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https://www.readbyqxmd.com/read/28922168/evaluation-of-rna-blood-biomarkers-in-individuals-at-risk-of-parkinson-s-disease
#1
Jose A Santiago, Judith A Potashkin
BACKGROUND: Substantial progress has been made in the discovery of blood biomarkers for Parkinson's disease (PD), a progressive neurodegenerative disease that affects more than 4 million worldwide. Olfactory dysfunction and dopamine deficits usually precede motor symptoms years before the onset of PD. A readily accessible biomarker useful for identifying patients at risk of PD is expected to accelerate clinical trials. OBJECTIVE: To evaluate previously identified PD blood RNA biomarkers in a cohort of asymptomatic individuals at risk of PD...
September 11, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28871187/prolonged-fasting-elicits-increased-hepatic-triglyceride-accumulation-in-rats-born-to-dexamethasone-treated-mothers
#2
Lucas Carminatti Pantaleão, Gilson Murata, Caio Jordão Teixeira, Tanyara Baliani Payolla, Junia Carolina Santos-Silva, Daniella Esteves Duque-Guimaraes, Frhancielly S Sodré, Camilo Lellis-Santos, Juliana Camargo Vieira, Dailson Nogueira de Souza, Patrícia Rodrigues Gomes, Sandra Campos Rodrigues, Gabriel Forato Anhe, Silvana Bordin
We investigated the effect of dexamethasone during the last week of pregnancy on glucose and lipid metabolism in male offspring. Twelve-week old offspring were evaluated after fasting for 12-hours (physiological) and 60-hours (prolonged). Physiological fasting resulted in glucose intolerance, decreased glucose clearance after pyruvate load and increased PEPCK expression in rats born to dexamethasone-treated mothers (DEX). Prolonged fasting resulted in increased glucose tolerance and increased glucose clearance after pyruvate load in DEX...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28858851/epigenetic-silencing-of-mir-338-facilitates-glioblastoma-progression-by-de-repressing-the-pyruvate-kinase-m2-%C3%AE-catenin-axis
#3
Bo Han, Xiangqi Meng, Hui Chen, Lingchao Chen, Xing Liu, Hongjun Wang, Daming Liu, Fei Gao, Lin Lin, Jianguang Ming, Bo Sun, Shi Yin, Ruijia Wang, Pengfei Wu, Jinquan Cai, Chuanlu Jiang
Glioblastoma is the most malignant type of brain tumor, and its high invasiveness and multiplication severely shortens patients' overall survival. The embryonic pyruvate kinase M2 (PKM2) isoform is highly expressed in human cancer. We used computational target gene prediction, in vitro cell culture, immunoblotting, quantitative real-time PCR, ATP measurements, luciferase reporter assays, wound-healing assays, Transwell assays, RNA immunoprecipitation PCR, co-immunoprecipitation, flow cytometry and tumor xenografts to study the regulation of the PKM2/β-catenin axis in glioma...
August 2, 2017: Aging
https://www.readbyqxmd.com/read/28829588/apigenin-restrains-colon-cancer-cell-proliferation-via-targeted-blocking-of-pyruvate-kinase-m2-dependent-glycolysis
#4
Shuhua Shan, Jiangying Shi, Peng Yang, Bin Jia, Haili Wu, Xiaoli Zhang, Zhuoyu Li
Apigenin (AP), as an anticancer agent, has been widely explored. However, the molecular targets of apigenin on tumor metabolism are unclear. Herein, we found that AP could block cellular glycolysis through restraining the tumor-specific pyruvate kinase M2 (PKM2) activity and expression and further significantly induce anti-colon cancer effects. The IC50 values of AP against HCT116, HT29, and DLD1 cells were 27.9 ± 2.45, 48.2 ± 3.01 and 89.5 ± 4.89 μM, respectively. Fluorescence spectra and solid-phase AP extraction assays proved that AP could directly bind to PKM2 and markedly inhibit PKM2 activity in vitro and in HCT116 cells...
September 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28827059/enhanced-aerobic-glycolysis-of-nasopharyngeal-carcinoma-cells-by-epstein-barr-virus-latent-membrane-protein-1
#5
Wei-Wen Sung, Peir-Rong Chen, Ming-Hui Liao, Jeng-Woei Lee
Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells...
August 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28818096/immunohistochemical-prognostic-markers-of-esophageal-squamous-cell-carcinoma-a-systematic-review
#6
Chunni Wang, Jingnan Wang, Zhaoli Chen, Yibo Gao, Jie He
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the prognosis of ESCC, but none has been widely accepted to guide clinical care. This study aimed to identify proteins with great potential for predicting prognosis of ESCC. METHODS: We conducted a systematic review on immunohistochemical (IHC) prognostic markers of ESCC according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines...
