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Phospho-AKT

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https://www.readbyqxmd.com/read/29137974/effects-and-mechanisms-of-matrix-metalloproteinase2-on-neural-differentiation-of-induced-pluripotent-stem-cells
#1
Tao Shu, Chang Liu, Mao Pang, Juan Wang, Bin Liu, Wei Zhou, Xuan Wang, Tao Wu, Qiyou Wang, Limin Rong
Induced pluripotent stem cells (iPSCs) possess the potential to differentiate into neural lineage cells. Matrix metalloproteinase 2 (MMP2), an endopeptidase in the extracellular matrix, has been shown to protect neural cells from injury. However, the mechanisms and effects of MMP2 on neural differentiation of iPSCs remain poorly understood. Here, we demonstrated a role for MMP2 in the differentiation of iPSCs to neurons via the AKT pathway. Treatment of iPSCs with MMP2 promoted their proliferation and differentiation into neural stem cells (NSCs), and then into neurons...
November 11, 2017: Brain Research
https://www.readbyqxmd.com/read/29130531/acute-hypoxic-preconditioning-prevents-palmitic-acid-induced-cardiomyocyte-apoptosis-via-switching-metabolic-glut4-glucose-pathway-back-to-cd36-fatty-acid-dependent
#2
Yeh-Peng Chen, Wei-Wen Kuo, Rathinasamy Baskaran, Cecilia-Hsuan Day, Ray-Jade Chen, Su-Ying Wen, Tsung-Jung Ho, Viswanadha Vijaya Padma, Chia-Hua Kuo, Chih-Yang Huang
Metabolic syndrome is a risk factor for the development of cardiovascular diseases. Myocardial cell damage leads to an imbalance of energy metabolism, and many studies have indicated that short-term hypoxia during myocardial cell injury has a protective effect. In our previous animal studies, we found that short-term hypoxia in the heart has a protective effect, but long-term hypoxia increases myocardial cell injury. Palmitic acid (PA)-treated H9c2 cardiomyoblasts and neonatal rat ventricle cardiomyocytes were used to simulate hyperlipidemia model, which suppress cluster of differentiation 36 (CD36) and activate glucose transporter type 4 (GLUT4)...
November 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29122578/a-carvedilol-responsive-microrna-mir-125b-5p-protects-the-heart-from-acute-myocardial-infarction-by-repressing-pro-apoptotic-bak1-and-klf13-in-cardiomyocytes
#3
Ahmed S Bayoumi, Kyoung-Mi Park, Yongchao Wang, Jian-Peng Teoh, Tatsuya Aonuma, Yaoliang Tang, Huabo Su, Neal L Weintraub, Il-Man Kim
BACKGROUND: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β1-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart...
November 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29113312/fkbp51-decreases-cell-proliferation-and-increases-progestin-sensitivity-of-human-endometrial-adenocarcinomas-by-inhibiting-akt
#4
Jing Dong, Yulian Jiao, Wenli Mu, Bingru Lu, Muyun Wei, Linying Sun, Shengnan Hu, Bin Cui, Xiaowen Liu, Zijiang Chen, Yueran Zhao
In this study, we investigated the role of FK506 binding protein 51 (FKBP51) in human endometrial adenocarcinoma progression. Immunohistochemical analysis showed decreased FKBP51 expression in endometrial adenocarcinoma tissues. Moreover, higher FKBP51 expression was observed in the normal secretory phase than in proliferative-phase endometrial tissues. FKBP51-shRNA transfected KLE cells showed high Ser473-phospho Akt with decreased p21 and p27 levels, which promoted S-G2/M phase cell cycle progression and proliferation...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101404/autoreactive-t-cells-in-immunopathogenesis-of-tb-associated-uveitis
#5
Ravichandra Tagirasa, Shaifaly Parmar, Manas R Barik, Satish Devadas, Soumyava Basu
