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https://www.readbyqxmd.com/read/28231640/mind-the-gap-mechanisms-regulating-the-endothelial-barrier
#1
REVIEW
Mariya Y Radeva, Jens Waschke
The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sieve-like manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracelullar permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue...
February 23, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28231625/experimental-study-on-1-25-oh-2-d3-amelioration-of-oral-lichen-planus-through-regulating-nf-%C3%AE%C2%BAb-signaling-pathway
#2
Jie Du, Ran Li, Feiyan Yu, Fang Yang, Jinhua Wang, Qingyong Chen, Xiangyu Wang, Bin Zhao, Fang Zhang
OBJECTIVE: To explore the protective function of vitamin D (VD)/vitamin D receptor (VDR) on the development of oral lichen planus (OLP) and elaborate the underling mechanism of it. METHODS: H&E staining, myeloid Peroxidase (MPO) assays, quantitative PCR (qPCR), western blotting and Elisa were used to test the human biopsies and serum. QPCR, western blotting, Elisa and siRNA transfection were also performed in LPS-induced keratinocytes to observe the functions of vitamin D and VDR...
February 23, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28231592/cxcr4-a-new-player-in-an-old-scene
#3
Andreas Knopf, Marie Kristin Fritsche, Yin Li
Transmembrane C-X-C chemokine receptor 4 (CXCR4) and its ligand C-X-C motif chemokine 12 (CXCL12) came into focus in many solid cancers, allowing a more fundamental diagnostic and therapeutic approach by modulating the immune response against cancer cells. CXCR4 and CXCL12 mediate cell proliferation, migration, and metastatic outgrowth in head and neck squamous cell carcinoma (HNSCC) and are strongly associated with cancer recurrence and patient survival. Despite recent advances in molecular imaging and cancer therapy in lymphoma using CXCL12 analogues, clinical trials evaluating the diagnostic and therapeutic impact on HNSCC are missing...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28231567/innate-lung-defense-during-invasive-aspergillosis-new-mechanisms
#4
Jaleesa M Garth, Chad Steele
Invasive aspergillosis (IA) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. Continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for IA. However, IA is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. The innate immune response to Aspergillus fumigatus, the primary agent in IA, plays a pivotal role in the recognition and elimination of organisms from the pulmonary system...
February 24, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28231545/aqueous-extract-of-cortex-dictamni-protects-h9c2-cardiomyocytes-from-hypoxia-reoxygenation-induced-oxidative-stress-and-apoptosis-by-pi3k-akt-signaling-pathway
#5
Lin Li, Yunfeng Zhou, Yanlin Li, Lili Wang, Lan Sun, Lidong Zhou, Hiderori Arai, Yun Qi, Yang Xu
Ischemia-reperfusion injury is the major manifestation of ischemic heart disease, which facilitates cardiac arrhythmias, heart failure and death. Oxidative stress and apoptosis have been involved in the pathogenesis of myocardial ischemia-reperfusion injury. Modern pharmacological studies have indicated that the extracts and active compounds of Cortex Dictamni exhibit antioxidative and cardiovascular protective activities. This study was designed to investigate the protective effect of aqueous extract of Cortex Dictamni (CDAE) on regulating hypoxia/reoxygenation (H/R)-induced cardiomyocytes oxidative stress and apoptosis...
February 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28231524/discovery-of-novel-cdk8-inhibitors-using-multiple-crystal-structures-in-docking-based-virtual-screening
#6
Taijin Wang, Zhuang Yang, Yongguang Zhang, Wei Yan, Fang Wang, Linhong He, Yuanyuan Zhou, Lijuan Chen
The cyclin dependent kinase CDK8, along with Med12 and Med13, form the kinase module of the Mediator complex. CDK8 expression associates with the activation of β-catenin in colon and gastric cancers. Herein, we applied docking-based virtual screening (VS) using the multiple crystal structures to identify several potent CDK8 inhibitors. The appropriate use of multiple crystal structures obtained a better enrichment of CDK8 conformations to cope with the protein flexibility. Later on, the 2D similarity search was used to find the derivatives of the high inhibitory CDK8 inhibitors we discovered by VS...
February 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28231467/synaptic-vesicle-endocytosis-occurs-on-multiple-timescales-and-is-mediated-by-formin-dependent-actin-assembly
#7
Tolga Soykan, Natalie Kaempf, Takeshi Sakaba, Dennis Vollweiter, Felix Goerdeler, Dmytro Puchkov, Natalia L Kononenko, Volker Haucke
Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Recent data suggest that at physiological temperature SVs are internalized via clathrin-independent ultrafast endocytosis (UFE) within hundreds of milliseconds, while other studies have postulated a key role for clathrin-mediated endocytosis (CME) of SV proteins on a timescale of seconds to tens of seconds. Here we demonstrate using cultured hippocampal neurons as a model that at physiological temperature SV endocytosis occurs on several timescales from less than a second to several seconds, yet, is largely independent of clathrin...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231442/ethnomethodological-studies-of-nurse-patient-and-nurse-relative-interactions-a-scoping-review
#8
REVIEW
Eric Mayor, Lucas Bietti
OBJECTIVES: Researchers in nursing science interested in the study of nurse-patient and nurse-relative interactions have displayed an ever increasing interest in ethnomethodology and conversation analysis. This review assesses the scope of this literature. We categorize the papers in thematic categories determined both inductively and deductively and synthesize the main findings of this literature within category. Finally we discuss the interactional determinants of the lack patient participation, the limitations of the field, and focus on implications...
