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Padmanaban Mohanan, Sathiyamoorthy Subramaniyam, Ramya Mathiyalagan, Deok-Chun Yang
Ginseng has gained its popularity as an adaptogen since ancient days because of its triterpenoid saponins, known as ginsenosides. These triterpenoid saponins are unique and classified as protopanaxatriol and protopanaxadiol saponins based on their glycosylation patterns. They play many protective roles in humans and are under intense research as various groups continue to study their efficacy at the molecular level in various disorders. Ginsenosides Rb1 and Rg1 are the most abundant ginsenosides present in ginseng roots, and they confer the pharmacological properties of the plant, whereas ginsenoside Rg3 is abundantly present in Korean Red Ginseng preparation, which is highly known for its anticancer effects...
April 2018: Journal of Ginseng Research
Juhi Bagaitkar, Jing Huang, Melody Yue Zeng, Nancy K Pech, Darlene A Monlish, Lizet J Perez-Zapata, Irina Miralda, Laura G Schuettpelz, Mary C Dinauer
The phagocyte reduced NAD phosphate (NADPH) oxidase generates superoxide, the precursor to reactive oxygen species (ROS) that has both antimicrobial and immunoregulatory functions. Inactivating mutations in NADPH oxidase alleles cause chronic granulomatous disease (CGD), characterized by enhanced susceptibility to life-threatening microbial infections and inflammatory disorders; hypomorphic NADPH oxidase alleles are associated with autoimmunity. Impaired apoptotic cell (AC) clearance is implicated as an important contributing factor in chronic inflammation and autoimmunity, but the role of NADPH oxidase-derived ROS in this process is incompletely understood...
May 24, 2018: Blood
Shanshan Sun, Yansheng Wu, Wenyu Guo, Feng Yu, Lingping Kong, Yu Ren, Yu Wang, Xiaofeng Yao, Chao Jing, Chao Zhang, Mingyang Liu, Yuqing Zhang, Minghui Zhao, Zhaoqing Li, Chuanqiang Wu, Yu Qiao, Jingxuan Yang, Xudong Wang, Lun Zhang, Min Li, Xuan Zhou
Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA ( HOTAIR ) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Huguette Gaelle Ngassa Mbenda, Weilin Zeng, Yao Bai, Faiza Amber Siddiqui, Zhaoqing Yang, Liwang Cui
Artemisinin resistance in Plasmodium falciparum was associated with mutations in the propeller domain of the PfK13 gene and increased phosphatidylinositol-3'-kinase (PfPI3K) activity. Assessment of the genetic diversity of the PfK13 ortholog PvK12 in Plasmodium vivax field samples from the same hotspots of P. falciparum artemisinin resistance revealed a limited genetic diversity of PvK12. Following the same logic, we analyzed genetic variations of the PvPI3K gene in 188 P. vivax field isolates from two geographic locations along the China-Myanmar border...
July 2018: Infection, Genetics and Evolution
Dai-Qiao Ouyang, Li-Zhong Liang, Zun-Fu Ke, Guang-Sen Zheng, De-Sheng Weng, Wei-Fa Yang, Yu-Xiong Su, Gui-Qing Liao
BACKGROUND: Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported. METHODS: P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data...
June 2017: Head & Neck
L W R Tay, Z Wang, G Du
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a lipid second messenger that regulates a wide array of essential cellular events, such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, adhesion, and motility. To control the spatiotemporal production of PI(4,5)P2, the activity of type 1 phosphotidylinositol-4-phosphate-5-kinases (PIPKIs) is tightly regulated by small GTPases and another signaling lipid, phosphatidic acid (PA). It is of interest that PI(4,5)P2 is also a critical cofactor for the activation of the PA-generating enzyme, phospholipase D (PLD)...
2017: Methods in Enzymology
Alexandre Bozec, Nathalie Ebran, Nina Radosevic-Robin, Emmanuel Chamorey, Hedi Ben Yahia, Serge Marcie, Mathieu Gautier, Frédérique Penault-Llorca, Gérard Milano
BACKGROUND: The purpose of this study was to investigate the effects of combining the phosphotidylinositol-3-kinase (PI3K) inhibitor buparlisib (BKM)120 with the anti-epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy (RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC). METHODS: We evaluated the antitumor efficacy of BKM120, cetuximab, and RT, administered alone or in combination, using the human PIK3CA-mutated HNSCC cell line, CAL33, injected into the floor of the mouth of nude mice...
