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https://www.readbyqxmd.com/read/28724211/dexmedetomidine-preconditioning-protects-against-retinal-ischemia-reperfusion-injury-and-inhibits-inflammation-response-via-toll-like-receptor-4-tlr4-pathway
#1
Zong Chen, Ping-Yang Qiu, Chuan-Gen Ma
BACKGROUND: Retinal ischemia/reperfusion (I/R) injury is one of significant cause of visual dysopia and causes inflammatory response. Dexmedetomidine is widely applied to general/local anaesthesia and has been reported to have extensive anti-inflammatory effect. However, the role of dexmedetomidine in retinal I/R injury is currently unknown. This study investigates the effect of dexmedetomidine preconditioning on retinal I/R injury and explore the related signal mechanism toll-like receptor 4 (TLR4) pathway...
July 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28723961/dysfunctional-gpr40-ffar1-signaling-exacerbates-pain-behavior-in-mice
#2
Kazuo Nakamoto, Fuka Aizawa, Kei Miyagi, Takuya Yamashita, Mitsumasa Mankura, Yutaka Koyama, Fumiyo Kasuya, Akira Hirasawa, Takashi Kurihara, Atsuro Miyata, Shogo Tokuyama
We previously showed that activation of G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) signaling modulates descending inhibition of pain. In this study, we investigated the involvement of fatty acid-GPR40/FFAR1 signaling in the transition from acute to chronic pain. We used GPR40/FFAR1-knockout (GPR40KO) mice and wild-type (WT) mice. A plantar incision was performed, and mechanical allodynia and thermal hyperalgesia were evaluated with a von Frey filament test and plantar test, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#3
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#4
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723864/sacral-neuromodulation-for-fecal-incontinence-a-review-of-the-central-mechanisms-of-action
#5
Paul T J Janssen, Niels Komen, Jarno Melenhorst, Nicole D Bouvy, Ali Jahanshahi, Yasin Temel, Stephanie O Breukink
OBJECTIVE: Fecal incontinence (FI) has a devastating effect on the quality of life and results in social isolation. Sacral neuromodulation (SNM) is proven to be an effective, minimal invasive treatment modality for FI. Despite the increasing application of SNM, the exact mechanisms of action remain unclear. The initial assumption of peripheral motor neurostimulation is not supported by increasing evidence, which report effects of SNM outside the pelvic floor. A new hypothesis states that afferent signals to the brain are essential for a successful therapy...
July 18, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28723692/angiotensin-ii-regulates-dendritic-cells-through-activation-of-nf-%C3%AE%C2%BAb-p65-erk1-2-and-stat1-pathways
#6
Yan Meng, Chen Chen, Yang Liu, Cui Tian, Hui-Hua Li
BACKGROUND: Activation of dendritic cells (DCs) is necessary to initiate immune responses. Angiotensin II (Ang II) has been reported to have a proinflammatory and immunomodulatory function. However, the role of Ang II in regulation of DCs and the underlying mechanisms remain illdefined. METHODS: The effects of Ang II on the proliferation, maturation, phagocytosis, migration, and communication with T cells of DCs were analysed utilizing MTT, flow cytometry, ELISA, transwell assay and mixed lymphocyte culture...
July 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28723681/inhibition-of-necroptosis-attenuates-kidney-inflammation-and-interstitial-fibrosis-induced-by-unilateral-ureteral-obstruction
#7
Xia Xiao, Chunyang Du, Zhe Yan, Yonghong Shi, Huijun Duan, Yunzhuo Ren
BACKGROUND: Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury...
