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https://www.readbyqxmd.com/read/28646549/inhibition-of-jnk-signaling-mediates-ppar%C3%AE-dependent-protection-against-intrahepatic-cholestasis-by-fenofibrate
#1
Manyun Dai, Julin Yang, Minzhu Xie, Jiao Lin, Min Luo, Huiying Hua, Gangming Xu, Hante Lin, Danjun Song, Yuqing Cheng, Bin Guo, Jinshun Zhao, Frank J Gonzalez, Aiming Liu
BACKGROUND AND PURPOSE: Fenofibrate, a PPARα agonist, is the most widely prescribed drug for the treatment of hyperlipidemia. Although fibrate drugs were reported to be beneficial for cholestasis, the underlying mechanism has not been determined. EXPERIMENTAL APPROACH: Wild-type mice and Pparα-null mice were orally pretreated with fenofibrate for three days, following which ANIT was administered to induce cholestasis. The potent experimental PPARα agonist WY14643 was used to validate the role of PPARα, and the JNK inhibitor SP600125 was employed to explore the role of the JNK pathway in cholestatic liver injury...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28645294/3-5-4-trihydroxy-6-7-3-trimethoxyflavone-protects-against-beta-amyloid-induced-neurotoxicity-through-antioxidative-activity-and-interference-with-cell-signaling
#2
Alona Telerman, Rivka Ofir, Yoel Kashman, Anat Elmann
BACKGROUND: Alzheimer's disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain. Amyloid beta (Aβ) protein and oxidative stress are major contributors to Alzheimer's disease, therefore, protecting neuronal cells against Aβ-induced toxicity and oxidative stress might form an effective approach for treatment of this disease. 3,5,4'-trihydroxy-6,7,3'-trimethoxyflavone (TTF) is a flavonoid we have purified from the plant Achillea fragrantissima; and the present study examined, for the first time, the effects of this compound on Aβ-toxicity to neuronal cells...
June 23, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28643937/proinflammatory-effects-and-mechanisms-of-calprotectin-on-human-gingival-fibroblasts
#3
H Gao, J Hou, H Meng, X Zhang, Y Zheng, L Peng
BACKGROUND AND OBJECTIVE: Calprotectin (S100A8/A9) is a heterodimer of S100A8 and S100A9 and is associated with multiple inflammatory diseases, including Crohn's disease, rheumatoid arthritis and periodontitis. Levels of calprotectin are elevated in the gingival crevicular fluid of patients with periodontitis; however, the effects of calprotectin on human gingival fibroblasts (HGFs) remain unknown. This study investigated the proinflammatory activity of calprotectin on HGFs and the functional receptors and signaling pathways engaged by calprotectin...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28643288/inhibitory-effect-of-fsllry-nh2-on-inflammatory-responses-induced-by-hydrogen-peroxide-in-hepg2-cells
#4
Yeon Joo Lee, Su Jin Kim, Kyoung Wan Kwon, Won Mo Lee, Wi Joon Im, Uy Dong Sohn
Proteinase activated receptor 2 (PAR2), which is localized in the GI tract, the respiratory system, and the kidney tubules is a G protein-coupled receptor associated with inflammation, metabolism, and disease. The aim of this study was to explore the role of PAR2 in hydrogen peroxide (H2O2)-induced HepG2 cells by using FSLLRY-NH2 a PAR2 antagonist. H2O2 treatment resulted in induction of PAR2 in esophageal, gastric, and liver cells, with the most robust response being in HepG2 cells. Furthermore, this effect was dose-dependent in HepG2 cells...
June 22, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28642593/transforming-growth-factor-%C3%AE-1-regulates-the-nascent-hematopoietic-stem-cell-niche-by-promoting-gluconeogenesis
#5
C-Y Zhang, H-M Yin, H Wang, D Su, Y Xia, L-F Yan, B Fang, W Liu, Y-M Wang, A-H Gu, Y Zhou
The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-β1 in the metabolic niche of HSC emergence using the tgf-β1b(-/-) zebrafish. Our findings first showed that Tgf-β1 transcripts were enriched in the nascent HSCs. Loss of tgf-β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-β1b(+) cells were runx1(+) HSCs and underwent an endothelial-to-hematopoietic-transition process...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28642580/a-snake-venom-group-iia-pla2-with-immunomodulatory-activity-induces-formation-of-lipid-droplets-containing-15-d-pgj2-in-macrophages
#6
Karina Cristina Giannotti, Elbio Leiguez, Ana Eduarda Zulim de Carvalho, Neide Galvão Nascimento, Márcio Hideki Matsubara, Consuelo Latorre Fortes-Dias, Vanessa Moreira, Catarina Teixeira
Crotoxin B (CB) is a catalytically active group IIA sPLA2 from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA2s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28640441/adipose-tissue-derived-omentin-1-function-and-regulation
#7
Takuya Watanabe, Kaho Watanabe-Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe
