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https://www.readbyqxmd.com/read/29351437/metabolic-reprogramming-in-the-pathogenesis-of-chronic-lung-diseases-including-bpd-copd-and-pulmonary-fibrosis
#1
Haifeng Zhao, Phyllis A Dennery, Hongwei Yao
The metabolism of nutrient substrates including glucose, glutamine and fatty acids provides acetyl-CoA for the tricarboxylic acid cycle to generate energy, and metabolites for the biosynthesis of biomolecules including nucleotides, proteins, and lipids. It has been shown that metabolism of glucose, fatty acid, and glutamine plays important roles in modulating cellular proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses. All these cellular processes contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351407/pedf-expression-affects-the-oxidative-and-inflammatory-state-of-choroidal-endothelial-cells
#2
Mitra Farnoodian, Christine M Sorenson, Nader Sheibani
Age related macular degeneration (AMD) is the leading cause of vision loss among the elderly population, and is associated with severe macular degeneration and choroidal neovascularization (CNV). Although the pathogenesis of AMD is associated with choroidal dysfunction and CNV, the detailed underlying mechanisms remain unresolved. Altered production of pigment epithelium derived factor (PEDF), a neuroprotective and anti-angiogenic factor, contributes to CNV. Furthermore, exogenous PEDF mitigates angiogenesis in preclinical CNV models...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29350825/ang-ii-facilitated-cd11-ly6chi-cells-reprogramming-into-m1-like-macrophage-through-erk1-2-or-p38-stat3-pathway-and-involved-in-eam
#3
Hongxiang Lu, Yan Wu, Xiaoyi Shao, Shanshan Zhou, Yuanyuan Jiang, Rong Chen, Gangjun Zong, Huaxi Xu, Zhaoliang Su
Macrophage, a highly plastic population, is widely distributed. Macrophage functions are settled and acquired polarization programs in response to microenvironmental signals and involved in many inflammatory disorders, such as experimental autoimmune myocarditis (EAM). Phenotypic and functional changes in macrophage are considered as an important determinant of disease progression and/or regression. Angiotensin II (ANG II), as a powerful proinflammatory factor, plays critical roles in inflammatory diseases and macrophage recruitment...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350802/cellular-reprogramming-a-new-way-to-understand-aging-mechanisms
#4
REVIEW
Burcu Yener Ilce, Umut Cagin, Acelya Yilmazer
Increased life expectancy, due to the rise in life quality and the decline in mortality rates, is leading to a society in which the population aged 60 and over is growing more rapidly than the entire population. Although various models and model organisms have been employed to investigate the mechanism of aging, induced pluripotent stem cells (iPSCs) are useful candidates to study human aging and age-related human diseases. This work discusses how iPSCs can be used as an alternative to the model organisms such as yeast, Caenorhabditis elegans, Drosophila melanogaster, or the mouse...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29349669/positive-correlation-between-matrix-metalloproteinases-and-epithelial-to-mesenchymal-transition-and-its-association-with-clinical-outcome-in-bladder-cancer-patients
#5
R Singh, A Mandhani, V Agrawal, Minal Garg
Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease...
January 18, 2018: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/29348817/a-mitochondrial-targeted-purine-based-hsp90-antagonist-for-leukemia-therapy
#6
Kelly G Bryant, Young Chan Chae, Rogelio L Martinez, John C Gordon, Khaled M Elokely, Andrew V Kossenkov, Steven Grant, Wayne E Childers, Magid Abou-Gharbia, Dario C Altieri
Reprogramming of mitochondrial functions sustains tumor growth and may provide therapeutic opportunities. Here, we targeted the protein folding environment in mitochondria by coupling a purine-based inhibitor of the molecular chaperone Heat Shock Protein-90 (Hsp90), PU-H71 to the mitochondrial-targeting moiety, triphenylphosphonium (TPP). Binding of PU-H71-TPP to ADP-Hsp90, Hsp90 co-chaperone complex or mitochondrial Hsp90 homolog, TRAP1 involved hydrogen bonds, π-π stacking, cation-π contacts and hydrophobic interactions with the surrounding amino acids in the active site...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348686/defects-in-the-mitochondrial-trna-modification-enzymes-mto1-and-gtpbp3-promote-different-metabolic-reprogramming-through-a-hif-ppar%C3%AE-ucp2-ampk-axis
#7
Rachid Boutoual, Salvador Meseguer, Magda Villarroya, Elena Martín-Hernández, Mohammed Errami, Miguel A Martín, Marta Casado, M-Eugenia Armengod
