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https://www.readbyqxmd.com/read/28931214/baicalin-alleviates-radiation-induced-epithelial-mesenchymal-transition-of-primary-type-ii-alveolar-epithelial-cells-via-tgf-%C3%AE-and-erk-gsk3%C3%AE-signaling-pathways
#1
Jinhua Lu, Yazhen Zhong, Zechen Lin, Xianlei Lin, Zhaohui Chen, Xuping Wu, Nan Wang, Haiqiao Zhang, Siyu Huang, Yuan Zhu, Yuanyuan Wang, Shengyou Lin
BACKGROUND: Radiation therapy is commonly used to treat thoracic malignancies. However, it may lead to severe lung pneumonitis and ultimately fibrosis. Irradiation has been reported to increase epithelial-mesenchymal transition (EMT) of type II alveolar epithelial cells (AEC), which play an important role in pulmonary fibrosis. The transforming growth factor-β (TGF-β) and ERK/glycogen synthase kinase 3β (GSK3β) pathways are critically involved in radiation-induced EMT. In the present study, we investigated whether baicalin was a novel therapeutic candidate for radiation-induced EMT in type II AEC...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28930226/shenlinglan-influences-the-attachment-and-migration-of-ovarian-cancer-cells-potentially-through-the-gsk3-pathway
#2
Sioned Owen, Fiona Ruge, Yunong Gao, Ying Yang, Jianqing Hou, Jian Chen, Yi Feng, Huiming Zhang, Yong Gao, Hongtao Wang, Cong Wei, Yiling Wu, Wen G Jiang
Background: Ovarian cancer presents a major clinical challenge in the UK. Glycogen synthase kinase-3 (GSK-3) has been linked to cancer. This study tested the impact of ShenLingLan (SLDM) on ovarian cancer cell behaviour and its links to GSK-3. Methods: Fresh ovarian tumours (n = 52) were collected and processed. Histopathologcial and clinical information were collected and analysed against GSK-3 transcript levels using quantitative PCR (qPCR). Immortalised ovarian cancer cells' protein alterations in response to SLDM were identified using a Kinexus™ protein kinase array...
February 21, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929374/inhibition-of-gsk-3%C3%AE-activation-protects-sd-rat-retina-against-n-methyl-n-nitrosourea-induced-degeneration-by-modulating-the-wnt-%C3%AE-catenin-signaling-pathway
#3
Baoying Wang, Chenghu Hu, Xiaobei Yang, Fangying Du, Yan Feng, Hongbo Li, Chunhui Zhu, Xiaorui Yu
Retinal degenerative diseases are characterized by photoreceptor cell loss. Photoreceptor cell loss leading to retinal degeneration can be induced by N-methyl-N-nitrosourea (MNU), which was widely used to mimic the pathology. However, the mechanism by which MNU induces photoreceptor cell loss is still largely unknown. The purpose of the present study was to investigate whether phosphorylation of glycogen synthase kinase-3β (p-GSK-3β) is a potent mediator of MNU-induced retinal degeneration and how p-GSK-3β affects the process...
September 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28928905/fucoxanthin-a-marine-carotenoid-attenuates-%C3%AE-amyloid-oligomer-induced-neurotoxicity-possibly-via-regulating-the-pi3k-akt-and-the-erk-pathways-in-sh-sy5y-cells
#4
Jiajia Lin, Jie Yu, Jiaying Zhao, Ke Zhang, Jiachen Zheng, Jialing Wang, Chunhui Huang, Jingrong Zhang, Xiaojun Yan, William H Gerwick, Qinwen Wang, Wei Cui, Shan He
Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by neurofibrillary tangles, synaptic impairments, and loss of neurons. Oligomers of β-amyloid (Aβ) are widely accepted as the main neurotoxins to induce oxidative stress and neuronal loss in AD. In this study, we discovered that fucoxanthin, a marine carotenoid with antioxidative stress properties, concentration dependently prevented Aβ oligomer-induced increase of neuronal apoptosis and intracellular reactive oxygen species in SH-SY5Y cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28928604/kaempferide-protects-against-myocardial-ischemia-reperfusion-injury-through-activation-of-the-pi3k-akt-gsk-3%C3%AE-pathway
#5
Dong Wang, Xinjie Zhang, Defang Li, Wenjin Hao, Fanqing Meng, Bo Wang, Jichun Han, Qiusheng Zheng
The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28927088/pcdh8-inhibits-glioma-cell-proliferation-by-negatively-regulating-the-akt-gsk3%C3%AE-%C3%AE-catenin-signaling-pathway
#6
Zhenkun Zong, Hui Pang, Rutong Yu, Yunqi Jiao
Protocadherin-8 (PCDH8), a member of the protocadherin superfamily of proteins, is frequently lost in numerous types of cancer. However, the role that PCDH8 serves in human glioma, and the molecular mechanisms underlying this, remain unclear. Data from the present study demonstrated that the expression levels of PCDH8 mRNA and protein were significantly decreased in human glioma tissue compared with normal brain tissue. This suggested that PCDH8 is associated with the development of glioma. Thus, the role of PCDH8 in glioma cell proliferation was investigated by silencing and overexpressing PCDH8 in U251 glioma cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28918013/mir-135b-stimulates-osteosarcoma-recurrence-and-lung-metastasis-via-notch-and-wnt-%C3%AE-catenin-signaling
#7
Hua Jin, Song Luo, Yun Wang, Chang Liu, Zhenghao Piao, Meng Xu, Wei Guan, Qing Li, Hua Zou, Qun-You Tan, Zhen-Zhou Yang, Yan Wang, Dong Wang, Cheng-Xiong Xu
Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/β-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/β-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/β-catenin and Notch signaling...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917666/hippocampal-neurophysiology-is-modified-by-a-disease-associated-c-terminal-fragment-of-tau-protein
#8
Francesco Tamagnini, Darren A Walsh, Jon T Brown, Marie K Bondulich, Diane P Hanger, Andrew D Randall
The accumulation of cleaved tau fragments in the brain is associated with several tauopathies. For this reason, we recently developed a transgenic mouse that selectively accumulates a C-Terminal 35 kDa human tau fragment (Tau35). These animals develop progressive motor and spatial memory impairment, paralleled by increased hippocampal glycogen synthase kinase 3β activity. In this neurophysiological study, we focused on the CA1 subfield of the hippocampus, a brain area involved in memory encoding. The accumulation of Tau35 results in a significant increase of short-term facilitation of the synaptic response in the theta frequency range (10 Hz), without affecting basal synaptic transmission and long-term synaptic plasticity...