January 2017: Head & Neck
Jessica L Geiger, Julie E Bauman, Michael K Gibson, William E Gooding, Prakash Varadarajan, Athanasios Kotsakis, Daniel Martin, Jorge Silvio Gutkind, Matthew L Hedberg, Jennifer R Grandis, Athanassios Argiris
BACKGROUND: Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. METHODS: This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy...
December 2016: Head & Neck
Daniel W Bowles, Mark Kochenderfer, Allen Cohn, Lucas Sideris, Nghia Nguyen, Vivian Cline-Burkhardt, Ian Schnadig, Minsig Choi, Lisle Nabell, Arvind Chaudhry, Robert Ruxer, Antonio Ucar, Diana Hausman, Luke Walker, Alexander Spira, Antonio Jimeno
BACKGROUND: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase/mammalian target of rapamycin signaling pathway is frequently altered in colorectal cancer (CRC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. This randomized phase II study evaluated cetuximab with or without PX-866 in patients with metastatic, anti-epidermal growth factor receptor-naive, KRAS codon 12 and 13 wild-type CRC. PATIENTS AND METHODS: Patients with metastatic CRC who had received both oxaliplatin and irinotecan were randomized (1:1) to cetuximab (400 mg/m2 loading then 250 mg/m2 weekly) with or without PX-866 (8 mg orally daily; arms A and B, respectively)...
December 2016: Clinical Colorectal Cancer
Bénédicte Rysman, François Mouawad, Abigaëlle Gros, Amélie Lansiaux, Dominique Chevalier, Samuel Meignan
Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptor (HER) family. The main characteristic of HER3 is that it does not possess tyrosine kinase activity, unlike other HERs. The role of HER3 in tumorigenesis has now been recognized, particularly in head and neck squamous cell carcinomas (HNSCCs). Despite conflicting studies, HER3 was found to be overexpressed in HNSCC samples, and correlates with disease progression and poor survival, especially when it is coexpressed with other HERs...
April 2016: Head & Neck
Xiao-Jun Li, Su-Juan Dai, Shao-Wei Liu, Jia-Meng Liu, Li Chen, Lin Hu, Cheng-Hang Sun
A novel actinomycete, designated strain S6R2A4-9(T), was isolated from a soil sample collected from a karst cave in Henan Province, China, and subjected to a polyphasic taxonomic study. This isolate grew optimally at 25-28 °C, pH 6.5-8.0 and in the absence of NaCl. The substrate mycelium of the isolate was well developed with irregular branches. Aerial mycelium fragmented into long, rod-shaped elements. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain S6R2A4-9(T) resided in the cluster of the genus Tenggerimyces within the family Nocardioidaceae and shared the highest 16S rRNA gene sequence similarity (98...
March 2016: International Journal of Systematic and Evolutionary Microbiology
I K H Hadem, R Sharma
Insulin-like growth factor-1 (IGF-1), a key mediator of growth hormone action in mammals, plays an important role in the regulation of cellular and tissue functions. In the present investigation, the normal age-dependent and effect of dietary restriction on the expression levels of serum IGF-1, phosphotidylinositol 3-kinase (PI3K), and protein kinase B (PKB/Akt) in the liver, kidney and skeletal muscles of 1-, 9-, and 21-month-old female mice were ascertained using ELISA and Western blot analysis. Results showed that serum IGF-1 peaks at 9-month-old and decreases in older age...
March 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Hong-Min Sun, Tao Zhang, Yu-Zhen Wei, Hong-Yu Liu, Li-Yan Yu, Yu-Qin Zhang
A novel aerobic actinomycete, designated strain I12A-02601T, was isolated from a desert soil crusts sample collected from the Shapotou region of Tengger Desert, north-west China. The substrate mycelia of this isolate were well-developed and branched, but not fragmented. The maturity aerial mycelia formed short chains of small, rod-shaped spores. The strain contained ll-diaminopimelic acid, dd-diaminopimelic acid, galactose, glucose, ribose and xylose in its whole-cell hydrolysates. The polar lipids consisted of diphosphatidylglycerol, N-acetylglucosamine-containing phospholipids, phosphatidylinositolmannoside and glycolipids...
