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https://www.readbyqxmd.com/read/28431986/ninj2-a-novel-regulator-of-endothelial-inflammation-and-activation
#1
Jingjing Wang, Jingjing Fa, Pengyun Wang, Xinzhen Jia, Huixin Peng, Jing Chen, Yifan Wang, Chenhui Wang, Qiuyun Chen, Xin Tu, Qing K Wang, Chengqi Xu
Previous genetic studies suggested that variants in NINJ2 (encode ninjurin2) confer risk to ischemic stroke or large artery atherosclerotic stroke. However, the underlying mechanisms of NINJ2 in ischemic stroke or atherosclerosis are still unknown. In this study, we hypothesized that NINJ2 may play a role in endothelial inflammation and activation, and regulate the process of atherosclerosis. Here, we demonstrated that NINJ2 can regulate the expression of a panel of genes that are associated with inflammation and atherosclerosis (e...
April 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28430744/activation-of-a-c-jun-n-terminal-kinase-mediated-autophagy-pathway-attenuates-the-anticancer-activity-of-gemcitabine-in-human-bladder-cancer-cells
#2
Xiao-Long Huang, Hao Zhang, Xiao-Yu Yang, Xiao-Yong Dong, Xiang-Yu Xie, Hu-Bin Yin, Xin Gou, Yong Lin, Wei-Yang He
The role of autophagy in the anticancer activity of gemcitabine (GEM) in bladder cancer is unclear. The aim of this study is to determine whether GEM activates autophagy, the role of autophagy in the anticancer activity of GEM, and the underlying mechanism by which GEM induces autophagy. Human bladder cancer cell lines T24 and BIU87 were treated with GEM in vitro. Cell viability was measured using the Cell Counting Kit-8 assay. Apoptosis was detected by annexin V assay and western blot. Autophagy was measured by western blot and transmission electron microscopy...
April 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28429284/foxo1-attenuates-naf-induced-apoptosis-of-ls8-cells-through-the-jnk-and-mitochondrial-pathways
#3
Juedan Li, Lin Zhao, Xiaomeng Zhao, Peng Wang, Yan Liu, Jianping Ruan
Fluoride-induced ameloblast apoptosis is a key event in dental fluorosis development. Forkhead box o1 (Foxo1) is a transcription factor involved in cell apoptosis. The present study aims to investigate the effect of Foxo1 on ameloblast apoptosis induced by fluoride in vitro and to explore its possible mechanism. Ameloblast-like cells (LS8 cells) were exposed to various concentrations of NaF for up to 48 h. Foxo1 activation was modulated using lentiviral vectors, and cell apoptosis was measured by flow cytometry...
April 20, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28428258/deletion-of-inositol-requiring-enzyme-1%C3%AE-in-podocytes-disrupts-glomerular-capillary-integrity-and-autophagy
#4
Daniel Robert Kaufman, Joan Papillon, Louise Larose, Takao Iwawaki, Andrey V Cybulsky
Inositol-requiring enzyme-1α (IRE1α) is an endoplasmic reticulum (ER)-transmembrane endoribonuclease-kinase, which plays an essential function in extraembryonic tissues during normal development, and is activated during ER stress. To address the functional role of IRE1α in glomerular podocytes, we produced podocyte-specific IRE1α deletion mice. In male mice, deletion of IRE1α in podocytes resulted in albuminuria beginning at 5 months of age, and worsening with time. Electron microscopy revealed focal podocyte foot process effacement in 9-month old male IRE1α deletion mice, as well as microvillous transformation of podocyte plasma membranes...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28427146/microrna-200c-141-upregulates-serpinb2-to-promote-breast-cancer-cell-metastasis-and-reduce-patient-survival
#5
Tiefeng Jin, Hoe Suk Kim, Sul Ki Choi, Eun Hye Hwang, Jisu Woo, Han Suk Ryu, Kwangsoo Kim, Aree Moon, Woo Kyung Moon
The microRNA-200 (miR-200) family is associated with tumor metastasis and poor patient prognosis. We found that miR-200c/141 cluster overexpression upregulated SerpinB2 in the MDA-MB-231 triple-negative (TN) breast cancer cell line. We observed transcription factor (c-Jun, c-Fos, and FosB) upregulation, nuclear localization of c-Jun, and increased SerpinB2 promoter-directed chloramphenicol acetyltransferase activity in miR-200c/141 cluster-overexpressing cells relative to controls. Additionally, miR-124a and miR-26b, which directly target SepinB2, were downregulated compared to controls...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424250/unifying-mechanism-for-different-fibrotic-diseases
#6
Gerlinde Wernig, Shih-Yu Chen, Lu Cui, Camille Van Neste, Jonathan M Tsai, Neeraja Kambham, Hannes Vogel, Yaso Natkunam, D Gary Gilliland, Garry Nolan, Irving L Weissman
Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts...