July 20, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28723670/quaking-5-suppresses-aggressiveness-of-lung-cancer-cells-through-inhibiting-%C3%AE-catenin-signaling-pathway
#8
Xuexia Zhou, Xuebing Li, Cuiyun Sun, Cuijuan Shi, Dan Hua, Lin Yu, Yanjun Wen, Feng Hua, Qian Wang, Qinghua Zhou, Shizhu Yu
Quaking-5 (QKI-5) belongs to the STAR (signal transduction and activation of RNA) family of RNA binding proteins and functions as a tumor suppressor in several human malignancies. In this study, we attempt to elucidate the role of QKI-5 in the pro-metastasis processes of lung cancer (LC) cells and the underlying mechanisms. We confirmed that QKI-5 was decreased in human LC tissues and cell lines, especially in high-metastatic cells. Moreover, QKI expression was positively correlated with LC patients' survival...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723662/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#9
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723658/derlin-1-is-a-target-to-improve-radiotherapy-effect-of-esophageal-squamous-cell-carcinoma
#10
Qianze Dong, Lin Fu, Yue Zhao, Yang Liu, Qingchang Li, Xueshan Qiu, Enhua Wang
Radiotherapy is widely used for treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the role of Derlin-1 on the sensitivity of ESCC to radiotherapy and its underlying mechanism. We examined the clinical significance of Derlin-1 in 125 ESCC tissues. We found that Derlin-1 protein was higher in ESCC tissues than that in normal esophageal epithelial tissues. Derlin-1 overexpression was correlated with chemoradiotherapy resistance in ESCC patients and served an independent predictor for short overall survival...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723653/inhibition-of-notch-1-pathway-is-involved-in-rottlerin-induced-tumor-suppressive-function-in-nasopharyngeal-carcinoma-cells
#11
Yingying Hou, Shaoyan Feng, Lixia Wang, Zhe Zhao, Jingna Su, Xuyuan Yin, Nana Zheng, Xiuxia Zhou, Jun Xia, Zhiwei Wang
Recent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Therefore, regulation of Notch pathway could be beneficial for the treatment of human cancer. The aims of our current study were to explore whether rottlerin could suppress Notch-1 expression, which leads to inhibition of cell proliferation, migration and invasion in nasopharyngeal carcinoma cells...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723647/set-contributes-to-the-epithelial-mesenchymal-transition-of-pancreatic-cancer
#12
Hardik R Mody, Sau Wai Hung, Kineta Naidu, Haesung Lee, Caitlin A Gilbert, Toan Thanh Hoang, Rakesh K Pathak, Radhika Manoharan, Shanmugam Muruganandan, Rajgopal Govindarajan
Pancreatic cancer has a devastating prognosis due to 80-90% of diagnostic cases occurring when metastasis has already presented. Activation of the epithelial-mesenchymal transition (EMT) is a prerequisite for metastasis because it allows for the dissemination of tumor cells to blood stream and secondary organs. Here, we sought to determine the role of SET oncoprotein, an endogenous inhibitor of PP2A, in EMT and pancreatic tumor progression. Among the two major isoforms of SET (isoform 1 and isoform 2), higher protein levels of SET isoform 2 were identified in aggressive pancreatic cancer cell lines...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723640/trim22-confers-poor-prognosis-and-promotes-epithelial-mesenchymal-transition-through-regulation-of-akt-gsk3%C3%AE-%C3%AE-catenin-signaling-in-non-small-cell-lung-cancer
#13
Li Liu, Xiao-Ming Zhou, Fang-Fei Yang, Yuan Miao, Yan Yin, Xue-Jun Hu, Gang Hou, Qiu-Yue Wang, Jian Kang
Expression pattern and biological roles of TRIM22 remains unknown in most human cancers. The present study aims to discover its clinical significance and function in human non-small cell lung cancer (NSCLC). Immunohistochemistry was used to examine TRIM22 expression in 126 cases of NSCLC specimens. TRIM22 protein was upregulated in 70/126 (55.6%) non-small cell lung cancer tissues compared with normal lung tissue. TRIM22 overexpression was associated with advanced TNM stage, positive nodal metastasis and poor prognosis...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723618/mir-223-3p-inhibits-angiogenesis-and-promotes-resistance-to-cetuximab-in-head-and-neck-squamous-cell-carcinoma
#14
Alexandre Bozec, Joséphine Zangari, Mathilde Butori-Pepino, Marius Ilie, Salomé Lalvee, Thierry Juhel, Catherine Butori, Patrick Brest, Paul Hofman, Valérie Vouret-Craviari