February 9, 2017: International Journal of Nursing Studies
https://www.readbyqxmd.com/read/28231433/discovery-of-a-potent-and-selective-sphingosine-kinase-1-inhibitor-through-the-molecular-combination-of-chemotype-distinct-screening-hits
#9
Mark E Schnute, Matthew D McReynolds, Jeffrey Carroll, Jill E Chrencik, Maureen K Highkin, Kaliapan Iyanar, Gina Jerome, John W Rains, Matthew Saabye, Jeffrey A Scholten, Matthew Yates, Marek M Nagiec
Sphingosine kinase (SphK) is the major source of the lipid mediator and GPCR agonist sphingosine-1-phosphate (S1P). S1P promotes cell growth, survival and migration and is a key regulator of lymphocyte trafficking. Inhibition of S1P signaling has been proposed as a strategy for treatment of inflammatory diseases and cancer. Two different formats of an enzyme based high-throughput screen yielded two attractive chemotypes capable of inhibiting S1P formation in cells. The molecular combination of these screening hits led to compound 22a (PF-543) with two orders of magnitude improved potency...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28231426/engineering-of-anti-cd133-tri-specific-molecule-capable-of-inducing-nk-expansion-and-driving-antibody-dependent-cell-mediated-cytotoxicity-adcc
#10
Jörg U Schmohl, Martin Felices, Felix Oh, Alexander J Lenvik, Aaron M Lebeau, Jayanth Panyam, Jeffrey S Miller, Daniel A Vallera
Purpose: The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 BiKE, consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified IL-15 crosslinker capable of stimulating NK effector cells was introduced. Materials and Methods: DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE)...
February 20, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28231380/perioperative-medications-for-preventing-temporarily-increased-intraocular-pressure-after-laser-trabeculoplasty
#11
REVIEW
Linda Zhang, Jennifer S Weizer, David C Musch
BACKGROUND: Glaucoma is the international leading cause of irreversible blindness. Intraocular pressure (IOP) is the only currently known modifiable risk factor; it can be reduced by medications, incisional surgery, or laser trabeculoplasty (LTP). LTP reduces IOP by 25% to 30% from baseline, but early acute IOP elevation after LTP is a common adverse effect. Most of these IOP elevations are transient, but temporarily elevated IOP may cause further optic nerve damage, worsening of glaucoma requiring additional therapy, and permanent vision loss...
February 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28231365/alteration-of-serum-levels-of-inflammatory-cytokines-and-polysomnographic-indices-after-uvulopalatal-flap-surgery-in-obstructive-sleep-apnea
#12
Murad Mutlu, Erkan Vuralkan, Istemihan Akin, Hikmet Firat, Sadik Ardic, Sevgi Akaydin, Ece Miser
The aim of the current study was to compare the changes in polysomnographic indices and serum levels of C-reactive protein (CRP), cystatin C, tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in patients with obstructive sleep apnea (OSA) who were treated surgically via a uvulopalatal flap (UPF) technique. Twenty-five patients (14 men, 11 women), average age 46.2 ± 9.3 years, who underwent UPF surgery were included in this study. Serum biochemical analyses and polysomnographic examinations were performed before and 6 months after the surgery...
February 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28231321/argonaute10-promotes-the-degradation-of-mir165-6-through-the-sdn1-and-sdn2-exonucleases-in-arabidopsis
#13
Yu Yu, Lijuan Ji, Brandon H Le, Jixian Zhai, Jiayi Chen, Elizabeth Luscher, Lei Gao, Chunyan Liu, Xiaofeng Cao, Beixin Mo, Jinbiao Ma, Blake C Meyers, Xuemei Chen
The degradation of small RNAs in plants and animals is associated with small RNA 3' truncation and 3' uridylation and thus relies on exonucleases and nucleotidyl transferases. ARGONAUTE (AGO) proteins associate with small RNAs in vivo and are essential for not only the activities but also the stability of small RNAs. AGO1 is the microRNA (miRNA) effector in Arabidopsis, and its closest homolog, AGO10, maintains stem cell homeostasis in meristems by sequestration of miR165/6, a conserved miRNA acting through AGO1...
