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Cellular Reprogramming

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https://www.readbyqxmd.com/read/29165472/intracellular-delivery-of-more-than-one-protein-with-spatio-temporal-control
#1
Miguel M Lino, Susana Simões, Sónia Pinho, Lino Ferreira
Transient, non-integrative modulation of cell function by intracellular delivery of proteins has high potential in cellular reprogramming, gene editing and therapeutic medicine applications. Unfortunately, the capacity to deliver multiple proteins intracellularly with temporal and spatial control has not been demonstrated. Here, we report a near infrared (NIR) laser-activatable nanomaterial that allows for precise control over the release of two proteins from a single nanomaterial. The nanomaterial is formed by gold nanorods (AuNRs) modified with single stranded DNA (ssDNA) to which complementary DNA-conjugated proteins are hybridized...
November 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/29165041/akt-mediated-phosphorylation-of-atg4b-impairs-mitochondrial-activity-and-enhances-the-warburg-effect-in-hepatocellular-carcinoma-cells
#2
Zhenhong Ni, Jintao He, Yaran Wu, Changjiang Hu, Xufang Dai, Xiaojing Yan, Bo Li, Xinzhe Li, Haojun Xiong, Yuming Li, Song Li, Liang Xu, Yongsheng Li, Jiqin Lian, Fengtian He
Phosphorylation is a major type of post-translational modification, which can influence the cellular physiological function. ATG4B, a key macroautophagy/autophagy-related protein, has a potential effect on the survival of tumor cells. However, it is still unknown as to the role of ATG4B phosphorylation in cancers. In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells. The phosphorylation of ATG4B at Ser34 had little effect on autophagic flux, but promoted the Warburg effect including the increase of L-lactate production and glucose consumption, and the decrease of oxygen consumption in HCC cells...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29163707/n-myc-downstream-regulated-gene-2-restrains-glycolysis-and-glutaminolysis-in-clear-cell-renal-cell-carcinoma
#3
Wei Shi, Xinyuan Xu, Fei Yan, Bao Wang, Hang Zhao, Aaron Chan, Zhen Ren, Yongzheng Ma, Fuli Wang, Jianlin Yuan
Glycolysis and glutaminolysis are heavily involved in the metabolic reprogramming of cancer cells. The activation of oncogenes and inactivation of tumor suppressor genes has a marked effect on the cellular metabolic processes glycolysis and glutaminolysis. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene that previous studies have demonstrated can inhibit the growth, proliferation and metastasis of clear cell renal cell carcinoma (ccRCC) cells. However, the function of NDRG2 in ccRCC metabolism remains unknown...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29163504/butyrate-conditions-human-dendritic-cells-to-prime-type-1-regulatory-t-cells-via-both-histone-deacetylase-inhibition-and-g-protein-coupled-receptor-109a-signaling
#4
Maria M M Kaisar, Leonard R Pelgrom, Alwin J van der Ham, Maria Yazdanbakhsh, Bart Everts
Recently, it has become clear that short-chain fatty acids (SCFAs), and in particular butyrate, have anti-inflammatory properties. Murine studies have shown that butyrate can promote regulatory T cells via the induction of tolerogenic dendritic cells (DCs). However, the effects of SCFAs on human DCs and how they affect their capacity to prime and polarize T-cell responses have not been addressed. Here, we report that butyrate suppresses LPS-induced maturation and metabolic reprogramming of human monocyte-derived DCs (moDCs) and conditions them to polarize naive CD4(+) T cells toward IL-10-producing type 1 regulatory T cells (Tr1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163371/cofactors-as-metabolic-sensors-driving-cell-adaptation-in-physiology-and-disease
#5
REVIEW
Nabil Rabhi, Sarah Anissa Hannou, Philippe Froguel, Jean-Sébastien Annicotte
Chromatin architectures and epigenetic fingerprint regulation are fundamental for genetically determined biological processes. Chemical modifications of the chromatin template sensitize the genome to intracellular metabolism changes to set up diverse functional adaptive states. Accumulated evidence suggests that the action of epigenetic modifiers is sensitive to changes in dietary components and cellular metabolism intermediates, linking nutrition and energy metabolism to gene expression plasticity. Histone posttranslational modifications create a code that acts as a metabolic sensor, translating changes in metabolism into stable gene expression patterns...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29163034/direct-reprogramming-rather-than-ipsc-based-reprogramming-maintains-aging-hallmarks-in-human-motor-neurons
#6
Yu Tang, Meng-Lu Liu, Tong Zang, Chun-Li Zhang
