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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/28231612/the-pro-inflammatory-cytokine-tnf-%C3%AE-inhibits-lymphatic-pumping-via-activation-of-the-nf-%C3%AE%C2%BAb-inos-signaling-pathway
#3
Yingxuan Chen, Sonia Rehal, Simon Roizes, Hai-Lei Zhu, William C Cole, Pierre-Yves von der Weid
OBJECTIVE: Mesenteric lymphatic vessels pumping, important to propel lymph and immune cells from the intestinal interstitium to the mesenteric lymph nodes, is compromised during intestinal inflammation. The objective of this study was to test the hypothesis that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), is a significant contributor to the inflammation-induced lymphatic contractile dysfunction, and to determine its mode of action. METHODS: Contractile parameters were obtained form isolated rat mesenteric lymphatic vessels mounted on a pressure myograph after 24-h incubation with or without TNF-α...
February 23, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28231588/checkpoint-inhibition-in-head-and-neck-cancer-immune-therapeutic-options-limitations-and-beyond
#4
Bastian Höchst, Percy A Knolle
The immune system functions to defend the organism against infectious microorganisms but also against transformed cells. This key role of the immune system, in particular cancer-specific T cells, in eliminating cancer cells is compromised by various immune escape strategies employed by cancer cells and the cancer microenvironment. Here, we review the current knowledge about the immune escape mechanisms of cancer and the attempts to reconstitute cancer-specific immunity by using checkpoint inhibitors in head and neck squamous cell carcinoma...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28231560/the-expanding-role-of-immunotherapy
#5
REVIEW
Juan Martin-Liberal, María Ochoa de Olza, Cinta Hierro, Alena Gros, Jordi Rodon, Josep Tabernero
The use of agents able to modulate the immune system to induce or potentiate its anti-tumour activity is not a new strategy in oncology. However, the development of new agents such as immune checkpoint inhibitors has achieved unprecedented efficacy results in a wide variety of tumours, dramatically changing the landscape of cancer treatment in recent years. Ipilimumab, nivolumab, pembrolizumab or atezolizumab are now standard of care options in several malignancies and new indications are being approved on a regular basis in different tumours...
February 11, 2017: Cancer Treatment Reviews
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
#6
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/28231544/ginsenoside-rg3-promotes-cytotoxicity-of-paclitaxel-through-inhibiting-nf-%C3%AE%C2%BAb-signaling-and-regulating-bax-bcl-2-expression-on-triple-negative-breast-cancer
#7
Zuguo Yuan, Hao Jiang, Xinhai Zhu, Xinge Liu, Jinhui Li
Taxane-based chemotherapy regimen is the most effective therapeutic strategy for triple-negative breast cancer (TNBC) which is an aggressive subtype of breast cancer with high rate of recurrence and distant metastasis. Ginsenoside Rg3 is isolated from Panax ginseng with anti-cancer activity against carcinomas. We aim to evaluate the chemosensitizing effects of Ginsenoside Rg3 on TNBC cells and xenograft and explore the underlying mechanism. Human triple-negative breast cancer lines MDA-MB-231, MDA-MB-453 and BT-549 were used...
February 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#8
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231509/a-single-injection-of-protein-loaded-coacervate-gel-significantly-improves-cardiac-function-post-infarction
#9
H K Awada, D W Long, Z Wang, M P Hwang, K Kim, Y Wang
After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period...
February 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231508/regulating-dynamic-signaling-between-hematopoietic-stem-cells-and-niche-cells-via-a-hydrogel-matrix
#10
Bhushan P Mahadik, Narayanan A K Bharadwaj, Randy H Ewoldt, Brendan A C Harley
Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin(+)) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin(+) cells increased myeloid differentiation...
February 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231490/lipid-droplet-growth-regulation-of-a-dynamic-organelle
#11
REVIEW
David Barneda, Mark Christian
Intracellular lipid droplets (LDs) are remarkably dynamic and complex organelles that enact regulated storage and release of lipids to fulfil their fundamental roles in energy metabolism, membrane synthesis and provision of lipid-derived signaling molecules. Although small LDs are observed in all types of eukaryotic cells, it is adipocytes that present the widest range of sizes up to the massive unilocular droplet of a white adipocyte. Our knowledge of the proteins and associated processes that control LD dynamics is improving...
February 20, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28231483/a-novel-redox-regulator-mntnbuoe-2-pyp-5-enhances-normal-hematopoietic-stem-progenitor-cell-function
#12
Y Zhao, D W Carroll, Y You, L Chaiswing, R Wen, I Batinic-Haberle, S Bondada, Y Liang, D K St Clair
The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP(5+)(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs...
February 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28231470/rapid-integration-of-artificial-sensory-feedback-during-operant-conditioning-of-motor-cortex-neurons
#13
Mario Prsa, Gregorio L Galiñanes, Daniel Huber
Neuronal motor commands, whether generating real or neuroprosthetic movements, are shaped by ongoing sensory feedback from the displacement being produced. Here we asked if cortical stimulation could provide artificial feedback during operant conditioning of cortical neurons. Simultaneous two-photon imaging and real-time optogenetic stimulation were used to train mice to activate a single neuron in motor cortex (M1), while continuous feedback of its activity level was provided by proportionally stimulating somatosensory cortex...
