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Phospho-AKT

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https://www.readbyqxmd.com/read/29775658/hydroxysafflor-yellow-a-protects-brain-microvascular-endothelial-cells-against-oxygen-glucose-deprivation-reoxygenation-injury-involvement-of-inhibiting-autophagy-via-class-i-pi3k-akt-mtor-signaling-pathway
#1
Guang Yang, Ning Wang, Sai Wang Seto, Dennis Chang, Huazheng Liang
The present study aimed to test whether Hydroxysafflor yellow A (HSYA) protects the brain microvascular endothelial cells (BMECs) injury induced by oxygen glucose deprivation/reoxygenation (OGD/R) via the PI3K/Akt/mTOR autophagy signaling pathway. Primary rat BMECs were cultured and identified by the expression of factor VIII-related antigen before being exposed to OGD/R to imitate ischemia/reperfusion (I/R) damage in vitro. The protective effect of HSYA was evaluated by assessing (1) cellular morphologic and ultrastructural changes; (2) cell viability and cytotoxicity; (3) transendothelial electrical resistance (TEER) of monolayer BMECs; (4) cell apoptosis; (5) fluorescence intensity of LC3B; (6) LC3 mRNA expression; (7) protein expressions of LC3, Beclin-1, Zonula occludens-1 (ZO-1), phospho-Akt (p-Akt), Akt, phospho-mTOR (p-mTOR) and mTOR...
May 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29775456/maternal-obesogenic-diet-induces-endometrial-hyperplasia-an-early-hallmark-of-endometrial-cancer-in-a-diethylstilbestrol-mouse-model
#2
Theresa O Owuor, Michaela Reid, Lauren Reschke, Ian Hagemann, Suellen Greco, Zeel Modi, Kelle H Moley
Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29760351/leptin-aggravates-reflux-esophagitis-by-increasing-tissue-levels-of-macrophage-migration-inhibitory-factor-in-rats
#3
Tsugihiro Murata, Kiyotaka Asanuma, Nobuyuki Ara, Katsunori Iijima, Waku Hatta, Shin Hamada, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atsushi Masamune, Tooru Shimosegawa
Leptin, produced primarily by the adipose tissue, acts as a pro-inflammatory modulator, thereby contributing to the development of obesity-related disease. Although high levels of leptin in the obese are closely related to gastroesophageal reflux disease, the mechanism by which leptin influences esophageal inflammation remains unknown. Macrophage migration inhibitory factor (MIF) is produced by immune cells, such as T lymphocytes and macrophages, and MIF is known to induce the production of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6)...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29757257/mtor-pathway-in-papillary-thyroid-carcinoma-different-contributions-of-mtorc1-and-mtorc2-complexes-for-tumor-behavior-and-slc5a5-mrna-expression
#4
Catarina Tavares, Catarina Eloy, Miguel Melo, Adriana Gaspar da Rocha, Ana Pestana, Rui Batista, Luciana Bueno Ferreira, Elisabete Rios, Manuel Sobrinho Simões, Paula Soares
The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex...
May 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29742928/an-integrated-study-on-the-antitumor-effect-and-mechanism-of-triphala-against-gynecological-cancers-based-on-network-pharmacological-prediction-and-in-vitro-experimental-validation
#5
Yuhang Zhao, Min Wang, Jokyab Tsering, Hanluo Li, Simin Li, Yuepeng Li, Yinghua Liu, Xianda Hu
OBJECTIVES: Triphala is a herbal medicine that has been widely used for treating a variety of ailments. This study aims to systematically analyze the antitumor effects of Triphala on gynecological cancers. METHODS: The antineoplastic activities of Triphala on gynecological cancers were analyzed using network pharmacology-based strategies. Afterward, the human ovarian cancer cell line SK-OV-3, cervical cancer cell line HeLa, and endometrial cancer cell line HEC-1-B were selected for experimetal valification...
