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Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: Inhibitory receptor programmed cell death protein-1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic virus infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine what effect PD-1 signaling has on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
Sevket Gorgulu, Tugrul Norgaz, Ilke Sipahi
BACKGROUND: We planned a three arm randomized study to evaluate the safety and efficacy of a new blood stopper, Ankaferd blood stopper (ABS) along with short-time compression, compared to either short-time compression with conventional sterile gauzes (CSG) or with a TR band after transradial (TRA) procedures. METHODS: The Ankaferd blood stopper as a new strategy to avoid early complications. After transradial procedures (ABS transradial) trial is designed in a prospective, randomized, placebo-controlled fashion and registered with http://clinicaltrials...
April 17, 2018: Journal of Interventional Cardiology
Xiaoying Zhang, Yinhui Xu, Hongbo Liu, Pan Zhao, Yafang Chen, Zhijie Yue, Zhiqing Zhang, Xiaofang Wang
Mesenchymal stromal cells are proven to be likely induce the angiogenic response in multiple myeloma and thus represent an enticing target for antiangiogenesis therapies for multiple myeloma. Substantial evidence indicates that angiogenesis in multiple myeloma is complex and involves direct production of angiogenic cytokines by abnormal plasma cells and these B-cell neoplasia generated pathophysiology change within the microenvironment. In this study, we demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic conditions resulted in an increased α-smooth muscle actin expression and high productive levels of both hypoxia-inducible factor-2α and integrin-linked kinase proteins...
January 1, 2018: Technology in Cancer Research & Treatment
Xiu-Mei Yang, Chun-Guang Duan, Jian Zhang, Xiao-Jie Qu, Yu-Sheng Wang
Purpose: Vasculogenesis has been shown to contribute to the formation of choroidal neovascularization (CNV). However, the mechanism behind the recruitment of endothelial progenitor cells (EPC) to CNV is not well understood. Therefore, we were interested to know whether integrin-linked kinase (ILK) plays a role in recruiting EPC to CNV, and its possible mechanism. Methods: We investigated the effect of hypoxia on retinal pigment epithelium (RPE) cells expressing ILK, hypoxia-inducible factor 1α (HIF-1α), stromal-derived factor-1 (SDF-1), and vascular endothelial growth factor (VEGF), and we further examined the effect of ILK small interfering RNA (siRNA) on their expression...
April 1, 2018: Investigative Ophthalmology & Visual Science
Ioanna Akrida, Sofia Nikou, Konstantinos Gyftopoulos, Marianna Argentou, Sofia Kounelis, Vassiliki Zolota, Vasiliki Bravou, Helen Papadaki
Phyllodes tumors (PTs) of the breast constitute an uncommon group of mammary fibroepithelial lesions with ambiguous biologic behavior. Recent evidence suggests that epithelial mesenchymal transition (EMT), a driving force of cancer progression is implicated in PTs pathogenesis. Integrin-linked kinase (ILK), a focal adhesion kinase, has been implicated in cancer and EMT and represents a novel cancer therapeutic target. In this study, we aimed to investigate ILK and EMT markers expression in phyllodes breast tumors in relation to tumor grade...
April 2, 2018: Histology and Histopathology
Siyang Han, Mei-Fong Pang, Celeste M Nelson
The Wnt/β-catenin pathway controls a variety of cellular behaviors, aberrant activation of which are associated with tumor progression in several types of cancer. The same cellular behaviors are also affected by the mechanical properties of the extracellular matrix (ECM) substratum, which induces signaling through integrins and integrin-linked kinase (ILK). Here, we examined the role of substratum stiffness in the regulation of cell proliferation downstream of Wnt3a. We found that treatment with Wnt3a increased proliferation of cells cultured on stiff substrata, with compliances characteristic of breast tumors, but not of cells on soft substrata, with compliances comparable to that of normal mammary tissue...
