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Phospho-AKT

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https://www.readbyqxmd.com/read/28928604/kaempferide-protects-against-myocardial-ischemia-reperfusion-injury-through-activation-of-the-pi3k-akt-gsk-3%C3%AE-pathway
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28912644/tlr5-activation-through-nf-%C3%AE%C2%BAb-is-a-neuroprotective-mechanism-of-postconditioning-after-cerebral-ischemia-in-mice
#4
Jaewon Jeong, Soojin Kim, Da-Sol Lim, Seo-Hea Kim, Heeju Doh, So-Dam Kim, Yun Seon Song
Postconditioning has been shown to protect the mouse brain from ischemic injury. However, the neuroprotective mechanisms of postconditioning remain elusive. We have found that toll-like receptor 5 (TLR5) plays an integral role in postconditioning-induced neuroprotection through Akt/nuclear factor kappa B (NF-κB) activation in cerebral ischemia. Compared to animals that received 30 min of transient middle cerebral artery occlusion (tMCAO) group, animals that also underwent postconditioning showed a significant reduction of up to 60...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28882951/the-immunoreactivity-of-pi3k-akt-pathway-after-prenatal-hypoxic-damage
#5
Huisun Wang, Yoonyoung Chung, Sun-Kyoung Yu, Yonghyun Jun
BACKGROUND/AIM: There is no consensus on the effect of hypoxia on neurogenesis. In this study, we investigated the immunoreactivity of BDNF and PI3K/Akt signaling after uterine artery ligation in pregnant rats. MATERIALS AND METHODS: Unilateral uterine artery ligation was performed at 16 days of gestation (dg). Fetuses from one horn with ligated artery were allocated to the hypoxic group. Immunohistochemistry was performed with primary antibodies; NeuN, BDNF, PI3K, Akt and phospho-Akt (pAkt)...
September 2017: In Vivo
https://www.readbyqxmd.com/read/28881824/differential-gene-and-lncrna-expression-in-the-lower-thoracic-spinal-cord-following-ischemia-reperfusion-induced-acute-kidney-injury-in-rats
#6
Qing-Quan Liu, Hui Liu, Zhi-Gang He, Shi-Jie Zhang, Bao-Wen Liu, Le Wang, Wen-Hui Qiu, Qing Xu, Hong-Bing Xiang, Yong-Man Lv
We used high-throughput RNA sequencing to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord during ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) in rats. We observed that of 32662 mRNAs, 4296 out were differentially expressed in the T8-12 segments of the spinal cord upon I/R-induced AKI. Among these, 62 were upregulated and 34 were downregulated in response to I/R (FDR < 0.05, |log2FC| > 1). Further, 52 differentially expressed lncRNAs (35 upregulated and 17 downregulated) were identified among 3849 lncRNA transcripts...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877257/rosmarinic-acid-potentiates-carnosic-acid-induced-apoptosis-in-lung-fibroblasts
#7
Sana Bahri, Frédérique Mies, Ridha Ben Ali, Mona Mlika, Saloua Jameleddine, Kathleen Mc Entee, Vadim Shlyonsky
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11...
2017: PloS One
https://www.readbyqxmd.com/read/28871105/convergent-akt-activation-drives-acquired-egfr-inhibitor-resistance-in-lung-cancer
#8
Kirstine Jacobsen, Jordi Bertran-Alamillo, Miguel Angel Molina, Cristina Teixidó, Niki Karachaliou, Martin Haar Pedersen, Josep Castellví, Mónica Garzón, Carles Codony-Servat, Jordi Codony-Servat, Ana Giménez-Capitán, Ana Drozdowskyj, Santiago Viteri, Martin R Larsen, Ulrik Lassen, Enriqueta Felip, Trever G Bivona, Henrik J Ditzel, Rafael Rosell
Non-small-cell lung cancer patients with activating epidermal growth factor receptor (EGFR) mutations typically benefit from EGFR tyrosine kinase inhibitor treatment. However, virtually all patients succumb to acquired EGFR tyrosine kinase inhibitor resistance that occurs via diverse mechanisms. The diversity and unpredictability of EGFR tyrosine kinase inhibitor resistance mechanisms presents a challenge for developing new treatments to overcome EGFR tyrosine kinase inhibitor resistance. Here, we show that Akt activation is a convergent feature of acquired EGFR tyrosine kinase inhibitor resistance, across a spectrum of diverse, established upstream resistance mechanisms...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28844959/reversal-of-aberrant-pi3k-akt-signaling-by-salubrinal-in-a-galt-deficient-mouse-model
#9
B Balakrishnan, C Nicholas, A Siddiqi, W Chen, E Bales, M Feng, J Johnson, K Lai
