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Stem cell metabolism

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https://www.readbyqxmd.com/read/28541695/discovery-of-potent-selective-stem-cell-factor-receptor-platelet-derived-growth-factor-receptor-alpha-c-kit-pdgfr%C3%AE-dual-inhibitor-for-the-treatment-of-imatinib-resistant-gastrointestinal-stromal-tumors-gists
#1
Yanli Lu, Fei Mao, Xiaokang Li, Xinyu Zheng, Manjiong Wang, Qing Xu, Jin Zhu, Jian Li
c-KIT and platelet derived growth factor receptor alpha (PDGFRα) kinase play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFRα dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRα. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PDGFRα-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28541657/chemical-modulation-of-protein-o-glcnacylation-via-ogt-inhibition-promotes-human-neural-cell-differentiation
#2
Lissette M Andres, Ian W Blong, Angela C Evans, Neil G Rumachik, Teppei Yamaguchi, Nam D Pham, Pamela Thompson, Jennifer J Kohler, Carolyn R Bertozzi
The enzymes that determine protein O-GlcNAcylation, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), act on key transcriptional and epigenetic regulators and both are abundantly expressed in the brain. However, little is known about how alterations in O-GlcNAc cycling affect human embryonic stem cell (hESC) neural differentiation. Here, we studied the effects of perturbing O-GlcNAcylation during neural induction of hESCs using the metabolic inhibitor of OGT, peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc)...
May 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28540498/metabolic-regulation-of-hematopoietic-and-leukemic-stem-progenitor-cells-under-homeostatic-and-stress-conditions
#3
REVIEW
Daiki Karigane, Keiyo Takubo
Hematopoietic stem cells (HSCs) exhibit multilineage differentiation and self-renewal activities that maintain the entire hematopoietic system during an organism's lifetime. These abilities are sustained by intrinsic transcriptional programs and extrinsic cues from the microenvironment or niche. Recent studies using metabolomics technologies reveal that metabolic regulation plays an essential role in HSC maintenance. Metabolic pathways provide energy and building blocks for other factors functioning at steady state and in stress...
May 24, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28539263/nutrients-neurogenesis-and-brain-ageing-from-disease-mechanisms-to-therapeutic-opportunities
#4
REVIEW
Marco Fidaleo, Virve Cavallucci, Giovambattista Pani
Appreciation of the physiological relevance of mammalian adult neurogenesis has in recent years rapidly expanded from a phenomenon of homeostatic cell replacement and brain repair to the current view of a complex process involved in high order cognitive functions. In parallel, an array of endogenous or exogenous triggers of neurogenesis have also been identified, among which metabolic and nutritional cues have drawn significant attention. Converging evidence from animal and in vitro studies point to nutrient sensing and energy metabolism as major physiological determinants of neural stem cell fate, and modulators of the whole neurogenic process...
May 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28537488/capturing-human-na%C3%A3-ve-pluripotency-in-the-embryo-and-in-the-dish
#5
Ludovic Zimmerlin, Tea Soon Park, Elias T Zambidis
Although human embryonic stem cells (hESC) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to post-implantation lineage-primed murine epiblast stem cells (EpiSC) than to naïve pre-implantation ICM-derived mouse embryonic stem cells (ESC). A myriad of transcriptional, epigenetic, biochemical, and metabolic attributes have now been described that distinguish naïve and primed pluripotent states in both rodents and humans. Conventional hESC and human induced pluripotent stem cells (hiPSC) appear to lack many of the defining hallmarks of naïve mouse ESC...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28537457/inhibition-of-mtor-kinase-as-a-therapeutic-target-for-acute-myeloid-leukemia
#6
Yoko Tabe, Agostino Tafuri, Kazumasa Sekihara, Haeun Yang, Marina Konopleva
Acute myeloid leukemia (AML), the most common acute leukemia in adults, remains a therapeutic challenge. The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is one of the key aberrant intracellular axes involved in AML. Areas covered: mTOR plays a critical role in sensing and responding to environmental determinants such as nutrient availability, stress, and growth factor concentrations; and in modulating key cellular functions such as proliferation, metabolism, and survival...