March 27, 2018: Journal of Cell Science
Nicoletta Zoppi, Nicola Chiarelli, Marco Ritelli, Marina Colombi
The αvβ3 integrin, an endothelial cells' receptor-binding fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts...
March 26, 2018: International Journal of Molecular Sciences
Michelle Im, Lina Dagnino
The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults...
March 2, 2018: Oncotarget
Najat Dzaki, Ghows Azzam
Members of the Aedes genus of mosquitoes are widely recognized as vectors of viral diseases. Ae.albopictus is its most invasive species, and are known to carry viruses such as Dengue, Chikugunya and Zika. Its emerging importance puts Ae.albopictus on the forefront of genetic interaction and evolution studies. However, a panel of suitable reference genes specific for this insect is as of now undescribed. Nine reference genes, namely ACT, eEF1-γ, eIF2α, PP2A, RPL32, RPS17, PGK1, ILK and STK were evaluated. Expression patterns of the candidate reference genes were observed in a total of seventeen sample types, separated by stage of development and age...
2018: PloS One
Thiago Verano-Braga, Vladimir Gorshkov, Sune Munthe, Mia D Sørensen, Bjarne W Kristensen, Frank Kjeldsen
Glioblastoma (GBM) is a highly aggressive brain cancer with poor prognosis and low survival rate. Invasive cancer stem-like cells (CSCs) are responsible for tumor recurrence because they escape current treatments. Our main goal was to study the proteome of three GBM subpopulations to identify key molecules behind GBM cell phenotypes and potential cell markers for migrating cells. We used SuperQuant-an enhanced quantitative proteome approach-to increase proteome coverage. We found 148 proteins differentially regulated in migrating CSCs and 199 proteins differentially regulated in differentiated cells...
February 6, 2018: Oncotarget
Kieran James, Mary O'Connell Motherway, Christophe Penno, Rebecca Louise O'Brien, Douwe van Sinderen
Bifidobacterial carbohydrate metabolism has been studied in considerable detail for a variety of both plant and human-derived glycans, particularly involving the bifidobacterial prototype Bifidobacterium breve UCC2003. We recently elucidated the metabolic pathways by which the <u>h</u>uman <u>m</u>ilk <u>o</u>ligosaccharide (HMO) constituents lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT) and lacto-N-biose (LNB) are utilized by B. breve UCC2003. However, to date no work has been carried out on the regulatory mechanisms that control expression of the genetic loci involved in these HMO metabolic pathways...
March 2, 2018: Applied and Environmental Microbiology
Alain Boussac, Ilke Ugur, Antoine Marion, Miwa Sugiura, Ville R I Kaila, A William Rutherford
In Photosystem II (PSII), the Mn4 CaO5 -cluster of the active site advances through five sequential oxidation states (S0 to S4 ) before water is oxidized and O2 is generated. Here, we have studied the transition between the low spin (LS) and high spin (HS) configurations of S2 using EPR spectroscopy, quantum chemical calculations using Density Functional Theory (DFT), and time-resolved UV-visible absorption spectroscopy. The EPR experiments show that the equilibrium between S2 LS and S2 HS is pH dependent, with a pKa  ≈ 8...
February 27, 2018: Biochimica et Biophysica Acta
Dimitrios Tsoumas, Sofia Nikou, Efstathia Giannopoulou, Spyridon Champeris Tsaniras, Chaido Sirinian, Ioannis Maroulis, Stavros Taraviras, Vassiliki Zolota, Haralabos P Kalofonos, Vasiliki Bravou
BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers. PATIENTS AND METHODS: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples. We also generated colon cancer cells resistant to 5-FU and oxaliplatin and studied the effect of ILK inhibition on drug response by MTT assay and on EMT and CSC markers' expression...
