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https://www.readbyqxmd.com/read/28936799/proteomic-features-of-colorectal-cancer-identify-tumor-subtypes-independent-of-oncogenic-mutations-and-independently-predict-relapse-free-survival
#1
Callisia N Clarke, Michael S Lee, Wei Wei, Ganiraju Manyam, Zhi-Qin Jiang, Yiling Lu, Jeffrey Morris, Bradley Broom, David Menter, Eduardo Vilar-Sanchez, Kanwal Raghav, Cathy Eng, George J Chang, Iris Simon, Rene Bernards, Michael Overman, Gordon B Mills, Dipen Maru, Scott Kopetz
BACKGROUND: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. METHODS: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis...
September 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28931237/histone-methyltransferase-set8-epigenetically-reprograms-host-immune-responses-to-assist-mycobacterial-survival
#2
Vikas Singh, Praveen Prakhar, R S Rajmani, Kasturi Mahadik, Salik Miskat Borbora, Kithiganahalli Narayanaswamy Balaji
NQO1 and TRXR1 are important host reductases implicated in the regulation of inflammation and apoptosis. Although the transcriptional machinery governing these processes have been extensively investigated, the associated epigenetic regulatory events remain unclear. Here, we report that SET8, a histone H4 lysine 20 monomethylase (H4K20me1), is highly induced during Mycobacterium tuberculosis infection that orchestrates immune evasion strategies through the induction of NQO1 and TRXR1 in vivo. SET8, along with FoxO3a, mediates an active NQO1-PGC1-α complex, which promotes the anti-inflammatory M2 macrophage phenotype, and assists TRXR1-regulated arrest of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28930190/oligonol-a-low-molecular-weight-polyphenol-derived-from-lychee-alleviates-muscle-loss-in-diabetes-by-suppressing-atrogin-1-and-murf1
#3
Hung-Wen Liu, Yen-Ju Chen, Yun-Ching Chang, Sue-Joan Chang
Stimulation of the ubiquitin-proteasome pathway-especially E3 ubiquitin ligases Atrogin-1 and MuRF1-is associated with muscle loss in diabetes. Elevated lipid metabolites impair myogenesis. Oligonol, a low molecular weight polyphenol derived from lychee, exhibited anti-diabetic and anti-obesity properties, suggesting it could be a proper supplement for attenuating muscle loss. Dietary (10 weeks) oligonol supplementation (20 or 200 mg/kg diet) on the skeletal muscle loss was investigated in diabetic db/db mice...
September 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28922408/the-role-of-the-pi3k-akt-signaling-pathway-in-the-developmental-competence-of-bovine-oocytes
#4
Gabriella Mamede Andrade, Juliano Coelho da Silveira, Claudia Perrini, Maite Del Collado, Samuel Gebremedhn, Dawit Tesfaye, Flávio Vieira Meirelles, Felipe Perecin
The ovarian follicle encloses oocytes in a microenvironment throughout their growth and acquisition of competence. Evidence suggests a dynamic interplay among follicular cells and oocytes, since they are constantly exchanging "messages". We dissected bovine ovarian follicles and recovered follicular cells (FCs-granulosa and cumulus cells) and cumulus-oocyte complexes (COCs) to investigate whether the PI3K-Akt signaling pathway impacted oocyte quality. Following follicle rupture, COCs were individually selected for in vitro cultures to track the follicular cells based on oocyte competence to reach the blastocyst stage after parthenogenetic activation...
