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https://www.readbyqxmd.com/read/28625483/silymarin-protects-against-renal-injury-through-normalization-of-lipid-metabolism-and-mitochondrial-biogenesis-in-high-fat-fed-mice
#1
Bin Feng, Ran Meng, Bin Huang, Yan Bi, Shanmei Shen, Dalong Zhu
Obesity is associated with an increased risk of chronic kidney diseases and the conventional treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors is not enough to prevent renal injury and prolong the progression of disease. Recently, silymarin has shown protective effects on renal tissue injury, but the underlying mechanisms remain elusive. The goal of this study was to investigate the potential capacity of silymarin to prevent renal injury during obesity induced by high fat diet (HFD) in mice...
June 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28622688/integration-of-metabolomics-transcriptomics-and-microrna-expression-profiling-reveals-a-mir-143-hk2-glucose-network-underlying-zinc-deficiency-associated-esophageal-neoplasia
#2
Louise Y Fong, Ruiyan Jing, Karl J Smalley, Cristian Taccioli, Johannes Fahrmann, Dinesh K Barupal, Hansjuerg Alder, John L Farber, Oliver Fiehn, Carlo M Croce
Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats vs sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry (n = 8/group). The Zn-deficient proliferative esophagus exhibits a distinct metabolic profile with glucose down 153-fold and lactic acid up 1...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618048/transcriptomic-profiling-in-human-decidua-of-severe-preeclampsia-detected-by-rna-sequencing
#3
Jing Tong, Weixiu Zhao, Hong Lv, Wei-Ping Li, Zi-Jiang Chen, Cong Zhang
Maternal decidua plays a critical role in implantation and placentation. Impaired decidualization causes failed intravascular trophoblast invasion and inadequate placentation and then increases the risk of preeclampsia (PE). RNA sequencing (RNA-Seq) has achieved great advances in the characterization and quantification of transcriptomes, is a powerful tool for new transcript discovery, genome annotation and expression profiling. In the present study, we conducted a RNA-Seq analysis to compare gene expression between decidua of PE (n = 3, early-onset severe PE, EOSPE; n = 3, late-onset severe PE, LOSPE) and normal pregnancies (n = 3)...
June 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28612526/-mir-155-inhibits-the-expression-of-mmps-in-hk2-cells-by-targeting-klf4
#4
Ya-Xian Ning, Jian-Qin Wang, Xiao-Yuan Wang
OBJECTIVES: To determine whether miR -155 inhibits the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in HK2 cells by targeting Kruppel-like factor 4 (KLF4). METHODS: MiR -155-mimic, miR -155-NC empty plasmid, and culture medium were transfected into renal tubular epithelial cells, respectively. Six hours later, the expression of miR -155 was detected by real time-PCR; the expressions of MMP-2, MMP-9 and KLF4 were detected by Western blot; and the activity of MMP-2 and MMP-9 in the cells was detected by gelatin zymography...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28602700/long-non-coding-rna-pvt1-promotes-glycolysis-and-tumor-progression-by-regulating-mir-497-hk2-axis-in-osteosarcoma
#5
Jingyi Song, Xiaolin Wu, Fengxia Liu, Maohua Li, Yuerong Sun, Yan Wang, Chao Wang, Kai Zhu, Xiujuan Jia, Bing Wang, Xuexiao Ma
Cancer cells usually utilize glucose as a carbon source for aerobic glycolysis, a phenomenon known as the Warburg effect. Increasing studies have shown that PVT1 (a long non-coding RNA, lncRNA) functions as critical regulator of multiple cancers. However, it remains totally unknown whether and how PVT1 regulates glucose metabolism in OS cells. In this study, we found that the expression of PVT1 were specifically increased in OS cells and tissues, and the upregulated PVT1 indicated poor prognosis. Glucose uptake, lactate production, and the expression of HK2 in OS cells were increased by overexpression of PVT1, while decreased by PVT1 knockdown...
June 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28598954/role-of-the-sympathetic-nervous-system-in-regulation-of-the-sodium-glucose-cotransporter-2
#6
Vance B Matthews, Rosemary H Elliot, Caroline Rudnicka, Jana Hricova, Lakshini Herat, Markus P Schlaich
BACKGROUND: The sympathetic nervous system (SNS) regulates glucose metabolism in various organs including the kidneys. The sodium glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in renal proximal tubules and its inhibition has been shown to improve glucose control, cardiovascular and renal outcomes. We hypothesized that SNS-induced alterations of glucose metabolism may be mediated via regulation of SGLT2. METHOD: We used human renal proximal tubule cells to investigate the effects of noradrenaline on SGLT2 regulation...
