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https://www.readbyqxmd.com/read/28102399/microsphere-cytometry-to-interrogate-microenvironment-dependent-cell-signaling
#1
Henriette Christie Ertsås, Garry P Nolan, Mark A LaBarge, James B Lorens
Microenvironmental cues comprising surface-mediated and soluble factors control cellular signaling mechanisms underlying normal cellular responses that define homeostatic and diseased cell states. In order to measure cell signaling in single adherent cells, we developed a novel microsphere-based flow cytometry approach. Single normal or neoplastic cells were adhered to uniform microspheres that display mimetic-microenvironments comprising surface combinations of extracellular matrix (ECM) in the presence of soluble agonists/antagonists...
January 19, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28101472/the-effects-of-hypoxia-on-u937-cell-line-in-mesenchymal-stem-cells-co-culture-system
#2
Mostafa Ejtehadifar, Karim Shamsasenjan, Parvin Akbarzadehlaleh, Sarah Zahedi, Narjes Kazemi
Purpose: Mesenchymal Stem Cells (MSCs) are the most important members of Bone Marrow (BM) milieu. MSCs affect different kinds of cells, particularly malignant cells of hematologic malignancies, but the effects of MSCs are unclear exactly. Here we analyzed the effects of derived Umbilical Cord Blood-MSCs on proliferation, cell death and some surface markers of U937 cell line in a Co-culture system with MSCs. Methods: Here we designed Co-culture systems as a model of BM milieu. We cultured U937 cells on UCB-MSCs and MSCs Conditioned Medium (C...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28100839/tyrosine-kinase-blocking-collagen-iv-derived-peptide-suppresses-ocular-neovascularization-and-vascular-leakage
#3
Raquel Lima E Silva, Yogita Kanan, Adam C Mirando, Jayoung Kim, Ron B Shmueli, Valeria E Lorenc, Seth D Fortmann, Jason Sciamanna, Niranjan B Pandey, Jordan J Green, Aleksander S Popel, Peter A Campochiaro
Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefit in several retinal and choroidal vascular diseases, but some patients still experience suboptimal outcomes, and the need for frequent intraocular injections is a barrier to good outcomes. A mimetic peptide derived from collagen IV, AXT107, suppressed subretinal neovascularization (NV) in two mouse models predictive of effects in neovascular age-related macular degeneration (NVAMD) and inhibited retinal NV in a model predictive of effects in ischemic retinopathies...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100580/venetoclax-in-patients-with-previously-treated-chronic-lymphocytic-leukemia
#4
Andrew W Roberts, Stephan Stilgenbauer, John F Seymour, David C S Huang
Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacological mimic of the proteins that initiate apoptosis (a so-called BH3-mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a Phase 1 study, including complete remissions in 20% of patients...
January 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28100020/independent-evolution-of-sexual-dimorphism-and-female-limited-mimicry-in-swallowtail-butterflies-papilio-dardanus-and-p-phorcas
#5
M J T N Timmermans, M J Thompson, S Collins, A P Vogler
Several species of Swallowtail butterflies (genus Papilio) are Batesian mimics that express multiple mimetic female forms, while the males are monomorphic and non-mimetic. The evolution of such sex-limited mimicry may involve sexual dimorphism arising first and mimicry subsequently. Such a stepwise scenario through a non-mimetic, sexually dimorphic stage has been proposed for two closely related sexually dimorphic species; P. phorcas, a non-mimetic species with two female forms, and P. dardanus, a female-limited polymorphic mimetic species...
January 18, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28098880/the-role-of-gap-junctions-in-inflammatory-and-neoplastic-disorders-review
#6
Pui Wong, Victoria Laxton, Saurabh Srivastava, Yin Wah Fiona Chan, Gary Tse
Gap junctions are intercellular channels made of connexin proteins, mediating both electrical and biochemical signals between cells. The ability of gap junction proteins to regulate immune responses, cell proliferation, migration, apoptosis and carcinogenesis makes them attractive therapeutic targets for treating inflammatory and neoplastic disorders in different organ systems. Alterations in gap junction profile and expression levels are observed in hyperproliferative skin disorders, lymphatic vessel diseases, inflammatory lung diseases, liver injury and neoplastic disorders...
January 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28097017/study-of-myoblast-differentiation-using-multi-dimensional-scaffolds-consisting-of-nano-and-micropatterns
#7
Sung Ho Cha, Hyun Jong Lee, Won-Gun Koh
BACKGROUND: The topographical cue is major influence on skeletal muscle cell culture because the structure is highly organized and consists of long parallel bundles of multinucleated myotubes that are formed by differentiation and fusion of myoblast satellite cells. In this technical report, we fabricated a multiscale scaffold using electrospinning and poly (ethylene glycol) (PEG) hydrogel micropatterns to monitor the cell behaviors on nano- and micro-alignment combined scaffolds with different combinations of angles...
2017: Biomaterials Research
https://www.readbyqxmd.com/read/28095907/the-targeted-smac-mimetic-sw-iv-134-is-a-strong-enhancer-of-standard-chemotherapy-in-pancreatic-cancer
#8
Yassar M Hashim, Suwanna Vangveravong, Narendra V Sankpal, Pratibha S Binder, Jingxia Liu, S Peter Goedegebuure, Robert H Mach, Dirk Spitzer, William G Hawkins
BACKGROUND: Pancreatic cancer is a lethal malignancy that frequently acquires resistance to conventional chemotherapies often associated with overexpression of inhibitors of apoptosis proteins (IAPs). We have recently described a novel means to deliver second mitochondria-derived activator of caspases (SMAC) mimetics selectively to cancer cells employing the sigma-2 ligand/receptor interaction. The intrinsic death pathway agonist SMAC offers an excellent opportunity to counteract the anti-apoptotic activity of IAPs...
