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https://www.readbyqxmd.com/read/27908730/mtor-activation-is-critical-for-betulin-treatment-in-renal-cell-carcinoma-cells
#1
Wenlong Cheng, Shiqi Ji, Haijian Zhang, Zhixing Han, Qingjun Liu, Jianwen Wang, Hao Ping
Betulin, a natural product isolated from the bark of the birch trees, exhibits multiple anticancer effects. Activation of mTOR signaling pathway has been found in numerous cancers, including renal cell carcinoma (RCC). Here, we attempted to study whether mTOR signaling was essential for betulin to treat RCC. Based on cell survival and colony formation assays, we found that mTOR hyperactive RCC cell line 786-O cells were more sensitive to betulin treatment compared with mTOR-inactive Caki-2 cells. Knockdown of TSC2 in Caki-2 cells had similar results to 786-O cells, and mTOR silencing in 786-O cells rescued the inhibitory effect of betulin, indicating that betulin inhibited RCC cell proliferation in an mTOR-dependent manner...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27906079/muscle-specific-loss-of-bmal1-leads-to-disrupted-tissue-glucose-metabolism-and-systemic-glucose-homeostasis
#2
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 (-/-))...
March 30, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903863/internalization-of-secreted-antigen-targeted-antibodies-by-the-neonatal-fc-receptor-for-precision-imaging-of-the-androgen-receptor-axis
#3
Daniel L J Thorek, Philip A Watson, Sang-Gyu Lee, Anson T Ku, Stylianos Bournazos, Katharina Braun, Kwanghee Kim, Kjell Sjöström, Michael G Doran, Urpo Lamminmäki, Elmer Santos, Darren Veach, Mesruh Turkekul, Emily Casey, Jason S Lewis, Diane S Abou, Marise R H van Voss, Peter T Scardino, Sven-Erik Strand, Mary L Alpaugh, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27898408/sulodexide-protects-contrast-induced-nephropathy-in-sprague-dawley-rats
#4
Qing Zhao, Jianyong Yin, Zeyuan Lu, Yiwei Kong, Guangyuan Zhang, Binghui Zhao, Feng Wang
BACKGROUND: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. METHODS: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide)...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27888806/decreased-dach1-expression-in-glomerulopathy-is-associated-with-disease-progression-and-severity
#5
Qing-Quan Liu, Ya-Qun Zhou, Hui-Quan Liu, Wen-Hui Qiu, Hui Liu, Ting-Yang Hu, Qing Xu, Yong-Man Lv, Kong-Ming Wu
Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated protein that regulates cellular differentiation throughout development. Recent genome-wide association studies have show that missense mutation in DACH1 leads to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate glomerular filtration rate (eGFR). We firstly characterized the function of DACH1 in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN) patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal change disease (MCD) patients...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27881486/lysine-63-ubiquitination-is-involved-in-the-progression-of-tubular-damage-in-diabetic-nephropathy
#6
Paola Pontrelli, Francesca Conserva, Massimo Papale, Annarita Oranger, Mariagrazia Barozzino, Grazia Vocino, Maria Teresa Rocchetti, Margherita Gigante, Giuseppe Castellano, Michele Rossini, Simona Simone, Luigi Laviola, Francesco Giorgino, Giuseppe Grandaliano, Salvatore Di Paolo, Loreto Gesualdo
The purpose of our study was to evaluate how hyperglycemia (HG) influences Lys63 protein ubiquitination and its involvement in tubular damage and fibrosis in diabetic nephropathy (DN). Gene and protein expression of UBE2v1, a ubiquitin-conjugating E2-enzyme variant that mediates Lys63-linked ubiquitination, and Lys63-ubiquitinated proteins increased in HK2 tubular cells under HG. Matrix-assisted laser desorption/ionization-time of flight/tandem mass spectrometry identified 30 Lys63-ubiquitinated proteins, mainly involved in cellular organization, such as β-actin, whose Lys63 ubiquitination increased under HG, leading to cytoskeleton disorganization...
October 24, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27862254/hk2-proximal-tubule-epithelial-cells-synthesize-and-secrete-plasma-proteins-predominantly-through-the-apical-surface
#7
Ke-Wei Zhao, Elsa J Brochmann Murray, Samuel S Murray
Renal proximal tubule epithelial cells (PTECs) are known to reabsorb salts and small plasma proteins filtered through Bowman's capsule. Following acute kidney injury, PTECs assume some characteristics of hepatocytes in producing various plasma proteins. We now demonstrate that even at a resting state, a PTEC cell line, HK2 expresses mRNAs for and synthesizes and secretes plasma proteins in a complex with complement C3, an α2 -macroglobulin family chaperone, including albumin, transferrin, α1 -antitrypsin, α1 -antichymotrypsin, α2 -HS-glycoprotein, ceruloplasmin, haptoglobin, C1-inhibitor, secreted phosphoprotein-24, and insulin-like growth factor-1...
