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https://www.readbyqxmd.com/read/29777753/characterization-of-impaired-cerebrovascular-structure-in-app-ps1-mouse-brains
#1
Kee-Chan Ahn, Cameron R Learman, Gary L Dunbar, Panchanan Maiti, Won-Cheoul Jang, Hyeon-Cheol Cha, Mee-Sook Song
Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD...
May 16, 2018: Neuroscience
https://www.readbyqxmd.com/read/29770652/-effects-of-glycolytic-pathway-on-generation-of-regulatory-t-cells-during-schistosoma-japonicum-infection
#2
Wang Xiao-Fan, Qi Qian-Qian, Zhang Li-Na, Xu Lei, Dong Li-Yang, Li Ya-Lin, Pu Ya-Nan, Wei Chuan, Zhou Sha, Zhu Ji-Feng, Chen Xiao-Jun, Su Chuan
OBJECTIVE: To assess the influence of glycolytic pathway on the proportion and numbers of regulatory T cells during Schistosoma japonicum infection. METHODS: A S. japonicum -infected mouse model was established, and C57/BL6 male mice infected with S. japonicum were subjected to intraperitoneal injections of with the glycolytic inhibitor 2-Deoxy-D-glucose (2DG) or PBS for 6 times, and then the cells from spleen or mesenteric lymph nodes (LNs) were isolated and analyzed by flow cytometry (FCM) to detect the percentage of Glut1+ CD4+ T cells and Treg cells...
April 20, 2018: Zhongguo Xue Xi Chong Bing Fang Zhi za Zhi, Chinese Journal of Schistosomiasis Control
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#3
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29749314/glycolysis-inhibition-as-a-strategy-for-hepatocellular-carcinoma-treatment
#4
Andreia Alves, Ana Catarina Mamede, Marco Alves, Pedro F Oliveira, Sandra Moreira Rocha, Filomena Botelho, Claudio Jorge Maia
Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis...
April 30, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29741792/frontline-science-pathological-conditioning-of-human-neutrophils-recruited-to-the-airway-milieu-in-cystic-fibrosis
#5
Osric A Forrest, Sarah A Ingersoll, Marcela K Preininger, Julie Laval, Dominique H Limoli, Milton R Brown, Frances E Lee, Brahmchetna Bedi, Ruxana T Sadikot, Joanna B Goldberg, Vin Tangpricha, Amit Gaggar, Rabindra Tirouvanziam
RATIONALE: Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies...
May 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29741207/genetic-generalized-epilepsies
#6
Saul A Mullen, Samuel F Berkovic
The genetic generalized epilepsies (GGEs) are mainly genetically determined disorders. Although inheritance in most cases appears to be complex, involving multiple genes, variants of a number of genes are known to contribute. Pathogenic variants of SLC2A1 leading to autosomal-dominant GLUT1 deficiency account for up to 1% of cases, increasing to 10% of those with absence seizures starting before age 4 years. Copy number variants are found in around 3% of cases, acting as risk alleles. Copy number variation is much more common in those with comorbid learning disability...
May 9, 2018: Epilepsia
https://www.readbyqxmd.com/read/29730803/paroxysmal-ocular-movements-an-early-sign-in-glut1-deficiency-syndrome
#7
Sofia Reis, Joana Matias, Raquel Machado, José Paulo Monteiro
The authors describe a 3-year-old female, diagnosed with GLUT1 deficiency Syndrome, with a previously unreported mutation in exon 7 of the SLC2A1 gene: c.968_972 + 3del P. (Val323Alafs*53), characterized by a classic phenotypic of acquired microcephaly, developmental delay, ataxia, spasticity, and epilepsy. Ketogenic diet was started at the age of 30 months with epilepsy improvement. She presented paroxysmal ocular movements in the first 12 months of life, recently defined as "aberrant gaze saccades", that are present in the early phase of visual system development, being one of the first disease signs, but easily disregarded...
