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https://www.readbyqxmd.com/read/28445989/tmprss2-erg-gene-fusion-variants-induce-tgf-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-in-human-prostate-cancer-cells
#1
Leonie Ratz, Mark Laible, Lukasz A Kacprzyk, Stephanie M Wittig-Blaich, Yanis Tolstov, Stefan Duensing, Peter Altevogt, Sabine M Klauck, Holger Sültmann
TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is associated with clinicopathological parameters, while the underlying molecular processes remain unclear. We characterized the molecular mechanisms and functional implications caused by doxycycline (Dox)-inducible overexpression of the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E expression resulted in increased cellular migratory and invasive potential, and reduced proliferation and accumulation in G1 phase...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444734/highly-electronegative-low-density-lipoprotein-l5-evokes-microglial-activation-and-creates-a-neuroinflammatory-stress-via-toll-like-receptor-4-signaling
#2
Liang-En Yu, Chiou-Lian Lai, Ching-Tien Lee, Jiz-Yuh Wang
Atherogenic risk factors, such as hypercholesterolemia, are associated with increased risk of neurodegeneration, especially Alzheimer's dementia. Human plasma electronegative low-density lipoprotein [LDL(-)], especially L5, may serve as an important contributing factor. L5 promoting an inflammatory action in atherosclerosis has been extensively studied. However, the role of L5 in inducing neuroinflammation remains unknown. Here, we examined the impact of L5 on immune activation and cell viability in cultured BV-2 microglia...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28443475/microrna-140-5p-inhibits-cell-proliferation-and-invasion-by-regulating-vegfa-mmp2-signaling-in-glioma
#3
Yuan Hu, Yanyan Li, Chun Wu, Liang Zhou, Xiaoxiao Han, Qingyue Wang, Xueshun Xie, Youxin Zhou, Ziwei Du
Glioma is the most common primary malignant tumor of the central nervous system, which results in both a poor prognosis and outcome because of the aggressive progression of disease, growth and resistance to surgery, chemotherapy, and radiotherapy. MiR-140-5p is a small, non-coding single-stranded RNA molecule, which was previously studied in the settings of human tongue cancer, hepatocellular carcinoma, and colorectal cancer. However, detailed data that formally demonstrate the contribution of miR-140-5p to glioma development are missing...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28437857/influence-of-inflammation-and-nitric-oxide-upon-platelet-aggregation-following-deposition-of-diesel-exhaust-particles-in-the-airways
#4
E Smyth, A Solomon, M A Birrell, M J Smallwood, P G Winyard, T D Tetley, M Emerson
BACKGROUND AND PURPOSE: Exposure to nanoparticulate pollution has been implicated in platelet-driven thrombotic events such as myocardial infarction. Inflammation and impairment of nitric oxide (NO) bioavailability have been proposed as potential causative mechanisms. It is unclear, however, whether airways exposure to combustion-derived nanoparticles such as diesel exhaust particles (DEP) or carbon black (CB) can augment platelet aggregation in vivo and the underlying mechanisms remain undefined...
April 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28437187/synergy-between-choroid-plexus-epithelial-cells-conditioned-medium-and-knockout-serum-replacement-converts-human-adipose-derived-stem-cells-to-dopamine-secreting-neurons
#5
Mahdi Eskandarian Boroujeni, Mossa Gardaneh, Mehrnoosh Hasan Shahriari, Abbas Aliaghaei, Sanaz Hasani
Human adipose-derived stem cells (hADSCs) have great capacity to differentiate into mesodermal origins as well as non-mesodermal lineages including neural cells. This valuable feature paves the way for the therapeutic application of hADSCs for neurodegenerative maladies such as Parkinson's disease (PD). We tested the capacity of Choroid Plexus epithelial cells-conditioned medium (CPEC-CM) alone or cocktailed with knock-out serum (KS) to induce dopaminergic differentiation of hADSCs. To this end, hADSCs from lipoaspirate were phenotypically characterized and shown to maintain mesodermal multipotency so selected media easily differentiated them into osteoblasts, chondrocytes and adipocytes...