2017: PloS One
https://www.readbyqxmd.com/read/28912098/melatonin-mediated-upregulation-of-sirt3-attenuates-sodium-fluoride-induced-hepatotoxicity-by-activating-the-mt1-pi3k-akt-pgc-1%C3%AE-signaling-pathway
#5
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
September 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28903387/hyperactivated-mtorc1-downregulation-of-foxo3a-pdgfr%C3%AE-akt-cascade-restrains-tuberous-sclerosis-complex-associated-tumor-development
#6
Li Wang, Zhaofei Ni, Yujie Liu, Shuang Ji, Fuquan Jin, Keguo Jiang, Junfang Ma, Cuiping Ren, Hongbing Zhang, Zhongdong Hu, Xiaojun Zha
Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss-of-function mutations in either the TSC1 or TSC2 gene, leads to the development of tuberous sclerosis complex (TSC), a benign tumor syndrome with multiple affected organs. mTORC1-mediated inhibition of AKT constrains the tumor progression of TSC, but the exact mechanisms remain unclear. Herein we showed that loss of TSC1 or TSC2 downregulation of platelet-derived growth factor receptor α (PDGFRα) expression was mediated by mTORC1...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899782/the-lncrna-gas5-mir-23a-foxo3a-axis-regulates-cardiac-hypertrophy-by-wnt-%C3%AE-catenin-signal-pathway
#7
Wei Wei, Yan Chen, Jing Gao, Chenyi Li
Cardiac hypertrophy (CH) is related to a variety of physiological as well as pathological stimuli and eventually increases the risk of heart failure. lncRNA GAS5 has been identified as a competing endogenous RNA in multiple human biological processes. Whether lncRNA GAS5 is involved in the progress of CH and how it works still remain unknown. Here, we found that the expression of lncRNA-GAS5 was increased in the AngII-induced Cardiac hypertrophy model. lncRNA-GAS5 inhibited the total protein per well, as well as the expression of hypertrophic markers, ANF and β-MHC...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28894133/5-methoxytryptophan-protects-mscs-from-stress-induced-premature-senescence-by-upregulating-foxo3a-and-mtor
#8
Tzu-Ching Chang, Min-Fen Hsu, Chiu-Yueh Shih, Kenneth K Wu
5-methoxytryptophan (5-MTP) is a newly discovered tryptophan metabolite which controls stress-induced inflammatory signals. To determine whether 5-MTP protects against stress-induced mesenchymal stem cell (MSC) senescence, we incubated bone marrow-derived MSC (BM-MSC) in high-glucose medium or regular medium for 2 weeks followed by addiction of 5-MTP (10 μM) or vehicle for 48 h. 5-MTP reduced p16 and p21 expression, senescence-associated β-Gal (SA-β-Gal) and IL-6 secretion and increased BrdU incorporation...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889023/suppression-of-foxo3a-attenuates-neurobehavioral-deficits-after-traumatic-brain-injury-through-inhibiting-neuronal-autophagy
#9
Liqian Sun, Manman Zhao, Man Liu, Peng Su, Jingbo Zhang, Youxiang Li, Xinjian Yang, Zhongxue Wu
Traumatic brain injury (TBI) is a serious insult that frequently leads to neurological impairments. Forkhead box O (FoxO) 3a, as transcription factor, has been confirmed to modulate autophagic process. Moreover, FoxO3a is expressed throughout the brain including the hippocampus. However, the role of FoxO3a in the pathophysiology of TBI is unclear. The present study is designed to investigate whether FoxO3a has the neuroprotective effects on rats subjected to TBI, and further to explore the potential molecular mechanisms...
September 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28883855/five-gene-variants-in-nonagenarians-centenarians-and-average-individuals
#10
Vana Kolovou, Helen Bilianou, Vasiliki Giannakopoulou, Petros Kalogeropoulos, Constantinos Mihas, Markos Kouris, Dennis V Cokkinos, Maria Boutsikou, Ioannis Hoursalas, Sophie Mavrogeni, Niki Katsiki, Genovefa Kolovou
INTRODUCTION: Genetic factors contribute to the variation of human life span which is believed to be more profound after 85 years of age. The aim of the present study was to evaluate the frequency of 5 gene polymorphisms between nonagenarians, centenarians and average individuals. MATERIAL AND METHODS: Single nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase (TERT; rs2736098), insulin-like growth factor-1 binding protein-3 (IGFBP3; A-202C, rs2857744), fork-head box O3A (FOXO3A; rs13217795 and rs2764264) factor and adiponectin (ADIPOQ; rs2241766) were evaluated in 405 individuals: n = 256 nonagenarians and centenarians (study group) and n = 149 average lifespan individuals (control group aged 18 - < 80 years)...
