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https://www.readbyqxmd.com/read/27933650/up-regulation-of-microrna-133a-inhibits-the-mek-erk-signaling-pathway-to-promote-cell-apoptosis-and-enhance-radio-sensitivity-by-targeting-egfr-in-esophageal-cancer-in-vivo-and-in-vitro
#1
Qing-Shan Yang, Li-Peng Jiang, Chun-Yan He, Yu-Na Tong, Yuan-Yuan Liu
This study aims to explore how microRNA-133a (miR-133a) affects cell apoptosis and radio-sensitivity by targeting EGFR via regulating MEK/ERK pathway in esophageal cancer (EC). A total of 358 EC patients were selected and assigned into the resistant and sensitive groups. Human EC KYSE 150 cell line was assigned into the blank, negative control (NC), miR-133a mimic, miR-133a inhibitors, si-EGFR, miR-133a inhibitors + si-EGFR groups after transfection. MiR-133a and EGFR mRNA expressions were detected by qRT-PCR and EGFR, MEK/ERK pathway-related protein expressions were detected by Western blotting...
December 8, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27933551/pentoxifylline-alleviates-early-brain-injury-after-experimental-subarachnoid-hemorrhage-in-rats-possibly-via-inhibiting-tlr-4-nf-%C3%AE%C2%BAb-signaling-pathway
#2
Da-Yong Xia, Hua-Sheng Zhang, Ling-Yun Wu, Xiang-Sheng Zhang, Meng-Liang Zhou, Chun-Hua Hang
Early brain injury (EBI) after subarachnoid hemorrhage (SAH) generally causes significant and lasting damage. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, has shown anti-inflammatory and neuroprotective properties in several brain injury models, but the role of PTX with respect to EBI following SAH remains uncertain. The purpose of this study was to investigate the effects of PTX on EBI after SAH in rats. Adult male Sprauge-Dawley rats were randomly assigned to the sham and SAH groups. PTX (30 or 60 mg/kg) or an equal volume of the administration vehicle (normal saline) was administrated at 30 min intervals following SAH...
December 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27933293/differences-in-the-mechanical-properties-of-the-developing-cerebral-cortical-proliferative-zone-between-mice-and-ferrets-at-both-the-tissue-and-single-cell-levels
#3
Arata Nagasaka, Tomoyasu Shinoda, Takumi Kawaue, Makoto Suzuki, Kazuaki Nagayama, Takeo Matsumoto, Naoto Ueno, Ayano Kawaguchi, Takaki Miyata
Cell-producing events in developing tissues are mechanically dynamic throughout the cell cycle. In many epithelial systems, cells are apicobasally tall, with nuclei and somata that adopt different apicobasal positions because nuclei and somata move in a cell cycle-dependent manner. This movement is apical during G2 phase and basal during G1 phase, whereas mitosis occurs at the apical surface. These movements are collectively referred to as interkinetic nuclear migration, and such epithelia are called "pseudostratified...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27933185/circulating-serpinb1-levels-and-clinical-features-in-patients-with-type-2-diabetes
#4
Kohzo Takebayashi, Kenji Hara, Tomoko Terasawa, Rika Naruse, Mariko Suetsugu, Takafumi Tsuchiya, Toshihiko Inukai
OBJECTIVE: The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic β cells, and may decrease insulin resistance...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/27932981/proton-pump-inhibitors-display-antitumor-effects-in-barrett-s-adenocarcinoma-cells
#5
Eduardo Chueca, Nadezda Apostolova, Juan V Esplugues, María A García-González, Ángel Lanas, Elena Piazuelo
Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H(+)-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H(+)-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932980/tnf-%C3%AE-induced-cpla2-expression-via-nadph-oxidase-reactive-oxygen-species-dependent-nf-%C3%AE%C2%BAb-cascade-on-human-pulmonary-alveolar-epithelial-cells
#6
Chih-Chung Lin, Wei-Ning Lin, Rou-Ling Cho, Chen-Yu Wang, Li-Der Hsiao, Chuen-Mao Yang