November 9, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27830690/-detection-of-novel-genetic-markers-of-susceptibility-to-preeclampsia-based-on-an-analysis-of-the-regulatory-genes-in-the-placental-tissue
#8
V N Serebrova, E A Trifonova, T V Gabidulina, I Yu Bukharina, T A Agarkova, I D Evtushenko, N R Maksimova, V A Stepanov
Regulatory single nucleotide polymorphisms (rSNPs) are the least-studied group of SNP; however, they play an essential role in the development of human pathology by altering the level of candidate genes expression. In this work, we analyzed 29 rSNPs in 17 new candidate genes associated with preeclampsia (PE) according to the analysis of the transcriptome in placental tissue. Three ethnic groups have been studied (yakut, russian, and buryat). We have detected significant associations of PE with eight rSNPs in six differentially expressed genes, i...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27829129/resveratrol-inhibits-hexokinases-ii-mediated-glycolysis-in-non-small-cell-lung-cancer-via-targeting-akt-signaling-pathway
#9
Wei Li, Xiaoqian Ma, Na Li, Huasheng Liu, Qiong Dong, Juan Zhang, Cejun Yang, Yin Liu, Qi Liang, Shengwang Zhang, Chang Xu, Wei Song, Shiming Tan, Pengfei Rong, Wei Wang
Deregulation of glycolysis was often observed in human cancer cells. In the present study, we reported resveratrol, a small polyphenol, which has been intensively studied in various tumor models, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via regulation of glycolysis. Resveratrol impaired hexokinase II (HK2)-mediated glycolysis, and markedly inhibited anchorage-dependent and -independent growth of NSCLC cells. Exposure to resveratrol decreased EGFR and downstream kinases Akt and ERK1/2 activation...
November 6, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27824926/prognostic-significance-of-the-metabolic-marker-hexokinase-2-in-various-solid-tumors-a-meta-analysis
#10
Yulin Liu, Ke Wu, Liang Shi, Fan Xiang, Kaixiong Tao, Guobin Wang
OBJECTIVE: Recently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor. METHODS: Eligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27819540/fine-mapping-of-a-new-race-specific-blast-resistance-gene-pi-hk2-in-japonica-heikezijing-from-taihu-region-of-china
#11
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 the Taihu region of China, exhibited broad-spectrum resistance to more than 300 isolates of the blast pathogen (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 races of blast in the Taihu Lake region of China, was inoculated into 162 recombinant inbred lines (RIL) and two parents, Heikezijing and Suyunuo, for mapping the resistance-blast quantitative trait loci (QTL)...
November 7, 2016: Phytopathology
https://www.readbyqxmd.com/read/27796318/jolkinolide-b-induces-apoptosis-and-inhibits-tumor-growth-in-mouse-melanoma-b16f10-cells-by-altering-glycolysis
#12
Caixia Gao, Xinyan Yan, Bo Wang, Lina Yu, Jichun Han, Defang Li, Qiusheng Zheng
Most cancer cells preferentially rely on glycolysis to produce the energy (adenosine triphosphate, ATP) for growth and proliferation. Emerging evidence demonstrates that the apoptosis in cancer cells could be closely associated with the inhibition of glycolysis. In this study, we have found that jolkinolide B (JB), a bioactive diterpenoid extracted from the root of Euphorbia fischeriana Steud, induced tumor cells apoptosis and decreased the production of ATP and lactic acid in mouse melanoma B16F10 cells. Furthermore, we found that JB downregulated the mRNA expression of glucose transporter genes (Glut1, Glut3 and Glut4) and glycolysis-related kinase genes (Hk2 and Ldha) in B16F10 cells...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27784694/deficiency-of-mpges-1-exacerbates-renal-fibrosis-and-inflammation-in-mice-with-unilateral-ureteral-obstruction
#13
Renfei Luo, Yutaka Kakizoe, Feifei Wang, Xiang Fan, Shan Hu, Tianxin Yang, Weidong Wang, Chunling Li
Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 to prostaglandin E2 (PGE2), plays an important role in a variety of inflammatory diseases. We investigated the contribution of mPGES-1 to renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) for 7 days using wild type (WT) and mPGES-1 knockout (KO) mice. UUO induced increased mRNA and protein expression of mPGES-1 and cyclooxygenase-2 in WT mice. UUO was associated with increased renal PGE2 content and upregulated PGE2 receptor (EP) 4 expression in obstructed kidneys of both WT and KO mice; EP4 expression levels were higher in KO mice with UUO than that in WT mice...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784456/-the-role-of-hexokinase-2-in-the-metastasis-of-hepatocellular-carcinoma-cells
#14
X L Geng, W H Long, J Hai, Y Zhang, W Zheng, Z Y Zhang, L X Du
Objective: To investigate the regulatory role of HK2 in the metastasis of hepatocellular carcinoma (HCC). Methods: The protein expressions of HK2 in 73 HCC tumor tissues and paired adjacent non-tumor tissues were evaluated by using immunohistochemical analysis. The scratch wound healing assay and Transwell assay had been used to analyze the migration and invasion of HCC cells with HK2 knockdown. Expressions of epithelial-to-mesenchymal transition (EMT)markers, such as E-cadherin, ZO-1, N-cadherin and vimentin, in HCC cells with HK2 knockdown were determined by qRT-PCR and Western blot analysis...