Classic Galactosemia is an autosomal recessive disorder caused by deleterious mutations in the GALT gene, which encodes galactose-1 phosphate uridylyltransferase enzyme (GALT: EC 2.7.7.12). Recent studies of primary skin fibroblasts isolated from the GalT-deficient mice demonstrated a slower growth rate, a higher level of endoplasmic reticulum (ER) stress, and down-regulation of the Phosphoinositide 3 kinase/Protein kinase B (PI3K/Akt) signaling pathway. In this study, we compared the expression levels of the PI3K/Akt signaling pathway in normal and GalT-deficient mouse tissues...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28842826/environmental-enrichment-reverses-tyrosine-kinase-inhibitor-mediated-impairment-through-bdnf-trkb-pathway
#10
Harkaitz Bengoetxea, Irantzu Rico-Barrio, Naiara Ortuzar, Ane Murueta-Goyena, José V Lafuente
Exposure to an enriched environment (EE) has neuroprotective benefits and improves recovery from brain injury due to, among other, increased neurotrophic factor expression. Through these neurotrophins, important cortical and hippocampal changes occur. Vandetanib acts as a tyrosine kinase inhibitor of cell receptors, among others, the vascular endothelial growth factor receptor (VEGFR). Our aim was to investigate the effectiveness of EE counteracting cognitive and cellular effects after tyrosine kinase receptor blockade...
August 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28842516/mir-494-upregulates-the-pi3k-akt-pathway-via-targeting-pten-and-attenuates-hepatic-ischemia-reperfusion-injury-in-a-rat-model
#11
Song Su, De Luo, Xiangdong Liu, Jiang Liu, Fangyi Peng, Cheng Fang, Bo Li
A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir-miR-494 or agomir-NC for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI+agomir-miR-494 and HIRI+agomir-NC were compared. The effect of miR-494 was also assessed in an H2O2-induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or miR-494 mimics, followed by 6-h H2O2 treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively...
August 25, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28842423/activation-of-liver-x-receptor-suppresses-angiogenesis-via-induction-of-apod
#12
Chih-Jen Lai, Hsu-Chen Cheng, Ching-Yu Lin, Shih-Han Huang, Ting-Huan Chen, Chi-Jung Chung, Chung-Ho Chang, Horng-Dar Wang, Chih-Pin Chuu
Liver X receptors (LXRs) are important sensors and regulators for cholesterol, fatty acid, and glucose. LXRs play essential roles in the development and progression of cardiovascular diseases. We examined the effects of T0901317, a potent LXR agonist, on angiogenesis of human umbilical vein endothelial cells (HUVECs). Treatment with T0901317 inhibited the tube formation and migration of HUVECs as well as reduced the in vivo angiogenesis determined by chorioallantoic membrane assay. T0901317 stimulated gene and protein expression of LXR target gene apolipoprotein D (ApoD)...
August 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#13
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28800461/design-synthesis-and-biological-evaluation-of-novel-3-substituted-imidazo-1-2-a-pyridine-and-quinazolin-4-3h-one-derivatives-as-pi3k%C3%AE-inhibitors
#14
Yan-Hua Fan, Wei Li, Dan-Dan Liu, Meng-Xuan Bai, Hong-Rui Song, Yong-Nan Xu, SangKook Lee, Zhi-Peng Zhou, Jian Wang, Huai-Wei Ding
Phosphatidylinositol 3-kinase (PI3K) is a pivotal regulator of intracellular signaling pathways and considered as a promising target in the development of a therapeutic treatment of cancer. Among the different PI3K subtypes, the PIK3CA gene encoding PI3K p110α is frequently mutated and overexpressed in majority of human cancers. Therefore, the inhibition of PI3Kα has been considered to be an efficient approach for the treatment of cancer. In this study, two series compounds containing hydrophilic group in imidazo[1,2-a]pyridine and quinazolin-4(3H)-one were synthesized and their antiproliferative activities against five cancer cell lines, including HCT-116, SK-HEP-1, MDA-MB-231, SNU638 and A549, were evaluated...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28795272/pet-imaging-on-dynamic-metabolic-changes-after-combination-therapy-of-paclitaxel-and-the-traditional-chinese-medicine-in-breast-cancer-bearing-mice
#15
Yao Chen, Ling Wang, Hao Liu, Fahuan Song, Caiyun Xu, Kai Zhang, Qing Chen, Shuang Wu, Yunqi Zhu, Ying Dong, Min Zhou, Hong Zhang, Mei Tian
PURPOSE: The aim of the study was to non-invasively evaluate the anticancer activity of a traditional Chinese medicine-Huaier, combined with paclitaxel (PTX) in breast cancer bearing mice by detecting dynamic metabolic changes with positron emission tomography (PET). PROCEDURES: Balb/c nude mice were randomly divided into one of the four groups: Huaier, PTX, PTX + Huaier, or the control. PET imaging with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) was performed to monitor the metabolic changes in BT474 (luminal B) and MDA-MB-231 (triple-negative) breast cancer xenografts...