August 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28881660/activation-of-perk-branch-of-er-stress-mediates-homocysteine-induced-bkca-channel-dysfunction-in-coronary-artery-via-foxo3a-dependent-regulation-of-atrogin-1
#11
Wen-Tao Sun, Xiang-Chong Wang, Shiu-Kwong Mak, Guo-Wei He, Xiao-Cheng Liu, Malcolm John Underwood, Qin Yang
The molecular mechanism of endoplasmic reticulum (ER) stress in vascular pathophysiology remains inadequately understood. We studied the role of ER stress in homocysteine-induced impairment of coronary dilator function, with uncovering the molecular basis of the effect of ER stress on smooth muscle large-conductance Ca(2+)-activated K(+) (BKCa) channels. The vasodilatory function of BKCa channels was studied in a myograph using endothelium-denuded porcine small coronary arteries. Primary cultured porcine coronary artery smooth muscle cells were used for mRNA and protein measurements and current recording of BKCa channels...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879560/involvement-of-mir-155-foxo3a-and-mir-222-pten-in-acquired-radioresistance-of-colorectal-cancer-cell-line
#12
Hamed Manoochehri Khoshinani, Saeid Afshar, Abdolazim Sedighi Pashaki, Ali Mahdavinezhad, Safora Nikzad, Rezvan Najafi, Razieh Amini, Mohammad Hadi Gholami, Alireza Khoshghadam, Massoud Saidijam
PURPOSE: Finding a novel biomarker for determining the radiosensitivity of colorectal cancer (CRC) is critical. The aim of this study is to evaluate the role of two main miRNAs including miR-222 and miR-155 in radiation response of CRC. MATERIALS AND METHODS: The radioresistant CRC cell lines were established by exposing the HCT 116 cell line to fractional X-ray radiation. SubG1 fraction analysis, MTT and clonogenic assays were applied to evaluate acquired radioresistant cell line radiosensitivity...
September 6, 2017: Japanese Journal of Radiology
https://www.readbyqxmd.com/read/28855204/regulation-of-macrophage-apoptosis-and-atherosclerosis-by-lipid-induced-pkc%C3%AE-isoform-activation
#13
Qian Li, Kyoungmin Park, Yu Xia, Motonobu Matsumoto, Weier Qi, Jialin Fu, Hisashi Yokomizo, Mogher Khamaisi, Xuanchun Wang, Christian Rask-Madsen, George L King
Rationale: Activation of monocytes/macrophages by hyperlipidemia associated with diabetes and obesity contributes to the development of atherosclerosis. PKCδ expression and activity in monocytes were increased by hyperlipidemia and diabetes with unknown consequences to atherosclerosis. Objective: To investigate the effect of PKCδ activation in macrophages on the severity of atherosclerosis. Methods and Results: PKCδ expression and activity were increased in Zucker diabetic rats. Mice with selective deletion of PKCδ in macrophages were generated by breeding PKCδ flox/flox mice with LyzM-Cre and ApoE(-/-) mice (MPKCδKO/ApoE(-/-) mice) and studied in atherogenic (AD) and very high fat diet (HFD)...
August 30, 2017: Circulation Research
https://www.readbyqxmd.com/read/28851713/scp4-promotes-gluconeogenesis-through-foxo1-3a-dephosphorylation
#14
Jin Cao, Yi Yu, Zhengmao Zhang, Xi Chen, Zhaoyong Hu, Qiang Tong, Jiang Chang, Xin-Hua Feng, Xia Lin
FoxO1 and FoxO3a (collectively FoxO1/3a) proteins regulate a wide array of cellular processes including hepatic gluconeogenesis. Phosphorylation of FoxO1/3a is a key event that determines its subcellular location and transcriptional activity. During glucose synthesis, the activity of FoxO1/3a is negatively regulated by Akt-mediated phosphorylation, which leads to the cytoplasmic retention of FoxO1/3a. However, the nuclear phosphatase that directly regulates FoxO1/3a remains to be identified. In this study, we discovered a nuclear phosphatase SCP4/CTDSPL2 that dephosphorylated FoxO1/3a and promoted FoxO1/3a transcription activity...