June 8, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28596599/the-mir-125a-hk2-axis-regulates-cancer-cell-energy-metabolism-reprogramming-in-hepatocellular-carcinoma
#7
Fangfang Jin, Yanbo Wang, Yanan Zhu, Shan Li, Ying Liu, Cheng Chen, Xiaohua Wang, Ke Zen, Limin Li
The Warburg effect is a metabolic hallmark of cancer. Tumor cells rapidly adjust their energy source to glycolysis in order to efficiently proliferate in a hypoxic environment, but the mechanism underlying this switch remains incompletely understood. Here, we show that hypoxia potently induces the down-regulation of miR-125a expression in hepatocellular carcinoma (HCC) cells and tumors. Furthermore, we demonstrate that miR-125a could decrease the production of lactate, the uptake of glucose, and the levels of ATP and reactive oxygen species (ROS) in HCC cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28577326/trivalent-chromium-induces-autophagy-by-activating-sphingomyelin-phosphodiesterase-2-and-increasing-cellular-ceramide-levels-in-renal-hk2-cells
#8
Cheng-Lin Yang, Shiow-Her Chiou, Wei-Chun Tai, Nithila A Joseph, Kuan-Chih Chow
In this study, we examined the role of autophagy in the initiation of lipid increases in renal epithelial HK2 cells. We found that trivalent chromium [Cr(III)] induced autophagy by activating sphingomyelin phosphodiesterase 2 (SMPD2). SMPD2 increases levels of ceramide and other lipids. Confocal immunofluorescence microscopy showed that signals of ceramide overlapped with LC3, suggesting that ceramide might play an important role in the formation of autophagosome. In conclusion, our data indicate that Cr(III) induces autophagy via structural aberration of organelle membrane, in particular by the increase of lipid compositions in addition to autophagy-associated proteins...
June 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28561419/endothelial-cells-co-cultured-with-renal-carcinoma-cells-significantly-reduce-reck-expression-under-chemical-hypoxia
#9
Xiaoyi Zhang, Lei Liu, Jing Liu, Zhengyuan Cheng, Zhi Wang, Chuanbing Shi, Fengan Ding, Sijie Chen, Pingsheng Chen
Renal cell carcinoma (RCC) is characterized by excessive angiogenesis, while chronic kidney disease (CKD) suffers from the opposite problem-failure of reparative angiogenesis. It can be due to their different responses to hypoxic environment. But the specific molecular regulators are still unclear. This study is aimed to explore the influence of human renal cell cancer cells (786-0) and human renal tubular epithelial cells (HK-2) on RECK expression, proliferation, and angiogenesis of adjacent microvascular endothelial cells (HMEC-1) under chemical hypoxia...
May 31, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28550410/different-exogenous-sugars-affect-the-hormone-signal-pathway-and-sugar-metabolism-in-red-globe-vitis-vinifera-l-plantlets-grown-in-vitro-as-shown-by-transcriptomic-analysis
#10
Juan Mao, Wenfang Li, Baoqin Mi, Mohammed Mujitaba Dawuda, Alejandro Calderón-Urrea, Zonghuan Ma, Yongmei Zhang, Baihong Chen
Exogenously applied 2% fructose is the most appropriate carbon source that enhances photosynthesis and growth of grape plantlets compared with the same concentrations of sucrose and glucose. The role of the sugars was regulated by the expression of key candidate genes related to hormones, key metabolic enzymes, and sugar metabolism of grape plantlets ( Vitis vinifera L.) grown in vitro. The addition of sugars including sucrose, glucose, and fructose is known to be very helpful for the development of grape (V...
May 26, 2017: Planta
https://www.readbyqxmd.com/read/28536108/inflammatory-stress-promotes-the-development-of-obesity-related-chronic-kidney-disease-via-cd36-in-mice
#11
Ping Yang, Yayun Xiao, Xuan Luo, Yunfei Zhao, Lei Zhao, Yan Wang, Tingting Wu, Li Wei, Zac Varghese, John F Moorhead, Yaxi Chen, Xiong Z Ruan
Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase CD36. HFD feeding alone resulted in obesity, hyperlipidemia and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression...
May 23, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28532652/inhibition-of-glycolysis-by-a-novel-egfr-her2-inhibitor-ku004-suppresses-the-growth-of-her2-cancer
#12
Chongchong Tian, Ziqiao Yuan, Dengqiu Xu, Pingping Ding, Tao Wang, Luyong Zhang, Zhenzhou Jiang
Upregulation of glycolysis was often observed in human HER2-overexpressing cancers. In this study, we demonstrated that KU004, a dual novel EGFR/HER2 inhibitor, disrupted cancer cell proliferation via modulation of glycolysis. KU004, inhibited the Warburg effect by suppressing hexokinase II (HK2) expression at the transcptional and post-translational levels. Further study demonstrated that the downregulation of HKII by KU004 was mainly mediated by the PI3K/Akt signaling pathway. Furthermore, the role of HKII downregulation in KU004-mediated antitumor effect was also confirmed in our in vivo xenograft model...