Purpose: Intraocular inflammation in tuberculosis-associated uveitis (TBU) is usually widespread, and responds unpredictably to treatment. Herein, we analyze the intraocular T-cell response in TBU for its surface phenotype, antigenic specificity, and functional characteristics to explain the above observations. Methods: We isolated T cells from vitreous humor samples of patients with TBU and non-TB uveitis (controls). These were directly stained for surface markers CD4, CD8, CD45RO, CD45RA, CCR7, as well as intracellular cytokines IFN-γ, TNF-α, and IL-17 and analyzed on flow cytometry...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29099085/eburicoic-acid-a-triterpenoid-compound-from-antrodia-camphorata-displays-antidiabetic-and-antihyperlipidemic-effects-in-palmitate-treated-c2c12-myotubes-and-in-high-fat-diet-fed-mice
#6
Cheng-Hsiu Lin, Yueh-Hsiung Kuo, Chun-Ching Shih
This study was designed to investigate the antidiabetic and antihyperlipidemic effects and mechanisms of eburicoic acid (TRR); one component of Antrodia camphorata in vitro and in an animal model for 14 weeks. Expression levels of membrane glucose transporter type 4 (GLUT4); phospho-5'-adenosine monophosphate-activated protein kinase (AMPK)/total AMPK; and phospho-Akt/total-Akt in insulin-resistant C2C12 myotube cells were significantly decreased by palmitate; and such decrease was prevented and restored by TRR at different concentrations...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29093526/spermine-oxidase-promotes-bile-canalicular-lumen-formation-through-acrolein-production
#7
Takeshi Uemura, Tomokazu Takasaka, Kazuei Igarashi, Hiroshi Ikegaya
Spermine oxidase (SMOX) catalyzes oxidation of spermine to generate spermidine, hydrogen peroxide (H2O2) and 3-aminopropanal, which is spontaneously converted to acrolein. SMOX is induced by a variety of stimuli including bacterial infection, polyamine analogues and acetaldehyde exposure. However, the physiological functions of SMOX are not yet fully understood. We investigated the physiological role of SMOX in liver cells using human hepatocellular carcinoma cell line HepG2. SMOX localized to the bile canalicular lumen, as determined by F-actin staining...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080749/flubendazole-overcomes-trastuzumab-resistance-by-targeting-cancer-stem-like-properties-and-her2-signaling-in-her2-positive-breast-cancer
#8
Yoon-Jae Kim, Daeil Sung, Eunhye Oh, Youngkwan Cho, Tae-Min Cho, Lee Farrand, Jae Hong Seo, Ji Young Kim
Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Trastuzumab resistance is a multi-factorial phenomenon thought to arise from the presence of cancer stem cells and interactions between truncated p95HER2 and HER family members. Flubendazole (FLU) is a potent anthelmintic agent with an exceptional safety profile. Evidence also suggests that it can act as an anticancer agent in several cancer cell types. We sought to investigate the effect of FLU on apoptosis, HER2/Akt signaling, breast cancer stem cell (BCSC)-like properties and trastuzumab resistance in HER2-positive breast cancer cells...
November 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29080395/microrna-200c-inhibits-epithelial-mesenchymal-transition-by-targeting-the-bmi-1-gene-through-the-phospho-akt-pathway-in-endometrial-carcinoma-cells-in-vitro
#9
Fengling Li, Aihua Liang, Yan Lv, Guohong Liu, Aili Jiang, Peishu Liu
BACKGROUND MicroRNA-200c (miR-200c) is a short non-coding RNA that has a role in tumorigenesis and cancer progression. The aims of this study were to investigate the role of miR-200c in cell migration and epithelial-mesenchymal transition (EMT) in endometrial carcinoma cells in vitro. MATERIAL AND METHODS Potential direct targets of miR-200c were identified through the TargetScan database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used study the expression of miR-200c in the endometrial carcinoma cell lines, Ishikawa and JEC, in vitro...
