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https://www.readbyqxmd.com/read/27926982/trpv4-channels-mediate-na-k-cl-co-transporter-induced-brain-edema-after-traumatic-brain-injury
#1
Kwok-Tung Lu, Tai-Chun Huang, Ya-Hsin Tsai, Yi-Ling Yang
Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the mitogen-activated protein kinases (MAPK) cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 and the related signaling pathways in TBI-induced brain edema and neuronal damage. TBI was induced by the calibrated weight-drop device...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926980/role-and-regulation-of-p27-in-neuronal-apoptosis
#2
Surbhi Jaiswal, Pushkar Sharma
It is necessary for the cell cycle machinery of neurons to be suppressed to promote differentiation and maintenance of their terminally differentiated state. Reactivation of the cell cycle in response to neurotoxic insults leads to neuronal cell death and some cell cycle related proteins contribute to the process. p27 kip1 (p27), an inhibitor of Cyclin Dependent Kinases (CDKs), prevents unwarranted CDK activation. In the present study, we have elucidated a novel mechanism via which p27 promotes apoptosis of neurons stimulated by neurotoxic amyloid peptide Aβ42 (Amyloid β1-42 peptide)...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926878/the-csk-associated-adaptor-pag-inhibits-effector-t-cell-activation-in-cooperation-with-phosphatase-ptpn22-and-dok-adaptors
#3
Dominique Davidson, Ming-Chao Zhong, Pier Paolo Pandolfi, Silvia Bolland, Ramnik J Xavier, Brian Seed, Xin Li, Hua Gu, André Veillette
The transmembrane adaptor PAG (Cbp) has been proposed to mediate membrane recruitment of Csk, a cytoplasmic protein tyrosine kinase playing a critical inhibitory role during T cell activation, by inactivating membrane-associated Src kinases. However, this model has not been validated by genetic evidence. Here, we demonstrate that PAG-deficient mice display enhanced T cell activation responses in effector, but not in naive, T cells. PAG-deficient mice also have augmented T cell-dependent autoimmunity and greater resistance to T cell anergy...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926876/potentiation-of-synaptic-glun2b-nmdar-currents-by-fyn-kinase-is-gated-through-bdnf-mediated-disinhibition-in-spinal-pain-processing
#4
Michael E Hildebrand, Jian Xu, Annemarie Dedek, Yi Li, Ameet S Sengar, Simon Beggs, Paul J Lombroso, Michael W Salter
In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropathic pain. We find that BDNF mediates NMDAR potentiation through activation of TrkB and phosphorylation of the GluN2B subunit by the Src-family kinase Fyn...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926875/ship2-regulates-lumen-generation-cell-division-and-ciliogenesis-through-the-control-of-basolateral-to-apical-lumen-localization-of-aurora-a-and-hef-1
#5
Ola Hamze-Komaiha, Sokavuth Sarr, Yannick Arlot-Bonnemains, Didier Samuel, Ama Gassama-Diagne
Lumen formation during epithelial morphogenesis requires the creation of a luminal space at cell interfaces named apical membrane-initiation sites (AMISs). This is dependent upon integrated signaling from mechanical and biochemical cues, vesicle trafficking, cell division, and processes tightly coupled to ciliogenesis. Deciphering relationships between polarity determinants and lumen or cilia generation remains a fundamental issue. Here, we report that Src homology 2 domain-containing inositol 5-phosphatase 2 (SHIP2), a basolateral determinant of polarity, regulates RhoA-dependent actin contractility and cell division to form AMISs...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#6
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926856/insulin-dependent-activation-of-mch-neurons-impairs-locomotor-activity-and-insulin-sensitivity-in-obesity
#7
A Christine Hausen, Johan Ruud, Hong Jiang, Simon Hess, Hristo Varbanov, Peter Kloppenburg, Jens C Brüning
Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926800/interobserver-reproducibility-of-cytologic-p16-ink4a-ki-67-dual-immunostaining-in-human-papillomavirus-positive-women
#8
Maria Benevolo, Elena Allia, Daniela Gustinucci, Francesca Rollo, Simonetta Bulletti, Elena Cesarini, Basilio Passamonti, Maria Rosaria Giovagnoli, Elisabetta Carico, Francesca M Carozzi, Alessandra Mongia, Giulia Fantacci, Massimo Confortini, Teresa Rubino, Cristina Fodero, Sonia Prandi, Natalina Marchi, Angelo Farruggio, Anna Coccia, Luigia Macrì, Bruno Ghiringhello, Guglielmo Ronco, Emma Bragantini, Enzo Polla, Vincenzo Maccallini, Giovanni Negri, Paolo Giorgi Rossi
BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16(ink4a) ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16(ink4a) and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed. METHODS: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports...