Tumor necrosis factor-α (TNF-α) triggers activation of cytosolic phospholipase A2 (cPLA2) and then enhancing the synthesis of prostaglandin (PG) in inflammatory diseases. However, the detailed mechanisms of TNF-α induced cPLA2 expression were not fully defined in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that TNF-α-stimulated increases in cPLA2 mRNA (5.2 folds) and protein (3.9 folds) expression, promoter activity (4.3 folds), and PGE2 secretion (4.7 folds) in HPAEpiCs, determined by Western blot, real-time PCR, promoter activity assay and PGE2 ELISA kit...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932979/madagascine-induces-vasodilatation-via-activation-of-ampk
#7
Dapeng Chen, Bochao Lv, Sei Kobayashi, Yongjian Xiong, Pengyuan Sun, Yuan Lin, Salvatore Genovese, Francesco Epifano, Shanshan Hou, Fusheng Tang, Yunyan Ji, Dandan Yu
Madagascine (3-isopentenyloxyemodin) can be chemically synthesized or purified from several Rhamnus species, and it is found to have more potent biological activities than the parent compound emodin. The aim of this study is to characterize the vasodilatory effect of madagascine on vasoconstriction and sphingosylphosphorylcholine induced vasospasm in ex vivo and reveal the potential mechanisms in vitro. The effects of madagascine on vasoconstriction of rat mesenteric resistance arteries (MRAs) induced by K(+), methoxamine, and endothelin-1 were, respectively, studied...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932893/let-7a-enhances-the-sensitivity-of-hepatocellular-carcinoma-cells-to-cetuximab-by-regulating-stat3-expression
#8
Fei Xue, Yanhui Liu, Hongwei Zhang, Yu Wen, Lei Yan, Qiang Tang, Erhui Xiao, Dongyi Zhang
BACKGROUND: Let-7 miRNAs are reported to play an inhibitory role in carcinogenesis, tumor progression, recurrence, and pluripotency of cancer. However, few studies have reported the relationship between let-7 and drug sensitivity, especially for let-7a (a subtype of let-7). This study aimed to investigate the function of let-7a in regulating the sensitivity of hepatocellular carcinoma (HCC) cell lines to cetuximab. METHODS: The cytotoxicity of cetuximab on HCC cell lines (Huh7, Hep3B, HepG2, SNU449, and SNU387) was evaluated using a cell viability assay (the Cell Counting Kit-8 assay) and a cell proliferation assay (the Click-iT EdU Imaging Kit) in the presence of a control, a let-7a mimic, and a let-7a inhibitor...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27932800/timps-versatile-extracellular-regulators-in-cancer
#9
Hartland W Jackson, Virginie Defamie, Paul Waterhouse, Rama Khokha
A compelling long-term goal of cancer biology is to understand the crucial players during tumorigenesis in order to develop new interventions. Here, we review how the four non-redundant tissue inhibitors of metalloproteinases (TIMPs) regulate the pericellular proteolysis of a vast range of matrix and cell surface proteins, generating simultaneous effects on tumour architecture and cell signalling. Experimental studies demonstrate the contribution of TIMPs to the majority of cancer hallmarks, and human cancers invariably show TIMP deregulation in the tumour or stroma...
December 9, 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27932778/expression-of-long-non-coding-rna-lncrna-small-nucleolar-rna-host-gene-1-snhg1-exacerbates-hepatocellular-carcinoma-through-suppressing-mir-195
#10
Hui Zhang, Dong Zhou, Mingang Ying, Minyong Chen, Peng Chen, Zhaoshuo Chen, Fan Zhang
BACKGROUND Aberrant expression of lncRNA has been suggested to have an association with tumorigenesis. Our study was designed to reveal the underlying connection between lncRNA SNHG1 and hepatocellular carcinoma (HCC) pathogenesis. MATERIAL AND METHODS A total of 122 pairs of HCC tissues (case group) and matched adjacent non-tumor liver tissues (control group) were collected for this study. RT-PCR and in situ hybridization were conducted to investigate differences in lncRNA SNHG1 expression between the case and control group...