October 28, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29069801/effect-of-weekly-or-daily-dosing-regimen-of-gefitinib-in-mouse-models-of-lung-cancer
#10
Qi Zhang, Ruichao Li, Xu Chen, Sang Beom Lee, Jing Pan, Donghai Xiong, Jiaqi Hu, Mark Steven Miller, Eva Szabo, Ronald A Lubet, Yian Wang, Ming You
Gefitinib showed response in phase II clinical trials and with better clinical response in lung cancer with activating mutations in the tyrosine kinase domain of the EGFR. Questions of toxicity and potential dosing regimens impede the use in a prevention setting. This study will provide scientific evidence for the utility of testing and comparing weekly and daily dosing regimens in clinical trials. We employed the adenocarcinoma (AD) and squamous cell carcinoma (SCC) models to compare the efficacy of Gefitinib in daily or weekly dosing regimens...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29061016/-clinical-significance-and-mechanism-of-upregulation-of-pi3kp110%C3%AE-in-non-small-cell-lung-carcinoma
#11
Y Xiong, L L Qu, D Li, Y Wang, T Li
Objective: To investigate the clinical significance and mechanism of upregulation of phosphoinositide 3-kinase p110α(PI3Kp110α)in non-small cell lung carcinoma (NSCLC). Methods: Expressions of PI3Kp110α and other components in PI3K signaling pathway (including phospho-Akt (p-Akt, Ser 473), MET, ROS1, HER-2, ALK, total EGFR and mutant EGFR) and p53 (the transcription factor of PIK3CA) mutation in NSCLC were detected by immunohistochemistry. The relationships between PI3Kp110α expression and clinicopathological characteristics, expressions of other proteins in PI3K pathway and p53 mutation were analyzed...
October 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/29045061/suppression-of-mapk-signaling-in-braf-activated-pten-deficient-melanoma-by-blocking-%C3%AE-catenin-signaling-in-cancer-associated-fibroblasts
#12
Linli Zhou, Kun Yang, Spencer Dunaway, Zalfa Abdel-Malek, Thomas Andl, Ana Luisa Kadekaro, Yuhang Zhang
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs...
October 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29030784/anti-tnf-%C3%AE-antibody-alleviates-insulin-resistance-in-rats-with-sepsis-induced-stress-hyperglycemia
#13
W Qu, C Han, M Li, J Zhang, Z Jiang
PURPOSE: To explore the effects and mechanisms of anti-tumor necrosis factor-α (TNF-α) antibody on insulin resistance (IR) in rats with sepsis-induced stress hyperglycemia. METHODS: The sepsis-induced stress hyperglycemic rat model was constructed by cecal ligation and puncture combined with the intraperitoneal injection of lipopolysaccharide. The rats were randomly divided into six groups: normal control (NC) group, surgical rats (Cntl) group, high-dose anti-TNF-α antibody therapy (TNF, 6 mg/kg) group, low-dose anti-TNF-α antibody therapy (Tnf, 3 mg/kg) group, insulin therapy (INS) group, and INS + Tnf group...
October 13, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29021381/activation-of-fak-and-src-mediates-acquired-sorafenib-resistance-in-a549-human-lung-adenocarcinoma-xenografts
#14
Qingyu S Zhou, Xiaofang Guo, Riya Choksi
Despite encouraging clinical results with sorafenib monotherapy in patients with KRAS-mutant non-small cell lung cancer (NSCLC), the overall survival benefit of this drug is limited by the inevitable development of acquired resistance. The exact mechanism underlying acquired sorafenib resistance in KRAS-mutant NSCLC is unclear. In this study, the mechanism of acquired sorafenib resistance was explored using a biologically relevant xenograft model, which was established by using the A549 human lung adenocarcinoma cell line and an in-vivo derived sorafenib-resistant A549 subline (A549/SRFres)...