MicroRNAs (miRs) participate in tumor growth and dissemination by regulating expression of various target genes. MiR-223-3p is suspected of being involved in head and neck squamous cell carcinoma (HNSCC) growth although its precise role has not been elucidated. In this study, we showed that miR-223-3p is present in biopsies of HNSCC patients and that its presence is correlated with high neutrophil infiltrate. We found that overexpression of miR-223-3p slightly increased proliferation of the CAL27 squamous carcinoma cell line both in vitro and in vivo...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723554/hypoxia-sensitive-commd1-integrates-signaling-and-cellular-metabolism-in-human-macrophages-and-suppresses-osteoclastogenesis
#15
Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723516/the-molecular-evolution-of-castration-resistant-prostate-cancer
#16
REVIEW
Yvonne Ceder, Anders Bjartell, Zoran Culig, Mark A Rubin, Scott Tomlins, Tapio Visakorpi
CONTEXT: Androgen deprivation therapy (ADT) is the backbone of treatment for advanced prostate cancer. However, castration-resistant prostate cancer (CRPC) nearly invariably develops through a range of different molecular mechanisms accompanied by progression to a more aggressive phenotype. OBJECTIVE: To understand the key molecular mechanisms leading to CRPC and the functional implications of this progression. Understanding molecular evolutionary mechanisms in CRPC is essential for the development of novel curative therapeutic approaches...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723420/plant-and-yeast-cornichon-possess-a-conserved-acidic-motif-required-for-correct-targeting-of-plasma-membrane-cargos
#17
Paul Rosas-Santiago, Daniel Lagunas-Gomez, Carolina Yáñez-Domínguez, Rosario Vera-Estrella, Olga Zimmermannova, Hana Sychrová, Omar Pantoja
The export of membrane proteins along the secretory pathway is initiated at the endoplasmic reticulum after proteins are folded and packaged inside this organelle by their recruiting into the coat complex COPII vesicles. It is proposed that cargo receptors are required for the correct transport of proteins to its target membrane, however, little is known about ER export signals for cargo receptors. Erv14/Cornichon belong to a well conserved protein family in Eukaryotes, and have been proposed to function as cargo receptors for many transmembrane proteins...
July 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28723419/nf-%C3%AE%C2%BAb-p65-serine-467-phosphorylation-sensitizes-mice-to-weight-gain-and-tnf%C3%AE-or-diet-induced-inflammation
#18
Tabea Riedlinger, Marleen B Dommerholt, Tobias Wijshake, Janine K Kruit, Nicolette Huijkman, Daphne Dekker, Mirjam Koster, Niels Kloosterhuis, Debby P Y Koonen, Alain de Bruin, Darren Baker, Marten H Hofker, Jan van Deursen, Johan W Jonker, M Lienhard Schmitz, Bart van de Sluis
The NF-κB family of transcription factors is essential for an effective immune response, but also controls cell metabolism, proliferation and apoptosis. Its broad relevance and the high connectivity to diverse signaling pathways require a tight control of NF-κB activity. To investigate the control of NF-κB activity by phosphorylation of the NF-κB p65 subunit, we generated a knock-in mouse model in which serine 467 (the mouse homolog of human p65 serine 468) was replaced with a non-phosphorylatable alanine (S467A)...
July 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28723343/%C3%AE-catenin-is-involved-in-oleanolic-acid-dependent-promotion-of-proliferation-in-human-hair-matrix-cells-in-an-in-vitro-organ-culture-model
#19
Ben Liu, Xianyan Chen, Huan Yi, Le Han, Bin Ji, Haiyan Chen, Wenjia Deng, Miaojian Wan
Oleanolic acid (OA), a pentacyclic triterpenoid compound which can be found in >1600 plants, has been shown to promote hair growth. To study the mechanisms of OA on hair growth, we investigated hair follicle (HF) growth on four different concentration OA using human hair follicle organ culture model. We found that HFs treated with 1 or 10μg/mL OA showed statistically enhanced elongation of the hair shaft and anagen-like stage. Moreover, higher positive rate of Ki-67, a matrix cellular marker of proliferation, was detected in the same groups treated with 1 or 10μg/mL than those treated with vehicle...
July 16, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28723232/mechanism-for-g2-phase-specific-nuclear-export-of-the-kinetochore-protein-cenp-f
#20
Kyle M Loftus, Heying Cui, Elias Coutavas, David S King, Amanda Ceravolo, Dylan Pereiras, Sozanne R Solmaz
Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive...
July 19, 2017: Cell Cycle
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