October 2015: International Journal of Systematic and Evolutionary Microbiology
C Zhu, S Wang, B Wang, F Du, C Hu, H Li, Y Feng, R Zhu, M Mo, Y Cao, A Li, X Yu
Human age-related retinal diseases, such as age-related macular degeneration (AMD), are intimately associated with decreased tissue oxygenation and hypoxia. Different antioxidants have been investigated to reverse AMD. In the present study, we describe the antioxidant 17β-estradiol (βE2) and investigate its protective effects on retinal neurons. Fourteen days after ovariectomy, adult Sprague-Dawley rats were exposed to 8000-lux light for 12h to induce retinal degeneration. Reactive oxygen species (ROS) levels were assessed by confocal fluorescence microscopy using 2,7-dichlorofluorescein diacetate...
September 24, 2015: Neuroscience
Jun Feng, Blake Mertz
Focal adhesion kinase (FAK) is a protein tyrosine kinase that is ubiquitously expressed, recruited to focal adhesions, and engages in a variety of cellular signaling pathways. Diverse cellular responses, such as cell migration, proliferation, and survival, are regulated by FAK. Prior to activation, FAK adopts an autoinhibited conformation in which the FERM domain binds the kinase domain, blocking access to the activation loop and substrate binding site. Activation of FAK occurs through conformational change, and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) are known to facilitate this process...
2015: PloS One
E I Tyulkova, L A Vataeva, O V Vetrovoy, D Yu Romanovsky
The present study was aimed at the analysis of spatial learning abilities in the Morris water maze (working memory) as well as hippocampal levels of phosphatidylinositol 4,5-diphosphates (TPI), phosphatidylinositol 4-phosphates (DPI), phosphotidylinositols (MPI), and expression of the type 1 inositol 1,4,5-trisphosphate receptor (IR3R1) in rats exposed to severe hypobaric hypoxia (ascent to 11 km, 3 h) on prenatal days 14-16 (group 1) or 17-19 (group 2). Exposure to severe hypoxia led to significant elevation of TP 1 and DPI hippocampal levels in juvenile and adult rats in the group 1, however these changes were more pronounced in juvenile rats than in adults...
March 2015: Zhurnal Evoliutsionnoĭ Biokhimii i Fiziologii
Yue Wang, Xiu Long Niu, Xiao Qin Guo, Jing Yang, Ling Li, Ye Qu, Cun Xiu Hu, Li Qun Mao, Dan Wang
About 40-60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1...
June 2015: Journal of Molecular Endocrinology
Hong Wang, Aileen X Wang, Kevin Aylor, Eugene J Barrett
AIMS/HYPOTHESIS: As insulin entry into muscle interstitium is rate-limiting for its overall peripheral action, defining the route and regulation of its entry is critical. Caveolin-1 is required for caveola formation in vascular endothelial cells (ECs) and for EC insulin uptake. Whether this requirement reflects simply the need for caveola availability or involves a more active role for caveolae/caveolin-1 is not known. Here, we examined the role of insulin-stimulated tyrosine 14 (Tyr(14))-caveolin-1 phosphorylation in mediating EC insulin uptake and the role of cellular Src-kinase (cSrc), TNF-α/IL-6 and high fat diet (HFD) in regulating this process...
June 2015: Diabetologia
Yi Xie, Takeo Nakanishi, Karthika Natarajan, Lowell Safren, Anne W Hamburger, Arif Hussain, Douglas D Ross
Phosphorylated cyclic-AMP (cAMP) response element binding protein (p-CREB) is a downstream effector of a variety of important signaling pathways. We investigated whether the human BCRP promoter contains a functional cAMP response element (CRE). 8Br-cAMP, a cAMP analogue, increased the activity of a BCRP promoter reporter construct and BCRP mRNA in human carcinoma cells. Epidermal growth factor receptor (EGFR) pathway activation also led to an increase in p-CREB and in BCRP promoter reporter activity via two major downstream EGFR signaling pathways: the phosphotidylinositol-3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinase (MAPK) pathway...
March 2015: Biochimica et Biophysica Acta
Antonio Jimeno, Julie E Bauman, Charles Weissman, Douglas Adkins, Ian Schnadig, Patrice Beauregard, Daniel W Bowles, Alexander Spira, Benjamin Levy, Nagashree Seetharamu, Diana Hausman, Luke Walker, Charles M Rudin, Keisuke Shirai
INTRODUCTION: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is frequently altered in head and neck squamous cell cancer (HNSCC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory HNSCC...
April 2015: Oral Oncology
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