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Hyoung Sook Park, Ji Hye Kim, Bo Kyung Sun, Sun U Song, Wonhee Suh, Jong-Hyuk Sung
It has previously been demonstrated that hypoxia has diverse stimulatory effects on adipose‑derived stem cells (ASCs), however, metabolic responses under hypoxia remain to be elucidated. Thus, the present study aimed to investigate the glucose uptake and metabolism of ASCs under hypoxic conditions, and to identify the underlying molecular mechanisms. ASCs were cultured in 1% oxygen, and experiments were conducted in vitro. As determined by proteomic analysis and western blotting, GAPDH and enolase 1 (ENO1) expression were upregulated under hypoxia...
October 5, 2016: Molecular Medicine Reports
Wanwan He, Nengyan Fang, Ruisen Wang, Yunyu Wu, Guoying Zeng, Changhong Guan, Hao Chen, Ji Huang, Jianfei Wang, Yongmei Bao, Hongsheng Zhang
Heikezijing, a japonica rice landrace from Taihu region of China, exhibited broad-spectrum resistance to more than 300 isolates of the blast (Magnaporthe oryzae). In our previous research, we fine mapped a broad-spectrum resistance gene Pi-hk1 in chromosome 11. In this research, 2010-9(G1), one of the predominant race of the blast in Taihu Lake region of China, was inoculated into 162 recombinant inbred lines (RILs) and two parents Heikezijing and Suyunuo for mapping the resistance-blast quantitative trait loci (QTLs)...
September 27, 2016: Phytopathology
Markus Schlaich, Rosemary Elliott, Caroline Rudnicka, Vance Matthews
OBJECTIVE: Sympathetic nervous system activation is a common feature in various metabolic disorders such as obesity, metabolic syndrome, and type-2 diabetes. The sodium glucose co-transporter 2 (SGLT-2) mediates re-absorption of glucose from the renal proximal tubules. SGLT-2 inhibitors have attracted substantial attention due to their glucose and blood pressure lowering effects. Furthermore, the SGLT-2 inhibitor empagliflozin has recently been associated with improved cardiovascular outcomes in patients with type 2 diabetes...
September 2016: Journal of Hypertension
Timokratis Karamitros, Dimitrios Paraskevis, Angelos Hatzakis, Mina Psichogiou, Ioannis Elefsiniotis, Tara Hurst, Anna-Maria Geretti, Apostolos Beloukas, John Frater, Paul Klenerman, Aris Katzourakis, Gkikas Magiorkinis
Endogenous retroviruses (ERVs) comprise 6-8% of the human genome. HERVs are silenced in most normal tissues, up-regulated in stem cells and in placenta but also in cancer and HIV-1 infection. Crucially, there are conflicting reports on detecting HERV RNA in non-cellular clinical samples such as plasma that suggest the study of HERV RNA can be daunting. Indeed, we find that the use of real-time PCR in a quality assured clinical laboratory setting can be sensitive to low-level proviral contamination. We developed a mathematical model for low-level contamination that allowed us to design a laboratory protocol and standard operating procedures for robust measurement of HERV RNA...
2016: Scientific Reports
Hweixian Leong Penny, Je Lin Sieow, Giulia Adriani, Wei Hseun Yeap, Peter See Chi Ee, Boris San Luis, Bernett Lee, Terence Lee, Shi Ya Mak, Ying Swan Ho, Kong Peng Lam, Choon Kiat Ong, Ruby Y J Huang, Florent Ginhoux, Olaf Rotzschke, Roger D Kamm, Siew Cheng Wong
Patients with pancreatic ductal adenocarcinoma (PDAC) face a clinically intractable disease with poor survival rates, attributed to exceptionally high levels of metastasis. Epithelial-to-mesenchymal transition (EMT) is pronounced at inflammatory foci within the tumor; however, the immunological mechanisms promoting tumor dissemination remain unclear. It is well established that tumors exhibit the Warburg effect, a preferential use of glycolysis for energy production, even in the presence of oxygen, to support rapid growth...
August 2016: Oncoimmunology
Alenoush Vartanian, Sameer Agnihotri, Mark R Wilson, Kelly E Burrell, Peter D Tonge, Amir Alamsahebpour, Shahrzad Jalali, Michael S Taconne, Brian Golbourn, Kenneth D Aldape, Gelareh Zadeh
First-line cancer therapies such as alkylating agents and radiation have limited survival benefits for Glioblastoma (GBM) patients. Current research strongly supports the notion that inhibition of aberrant tumor metabolism holds promise as a therapeutic strategy when used in combination with radiation and chemotherapy. Hexokinase 2 (HK2) has been shown to be a key driver of altered metabolism in GBM, and presents an attractive therapeutic target. To date, no study has fully assessed the therapeutic value of targeting HK2 as a mechanism to sensitize cells to standard therapy, namely in the form of radiation and temozolomide (TMZ)...
