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https://www.readbyqxmd.com/read/28538980/downregulation-of-lysyl-oxidase-protects-retinal-endothelial-cells-from-high-glucose-induced-apoptosis
#1
Dongjoon Kim, Robert P Mecham, Philip C Trackman, Sayon Roy
Purpose: To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods: Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX small interfering RNA (siRNA), scrambled siRNA as control, or exposed to β-aminopropionitrile (BAPN), a LOX inhibitor...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28538666/melatonin-attenuates-pulmonary-hypertension-in-chronically-hypoxic-rats
#2
Ming Wai Hung, Hang Mee Yeung, Chi Fai Lau, Angela Ming See Poon, George L Tipoe, Man Lung Fung
Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological processes in COPD. We examined the hypothesis that daily administration of melatonin (10 mg/kg) mitigates the pulmonary hypertension and vascular remodeling in chronically hypoxic rats. The right ventricular systolic pressure (RVSP) and the thickness of pulmonary arteriolar wall were measured from normoxic control, vehicle- and melatonin-treated hypoxic rats exposed to 10% O₂ for 14 days...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538660/regulatory-plasticity-of-earthworm-wmt-2-gene-expression
#3
Victoria Drechsel, Karl Schauer, Maja Šrut, Martina Höckner
Metallothioneins (MTs) are multifunctional proteins occurring throughout the animal kingdom. While the expression and transcriptional regulation of MTs is well-studied in vertebrates, the mechanism of MT activation is still unknown for most invertebrates. Therefore, we examined wMT-2 gene regulation and expression patterns in Lumbricus rubellus and L. terrestris. Transcription levels, the occupation of DNA binding sites, the expression of putative transcriptional regulators, and promotor DNA methylation were determined...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538182/targeting-metabolic-reprogramming-by-influenza-infection-for-therapeutic-intervention
#4
Heather S Smallwood, Susu Duan, Marie Morfouace, Svetlana Rezinciuc, Barry L Shulkin, Anang Shelat, Erika E Zink, Sandra Milasta, Resha Bajracharya, Ajayi J Oluwaseum, Martine F Roussel, Douglas R Green, Ljiljana Pasa-Tolic, Paul G Thomas
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538018/low-serum-angiopoietin-1-high-serum-angiopoietin-2-and-high-ang-2-ang-1-protein-ratio-are-associated-with-early-onset-sepsis-in-surinamese-newborns
#5
Rens Zonneveld, Rianne Jongman, Amadu Juliana, Wilco Zijlmans, Frans Plötz, Grietje Molema, Matijs van Meurs
PURPOSE: Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and -2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. Levels of Ang-2 change in adults and children during sepsis, which is associated with severity of sepsis. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 hours after birth. METHODS: A prospective cohort study was performed amongst 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns...
May 22, 2017: Shock
https://www.readbyqxmd.com/read/28537922/cooperative-but-distinct-early-co-signaling-events-originate-from-erbb2-and-erbb1-receptors-upon-trastuzumab-treatment-in-breast-cancer-cells
#6
Paola Bagnato, Alessia Castagnino, Katia Cortese, Maria Bono, Silvia Grasso, Grazia Bellese, Tiziana Daniele, Richard Lundmark, Paola Defilippi, Patrizio Castagnola, Carlo Tacchetti
ERBB2 receptor belongs to the ERBB tyrosine kinase receptor family. At variance to the other family members, ERBB2 is a constitutively active orphan receptor. Upon ligand binding and activation, ERBB receptors form homo- or hetero-dimers with the other family members, including ERBB2, promoting an intracellular signaling cascade. ERBB2 is the preferred dimerization partner and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. The specific contribution of ERBB2 in heterodimer signaling is still undefined...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537913/interaction-of-microrna-21-145-and-smad3-domain-specific-phosphorylation-in-hepatocellular-carcinoma
#7
Ji Yu Wang, Meng Fang, Alex Boye, Chao Wu, Jia Jun Wu, Ying Ma, Shu Hou, Yue Kan, Yan Yang