April 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28422377/intraperitoneal-gardiquimod-protects-against-hepatotoxicity-through-inhibition-of-oxidative-stress-and-inflammation-in-mice-with-sepsis
#7
Suqian Guo, Yu Zhang, Zhifen Wang, Yonghao Yu, Guolin Wang
Many reports recapitulate the contribution of reactive oxygen species (ROS) over-accumulation to the organ damage; it is of significance to strictly target ROS production. In this study, we evaluated the potential role of TLR7 agonist gardiquimod (GDQ) in oxidative stress (OS) in liver injury induced by sepsis. Here, we observed that intraperitoneal pretreatment with GDQ dramatically elevated the septic survival rate and effectively attenuated the septic liver injury. Interestingly, the increased ROS and inflammatory factor IL-6 levels were reversed after GDQ intervention...
April 19, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28422048/sak-hv-decreases-the-self-ubiquitination-of-mekk1-to-promote-macrophage-proliferation-via-mapk-erk-and-jnk-pathways
#8
Chao Zhang, Yao Chen, Xiangdong Gan, Zhiguang Huang, Minji Zou, Wenliang Fu, Weiwei Xing, Donggang Xu
SAK-HV is an anti-atherosclerosis recombinant fusion protein developed by our lab. Our study determined that SAK-HV promoted macrophage proliferation, of which the mechanism was explored by both RAW264.7 cells and primary macrophages. Mass spectrometric analysis and co-immunoprecipitation were combined to screen the SAK-HV-interacting proteins in RAW264.7 cells. Confocal microscopy was adopted to detect the localization of SAK-HV in cells. The results indicated that SAK-HV triggered macrophage proliferation via the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK) pathways by its SAK-mutant functional domain...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421075/activation-of-adhesion-gpcr-emr2-adgre2-induces-macrophage-differentiation-and-inflammatory-responses-via-g%C3%AE-16-akt-mapk-nf-%C3%AE%C2%BAb-signaling-pathways
#9
Kuan-Yu I, Yi-Shu Huang, Ching-Hsun Hu, Wen-Yi Tseng, Chia-Hsin Cheng, Martin Stacey, Siamon Gordon, Gin-Wen Chang, Hsi-Hsien Lin
EMR2/ADGRE2 is a human myeloid-restricted adhesion G protein-coupled receptor critically implicated in vibratory urticaria, a rare type of allergy caused by vibration-induced mast cell activation. In addition, EMR2 is also highly expressed by monocyte/macrophages and has been linked to neutrophil migration and activation. Despite these findings, little is known of EMR2-mediated signaling and its role in myeloid biology. In this report, we show that activation of EMR2 via a receptor-specific monoclonal antibody promotes the differentiation of human THP-1 monocytic cell line and induces the expression of pro-inflammatory mediators, including IL-8, TNF-α, and MMP-9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420170/fisetin-protects-pc12-cells-from-tunicamycin-mediated-cell-death-via-reactive-oxygen-species-scavenging-and-modulation-of-nrf2-driven-gene-expression-sirt1-and-mapk-signaling-in-pc12-cells
#10
Jui-Hung Yen, Pei-Shan Wu, Shu-Fen Chen, Ming-Jiuan Wu
BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418880/contributions-of-met-activation-to-bcr-abl1-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia-cells
#11