December 9, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27932698/identification-of-inhibitors-of-the-association-of-zap-70-with-the-t-cell-receptor-by-high-throughput-screen
#11
Patrick R Visperas, Christopher G Wilson, Jonathan A Winger, Qingrong Yan, Kevin Lin, Michelle R Arkin, Arthur Weiss, John Kuriyan
ZAP-70 is a critical molecule in the transduction of T cell antigen receptor signaling and the activation of T cells. Upon activation of the T cell antigen receptor, ZAP-70 is recruited to the intracellular ζ-chains of the T cell receptor, where ZAP-70 is activated and colocalized with its substrates. Inhibitors of ZAP-70 could potentially function as treatments for autoimmune diseases or organ transplantation. In this work, we present the design, optimization, and implementation of a screen for inhibitors that would disrupt the interaction between ZAP-70 and the T cell antigen receptor...
December 8, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27932490/c-terminus-of-the-p4-atpase-atp8a2-functions-in-protein-folding-and-regulation-of-phospholipid-flippase-activity
#12
Madhavan Chalat, Kody Moleschi, Robert S Molday
ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We have investigated the role of the C-terminus of ATP8A2 in its expression, subcellular localization, interaction with its subunit CDC50A, and function as a phosphatidylserine flippase. C-terminal deletion mutants exhibited a reduced tendency to solubilize in mild detergent and exit the endoplasmic reticulum...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27932443/pd-l1-blockade-enhances-response-of-pancreatic-ductal-adenocarcinoma-to-radiotherapy
#13
Abul Azad, Su Yin Lim, Zenobia D'Costa, Keaton Jones, Angela Diana, Owen J Sansom, Philipp Kruger, Stanley Liu, W Gillies McKenna, Omer Dushek, Ruth J Muschel, Emmanouil Fokas
Pancreatic ductal adenocarcinoma (PDAC) is considered a non-immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD-L1 expression in a JAK/Stat1-dependent manner. In vitro, PD-L1 inhibition did not alter radio- and chemosensitivity. In vivo, addition of anti-PD-L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts...
December 8, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27932422/significance-of-low-mtorc1-activity-in-defining-the-characteristics-of-brain-tumor-stem-cells
#14
Yi-Peng Han, Atsushi Enomoto, Yukihiro Shiraki, Shen-Qi Wang, Xiaoze Wang, Shinya Toyokuni, Naoya Asai, Kaori Ushida, Hosne Ara, Fumiharu Ohka, Toshihiko Wakabayashi, Jie Ma, Atsushi Natsume, Masahide Takahashi
BACKGROUND: The significance of mammalian target of rapamycin complex 1 (mTORC1) activity in the maintenance of cancer stem cells (CSCs) remains controversial. Previous findings showed that mTORC1 activation depleted the population of leukemia stem cells in leukemia, while maintaining the stemness in pancreatic CSCs. The purpose of this study was to examine the currently unknown role and significance of mTORC1 activity in brain tumor stem cells (BTSCs). METHODS: Basal mTORC1 activity and its kinetics were investigated in BTSC clones isolated from patients with glioblastoma and their differentiated progenies (DIFFs)...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27932350/role-of-noncanonical-wnts-signaling-pathway-in-human-aortic-valve-calcification
#15
Isabella Albanese, Bin Yu, Hamood Al-Kindi, Bianca Barratt, Leah Ott, Mohammad Al-Refai, Benoit de Varennes, Dominique Shum-Tim, Marta Cerruti, Ophélie Gourgas, Eric Rhéaume, Jean-Claude Tardif, Adel Schwertani
OBJECTIVE: The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification. APPROACH AND RESULTS: Using immunohistochemistry, RT-PCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs)...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27932349/nadph-oxidase-2-and-atherothrombosis-insight-from-chronic-granulomatous-disease
