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Metabolic reprogramming

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https://www.readbyqxmd.com/read/29471209/genetic-engineering-of-host-organisms-for-pharmaceutical-synthesis
#1
REVIEW
Joseph H Collins, Eric M Young
Pharmaceutical production hosts may be derived from almost any organism, from Chinese Hamster Ovary (CHO) cell lines to isolated actinomycetes. Each host can be improved, historically only through adaptive evolution. Recently, the maturation of organism engineering has expanded the available models, methods, and tools for altering host phenotypes. New tools like CRISPR-associated endonucleases promise to enable precise cellular reprogramming and to access previously intractable hosts. In this review, we discuss the most recent advances in engineering several types of pharmaceutical production hosts...
February 19, 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29467007/enhanced-glycolysis-contributes-to-the-pathogenesis-of-experimental-autoimmune-neuritis
#2
Ru-Tao Liu, Min Zhang, Chun-Lin Yang, Peng Zhang, Na Zhang, Tong Du, Meng-Ru Ge, Long-Tao Yue, Xiao-Li Li, Heng Li, Rui-Sheng Duan
BACKGROUND: With the recognition of the key roles of cellular metabolism in immunity, targeting metabolic pathway becomes a new strategy for autoimmune disease treatment. Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory demyelinating disease of the peripheral nervous system, characterized by inflammatory cell infiltration. These inflammatory cells, including activated macrophages, Th1 cells, and Th17 cells, generally undergo metabolic reprogramming and rely mainly on glycolysis to exert functions...
February 21, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29466368/untargeted-metabolomics-reveals-distinct-metabolic-reprogramming-in-endothelial-cells-co-cultured-with-csc-and-non-csc-prostate-cancer-cell-subpopulations
#3
Anusha Jayaraman, Praveen Kumar, Silvia Marin, Pedro de Atauri, Francesca Mateo, Timothy M Thomson, Josep J Centelles, Stewart F Graham, Marta Cascante
Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities. Human umbilical vein endothelial cells (HUVECs) were subjected to different microenvironmental conditions, such as the presence of highly metastatic PC-3M and highly invasive PC-3S prostate cancer cell lines, in addition to the angiogenic activator vascular endothelial growth factor (VEGF), under normoxia...
2018: PloS One
https://www.readbyqxmd.com/read/29466297/a-metabolomic-approach-to-predict-breast-cancer-behavior-and-chemotherapy-response
#4
REVIEW
Marcella Regina Cardoso, Juliana Carvalho Santos, Marcelo Lima Ribeiro, Maria Cecília Ramiro Talarico, Lais Rosa Viana, Sophie Françoise Mauricette Derchain
Although the classification of breast carcinomas into molecular or immunohistochemical subtypes has contributed to a better categorization of women into different therapeutic regimens, breast cancer nevertheless still progresses or recurs in a remarkable number of patients. Identifying women who would benefit from chemotherapy could potentially increase treatment effectiveness, which has important implications for long-term survival. Metabolomic analyses of fluids and tissues from cancer patients improve our knowledge of the reprogramming of metabolic pathways involved in resistance to chemotherapy...
February 21, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29466211/-the-role-of-macrophages-in-repair-of-injured-myocardium-and-perspectives-of-metabolic-reprogramming-of-immune-cells-for-myocardial-post-infarction-recovery
#5
I S Stafeev, M Y Menshikov, V A Tkachuk, E V Parfenova
A new trend in modern experimental cardiology is the development of approaches to correction of reparation after myocardial infarction (MI) with the use of specific effects on immune cells. One of the main targets for such interventions is the process of macrophage's polarization in the infarction zone. Proinflammatory M1‑macrophages contribute to hampered myocardial repair, in contrast to M2‑macrophages that promote regeneration. Currently, there are two main ways of targeted delivery of agents necessary for macrophage reprogramming - inlipoid and inglycan-encapsulated particles...
December 2017: Kardiologiia
https://www.readbyqxmd.com/read/29464059/characterization-and-metabolic-synthetic-lethal-testing-in-a-new-model-of-sdh-loss-familial-pheochromocytoma-and-paraganglioma
#6
John Smestad, Oksana Hamidi, Lin Wang, Molly Nelson Holte, Fatimah Al Khazal, Luke Erber, Yue Chen, L James Maher
Succinate dehydrogenase (SDH)-loss pheochromocytoma and paraganglioma (PPGL) are tumors driven by metabolic derangement. SDH loss leads to accumulation of intracellular succinate, which competitively inhibits dioxygenase enzymes, causing activation of pseudohypoxic signaling and hypermethylation of histones and DNA. The mechanisms by which these alterations lead to tumorigenesis are unclear, however. In an effort to fundamentally understand how SDH loss reprograms cell biology, we developed an immortalized mouse embryonic fibroblast cell line with conditional disruption of Sdhc and characterize the kinetics of Sdhc gene rearrangement, SDHC protein loss, succinate accumulation, and the resultant hypoproliferative phenotype...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29463782/endogenous-volatile-organic-compounds-in-acute-myeloid-leukemia-origins-and-potential-clinical-applications
#7
Dibyendu Dutta, Ngee S Chong, Seah H Lim
Not unlike many cancer types, acute myeloid leukemia (AML) exhibits many metabolic changes and reprogramming, causing changes in lipid metabolism. Some of the distinct molecular abnormalities associated with AML also modify the metabolic changes. Both processes result in changes in the production of endogenous volatile organic compounds (VOCs). The increasing availability of highly sensitive methods for detecting trace chemicals provides the opportunity to investigate the role of patient-specific VOC finger-prints as biomarkers for detecting early relapse or minimal residual disease (MRD) in AML...