Human proteins MTO1 and GTPBP3 are thought to jointly catalyze the modification of the wobble uridine in mitochondrial tRNAs. Defects in each protein cause infantile hypertrophic cardiomyopathy with lactic acidosis. However, the underlying mechanisms are mostly unknown. Using fibroblasts from an MTO1 patient and MTO1 silenced cells, we found that the MTO1 deficiency is associated with a metabolic reprogramming mediated by inactivation of AMPK, down regulation of the uncoupling protein 2 (UCP2) and transcription factor PPARγ, and activation of the hypoxia inducible factor 1 (HIF-1)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348439/dual-suppression-of-inner-and-outer-mitochondrial-membrane-functions-augments-apoptotic-responses-to-oncogenic-mapk-inhibition
#8
Madhavika N Serasinghe, Jesse D Gelles, Kent Li, Lauren Zhao, Franco Abbate, Marie Syku, Jarvier N Mohammed, Brateil Badal, Cuahutlehuanitzin A Rangel, Kyle L Hoehn, Julide Tok Celebi, Jerry Edward Chipuk
Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in treating melanoma, but are unsuccessful in achieving long-term remission. Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or Trametinib, respectively. Consequently, exposure to these therapies reprograms cellular metabolism to increase mitochondrial respiration and restrain cell death commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is the major site of anti-apoptotic BCL-2 protein function, we hypothesized that suppressing these critical mitochondrial membrane functions would be a rational approach to maximize the pro-apoptotic effect of MAPK inhibition...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348240/snf1-related-kinase1-controlled-c-s1-bzip-signaling-activates-alternative-mitochondrial-metabolic-pathways-to-ensure-plant-survival-in-extended-darkness
#9
Lorenzo Pedrotti, Christoph Weiste, Thomas Nägele, Elmar Wolf, Francesca Lorenzin, Katrin Dietrich, Andrea Mair, Wolfram Weckwerth, Markus Teige, Elena Baena-González, Wolfgang Dröge-Laser
Sustaining energy homeostasis is of pivotal importance for all living organisms. In Arabidopsis thaliana, evolutionarily conserved SnRK1 kinases (Snf1-RELATED KINASE1) control metabolic adaptation during low energy stress. To unravel starvation-induced transcriptional mechanisms, we performed transcriptome studies of inducible knock-down lines and found that S1-basic leucine Zipper transcription factors (S1-bZIPs) control a defined subset of genes downstream of SnRK1. For example, S1-bZIPs coordinate the expression of genes involved in branched-chain amino acid catabolism, which constitutes an alternative mitochondrial respiratory pathway that is crucial for plant survival during starvation...
January 18, 2018: Plant Cell
https://www.readbyqxmd.com/read/29347847/combining-cell-and-gene-therapy-to-advance-cardiac-regeneration
#10
Pina Marotta, Eleonora Cianflone, Iolanda Aquila, Carla Vicinanza, Mariangela Scalise, Fabiola Marino, Teresa Mancuso, Michele Torella, Ciro Indolfi, Daniele Torella
The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial...
January 19, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29346528/a-novel-stromal-lncrna-signature-reprograms-fibroblasts-to-promote-the-growth-of-oral-squamous-cell-carcinoma-via-lncrna-caf-interleukin-33
#11
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, Xiaofeng Huang, Qingang Hu, Hui Wang, Yuxian Song, Yanhong Ni, Yayi Hou
Stromal carcinoma-related fibroblasts (CAFs) are the main type of non-immune cells in the tumor microenvironment (TME). CAFs interact with cancer cells to promote tumor proliferation. Long non-coding RNAs (lncRNAs) are known to regulate cell growth, apoptosis, and metastasis of cancer cells, but their role in stromal cells is unclear. Using RNA sequencing, we identified a stromal lncRNA signature during the transformation of CAFs from normal fibroblasts (NFs) in oral squamous cell carcinoma (OSCC). We uncovered an uncharacterized lncRNA, FLJ22447, which was remarkably up-regulated in CAFs, referred to LncRNA-CAF (Lnc-CAF) hereafter...
January 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#12
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29346164/the-nuclear-receptor-nor-1-is-a-pleiotropic-regulator-of-exercise-induced-adaptations
#13
Michael A Pearen, George E O Muscat
Exercise induces various physical and metabolic changes in skeletal muscle that adaptively reprograms this tissue to current physiological and environmental demands. Underlying these changes are broad modifications to gene expression. We postulate that the nuclear hormone receptor, Nor-1, is activated following exercise and this transcription factor modifies gene expression to drive the molecular and cellular adaptations associated with contractile reorganization.