July 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28916781/6-bromo-indirubin-3-oxime-6bio-a-glycogen-synthase-kinase-3%C3%AE-inhibitor-activates-cytoprotective-cellular-modules-and-suppresses-cellular-senescence-mediated-biomolecular-damage-in-human-fibroblasts
#9
Aimilia D Sklirou, Nicolas Gaboriaud-Kolar, Issidora Papassideri, Alexios-Leandros Skaltsounis, Ioannis P Trougakos
As genetic interventions or extended caloric restriction cannot be applied in humans, many studies have been devoted to the identification of natural products that can prolong healthspan. 6-bromoindirubin-3'-oxime (6BIO), a hemi-synthetic derivative of indirubins found in edible mollusks and plants, is a potent inhibitor of Glycogen synthase kinase 3β (Gsk-3β). This pleiotropic kinase has been implicated in various age-related diseases including tumorigenesis, neurodegeneration and diabetes. Accordingly, 6BIO has shown anti-tumor and anti-neurodegenerative activities; nevertheless, the potential role of 6BIO in normal human cells senescence remains largely unknown...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916722/phosphoproteomics-reveals-that-glycogen-synthase-kinase-3-phosphorylates-multiple-splicing-factors-and-is-associated-with-alternative-splicing
#10
Mansi Y Shinde, Simone Sidoli, Katarzyna Kulej, Michael J Mallory, Caleb M Radens, Amanda Reicherter, Rebecca L Myers, Yoseph Barash, Kristen W Lynch, Benjamin A Garcia, Peter S Klein
Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif (pS/pTXXXS/T), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry (MS) techniques to analyze the repertoire of GSK-3-dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ~2...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916327/glycogen-metabolism-in-brain-and-neurons-astrocytes-metabolic-cooperation-can-be-altered-by-pre-and-neonatal-lead-pb-exposure
#11
Irena Baranowska-Bosiacka, Anna Falkowska, Izabela Gutowska, Magdalena Gąssowska, Agnieszka Kolasa-Wołosiuk, Maciej Tarnowski, Karina Chibowska, Marta Goschorska, Dariusz Chlubek
Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB)...
September 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28914437/salutary-potential-of-ethanolic-extract-of-avocado-fruit-on-anomalous-carbohydrate-metabolic-key-enzymes-in-hepatic-and-renal-tissues-of-hyperglycaemic-albino-rats
#12
U S Mahadeva Rao
OBJECTIVE: To assess the beneficial potential of ethanolic extract of avocado fruit on abnormal carbohydrate metabolic key enzymes in hepatic and renal tissues in streptozotocin (STZ) induced hyperglycemic albino rats. METHODS: Twenty-four male albino rats were randomly divided into four groups with six in each group by simple random sampling method. Group 1 as control rats; Group 2 as STZ induced diabetic rats; Group 3 as diabetic rats treated with avocado fruit extract (AFE), 300 mg/kg as aqueous suspension orally for 30 days; Group 4 as diabetic rats treated with gliclazide (5 mg/kg) in aqueous solution orally for 30 days...
