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https://www.readbyqxmd.com/read/28324760/trpv1-agonism-inhibits-endothelial-cell-inflammation-via-activation-of-enos-no-pathway
#1
Youping Wang, Lin Cui, Hui Xu, Suxiao Liu, Feiyun Zhu, Fengna Yan, Si Shen, Mingjun Zhu
BACKGROUND AND AIMS: Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca(2+)-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation...
March 10, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#2
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324019/no-mediated-regulation-of-glut-by-t3-and-fsh-in-rat-granulosa-cells
#3
Ye Tian, Yu Ding, Juan Liu, Dai Heng, Kaili Xu, Wenbo Liu, Cheng Zhang
Thyroid hormones (THs) are important for normal reproductive function. Although 3,5,3'-triiodothyronine (T3) enhances follicle-stimulating hormone (FSH)-induced preantral follicle growth and granulosa cells development in vitro, little is known about the molecular mechanisms regulating ovarian development via glucose. In this study, we investigated whether and how T3 combines with FSH to regulate glucose transporter protein (GLUT) expression and glucose uptake in granulosa cells. Here, we present evidence that T3 and FSH co-treatment significantly increased GLUT-1/GLUT-4 expression, and translocation in cells, as well as glucose uptake...
March 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323869/tyrosine-mutated-aav2-mediated-shrna-silencing-of-pten-promotes-axon-regeneration-of-adult-optic-nerve
#4
ZhengRu Huang, ZiZhong Hu, Ping Xie, QingHuai Liu
Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm...
2017: PloS One
https://www.readbyqxmd.com/read/28320107/pre-conditioning-with-tanshinone-iia-attenuates-the-ischemia-reperfusion-injury-caused-by-liver-grafts-via-regulation-of-hmgb1-in-rat-kupffer-cells
#5
Xuanfei Li, Yakun Wu, Wenfeng Zhang, Jianping Gong, Yao Cheng
OBJECTIVE: We have evaluated the protective mechanism of tanshinone IIA in ischemia/reperfusion injury (IRI) induced by liver grafts, revealing novel supplementary immunotherapy for liver transplantation. METHODS: The tanshinone IIA preconditioning group (TP group) was pretreated with tanshinone IIA via intraperitoneal injection for 1 week before receiving orthotopic liver transplantation with hepatic arterial ischemia for 30min. The sham-operation group (SO group), control graft group (CG group) and IRI group were pretreated with an equivalent volume of normal saline...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320094/lncrna-meg3-had-anti-cancer-effects-to-suppress-pancreatic-cancer-activity
#6
Lei Gu, Jiaqiang Zhang, Minmin Shi, Qian Zhan, Baiyong Shen, Chenghong Peng
AIM: The aim of this study was to explain the mechanism of lncRNA MEG 3 in pancreatic cancer. METHODS: We were collecting 30 pancreatic cancer patients, taking the sample from these patients. We measured the PI3K protein expressions from 30 patients by IHC and WB methods and MEG 3 expression by RT-PCR, and analyzed the relationship between PI3K protein expression and pancreatic cancer patients' clinical pathology and the correlation between lncRNA MEG 3 and PI3K...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320092/inhibition-of-pi3k-akt-mtor-signaling-pathway-promotes-autophagy-of-articular-chondrocytes-and-attenuates-inflammatory-response-in-rats-with-osteoarthritis
#7
Jian-Feng Xue, Zhong-Min Shi, Jian Zou, Xiao-Lin Li
OBJECTIVE: This study aims to explore the relationship between PI3K/AKT/mTOR signaling pathway and autophagy of articular chondrocytes in rats with osteoarthritis (OA). METHODS: Rat articular chondrocytes were isolated and cultured, and then induced by protein inhibitors of PI3K/AKT/mTOR signaling pathway. Chondrocytes were assigned into blank group, IL-1β induction group (IL-1β group), PI3K inhibitor+IL-1β induction group (PI3Ki+IL-1β group), AKT inhibitor+IL-1β induction group (AKTi+IL-1β group) and mTOR inhibitor+IL-1β induction group (mTORi+IL-1β group)...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319194/genome-wide-analysis-of-brain-and-gonad-transcripts-reveals-changes-of-key-sex-reversal-related-genes-expression-and-signaling-pathways-in-three-stages-of-monopterus-albus
#8
Wei Chi, Yu Gao, Qing Hu, Wei Guo, Dapeng Li
BACKGROUND: The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus). How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male) from the rice field eel to investigate changes in transcriptional level during the sex reversal process...
