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Yuan Li, Haisheng Wang, Fei Pei, Zhi Chen, Lu Zhang
INTRODUCTION: FoxO3a is a member of FoxO transcription factor family that participates in the transcriptional regulation of autophagy. In this study we explored the anti-inflammatory function of FoxO3a-regulated autophagy in inflamed human dental pulp and lipopolysaccharide-treated mDPC6T cells. METHODS: The expression of FoxO3a and autophagy markers in caries and pulpitis from human dental pulp were examined by immunohistochemistry and Western blot. We conducted in vitro studies by treating mDPC6T cells with lipopolysaccharide for various lengths of time...
March 15, 2018: Journal of Endodontics
Xi Yang, Jun Zhang, Linmu Chen, Qiong Wu, Chao Yu
Chitosan oligosaccharides (COS), linear polymers of N-acetyl-D-glucosamine and deacetylated glucosamine, exhibit diverse pharmacological effects such as antimicrobial, antitumor, antioxidant and anti-inflammatory activities. Here, we explored their hypocholesterolemic effects in vivo and the molecular mechanisms of COS in hepatic cells. Our in vivo study of dyslipidemic ApoE-/- male mice showed that COS treatment of 500mg·kg-1 ·d-1 for 4 weeks clearly reduced the lipid deposits in the aorta and significantly decreased the hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels versus HFD groups (p < 0...
March 13, 2018: Experimental Cell Research
Lijun Ding, Guijun Yan, Bin Wang, Lu Xu, Yan Gu, Tong Ru, Xiaoying Cui, Lei Lei, Jingyu Liu, Xiaoqiang Sheng, Bin Wang, Chunxue Zhang, Yanjun Yang, Ruiwei Jiang, Jianjun Zhou, Na Kong, Feifei Lu, Huaijun Zhou, Yannan Zhao, Bing Chen, Yali Hu, Jianwu Dai, Haixiang Sun
Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles...
March 13, 2018: Science China. Life Sciences
Brent E Fitzwalter, Christina G Towers, Kelly D Sullivan, Zdenek Andrysik, Maria Hoh, Michael Ludwig, Jim O'Prey, Kevin M Ryan, Joaquin M Espinosa, Michael J Morgan, Andrew Thorburn
Macroautophagy (autophagy) is intimately linked with cell death and allows cells to evade apoptosis. This has prompted clinical trials to combine autophagy inhibitors with other drugs with the aim of increasing the likelihood of cancer cells dying. However, the molecular basis for such effects is unknown. Here, we describe a transcriptional mechanism that connects autophagy to apoptosis. The autophagy-regulating transcription factor, FOXO3a, is itself turned over by basal autophagy creating a potential feedback loop...
March 12, 2018: Developmental Cell
Patrice Codogno, Etienne Morel
FOXO3a, a member of the Forkhead transcription factor family, has roles in apoptosis and autophagy. In this issue of Developmental Cell, Fitzwalter et al. (2018) describe how the blockade of FOXO3a turnover, which normally occurs through autophagy, sensitizes cancer cells to apoptosis through FOXO3a-mediated stimulation of pro-apoptotic PUMA/BBC3 expression.
March 12, 2018: Developmental Cell
Di Yang, ChenXi Xiao, Fen Long, ZhengHua Su, WanWan Jia, Ming Qin, MengWei Huang, WeiJun Wu, Rinkiko Suguro, XinHua Liu, YiZhun Zhu
Aims: Angiotensin II (Ang II) causes vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of cardiovascular diseases. Therefore, interventions in inflammation may contribute to the reduction of cardiovascular diseases. Here, we aim to demonstrate that HDAC4, one of class IIa family histone deacetylases (HDACs) members, promotes autophagy-dependent vascular inflammation. Methods and results: By loss-of-function approaches, our study provides the first evidence that HDAC4 mediates Ang II-induced vascular inflammation in vitro and in vivo...
February 24, 2018: Cardiovascular Research
Sinae Kim, Eunji Lee, Jaeyun Jung, Jong Won Lee, Hee Jung Kim, Jisun Kim, Hyun Ju Yoo, Hee Jin Lee, Sun Young Chae, Sang Min Jeon, Byung Ho Son, Gyungyup Gong, Shyam K Sharan, Suhwan Chang
MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway...
March 12, 2018: Oncogene
Lisha Zhao, Xufeng Tao, Yan Qi, Lina Xu, Lianhong Yin, Jinyong Peng
Clinical application of doxorubicin (DOX) is limited because of its cardiotoxicity. Thus, exploration of effective lead compounds against DOX-induced cardiotoxicity is necessary. The aim of the present study was to investigate the effects and possible mechanisms of dioscin against DOX-induced cardiotoxicity. The in vitro model of DOX- treated H9C2 cells and the in vivo models of DOX-treated rats and mice were used in this study. The results showed that discoin markedly increased H9C2 cell viability, decreased the levels of CK, LDH, and improved histopathological and electrocardio- gram changes in rats and mice to protect DOX-induced cardiotoxicity...