August 9, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28775169/loss-of-igf2-gene-imprinting-in-murine-prostate-promotes-widespread-neoplastic-growth
#16
Nathan Damaschke, Bing Yang, Sachin Bhusari, Mele Avilla, Weixiong Zhong, Michael L Blute, Wei Huang, David F Jarrard
Loss of imprinting (LOI) is an epigenetic event which relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor IGF2, which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between IGF2 LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF binding site mutations at the Igf2-H19 imprint control region that abolishes CTCF insulator activity, resulting in biallelic Igf2 expression that mimics increased levels seen with aging-induced LOI...
August 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28774332/baicalin-attenuates-chronic-hypoxia-induced-pulmonary-hypertension-via-adenosine-a2a-receptor-induced-sdf-1-cxcr4-pi3k-akt-signaling
#17
Xiaoying Huang, Peiliang Wu, Feifei Huang, Min Xu, Mayun Chen, Kate Huang, Guo-Ping Li, Manhuan Xu, Dan Yao, Liangxing Wang
BACKGROUND: Baicalin, an important flavonoid in Scutellaria baicalensis Georgi extracts, exerts a variety of pharmacological effects. In this study, we explored the effects of baicalin on chronic hypoxia-induced pulmonary arterial hypertension (PAH) and investigated the mechanism underlying these effects. Moreover, we examined whether the inflammatory response was mediated by the A2A receptor (A2AR) and stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-induced phosphatidyl inositol-3-kinase (PI3K) signaling in vivo...
August 3, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28769006/mechanistic-study-of-inhibitory-effects-of-metformin-and-atorvastatin-in-combination-on-prostate-cancer-cells-in-vitro-and-in-vivo
#18
Zhen-Shi Wang, Hua-Rong Huang, Lan-Yue Zhang, Seungkee Kim, Yan He, Dong-Li Li, Chelsea Farischon, Kun Zhang, Xi Zheng, Zhi-Yun Du, Susan Goodin
Metformin is a commonly used drug for the treatment of type II diabetes and atorvastatin is the most prescribed cholesterol-lowering statin. The present study investigated the effects and mechanisms of metformin and atorvastatin in combination on human prostate cancer cells cultured in vitro and grown as xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28759294/epidermal-growth-factor-receptor-activation-promotes-ada3-acetylation-through-the-akt-p300-pathway
#19
Shashank Srivastava, Shakur Mohibi, Sameer Mirza, Hamid Band, Vimla Band
The ADA3 (Alteration/Deficiency in Activation 3) protein is an essential adaptor component of several Lysine Acetyltransferase (KAT) complexes involved in chromatin modifications. Previously, we and others have demonstrated a crucial role of ADA3 in cell cycle progression and in maintenance of genomic stability. Recently, we have shown that acetylation of ADA3 is key to its role in cell cycle progression. Here, we demonstrate that AKT activation downstream of Epidermal Growth Factor Receptor (EGFR) family proteins stimulation leads to phosphorylation of p300, which in turn promotes the acetylation of ADA3...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28748356/pd-l1-induced-by-ifn-%C3%AE-from-tumor-associated-macrophages-via-the-jak-stat3-and-pi3k-akt-signaling-pathways-promoted-progression-of-lung-cancer
#20
Xiaohui Zhang, Yuanyuan Zeng, Qiuxia Qu, Jianjie Zhu, Zeyi Liu, Weiwei Ning, Hui Zeng, Nan Zhang, Wenwen Du, Cheng Chen, Jian-An Huang
BACKGROUND: Interferon-γ (IFN-γ) is conventionally regarded as an inflammatory cytokine that has a pivotal role in anti-infection and tumor immune surveillance. It has been used clinically to treat a variety of malignancies. However, increased evidence has suggested IFN-γ can act to induce tumor progression. The role of IFN-γ in regulating antitumor immunity appears to be complex and paradoxical. The mechanism underlying the dual aspects of IFN-γ function in antitumor immunity is not clear...
July 26, 2017: International Journal of Clinical Oncology
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