In vitro generation of motor neurons (MNs) is a promising approach for modeling motor neuron diseases (MNDs) such as amyotrophic lateral sclerosis (ALS). As aging is a leading risk factor for the development of neurodegeneration, it is important to recapitulate age-related characteristics by using MNs at pathogenic ages. So far, cell reprogramming through induced pluripotent stem cells (iPSCs) and direct reprogramming from primary fibroblasts are two major strategies to obtain populations of MNs. While iPSC generation must go across the epigenetic landscape toward the pluripotent state, directly converted MNs might have the advantage of preserving aging-associated features from fibroblast donors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29158348/galectin-1-a-jack-of-all-trades-in-the-resolution-of-acute-and-chronic-inflammation
#7
REVIEW
Victoria Sundblad, Luciano G Morosi, Jorge R Geffner, Gabriel A Rabinovich
Regulatory signals provide negative input to immunological networks promoting resolution of acute and chronic inflammation. Galectin-1 (Gal-1), a member of a family of evolutionarily conserved glycan-binding proteins, displays broad anti-inflammatory and proresolving activities by targeting multiple immune cell types. Within the innate immune compartment, Gal-1 acts as a resolution-associated molecular pattern by counteracting the synthesis of proinflammatory cytokines, inhibiting neutrophil trafficking, targeting eosinophil migration and survival, and suppressing mast cell degranulation...
December 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29156376/comparative-transcriptomic-analysis-of-endothelial-progenitor-cells-derived-from-umbilical-cord-blood-and-adult-peripheral-blood-implications-for-the-generation-of-induced-pluripotent-stem-cells
#8
Xiugong Gao, Jeffrey J Yourick, Robert L Sprando
Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29155818/snail1-mediated-downregulation-of-foxa-proteins-facilitates-the-inactivation-of-transcriptional-enhancer-elements-at-key-epithelial-genes-in-colorectal-cancer-cells
#9
Sabine Jägle, Hauke Busch, Vivien Freihen, Sven Beyes, Monika Schrempp, Melanie Boerries, Andreas Hecht
Phenotypic conversion of tumor cells through epithelial-mesenchymal transition (EMT) requires massive gene expression changes. How these are brought about is not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anticorrelated in transcriptomes of colorectal tumors and cell lines...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155716/evaluation-of-injury-induced-senescence-and-in-vivo-reprogramming-in-the-skeletal-muscle
#10
Coralie Cazin, Aurelie Chiche, Han Li
Cellular senescence is a stress response that is characterized by a stable cellular growth arrest, which is important for many physiological and pathological processes, such as cancer and ageing. Recently, senescence has also been implicated in tissue repair and regeneration. Therefore, it has become increasingly critical to identify senescent cells in vivo. Senescence-associated β-galactosidase (SA-β-Gal) assay is the most widely used assay to detect senescent cells both in culture and in vivo. This assay is based on the increased lysosomal contents in the senescent cells, which allows the histochemical detection of lysosomal β-galactosidase activity at suboptimum pH (6 or 5...
October 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29151926/the-glycolytic-switch-in-tumors-how-many-players-are-involved
#11
REVIEW
Li Yu, Xun Chen, Xueqi Sun, Liantang Wang, Shangwu Chen
Reprogramming of cellular metabolism is a hallmark of cancers. Cancer cells more readily use glycolysis, an inefficient metabolic pathway for energy metabolism, even when sufficient oxygen is available. This reliance on aerobic glycolysis is called the Warburg effect, and promotes tumorigenesis and malignancy progression. The mechanisms of the glycolytic shift in tumors are not fully understood. Growing evidence demonstrates that many signal molecules, including oncogenes and tumor suppressors, are involved in the process, but how oncogenic signals attenuate mitochondrial function and promote the switch to glycolysis remains unclear...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29150086/the-ex-vivo-toll-like-receptor-7-tolerance-induction-in-donor-lymphocytes-prevents-murine-acute-graft-versus-host-disease
#12
Nikolaos Zogas, Garyfalia Karponi, Fotios Iordanidis, Stylianos Malasidis, Vasilios Paraskevas, Anastasia Papadopoulou, Zaharias George Scouras, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND AIMS: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, mediated by alloreactive donor T cells. Toll-like receptors (TLRs), a family of conserved pattern-recognition receptors (PRRs), represent key players in donors' T-cell activation during aGVHD; however, a regulatory, tolerogenic role for certain TLRs has been recognized in a different context. We investigated whether the ex vivo-induced TLR-2,-4,-7 tolerance in donor cells could prevent alloreactivity in a mismatched transplantation model...
