev, Frederick M Ausubel
BACKGROUND: Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. RESULTS: We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P...
December 7, 2016: BMC Biology
https://www.readbyqxmd.com/read/27925454/rap1a-promotes-ovarian-cancer-metastasis-via-activation-of-erk-p38-and-notch-signaling
#8
Lili Lu, Jingshu Wang, Yougen Wu, Ping Wan, Gong Yang
As one of the Ras-associated proteins, Rap1A has been linked to cancer initiation and development. However, the precise function of Rap1A in ovarian cancer is still not understood. Here, we show that Rap1A promotes ovarian cancer tumorigenesis and metastasis via stimulating cell proliferation, migration and invasion both in vivo and in vitro. Mechanistic study showed that Rap1A activates extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and Notch pathways, leading to the enhanced expression of several epithelial-mesenchymal transition (EMT) markers such as slug, zeb1, vimentin, fibronectin, and MMP9...
December 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27923872/dopamine-directly-increases-mitochondrial-mass-and-thermogenesis-in-brown-adipocytes
#9
Rose Kohlie, Nina Perwitz, Julia Resch, Sebastian Michael Schmid, Hendrik Lehnert, Johannes Klein, Karl Alexander Iwen
Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential it may dissipate excessive energy, regulate body weight, and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT-thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT-thermogenesis but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells...
December 6, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27923689/eupafolin-nanoparticle-improves-acute-renal-injury-induced-by-lps-through-inhibiting-ros-and-inflammation
#10
Hao Zhang, Ming-Kun Chen, Ke Li, Cheng Hu, Min-Hua Lu, Jie Situ
Acute renal injury is a common severe clinical syndrome, occurring in many clinical situations. It is necessary to explore effective drugs to treat it. Eupafolin is a flavonoid compound, derived from Phyla nodiflora, which has been previously reported to possess a variety of pharmacological activities, including anti-inflammatory and antioxidant effects. However, it is known little about how it works in acute renal injury. Also, eupafolin is characterized by skin penetration and poor water solubility, limiting its clinical applications...
December 3, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27923151/a-novel-role-for-the-kr%C3%A3-ppel-like-factor-14-on-macrophage-inflammatory-response-and-atherosclerosis-development
#11
Xiao Wei, Ruomei Yang, Chengpan Wang, Xun Jian, Ling Li, Hua Liu, Gangyi Yang, Zhiyong Li
Genome-wide association studies have shown that Krüppel-like factor 14 (KLF14) is associated with both Type 2 diabetes mellitus and lipid metabolism. However, its role in chronic inflammatory responses and the pathogenesis of atherosclerosis remains unknown. The present study was designed to investigate both in vivo and in vitro the impact of KLF14 on chronic inflammatory responses and atherosclerosis. ApoE KO mice, a well-established animal model of atherosclerosis, had higher expressions of KLF14 in aorta tissues than that in C57BL/6 J mice when fed the high-fat diet (HFD) or standard chow diet...
November 14, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27923061/comparative-transcriptomic-and-epigenomic-analyses-reveal-new-regulators-of-murine-brown-adipogenesis
#12
Reinhard Brunmeir, Jingyi Wu, Xu Peng, Sun-Yee Kim, Sofi G Julien, Qiongyi Zhang, Wei Xie, Feng Xu
Increasing energy expenditure through brown adipocyte recruitment is a promising approach to combat obesity. We report here the comprehensive profiling of the epigenome and transcriptome throughout the lineage commitment and differentiation of C3H10T1/2 mesenchymal stem cell line into brown adipocytes. Through direct comparison to datasets from differentiating white adipocytes, we systematically identify stage- and lineage-specific coding genes, lncRNAs and microRNAs. Utilizing chromatin state maps, we also define stage- and lineage-specific enhancers, including super-enhancers, and their associated transcription factor binding motifs and genes...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27922670/downregulation-of-laptm5-suppresses-cell-proliferation-and-viability-inducing-cell-cycle-arrest-at-g0-g1-phase-of-bladder-cancer-cells
#13
Liang Chen, Gang Wang, Yi Luo, Yongzhi Wang, Conghua Xie, Wei Jiang, Yu Xiao, Guofeng Qian, Xinghuan Wang
Our transcriptome analysis revealed in bladder cancer (BCa) tissues a significant induction of lysosomal-associated multispanning membrane protein 5 (LAPTM5), a lysosomal membrane protein preferentially expressing in immune cells and hematopoietic cells. Transportation of LAPTM5 from Golgi to lysosome could be inhibited by deficiency of Nedd4, a key member of E3 ubiquitin ligase family overexpressing in invasive BCa and promoting its progression. Therefore, we hypothesize that LAPTM5 may be closely correlated with BCa tumorigenesis...