May 1, 2018: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/29718116/interleukin-6-knock-out-inhibits-aging-related-accumulation-of-p53-in-the-mouse-myocardium
#6
Tomasz A Bonda, Magdalena Dziemidowicz, Magdalena Cieslinska, Ewa Tarasiuk, Natalia Wawrusiewicz-Kurylonek, Izabela Bialuk, Maria M Winnicka, Karol A Kaminski
Interleukin 6 (IL6) and p53 are linked by mutual regulatory mechanisms and are both upregulated in aging. The aim of this study was to evaluate the effects of aging and IL-6 on expression of p53 in the mouse heart. Male C57BL6/J wild-type (WT) and IL6 knock-out (IL6KO) mice at the age of 4-5 months (young adult) and 24-30 months (old) were used. Myocardial expression of proteins: p53, p21, Mdm2, and phospho-Akt/Akt was estimated using western blotting and expression of p53 and p21 mRNA using real-time-PCR. Expression of p53 protein was lower in IL6KO than in WT hearts...
April 28, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29699606/insulin-receptor-substrate-2-a-bridge-between-hippo-and-akt-pathways
#7
Sun-Hye Jeong, Dae-Sik Lim
NAFLD induces the development of advanced liver diseases such as NASH and liver cancer. Therefore, understanding the mechanism of NAFLD development is critical for its prevention and treatment. Ablation of PTEN or Hippo pathway components induces liver cancer in a murine model by hyperactive AKT or YAP/TAZ, respectively. Although the regulation of these two pathways occurs in the same hepatocyte, the details of crosstalk between Hippo-YAP/TAZ and PTEN-AKT pathways in liver homeostasis and tumorigenesis still remain unclear...
April 27, 2018: BMB Reports
https://www.readbyqxmd.com/read/29694984/camel-milk-ameliorates-5-fluorouracil-induced-renal-injury-in-rats-targeting-mapks-nf-%C3%AE%C2%BAb-and-pi3k-akt-enos-pathways
#8
Hany H Arab, Samir A Salama, Ibrahim A Maghrabi
BACKGROUND/AIMS: The clinical utility of 5-fluorouracil (5-FU) is limited by its nephrotoxicity. Camel milk (CM) has previously displayed beneficial effects in toxicant-induced nephropathies. The current study aimed to investigate the potential of CM to attenuate 5-FU-induced nephrotoxicity in rats. METHODS: Renal tissues were studied in terms of oxidative stress, inflammation and apoptosis. The levels of renal injury markers, inflammatory cytokines along with NOX-1, Nrf-2 and HO-1 were assessed by ELISA...
April 20, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29687202/attenuation-of-aluminum-chloride-induced-neuroinflammation-and-caspase-activation-through-the-akt-gsk-3%C3%AE-pathway-by-hesperidin-in-wistar-rats
#9
Arokiasamy Justin-Thenmozhi, Mathiyazahan Dhivya Bharathi, Ramaraj Kiruthika, Thamilarasan Manivasagam, Anupom Borah, Musthafa Mohamed Essa
Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. Previous reports from our laboratory indicated the neuroprotective effect of hesperidin against aluminum chloride (AlCl3 )-induced memory loss, acetylcholine esterase hyperactivity, oxidative stress, and enhanced expression of amyloid β protein biosynthesis-related markers. However, their role on AlCl3 -induced inflammation, caspase activation, Tau pathology, altered Akt/GSK 3β signaling pathway, and Aβ clearance marker has not yet been fully elucidated...
April 23, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29678610/nrf2-protects-against-acute-lung-injury-and-inflammation-by-modulating-tlr4-and-akt-signaling
#10
Jia Yan, Jingjie Li, Lei Zhang, Yu Sun, Jue Jiang, Yan Huang, Hui Xu, Hong Jiang, Rong Hu
Lung injury, which is associated with systemic inflammatory responses, is a common problem with significant morbidity and mortality. Here, we examined the involvement of toll-like receptor 4 (TLR4) and nuclear factor erythroid 2-related factor 2 (Nrf2) on intestinal ischemia-reperfusion (I/R)-induced lung injury in vivo and in vitro. Analysis of lung tissues in Nrf2-knockout mice by western blotting, immunohistochemistry, and TUNEL assay, and analysis of bronchoalveolar lavage fluid showed that Nrf2 deficiency upregulated TLR4, enhanced I/R-induced lung injury, apoptosis, inflammation, and autophagy, and increased the I/R-induced inactivation of Akt...