December 7, 2016: Cancer
https://www.readbyqxmd.com/read/27926778/met-tyrosine-kinase-receptor-expression-and-amplification-as-prognostic-biomarkers-of-survival-in-gastroesophageal-adenocarcinoma
#9
Daniel V T Catenacci, Agnes Ang, Wei-Li Liao, Jing Shen, Emily O'Day, Robert D Loberg, Fabiola Cecchi, Todd Hembrough, Annamaria Ruzzo, Francesco Graziano
BACKGROUND: MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry-based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC)...
December 7, 2016: Cancer
https://www.readbyqxmd.com/read/27926694/involvement-of-activated-cdc42-kinase1-in-colitis-and-colorectal-neoplasms
#10
Chaolan Lv, Hongxiang Gu, Xinmei Zhao, Liyun Huang, Sanxi Zhou, Fachao Zhi
BACKGROUND Activated Cdc42 kinase1 (ACK1) is a non-receptor tyrosine kinase which is critical for cell survival, proliferation, and migration. Genomic amplification of ACK1 has been reported in multiple human cancers. We aimed to investigate ACK1 protein expression in colorectal mucosa with inflammation and neoplasm, and to evaluate its correlation with disease activity and severity. MATERIAL AND METHODS A total of 250 individuals who underwent total colonoscopy were collected randomly from January 2007 to May 2013 in Nanfang Hospital, Guangzhou, China...
December 7, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27926612/inhibitory-effect-of-a-redox-silent-analogue-of-tocotrienol-on-hypoxia-adaptation-in-prostate-cancer-cells
#11
Nobuya Shiozawa, Ryosuke Sugahara, Kozue Namiki, Chiaki Sato, Akira Ando, Ayami Sato, Nantiga Virgona, Tomohiro Yano
Prostate cancer (PCa) is one of the most common cancers in Western countries and acquires a malignant phenotype, androgen-independent growth. PCa under hypoxia often has resistance to chemotherapy and radiotherapy. However, an effective therapy against PCa under hypoxia has not yet been established. In this report, we investigated the inhibitory effect of a redox-silent analogue of tocotrienol on the survival of a human androgen-independent PCa cell line (PC3) under hypoxia. We found that the redox-silent analogue exerted a cytotoxic effect on PC3 cells in a dose-dependent manner irrespective of either hypoxia or normoxia...
