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https://www.readbyqxmd.com/read/28431037/gestational-diabetes-alters-functions-in-offspring-s-umbilical-cord-cells-with-implications-for-cardiovascular-health
#1
Ajith Isaac Amrithraj, Anjaneyulu Kodali, Linh Nguyen, Adrian Kee Keong Teo, Cheng Wei Chang, Neerja Karnani, Kai Lyn Ng, Peter D Gluckman, Yap Seng Chong, Walter Stünkel
As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. We have assessed primary umbilical cord derived cells such as human umbilical vein endothelial cells (HUVECs) and Wharton's jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and non-GDM mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, and the ability to support blood vessel growth...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430338/yap-taz-and-areg-expression-in-eighth-cranial-nerve-schwannoma
#2
Alessandro Martini, Gino Marioni, Elisabetta Zanoletti, Rocco Cappellesso, Roberto Stramare, Elena Fasanaro, Chiara Faccioli, Luciano Giacomelli, Luca Denaro, Domenico D'Avella, Antonio Mazzoni, Ambrogio Fassina
BACKGROUND: Although the diagnosis and treatment of eighth cranial nerve (VIII CN) schwannoma (acoustic neuroma) has improved over the years, no factors capable of predicting tumor growth have been identified as yet. This study is a preliminary investigation of the expression in sporadic VIII CN schwannomas of Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), and amphiregulin (AREG), a direct target gene of YAP and TAZ. The expression of YAP, TAZ and AREG was correlated with the volumetric dimensions of tumors on contrast-enhanced magnetic resonance imaging (ceMRI)...
April 7, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28430104/dissection-of-the-interaction-between-the-intrinsically-disordered-yap-protein-and-the-transcription-factor-tead
#3
Yannick Mesrouze, Fedir Bokhovchuk, Marco Meyerhofer, Patrizia Fontana, Catherine Zimmermann, Typhaine Martin, Clara Delaunay, Dirk Erdmann, Tobias Schmelzle, Patrick Chène
TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation...
April 21, 2017: ELife
https://www.readbyqxmd.com/read/28429726/verteporfin-induced-formation-of-protein-cross-linked-oligomers-and-high-molecular-weight-complexes-is-mediated-by-light-and-leads-to-cell-toxicity
#4
Eleni K Konstantinou, Shoji Notomi, Cassandra Kosmidou, Katarzyna Brodowska, Ahmad Al-Moujahed, Fotini Nicolaou, Pavlina Tsoka, Evangelos Gragoudas, Joan W Miller, Lucy H Young, Demetrios G Vavvas
Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428044/transcriptional-co-activator-yap-regulates-camp-signaling-in-sertoli-cells
#5
Souvik Sen Sharma, Subeer S Majumdar
FSH mediated cyclic AMP (cAMP) signaling is crucial for function of testicular Sertoli cells (Sc) during puberty. Yes-kinase Associated Protein (YAP), a transcriptional co-activator, regulates cell proliferation and differentiation. However, its role in testicular function is not known. In present study, we have identified YAP as an important regulator of cAMP signaling in Sc, in-vitro. Verteporfin, a YAP-inhibitor, down regulated the expression of cAMP responsive genes necessary for spermatogenesis in Sc. Action of forskolin, which acts via cAMP, was also antagonized by verteporfin, limiting expression of these genes...
April 17, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28427246/nanotechnology-and-diabetic-wound-healing-a-review
#6
Dinesh Kumar Chellappan, Yap Yenese, Chew Chian Wei, Gaurav Gupta
The incidence of diabetes has been on the rise and the rate of rise since the turn of this century has been phenomenal. One of the various battling issues faced by diabetics all over the globe is the management of diabetic wounds. Currently there are several management strategies to deal with the treatment of diabetic wounds. The conventional methods have several limitations. One of the major limitations is the rate and progression of healing of a diabetic wound when adopting a conventional diabetic wound management therapy...