MicroRNAs 21 and 145 exhibit inverse expression in Hepatocellular carcinoma (HCC), but how they relate to Smad3 C-terminal and Link region phosphorylation (pSmad3C and pSmad3L) downstream of TGF-β/MAPK signaling, remains inconclusive. Our results suggest microRNA-145 targets Smad3 in HepG2 cells. Decreased tumor volume and increased apoptosis were produced in both microRNA-21 antagomir and microRNA-145 agomir groups compared to controls. Inhibition of TβRI and MAPK (ERK, JNK, and p38) activation respectively produced decreased microRNA-21 but increased microRNA-145 expression...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537903/amyloid-precursor-like-protein-1-promotes-jnk-mediated-cell-migration-in-drosophila
#8
Xingjun Wang, Ying Sun, Shilong Han, Chenxi Wu, Yeqing Ma, Yu Zhao, Yingyao Shao, Yujun Chen, Lingzhi Kong, Wenzhe Li, Fan Zhang, Lei Xue
The amyloid precursor like protein-1 (APLP1) is a member of the amyloid precursor protein (APP) family in mammals. While many studies have been focused on the pathologic role of APP in Alzheimer's disease, the physiological functions of APLP1 have remained largely elusive. Here we report that ectopic expression of APLP1 in Drosophila induces cell migration, which is suppressed by the loss of JNK signaling and enhanced by the gain of JNK signaling. APLP1 activates JNK signaling through phosphorylation of JNK, which up-regulates the expression of matrix metalloproteinase MMP1 required for basement membranes degradation and promotes actin remodeling essential for cell migration...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537883/preclinical-characterization-of-abemaciclib-in-hormone-receptor-positive-breast-cancer
#9
Raquel Torres-Guzmán, Bruna Calsina, Ana Hermoso, Carmen Baquero, Beatriz Alvarez, Joaquín Amat, Ann M McNulty, Xueqian Gong, Karsten Boehnke, Jian Du, Alfonso de Dios, Richard P Beckmann, Sean Buchanan, María José Lallena
Abemaciclib is an ATP-competitive, reversible kinase inhibitor selective for CDK4 and CDK6 that has shown antitumor activity as a single agent in hormone receptor positive (HR+) metastatic breast cancer in clinical trials. Here, we examined the mechanistic effects of abemaciclib treatment using in vitro and in vivo breast cancer models. Treatment of estrogen receptor positive (ER+) breast cancer cells with abemaciclib alone led to a decrease in phosphorylation of Rb, arrest at G1, and a decrease in cell proliferation...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537848/influence-of-endurance-training-on-skeletal-muscle-mitophagy-regulatory-proteins-in-type-2-diabetic-men
#10
Christian Brinkmann, Axel Przyklenk, Alexander Metten, Thorsten Schiffer, Wilhelm Bloch, Klara Brixius, Sebastian Gehlert
BACKGROUND: Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients...
May 24, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28537766/pirfenidone-induces-g1-arrest-in-human-tenon-s-fibroblasts-in-vitro-involving-akt-and-mapk-signaling-pathways
#11
Xiujuan Guo, Yangfan Yang, Liling Liu, Xiaoan Liu, Jiangang Xu, Kaili Wu, Minbin Yu
PURPOSE: To investigate the underlying mechanism by which pirfenidone blocks the transition from the G1 to S phase in primary human Tenon's fibroblasts. METHODS: Primary human Tenon's fibroblasts were characterized by immunocytofluorescence staining with vimentin, fibroblast surface protein, and cytokeratin. After treating Tenon's fibroblasts with pirfenidone under proliferation conditions (10% fetal bovine serum), cell proliferation was measured using a WST-1 assay...
May 24, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28535665/l1-cell-adhesion-molecule-promotes-migration-and-invasion-via-jnk-activation-in-extrahepatic-cholangiocarcinoma-cells-with-activating-kras-mutation
#12
Haejung Kim, Haein Hwang, Hansoo Lee, Hyo Jeong Hong
Extrahepatic cholangiocarcinoma (ECC), a malignant tumor of biliary origin, has a poor prognosis with limited treatment options. The KRAS oncogene is the most commonly mutated gene in ECC and one of the factors that predicts a poor prognosis and low survival rate. L1 cell adhesion molecule (L1CAM) is expressed in ECC cells and acts as an independent poor prognostic factor in predicting patient survival. In this study we investigate the functional significance of L1CAM in ECC cells with activating KRAS mutation...