March 2018: Cancer Genomics & Proteomics
Ilke S Turan, Gurcan Gunaydin, Seylan Ayan, Engin U Akkaya
Molecular logic gates are expected to play an important role on the way to information processing therapeutic agents, especially considering the wide variety of physical and chemical responses that they can elicit in response to the inputs applied. Here, we show that a 1:2 demultiplexer based on a Zn2+ -terpyridine-Bodipy conjugate with a quenched fluorescent emission, is efficient in photosensitized singlet oxygen generation as inferred from trap compound experiments and cell culture data. However, once the singlet oxygen generated by photosensitization triggers apoptotic response, the Zn2+ complex then interacts with the exposed phosphatidylserine lipids in the external leaflet of the membrane bilayer, autonomously switching off singlet oxygen generation, and simultaneously switching on a bright emission response...
February 23, 2018: Nature Communications
Valérie Bernard, Chiara Villa, Aurélie Auguste, Sophie Lamothe, Anne Guillou, Agnès Martin, Sandrine Caburet, Jacques Young, Reiner A Veitia, Nadine Binart
Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development...
January 19, 2018: Oncotarget
Judit Balazs, Monika Miklosi, Jozsef Halasz, Lili Olga Horváth, Dóra Szentiványi, Péter Vida
Background: According to literature data, psychopathology is associated with both quality of life (QoL) and suicidal risk in adolescents, but the literature does not fully support a direct association between psychopathology and suicidal thoughts and behaviors. The aim of this study was to investigate the possible mediational role of QoL in the relationship between psychopathology and level of suicidal risk in a clinical sample of adolescents. Method: The authors examined a clinical population of 134 adolescents, aged 13-18 years...
2018: Frontiers in Psychiatry
Ilke Akpinar, Philip Jacobs, Tien Dat Tran
BACKGROUND: Economic evaluation helps policy makers and healthcare payers make decisions on drug listing, coverage, and reimbursement. When economic evaluations are conducted before a product launch, the prices of the pharmaceuticals have to be forecast. OBJECTIVE: The aim of this study was to examine the methods of establishing proxy prices and their accuracies compared with actual market prices after the product launch. METHODS: We searched the literature for evaluations for drugs that were licensed in the US between 2010 and 2015...
March 2017: PharmacoEconomics Open
Joost Wegman, Ilke van Loon, Paul A M Smeets, Roshan Cools, Esther Aarts
Labels on food packages inform our beliefs, shaping our expectations of food properties, such as its expected taste and healthiness. These beliefs can influence the processing of caloric rewards beyond objective sensory properties and have the potential to impact decision making. However, no studies, within or beyond the food domain, have assessed how written information, such as food labels, affect implicit motivation to obtain rewards, even though choices in daily life might be strongly driven by implicit motivational biases...
February 10, 2018: NeuroImage
Fang-Hua Qi, Ping-Ping Cai, Xiang Liu, Guo-Min Si
Epithelial-mesenchymal transition (EMT) is a critical step and key factor during renal fibrosis. Preventing renal tubular EMT is important for delaying the progression of chronic kidney disease (CKD). P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. However, the related studies on P311 on renal fibrosis are limited and the mechanisms of P311 in the progression of renal tubulointerstitial fibrosis remain largely unknown...
February 12, 2018: International Journal of Molecular Medicine
Semiha Kevser Bali, Antoine Marion, Ilke Ugur, Ayse Kumru Dikmenli, Saron Catak, Viktorya Aviyente
Topotecan (TPT) is a non-toxic anti-cancer drug characterized by a pH dependent lactone/carboxyl equilibrium. TPT acts on the covalently bonded DNA/Topoisomerase I (DNA/TopoI) complex by intercalating between two DNA bases at the active site. This turns TopoI into a DNA-damaging agent and inhibits supercoil relaxation. Although only the lactone form of the drug is active and effectively inhibits TopoI, both forms have been co-crystalized at the same location within the DNA/TopoI complex. To gain further insights into the pH dependent activity of TPT, the differences between two TPT:DNA/TopoI complexes presenting either the lactone (acidic pH) or the carboxyl (basic pH) form of TPT were studied by means of molecular dynamic simulations, QM/MM calculations, and topological analysis...
February 7, 2018: Biochemistry
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