May 5, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29725302/brain-transport-profiles-of-ginsenoside-rb-1-by-glucose-transporter-1-in-vitro-and-in-vivo
#8
Yu-Zhu Wang, Qing Xu, Wei Wu, Ying Liu, Ying Jiang, Qing-Qing Cai, Qian-Zhou Lv, Xiao-Yu Li
Ginsenoside Rb1 (Rb1 ) has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb1 transport at the blood-brain barrier (BBB) using primary cultured rat brain microvascular endothelial cells (rBMEC), an in vitro BBB model. The initial uptake velocity of Rb1 in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29719622/glucose-transporter-1-expression-as-a-marker-of-prognosis-in-oesophageal-adenocarcinoma
#9
Jaine K Blayney, Lauren Cairns, Gerald Li, Niamh McCabe, Leanne Stevenson, Christopher J Peters, Nathan B Reid, Veronica J Spence, Chintapuza Chisambo, Damian McManus, Jacqueline James, Stephen McQuaid, Stephanie Craig, Kenneth Arthur, Darragh McArt, Chin-Ann J Ong, Pierre Lao-Sirieix, Peter Hamilton, Manuel Salto-Tellez, Martin Eatock, Helen G Coleman, Rebecca C Fitzgerald, Richard D Kennedy, Richard C Turkington
Background: The current TNM staging system for oesophageal adenocarcinoma (OAC) has limited ability to stratify patients and inform clinical management following neo-adjuvant chemotherapy and surgery. Results: Functional genomic analysis of the gene expression data using Gene Set Enrichment Analysis (GSEA) identified GLUT1 as putative prognostic marker in OAC.In the discovery cohort GLUT1 positivity was observed in 114 patients (80.9%) and was associated with poor overall survival (HR 2...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719086/overexpression-of-genes-associated-with-hypoxia-in-cattle-adapted-to-trans-himalayan-region-of-ladakh
#10
Preeti Verma, Ankita Sharma, Monika Sodhi, Kiran Thakur, Vijay Bharti, Prabhat Kumar, Arup Giri, Sahil Kalia, Shelesh Kumar Swami, Manishi Mukesh
Ladakh is an important part of the Trans-Himalayan region located between the Kunlun mountain range in the north and the main Great Himalayas to the south in the state of Jammu and Kashmir of India. The local cattle from Leh and Ladakh region, known as "Ladakhi cattle" is a unique germplasm having excellent adaptation potential to high altitude hypobaric stress. In the present study, an effort was made to evaluate the transcriptional pattern of hypoxia inducing factor-1 (HIF-1) and several of its regulated genes in PBMCs of local Ladakhi cattle, Holstein Frisian crosses, Jersey (exotic) maintained at high altitude region and Sahiwal (Bos indicus) and Karan Fries (cross bred) cattle maintained in tropical environment...
May 2, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29700126/imaging-melphalan-therapy-response-in-preclinical-extramedullary-myeloma-with-18-f-fdopa-and-18-f-fdg-pet
#11
Deep Hathi, Elizabeth DeLassus, Samuel Achilefu, Jonathan McConathy, Monica Shokeen
Multiple myeloma (MM) is a debilitating neoplasm of terminally differentiated plasma B-cells that has resulted in over 13,000 deaths in 2017 alone. Combination therapies involving melphalan, a small molecule DNA alkylating agent, are commonly prescribed to patients with relapsed/refractory MM, which necessitates the stratification of responding patients to minimize toxicities and improve quality of life. Here, we evaluated the use of 18 F-FDOPA, a clinically available positron emission tomography (PET) radiotracer with specificity to the L-type amino acid transporter-1 (LAT1), which also mediates melphalan uptake, for imaging melphalan therapy response in a preclinical immunocompetent model of MM...