March 6, 2018: Redox Biology
Michele Pellegrino, Pietro Rizza, Alessandra Nigro, Rosangela Ceraldi, Elena Ricci, Ida Perrotta, Saveria Aquila, Marilena Lanzino, Sebastiano Andò, Catia Morelli, Diego Sisci
Breast cancer (BC) is a complex and heterogeneous disease, with distinct histological features dictating the therapy. Although the clinical outcome of BC patients has been considerably improved, the occurrence of resistance to common endocrine and chemotherapy treatments remains the major cause of relapse and mortality. Thus, efforts in identifying new molecules to be employed in BC therapy are needed. As a "faster" alternative to reach this aim, we evaluated if Lamotrigine (LTG), a broadly used anticonvulsivant, could be "repurposed" as an antitumoral drug in BC...
March 9, 2018: Molecular Cancer Research: MCR
Satoru Yanagisawa, Jonathan R Baker, Chaitanya Vuppusetty, Takeshi Koga, Thomas Colley, Peter Fenwick, Louise E Donnelly, Peter J Barnes, Kazuhiro Ito
SIRT1 (silent information regulator 2 homolog 1) is a crucial cellular survival protein especially in oxidative stress environments, and has been thought to locate within the nuclei, but also known to shuttle between cytoplasm and nuclei in some cell types. Here, we show for the first time the dynamics of SIRT1 in the presence of single or concurrent cigarette smoke extract (CSE) exposure in human bronchial epithelial cells (HBEC). In BEAS-2B HBEC or primary HBEC, SIRT1 was localized predominantly in cytoplasm, and the CSE (3%) induced nuclear translocation of SIRT1 from cytoplasm in the presence of L-buthionine sulfoximine (an irreversible inhibitor of γ-glutamylcystein synthetase), mainly through the activation of phosphatidylinositol 3-kinase (PI3K) α subunit...
2018: PloS One
Xin Yu, Heyi Zheng, Matthew T V Chan, William K K Wu
Increasing studies have suggested that dysregulation of RNA-binding proteins (RBPs) contributes to cancer progression. Neuro-oncological ventral antigen 1 (NOVA1) is a novel RBP and plays an important role in tumour development. However, the expression and role of NOVA1 in melanoma remain unknown. In this study, we indicated that NOVA1 expression was up-regulated in melanoma samples and cell lines. Moreover, we demonstrated that knockdown of NOVA1 suppressed melanoma cell proliferation, migration and invasion in both A375 and A875 cell lines...
March 2, 2018: Journal of Cellular and Molecular Medicine
Ying Xie, Daofang Jiang, Jing Xiao, Chensheng Fu, Zhenxing Zhang, Zhibin Ye, Xiaoli Zhang
Ischemic preconditioning (IPC) has a strong renoprotective effect during renal ischemia/reperfusion (I/R) injury that is thought to relate to autophagy. However, the role of autophagy during IPC-afforded renoprotection and the precise mechanisms involved are unknown. In this study, an in vitro hypoxia/reoxygenation (H/R) model was established in which oxygen and glucose deprivation (OGD) was applied to renal cells for 15 h followed by reoxygenation under normal conditions for 30 min, 2 h or 6 h; transient OGD and subsequent reoxygenation were implemented before prolonged H/R injury to achieve hypoxic preconditioning (HPC)...
March 1, 2018: Cell Death & Disease
Valentina Celestini, Tugsan Tezil, Luciana Russo, Candida Fasano, Paola Sanese, Giovanna Forte, Alessia Peserico, Martina Lepore Signorile, Giovanna Longo, Domenico De Rasmo, Anna Signorile, Raffaella Maria Gadaleta, Natasha Scialpi, Mineko Terao, Enrico Garattini, Tiziana Cocco, Gaetano Villani, Antonio Moschetta, Valentina Grossi, Cristiano Simone
While aberrant cancer cell growth is frequently associated with altered biochemical metabolism, normal mitochondrial functions are usually preserved and necessary for full malignant transformation. The transcription factor FoxO3A is a key determinant of cancer cell homeostasis, playing a dual role in survival/death response to metabolic stress and cancer therapeutics. We recently described a novel mitochondrial arm of the AMPK-FoxO3A axis in normal cells upon nutrient shortage. Here, we show that in metabolically stressed cancer cells, FoxO3A is recruited to the mitochondria through activation of MEK/ERK and AMPK, which phosphorylate serine 12 and 30, respectively, on FoxO3A N-terminal domain...