February 2017: PLoS Biology
https://www.readbyqxmd.com/read/28231297/cytoplasmic-deadenylase-ccr4-is-required-for-translational-repression-of-lrg1-mrna-in-the-stationary-phase
#14
Duong Long Duy, Yasuyuki Suda, Kenji Irie
Ccr4 is a major cytoplasmic deadenylase involved in mRNA poly(A) tail shortening in Saccharomyces cerevisiae. We have previously shown that Ccr4 negatively regulates expression of LRG1 mRNA encoding a GTPase-activating protein for the small GTPase Rho1, a component of cell wall integrity pathway, and deletion of LRG1 suppresses the temperature-sensitive growth defect of the ccr4Δ mutant. We have also shown that the slow growth of the ccr4Δ mutant is suppressed by deletion of another gene, PBP1, encoding a poly(A)-binding protein (Pab1)-binding protein 1; however, the underlying mechanism still remains unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28231281/the-intron-in-centromeric-noncoding-rna-facilitates-rnai-mediated-formation-of-heterochromatin
#15
Masatoshi Mutazono, Misato Morita, Chihiro Tsukahara, Madoka Chinen, Shiori Nishioka, Tatsuhiro Yumikake, Kohei Dohke, Misuzu Sakamoto, Takashi Ideue, Jun-Ichi Nakayama, Kojiro Ishii, Tokio Tani
In fission yeast, the formation of centromeric heterochromatin is induced through the RNA interference (RNAi)-mediated pathway. Some pre-mRNA splicing mutants (prp) exhibit defective formation of centromeric heterochromatin, suggesting that splicing factors play roles in the formation of heterochromatin, or alternatively that the defect is caused by impaired splicing of pre-mRNAs encoding RNAi factors. Herein, we demonstrate that the splicing factor spPrp16p is enriched at the centromere, and associates with Cid12p (a factor in the RNAi pathway) and the intron-containing dg ncRNA...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28231279/lysine-acetyltransferase-nua4-and-acetyl-coa-regulate-glucose-deprived-stress-granule-formation-in-saccharomyces-cerevisiae
#16
Meaghen Rollins, Sylvain Huard, Alan Morettin, Jennifer Takuski, Trang Thuy Pham, Morgan D Fullerton, Jocelyn Côté, Kristin Baetz
Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants...
February 23, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#17
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28231257/targeted-sequencing-identifies-a-novel-sh2d1a-pathogenic-variant-in-a-chinese-family-carrier-screening-and-prenatal-genetic-testing
#18
Jun-Yu Zhang, Song-Chang Chen, Yi-Yao Chen, Shu-Yuan Li, Lan-Lan Zhang, Ying-Hua Shen, Chun-Xin Chang, Yu-Qian Xiang, He-Feng Huang, Chen-Ming Xu
X-linked lymphoproliferative disease type 1 (XLP1) is a rare primary immunodeficiency characterized by a clinical triad consisting of severe EBV-induced hemophagocytic lymphohistiocytosis, B-cell lymphoma, and dysgammaglobulinemia. Mutations in SH2D1A gene have been revealed as the cause of XLP1. In this study, a pregnant woman with recurrence history of birthing immunodeficiency was screened for pathogenic variant because the proband sample was unavailable. We aimed to clarify the genetic diagnosis and provide prenatal testing for the family...
2017: PloS One
https://www.readbyqxmd.com/read/28231254/rapid-generation-of-drug-resistance-alleles-at-endogenous-loci-using-crispr-cas9-indel-mutagenesis
#19
Jonathan J Ipsaro, Chen Shen, Eri Arai, Yali Xu, Justin B Kinney, Leemor Joshua-Tor, Christopher R Vakoc, Junwei Shi
Genetic alterations conferring resistance to the effects of chemical inhibitors are valuable tools for validating on-target effects in cells. Unfortunately, for many therapeutic targets such alleles are not available. To address this issue, we evaluated whether CRISPR-Cas9-mediated insertion/deletion (indel) mutagenesis can produce drug-resistance alleles at endogenous loci. This method takes advantage of the heterogeneous in-frame alleles produced following Cas9-mediated DNA cleavage, which we show can generate rare alleles that confer resistance to the growth-arrest caused by chemical inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28231144/effects-of-two-step-transamidation-of-wheat-semolina-on-the-technological-properties-of-gluten
#20
Salvatore Moscaritolo, Lucia Treppiccione, Antonio Ottombrino, Mauro Rossi
Celiac disease (CD) is an immune-mediated disorder caused by the ingestion of wheat gluten. A lifelong, gluten-free diet is required to alleviate symptoms and to normalize the intestinal mucosa. We previously found that transamidation reaction by microbial transglutaminase (mTG) was effective in down-regulating the gliadin-specific immune response in CD patients. In this study, the two-step transamidation protocol was adopted to treat commercial wheat semolina on a pilot scale. The effectiveness of the enzymatic reaction was tested by means of consolidated biochemical and immunological methods on isolated prolamins...
June 29, 2016: Foods (Basel, Switzerland)
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