#16
REVIEW
Francesco Violi, Roberto Carnevale, Lorenzo Loffredo, Pasquale Pignatelli, John I Gallin
The phagocytic cell enzyme NADPH oxidase-2 (Nox2) is critical for killing micro-organisms via production of reactive oxygen species and thus is a key element of the innate immune system. Nox2 is also detectable in endothelial cells and platelets where it has vasoconstrictive and aggregating properties, respectively. Patients with X-linked chronic granulomatous disease with hereditary Nox2 deficiency not only have impaired bacterial killing but, in association with loss of Nox2 function, also have enhanced carotid artery dilation, impaired platelet-related thrombosis, and reduced carotid atherosclerotic burden...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27932311/daclatasvir-prevents-hepatitis-c-virus-by-blocking-transfer-of-viral-genome-to-assembly-sites
#17
Bertrand Boson, Solène Denolly, Fanny Turlure, Christophe Chamot, Marlène Dreux, François-Loïc Cosset
BACKGROUND & AIMS: Daclatasvir is a direct-acting antiviral agent and potent inhibitor of NS5A, which is involved in replication of the hepatitis C virus (HCV) genome, presumably via membranous web shaping, and assembly of new virions, likely via transfer of the HCV RNA genome to viral particle assembly sites. Daclatasvir inhibits the formation of new membranous web structures and, ultimately, of replication complex vesicles, but also inhibits an early assembly step. We investigated the relationship between daclatasvir-induced clustering of HCV proteins, intracellular localization of viral RNAs and inhibition of viral particle assembly...
December 5, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27932247/crystal-structure-of-the-pdz-domain-of-mouse-dishevelled-1-and-its-interaction-with-cxxc5
#18
Inhwan Lee, Sooho Choi, Ji-Hye Yun, Seolhwa Seo, Sehee Choi, Kang-Yell Choi, Weontae Lee
Dishevelled (Dvl) plays a crucial role in Wnt signaling by interacting with membrane-bound receptors and downstream molecules through its PDZ domain. CXXC5 is one of the key molecules that interacts with Dvl and negatively regulates the Wnt/β-catenin pathway in osteoblast differentiation. Recently, the Dvl-CXXC5 interaction has been identified as an excellent target for osteoporosis treatment. Therefore, it is desirable to have detailed structural information for the Dvl-CXXC5 interaction. Although solution structures of the Dvl1 PDZ domain have been reported, a high-resolution crystal structure would provide detailed sidechain information that is essential for drug development...
December 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27932245/knockdown-of-trem-1-suppresses-il-1%C3%AE-induced-chondrocyte-injury-via-inhibiting-the-nf-%C3%AE%C2%BAb-pathway
#19
Jianfei Tang, Qirong Dong
Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently discovered molecule that modulates inflammatory responses. This study aimed to investigate the specific function of TREM-1 in chondrocytes and its association with the pathophysiology of osteoarthritis (OA). We observed upregulation of TREM-1 in OA cartilage compared to normal tissues. Knockdown of TREM-1 suppressed interleukin 1 beta (IL-1β)-induced extracellular matrix (ECM) metabolic imbalance, pro-inflammatory cytokine production, decrease in cell viability and apoptosis...
December 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27932157/belatacept-and-eculizumab-for-treatment-of-calcineurin-inhibitor-induced-thrombotic-microangiopathy-after-kidney-transplantation-case-report
#20
J Merola, P S Yoo, J Schaub, J D Smith, M I Rodriguez-Davalos, E Tichy, D C Mulligan, W Asch, R Formica, M Kashgarian, S Kulkarni
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome...
November 2016: Transplantation Proceedings
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