October 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29018142/adiponectin-has-a-pivotal-role-in-the-cardioprotective-effect-of-cp-3-iv-a-selective-cd36-azapeptide-ligand-after-transient-coronary-artery-occlusion-in-mice
#15
David N Huynh, Valérie L Bessi, Liliane Ménard, Jérôme Piquereau, Caroline Proulx, Maria Febbraio, William D Lubell, André C Carpentier, Yan Burelle, Huy Ong, Sylvie Marleau
CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-activated receptor-γ, a transcriptional regulator of adiponectin. CP-3(iv) pretreatment reduced infarct size by 54% and preserved hemodynamics in C57BL/6 mice subjected to 30 min coronary ligation and reperfusion but had no effect in CD36-deficient mice...
October 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29017516/identification-of-a-rac-akt-like-gene-in-leishmania-parasites-as-a-putative-therapeutic-target-in-leishmaniasis
#16
Rubén E Varela-M, Rodrigo Ochoa, Carlos E Muskus, Antonio Muro, Faustino Mollinedo
BACKGROUND: Leishmaniasis is one of the world's most neglected diseases caused by at least 20 different species of the protozoan parasite Leishmania. Although new drugs have become recently available, current therapy for leishmaniasis is still unsatisfactory. A subgroup of serine/threonine protein kinases named as related to A and C protein kinases (RAC), or protein kinase B (PKB)/AKT, has been identified in several organisms including Trypanosoma cruzi parasites. PKB/AKT plays a critical role in mammalian cell signaling promoting cell survival and is a major drug target in cancer therapy...
October 10, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28939847/dual-mab-her-family-blockade-in-head-and-neck-cancer-human-cell-lines-combined-with-photon-therapy
#17
Jean-Baptiste Guy, Benoîte Méry, Edouard Ollier, Sophie Espenel, Alexis Vallard, Anne-Sophie Wozny, Stéphanie Simonet, Alexandra Lauret, Priscillia Battiston-Montagne, Dominique Ardail, Gersende Alphonse, Chloé Rancoule, Claire Rodriguez-Lafrasse, Nicolas Magné
Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928604/kaempferide-protects-against-myocardial-ischemia-reperfusion-injury-through-activation-of-the-pi3k-akt-gsk-3%C3%AE-pathway
#18
Dong Wang, Xinjie Zhang, Defang Li, Wenjin Hao, Fanqing Meng, Bo Wang, Jichun Han, Qiusheng Zheng
The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28923649/hypothermic-machine-perfusion-s-protection-on-porcine-kidney-graft-uncovers-greater-akt-erk-phosphorylation
#19
N He, J-H Li, J-J Jia, K-D Xu, Y-F Zhou, L Jiang, H-H Lu, S-Y Yin, H-Y Xie, L Zhou, S-S Zheng
BACKGROUND: To investigate the potential mechanisms of hypothermic machine perfusion (HMP)'s beneficial effects on kidney graft over static cold storage (SCS) in vitro. METHODS: Ten kidneys of 5 Bama miniature male pigs were paired into 2 groups: SCS group and HMP group. Preservation solutions were taken at 0, 1, 3, and 6 hours for the measurement of K(+), Na(+), Cl(-), blood urea nitrogen (BUN), creatinine (Cr), and lactate dehydrogenase (LDH) using the standard laboratory methods...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28914370/thioredoxin-1-is-associated-with-the-proliferation-and-apoptosis-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#20
Tianbao Lu, Ming Zong, Shasha Fan, Ying Lu, Shanhan Yu, Lieying Fan
We aimed to investigate the possible effects of thioredoxin 1 (Trx1) on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and elucidate the possible mechanisms involved. We investigated the distribution and expression of Trx1 in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analyses. RA-FLSs were isolated and cultured under normoxic (21% oxygen) or hypoxic (3% oxygen) concentrations...
September 15, 2017: Clinical Rheumatology
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