May 24, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28535647/-effects-of-overexpression-of-mir-17-92-gene-cluster-on-the-biological-characteristics-of-prostate-cancer-cells-and-its-mechanism
#13
P Zhou, L Ma, J Zhou, J J Xu, F Liu, F Guo
Objective: To explore the effect and mechanism of over-expression of miR-17-92 gene cluster on the biological characteristics of prostate cancer cells. Methods: DU145 cells were transfected with miR-17-92 gene expression plasmid and clones with stable ectopic miR-17-92 overexpression were established. The cell viabilities of DU145-17-92 and DU145-control cells were monitored by xCELLigence system. Cell proliferation and apoptosis were analyzed by Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535625/-expression-and-clinical-significance-of-ser10-phosphorylated-p27-kip1-protein-in-human-breast-carcinoma
#14
Z Q Guo, Q S Lü, Z Wang, L H Lu, N Lu, X W Wen, W X Wu, M Yao
Objective: To explore the expression and clinicopathological significance of Ser10 phosphorylated p27(kip1)(P-p27Ser10) protein in human breast carcinoma tissue. Methods: Tissue specimens were obtained from 111 cases with breast carcinoma from January 2004 to December 2005. And the expression of P-p27Ser10 protein for each specimen was detected by immunohistochemical (EnVision) analysis. Six representative paired samples of cancerous and paired adjacent normal tissues were collected and detected by Western blot...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535510/heat-shock-protein-a12b-protects-vascular-endothelial-cells-against-sepsis-induced-acute-lung-injury-in-mice
#15
Yi Chen, Lei Wang, Qiuxiang Kang, Xu Zhang, Guifang Yu, Xiaojian Wan, Jiafeng Wang, Keming Zhu
BACKGROUND: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. METHODS: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535500/transient-receptor-potential-vanilloid-5-mediates-ca2-influx-and-inhibits-chondrocyte-autophagy-in-a-rat-osteoarthritis-model
#16
Yingliang Wei, Yanfang Wang, Yutong Wang, Lunhao Bai
BACKGROUND: Autophagy, a self-protective mechanism of chondrocytes, has become a promising target to impede the progress of osteoarthritis (OA). Autophagy is regulated by cytosolic Ca2+ activity and may thus be modified by the Ca2+ permeable transient receptor potential channel vanilloid 5 (TRPV5). Therefore, we investigated the potential role of TRPV5 in mediating Ca2+ influx and in inhibiting chondrocyte autophagy in a rat OA model. METHODS: The rat OA model was assessed by macroscopic and histological analyses...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535417/ezrin-nf-kb-activation-regulates-epithelial-mesenchymal-transition-induced-by-egf-and-promotes-metastasis-of-colorectal-cancer
#17
Yingru Li, Zhaoyu Lin, Bin Chen, Shuang Chen, Zhipeng Jiang, Taicheng Zhou, Zehui Hou, Youyuan Wang
There is growing evidence that epithelial mesenchymal-transition (EMT) plays significant roles in terms of tumor metastasis. There are a lot of cytokines inducing EMT of tumor cells, EGF is one of the important cytokines.Ezrin is a connexin between the cytoskeleton and the cell membrane, which is closely related to the morphological movement and metastasis of tumor cells.EGF can activate Ezrin and affects cell motility. In recent years, many studies have shown that NF-kB acts as an important transcription factor, involving in the process of EMT...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28535415/dual-hypopigmentary-effects-of-punicalagin-via-the-erk-and-akt-pathways
#18
Jun Seob Shin, Jun Hee Cho, Hana Lee, Hyo-Soon Jeong, Myo-Kyoung Kim, Hye-Young Yun, Nyoun Soo Kwon, Dong-Seok Kim
Punicalagin is a phenolic compound with antioxidant properties. However, the effects of punicalagin on melanin synthesis have been poorly evaluated. Therefore, we investigated the effects of punicalagin on melanogenesis in Mel-Ab cells. Punicalagin significantly inhibited melanin synthesis in a dose-dependent manner. In accordance with the melanin content, punicalagin also dose-dependently decreased tyrosinase activity. Punicalagin did not directly inhibit tyrosinase in a cell-free system but did downregulate the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28535376/dephosphorylation-of-the-ndc80-tail-stabilizes-kinetochore-microtubule-attachments-via-the-ska-complex
#19
Dhanya K Cheerambathur, Bram Prevo, Neil Hattersley, Lindsay Lewellyn, Kevin D Corbett, Karen Oegema, Arshad Desai
During cell division, genome inheritance is orchestrated by microtubule attachments formed at kinetochores of mitotic chromosomes. The primary microtubule coupler at the kinetochore, the Ndc80 complex, is regulated by Aurora kinase phosphorylation of its N-terminal tail. Dephosphorylation is proposed to stabilize kinetochore-microtubule attachments by strengthening electrostatic interactions of the tail with the microtubule lattice. Here, we show that removal of the Ndc80 tail, which compromises in vitro microtubule binding, has no effect on kinetochore-microtubule attachments in the Caenorhabditis elegans embryo...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#20
Aurelie Badillo, Veronique Brechot, Stephane Sarrazin, François-Xavier Cantrelle, Frederic Delolme, Marie-Laure Fogeron, Jennifer Molle, Roland Montserret, Anja Bockmann, Ralf Bartenschlager, Volker Lohmann, Guy Lippens, Sylvie Ricard-Blum, Xavier Hanoulle, Francois Penin
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1) and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations...
May 23, 2017: Biochemistry
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