February 14, 2018: Cell Death & Disease
Clarissa D Osswald, Linka Xie, Hanfeng Guan, Franziska Herrmann, Sarah M Pick, Marion J Vogel, Franziska Gehringer, Fong Chun Chan, Christian Steidl, Thomas Wirth, Alexey Ushmorov
We recently found that FOXO1 repression contributes to the oncogenic program of classical Hodgkin lymphoma (cHL). Interestingly, FOXO3A, another member of the FOXO family, was reported to be expressed in the malignant Hodgkin-Reed Sternberg (HRS) cells of cHL at higher levels than in Non-Hodgkin lymphoma (NHL) subtypes. We thus aimed to investigate mechanisms responsible for the maintenance of FOXO3A as well as the potential role of FOXO3A in cHL. Here we show that high FOXO3A levels in cHL reflect a B-cell-differentiation specific pattern...
February 13, 2018: Blood
Honghui Lu, Li-Hai Zhang, Lin Yang, Pei-Fu Tang
The aim of the present study was to elucidate the expression and role of the phosphatidylinositol 3‑kinase (PI3K)/Akt/forkhead box O3 (FOXO3a) pathway in the regeneration of the spinal cord following spinal cord injury (SCI), and its regulatory effect on tumor necrosis factor (TNF)-α and cyclin-dependent kinase inhibitor 1B (p27kip1) expression. Firstly, in a Sprague-Dawley rat model of SCI, western blot analysis revealed that the protein levels of PI3K, phosphorylated Akt and FOXO3a were markedly inhibited compared with those in the sham control group...
February 6, 2018: International Journal of Molecular Medicine
Pim Knuiman, Maria T E Hopman, Jeroen A Wouters, Marco Mensink
Background: Substantial research has been done on the impact of carbohydrate and fat availability on endurance exercise adaptation, though its role in the acute adaptive response to resistance exercise has yet to be fully characterized. Purpose: We aimed to assess the effects of a pre-resistance exercise isocaloric mixed meal containing different amounts of carbohydrates and fat, on post-resistance exercise gene expression associated with muscle adaptation. Methods: Thirteen young (age 21.2 ± 1.6 year), recreationally trained (VO2max 51...
2018: Frontiers in Physiology
Rong Li, Yizhou Quan, Weiliang Xia
SIRT3, a mitochondrial NAD+-dependent deacetylase, has been reported to restrain prostate cancer growth both in vitro and in vivo, however, its role in metastatic prostate cancer has not been revealed. In this study, we reported that SIRT3 inhibited the epithelial-mesenchymal transition (EMT) and migration of prostatic cancer cells in vitro and their metastasis in vivo. Consistently, based on analyses of tissue microarray and microarray datasets, lower SIRT3 expression level was correlated with higher prostate cancer Gleason scores, and SIRT3 expression were significantly decreased in metastatic tissues compared with prostate tumor tissues...
February 5, 2018: Experimental Cell Research
Neha Mishra, Sonam Lata, Priyanka Deshmukh, Kajal Kamat, Avadhesha Surolia, Tanushree Banerjee
Cellular stress like ER and oxidative stress are the principle causative agents of various proteinopathies. Multifunctional protein PARK7/DJ-1 provides protection against cellular stress. Recently, insulin/IGF also has emerged as a neuro-protective molecule. However, it is not known whether DJ-1 and insulin/IGF complement each other for cellular protection in response to stress. In this study, we show for the first time, that in human and mouse neuronal cell lines, down regulation of DJ-1 for 48 h leads to compensatory upregulation of insulin/IGF signaling (IIS) pathway genes, namely, insulin receptor, insulin receptor substrate, and Akt under normal physiological conditions as well as in cellular stress conditions...
February 7, 2018: BioFactors
Xin Zhu, Yunfang Yu, Xiuxiu Hou, Jiajie Xu, Zhuo Tan, Xilin Nie, Zhiqiang Ling, Minghua Ge
Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) phosphorylates a series of substrates to exert its oncogenic function in numerous malignancies. The present study investigated the clinical significance of the PIM-1 protein, apoptosis status and apoptosis-associated proteins, including forkhead box O3a (FOXO3a), B cell lymphoma-2 (BCL-2) and BCL-2-associted agonist of cell death (BAD), were investigated in salivary gland adenoid cystic carcinoma (ACC) tissues. PIM-1 expression levels in 4 pairs of ACC tissues and corresponding normal salivary gland tissues were determined by western blot analysis...
January 2018: Oncology Letters
Ming Lu, Yong Wang, Shizhen Zhou, Jun Xu, Jing Li, Rongjie Tao, Yufang Zhu
Certain microRNAs (miRs) regulate the progression and metastasis of various cancer types. In the present study, the role of miR-370 in the progression and proliferation of human astrocytoma and glioblastoma cells was assessed and the underlying molecular mechanism was investigated. miR-370 levels in clinical specimens of human glioma and peritumoral tissues were determined by reverse-transcription quantitative PCR. Oligonucleotide mimics and inhibitors were transfected into the U-251MG human astrocytoma cell line and the and U-87MG glioblastoma cell line and the cell viability of was determined by an MTT assay...
January 2018: Experimental and Therapeutic Medicine
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