August 29, 2016: Oncotarget
Bin Yi, Jing Huang, Wei Zhang, Ai Mei Li, Shi Kun Yang, Jian Sun, Jian Wen Wang, Yan Chun Li, Hao Zhang
CONTEXT: Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities. OBJECTIVE: To investigate the correlation between VDR expression and albuminuria in T2DM. DESIGN/SETTING/PATIENTS: Renal biopsies from T2DM patients with albuminuria (n=8) and non-diabetic subjects (n=4) were compared for VDR expression by immunohistochemistry. Recruited T2DM patients (n=242, eGFR>60ml/min/1...
August 23, 2016: Journal of Clinical Endocrinology and Metabolism
Afiat Berbudi, Jayagopi Surendar, Jesuthas Ajendra, Fabian Gondorf, David Schmidt, Anna-Lena Neumann, Ajeng P F Wardani, Laura E Layland, Linda S Hoffmann, Alexander Pfeifer, Achim Hoerauf, Marc P Hübner
Helminths induce type 2 immune responses and establish an anti-inflammatory milieu in their hosts. This immunomodulation was previously shown to improve diet-induced insulin resistance which is linked to chronic inflammation. In the current study, we demonstrate that infection with the filarial nematode Litomosoides sigmodontis increased the eosinophil number and alternatively activated macrophage abundance within epididymal adipose tissue (EAT) and improved glucose tolerance in diet-induced obese mice in an eosinophil-dependent manner...
August 20, 2016: Journal of Innate Immunity
Dawei Zhang, Yew Mun Yip, Liben Li
Hexokinase 2 (HK2) binds to Voltage-Dependent Anion Channel 1 (VDAC1) on mitochondrial outer membrane (MOM) to facilitate a preferential access of ATP to HK2 for glycolysis, in order to maintain a constant energy source for cell proliferation in cancer especially. While previous studies have discovered that the VDAC1 N-terminal helix is responsible for regulating molecules from within mitochondria to cytoplasm, the molecular mechanism of how HK2 is able to regulate the ATP access remains elusive. We hereby propose a model for the HK2-VDAC1 association...
September 2016: Mitochondrion
Evanka Madan, Bhawana Dikshit, Srinivas H Gowda, Chitrangda Srivastava, Chitra Sarkar, Parthaprasad Chattopadhyay, Subrata Sinha, Kunzang Chosdol
The hypoxic microenvironment is an important contributor of glioblastoma (GBM) aggressiveness via HIF1α, while tumour inflammation is profoundly influenced by FAT Atypical Cadherin (FAT1). This study was designed to explore the functional interaction and significance of FAT1 and HIF1α under severe hypoxia-mimicking tumour microenvironment in primary human tumours. We first identified a positive correlation of FAT1 with HIF1α and its target genes in GBM tumour specimens, revealing the significance of the FAT1-HIF1α axis in glioma cells...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
D O Minchenko, Y E Novik, H S Maslak, O V Tiazhka, O H Minchenko
We studied the peculiarity of the expression of several key genes related to dysregulation of cell proliferation and surviving processes in pediatric glioma (glioblastoma multiforme) tissue from five children with age from 5 to 8 years as well a sin corresponding nonmalignant tissue counterparts as control from the same patients. RNA was isolated from glioma tissue and corresponding non-malignant tissue counterparts and PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 gene expressions were studied by quantitative polymerase chain reaction...
October 2015: Likars'ka Sprava
Brianna D Harfmann, Elizabeth A Schroder, Maureen T Kachman, Brian A Hodge, Xiping Zhang, Karyn A Esser
BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-))...
2016: Skeletal Muscle
Feifei Sun, Yangchun Cao, Chao Yu, Xiaoshi Wei, Junhu Yao
BACKGROUND: Calcium is a vital mineral and an indispensable component of milk for ruminants. The regulation of transcellular calcium transport by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3, the active form of vitamin D) has been confirmed in humans and rodents, and regulators, including vitamin D receptor (VDR), calcium binding protein D9k (calbindin-D9k), plasma membrane Ca(2+)-ATPase 1b (PMCA1b), PMAC2b and Orai1, are involved in this process. However, it is still unclear whether 1,25-(OH)2D3 could stimulate calcium transport in the ruminant mammary gland...
