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https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#1
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28432132/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-epigenome-a-dynamic-vehicle-for-transmitting-and-recording-cytokine-signaling
#2
John L Johnson, Golnaz Vahedi
CD4(+) T cells are critical for the elimination of an immense array of microbial pathogens. Although there are aspects of helper T-cell differentiation that can be modeled as a classic cell-fate commitment, CD4(+) T cells also maintain considerable flexibility in their transcriptional program. Here, we present an overview of chromatin biology during cellular reprogramming and, within this context, envision how the scope of cellular reprogramming may be expanded to further our understanding of the controversy surrounding CD4(+) T lymphocyte plasticity or determinism...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28431263/epigenetic-therapy-and-chemosensitization-in-solid-malignancy
#3
REVIEW
Sean M Ronnekleiv-Kelly, Anup Sharma, Nita Ahuja
Epigenetic modifications result in dynamic shifts between transcriptionally active and suppressed states. The potentially reversible nature of epigenetic changes underlies the concept of epigenetic therapy, which serves to reprogram cancer cells as opposed to inducing cytotoxicity that occurs with standard chemotherapeutics. There are numerous enzymes involved in epigenetic changes and each can be potentially targetable. Although many investigations have evaluated the clinical potential of the various epigenetic therapies, currently only histone deacetylase inhibitors and DNA methyltransferase inhibitors are approved for use in specific hematologic malignancies...
April 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28430184/the-ubiquitin-ligase-lin41-trim71-targets-p53-to-antagonize-cell-death-and-differentiation-pathways-during-stem-cell-differentiation
#4
Duong Thi Thuy Nguyen, Daniel Richter, Geert Michel, Sibylle Mitschka, Waldemar Kolanus, Elisa Cuevas, F Gregory Wulczyn
Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#5
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28430113/should-physicians-instead-of-industry-representatives-be-the-main-actor-of-cardiac-implantable-electronic-device-follow-up-super-follow-up
#6
Çağın Mustafa Üreyen, Cem Yunus Baş, İsa Öner Yüksel, Görkem Kuş, Göksel Çağırcı, Şakir Arslan
OBJECTIVE: This retrospective study sought to research the adequacy of the follow-up and optimization of cardiac implantable electronic devices (CIEDs) performed by industry representatives. METHODS: A total of 403 consecutive patients (35% females; median age, 67 years; age range 18-97 years) with either pacemakers (n=246), implantable cardioverter-defibrillators (ICDs), (n=117) or cardiac resynchronization therapy with defibrillator (CRT-D) (n=40) applied to our hospital's outpatient pacemaker clinic for follow-up...
April 19, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28429802/parkinson-disease-in-situ-astrocyte-reprogramming-simpler-cell-replacement-therapy-in-pd
#7
Ian Fyfe
No abstract text is available yet for this article.
April 21, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28429769/gene-and-mutation-independent-therapy-via-crispr-cas9-mediated-cellular-reprogramming-in-rod-photoreceptors
#8
Jie Zhu, Chang Ming, Xin Fu, Yaou Duan, Duc Anh Hoang, Jeffrey Rutgard, Runze Zhang, Wenqiu Wang, Rui Hou, Daniel Zhang, Edward Zhang, Charlotte Zhang, Xiaoke Hao, Wenjun Xiong, Kang Zhang
No abstract text is available yet for this article.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429765/repolarizing-macrophages-improves-breast-cancer-therapy
#9
Luca Cassetta, Jeffrey W Pollard
Tumor-associated macrophages (TAMs) contribute to breast cancer progression and dissemination; TAM-targeting strategies aimed at their reprogramming show promising preclinical results. In a new report Guerriero and colleagues demonstrate that a novel HDAC Class IIa inhibitor, TMP195, can reprogram monocytes and macrophages in the tumor into cells able to sustain a robust CD8 T cell-mediated anti-tumoral immune response.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429725/estrogen-reprograms-the-activity-of-neutrophils-to-foster-protumoral-microenvironment-during-mammary-involution
#10
Hwa Hwa Chung, Yu Zuan Or, Smeeta Shrestha, Jia Tong Loh, Chew Leng Lim, Zoe Ong, Amanda Rui En Woo, I-Hsin Su, Valerie C L Lin
Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Microarray analysis shows that estrogen induces an extensive proinflammatory gene signature in the involuting mammary tissue. This is associated with estrogen-induced neutrophil infiltration. Furthermore, estrogen induces the expression of protumoral cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary neutrophils and systemic neutrophil depletion abolished estrogen-induced expression of these genes in mammary tissue...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429718/a-computational-systems-approach-identifies-synergistic-specification-genes-that-facilitate-lineage-conversion-to-prostate-tissue
#11
Flaminia Talos, Antonina Mitrofanova, Sarah K Bergren, Andrea Califano, Michael M Shen
To date, reprogramming strategies for generating cell types of interest have been facilitated by detailed understanding of relevant developmental regulatory factors. However, identification of such regulatory drivers often represents a major challenge, as specific gene combinations may be required for reprogramming. Here we show that a computational systems approach can identify cell type specification genes (master regulators) that act synergistically, and demonstrate its application for reprogramming of fibroblasts to prostate tissue...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429085/the-role-of-rna-alternative-splicing-in-regulating-cancer-metabolism
#12
REVIEW
Itamar Kozlovski, Zahava Siegfried, Adi Amar-Schwartz, Rotem Karni
Tumor cells alter their metabolism by a wide array of mechanisms to promote growth and proliferation. Dysregulated expression and/or somatic mutations of key components of the glycolytic pathway/TCA cycle as well as other metabolic pathways allow tumor cells to improve their ability to survive harsh conditions such as hypoxia and the presence of reactive oxygen species, as well as the ability to obtain nutrients to increase lipids, protein, and nucleic acids biogenesis. Approximately 95% of the human protein encoding genes undergo alternative splicing (AS), a regulated process of gene expression that greatly diversifies the proteome by creating multiple proteins from a single gene...