December 5, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27922667/pituitary-sex-hormones-enhance-the-pro%C3%A2-metastatic-potential-of-human-lung-cancer-cells-by-downregulating-the-intracellular-expression-of-heme-oxygenase%C3%A2-1
#14
Ahmed Abdelbaset-Ismail, Daniel Pedziwiatr, Gabriela Schneider, Jacek Niklinski, Radoslaw Charkiewicz, Marcin Moniuszko, Magda Kucia, Mariusz Z Ratajczak
We report that human lung cancer cell lines express functional receptors for pituitary sex hormones (SexHs) and respond to stimulation by follicle‑stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL). Expression of these receptors has also been confirmed in patient lung cancer samples at the mRNA level. Stimulation of human lung cancer cell lines with FSH, LH, or PRL stimulated migration and chemotaxis, and some cell lines responded by enhanced proliferation. Moreover, priming of human lung cancer cells by exposing them to pituitary SexHs resulted in enhanced seeding efficiency of injected human lung cancer cells into bone marrow, liver, and lungs in an immunodeficient mouse model...
December 2, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27922122/identification-of-critical-paralog-groups-with-indispensable-roles-in-the-regulation-of-signaling-flow
#15
Dezso Modos, Johanne Brooks, David Fazekas, Eszter Ari, Tibor Vellai, Peter Csermely, Tamas Korcsmaros, Katalin Lenti
Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920521/celastrol-nanomicelles-attenuate-cytokine-secretion-in-macrophages-and-inhibit-macrophage-induced-corneal-neovascularization-in-rats
#16
Zhanrong Li, Jingguo Li, Lei Zhu, Ying Zhang, Junjie Zhang, Lin Yao, Dan Liang, Liya Wang
The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919568/all-trans-retinoic-acid-suppresses-the-adhering-ability-of-arpe-19-cells-via-mitogen-activated-protein-kinase-and-focal-adhesion-kinase
#17
Yo-Chen Chang, Yuh-Shin Chang, Ming-Chu Hsieh, Horng-Jiun Wu, Meng-Hsien Wu, Chia-Wei Lin, Wen-Chuan Wu, Ying-Hsien Kao
This study investigated the signaling mechanism underlying the anti-adhesive effect of all-trans retinoic acid (ATRA) on retinal pigment epithelial ARPE-19 cells. Adhesion kinetics with or without ATRA treatment were profiled by adhesion assay. Surface coating with type IV collagen, fibronectin, laminin, but not type I collagen, significantly enhanced adhesion and spreading of ARPE-19 cells, while ATRA at subtoxic doses (ranging from 10(-7) to 10(-6) M) profoundly suppressed the extracellular matrix-enhanced adhesion ability...
November 16, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27913845/mitogen-activated-protein-kinases-are-involved-in-hepatocanalicular-dysfunction-and-cholestasis-induced-by-oxidative-stress
#18
Flavia D Toledo, Cecilia L Basiglio, Ismael R Barosso, Andrea C Boaglio, Andrés E Zucchetti, Enrique J Sánchez Pozzi, Marcelo G Roma
In previous studies, we showed that the pro-oxidant model agent tert-butyl hydroperoxide (tBuOOH) induces alterations in hepatocanalicular secretory function by activating Ca(2+)-dependent protein kinase C isoforms (cPKC), via F-actin disorganization followed by endocytic internalization of canalicular transporters relevant to bile formation (Mrp2, Bsep). Since mitogen-activated protein kinases (MAPKs) may be downstream effectors of cPKC, we investigated here the involvement of the MAPKs of the ERK1/2, JNK1/2, and p38(MAPK) types in these deleterious effects...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913436/erk-and-p38-mapk-activities-determine-sensitivity-to-pi3k-mtor-inhibition-via-regulation-of-myc-and-yap
#19
Taru Muranen, Laura M Selfors, Julie Hwang, Lisa L Gallegos, Jonathan L Coloff, Carson C Thoreen, Seong A Kang, David M Sabatini, Gordon B Mills, Joan S Brugge
Aberrant activation of the PI3K/mTOR pathway is a common feature of many cancers and an attractive target for therapy, but resistance inevitably evolves as is the case for any cancer cell-targeted therapy. In animal tumor models, chronic inhibition of PI3K/mTOR initially inhibits tumor growth, but over time, tumor cells escape inhibition. In this study, we identified a context-dependent mechanism of escape whereby tumor cells upregulated the proto-oncogene transcriptional regulators c-MYC and YAP1. This mechanism was dependent on both constitutive ERK activity as well as inhibition of the stress kinase p38...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27913297/phospholipase-c%C3%AE-1-suppresses-foreign-body-giant-cell-formation-by-maintaining-runx1-expression-in-macrophages
#20
Ye Seon Kim, Chang Youp Ok, Joon Seong Park, Ha Young Lee, Yoe-Sik Bae
Foreign body giant cell (FBGC) formation is associated with the inflammatory response following material implantation. However, the intracellular signaling events that regulate the process remain unclear. Here, we investigated the potential role of phospholipase C (PLC)γ1, a crucial enzyme required for growth factor-induced signaling, on FBGC formation. Knock-down of PLCγ1 using shRNA induced FBGC formation accompanied by increased expression of cathepsin K, DC-STAMP and CD36. Re-addition of PLCγ1 decreased FBGC formation...
November 30, 2016: Biochemical and Biophysical Research Communications
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