2016: Journal of Animal Science and Biotechnology
Taiki Sato, Yu Kishimoto, Sanki Asakawa, Natsumi Mizuno, Masahiro Hiratsuka, Noriyasu Hirasawa
Many types of medical alloys include nickel (Ni), and the elution of Ni ions from these materials causes toxicities and inflammation. We have previously reported that inflammation enhances Ni elution, although the molecular mechanisms underlying this effect remain unclear. In this study, we investigated how inflammatory responses enhanced Ni elution in a wire-implantation mouse model. Subcutaneous implantation of Ni wire induced the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) mRNA in the surrounding tissues...
July 1, 2016: Toxicology
Wei-Jun Wei, Chen-Tian Shen, Hong-Jun Song, Zhong-Ling Qiu, Quan-Yong Luo
Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study...
September 2016: Oncology Reports
Sin Y Choi, Hae J Kee, Thomas Kurz, Finn K Hansen, Yuhee Ryu, Gwi R Kim, Ming Q Lin, Li Jin, Zhe H Piao, Myung H Jeong
Epithelial-mesenchymal transition (EMT) and renal fibrosis are closely involved in chronic kidney disease. Inhibition of histone deacetylase (HDAC) has an anti-fibrotic effect in various diseases. However, the pathophysiological role of isoform-specific HDACs or class-selective HDACs in renal fibrosis remains unknown. Here, we investigated EMT markers and extracellular matrix (ECM) proteins in a human proximal tubular cell line (HK-2) by using HDAC inhibitors or by knockdown of class I HDACs (HDAC1, 2, 3 and 8)...
July 15, 2016: Journal of Cellular and Molecular Medicine
Wen-Chin Lee, Chien-Hua Chiu, Jin-Bor Chen, Chiu-Hua Chen, Hsueh-Wei Chang
The aim of this study was to examine the effect of mitochondrial morphogenesis changes on apoptosis and autophagy of high-glucose-treated proximal tubular epithelial cells (HK2). Cell viability, apoptosis, and mitochondrial morphogenesis were examined using crystal violet, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and mitotracker staining, respectively. High glucose inhibited cell viability and induced mitochondrial fission in HK2 cells. After depleting mitofusin 1 (MFN1), the MFN1(-) HK2 cells (fission type) became more susceptible to high-glucose-induced apoptosis and mitochondrial fragmentation observed by TUNEL and mitotracker assays...
July 15, 2016: DNA and Cell Biology
Qingguo Li, Yi Qin, Ping Wei, Peng Lian, Yaqi Li, Ye Xu, Xinxiang Li, Dawei Li, Sanjun Cai
UNLABELLED: Growth arrest-specific 1 (Gas1) plays a critical role in growth suppression. Previous study indicated that Gas1 was closely associated with survival in patients with colorectal cancer; however, the underlying molecular mechanism remains unclear. In this study, we sought to determine the role of Gas1 in tumorigenesis and metastasis, and elucidate the possible mechanism. First, Gas1 was determined as a negative regulator of oncogenesis and metastasis in colorectal cancer. Mechanistically, Gas1 negatively regulated the aerobic glycolysis, a process that contributed to tumor progression and metastasis by providing energy source and building blocks for macromolecule synthesis...
September 2016: Molecular Cancer Research: MCR
Yoon-Kyung Chang, Hyunsu Choi, Jin Young Jeong, Ki-Ryang Na, Kang Wook Lee, Beom Jin Lim, Dae Eun Choi
Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated with or without SGLT2 inhibitor to investigate cell survival, the apoptosis signal pathway, and the induction of hypoxia-inducible factor 1 (HIF1) and associated proteins...
2016: PloS One
P L Martin, J-J Yin, V Seng, O Casey, E Corey, C Morrissey, R M Simpson, K Kelly
Prostate cancer is characterized by a dependence upon androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) is the accepted treatment for progressive prostate cancer. Although ADT is usually initially effective, acquired resistance termed castrate-resistant prostate cancer (CRPC) develops. PTEN and TP53 are two of the most commonly deleted or mutated genes in prostate cancer, the compound loss of which is enriched in CRPC. To interrogate the metabolic alterations associated with survival following ADT, we used an orthotopic model of Pten/Tp53 null prostate cancer...
July 4, 2016: Oncogene
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