Omentin-1, also known as intelectin-1, is a recently identified novel adipocytokine of 313 amino acids, which is expressed in visceral (omental and epicardial) fat as well as mesothelial cells, vascular cells, airway goblet cells, small intestine, colon, ovary, and plasma. The level of omentin-1 expression in (pre)adipocytes is decreased by glucose/insulin and stimulated by fibroblast growth factor-21 and dexamethasone. Several lines of experimental evidence have shown that omentin-1 plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects via AMP-activated protein kinase/Akt/nuclear factor-κB/mitogen-activated protein kinase (ERK, JNK, and p38) signaling...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28640248/voluntary-distance-running-prevents-tnf-mediated-liver-injury-in-mice-through-alterations-of-the-intrahepatic-immune-milieu
#8
Yvonne Huber, Nadine Gehrke, Jana Biedenbach, Susanne Helmig, Perikles Simon, Beate K Straub, Ina Bergheim, Tobias Huber, Detlef Schuppan, Peter R Galle, Marcus A Wörns, Marcus Schuchmann, Jörn M Schattenberg
Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28639904/role-of-jnk-signaling-in-oral-cancer-a-mini-review
#9
Ioannis Gkouveris, Nikolaos G Nikitakis
JNKs (c-Jun N-terminal kinases) belong to mitogen-activated protein kinases' family and become activated by several growth factors, stress, radiation, and other extracellular signals. In turn, JNK activation results in phosphorylation of downstream molecules involved in many normal cellular processes. Nevertheless, recent data have linked JNK signaling with several pathological conditions, including neurodegenerative diseases, inflammation, and cancer. The role of JNK in cancer remains controversial. Initially, JNK was thought to play a rather oncosuppressive role by mediating apoptosis in response to stress stimuli, inflammatory, or oncogenic signals...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639322/tnf-%C3%AE-induced-nod2-and-rip2-contribute-to-the-up-regulation-of-cytokines-induced-by-mdp-in-monocytic-thp-1-cells
#10
Xiaobin Chen, Zhilin Xiao, Xiumei Xie, Xueting Liu, Manli Jiang, Chuang Yuan, Li Yang, Jinyue Hu
Nucleotide-binding oligomerization domain containing 2 (NOD2)-induced signal transduction and cytokine production is regulated by a number of factors. However, the feedback effect of the pro-inflammatory TNF-α on NOD2-induced inflammation is not fully understood. In this study, we found unexpectedly that TNF-α up-regulated NOD2 ligand MDP-induced production of the CXC chemokines, including CXCL1, 2 and 8, and the pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α, in a dose-dependent manner at both mRNA and protein levels in monocytic THP-1 cells...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28638919/-analyses-of-exercise-induced-muscle-damage-specific-microrna-expression-and-molecular-target-of-sarcolemmal-damage-in-rats
#11
Yu-Ming Xu, Jian-Min Cao, Jun-Ping Li, Qiao-Ting Huang, Ping Wang
In the present study, we were to screen the specific microRNA (miRNA) of exercise-induced muscle damage (EIMD) and assess the EIMD-specific miRNAs-regulated target of sarcolemmal damage in rats. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into 3 groups, which included sedentary (C), 24 h post-exercise (E24) and 48 h post-exercise (E48) groups. Rat EIMD model was established by an acute eccentric exercise, i.e., a downhill running treatment at -16º gradient. EIMD characteristics were verified by Evans blue dye staining, differentially expressed miRNAs were detected by microarray assay, EIMD-specific miRNAs expressions were further validated by real-time quantitative RT-PCR (RT-qPCR), and targets of the miRNAs were predicted based on mRNA expressions of associated proteins and related pathway core molecules of sarcolemmal damage...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28637759/role-of-jnk-pathway-in-varicella-zoster-virus-lytic-infection-and-reactivation
#12
Sravya Kurapati, Tomohiko Sadaoka, Labchan Rajbhandari, Balaji Jagdish, Priya Shukla, Yong Jun Kim, Gabsang Lee, Jeffrey I Cohen, Arun Venkatesan
Mechanisms of neuronal infection by varicella-zoster virus (VZV) have been challenging to study due to the relatively strict human tropism of the virus and the paucity of tractable experimental models. Cellular mitogen activated protein kinases (MAPKs) have been shown to play a role in VZV infection of non-neuronal cells, with distinct consequences on infectivity in differing cell types. Here, we utilize several human neuronal culture systems to investigate the role of one such MAPK, the c-Jun N-terminal kinase (JNK), in VZV lytic infection and reactivation...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637673/lipopolysaccharide-downregulates-macrophage-derived-il-22-to-attenuate-alcohol-induced-hepatocyte-cell-death
#13
Yaming Liu, Vikas Verma, Harmeet Malhi, Gregory J Gores, Patrick S Kamath, Arun J Sanyal, Naga Chalasani, Bin Gao, Vijay H Shah
BACKGROUND/AIM: Interleukin 22 (IL-22) is a Th17 cell hepatoprotective cytokine that is undergoing clinical trials to treat patients with alcoholic hepatitis (AH). Lipopolysaccharide (LPS) activation of macrophage is implicated in hepatocyte cell death and pathogenesis of AH. The role of IL-22 production from macrophage, its regulation by LPS and effects on alcohol induced hepatocyte cell death are unexplored and were examined in this study. METHODS/RESULTS: Low levels of IL-22 mRNA/protein were detected in macrophage but were significantly upregulated by 6...