2017: PloS One
https://www.readbyqxmd.com/read/28319045/akt-mediated-stabilization-of-histone-methyltransferase-whsc1-promotes-prostate-cancer-metastasis
#9
Ni Li, Wei Xue, Huairui Yuan, Baijun Dong, Yufeng Ding, Yongfeng Liu, Min Jiang, Shan Kan, Tongyu Sun, Jiale Ren, Qiang Pan, Xiang Li, Peiyuan Zhang, Guohong Hu, Yan Wang, Xiaoming Wang, Qintong Li, Jun Qin
Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28317089/egcg-protects-against-homocysteine-induced-human-umbilical-vein-endothelial-cells-apoptosis-by-modulating-mitochondrial-dependent-apoptotic-signaling-and-pi3k-akt-enos-signaling-pathways
#10
Shumin Liu, Zhengwu Sun, Peng Chu, Hailong Li, Anil Ahsan, Ziru Zhou, Zonghui Zhang, Bin Sun, Jingjun Wu, Yalin Xi, Guozhu Han, Yuan Lin, Jinyong Peng, Zeyao Tang
Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study...
March 19, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28315368/the-emerging-role-of-pi3k-akt-mediated-epigenetic-regulation-in-cancer
#11
REVIEW
Jennifer M Spangle, Thomas M Roberts, Jean J Zhao
The PI3-kinase/AKT pathway integrates signals from external cellular stimuli to regulate essential cellular functions, and is frequently aberrantly activated in human cancers. Recent research demonstrates that tight regulation of the epigenome is critical in preserving and restricting transcriptional activation, which can impact cellular growth and proliferation. In this review we examine mechanisms by which the PI3K/AKT pathway regulates the epigenome to promote oncogenesis, and highlight how connections between PI3K/AKT and the epigenome may impact the future therapeutic treatment of cancers featuring a hyperactivated PI3K/AKT pathway...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315345/inositol-hexaphosphate-suppresses-colorectal-cancer-cell-proliferation-via-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling-cascade-in-a-1-2-dimethylhydrazine-induced-rat-model
#12
Wenyang Yu, Cuiping Liu, Xin Li, Fuguo Yang, Lixue Cheng, Chang Liu, Yang Song
Colorectal cancer (CRC) is common worldwide, and most treatments for CRC have undesirable side effects. Many researchers have demonstrated that inositol hexaphosphate (IP6) has potent anticarcinogenic activity against CRC and no apparent toxicity to normal cells. However, the underlying mechanism is still unclear. In this study, we investigated the anticancer and anti-proliferative properties of IP6 in CRC and its possible mechanisms during this chemopreventive process. We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28315323/increased-serotonin-signaling-contributes-to-the-warburg-effect-in-pancreatic-tumor-cells-under-metabolic-stress-and-promotes-growth-of-pancreatic-tumors-in-mice
#13
Shu-Heng Jiang, Jun Li, Fang-Yuan Dong, Jian-Yu Yang, De-Jun Liu, Xiao-Mei Yang, Ya-Hui Wang, Min-Wei Yang, Xue-Liang Fu, Xiao-Xin Zhang, Qing Li, Xiu-Feng Pang, Yan-Miao Huo, Jiao Li, Jun-Feng Zhang, Ho-Young Lee, Su-Jae Lee, Wen-Xin Qin, Jian-Ren Gu, Yong-Wei Sun, Zhi-Gang Zhang
BACKGROUND & AIMS: The desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. METHODS: We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+); Trp53(R172H/+); Pdx1-Cre; (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples...
March 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28315173/ricolinostat-a-selective-hdac6-inhibitor-shows-anti-lymphoma-cell-activity-alone-and-in-combination-with-bendamustine
#14
Maria Cosenza, Monica Civallero, Luigi Marcheselli, Stefano Sacchi, Samantha Pozzi
Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry...