April 17, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29674975/possible-role-of-nadph-oxidase-4-in-angiotensin-ii-induced-muscle-wasting-in-mice
#11
Tomoyasu Kadoguchi, Kazunori Shimada, Hiroshi Koide, Tetsuro Miyazaki, Tomoyuki Shiozawa, Shuhei Takahashi, Tatsuro Aikawa, Shohei Ouchi, Kenichi Kitamura, Yurina Sugita, Al Shahi Hamad, Mitsuhiro Kunimoto, Yayoi Sato-Okabayashi, Koji Akita, Kikuo Isoda, Hiroyuki Daida
Background: Muscle wasting is a debilitating phenotype associated with chronic heart failure (CHF). We have previously demonstrated that angiotensin II (AII) directly induces muscle wasting in mice through the activation of NADPH oxidase (Nox). In this study, we tested the hypothesis that deficiency of NADPH oxidase 4 (Nox4), a major source of oxidative stress, ameliorates AII-induced muscle wasting through the regulation of redox balance. Methods and Results: Nox4 knockout (KO) and wild-type (WT) mice were used...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29667662/camel-milk-attenuates-methotrexate-induced-kidney-injury-via-activation-of-pi3k-akt-enos-signaling-and-intervention-with-oxidative-aberrations
#12
Hany H Arab, Samir A Salama, Ibrahim A Maghrabi
Methotrexate (MTX) is a classical chemotherapeutic agent with nephrotoxicity as the most disturbing adverse effect. So far, its underlying molecular mechanisms, particularly PI3K/Akt/eNOS transduction, are inadequately explored. Several antioxidant modalities have been characterized to ameliorate MTX-induced renal injury. In this regard, Camel milk (CM) is a natural product with recognized antioxidant and anti-inflammatory features. Thus, the current study aimed to investigate the potential ameliorating effects of CM in MTX-induced kidney injury in rats...
April 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29644781/inpp4b-overexpression-and-c-kit-downregulation-in-human-achalasia
#13
E Bonora, F Bianco, A Stanzani, F Giancola, A Astolfi, V Indio, C Evangelisti, A M Martelli, E Boschetti, M Lugaresi, A Ioannou, F Torresan, V Stanghellini, P Clavenzani, M Seri, A Moonen, K Van Beek, M Wouters, G E Boeckxstaens, G Zaninotto, S Mattioli, R De Giorgio
BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders)...
April 11, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29614107/functional-disruption-of-the-golgi-apparatus-protein-arf1-sensitizes-mda-mb-231-breast-cancer-cells-to-the-antitumor-drugs-actinomycin-d-and-vinblastine-through-erk-and-akt-signaling
#14
Charlotte Luchsinger, Marcelo Aguilar, Patricia V Burgos, Pamela Ehrenfeld, Gonzalo A Mardones
Increasing evidence indicates that the Golgi apparatus plays active roles in cancer, but a comprehensive understanding of its functions in the oncogenic transformation has not yet emerged. At the same time, the Golgi is becoming well recognized as a hub that integrates its functions of protein and lipid biosynthesis to signal transduction for cell proliferation and migration in cancer cells. Nevertheless, the active function of the Golgi apparatus in cancer cells has not been fully evaluated as a target for combined treatment...
2018: PloS One
https://www.readbyqxmd.com/read/29601143/synthetic-%C3%AE-mangostin-dilaurate-strongly-suppresses-wide-spectrum-organ-metastasis-in-a-mouse-model-of-mammary-cancer
#15
Masa-Aki Shibata, Hitomi Hamaoka, Junji Morimoto, Tadashi Kanayama, Kentaro Maemura, Yuko Ito, Munekazu Iinuma, Yoichi Kondo
We previously reported that, in a mouse model of mammary cancer, α-mangostin alone exhibits anti-metastatic properties. To enhance this anti-metastatic effect, we examined the efficacy of synthetic α-mangostin dilaurate (MGD), prepared by adding lauric acid to α-mangostin, in the same experimental system wherein mice bearing mammary tumors are exposed to dietary MGD at 0, 2000, and 4000 ppm. Lauric acid has a high propensity for lymphatic absorbtion, which is the most common pathway of initial dissemination of many solid malignancies...