April 21, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28427193/targeting-high-aurora-kinases-expression-as-an-innovative-therapy-for-hepatocellular-carcinoma
#7
Fuchen Liu, Guangyong Wang, Xiaoqiang Wang, Zhihui Che, Wei Dong, Xinggang Guo, Zhenguang Wang, Ping Chen, Daisen Hou, Qi Zhang, Wenli Zhang, Yida Pan, Dongqin Yang, Hui Liu
The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, however, it remains unknown whether Aurora A and B overexpressed concomitantly and its clinical significance in hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co-overexpression (Aurora AHBH), associated with the worst prognosis, was an independent predictor for the survival. Importantly, with the lower IC50 and stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor of Aurora kinases, which induced YAP (Yes-associated protein) reduction and resulted in P21 accumulation, significantly promoted the polyploidy (> 4N) formation and apoptosis in HCC...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425446/yap-modulates-tgf-%C3%AE-1-induced-simultaneous-apoptosis-and-emt-through-upregulation-of-the-egf-receptor
#8
Yi Liu, Kai He, Ying Hu, Xiaojie Guo, Dongmei Wang, Weiwei Shi, Jingsong Li, Jianguo Song
YAP is a transcriptional co-regulator that plays important roles in various patho-physiological processes, including the survival and death of cells. However, the effect of YAP on apoptosis and EMT, simultaneously mediated by TGF-β1, is not known. In this study, we demonstrate that YAP can modulate cell fate of apoptosis versus EMT by acting as a surviving factor. Overexpression of YAP in mouse mammary epithelial (NMuMG) cells suppressed TGF-β1-induced apoptosis, which shifted the cellular response predominantly toward EMT...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424674/global-fecal-and-plasma-metabolic-dynamics-related-to-helicobacter-pylori-eradication
#9
Theresa Wan-Chen Yap, Alex Hwong-Ruey Leow, Ahmad Najib Azmi, Damien L Callahan, Guillermo I Perez-Perez, Mun-Fai Loke, Khean-Lee Goh, Jamuna Vadivelu
Background:Helicobacter pylori colonizes the gastric mucosa of more than half of the world's population. There is increasing evidence H. pylori protects against the development of obesity and childhood asthma/allergies in which the development of these diseases coincide with transient dysbiosis. However, the mechanism underlying the association of H. pylori eradication with human metabolic and immunological disorders is not well-established. In this study, we aimed to investigate the local and systemic effects of H...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28424630/hippo-pathway-and-skeletal-muscle-mass-regulation-in-mammals-a-controversial-relationship
#10
REVIEW
Olouyomi Gnimassou, Marc Francaux, Louise Deldicque
Skeletal muscle mass reflects a dynamic turnover between net protein synthesis and degradation. In addition, satellite cell inclusion may contribute to increase muscle mass while fiber loss results in a reduction of muscle mass. Since 2010, a few studies looked at the involvement of the newly discovered Hippo pathway in the regulation of muscle mass. In line with its roles in other organs, it has been hypothesized that the Hippo pathway could play a role in different regulatory mechanisms in skeletal muscle as well, namely proliferation and renewal of satellite cells, differentiation, death, and growth of myogenic cells...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28420424/a-novel-lncrna-uc-134-represses-hepatocellular-carcinoma-progression-by-inhibiting-cul4a-mediated-ubiquitination-of-lats1
#11
Wen Ni, Yuqin Zhang, Zetao Zhan, Feng Ye, Yonghao Liang, Jing Huang, Keli Chen, Longhua Chen, Yi Ding
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and tumor recurrence and metastasis are major factors that contribute to the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known to regulate different tumorigenic processes, and a growing body of evidence indicates that Hippo kinase signaling is inactivated in many cancers. However, the upstream lncRNA regulators of Hippo kinase signaling in HCC are poorly understood. METHODS: Using a lncRNA microarray, we identified a novel lncRNA, uc...
April 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28420004/hearing-loss-and-risk-of-mild-cognitive-impairment-and-dementia-findings-from-the-singapore-longitudinal-ageing-study
#12
Rebecca Heywood, Qi Gao, Ma Shwe Zin Nyunt, Lei Feng, Mei Sian Chong, Wee Shiong Lim, Philip Yap, Tih-Shih Lee, Keng Bee Yap, Shiou Liang Wee, Tze Pin Ng
AIM: To investigate the associations between hearing loss and prevalent and incident mild cognitive impairment (MCI), dementia and MCI or dementia (all cases). METHODS: Cross-sectional and longitudinal analyses of baseline and follow-up data were performed in a population-based cohort. The baseline sample of 2,599 adults aged ≥55 included 1,515 cognitively normal subjects who were followed up to 8 years. Hearing loss at baseline was determined by the whispered voice test, and MCI and dementia by Mini-Mental State Examination screening, Clinical Dementia Rating scale, neurocognitive tests, MRI, and panel consensus diagnosis...
April 19, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28419735/hospital-use-in-aboriginal-and-non-aboriginal-patients-with-chronic-disease
#13
David Whyatt, Matthew Yap, Raji Tenneti, Glenn Pearson, Alistair Vickery
OBJECTIVE: The objective of this study was to compare rates of hospital utilisation in Aboriginal and non-Aboriginal peoples before and after hospital admission for chronic obstructive pulmonary disease, heart failure and/or type 2 diabetes mellitus. METHODS: This was a longitudinal cohort study from 2002 to 2014, which was conducted in all hospitals in Western Australia. The participants of this study were Aboriginal and non-Aboriginal patients with a principal diagnosis of heart failure, type 2 diabetes or chronic obstructive pulmonary disease, on admission to hospital, where such an event had not occurred in the previous 3 years...