August 17, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28802581/pkm2-aggravates-palmitate-induced-insulin-resistance-in-hepg2-cells-via-stat3-pathway
#7
Ling Chen, Zhuqi Tang, Xiaohua Wang, Hong Ma, Dandan Shan, Shiwei Cui
Studies have identified that PKM2 is related to the development of glucose intolerance and insulin resistance in rodents and humans. However, the underlying mechanism remains largely unknown. In the present study, we found that PKM2 expression was significantly elevated in insulin-resistant hepatic tissues and hepatocytes, implicating an association between PKM2 expression and hepatic insulin resistance (IR). In vitro study revealed that overexpression of PKM2 impaired the insulin signaling pathway by decreasing the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK3β)...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28791350/prl-3-improves-colorectal-cancer-cell-proliferation-and-invasion-through-il-8-mediated-glycolysis-metabolism
#8
Heyang Xu, Yujie Zeng, Lu Liu, Qian Gao, Shaowen Jin, Qiusheng Lan, Wei Lai, Xingxi Luo, Heng Wu, Yongliang Huang, Zhonghua Chu
Phosphatase of regenerating liver-3 (PRL-3) has been found to be overexpressed in liver metastases of colorectal cancer and rarely expressed in primary tumors, which plays an important role in the metastasis of colorectal cancer cells. Metabolism reprogramming has been found to be a hallmark of cancer cells, and aerobic glycolysis is a metabolic adaption for cancer cells and promotes cell proliferation. However, the association between PRL-3 and glycolysis in colorectal cancer cells is not well understood. In the present study, we explored the association between PRL-3 and glycolysis...
August 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28778087/pkm2-activation-sensitizes-cancer-cells-to-growth-inhibition-by-2-deoxy-d-glucose
#9
Sui Seng Tee, Jae Mo Park, Ralph E Hurd, Kyle R Brimacombe, Matthew B Boxer, Tarik F Massoud, Brian K Rutt, Daniel M Spielman
Cancer metabolism has emerged as an increasingly attractive target for interfering with tumor growth. Small molecule activators of pyruvate kinase isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in increased glucose consumption, providing the rationale for combining PKM2 activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination treatment resulted in reduced viability of a range of cell lines in standard cell culture conditions at concentrations of drugs that had no effect when used alone...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28769740/discovery-and-validation-of-a-colorectal-cancer-classifier-in-a-new-blood-test-with-improved-performance-for-high-risk-subjects
#10
Lisa J Croner, Roslyn Dillon, Athit Kao, Stefanie N Kairs, Ryan Benz, Ib J Christensen, Hans J Nielsen, John E Blume, Bruce Wilcox
BACKGROUND: The aim was to improve upon an existing blood-based colorectal cancer (CRC) test directed to high-risk symptomatic patients, by developing a new CRC classifier to be used with a new test embodiment. The new test uses a robust assay format-electrochemiluminescence immunoassays-to quantify protein concentrations. The aim was achieved by building and validating a CRC classifier using concentration measures from a large sample set representing a true intent-to-test (ITT) symptomatic population...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28757909/metabolic-reprogramming-autophagy-and-reactive-oxygen-species-are-necessary-for-primordial-germ-cell-reprogramming-into-pluripotency
#11
D Sainz de la Maza, A Moratilla, V Aparicio, C Lorca, Y Alcaina, D Martín, M P De Miguel
Cellular reprogramming is accompanied by a metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Previous results from our laboratory showed that hypoxia alone is able to reprogram primordial germ cells (PGCs) into pluripotency and that this action is mediated by hypoxia-inducible factor 1 (HIF1). As HIF1 exerts a myriad of actions by upregulating several hundred genes, to ascertain whether the metabolic switch toward glycolysis is solely responsible for reprogramming, PGCs were cultured in the presence of a pyruvate kinase M2 isoform (PKM2) activator, or glycolysis was promoted by manipulating PPARγ...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28754874/pyruvate-kinase-m2-deregulation-enhances-the-metastatic-potential-of-tongue-squamous-cell-carcinoma
#12
Wei Wang, Qianting He, Jingjing Sun, Zhonghua Liu, Luodan Zhao, Zhiyuan Lu, Xiaofeng Zhou, Anxun Wang
Pyruvate kinase M2 (PKM2) has been verified to correlate with the prognosis of many types of cancer. However, its role in the development and metastasis of tongue squamous cell carcinoma (TSCC) remains unclear. The immunohistochemistry (IHC) results confirmed that PKM2 is overexpressed in patients with TSCC. PKM2 up-regulation was related to lymph node metastasis and associated with reduced overall survival. According to the microarray analysis and Western blots, PKM2 expression was up-regulated in TSCC cells with enhanced metastatic potential...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753677/pyruvate-kinase-m2-is-a-poor-prognostic-marker-of-and-a-therapeutic-target-in-ovarian-cancer
#13
Tai-Kuang Chao, Tien-Shuo Huang, Yu-Ping Liao, Rui-Lan Huang, Po-Hsuan Su, Hueng-Yuan Shen, Hung-Cheng Lai, Yu-Chi Wang
Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001) and pathogenesis models (p < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28746922/effects-of-pkm2-gene-silencing-on-the-proliferation-and-apoptosis-of-colorectal-cancer-ls-147t-and-sw620-cells
#14
Ran Ao, Lin Guan, Ying Wang, Jia-Ni Wang
BACKGROUND/AIMS: This paper aims to explore the effects of pyruvate kinase (PK) M2 gene silencing on the proliferation and apoptosis of colorectal cancer (CRC) LS-147T and SW620 cells. METHODS: CRC LS-147T and SW620 cells highly expressing PKM2 were randomly selected by quantitative real-time polymerase chain reaction (qRT-PCR) and then assigned into the blank (no transfection), PKM2-shRNA (transfection with shRNA) and empty plasmid (transfection with empty plasmid) groups...
