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Wendy N Jefferson, H Karimi Kinyamu, Tianyuan Wang, Adam X Miranda, Elizabeth Padilla-Banks, Alisa A Suen, Carmen J Williams
Little is known regarding how steroid hormone exposures impact the epigenetic landscape in a living organism. Here, we took a global approach to understanding how exposure to the estrogenic chemical, diethylstilbestrol (DES), affects the neonatal mouse uterine epigenome. Integration of RNA- and ChIP-sequencing data demonstrated that ∼80% of DES-altered genes had higher H3K4me1/H3K27ac signal in close proximity. Active enhancers, of which ∼3% were super-enhancers, had a high density of estrogen receptor alpha (ERα) binding sites and were correlated with alterations in nearby gene expression...
April 10, 2018: Nucleic Acids Research
Fan Wang, Salih Demir, Franziska Gehringer, Clarissa D Osswald, Felix Seyfried, Stefanie Enzenmüller, Sarah M Eckhoff, Thomas Maier, Karlheinz Holzmann, Klaus-Michael Debatin, Thomas Wirth, Lüder H Meyer, Alexey Ushmorov
The FOXO1 transcription factor plays an essential role in the regulation of proliferation and survival programs at early stages of B-cell differentiation. Here, we show that tightly-regulated FOXO1 activity is essential for maintenance of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Genetic and pharmacological inactivation of FOXO1 in BCP-ALL cell lines produced a strong anti-leukemic effect associated with CCND3 downregulation. Moreover, we demonstrated that CCND3 expression is critical for BCP-ALL survival and overexpression of CCND3 protected BCP-ALL cell lines from growth arrest and apoptosis induced by FOXO1 inactivation...
April 5, 2018: Blood
Chen Zhong, Liyong Pu, Mingming Fang, Jianhua Rao, Xuehao Wang
All-trans retinoic acid (ATRA) has been proved to protect liver from ischemia/reperfusion (IR) injury, however, its mechanism is still unclear. This study is to investigate the mechanism of effect of ATRA on innate immunity in mice liver IR injury. Before operation, mice were gavaged by ATRA at 15 mg/kg/d for two weeks, and then the liver was underwent 70% ischemia (90 min) and reperfusion (6 h). Liver function was assessed by serum alanine aminotransferase (sALT), serum aspartate aminotransferase (sAST)...
2018: Biological & Pharmaceutical Bulletin
Wen Zeng, Jiansong Tang, Haicheng Li, Haixia Xu, Hongyun Lu, Hangya Peng, Chuwen Lin, Rili Gao, Shuo Lin, Keyi Lin, Kunying Liu, Yan Jiang, Jianping Weng, Longyi Zeng
Lipotoxicity leads to insulin secretion deficiency, which is among the important causes for the onset of type 2 diabetes mellitus. Thus, the restoration of β-cell mass and preservation of its endocrine function are long-sought goals in diabetes research. Previous studies have suggested that the membrane protein caveolin-1 (Cav-1) is implicated in β-cell apoptosis and insulin secretion, however, the underlying mechanisms still remains unclear. Our objective is to explore whether Cav-1 depletion protects pancreatic β cells from lipotoxicity and what are the underlying mechanisms...
March 26, 2018: Cellular Signalling
Chang Liu, Guangyang Xing, Cailiang Wu, Jun Zhu, Min Wei, Dajiang Liu, Yan Ge, Yao Chen, Ting Lei, Yongxiu Yang
BACKGROUND The aim of this study was to investigate the expression and silencing of the S100A8 gene, which encodes the S100 calcium-binding protein A8 (S100A8), and apoptosis and phosphorylation of protein kinase B (Akt) in tissue samples of endometrial carcinoma and HEC-1A endometrial adenocarcinoma cells in vitro. MATERIAL AND METHODS Immunohistochemistry (IHC) was used to detect expression of the S100A8 protein in 74 tissue samples of endometrial cancer and 22 normal endometrial tissue samples. A stable S100A8 gene knockdown cell line was constructed using lentiviral packing short hairpin RNA (shRNA) transfected into HEC-1A cells...
March 29, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Daniel T Utzschneider, Arnaud Delpoux, Dominik Wieland, Xin Huang, Chen-Yen Lai, Maike Hofmann, Robert Thimme, Stephen M Hedrick
Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programming by FOXO1 is required for the functional maintenance of a memory population. Upon Foxo1 deletion following resolution of an infection, memory cells rapidly lost their characteristic gene expression, gradually declined in number, and were impaired in self-renewal...
March 27, 2018: Cell Reports
Yiu To Yeung, Faisal Aziz, Angelica Guerrero-Castilla, Sandro Arguelles
During the past decade, an abundance of new evidence highlighted the importance of inflammation in the development of chronic pathologies such as neurodegeneration, cancer, diabetes, cardiovascular disease and inflammatory bowel disease. However, most of the current therapies do not address the underlying problem and better therapies are urgently needed. A growing number of researchers have discovered various signaling pathways that are associated with the initiation and progression of inflammation. Among different pathways, we will focus on three classical inflammatory pathways: p38 MAPK, IL-6/JAK/STAT3 and PI3K; and a non-classical inflammatory pathway, the Hippo...