May 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28522551/inhibition-of-mir-143-during-ischemia-cerebral-injury-protects-neurons-through-recovery-of-the-hexokinase-2-mediated-glucose%C3%A2-uptake
#13
Xianzhu Zeng, Na Liu, Jing Zhang, Lei Wang, Zhecheng Zhang, Ju Zhu, Qian Li, Yuwen Wang
Ischemic stroke, a major cause of death, is caused by occlusion of a blood vessel, resulting in a significant reduction in regional cerebral blood flow. MicroRNAs (miRNAs) are a family of short noncoding RNAs (18 to 22 nucleotides) and bind the 3' un-translated region (UTR) of their target genes to post-transcriptionally suppress gene expression. In this study, we report miR-143 is downregulated in rat neurons but high expressed in astrocytes cells. In vivo middle cerebral artery occlusion (MCAO) and ex vivo oxygen-glucose deprivation (OGD) results showed miR-143 was significantly induced by ischemia injury...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28515149/pyruvate-kinase-inhibits-proliferation-during-postnatal-cerebellar-neurogenesis-and-suppresses-medulloblastoma-formation
#14
Katherine Tech, Andrey P Tikunov, Hamza Farooq, A Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C Green, Hedi Liu, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven J M Jones, Marco A Marra, Matthew G Vander Heiden, Michael D Taylor, Jeffrey M Macdonald, Timothy R Gershon
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNP) and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation, and tumorigenesis...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28498475/targeting-hexokinase-2-inhibition-promotes-radiosensitization-in-hpv16%C3%A2-e7-induced-cervical-cancer-and-suppresses-tumor-growth
#15
Yuan Liu, Tracy Murray-Stewart, Robert A Casero, Ioannis Kagiampakis, Lihua Jin, Jiawen Zhang, Huihui Wang, Qi Che, Huan Tong, Jieqi Ke, Feizhou Jiang, Fangyuan Wang, Xiaoping Wan
In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT...
June 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28483437/4-phenyl-butyric-acid-increases-particulate-hexokinase-activity-and-protects-against-ros-injury-in-l6-myotubes
#16
Michele Hinerasky da Silva, Flavia Letícia Martins Peçanha, Aline Machado de Oliveira, Wagner Seixas da-Silva
Hexokinase (HK) is the first enzyme in the glycolytic pathway and is responsible for glucose phosphorylation and fixation into the cell. HK (HK-II) is expressed in skeletal muscle and can be found in the cytosol or bound mitochondria, where it can protect cells against insults such as oxidative stress. 4-Phenyl butyric acid (4-PBA) is a chemical chaperone that inhibits endoplasmic reticulum stress and contributes to the restoring of glucose homeostasis. AIMS: Here, we decided to investigate whether HK activity and its interaction with mitochondria could be a target of 4-PBA action...
June 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28478957/sirt6-regulated-nucleosomal-occupancy-affects-hexokinase-2-expression
#17
Piyushi Gupta, Touseef Sheikh, Ellora Sen
To understand the molecular association between inflammation and dysregulated metabolism in glioblastoma, the effect of IL-1β on Hexokinase 2 (HK2) expression was investigated. IL-1β induced HK2 expression was accompanied by heightened SIRT6 and MZF1 levels. IL-1β mediated overall decrease in chromatin compactness on HK2 promoter involved diminished nucleosomal occupancy around the most labile region bearing MZF1 sites. Importantly, SIRT6 and MZF1 served as negative regulators of HK2. Ectopic SIRT6 induced formation and recruitment of MZF1-SIRT6 complex to MZF1 site was concomitant with increased nucleosomal occupancy...
August 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28471448/mir-1-suppresses-tumor-cell-proliferation-in-colorectal-cancer-by-inhibition-of-smad3-mediated-tumor-glycolysis
#18
Wanfu Xu, Zijing Zhang, Kejian Zou, Yang Cheng, Min Yang, Huan Chen, Hongli Wang, Junhong Zhao, Peiyu Chen, Liying He, Xinwen Chen, Lanlan Geng, Sitang Gong
Aberrant expression of microRNA (miR)-1 has been observed in many human malignancies. However, the function and underlying mechanism of miR-1 remains elusive. To address the specific role of miR-1 in tumor glycolysis using the gain- or loss-of-function studies. Metabolic studies combined with gene expression analysis were performed in vitro and in vivo. We demonstrated aberrant expression of miR-1 in aerobic glycolysis, the Warburg effect, in cancer cells. MiR-1 suppressed aerobic glycolysis and tumor cell proliferation via inactivation of Smad3 and targeting HIF-1α, leading to reduce HK2 and MCT4 expression, which illustrated a novel pathway to mediate aerobic glycolysis in cancer cells...
May 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28467822/fgf-dependent-metabolic-control-of-vascular-development
#19
Pengchun Yu, Kerstin Wilhelm, Alexandre Dubrac, Joe K Tung, Tiago C Alves, Jennifer S Fang, Yi Xie, Jie Zhu, Zehua Chen, Frederik De Smet, Jiasheng Zhang, Suk-Won Jin, Lele Sun, Hongye Sun, Richard G Kibbey, Karen K Hirschi, Nissim Hay, Peter Carmeliet, Thomas W Chittenden, Anne Eichmann, Michael Potente, Michael Simons
Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism, little is understood about the role of fibroblast growth factors (FGFs) in this context...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28448866/function-of-microrna-143-in-different-signal-pathways-in-cancer-new-insights-into-cancer-therapy
#20
REVIEW
Leila Karimi, Behzad Mansoori, Dariush Shanebandi, Ali Mohammadi, Mahyar Aghapour, Behzad Baradaran
MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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