May 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28536347/the-current-use-of-stem-cells-in-bladder-tissue-regeneration-and-bioengineering
#7
REVIEW
Yvonne Y Chan, Samantha K Sandlin, Eric A Kurzrock, Stephanie L Osborn
Many pathological processes including neurogenic bladder and malignancy necessitate bladder reconstruction, which is currently performed using intestinal tissue. The use of intestinal tissue, however, subjects patients to metabolic abnormalities, bladder stones, and other long-term sequelae, raising the need for a source of safe and reliable bladder tissue. Advancements in stem cell biology have catapulted stem cells to the center of many current tissue regeneration and bioengineering strategies. This review presents the recent advancements in the use of stem cells in bladder tissue bioengineering...
January 6, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536316/-adipose-stem-cell-system
#8
Yumiko Oishi, Ichiro Manabe
Adipose tissues are the major organ that controls systemic energy metabolism and maintain homeostasis by storing lipids, dissipating them as heat, and producing various adipokines. There are two major classes of adipocytes: white and brown adipocytes. White adipocytes store and release lipids, while brown adipocytes burn substrates to produce heat. In addition to classical brown adipose tissues consisting of brown adipocytes, cold exposure and β3 stimulation induce development of brown cell-like "beige" adipocytes in white adipose tissues...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28536314/-characterization-of-bone-marrow-mesenchymal-stem-cells
#9
Toshihide Mizoguchi
Bones support the body as part of the human musculoskeletal system. They also contain bone marrow, which is a site of hematopoiesis. Bone marrow mesenchymal stem cells play a vital role by regulating skeletal tissue formation and maintaining hematopoiesis. While the presence of bone marrow-derived mesenchymal stem cells has been indicated, they have yet to be fully understood in vivo. Recent studies using genetic mouse models revealed that perivascular stromal cells function as mesenchymal stem cells, and their differentiation status may vary during the early stage of life to adulthood...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28536247/circadian-networks-in-human-embryonic-stem-cell-derived-cardiomyocytes
#10
Pieterjan Dierickx, Marit W Vermunt, Mauro J Muraro, Menno P Creyghton, Pieter A Doevendans, Alexander van Oudenaarden, Niels Geijsen, Linda W Van Laake
Cell-autonomous circadian oscillations strongly influence tissue physiology and pathophysiology of peripheral organs including the heart, in which the circadian clock is known to determine cardiac metabolism and the outcome of for instance ischemic stress. Human pluripotent stem cells represent a powerful tool to study developmental processes in vitro, but the extent to which human embryonic stem (ES) cell-derived cardiomyocytes establish circadian rhythmicity in the absence of a systemic context is unknown...
May 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28536008/chemosensitization-and-inhibition-of-pancreatic-cancer-stem-cell-proliferation-by-overexpression-of-microrna-205
#11
Amit Kumar Chaudhary, Goutam Mondal, Virender Kumar, Krishna Kattel, Ram I Mahato
Treatment of pancreatic cancer with gemcitabine (GEM) is limited due to its rapid plasma metabolism and development of chemoresistance. MicroRNA (miRNA) regulates cancer stem cell (CSC) maintenance and induces chemoresistance in cancer cells. In this study, we observed differential downregulation of miR-205 (miR-205-5p) in human pancreatic cancer tissues and cells. Compared to GEM-sensitive MIA PaCa-2 cells, miR-205 was highly downregulated in GEM-resistant MIA PaCa-2R cells. Lentivirus-mediated overexpression of miR-205 inhibits MIA PaCa-2R cell proliferation after GEM-treatment...
May 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28528863/cross-linking-of-a-biopolymer-peptide-co-assembling-system
#12
Karla E Inostroza-Brito, Estelle C Collin, Anna Poliniewicz, Sherif Elsharkawy, Alistair Rice, Armando E Del Río Hernández, Xin Xiao, José Rodríguez-Cabello, Alvaro Mata
The ability to guide molecular self-assembly at the nanoscale into complex macroscopic structures could enable the development of functional synthetic materials that exhibit properties of natural tissues such as hierarchy, adaptability, and self-healing. However, the stability and structural integrity of these kinds of materials remains a challenge for many practical applications. We have recently developed a dynamic biopolymer-peptide co-assembly system with the capacity to grow and undergo morphogenesis into complex shapes...