February 21, 2018: Journal of Breath Research
https://www.readbyqxmd.com/read/29463682/metabolism-in-pluripotency-both-driver-and-passenger
#8
Perrine Dahan, Vivian Lu, Robert M T Nguyen, Stephanie A L Kennedy, Michael A Teitell
Pluripotent stem cells (PSCs) are highly proliferative cells characterized by robust metabolic demands to power rapid division. For many years considered a passive component or "passenger" of cell fate determination, cell metabolism is now starting to take center stage as a driver of cell fate outcomes. This review provides an update and analysis of our current understanding of PSC metabolism and its role in self-renewal, differentiation, and somatic cell reprogramming to pluripotency. Moreover, we present evidence on the active roles metabolism plays in shaping the epigenome to influence patterns of gene expression that may model key features of early embryonic development...
February 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29463472/interferon-gamma-induces-reversible-metabolic-reprogramming-of-m1-macrophages-to-sustain-cell-viability-and-pro-inflammatory-activity
#9
Feilong Wang, Song Zhang, Ryounghoon Jeon, Ivan Vuckovic, Xintong Jiang, Amir Lerman, Clifford D Folmes, Petras D Dzeja, Joerg Herrmann
Classical activation of M1 macrophages with lipopolysaccharide (LPS) is associated with a metabolic switch from oxidative phosphorylation to glycolysis. However, the generalizability of such metabolic remodeling to other modes of M1 macrophage stimulation, e.g. type II interferons (IFNs) such as IFNγ, has remained unknown as has the functional significance of aerobic glycolysis during macrophage activation. Here we demonstrate that IFNγ induces a rapid activation of aerobic glycolysis followed by a reduction in oxidative phosphorylation in M1 macrophages...
February 13, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29463261/hmgb2-is-associated-with-malignancy-and-regulates-warburg-effect-by-targeting-ldhb-and-fbp1-in-breast-cancer
#10
Deyuan Fu, Jing Li, Jinli Wei, Zhengquan Zhang, Yulin Luo, Haosheng Tan, Chuanli Ren
BACKGROUND: High-mobility group box 2 (HMGB2) is implicated in tumorigenesis in various cancers. However, the clinical significance of HMGB2 signaling in human breast cancer progression remains unknown. METHODS: We investigated HMGB2 expression in 185 cases of primary breast cancer and matched normal breast tissue specimens, and explored the underlying mechanisms of altered HMGB2 expression as well as the impact of this altered expression on breast cancer growth and on aerobic glycolysis using in vitro and animal models of breast cancer...
February 20, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29462345/dynamics-of-metabolic-responses-to-combined-heat-and-drought-spells-in-arabidopsis-thaliana-under-ambient-and-rising-atmospheric-co2
#11
Gaurav Zinta, Hamada AbdElgawad, Darin Peshev, James T Weedon, Wim Van den Ende, Ivan Nijs, Ivan A Janssens, Gerrit T S Beemster, Asard Han
As a consequence of global change processes, plants will be increasingly challenged by extreme climatic events, against a background of elevated atmospheric CO2. We analysed responses of Arabidopsis thaliana to a combination of heat wave and water deficit at ambient and elevated CO2, and provided mechanistic insight on changes in primary metabolism. Climate extreme-induced metabolic changes are dynamic and molecule class-specific. Concentrations of soluble sugars and amino acids increased transiently after short (4 d) exposure to heat and drought, and readjusted to control levels under prolonged (8 d) stress...