April 26, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29691457/metabolic-and-cardiac-adaptation-to-chronic-pharmacologic-blockade-of-facilitative-glucose-transport-in-murine-dilated-cardiomyopathy-and-myocardial-ischemia
#12
Monique R Heitmeier, Maria A Payne, Carla Weinheimer, Attila Kovacs, Richard C Hresko, Patrick Y Jay, Paul W Hruz
GLUT transgenic and knockout mice have provided valuable insight into the role of facilitative glucose transporters (GLUTs) in cardiovascular and metabolic disease, but compensatory physiological changes can hinder interpretation of these models. To determine whether adaptations occur in response to GLUT inhibition in the failing adult heart, we chronically treated TG9 mice, a transgenic model of dilated cardiomyopathy and heart failure, with the GLUT inhibitor ritonavir. Glucose tolerance was significantly improved with chronic treatment and correlated with decreased adipose tissue retinol binding protein 4 (RBP4) and resistin...
April 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29691252/high-usp6nl-levels-in-breast-cancer-sustain-chronic-akt-phosphorylation-and-glut1-stability-fueling-aerobic-glycolysis
#13
Daniele Avanzato, Emanuela Pupo, Nadia Ducano, Claudio Isella, Giovanni Bertalot, Chiara Luise, Salvatore Pece, Alejandra Bruna, Oscar M Rueda, Carlos Caldas, Pier Paolo Di Fiore, Anna Sapino, Letizia Lanzetti
USP6NL, also named RN-tre, is a GTPase activating protein (GAP) involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer (BC), mainly of the basal-like/integrative cluster 10 subtype. Increased USP6NL levels were accompanied by gene amplification and were associated with worse prognosis in the METABRIC dataset, retaining prognostic value in multivariable analysis. High levels of USP6NL in BC cells delayed endocytosis and degradation of the epidermal growth factor receptor (EGFR), causing chronic AKT activation...
April 24, 2018: Cancer Research
https://www.readbyqxmd.com/read/29686650/glucose-transporters-in-diabetic-kidney-disease-friends-or-foes
#14
REVIEW
Anita A Wasik, Sanna Lehtonen
Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a common cause of end-stage renal disease worldwide. DKD manifests as an increased urinary protein excretion (albuminuria). Multiple studies have shown that insulin resistance correlates with the development of albuminuria in non-diabetic and diabetic patients. There is also accumulating evidence that glomerular epithelial cells or podocytes are insulin sensitive and that insulin signaling in podocytes is essential for maintaining normal kidney function...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29684818/glut1-protects-prostate-cancer-cells-from-glucose-deprivation-induced-oxidative-stress
#15
Pedro Gonzalez-Menendez, David Hevia, Rebeca Alonso-Arias, Alejandro Alvarez-Artime, Aida Rodriguez-Garcia, Sandrina Kinet, Ivan Gonzalez-Pola, Naomi Taylor, Juan C Mayo, Rosa M Sainz
Glucose, chief metabolic support for cancer cell survival and growth, is mainly imported into cells by facilitated glucose transporters (GLUTs). The increase in glucose uptake along with tumor progression is due to an increment of facilitative glucose transporters as GLUT1. GLUT1 prevents cell death of cancer cells caused by growth factors deprivation, but there is scarce information about its role on the damage caused by glucose deprivation, which usually occurs within the core of a growing tumor. In prostate cancer (PCa), GLUT1 is found in the most aggressive tumors, and it is regulated by androgens...
April 12, 2018: Redox Biology
https://www.readbyqxmd.com/read/29681762/correlation-of-high-risk-soft-tissue-sarcoma-biomarker-expression-patterns-with-outcome-following-neoadjuvant-chemoradiation
#16
John M Kane, Anthony Magliocco, Qiang Zhang, Dian Wang, Alex Klimowicz, Jonathan Harris, Jeff Simko, Thomas DeLaney, William Kraybill, David G Kirsch
Background: Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. Methods: Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS)...