Masanobu Tsubaki, Tomoya Takeda, Toshiki Kino, Kazuko Sakai, Tatsuki Itoh, Motohiro Imano, Takashi Nakayama, Kazuto Nishio, Takao Satou, Shozo Nishida
Resistance to the breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitor (TKI) imatinib poses a major problem when treating chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, in the absence of a mutation in BCR-ABL1, the basis of BCR-ABL1-independent resistance must be elucidated. To gain insight into the mechanisms of BCR-ABL1-independent imatinib resistance, we performed an array-based comparative genomic hybridization. We identified various resistance-related genes, and focused on MET...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417011/chemical-biology-reveals-carf-as-a-positive-regulator-of-canonical-wnt-signaling-by-promoting-tcf-%C3%AE-catenin-transcriptional-activity
#12
Xiaoli He, Wenjuan Zhang, Chen Yan, Fen Nie, Chen Li, Xiaofen Liu, Cong Fei, Shengdi Li, Xiaomin Song, Yingying Jia, Rong Zeng, Dianqing Wu, Weijun Pan, Xiaojiang Hao, Lin Li
Wnt/β-catenin signaling regulates multiple biological processes and aberration of this pathway is frequently observed in human cancers. Previously, we uncovered NC043 as a small-molecule inhibitor of Wnt/β-catenin signaling. Here, we identified CARF as the cellular target of NC043. We found that NC043 binds directly to CARF through forming a covalent bond with the Cys-516 residue of CARF. Further study revealed that CARF interacts with Dvl, which potentiates the Dvl-c-Jun-β-catenin-TCF transcriptional complex and thus promotes Wnt signaling activation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28414098/cytosolic-calcium-mediates-rip1-rip3-complex-dependent-necroptosis-through-jnk-activation-and-mitochondrial-ros-production-in-human-colon-cancer-cells
#13
Wen Sun, Xiaxia Wu, Hongwei Gao, Jie Yu, Wenwen Zhao, Jin-Jian Lu, Jinhua Wang, Guanhua Du, Xiuping Chen
Necroptosis is a form of programmed necrosis mediated by signaling complexes with receptor-interacting protein 1 (RIP1) and RIP3 kinases as the main mediators. However, the underlying execution pathways of this phenomenon have yet to be elucidated in detail. In this study, a RIP1/RIP3 complex was formed in 2-methoxy-6-acetyl-7-methyljuglone (MAM)-treated HCT116 and HT29 colon cancer cells. With this formation, mitochondrial reactive oxygen species (ROS) levels increased, mitochondrial depolarization occurred, and ATP concentrations decreased...
April 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28414095/crosstalk-control-and-limits-of-physiological-c-jun-n-terminal-kinase-activity-for-cell-viability-and-neurite-stability-in-differentiated-pc12-cells
#14
Vicki Waetzig, Milana Belzer, Wiebke Haeusgen, Ruwen Boehm, Ingolf Cascorbi, Thomas Herdegen
The c-Jun N-terminal kinases (JNKs) are important mediators of cell viability and structural integrity in postmitotic neurons, which is required for maintaining synaptic connections and neural plasticity. In the present study, we chose differentiated PC12 cells as a well-characterised neuronal model system to selectively examine the regulation of basal JNK activity by extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt. We detected a complex interaction between the kinases to prevent cell death and neurite loss...