March 27, 2018: Current Pharmaceutical Design
Abdul Rehman, Yeseul Kim, Hyunsung Kim, Jongmin Sim, Hyein Ahn, Min Sung Chung, Su-Jin Shin, Kiseok Jang
AIMS: Forkhead box O (FOXO) transcription factors, consisting of FOXO1, FOXO3a, FOXO4 and FOXO6, are involved in carcinogenesis and tumour progression. Recent studies have suggested that FOXOs act as tumour suppressors in a variety of human cancers. This study investigated the clinicopathological significance of FOXOs in triple-negative breast cancer (TNBC). METHODS: FOXO protein expressions were assessed by immunohistochemistry in 125 TNBC tissues. Correlations between FOXO protein expression and various clinicopathological parameters, including patients' survival, were investigated...
March 27, 2018: Journal of Clinical Pathology
Aiqing Zhang, Min Li, Bin Wang, Janet D Klein, S Russ Price, Xiaonan H Wang
BACKGROUND: The treatment of muscle wasting is accompanied by benefits in other organs, possibly resulting from muscle-organ crosstalk. However, how the muscle communicates with these organs is less understood. Two microRNAs (miRs), miR-23a and miR-27a, are located together in a gene cluster and regulate proteins that are involved in the atrophy process. MiR-23a/27a has been shown to reduce muscle wasting and act as an anti-fibrotic agent. We hypothesized that intramuscular injection of miR-23a/27a would counteract both muscle wasting and renal fibrosis lesions in a streptozotocin-induced diabetic model...
March 26, 2018: Journal of Cachexia, Sarcopenia and Muscle
Anthony M J Sanchez, Robin B Candau, Henri Bernardi
AMP-activated protein kinase (AMPK) is a critical enzyme in conditions of cellular energy deficit such as exercise, hypoxia or nutritional stress. AMPK is well known to regulate protein degradation pathway notably through FOXO-related axis. In this study, we investigated the implication of AMPK activation in FOXO3 expression and stability in skeletal muscle primary myotubes. First, time course and dose response studies revealed optimal AICAR treatment duration and dose in skeletal muscle cells. Then, experiments with cycloheximide treatment of primary myotubes highlighted that AICAR infusion extends FOXO3 protein half-life...
March 23, 2018: Biochemical and Biophysical Research Communications
Amna Asif, Sajid Mushtaq, Usman Hassan, Noreen Akhtar, Mudassar Hussain, Muhammad Azam, Romena Qazi
Introduction:Soft tissue sarcomas are rare tumors comprising 1 percent of solid malignancies. The latest edition of WHO soft tissue pathology lists 94 benign and malignant soft tissue tumors. Many of these show a large degree of morphological overlap. Immunohistochemistry has been shown to be reliable in many cases for differential diagnosis of lesions, although cytogenetic tests are considered the gold standard for many entities.Fluorescence in-situ hybridization (FISH) is a cytogenetic technique that uses fluorescent probes that bind to only those parts of the chromosome which have a high degree of sequence complementarity...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Sugyeong Hong, Moon-Moo Kim
Aging study requires aging markers to measure the degree of aging process. The aging markers such as senescence associated-β-galactosidase (SA-β-gal), lipofuscin, telomere, p53 and p16 have been known in aging study until now. Therefore, we investigated the role of genes and proteins related to aging in young, senescent and H2 O2 -induced old cells to develop a novel aging marker involved in aging mechanism. After cellular aging was compared in young, senescent and H2 O2 -induced old cells using SA-β-galactosidase staining assay, the expression level of genes and proteins in senescent and H2 O2 -induced old cells were compared and analyzed with those of young cells using RT-PCR, western blot and immunofluorescence staining...
March 20, 2018: Environmental Toxicology and Pharmacology
Y Chen, X Y Ji, Y Y Fan, L S Yu
OBJECTIVES: To investigate FoxO1 expression and its time-dependent changes during the skin incised wound healing. METHODS: After the establishment of the skin incised wound model in mice, the FoxO1 expression of skin in different time periods was detected by immunohistochemistry and Western blotting. RESULTS: Immunohistochemistry staining showed that FoxO1 was weakly expressed in a few fibroblasts of epidermis, hair follicles, sebaceous glands, vessel endothelium and dermis in the control group...