May 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28527661/modulation-of-adipocyte-function-by-the-tgf-%C3%AE-family
#13
Yuhang Qiao, Shozo Tomonaga, Masashi Suenaga, Tohru Matsui, Masayuki Funaba
Members of the transforming growth factor-β (TGF-β) family are known to regulate the commitment of mesenchymal stem cells to an adipocyte lineage and the differentiation of preadipocytes to adipocytes. However, the roles of TGF-β family members in mature adipocytes are not known. The present study explored the modulation of cell function in 3T3-L1 adipocytes treated with the TGF-β family members TGF-β1, activin A, activin B, bone morphogenetic protein (BMP) 4, and BMP7. These TGF-β family members modulated the expression of some adipokines; activin A upregulated leptin expression, and activin B downregulated the expression of plasminogen activator inhibitor-1...
May 17, 2017: Cytokine
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#14
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28526089/adipose-derived-mesenchymal-stem-cells-from-liposuction-and-resected-fat-are-feasible-sources-for-regenerative-medicine
#15
Sandra Schneider, Marina Unger, Martijn van Griensven, Elizabeth R Balmayor
BACKGROUND: The use of mesenchymal stem cells (MSCs) in research and in regenerative medicine has progressed. Bone marrow as a source has drawbacks because of subsequent morbidities. An easily accessible and valuable source is adipose tissue. This type of tissue contains a high number of MSCs, and obtaining higher quantities of tissue is more feasible. Fat tissue can be harvested using different methods such as liposuction and resection. First, a detailed isolation protocol with complete characterization is described...
May 19, 2017: European Journal of Medical Research
https://www.readbyqxmd.com/read/28525352/evaluation-of-endocrine-and-metabolic-dysfunctions-after-hematopoietic-stem-cell-transplantation-in-children-a-study-from-turkey
#16
Dilek Gurlek Gokcebay, Fatih Azik, Cengiz Bayram, Arzu Yazal Erdem, Ali Fettah, Pamir Isik, Nese Yarali, Fatma Demirel, Bahattin Tunc, Namik Ozbek
BACKGROUND: Endocrine organs are highly susceptible to effects of high-dose chemotherapy. The objective of the study was to evaluate endocrine and metabolic complications after hematopoietic stem cell transplantation (HSCT) in children. METHODS: The patients who underwent HSCT in our center from April 2010 to October 2014 with at least 1 year follow-up were analyzed retrospectively. RESULTS: One-hundred children (M/F:59/41; mean age 8.9±4...
May 18, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28522553/glioblastoma-derived-cells-in-vitro-unveil-the-spectrum-of-drug-resistance-capabilty-comparative-study-of-tumour-chemosensitivity-in-different-culture-systems
#17
Monika Witusik-Perkowska, Magdalena Zakrzewska, Beata Sikorska, Wielislaw Papierz, Dariusz J Jaskolski, Janusz Szemraj, Pawel P Liberski
Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28521687/diet-and-contaminants-driving-the-rise-to-obesity-epidemics
#18
Agostino Di Ciaula, Piero Portincasa
The obesity epidemic is spreading worldwide without reversal trend and despite specific policies oriented to dietary habits and lifestyle, which seem to have modest effects. Genetic factors only partly explain the rise, whereas environmental factors seem to play a key role, mainly by gene-environment interactions through epigenetic mechanisms. A number of animal and human studies point to maternal diet, intestinal microbiota and chemicals introduced as contaminants with food, all factors able to increase the risk of obesity...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28518147/survivin-a-key-player-in-cancer-progression-increases-in-obesity-and-protects-adipose-tissue-stem-cells-from-apoptosis
#19
Miriam Ejarque, Victòria Ceperuelo-Mallafré, Carolina Serena, Gisela Pachón, Yaiza Núñez-Álvarez, Margarida Terrón-Puig, Enrique Calvo, Catalina Núñez-Roa, Wilfredo Oliva-Olivera, Francisco J Tinahones, Miguel Angel Peinado, Joan Vendrell, Sonia Fernández-Veledo
Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28518137/nerve-growth-factor-from-chinese-cobra-venom-stimulates-chondrogenic-differentiation-of-mesenchymal-stem-cells
#20
Zhenhui Lu, Danqing Lei, Tongmeng Jiang, Lihui Yang, Li Zheng, Jinmin Zhao
Growth factors such as transforming growth factor beta1 (TGF-β1), have critical roles in the regulation of the chondrogenic differentiation of mesenchymal stem cells (MSCs), which promote cartilage repair. However, the clinical applications of the traditional growth factors are limited by their high cost, functional heterogeneity and unpredictable effects, such as cyst formation. It may be advantageous for cartilage regeneration to identify a low-cost substitute with greater chondral specificity and easy accessibility...
May 18, 2017: Cell Death & Disease
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