February 15, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29459894/idiopathic-pulmonary-fibrosis-aging-mitochondrial-dysfunction-and-cellular-bioenergetics
#12
REVIEW
Daniel C Zank, Marta Bueno, Ana L Mora, Mauricio Rojas
At present, the etiology of idiopathic pulmonary fibrosis (IPF) remains elusive. Over the past two decades, however, researchers have identified and described the underlying processes that result in metabolic dysregulation, metabolic reprogramming, and mitochondrial dysfunction observed in the cells of IPF lungs. Metabolic changes and mitochondrial dysfunction in IPF include decreased efficiency of electron transport chain function with increasing production of reactive oxygen species, decreased mitochondrial biogenesis, and impaired mitochondrial macroautophagy, a key pathway for the removal of dysfunctional mitochondria...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29459863/a-role-for-the-krebs-cycle-intermediate-citrate-in-metabolic-reprogramming-in-innate-immunity-and-inflammation
#13
REVIEW
Niamh C Williams, Luke A J O'Neill
Metabolism in immune cells is no longer thought of as merely a process for adenosine triphosphate (ATP) production, biosynthesis, and catabolism. The reprogramming of metabolic pathways upon activation is also for the production of metabolites that can act as immune signaling molecules. Activated dendritic cells (DCs) and macrophages have an altered Krebs cycle, one consequence of which is the accumulation of both citrate and succinate. Citrate is exported from the mitochondria via the mitochondrial citrate- carrier...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29458370/the-critical-roles-of-activated-stellate-cells-mediated-paracrine-signaling-metabolism-and-onco-immunology-in-pancreatic-ductal-adenocarcinoma
#14
REVIEW
Yaojie Fu, Shanshan Liu, Shan Zeng, Hong Shen
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a "partner in crime" to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29457784/hiv-latency-is-reversed-by-acss2-driven-histone-crotonylation
#15
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29456966/metabolic-profile-of-oral-squamous-carcinoma-cell-lines-relies-on-a-higher-demand-of-lipid-metabolism-in-metastatic-cells
#16
Ana Carolina B Sant'Anna-Silva, Gilson C Santos, Samir P Costa Campos, André Marco Oliveira Gomes, Juan Alberto Pérez-Valencia, Franklin David Rumjanek
Tumor cells are subjected to a broad range of selective pressures. As a result of the imposed stress, subpopulations of surviving cells exhibit individual biochemical phenotypes that reflect metabolic reprograming. The present work aimed at investigating metabolic parameters of cells displaying increasing degrees of metastatic potential. The metabolites present in cell extracts fraction of tongue fibroblasts and of cell lines derived from human tongue squamous cell carcinoma lineages displaying increasing metastatic potential (SCC9 ZsG, LN1 and LN2) were analyzed by1 H NMR (nuclear magnetic resonance) spectroscopy...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29455645/pyruvate-kinase-m2-fuels-multiple-aspects-of-cancer-cells-from-cellular-metabolism-transcriptional-regulation-to-extracellular-signaling
#17
REVIEW
Ming-Chuan Hsu, Wen-Chun Hung
Originally identified as a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454183/the-fine-balance-between-mutualism-and-antagonism-in-the-epichlo%C3%A3-festucae-grass-symbiotic-interaction
#18
REVIEW
Barry Scott, Kimberly Green, Daniel Berry
Epichloë endophytes form mutualistic symbiotic associations with aerial tissues of temperate grasses. Intercalary growth of hyphae within the leaves enables fungal growth to be synchronized with host leaf growth, leading to formation of a highly structured and tightly regulated symbiotic network. Mutations in fungal genes that disrupt cell-cell fusion and other key signalling pathways lead to an antagonistic interaction characterized by unregulated growth of endophytic hyphae and detrimental effects on host growth...
February 14, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29452772/metabolic-and-lipidomic-reprogramming-in-renal-cell-carcinoma-subtypes-reflects-regions-of-tumor-origin
#19
Elke Schaeffeler, Florian Büttner, Anna Reustle, Verena Klumpp, Stefan Winter, Steffen Rausch, Pascale Fisel, Jörg Hennenlotter, Stephan Kruck, Arnulf Stenzl, Judith Wahrheit, Denise Sonntag, Marcus Scharpf, Falko Fend, Abbas Agaimy, Arndt Hartmann, Jens Bedke, Matthias Schwab
BACKGROUND: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid accumulation and metabolic alterations, whereas data on metabolic alterations in non-ccRCC are limited. OBJECTIVE: We assessed metabolic alterations and the lipid composition of RCC subtypes and ccRCC-derived metastases. Moreover, we elucidated the potential of metabolites/lipids for subtype classification and identification of therapeutic targets...
February 13, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29451682/metabolic-regulation-of-leukocyte-motility-and-migration
#20
REVIEW
Federica M Marelli-Berg, Maryam Jangani
Dynamic reorganization of the cytoskeleton is essential for numerous cellular processes including leukocyte migration. This process presents a substantial bioenergetic challenge to migrating cells as actin polymerization is dependent on ATP hydrolysis. Hence, migrating cells must increase ATP production to meet the increased metabolic demands of cytoskeletal reorganization. Despite this long-standing evidence, the metabolic regulation of leukocyte motility and trafficking has only recently begun to be investigated...
February 16, 2018: Journal of Leukocyte Biology
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