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https://www.readbyqxmd.com/read/28107504/sox10-nano-lantern-reporter-human-ips-cells-a-versatile-tool-for-neural-crest-research
#1
Tomoko Horikiri, Hiromi Ohi, Mitsuaki Shibata, Makoto Ikeya, Morio Ueno, Chie Sotozono, Shigeru Kinoshita, Takahiko Sato
The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL) reporter human induced pluripotent stem cells (hiPS) by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021...
2017: PloS One
https://www.readbyqxmd.com/read/28106087/dynamical-states-possibilities-and-propagation-of-stress-signal
#2
Md Zubbair Malik, Shahnawaz Ali, Soibam Shyamchand Singh, Romana Ishrat, R K Brojen Singh
The stress driven dynamics of Notch-Wnt-p53 cross-talk is subjected to a few possible dynamical states governed by simple fractal rules, and allowed to decide its own fate by choosing one of these states which are contributed from long range correlation with varied fluctuations due to active molecular interaction. The topological properties of the networks corresponding to these dynamical states have hierarchical features with assortive structure. The stress signal driven by nutlin and modulated by mediator GSK3 acts as anti-apoptotic signal in this system, whereas, the stress signal driven by Axin and modulated by GSK3 behaves as anti-apoptotic for a certain range of Axin and GSK3 interaction, and beyond which the signal acts as favor-apoptotic signal...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100707/the-rla1-smos1-transcription-factor-functions-with-osbzr1-to-regulate-brassinosteroid-signaling-and-rice-architecture
#3
Shenglong Qiao, Shiyong Sun, Linlin Wang, Zhihua Wu, Chengxiang Li, Xiaoming Li, Tao Wang, Linna Leng, Weisheng Tian, Tiegang Lu, Xuelu Wang
Brassinosteroids (BRs) are plant-specific steroid hormones that control plant growth and development. Recent studies have identified key components of the BR signaling pathway in Arabidopsis thaliana and in rice (Oryza sativa); however, the mechanism of BR signaling in rice, especially downstream of GSK3/SHAGGY-like kinase (GSK2), remains unclear. Here we identified a BR-insensitive rice mutant, reduced leaf angle 1 (rla1), and cloned the corresponding gene. RLA1 was identical to the previously reported SMALL ORGAN SIZE 1 (SMOS1) which was cloned from another allele...
January 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28098160/a-zip6-zip10-heteromer-controls-ncam1-phosphorylation-and-integration-into-focal-adhesion-complexes-during-epithelial-to-mesenchymal-transition
#4
Dylan Brethour, Mohadeseh Mehrabian, Declan Williams, Xinzhu Wang, Farinaz Ghodrati, Sepehr Ehsani, Elizabeth A Rubie, James R Woodgett, Jean Sevalle, Zhengrui Xi, Ekaterina Rogaeva, Gerold Schmitt-Ulms
The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096467/mir-21-mediated-radioresistance-is-via-promoting-repair-of-dna-double-strand-breaks
#5
Baocheng Hu, Xiang Wang, Suofeng Hu, Xiaomin Ying, Ping Wang, Xiangming Zhang, Jian Wang, Hongyan Wang, Ya Wang
MiR-21 as an oncogene that over-expresses in most human tumors involves radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance is through promoting repair of DNA double strand breaks, which includes to facilitate both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ is through targeting GSK3B (a novel target of miR-21) that affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR is through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase since GSK3B promotes degradation of both CDC25A and Cyclin D1, but CDC25A and Cyclin D1 have an opposite effect on HRR...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28094799/activation-of-wnt-%C3%AE-catenin-signalling-via-gsk3-inhibitors-direct-differentiation-of-human-adipose-stem-cells-into-functional-hepatocytes
#6
Jieqiong Huang, Xinyue Guo, Weihong Li, Haiyan Zhang
The generation of hepatocytes that are derived from human adipose stem cells (hASCs) represents an alternative to human hepatocytes for individualized therapeutic and pharmaceutical applications. However, the mechanisms facilitating hepatocyte differentiation from hASCs are not well understood. Here, we show that upon exposure to glycogen synthase kinase 3 (GSK3) inhibitors alone, the expression of definitive endoderm specific genes GATA4, FOXA2, and SOX17 in hASCs significantly increased in a manner with activation of Wnt/β-catenin signalling...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089951/bzr1-positively-regulates-freezing-tolerance-via-cbf-dependent-and-cbf-independent-pathways-in-arabidopsis
#7
Hui Li, Keyi Ye, Yiting Shi, Jinkui Cheng, Xiaoyan Zhang, Shuhua Yang
Cold stress is a major environmental factor that adversely affects plant growth and development. The C-repeat Binding Factor/DRE Binding Factor 1 (CBF/DREB1) transcriptional regulatory cascade has been shown to play important roles in plant response to cold. Here we demonstrate that two key components of BR signaling modulate freezing tolerance of plants. The loss-of-function mutant of the GSK3-like kinases involved in BR signaling, bin2-3 bil1 bil2, showed increased freezing tolerance, whereas overexpression of BIN2 resulted in hypersensitivity to freezing stress under both non-acclimated and acclimated conditions...