March 2, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28436964/swell1-is-a-regulator-of-adipocyte-size-insulin-signalling-and-glucose-homeostasis
#6
Yanhui Zhang, Litao Xie, Susheel K Gunasekar, Dan Tong, Anil Mishra, William J Gibson, Chuansong Wang, Trevor Fidler, Brodie Marthaler, Aloysius Klingelhutz, E Dale Abel, Isaac Samuel, Jessica K Smith, Lei Cao, Rajan Sah
Adipocytes undergo considerable volumetric expansion in the setting of obesity. It has been proposed that such marked increases in adipocyte size may be sensed via adipocyte-autonomous mechanisms to mediate size-dependent intracellular signalling. Here, we show that SWELL1 (LRRC8a), a member of the Leucine-Rich Repeat Containing protein family, is an essential component of a volume-sensitive ion channel (VRAC) in adipocytes. We find that SWELL1-mediated VRAC is augmented in hypertrophic murine and human adipocytes in the setting of obesity...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28436748/disruption-of-tetr-type-regulator-aden-by-mobile-genetic-element-confers-elevated-virulence-in-acinetobacter-baumannii
#7
Rajagopalan Saranathan, Sudhakar Pagal, Ajit R Sawant, Archana Tomar, M Madhangi, Suresh Sah, Annapurna Satti, K P Arunkumar, K Prashanth
Acinetobacter baumannii is an important human pathogen and considered as a major threat due to its extreme drug resistance. In this study, the genome of a hyper-virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was sequenced and analysed to understand its mechanisms of virulence, resistance and evolution. Comparative genomics analysis of PKAB07 revealed virulence and resistance related genes scattered throughout the genome, instead of being organized as an island, indicating the highly mosaic nature of the genome...
April 24, 2017: Virulence
https://www.readbyqxmd.com/read/28435065/influence-of-er-leak-on-resting-cytoplasmic-ca-2-and-receptor-mediated-ca-2-signalling-in-human-macrophage
#8
Janice A Layhadi, Samuel J Fountain
Mechanisms controlling endoplasmic reticulum (ER) Ca(2+) homeostasis are important regulators of resting cytoplasmic Ca(2+) concentration ([Ca(2+)]cyto) and receptor-mediated Ca(2+) signalling. Here we investigate channels responsible for ER Ca(2+) leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca(2+) we employ ionomycin action at the plasma membrane to stimulate ER Ca(2+) leak. Under these conditions ionomycin elevates [Ca(2+)]cyto revealing a Ca(2+) leak response which is abolished by thapsigargin...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28434830/bone-formation-of-demineralized-human-dentin-block-graft-with-different-demineralization-time-in%C3%A2-vitro-and-in%C3%A2-vivo-study
#9
So-Min Park, David-Hyungjin Kim, Eun-Kyoung Pang
OBJECTIVE: To evaluate structural and physicochemical characteristics of demineralized human dentin block with increasing demineralization time and to assess new bone formation when onlay grafted at different demineralization times in rat calvaria. STUDY DESIGN: Extracted human permanent teeth were pretreated and demineralized for 10-90 min. Scanning electron microscopy, X-ray diffraction analysis, inductively coupled plasma spectrometry, and energy dispersive X-ray analysis were performed...
March 21, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28433939/enhanced-proangiogenic-potential-of-mesenchymal-stem-cell-derived-exosomes-stimulated-by-a-nitric-oxide-releasing-polymer
#10
Wei Du, Kaiyue Zhang, Shuaiqiang Zhang, Ran Wang, Yan Nie, Hongyan Tao, Zhibo Han, Lu Liang, Di Wang, Jianfeng Liu, Na Liu, Zhongchao Han, Deling Kong, Qiang Zhao, Zongjin Li
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for the treatment of degenerative diseases or injury and may provide an alternative to cell-based therapy. However, the compositions in MSC-derived exosomes are highly influenced by the microenvironment in which their original cells reside. Here, we hypothesized that a nitric oxide (NO)-releasing polymer can boost the proangiogenic compositions of exosomes and enhance their proangiogenic capacity. Our results demonstrated that exosomes, released from human placenta-derived MSCs (hP-MSCs) by NO stimulation, augment the angiogenic effects of human umbilical vein endothelial cells (HUVECs) in vitro...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28433687/steroid-resistance-of-airway-type-2-innate-lymphoid-cells-ilc2s-from-severe-asthma-the-role-of-thymic-stromal-cell-lymphopoietin-tslp
#11
Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M Gorska, Richard J Martin, Rafeul Alam
BACKGROUND: ILC2s represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown. OBJECTIVE: To assess steroid resistance of human blood and airway ILC2s from asthmatic patients and examine its mechanism of induction. METHODS: We studied human blood and lung ILC2s from asthmatic and control subjects by flow cytometry and ELISA. RESULTS: Dexamethasone (Dex) inhibited (P=0.04) CRTH2 and type 2 cytokine expression by blood ILC2s stimulated with IL25 and IL33...
April 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28433431/application-of-structured-support-vector-machine-backpropagation-to-a-convolutional-neural-network-for-human-pose-estimation
#12
Peerajak Witoonchart, Prabhas Chongstitvatana
In this study, for the first time, we show how to formulate a structured support vector machine (SSVM) as two layers in a convolutional neural network, where the top layer is a loss augmented inference layer and the bottom layer is the normal convolutional layer. We show that a deformable part model can be learned with the proposed structured SVM neural network by backpropagating the error of the deformable part model to the convolutional neural network. The forward propagation calculates the loss augmented inference and the backpropagation calculates the gradient from the loss augmented inference layer to the convolutional layer...