April 20, 2017: Human Genetics
https://www.readbyqxmd.com/read/28428821/genome-wide-search-for-candidate-genes-for-yeast-robustness-improvement-against-formic-acid-reveals-novel-susceptibility-trk1-and-positive-regulators-and-resistance-haa1-regulon-determinants
#13
Sílvia F Henriques, Nuno P Mira, Isabel Sá-Correia
BACKGROUND: Formic acid is an inhibitory compound present in lignocellulosic hydrolysates. Understanding the complex molecular mechanisms underlying Saccharomyces cerevisiae tolerance to this weak acid at the system level is instrumental to guide synthetic pathway engineering for robustness improvement of industrial strains envisaging their use in lignocellulosic biorefineries. RESULTS: This study was performed to identify, at a genome-wide scale, genes whose expression confers protection or susceptibility to formic acid, based on the screening of a haploid deletion mutant collection to search for these phenotypes in the presence of 60, 70 and 80 mM of this acid, at pH 4...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28427897/boosters-and-barriers-for-direct-cardiac-reprogramming
#14
REVIEW
Mahmood Talkhabi, Elmira Rezaei Zonooz, Hossein Baharvand
Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs...
April 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28427560/stress-adaptive-response-in-ovarian-cancer-drug-resistance-role-of-trap1-in-oxidative-metabolism-driven-inflammation
#15
Maria Rosaria Amoroso, Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Francesca Maddalena, Valentina Condelli, Matteo Landriscina, Franca Esposito
Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427343/loss-of-pericyte-smoothened-activity-in-mice-with-genetic-deficiency-of-leptin
#16
Guanhua Xie, Marzena Swiderska-Syn, Mark L Jewell, Mariana Verdelho Machado, Gregory A Michelotti, Richard T Premont, Anna Mae Diehl
BACKGROUND: Obesity is associated with multiple diseases, but it is unclear how obesity promotes progressive tissue damage. Recovery from injury requires repair, an energy-expensive process that is coupled to energy availability at the cellular level. The satiety factor, leptin, is a key component of the sensor that matches cellular energy utilization to available energy supplies. Leptin deficiency signals energy depletion, whereas activating the Hedgehog pathway drives energy-consuming activities...
April 20, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28426686/reactive-oxygen-species-are-required-for-driving-efficient-and-sustained-aerobic-glycolysis-during-cd4-t-cell-activation
#17
Dana M Previte, Erin C O'Connor, Elizabeth A Novak, Christina P Martins, Kevin P Mollen, Jon D Piganelli
The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells...
2017: PloS One
https://www.readbyqxmd.com/read/28426281/identification-of-ssea-1-expressing-enhanced-reprogramming-seer-cells-in-porcine-embryonic-fibroblasts
#18
Dong Li, Jan O Secher, Morten Juhl, Kaveh Mashayekhi, Troels T Nielsen, Bjørn Holst, Poul Hyttel, Kristine K Freude, Vanessa J Hall
Previous research has shown that a subpopulation of cells within cultured human dermal fibroblasts, termed multilineage-differentiating stress enduring (Muse) cells, are preferentially reprogrammed into induced pluripotent stem cells. However, controversy exists over whether these cells are the only cells capable of being reprogrammed from a heterogeneous population of fibroblasts. Similarly, there is little research to suggest such cells may exist in embryonic tissues or other species. In order to address if such a cell population exists in pigs, we investigated porcine embryonic fibroblast populations (pEFs) and identified heterogeneous expression of several key cell surface markers...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28426026/generation-of-multipotent-induced-cardiac-progenitor-cells-from-mouse-fibroblasts-and-potency-testing-in-ex-vivo-mouse-embryos
#19
Pratik A Lalit, Adriana M Rodriguez, Karen M Downs, Timothy J Kamp
Here we describe a protocol to generate expandable and multipotent induced cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus differs from cell activation and signaling-directed (CASD) reprogramming to cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas CASD reprogramming can generate various cell types depending on culture conditions and raises the possibility of transitioning through a pluripotent cell state...
May 2017: Nature Protocols
https://www.readbyqxmd.com/read/28425976/prenatal-exposure-to-a-maternal-high-fat-diet-affects-histone-modification-of-cardiometabolic-genes-in-newborn-rats
#20
Bijaya Upadhyaya, Tricia Larsen, Shivon Barwari, Eli J Louwagie, Michelle L Baack, Moul Dey
Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0...
April 20, 2017: Nutrients
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