June 21, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28637660/interleukin-33-induces-growth-regulated-oncogene-%C3%AE-expression-and-secretion-in-human-umbilical-vein-endothelial-cells
#14
Masayoshi Yamamoto, Katsuyuki Umebashi, Akinori Tokito, Junichi Imamura, Michihisa Jougasaki
Although interleukin (IL)-33, a member of the IL-1 cytokine family, plays pro-inflammatory roles in immune cells as an "alarmin", little is known regarding the biological actions of IL-33 on vascular endothelial cells. To investigate the effects of IL-33 on vascular endothelial cells, we first screened the IL-33-regulated proteins in human umbilical vein endothelial cells (HUVECs) using a dot blot array, and observed that IL-33 markedly increased growth-regulated oncogene (GRO)-α, a chemokine that is also known as CXCL1...
June 21, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28636101/knockdown-of-lncrna-meg3-inhibits-viability-migration-and-invasion-and-promotes-apoptosis-by-sponging-mir-127-in-osteosarcoma-cell
#15
Yang Wang, Daliang Kong
Osteosarcoma (OS) is one of the most common bone malignancies and occurs almost exclusively in children and adolescents. This study aimed to explore the role of lncRNA maternally expressed gene 3 (MEG3) in OS cells growth and metastasis, and to uncover the possible underlying mechanism. In this study, the expressions of MEG3 in five OS cell lines (MG63, OS-732, SaOS, G292, and 143B) and in a human osteoblast cell line hFOB1.19 were measured by qRT-PCR analysis. The expressions of MEG3, miR-127 and ZEB1 in OS-732 cells were overexpressed or suppressed by transfection...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28634860/molecular-chaperone-hsp70-and-its-constitutively-active-form-hsc70-play-an-indispensable-role-during-eye-development-of-drosophila-melanogaster
#16
Ajay Kumar, Anand K Tiwari
In the present study, we demonstrate that molecular chaperone Hsp70 and Hsc70 is essential for normal organization and development of ommatidial cells in Drosophila melanogaster eye. An exogenously expressed dominant negative mutant of Hsp70 (K71E) and Hsc70.4 (K71S and D206S) in an eye-specific manner resulted in eye degeneration that includes loss of eye pigment, disorganized ommatidia, abnormality in bristle cell arrangement and reduction in the eye size. The developmental organization of ommatidial cells (cone, photoreceptor, pigment, and bristle cell complex) was disturbed in Hsp70 and Hsc70 mutants...
June 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28634323/intestinal-microbial-dysbiosis-aggravates-the-progression-of-alzheimer-s-disease-in-drosophila
#17
Shih-Cheng Wu, Zih-Syuan Cao, Kuo-Ming Chang, Jyh-Lyh Juang
Neuroinflammation caused by local deposits of Aβ42 in the brain is key for the pathogenesis and progression of Alzheimer's disease. However, inflammation in the brain is not always a response to local primary insults. Gut microbiota dysbiosis, which is recently emerging as a risk factor for psychiatric disorders, can also initiate a brain inflammatory response. It still remains unclear however, whether enteric dysbiosis also contributes to Alzheimer's disease. Here we show that in a Drosophila Alzheimer's disease model, enterobacteria infection exacerbated progression of Alzheimer's disease by promoting immune hemocyte recruitment to the brain, thereby provoking TNF-JNK mediated neurodegeneration...
June 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28633482/markers-of-adipogenesis-but-not-inflammation-in-adipose-tissue-are-independently-related-to-insulin-sensitivity
#18
Natalia Matulewicz, Magdalena Stefanowicz, Agnieszka Nikolajuk, Monika Karczewska-Kupczewska
Context: In obesity, adipose tissue (AT) undergoes dynamic remodeling, including an alternations in adipogenesis, AT-resident cell content, angiogenesis and turnover of extracellular matrix (ECM) components. Studies on AT in humans have been carried out mostly on people with severe metabolic abnormalities, like type 2 diabetes or morbid obesity. Objective: The purpose of the present study was to investigate subcutaneous AT gene expression of markers of adipogenesis, ECM remodeling and inflammation in young, healthy, overweight or obese subjects...
June 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#19
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28633020/apoptosis-and-compensatory-proliferation-signaling-are-coupled-by-crki-containing-microvesicles
#20
Kajal H Gupta, Josef W Goldufsky, Stephen J Wood, Nicholas J Tardi, Gayathri S Moorthy, Douglas Z Gilbert, Janet P Zayas, Eunsil Hahm, Mehmet M Altintas, Jochen Reiser, Sasha H Shafikhani
Apoptosis has been implicated in compensatory proliferation signaling (CPS), whereby dying cells induce proliferation in neighboring cells as a means to restore homeostasis. The nature of signaling between apoptotic cells and their neighboring cells remains largely unknown. Here we show that a fraction of apoptotic cells produce and release CrkI-containing microvesicles (distinct from exosomes and apoptotic bodies), which induce proliferation in neighboring cells upon contact. We provide visual evidence of CPS by videomicroscopy...
June 19, 2017: Developmental Cell
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