2018: Sarcoma
https://www.readbyqxmd.com/read/29677490/egfr-phosphorylated-platelet-isoform-of-phosphofructokinase-1-promotes-pi3k-activation
#17
Jong-Ho Lee, Rui Liu, Jing Li, Yugang Wang, Lin Tan, Xin-Jian Li, Xu Qian, Chuanbao Zhang, Yan Xia, Daqian Xu, Wei Guo, Zhiyong Ding, Linyong Du, Yanhua Zheng, Qianming Chen, Philip L Lorenzi, Gordon B Mills, Tao Jiang, Zhimin Lu
EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent translocation of PFKP to the plasma membrane, where the PFKP was phosphorylated at Y64 by EGFR. Phosphorylated PFKP binds to the N-terminal SH2 domain of p85α, which is distinct from binding of Gab1 to the C-terminal SH2 domain of p85α, and recruited p85α to the plasma membrane resulting in PI3K activation...
April 19, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29676955/mitochondrial-genome-modulates-myocardial-akt-glut-hk-salvage-pathway-in-spontaneously-hypertensive-rats-adapted-to-chronic-hypoxia
#18
Iveta Nedvedova, David Kolar, Barbara Elsnicova, Daniela Hornikova, Jiri Novotny, Martin Kalous, Michal Pravenec, Jan Neckar, Frantisek Kolar, Jitka M Zurmanova
Recently we have shown that adaptation to continuous normobaric hypoxia (CNH) decreases myocardial ischemia/reperfusion injury in spontaneously hypertensive rats (SHR) and in conplastic strain (SHR-mtBN ). The protective effect was stronger in the latter group characterized by a selective replacement of SHR mitochondrial genome with that of a more ischemia-resistant Brown Norway strain. The aim of the present study was to examine the possible involvement of the hypoxia inducible factor (HIF)-dependent pathway of the protein kinase B/glucose transporters/hexokinase (Akt/GLUT/HK) in this mitochondrial genome-related difference of the cardioprotective phenotype...
April 20, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29676131/-jatrorrhizine-regulates-gluts-with-multiple-manners-for-hypoglycemic-effect-in-insulin-resistance-3t3-l1-adipocytes
#19
Shui-Lan Zhu, Ting Lei, Xu Gao, Jun Tu
This paper aimed to investigate the hypoglycemic effect and relative mechanism of jatrorrhizine in insulin-resistance (IR)-3T3-L1 adipocytes. The 3T3-L1 preadipocytes were used to induce mature adipocytes, then the stable IR model was established with 1 μmol·L⁻¹ dexamethasone. The adipocytes were divided into normal group, IR model group, rosiglitazone positive group and jatrorrhizine group (0.5, 1, 5, 10, 20 μmol·L⁻¹). After different time points (12, 24, 30, 36, 48 h) treatment, glucose content of 3T3-L1 adipocytes was detected by the glucose oxidase peroxidase method and TG content was measured by glycerol phosphate oxidase method, whereas cell viability was detected by CCK-8 assay...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29675872/identification-and-quantification-of-blood-brain-barrier-transporters-in-isolated-rat-brain-microvessels
#20
Hajar Al Feteisi, Zubida M Al-Majdoub, Brahim Achour, Narciso Couto, Amin Rostami-Hodjegan, Jill Barber
The blood-brain barrier (BBB) maintains brain homeostasis by tightly regulating the exchange of molecules with systemic circulation. It consists primarily of microvascular endothelial cells surrounded by astrocytic endfeet, pericytes, and microglia. Understanding the make-up of transporters in rat BBB is essential to the translation of pharmacological and toxicological observations into humans. In this study, experimental workflows are presented in which the optimization of (a) isolation of rat brain microvessels, (b) enrichment of endothelial cells, and (c) extraction and digestion of proteins were evaluated, followed by identification and quantification of BBB proteins...
April 20, 2018: Journal of Neurochemistry
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