July 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28743549/pyruvate-kinase-m1-interacts-with-a-raf-and-inhibits-endoplasmic-reticulum-stress-induced-apoptosis-by-activating-mek1-erk-pathway-in-mouse-insulinoma-cells
#15
Yuta Horiuchi, Daiki Nakatsu, Fumi Kano, Masayuki Murata
Apoptotic death of pancreatic β cells is a major cause of type 2 diabetes mellitus (T2D) progression. Two isoforms of pyruvate kinase, PKM1 and PKM2, have been reported to participate in cell death in several cell types; however, little is known about their causal pathways in pancreatic β-cell death. We examined whether the suppression of PKM1 or PKM2 affects endoplasmic reticulum (ER) stress-induced apoptosis in a pancreatic β-cell line, MIN6, and Beta-TC-6 and found that knockdown of PKM1, but not of PKM2, leads to the induction of ER stress-induced apoptosis in these cells...
July 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28728385/effects-of-dietary-energy-sources-on-early-postmortem-muscle-metabolism-of-finishing-pigs
#16
Yanjiao Li, Changning Yu, Jiaolong Li, Lin Zhang, Feng Gao, Guanghong Zhou
Objective: This study investigated the effects of different dietary energy sources on early postmortem muscle metabolism of finishing pigs. Methods: Seventy-two barrow (Duroc × Landrace × Yorkshire, DLY) pigs (65.0 ± 2.0 kg) were allotted to three iso-energetic and iso-nitrogenous diets: A (44.1% starch, 5.9% crude fat and 12.6% neutral detergent fibre (NDF)), B (37.6% starch, 9.5% crude fat and 15.4% NDF) or C (30.9% starch, 14.3% crude fat and 17.8% NDF). After the duration of 28-day feeding experiment, 24 pigs (eight per treatment) were slaughtered and the M...
June 26, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28726775/oroxylin-a-activates-pkm1-hnf4-alpha-to-induce-hepatoma-differentiation-and-block-cancer-progression
#17
Libin Wei, Yuanyuan Dai, Yuxin Zhou, Zihao He, Jingyue Yao, Li Zhao, Qinglong Guo, Lin Yang
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28723644/fir-haplodeficiency-promotes-splicing-to-pyruvate-kinase-m2-in-mice-thymic-lymphoma-tissues-revealed-by-six-plex-tandem-mass-tag-quantitative-proteomic-analysis
#18
Asako Kimura, Kouichi Kitamura, Guzhanuer Ailiken, Mamoru Satoh, Toshinari Minamoto, Nobuko Tanaka, Fumio Nomura, Kazuyuki Matsushita
The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28715126/an-engineered-photoswitchable-mammalian-pyruvate-kinase
#19
Stefanie Gehrig, Jamie A Macpherson, Paul C Driscoll, Alastair Symon, Stephen R Martin, James I MacRae, Jens Kleinjung, Franca Fraternali, Dimitrios Anastasiou
Changes in allosteric regulation of glycolytic enzymes have been linked to metabolic reprogramming involved in cancer. Remarkably, allosteric mechanisms control enzyme function at significantly shorter time-scales compared to the long-term effects of metabolic reprogramming on cell proliferation. It remains unclear if and how the speed and reversibility afforded by rapid allosteric control of metabolic enzymes is important for cell proliferation. Tools that allow specific, dynamic modulation of enzymatic activities in mammalian cells would help address this question...
July 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28709426/xue-fu-zhu-yu-decoction-protects-rats-against-retinal-ischemia-by-downregulation-of-hif-1%C3%AE-and-vegf-via-inhibition-of-rbp2-and-pkm2
#20
Shu-Qiu Tan, Xue Geng, Jorn-Hon Liu, Wynn Hwai-Tzong Pan, Li-Xiang Wang, Hui-Kang Liu, Lei Hu, Hsiao-Ming Chao
BACKGROUND: Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia. METHODS: Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed...
July 14, 2017: BMC Complementary and Alternative Medicine
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