December 6, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27926507/macrophage-migration-inhibitory-factor-activates-inflammatory-responses-of-astrocytes-through-interaction-with-cd74-receptor
#12
Yu Su, Yingjie Wang, Yue Zhou, Zhenjie Zhu, Qing Zhang, Xuejie Zhang, Wenjuan Wang, Xiaosong Gu, Aisong Guo, Yongjun Wang
Astrocytes, the major glial cell population of the central nervous system (CNS), play important physiological roles related to CNS homeostasis. Growing evidence demonstrates that astrocytes trigger innate immune responses under challenge of a variety of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine mainly secreted from monocytes/macrophages, is involved in inflammation-associated pathophysiology. Here, we displayed that expression of MIF significantly increased following spinal cord injury, in colocalization with microglia and astrocytes...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926504/the-immunomodulatory-effects-of-tnf-%C3%AE-inhibitors-on-human-th17-cells-via-ror%C3%AE-t-histone-acetylation
#13
Yi-Ching Lin, Yu-Chih Lin, Cheng-Chin Wu, Ming-Yii Huang, Wen-Chan Tsai, Chih-Hsing Hung, Po-Lin Kuo
The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926500/the-association-between-clinical-prognostic-factors-and-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-egfr-tki-efficacy-in-advanced-non-small-cell-lung-cancer-patients-a-retrospective-assessment-of-94-cases-with-egfr-mutations
#14
Jing-Hui Lin, Dong Lin, Ling Xu, Qiang Wang, Hui-Hua Hu, Hai-Peng Xu, Zhi-Yong He
OBJECTIVE: This study aimed to examine the association of clinical prognostic factors with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The demographic and clinical characteristics of 94 patients with stage IV NSCLC were retrospectively reviewed, and the association between clinical factors and EGFR-TKIs efficacy was evaluated. RESULTS: Of the 94 stage IV NSCLC patients enrolled in this study, a 74...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926496/the-therapeutic-potential-of-targeting-the-pi3k-pathway-in-pediatric-brain-tumors
#15
REVIEW
Hazel A Rogers, Jasper Estranero, Keshni Gudka, Richard G Grundy
Central nervous system tumors are the most common cancer type in children and the leading cause of cancer related deaths. There is therefore a need to develop novel treatments. Large scale profiling studies have begun to identify alterations that could be targeted therapeutically, including the phosphoinositide 3-kinase (PI3K) signaling pathway, which is one of the most commonly activated pathways in cancer with many inhibitors under clinical development. PI3K signaling has been shown to be aberrantly activated in many pediatric CNS neoplasms...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926494/p38-and-jnk-pathways-control-e-selectin-dependent-extravasation-of-colon-cancer-cells-by-modulating-mir-31-transcription
#16
Liang Zhong, Bryan Simoneau, Jacques Huot, Martin J Simard
Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to vascular endothelial cells. It requires the interaction between adhesion receptors such as E-selectin present on endothelial cells and their ligands on cancer cells. Notably, E-selectin influences the metastatic potential of breast, bladder, gastric, pancreatic, and colorectal carcinoma as well as of leukemia and lymphoma. Here, we show that E-selectin expression induced by the pro-inflammatory cytokine IL-1β is directly and negatively regulated by miR-31...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926490/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#17
Jiang He, Feiyu Tang, Liyu Liu, Lin Chen, Jiang Li, Danming Ou, Lu Zhang, Zhi Li, Deyun Feng, Wenzheng Li, Lun-Quan Sun
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926485/axitinib-induces-senescence-associated-cell-death-and-necrosis-in-glioma-cell-lines-the-proteasome-inhibitor-bortezomib-potentiates-axitinib-induced-cytotoxicity-in-a-p21-waf-cip1-dependent-manner
#18
Maria Beatrice Morelli, Consuelo Amantini, Massimo Nabissi, Claudio Cardinali, Matteo Santoni, Giovanni Bernardini, Angela Santoni, Giorgio Santoni
Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma.Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925667/tracking-the-activity-of-mtorc1-in-living-cells-using-genetically-encoded-fret-based-biosensor-torcar
#19
Xin Zhou, Simin Li, Jin Zhang
Mechanistic target of rapamycin complex 1 (mTORC1) is a highly conserved serine/threonine protein kinase that responds to multiple distinct signals (e.g., growth factors, amino acids, stress, and energy level) and coordinates cell growth and proliferation. The underlying molecular mechanisms by which these stimuli regulate the activity of mTORC1 are still not fully understood. The spatial compartmentalization of mTORC1 signaling has been suggested as an important mechanism for mTORC1 to achieve the signal specificity and efficiency...
December 7, 2016: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/27925633/shock-wave-enhances-angiogenesis-through-vegfr2-activation-and-recycling
#20
Tien-Hung Huang, Cheuk-Kwan Sun, Yi-Ling Chen, Ching-Jen Wang, Tsung-Cheng Yin, Mel S Lee, Hon-Kan Yip
Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor 2 (VEGFR2) signaling and trafficking. Phosphorylation of VEGFR2-Akt-eNOS axis and production of nitric oxide (NO) were determined in human umbilical vein endothelial cells (HUVECs) treated with SW. Carotid artery in ob/ob mice was treated with SW before evaluation with sprouting assay...
December 6, 2016: Molecular Medicine
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