February 2018: Fa Yi Xue za Zhi
Hyeran Helen Jeon, Quan Yu, Yongjian Lu, Evelyn Spencer, Chanyi Lu, Tatyana Milovanova, Yang Yang, Chenying Zhang, Olga Stepanchenko, Rameen P Vafa, Paulo G Coelho, Dana T Graves
Angiogenesis is a critical aspect of wound healing. We investigated the role of keratinocytes in promoting angiogenesis in mice with lineage specific deletion of the transcription factor FOXO1. The results indicate that keratinocyte-specific deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads to the reduced endothelial cell proliferation, reduced angiogenesis and impaired re-epithelialization and granulation tissue formation. In vitro FOXO1 was needed for VEGFA transcription and expression...
March 25, 2018: Journal of Pathology
Hong Yao, Xufeng Tao, Lina Xu, Yan Qi, Lianhong Yin, Xu Han, Youwei Xu, Lingli Zheng, Jinyong Peng
Dioscin, one natural product, has active effect against non-alcoholic fatty liver disease (NAFLD) in our previous work. However, the pharmacological data are insufficient and the mechanisms have not been reported. Thus, this study aims to comprehensively investigate the effects and molecular mechanisms of dioscin against NAFLD. The primary cultured hepatocytes, AML-12 and HepG-2 cells were treated with palmic acid (PA) after dioscin treatment. The mice and rats were induced by high fat diet to establish the in vivo models of NAFLD...
March 21, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Ji Won Byun, Hye Young An, Seung Dohn Yeom, Seok Jong Lee, Ho Yun Chung
The etiopathogenesis of infantile hemangioma has not been well understood, and it is accepted that angiogenic mediator dysregulation is the main contributor to the abnormal hemangioma capillary formation. The role of NDRG1, a hypoxia-inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR complex 2 pathway in infantile hemangioma have not been studied yet. The purpose of this study was to investigate NDRG1 and FOXO1 expression in the infantile hemangioma and the correlation of these proteins with proliferation and involution...
March 23, 2018: Experimental Dermatology
Shurun Zhang, Xiaoling Chen, Zhiqing Huang, Daiwen Chen, Bing Yu, Hong Chen, Junqiu Luo, Jun He, Ping Zheng, Jie Yu
Leucine, one of the branched-chain amino acids, is the only amino acid to regulate protein turnover in skeletal muscle. Leucine not only increases muscle protein synthesis, but also decreases muscle protein degradation. It is well documented that leucine plays a positive role in differentiation of murine muscle cells. However, the role of leucine on porcine myoblast differentiation and its mechanism remains unclear. In this study, porcine myoblasts were induced to differentiate with differentiation medium containing different concentrations of leucine, and wortmannin was used to interdict the activity of protein kinase B (Akt)...
April 2018: British Journal of Nutrition
Ann W Kinyua, Khanh V Doan, Dong Joo Yang, My Khanh Q Huynh, Yun-Hee Choi, Dong Min Shin, Ki Woo Kim
Development of metabolic syndrome is associated with hyperactivity of the HPA axis characterized by elevated levels of circulating adrenal hormones including cortisol and aldosterone. However, the molecular mechanism leading to the dysregulation of the HPA axis is not well elucidated. In this study, we found that insulin regulates adrenal steroidogenesis by increasing the expression and activity of steroidogenic factor 1 (SF-1) both in vitro and in vivo and this insulin effect was partly through inhibition of FoxO1...
March 22, 2018: Scientific Reports
Patrick Schöffski, Agnieszka Wozniak, Michael G Leahy, Steinar Aamdal, Piotr Rutkowski, Sebastian Bauer, Stephan Richter, Viktor Grünwald, Maria Debiec-Rychter, Raf Sciot, Birgit Geoerger, Sandrine Marréaud, Sandra Collette, Axelle Nzokirantevye, Sandra J Strauss
BACKGROUND: Alveolar rhabdomyosarcomas (ARMSs) can harbour MET and anaplastic lymphoma kinase (ALK) alterations. We prospectively assessed crizotinib in patients with advanced/metastatic ARMS. METHODS: Eligible patients with a central diagnosis of ARMS received oral crizotinib 250 mg twice daily. Patients were attributed to MET/ALK+ or MET/ALK- subcohorts by assessing the presence or absence of the forkhead box O1 (FOXO1; a marker of MET upregulation) and/or ALK gene rearrangement...
March 19, 2018: European Journal of Cancer
Zhao-Jia Gao, Wei-Dong Yuan, Jun-Qiang Yuan, Kai Yuan, Yong Wang
PURPOSE: Lung cancer, the leading cause of cancer-related death worldwide, shows a poor 5-year overall survival rate. In our previous study, we demonstrated that miR-486-5p can be a potential blood-based biomarker for early diagnosis and recurrence prediction of non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the possible roles and related target genes of miR-486-5p in NSCLC progression. METHODS: pcDNA3.1(+)/Pri-miR486 recombinant plasmid and miR-486-5p inhibitor were transfected into NSCLC cells and theirs effects were evaluated by qRT-PCR...
March 15, 2018: Pathology, Research and Practice
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