September 15, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28911173/lithium-chloride-increases-cox-2-expression-and-pge2-production-in-a-human-granulosa-lutein-svog-cell-line-via-a-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway
#13
Long Bai, Hsun-Ming Chang, Jung-Chien Cheng, Guiyan Chu, Peter C K Leung, Gongshe Yang
Lithium chloride (LiCl) is widely prescribed for the treatment of bipolar disorders and is associated with a higher incidence of reproductive adverse effects. Cyclooxygenase (COX)-2 and its derivative, prostaglandin E2 (PGE2), play regulatory roles in the human ovulatory process. Whether LiCl affects ovulation by regulating COX2 expression and PGE2 production in the human ovary is still largely unknown. The aim of this study was to investigate the effect of LiCl on the expression of COX-2 and production of PGE2 in human granulosa-lutein (hGL) cells, as well as the mechanisms underlying this effect...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28910976/isochlorogenic-acid-a-promotes-melanin-synthesis-in-b16-cell-through-the-%C3%AE-catenin-signal-pathway
#14
Nuramina Mamat, Jun Dou, Xueying Lu, Aiden Eblimit, Aisa Haji Akber
Isochlorogenic acid A, also called 3,5-dicaffeoylquinic acid (3,5-diCQA), is a widespread phenolic compound in the plant. Recent studies have shown that it has antioxidant and anti-inflammatory activity. In addition, oxidative stress and inflammation induced by solar ultraviolet radiation is a very significant reason for skin depigmentation. Therefore, in this study, we evaluated the effect of 3,5-diCQA on B16 cells and explored its molecular mechanism. Results showed that 3,5-diCQA upregulated intracellular melanin production in a time- and dose-dependent manner...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28902708/the-effects-of-mlc901-on-tau-phosphorylation
#15
Wei Thye Lee, Christopher Chen Li Hsian, Yun-An Lim
Tauopathies are neurodegenerative diseases that are characterized by the presence of hyperphosphorylated tau-containing neurofibrillary tangles (NFTs) in the brain and include Alzheimer's disease and frontotemporal dementia, which lack effective disease-modifying treatments. The presence of NFTs is known to correlate with cognition impairment, suggesting that targeting tau hyperphosphorylation may be therapeutically effective. MLC901 is a herbal formulation that is currently used in poststroke recovery and consists of nine herbal components...
September 11, 2017: Neuroreport
https://www.readbyqxmd.com/read/28901469/glycogen-synthase-kinase%C3%A2-3%C3%AE-inhibitor-reduces-lps%C3%A2-induced-acute-lung-injury-in-mice
#16
Qi Ding, Gaoqin Liu, Yuanyuan Zeng, Jianjie Zhu, Zeyi Liu, Junhong Jiang, Jianan Huang
The aim of the present study was to examine the role of Wnt signaling in lipopolysaccharide (LPS)‑induced acute respiratory distress syndrome (ARDS). ARDS was induced by LPS and compared in mice treated with either glycogen synthase kinase‑3β inhibitor (GSKI) or PBS. The protein expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor (TNF)‑α, IL‑17, IL‑18 and IL‑1β in the bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific enzyme‑linked immunosorbent assays...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901188/engineered-microvasculature-in-pdms-networks-using-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells
#17
Amogh Sivarapatna, Mahboobe Ghaedi, Yang Xiao, Edward Han, Binod Aryal, Jing Zhou, Carlos Fernandez-Hernando, Yibing Qyang, Karen K Hirschi, Laura E Niklason
In this study, we used a polydimethylsiloxane (PDMS)-based platform for the generation of intact, perfusion-competent microvascular networks in vitro. COMSOL Multiphysics, a finite-element analysis and simulation software package, was used to obtain simulated velocity, pressure, and shear stress profiles. Transgene-free human induced pluripotent stem cells (hiPSCs) were differentiated into partially arterialized endothelial cells (hiPSC-ECs) in 5 d under completely chemically defined conditions, using the small molecule glycogen synthase kinase 3β inhibitor CHIR99021 and were thoroughly characterized for functionality and arterial-like marker expression...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28901173/cyclin-d2-is-a-critical-mediator-of-exercise-induced-cardiac-hypertrophy
#18
Stephen W Luckey, Chris D Haines, John P Konhilas, Elizabeth D Luczak, Antke Messmer-Kratzsch, Leslie A Leinwand
A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1(-/-)), and mice deficient in cyclin D2 (cyclin D2(-/-))...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28900205/apoe4-associated-phospholipid-dysregulation-contributes-to-development-of-tau-hyper-phosphorylation-after-traumatic-brain-injury
#19
Jiqing Cao, Farida El Gaamouch, James S Meabon, Kole D Meeker, Li Zhu, Margaret B Zhong, John Bendik, Gregory Elder, Ping Jing, Jiahong Xia, Wenjie Luo, David G Cook, Dongming Cai
The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP2) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP2 degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP2 levels in ApoE4 mice did not increase after blast TBI...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892081/a20-promotes-metastasis-of-aggressive-basal-like-breast-cancers-through-multi-monoubiquitylation-of%C3%A2-snail1
#20
Ji-Hyung Lee, Su Myung Jung, Kyung-Min Yang, Eunjin Bae, Sung Gwe Ahn, Jin Seok Park, Dongyeob Seo, Minbeom Kim, Jihoon Ha, Jaewon Lee, Jun-Hyeong Kim, Jun Hwan Kim, Akira Ooshima, Jinah Park, Donghyuk Shin, Youn Sook Lee, Sangho Lee, Geert van Loo, Joon Jeong, Seong-Jin Kim, Seok Hee Park
Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1...
September 11, 2017: Nature Cell Biology
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