October 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27775792/mir-143-is-involved-in-endothelial-cell-dysfunction-through-suppression-of-glycolysis-and-correlated-with-atherosclerotic-plaques-formation
#15
R-H Xu, B Liu, J-D Wu, Y-Y Yan, J-N Wang
OBJECTIVE: Atherosclerosis is recognized as a chronic inflammatory disease leading to hardening of the vessel wall and narrowing of arteries. Endothelial cells (ECs) exhibit highly active glycolysis, the dysfunction of which leads to accumulation of lipids in the arterial wall and formation of atherosclerotic plaque. MATERIALS AND METHODS: qRT-PCR was performed to compare the deregulated miR-143 between atherosclerotic plaque and normal vessel tissues. The direct target of miR-143 was verified by Western blot and luciferase assay...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27771605/biodegradability-of-dbp-precursors-after-drinking-water-ozonation
#16
Glen Andrew de Vera, Jurg Keller, Wolfgang Gernjak, Howard Weinberg, Maria José Farré
Ozonation is known to generate biodegradable organic matter, which is typically reduced by biological filtration to avoid bacterial regrowth in distribution systems. Post-chlorination generates halogenated disinfection byproducts (DBPs) but little is known about the biodegradability of their precursors. This study determined the effect of ozonation and biofiltration conditions, specifically ozone exposure and empty bed contact time (EBCT), on the control of DBP formation potentials in drinking water. Ozone exposure was varied through addition of H2O2 during ozonation at 1 mgO3/mgDOC followed by biological filtration using either activated carbon (BAC) or anthracite...
October 8, 2016: Water Research
https://www.readbyqxmd.com/read/27765905/integrative-genomics-reveals-hypoxia-inducible-genes-that-are-associated-with-a-poor-prognosis-in-neuroblastoma-patients
#17
Mark A Applebaum, Aashish R Jha, Clara Kao, Kyle M Hernandez, Gillian DeWane, Helen R Salwen, Alexandre Chlenski, Marija Dobratic, Christopher J Mariani, Lucy A Godley, Nanduri Prabhakar, Kevin White, Barbara E Stranger, Susan L Cohn
Neuroblastoma is notable for its broad spectrum of clinical behavior ranging from spontaneous regression to rapidly progressive disease. Hypoxia is well known to confer a more aggressive phenotype in neuroblastoma. We analyzed transcriptome data from diagnostic neuroblastoma tumors and hypoxic neuroblastoma cell lines to identify genes whose expression levels correlate with poor patient outcome and are involved in the hypoxia response. By integrating a diverse set of transcriptome datasets, including those from neuroblastoma patients and neuroblastoma derived cell lines, we identified nine genes (SLCO4A1, ENO1, HK2, PGK1, MTFP1, HILPDA, VKORC1, TPI1, and HIST1H1C) that are up-regulated in hypoxia and whose expression levels are correlated with poor patient outcome in three independent neuroblastoma cohorts...
October 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27754228/os-33-04-regulation-of-sglt-2-by-the-sympathetic-nervous-system
#18
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
https://www.readbyqxmd.com/read/27748854/hypoxia-induces-glucose-uptake-and-metabolism-of-adipose%C3%A2-derived-stem-cells
#19
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
https://www.readbyqxmd.com/read/27670771/fine-mapping-of-a-new-race-specific-blast-resistance-gene-pi-hk2-in-japonica-heikezijing-from-taihu-region-of-china
#20
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
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