February 16, 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28432356/a-role-of-human-rnase-p-subunits-rpp29-and-rpp21-in-homology-directed-repair-of-double-strand-breaks
#13
Enas R Abu-Zhayia, Hanan Khoury-Haddad, Noga Guttmann-Raviv, Raphael Serruya, Nayef Jarrous, Nabieh Ayoub
DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432145/bacterial-siderophores-hijack-neutrophil-functions
#14
Piu Saha, Beng San Yeoh, Rodrigo A Olvera, Xia Xiao, Vishal Singh, Deepika Awasthi, Bhagawat C Subramanian, Qiuyan Chen, Madhu Dikshit, Yanming Wang, Carole A Parent, Matam Vijay-Kumar
Neutrophils are the primary immune cells that respond to inflammation and combat microbial transgression. To thrive, the bacteria residing in their mammalian host have to withstand the antibactericidal responses of neutrophils. We report that enterobactin (Ent), a catecholate siderophore expressed by Escherichia coli, inhibited PMA-induced generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in mouse and human neutrophils. Ent also impaired the degranulation of primary granules and inhibited phagocytosis and bactericidal activity of neutrophils, without affecting their migration and chemotaxis...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28432124/regulation-of-neurite-morphogenesis-by-interaction-between-r7-regulator-of-g-protein-signaling-complexes-and-g-protein-subunit-g%C3%AE-13
#15
Stephanie L Scherer, Matthew D Cain, Stanley M Kanai, Kevin M Kaltenbronn, Kendall J Blumer
The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ5 and R7-RGS binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of Gi/o α-subunits, several neurological phenotypes of R7-RGS knockout mice are not readily explained by dysregulated Gi/o signaling...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431329/stealth-recombinant-human-serum-albumin-nanoparticles-conjugating-5-fluorouracil-augmented-drug-delivery-and-cytotoxicity-in-human-colon-cancer-ht-29-cells
#16
Ankita Sharma, Amanpreet Kaur, Upendra Kumar Jain, Ramesh Chandra, Jitender Madan
BACKGROUND AND OBJECTIVE: 5-Fluorouracil (5-FU) is a first-line chemotherapeutic drug in colorectal cancer. However, intravenous administration of 5-FU at the dose of 7-12mg/kg exhibits curbs like short half-life (20min) and toxic side-effects on bone marrow cells. Therefore, in present investigation, 5-FU was conjugated to poly (ethylene glycol) anchored recombinant human serum albumin nanoparticles (5-FU-rHSA-PEG-NPs) to improve the pharmacokinetic and therapeutic profiles. METHODS AND RESULTS: The mean particle size of 5-FU-rHSA-NPs was measured to be 44...
April 12, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28430717/multilateral-functional-alterations-of-human-neutrophils-in-sepsis-from-the-point-of-diagnosis-to-the-seventh-day
#17
Akira Endo, Miko Okamura, Shunsuke Yoshikawa, Yasuhiro Otomo, Tomohiro Morio
Neutrophil functional changes caused by sepsis itself and their time-course variation have not been fully elucidated because previous studies targeted patients who had received therapeutic interventions. We explored the multilateral functions of circulating neutrophils in patients with severe sepsis or septic shock who had not yet undergone interventions, and followed their changes. Patients were treated based on the Surviving Sepsis Campaign Guidelines 2012. Neutrophil functions were evaluated on days 0 (before therapeutic intervention), 3, and 7 in fifty-nine sepsis patients...
April 20, 2017: Shock
https://www.readbyqxmd.com/read/28430635/unsuccessful-mitosis-in-multicellular-tumour-spheroids
#18
Annie Molla, Morgane Couvet, Jean-Luc Coll
Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430599/tak1-inhibitor-5z-7-oxozeaenol-sensitizes-cervical-cancer-to-doxorubicin-induced-apoptosis
#19
Shan Guan, Jiaxiong Lu, Yanling Zhao, Sarah E Woodfield, Huiyuan Zhang, Xin Xu, Yang Yu, Jing Zhao, Shayahati Bieerkehazhi, Haoqian Liang, Jianhua Yang, Fuchun Zhang, Surong Sun
Aberrant activation of nuclear factor-κB (NF-κB) allows cancer cells to escape chemotherapy-induced cell death and acts as one of the major mechanisms of acquired chemoresistance in cervical cancer. TAK1, a crucial mediator that upregulates NF-κB activation in response to cellular genotoxic stress, is required for tumor cell viability and survival. Herein, we examined whether TAK1 inhibition is a potential therapeutic strategy for treating cervical cancer. We found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic effects of Dox in a panel of cervical cancer cell lines...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#20
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
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