March 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28314838/a-phase-i-study-of-abiraterone-acetate-combined-with-bez235-a-dual-pi3k-mtor-inhibitor-in-metastatic-castration-resistant-prostate-cancer
#15
Xiao X Wei, Andrew C Hsieh, Won Kim, Terence Friedlander, Amy M Lin, Mirela Louttit, Charles J Ryan
LESSONS LEARNED: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored. BACKGROUND: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28306514/park2-depletion-connects-energy-and-oxidative-stress-to-pi3k-akt-activation-via-pten-s-nitrosylation
#16
Amit Gupta, Sara Anjomani-Virmouni, Nikos Koundouros, Maria Dimitriadi, Rayman Choo-Wing, Adamo Valle, Yuxiang Zheng, Yu-Hsin Chiu, Sameer Agnihotri, Gelareh Zadeh, John M Asara, Dimitrios Anastasiou, Mark J Arends, Lewis C Cantley, George Poulogiannis
PARK2 is a gene implicated in disease states with opposing responses in cell fate determination, yet its contribution in pro-survival signaling is largely unknown. Here we show that PARK2 is altered in over a third of all human cancers, and its depletion results in enhanced phosphatidylinositol 3-kinase/Akt (PI3K/Akt) activation and increased vulnerability to PI3K/Akt/mTOR inhibitors. PARK2 depletion contributes to AMPK-mediated activation of endothelial nitric oxide synthase (eNOS), enhanced levels of reactive oxygen species, and a concomitant increase in oxidized nitric oxide levels, thereby promoting the inhibition of PTEN by S-nitrosylation and ubiquitination...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28304405/the-erbb3-receptor-tyrosine-kinase-negatively-regulates-paneth-cells-by-pi3k-dependent-suppression-of-atoh1
#17
Dana Almohazey, Yuan-Hung Lo, Claire V Vossler, Alan J Simmons, Jonathan J Hsieh, Edie B Bucar, Michael A Schumacher, Kathryn E Hamilton, Ken S Lau, Noah F Shroyer, Mark R Frey
Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn's disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche...
March 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28303961/the-metabolic-waste-ammonium-regulates-mtorc2-and-mtorc1-signaling
#18
Ahmad Merhi, Paul Delrée, Anna Maria Marini
Two structurally and functionally distinct mammalian TOR complexes control cell growth and metabolism in physiological and pathological contexts including cancer. Upregulated glutaminolysis is part of the metabolic reprogramming occurring in cancer, providing fuels for growth but also liberating ammonium, a potent neurotoxic waste product. Here, we identify ammonium as a novel dose-dependent signal mediating rapid mTORC2 activation and further regulating mTORC1. We show that ammonium induces rapid RICTOR-dependent phosphorylation of AKT-S473, a process requiring the PI3K pathway and further involving the Src-family kinase YES1, the FAK kinase and the ITGβ1 integrin...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303260/evidence-for-an-additive-neurorestorative-effect-of-simultaneously-administered-cdnf-and-gdnf-in-hemiparkinsonian-rats-implications-for-different-mechanism-of-action
#19
Merja H Voutilainen, Francesca De Lorenzo, Polina Stepanova, Susanne Bäck, Li-Ying Yu, Päivi Lindholm, Eeva Pörsti, Mart Saarma, Pekka T Männistö, Raimo K Tuominen
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28303030/formyl-peptide-receptors-promotes-neural-differentiation-in-mouse-neural-stem-cells-by-ros-generation-and-regulation-of-pi3k-akt-signaling
#20
Liang Zhang, Guan Wang, Xingxing Chen, Xin Xue, Qiaonan Guo, Mingyong Liu, Jianhua Zhao
This study aimed to determine whether formyl peptide receptors (FPRs) regulated the differentiation of neural stem cells (NSCs). FPRs promote the migration of NSCs both in vitro and in vivo. However, the role of FPRs during differentiation of NSCs is unknown. Analysis by Western blot showed significantly increased expression of FPR1 and FPR2 during differentiation of NSCs. The activation of FPRs promotes NSCs to differentiate into neurons with more primary neurites and branch points and longer neurites per cell...
March 16, 2017: Scientific Reports
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