March 30, 2018: Cancer Science
https://www.readbyqxmd.com/read/29595853/phenethyl-isothiocyanate-in-combination-with-dibenzoylmethane-inhibits-the-androgen-independent-growth-of-prostate-cancer-cells
#16
Huarong Huang, Yan He, Lanyue Zhang, Hongping Xiang, Dongli Li, Wenfeng Liu, Xue-Tao Xu, Susan Goodin, Kun Zhang, Xi Zheng
Phenethyl isothiocyanate (PEITC) is a naturally occurring compound found in some cruciferous vegetables. Dibenzoylmethane (DBM) is a minor constituent of licorice. Both compounds have been shown to exert anticancer activities. In the present study, we determined the effects of PEITC and DBM alone or in combination on androgen-independent growth of human prostate cancer cells cultured in vitro and prostate VCaP xenograft tumors in severe combined immunodeficient (SCID) mice. PEITC and DBM in combination had stronger effects on inhibiting the growth and inducing apoptosis than either compound alone in cultured prostate cancer cells...
March 29, 2018: Food & Function
https://www.readbyqxmd.com/read/29568075/inhibition-of-endothelial-nitric-oxide-synthase-reverses-the-effect-of-exercise-on-improving-cognitive-function-in-hypertensive-rats
#17
Liying Zhang, Haiqing Zheng, Jing Luo, Lili Li, Xiaona Pan, Ting Jiang, Chongjun Xiao, Zhong Pei, Xiquan Hu
Hypertension-induced endothelial dysfunction is associated with β-amyloid (Aβ) deposition, a typical pathology of Alzheimer's disease (AD). Endothelial nitric oxide synthase (eNOS) phosphorylation, impaired by phosphatidylinositol 3-kinase (PI3K)/protein kinase-B(Akt) pathway abnormalities in hypertensive rats, has a critical role in endothelial function. However, it is unknown whether eNOS participates in the hypertension-induced pathology of AD. In this study, we investigated the role of eNOS in Aβ deposition and cognitive function in stroke-prone spontaneously hypertensive (SHRSP) rats...
March 22, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29541346/-calbindin-d28k-in-the-brain-influences-the-expression-of-cellular-prion-protein
#18
Yeong-Min Yoo, Eui-Bae Jeung
The phenotypes of calbindin-D9k - ( CaBP-9k -) knockout (KO), calbindin - D28k - ( CaBP-28k -) KO, and CaBP-9k/28k -KO mice are similar to those of wild-type (WT) mice due to the compensatory action of other calcium transport proteins. In this study, we investigated the expression of cellular prion protein (PrPC ) in the brains of CaBP-9k -, CaBP-28k -, and CaBP-9k/28k -KO mice. PrPC expression was significantly upregulated in the brain of all three strains. Levels of phospho-Akt (Ser473) and phospho-Bad (Ser136) were significantly elevated, but those of phospho-ERK and phospho-Bad (Ser155 and 112) were significantly reduced in the brains of CaBP-9k -, CaBP-28k -, and CaBP-9k/28k -KO mice...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29512685/deguelin-exerts-anticancer-activity-of-human-gastric-cancer-mgc-803-and-mkn-45-cells-in-vitro
#19
Wen Kang, Xiao Zheng, Ping Wang, Shanyu Guo
During the pathogenesis of gastric cancer, Akt signaling is considered as a pivotal inducer of gastric cancer development. Here we report the identification of anticancer activities of deguelin, a natural agent that inhibits Akt signaling. When applied to MGC-803 and MKN-45 cells, deguelin suppressed the proliferation and arrested cell cycle by p21-mediated inhibition of cyclin E. We further present in vitro evidence that deguelin promoted apoptosis of cancer cells by decreasing the phospho-Akt signaling and affecting expression of the apoptosis-associated genes Bax and Bcl-2...
June 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29510727/eef1d-overexpression-promotes-osteosarcoma-cell-proliferation-by-facilitating-akt-mtor-and-akt-bad-signaling
#20
Dong-Dong Cheng, Shi-Jie Li, Bin Zhu, Shu-Min Zhou, Qing-Cheng Yang
BACKGROUND: Dysregulation of eukaryotic translation elongation factor 1 delta (EEF1D) in cancers has been reported; however, the role and mechanisms of EEF1D in osteosarcoma remain poorly understood. The aim of this study is to investigate the expression and role of EEF1D in osteosarcoma and to elucidate its underlying mechanisms. METHODS: The expression of EEF1D in osteosarcomas and cell lines was evaluated by qRT-PCR, Western blotting and immunohistochemistry...
March 6, 2018: Journal of Experimental & Clinical Cancer Research: CR
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