April 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28413329/protective-effect-of-ginsenoside-rh3-against-anticancer-drug-induced-apoptosis-in-llc-pk1-kidney-cells
#15
Hye Lim Lee, Ki Sung Kang
BACKGROUND: Ginsenosides are active components of Panax ginseng that exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22). METHODS: The present study investigated the kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a platinum based anticancer drug, induced apoptotic damage in renal proximal LLC-PK1 cells...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28412087/pregestational-type-2-diabetes-mellitus-induces-cardiac-hypertrophy-in-the-murine-embryo-through-cardiac-remodeling-and-fibrosis
#16
Xue Lin, Penghua Yang, E Albert Reece, Peixin Yang
BACKGROUND: Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Experimental evidence has implied that pregnant women with T2DM and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study has revealed that maternal T2DM induces structural heart defects in their offspring. OBJECTIVE: The present study aims to determine whether maternal T2DM induces embryonic heart hypertrophy in a murine model of diabetic embryopathy...
April 12, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28410397/a-bis-sulphamoylated-estradiol-derivative-induces-ros-dependent-cell-cycle-abnormalities-and-subsequent-apoptosis
#17
Michelle Helen Visagie, Iman van den Bout, Anna Margaretha Joubert
Clinical trials have revealed that the potential anticancer agent, 2-methoxyestradiol (2ME2) has limitations due to its low bioavailability. Subsequently, 2ME2 derivatives including (8R,13S,14S,17S)-2-ethyl-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrane-3,17-diyl bis(sulphamate) (EMBS) have shown improved efficacies in inducing apoptosis. However, no conclusive data exist to explain the mode of action exerted by these drugs. This study investigated the mode of action used by EMBS as a representative of the sulphamoylated 2ME2 derivatives...
2017: PloS One
https://www.readbyqxmd.com/read/28409880/osajin-inhibits-solar-uv-induced-cyclooxygenase-2-expression-through-direct-inhibition-of-rsk2
#18
Jong-Eun Kim, Yong-Seok Heo, Ki Won Lee
Solar ultraviolet light (sUV) has been shown to promote the development of skin disorders including inflammation, photoaging, and skin carcinogenesis. Osajin is the major bioactive isoflavone present in the fruit of Maclura pomifera, commonly referred to as the Osage orange. In this study, we observed that osajin inhibited sUV-induced cyclooxygenase (COX)-2 protein expression in both HaCaT and JB6 cells. COX-2 is a major mediator of skin inflammation. sUV activated the transcription factors nuclear factor- κB and activator protein-1 which, in turn, induces COX-2 expression...
April 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28409553/the-thyromimetic-kb2115-eprotirome-induces-rat-hepatocyte-proliferation
#19
Marta Szydlowska, Monica Pibiri, Andrea Perra, Elisabetta Puliga, Sandra Mattu, Giovanna Ledda-Columbano, Amedeo Columbano, Vera Leoni
Although the hepatomitogenic activity of T3 is well established, the wide range of harmful effects exerted by this hormone precludes its use in regenerative therapy. The aim of this study was to investigate whether an agonist of TR, KB2115 (Eprotirome) could exert a mitogenic effect in the liver, without most of the adverse T3/TR-dependent side effects. F-344 rats treated with KB2115 for one week displayed a massive increase in bromodeoxyuridine incorporation (from 20 to 40% vs. 5% of controls), which was associated with increased mitotic activity in the absence of significant signs of liver toxicity...
April 13, 2017: Gene Expression
https://www.readbyqxmd.com/read/28409295/metal-chelator-tpen-selectively-induces-apoptosis-in-k562-cells-through-reactive-oxygen-species-signaling-mechanism-implications-for-chronic-myeloid-leukemia
#20
Luisa Rojas-Valencia, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio
Chronic myeloid leukemia (CML) is a hematologic disorder characterized by the constitutive expression of BCR-ABL tyrosine kinase. Although successful implementation of tyrosine kinase inhibitors for the treatment of CML remain a traditional choice for molecularly targeted therapy, some patients present primary or secondary resistance to such therapy. Therefore, alternative therapeutic strategies are required to treat resistant CML cells. Accordingly, new anti-proliferative and/or pro-apoptotic compounds would be needed for clinical treatment...
April 13, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
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