January 13, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28081383/inhibiting-effect-of-lithium-chloride-on-endotoxin-induced-uveitis-in-rats
#8
Shuo Yang, Shuo Yu, Xinli Liu, Jinyi Yu, Xiaosheng Zhang, Hong Lu
PURPOSE: To evaluate the anti-inflammatory effect of lithium chloride in endotoxin-induced uveitis. METHODS: A total of 200 Wistar rats were randomly divided into four groups: a control group; EIU group; LiCl-treated control group; and LiCl-treated lipopolysaccharide group. Clinical score, slit-lamp photography, hematoxylin and eosin (H&E) staining were used to determine the degree of inflammatory reaction. Level of glycogen synthase kinase3-beta and nuclear factor-kappa B p65 in iris-ciliary body was examined by western blot and RT-PCR...
January 12, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28077400/differential-expression-of-hedgehog-and-snail-in-cutaneous-fibrosing-disorders-implications-for-targeted-inhibition
#9
Amrita Goyal, Katy R Linskey, Jonathan Kay, Lyn M Duncan, Rosalynn M Nazarian
OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition. METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 β (GSK3-β), β-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28076326/cytosolic-thumpd1-promotes-breast-cancer-cells-invasion-and-metastasis-via-the-akt-gsk3-snail-pathway
#10
Xiupeng Zhang, Guiyang Jiang, Mingfang Sun, Haijing Zhou, Yuan Miao, Mengyuan Liang, Enhua Wang, Yong Zhang
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28068632/hydroxysafflor-yellow-a-cardioprotection-in-ischemia-reperfusion-i-r-injury-mainly-via-akt-hexokinase-ii-independent-of-erk-gsk-3%C3%AE-pathway
#11
Jia Min, Cui Wei
Hydroxysafflor yellow A (HSYA) is the main active component of Carthamus tinctorius L which has been used for hundreds of years in Chinese folk medicine in the treatment cardiovascular disease. This study was designed to investigate whether HSYA exerts cardioprotection in ischemia-reperfusion (I/R) injury heart and the mechanisms involved. The protective effect and mechanisms in myocardial ischemia reperfusion injury of HSYA was evaluated by hypoxia-recover (H/R) injury cell model which induced by hypoxia and recovered with oxygen in H9c2 cells...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28068511/inhibition-of-glycogen-synthase-kinase-3-accelerated-liver-regeneration-after-acetaminophen-induced-hepatotoxicity-in-mice
#12
Bharat Bhushan, Samikshya Poudel, Michael W Manley, Nairita Roy, Udayan Apte
Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of β-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice...
January 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28067250/promotion-of-natural-tooth-repair-by-small-molecule-gsk3-antagonists
#13
Vitor C M Neves, Rebecca Babb, Dhivya Chandrasekaran, Paul T Sharpe
The restoration of dentine lost in deep caries lesions in teeth is a routine and common treatment that involves the use of inorganic cements based on calcium or silicon-based mineral aggregates. Such cements remain in the tooth and fail to degrade and thus normal mineral volume is never completely restored. Here we describe a novel, biological approach to dentine restoration that stimulates the natural formation of reparative dentine via the mobilisation of resident stem cells in the tooth pulp. Biodegradable, clinically-approved collagen sponges are used to deliver low doses of small molecule glycogen synthase kinase (GSK-3) antagonists that promote the natural processes of reparative dentine formation to completely restore dentine...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28064546/targeting-protein-kinase-b3-akt3-signaling-in-melanoma
#14
SubbaRao V Madhunapantula, Gavin P Robertson
Deregulated Akt activity leading to apoptosis inhibition, enhanced proliferation and drug resistance has been shown to be responsible for 35-70% of advanced metastatic melanomas. Of the three isoforms, the majority of melanomas have elevated Akt3 expression and activity. Hence, potent inhibitors targeting Akt are urgently required, which is possible only if (a) the factors responsible for the failure of Akt inhibitors in clinical trials is known; and (b) the information pertaining to synergistically acting targeted therapeutics is available...