April 16, 2017: Emergency Medicine Australasia: EMA
https://www.readbyqxmd.com/read/28417908/cytokinesis-failure-leading-to-chromosome-instability-in-v-src-induced-oncogenesis
#14
REVIEW
Yuji Nakayama, Shuhei Soeda, Masayoshi Ikeuchi, Keiko Kakae, Naoto Yamaguchi
v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active variant of c-Src. Activation of Src is observed frequently in colorectal and breast cancers, and is critical in tumor progression through multiple processes. However, in some experimental conditions, v-Src causes growth suppression and apoptosis. In this review, we highlight recent progress in our understanding of cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src-expressing cells. v-Src induces cell cycle changes-such as the accumulation of the 4N cell population-and increases the number of binucleated cells, which is accompanied by an excess number of centrosomes...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416665/hippo-pathway-mediates-resistance-to-cytotoxic-drugs
#15
Taranjit S Gujral, Marc W Kirschner
Chemotherapy is widely used for cancer treatment, but its effectiveness is limited by drug resistance. Here, we report a mechanism by which cell density activates the Hippo pathway, which in turn inactivates YAP, leading to changes in the regulation of genes that control the intracellular concentrations of gemcitabine and several other US Food and Drug Administration (FDA)-approved oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived xenograft models...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28416659/deubiquitinase-yod1-potentiates-yap-taz-activities-through-enhancing-itch-stability
#16
Youngeun Kim, Wantae Kim, Yonghee Song, Jeong-Rae Kim, Kyungjoo Cho, Hyuk Moon, Simon Weonsang Ro, Eunjeong Seo, Yeon-Mi Ryu, Seung-Jae Myung, Eek-Hoon Jho
Hippo signaling controls the expression of genes regulating cell proliferation and survival and organ size. The regulation of core components in the Hippo pathway by phosphorylation has been extensively investigated, but the roles of ubiquitination-deubiquitination processes are largely unknown. To identify deubiquitinase(s) that regulates Hippo signaling, we performed unbiased siRNA screening and found that YOD1 controls biological responses mediated by YAP/TAZ. Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances the stability of ITCH, which leads to reduced levels of LATS and a subsequent increase in the YAP/TAZ level...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28416241/circulating-tumor-dna-from-bench-to-bedside
#17
Joline S J Lim, Filip Janku, Timothy A Yap
In the era of personalized medicine, tumor sampling is paramount to enable the assessment of actionable molecular aberrations to help rationalize and guide treatment decisions. Longitudinal tracking of such aberrations may also be helpful to detect emerging drug resistance and to allow for timely modifications to ongoing therapies to improve patient outcomes. Nevertheless, tumor tissue sampling involves an invasive procedure with potential risks to patients and involves logistical challenges. As such, other less invasive and safer methods such as blood sampling for molecular profiling has been gaining traction...
March 1, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28416184/tiam1-antagonizes-taz-yap-both-in-the-destruction-complex-in-the-cytoplasm-and-in-the-nucleus-to-inhibit-invasion-of-intestinal-epithelial-cells
#18
Zoi Diamantopoulou, Gavin White, Muhammad Z H Fadlullah, Marcel Dreger, Karen Pickering, Joe Maltas, Garry Ashton, Ruth MacLeod, George S Baillie, Valerie Kouskoff, Georges Lacaud, Graeme I Murray, Owen J Sansom, Adam F L Hurlstone, Angeliki Malliri
Aberrant WNT signaling drives colorectal cancer (CRC). Here, we identify TIAM1 as a critical antagonist of CRC progression through inhibiting TAZ and YAP, effectors of WNT signaling. We demonstrate that TIAM1 shuttles between the cytoplasm and nucleus antagonizing TAZ/YAP by distinct mechanisms in the two compartments. In the cytoplasm, TIAM1 localizes to the destruction complex and promotes TAZ degradation by enhancing its interaction with βTrCP. Nuclear TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP target genes implicated in epithelial-mesenchymal transition, cell migration, and invasion, and consequently suppresses CRC cell migration and invasion...
April 7, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28415761/yap-promotes-tumorigenesis-and-cisplatin-resistance-in-neuroblastoma
#19
Chao Yang, Juan Tan, Jun Zhu, Shan Wang, Guanghui Wei
The transcriptional co-activator Yes-associated protein (YAP) is essential for Hippo pathway-driven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414584/screening-commercial-vehicle-drivers-for-obstructive-sleep-apnea-tools-barriers-and-recommendations
#20
Kelly A Evans, Tracey Yap, Barbara Turner
Obstructive sleep apnea (OSA) is a disorder characterized by a cessation of breathing during sleep, leading to poor sleep patterns and daytime somnolence. Daytime somnolence is of particular concern for commercial vehicle drivers, whose crash risk increases 50% with untreated OSA. The process of diagnosing and treating OSA in commercial drivers begins with effective and consistent screening. Therefore, the researchers screened drivers with both the STOP-Bang Questionnaire and the Obstructive Sleep Apnea Evaluation Worksheet (OSAEW) and compared the two tools...
April 1, 2017: Workplace Health & Safety
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