November 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29149942/mechanisms-of-organ-dysfunction-in-sepsis
#13
REVIEW
Rachel Pool, Hernando Gomez, John A Kellum
Sepsis-associated organ dysfunction involves multiple responses to inflammation, including endothelial and microvascular dysfunction, immune and autonomic dysregulation, and cellular metabolic reprogramming. The effect of targeting these mechanistic pathways on short- and long-term outcomes depends highly on the timing of therapeutic intervention. Furthermore, there is a need to understand the adaptive or maladaptive character of these mechanisms, to discover phase-specific biomarkers to guide therapy, and to conceptualize these mechanisms in terms of resistance and tolerance...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#14
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29143563/mammalian-target-of-rapamycin-complex-2-mtorc2-controls-glycolytic-gene-expression-by-regulating-histone-h3-lysine-56-acetylation
#15
Raghavendra Vadla, Devyani Haldar
Metabolic reprogramming is a hallmark of cancer cells, but the mechanisms are not well understood. The mammalian target of rapamycin complex 2 (mTORC2) controls cell growth and proliferation and plays a critical role in metabolic reprogramming in glioma. mTORC2 regulates cellular processes such as cell survival, metabolism, and proliferation by phosphorylation of AGC kinases. Components of mTORC2 are shown to localize to the nucleus, but whether mTORC2 modulates epigenetic modifications to regulate gene expression is not known...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29141558/modulation-of-cancer-metabolism-by-phytochemicals-a-brief-overview
#16
Danina Muntean, Sturza Adrian, Ioana Pavel, Oana Duicu
Despite tremendous research efforts for effective therapies, cancer remains the plague of the century and its burden is expected to increase worldwide in the near future. Metabolic reprogramming is a firmly established hallmark of all cancers, regardless their cellular or tissue origin, being a prerequisite for both tumor growth and invasion. Functional dependence of tumors on glycolysis and glutaminolysis and the crucial contribution of mitochondria to the tumor bioenergetic versatility are well recognized features and established therapeutic targets...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29137367/glycolytic-reprogramming-through-pck2-regulates-tumor-initiation-of-prostate-cancer-cells
#17
Jiangsha Zhao, Jieran Li, Teresa W M Fan, Steven X Hou
Tumor-initiating cells (TICs) play important roles in tumor progression and metastasis. Identifying the factors regulating TICs may open new avenues in cancer therapy. Here, we show that TIC-enriched prostate cancer cell clones use more glucose and secrete more lactate than TIC-low clones. We determined that elevated levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. Information from prostate cancer patient databases revealed that higher PCK2 levels correlated with more aggressive tumors and lower survival rates...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137280/ppar%C3%AE-sumoylation-mediated-lipid-accumulation-in-lung-cancer
#18
Ai N H Phan, Vu T A Vo, Tuyen N M Hua, Min-Kyu Kim, Se-Young Jo, Jong-Whan Choi, Hyun-Won Kim, Jaekyoung Son, Young-Ah Suh, Yangsik Jeong
Metabolic reprogramming as a crucial emerging hallmark of cancer is critical for tumor cells to maintain cellular bioenergetics, biosynthesis and reduction/oxidation (REDOX) balance. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor regulating transcription of diverse gene sets involved in inflammation, metabolism, and suppressing tumor growth. Thiazolidinediones (TZDs), as selective PPARγ ligands, are insulin-sensitizing drugs widely prescribed for type 2 diabetic patients in the clinic...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132538/immunometabolic-profiling-of-t-cells-from-patients-with-relapsing-remitting-multiple-sclerosis-reveals-an-impairment-in-glycolysis-and-mitochondrial-respiration
#19
Claudia La Rocca, Fortunata Carbone, Veronica De Rosa, Alessandra Colamatteo, Mario Galgani, Francesco Perna, Roberta Lanzillo, Vincenzo Brescia Morra, Giuseppe Orefice, Ilaria Cerillo, Ciro Florio, Giorgia Teresa Maniscalco, Marco Salvetti, Diego Centonze, Antonio Uccelli, Salvatore Longobardi, Andrea Visconti, Giuseppe Matarese
BACKGROUND: Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression...
December 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29130506/animal-models-of-acquired-epilepsy-insights-into-mechanisms-of-human-epileptogenesis
#20
Albert J Becker
In many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias (FCDs) and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, i...
November 12, 2017: Neuropathology and Applied Neurobiology
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