January 15, 2018: Exercise and Sport Sciences Reviews
https://www.readbyqxmd.com/read/29345901/playing-with-the-molecules-of-life
#14
Douglas D Young, Peter G Schultz
Our understanding of the complex molecular processes of living organisms is growing exponentially. This knowledge, togeth-er with a powerful arsenal of tools for manipulating the structures of biological macromolecules, is allowing chemists to begin to harness and reprogram the remarkable machinery of life. Here we review one such example in which the genetic code itself has been expanded with new building blocks that allow us to probe and manipulate the structures and functions of proteins in ways previously unimaginable...
January 18, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29345056/for-when-bacterial-infections-persist-toll-like-receptor-inducible-direct-antimicrobial-pathways-in-macrophages
#15
REVIEW
Claudia J Stocks, Mark A Schembri, Matthew J Sweet, Ronan Kapetanovic
Macrophages are linchpins of innate immunity, responding to invading microorganisms by initiating coordinated inflammatory and antimicrobial programs. Immediate antimicrobial responses, such as NADPH-dependent reactive oxygen species (ROS), are triggered upon phagocytic receptor engagement. Macrophages also detect and respond to microbial products through pattern recognition receptors (PRRs), such as TLRs. TLR signaling influences multiple biological processes including antigen presentation, cell survival, inflammation, and direct antimicrobial responses...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345024/being-pluripotent-bone-marrow-vsels-rather-than-hscs-have-the-potential-to-regenerate-other-adult-organs
#16
REVIEW
Deepa Bhartiya
Recent study by Deanne's group provides evidence that transplanted GFP positive bone marrow hematopoietic stem cells (HSCs) expressing CD45 do not regenerate the endometrium of irradiated mice. The results do not surprise us since global efforts to regenerate various organs by transplanting bone marrow (BM) mononuclear cells (presumably enriched for HSCs) have failed. HSCs can only regenerate/reconstitute BM as they are 'committed progenitors' that are specified from more primitive, CD45 negative stem cells...
January 18, 2018: Stem Cells
https://www.readbyqxmd.com/read/29345000/cell-death-under-epithelial-mesenchymal-transition-control-in-prostate-cancer-therapeutic-response
#17
REVIEW
Diane Begemann, Harry Anastos, Natasha Kyprianou
Prostate cancer is a widespread problem among men, with >160 000 new cases in 2017 alone. Androgen deprivation therapy is commonly used in prostate cancer treatment to block androgens required for cancer growth, but disease relapse after androgen deprivation therapy is both common and severe. Changes in androgen receptor signaling from androgen deprivation therapy have been linked to therapeutic resistance and tumor progression. Resistant cells can become reprogrammed to undergo epithelial-mesenchymal transition, a phenotypic switch from benign, epithelial cells to a mobile cell with mesenchymal traits...
January 17, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29344557/in-colonic-%C3%AF-0-rho0-cells-reduced-mitochondrial-function-mediates-transcriptomic-alterations-associated-with-cancer
#18
Harrison M Penrose, Sandra Heller, Chloe Cable, Hani Nakhoul, Nate Ungerleider, Melody Baddoo, Zachary F Pursell, Erik K Flemington, Susan E Crawford, Suzana D Savkovic
Background: Mitochondrial reprogramming has emerged as a hallmark of cancer pathobiology. Although it is believed this reprogramming is essential for cancer cells to thrive, how it supports cancer pathobiology is unclear. We previously generated colonic ρ0 (rho0) cells with reduced mitochondrial energy function and acquired their transcriptional signature. Here, we utilized a bioinformatics approach to identify their changes linked to cancer pathobiology. Methods: Human colon cancer HCT116 cells, control and ρ0, were used for qPCR...
November 2017: Oncoscience
https://www.readbyqxmd.com/read/29344553/reprogramming-patient-derived-tumor-cells-generates-model-cell-lines-for-tuberous-sclerosis-associated-lymphangioleiomyomatosis
#19
EDITORIAL
Lisa M Julian, William L Stanford
No abstract text is available yet for this article.
November 2017: Oncoscience
https://www.readbyqxmd.com/read/29344170/phosphorylation-of-ser6-in-hnrnpa1-by-s6k2-regulates-glucose-metabolism-and-cell-growth-in-colorectal-cancer
#20
Yan Sun, Man Luo, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao, Yu Hu
Abnormal glucose metabolism is critical in colorectal cancer (CRC) development. Expression of the pyruvate kinase (PK) M2 isoform, rather than the PKM1 isoform, serves important functions in reprogramming the glucose metabolism of cancer cells. Preferential expression of PKM2 is primarily driven by alternative splicing, which is coordinated by a group of splicing factors including heterogeneous nuclear ribonucleoprotein (hnRNP)A1, hnRNPA2 and RNA binding motif containing. However, the underlying molecular mechanisms associated with cancer cell expression of PKM2, instead of PKM1, remain unknown...
December 2017: Oncology Letters
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