February 22, 2017: Neuron
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
#14
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/28231431/enhancing-adoptive-cell-therapy-of-cancer-through-targeted-delivery-of-small-molecule-immunomodulators-to-internalizing-or-non-internalizing-receptors
#15
Yiran Zheng, Li Tang, Llian Mabardi, Sudha Kumari, Darrell J Irvine
Adoptive cell therapy (ACT) has achieved striking efficacy in B-cell leukemias, but less success treating other cancers, in part due to the rapid loss of ACT T-cell effector function in vivo due to immunosuppression in solid tumors. Transforming growth factor-β (TGF-β) signaling is an important mechanism of immune suppression in the tumor microenvironment, but systemic inhibition of TGF-β is toxic. Here we evaluated the potential of targeting a small molecule inhibitor of TGF-β to ACT T-cells using PEGylated immunoliposomes...
February 23, 2017: ACS Nano
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
#16
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/28231410/transcriptomic-analyses-of-rna-binding-proteins-reveal-eif3c-promotes-cell-proliferation-in-hepatocellular-carcinoma
#17
Tangjian Li, Shengli Li, Di Chen, Bing Chen, Tao Yu, Fangyu Zhao, Qifeng Wang, Ming Yao, Shenglin Huang, Zhiao Chen, Xianghuo He
RNA-binding proteins (RBPs) play fundamental roles in the RNA life cycle. The aberrant expression of RBPs is often observed in human disease, including cancer. In this study, we screened for the expression levels of 1,542 human RBPs in The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA LIHC) samples and found 92 consistently up-regulated RBP genes in HCC compared with normal samples. Additionally, we performed a Kaplan-Meier analysis and found that high expression of 15 RBP genes was associated with poor prognosis in patients with HCC...
February 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28231331/mesenchymal-stromal-cells-mscs-induce-ex-vivo-proliferation-and-erythroid-commitment-of-cord-blood-haematopoietic-stem-cells-cb-cd34-cells
#18
Simone Perucca, Andrea Di Palma, Pier Paolo Piccaluga, Claudia Gemelli, Elisa Zoratti, Giulio Bassi, Edoardo Giacopuzzi, Andrea Lojacono, Giuseppe Borsani, Enrico Tagliafico, Maria Teresa Scupoli, Simona Bernardi, Camilla Zanaglio, Federica Cattina, Valeria Cancelli, Michele Malagola, Mauro Krampera, Mirella Marini, Camillo Almici, Sergio Ferrari, Domenico Russo
A human bone marrow-derived mesenchymal stromal cell (MSCs) and cord blood-derived CD34+ stem cell co-culture system was set up in order to evaluate the proliferative and differentiative effects induced by MSCs on CD34+ stem cells, and the reciprocal influences on gene expression profiles. After 10 days of co-culture, non-adherent (SN-fraction) and adherent (AD-fraction) CD34+ stem cells were collected and analysed separately. In the presence of MSCs, a significant increase in CD34+ cell number was observed (fold increase = 14...
2017: PloS One
https://www.readbyqxmd.com/read/28231299/exploration-of-inhibitory-mechanisms-of-curcumin-in-lung-cancer-metastasis-using-a-mirna-transcription-factor-target-gene-network
#19
De-Min Jiao, Li Yan, Li-Shan Wang, Hui-Zhen Hu, Xia-Li Tang, Jun Chen, Jian Wang, You Li, Qing-Yong Chen
The present study was aimed to unravel the inhibitory mechanisms of curcumin for lung cancer metastasis via constructing a miRNA-transcription factor (TF)-target gene network. Differentially expressed miRNAs between human high-metastatic non-small cell lung cancer 95D cells treated with and without curcumin were identified using a TaqMan human miRNA array followed by real-time PCR, out of which, the top 6 miRNAs (miR-302b-3p, miR-335-5p, miR-338-3p, miR-34c-5p, miR-29c-3p and miR-34a-35p) with more verified target genes and TFs than other miRNAs as confirmed by a literature review were selected for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28231291/osteosarcoma-cell-proliferation-and-survival-requires-mglur5-receptor-activity-and-is-blocked-by-riluzole
#20
Sally Liao, Yuleisy Ruiz, Hira Gulzar, Zarina Yelskaya, Lyes Ait Taouit, Murielle Houssou, Trisha Jaikaran, Yuriy Schvarts, Kristina Kozlitina, Upal Basu-Roy, Alka Mansukhani, Shahana S Mahajan
Osteosarcomas are malignant tumors of bone, most commonly seen in children and adolescents. Despite advances in modern medicine, the poor survival rate of metastatic osteosarcoma has not improved in two decades. In the present study we have investigated the effect of Riluzole on a human and mouse metastatic osteosarcoma cells. We show that LM7 cells secrete glutamate in the media and that mGluR5 receptors are required for the proliferation of LM7 cells. Riluzole, which is known to inhibit glutamate release, inhibits proliferation, induces apoptosis and prevents migration of LM7 cells...
2017: PloS One
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