January 9, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28049917/synthesis-docking-study-and-kinase-inhibitory-activity-of-a-number-of-new-substituted-pyrazolo-3-4-c-pyridines
#15
Meropi Sklepari, Nikolaos Lougiakis, Athanasios Papastathopoulos, Nicole Pouli, Panagiotis Marakos, Vassilios Myrianthopoulos, Thomas Robert, Stéphane Bach, Emmanuel Mikros, Sandrine Ruchaud
A series of new pyrazolo[3,4-c]pyridines bearing various 1, 3, 5 or 1, 3, 7 pattern substitutions, were designed and synthesized. Some of them showed interesting inhibitory activity mainly against glycogen synthase kinase 3 (GSK3)α/β as well as against cdc2-like kinases 1 (CLK1) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), with good selectivity and remarkable structure-activity relationships (SARs), without being cytotoxic. Molecular simulations in correlation with biological data revealed the importance of the existence of N1-H as well as the absence of a bulky 7-substituent...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28049096/anti-diabetic-effect-of-three-new-norditerpenoid-alkaloids-in-vitro-and-potential-mechanism-via-pi3k-akt-signaling-pathway
#16
Dan Tang, Qi-Bin Chen, Xue-Lei Xin, Haji-Akber Aisa
Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A-C (compounds A-C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A-C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A-C...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28038351/microrna-29-impairs-the-early-phase-of-reprogramming-process-by-targeting-active-dna-demethylation-enzymes-and-wnt-signaling
#17
Mariane Serra Fráguas, Reto Eggenschwiler, Jeannine Hoepfner, Josiane Lilian Dos Santos Schiavinato, Rodrigo Haddad, Lucila Habib Bourguignon Oliveira, Amélia Góes Araújo, Marco Antônio Zago, Rodrigo Alexandre Panepucci, Tobias Cantz
Somatic cell reprogramming by transcription factors and other modifiers such as microRNAs has opened broad avenues for the study of developmental processes, cell fate determination, and interplay of molecular mechanisms in signaling pathways. However, many of the mechanisms that drive nuclear reprogramming itself remain yet to be elucidated. Here, we analyzed the role of miR-29 during reprogramming in more detail. Therefore, we evaluated miR-29 expression during reprogramming of fibroblasts transduced with lentiviral OKS and OKSM vectors and we show that addition of c-MYC to the reprogramming factor cocktail decreases miR-29 expression levels...
December 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/28025142/characterization-of-goat-inner-cell-mass-derived-cells-in-double-kinase-inhibition-condition
#18
Qiang Wei, Qihui Xi, Xiaokun Liu, Kai Meng, Xiaoe Zhao, Baohua Ma
The identification of small molecular inhibitors, which were reported to promote the derivation of mouse and human embryonic stem cells (ESCs), provides a potential strategy for the derivation of domesticated ungulate ESCs. In present study, goat inner cell mass (ICM) derived cells in the double inhibition (2i) condition, in which, mitogen-activated protein kinase kinase (MAP2K) and glycogen synthase kinase 3 (GSK3) were inhibited by PD0325901 and BIO respectively, were characterized. The results showed that goat ICM derived cells in 2i medium adding leukaemia inhibitor factor (LIF) possessed a mouse ES-like morphology...
December 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28012947/the-gsk-3-inhibitor-vp2-51-produces-antidepressant-effects-associated-with-adult-hippocampal-neurogenesis
#19
Paloma Pérez-Domper, Valle Palomo, Simona Gradari, Carmen Gil, María L de Ceballos, Ana Martínez, Jose Luis Trejo
Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that has been implicated in the mechanism of action of mood stabilizers. According to the neurogenic hypothesis of depression, newborn neurons in the adult dentate gyrus are required for the antidepressant effects of certain agents. We demonstrate that administration of the GSK-3 inhibitor VP2.51 (2.5 mg/kg ip, for 3.5 weeks) increases cell proliferation (pH3(+) cells), as well as the short- and long-term survival of newborn neurons (assessed by the 24 h survival of BrdU(+) and DCX(+) neurons), while significantly increasing the commitment of cells to the granule neuron lineage (Prox1 immunoreactivity)...
December 22, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28003464/nat1-promotes-translation-of-specific-proteins-that-induce-differentiation-of-mouse-embryonic-stem-cells
#20
Hayami Sugiyama, Kazutoshi Takahashi, Takuya Yamamoto, Mio Iwasaki, Megumi Narita, Masahiro Nakamura, Tim A Rand, Masato Nakagawa, Akira Watanabe, Shinya Yamanaka
Novel APOBEC1 target 1 (Nat1) (also known as "p97," "Dap5," and "Eif4g2") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation...
December 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
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