August 29, 2017: Diabetes
https://www.readbyqxmd.com/read/28840963/the-enhancement-of-combination-of-berberine-and-metformin-in-inhibition-of-dnmt1-gene-expression-through-interplay-of-sp1-and-pdpk1
#15
Fang Zheng, JingJing Wu, Qing Tang, Qian Xiao, WanYin Wu, Swei Sunny Hann
Berberine (BBR), one of active alkaloid found in the rhizome, exhibited anti-cancer properties. We have showed that BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a). However, the in-depth mechanism underlying the anti-tumor effects still remained to be elucidated. Herein, we further confirmed that BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells. Mechanistically, we observed that BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions...
August 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28831286/standardized-kaempferia-parviflora-extract-inhibits-intrinsic-aging-process-in-human-dermal-fibroblasts-and-hairless-mice-by-inhibiting-cellular-senescence-and-mitochondrial-dysfunction
#16
Ji-Eun Park, Seon Wook Woo, Mi-Bo Kim, Changhee Kim, Jae-Kwan Hwang
Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE) on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulated the expression of cell-cycle activators (E2F1 and E2F2)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28827681/sirt1-reduction-is-associated-with-sex-specific-dysregulation-of-renal-lipid-metabolism-and-stress-responses-in-offspring-by-maternal-high-fat-diet
#17
Long The Nguyen, Hui Chen, Carol Pollock, Sonia Saad
Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826225/low-oxidative-stress-mediated-proliferation-via-jnk-foxo3a-catalase-signaling-in-transplanted-adult-stem-cells-promotes-wound-tissue-regeneration
#18
Neha R Dhoke, Ramasatyaveni Geesala, Amitava Das
AIMS: Stem cells exposed to pathological levels of reactive oxygen species (ROS) at wound site fail to regenerate tissue. Molecular mechanism underlying differential levels of ROS-mediated regulation of stem cells remains elusive. This study elucidates mechanistic role of catalase at 10µM H<sub>2</sub>O<sub>2</sub>-induced proliferation of mouse bone marrow stromal (BMSC) and hematopoietic (HSPC) stem/progenitor cells. RESULTS: BMSCs and HSPCs depicted an increased growth rate and colony formation, in presence of 10µM but not 100µM concentration of H<sub>2</sub>O<sub>2</sub>, an effect that was perturbed by Vit...
August 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28819023/therapeutic-effects-of-xpo1-inhibition-in-thymic-epithelial-tumors
#19
Fabio Conforti, Xu Zhang, Guanhua Rao, Tommaso De Pas, Yoko Yonemori, Jose A Rodriguez, Justine N McCutcheon, Raneen Rahhal, Anna T Alberobello, Yisong Wang, Yu-Wen Zhang, Udayan Guha, Giuseppe Giaccone
Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export (SINE) compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins (TSP) including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells and induces p53-dependent and -independent antitumor activity in vitro...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28804541/a-potential-role-for-the-hippo-pathway-protein-yap-in-controlling-proliferation-cell-cycle-progression-and-autophagy-in-bcpap-and-ki-thyroid-papillary-carcinoma-cells
#20
Zeming Liu, Wen Zeng, Shi Wang, Xiangwang Zhao, Yawen Guo, Pan Yu, Xingjie Yin, Chunping Liu, Tao Huang
PURPOSE: The aims were two-fold: first, to examine the expression of Yes-activated protein (YAP), a key Hippo pathway regulator, in clinical thyroid papillary carcinoma samples and to correlate this with clinicopathological parameters; second, to explore the role of YAP in regulating cell growth and division in vitro. METHODS AND RESULTS: YAP expression was determined by immunohistochemistry of clinical thyroid papillary carcinoma tissue microarrays and expression was correlated with clinicopathological parameters...
2017: American Journal of Translational Research
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