January 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28095700/nanohybrids-consisting-of-magnetic-nanoparticles-and-gold-nanoclusters-as-effective-peroxidase-mimics-and-their-application-for-colorimetric-detection-of-glucose
#9
Seongyeon Cho, Ho Yun Shin, Moon Il Kim
Although protein-stabilized gold nanoclusters (AuNCs) have gathered recent attention as biocompatible peroxidase mimics, their practical utility has been critically limited by the low catalytic activity. Here, the authors have developed a nanohybrid material to significantly enhance the catalytic activity of AuNCs by combining them with other inorganic enzyme mimetics, Fe3O4 magnetic nanoparticles (MNPs), through electrostatic attraction. Owing to the synergistic effect by incorporating AuNCs and MNPs, the constructed nanohybrids yielded highly enhanced catalytic activity and enabled rapid catalytic oxidation of 3,3',5,5'-tetramethylbenzidine substrate to produce a blue-colored solution in proportional to the amount of H2O2...
January 17, 2017: Biointerphases
https://www.readbyqxmd.com/read/28094768/bcl-w-has-a-fundamental-role-in-b-cell-survival-and-lymphomagenesis
#10
Clare M Adams, Annette S Kim, Ramkrishna Mitra, John K Choi, Jerald Z Gong, Christine M Eischen
Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#11
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28093224/beta-2-adrenoreceptor-polymorphism-at-position-16-determines-the-clinical-severity-of-chronic-obstructive-pulmonary-disease
#12
Justyna Emeryk-Maksymiuk, Andrzej Emeryk, Paweł Krawczyk, Kamila Wojas-Krawczyk, Janusz Milanowski
The Arg/Arg homozygosity at codon 16 of the beta-2-adrenoreceptor (ADRB2) gene has been thought to predispose asthma patients to a poorer therapeutic response to beta-2-mimetics, or to worse control of the disease. In contrast, the results of the studies analysing the effect of ADRB2 polymorphisms on the response to beta-2-adrenoreceptor agonists in chronic obstructive pulmonary disease (COPD) patients are sparse and inconclusive. The aim of this research was to verify if p.Arg16Gly (c.46A > G) and p.Gly27Glu (c...
January 13, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28087486/enhanced-articular-cartilage-by-human-mesenchymal-stem-cells-in-enzymatically-mediated-transiently-rgds-functionalized-collagen-mimetic-hydrogels
#13
Paresh A Parmar, Jean-Philippe St-Pierre, Lesley W Chow, Christopher D Spicer, Violet Stoichevska, Yong Y Peng, Jerome A Werkmeister, John A M Ramshaw, Molly M Stevens
: Recapitulation of the articular cartilage microenvironment for regenerative medicine applications faces significant challenges due to the complex and dynamic biochemical and biomechanical nature of native tissue. Towards the goal of biomaterial designs that enable the temporal presentation of bioactive sequences, recombinant bacterial collagens such as Streptococcal collagen-like 2 (Scl2) proteins can be employed to incorporate multiple specific bioactive and biodegradable peptide motifs into a single construct...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087333/nicotinamide-nucleotide-transhydrogenase-activity-impacts-mitochondrial-redox-balance-and-the-development-of-hypertension-in-mice
#14
Igor Leskov, Amber Neville, Xinggui Shen, Sibile Pardue, Christopher G Kevil, D Neil Granger, David M Krzywanski
Oxidant stress contributes to the initiation and progression of hypertension (HTN) by enhancing endothelial dysfunction and/or causing perturbations in nitric oxide homeostasis. Differences in mitochondrial function may augment this process and provide insight into why age of onset and clinical outcomes differ among individuals from distinct ethnic groups. We have previously demonstrated that variation in normal mitochondrial function and oxidant production exists in endothelial cells from individuals of Caucasian and African-American ethnicity and that this variation contributes to endothelial dysfunction...
December 16, 2016: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/28079955/solubilization-of-membrane-proteins-into-functional-lipid-bilayer-nanodiscs-using-a-diisobutylene-maleic-acid-copolymer
#15
Abraham Olusegun Oluwole, Bartholomäus Danielczak, Annette Meister, Jonathan Oyebamiji Babalola, Carolyn Vargas, Sandro Keller
Once removed from their natural environment, membrane proteins depend on membrane-mimetic systems to retain their native structures and functions. To this end, lipid-bilayer nanodiscs that are bounded by scaffold proteins or amphiphilic polymers such as styrene/maleic acid (SMA) copolymers have been introduced as alternatives to detergent micelles and liposomes for in vitro membrane-protein research. Herein, we show that an alternating diisobutylene/maleic acid (DIBMA) copolymer shows equal performance to SMA in solubilizing phospholipids, stabilizes an integral membrane enzyme in functional bilayer nanodiscs, and extracts proteins of various sizes directly from cellular membranes...
January 12, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28079887/drp-1-is-required-for-bh3-mimetic-mediated-mitochondrial-fragmentation-and-apoptosis
#16
Mateus Milani, Dominic P Byrne, Georgia Greaves, Michael Butterworth, Gerald M Cohen, Patrick A Eyers, Shankar Varadarajan
The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079248/inhibition-of-matrix-metalloproteinase-9-by-a-barbiturate-nitrate-hybrid-ameliorates-dextran-sulphate-sodium-induced-colitis-effect-on-inflammation-related-genes
#17
Shane O'Sullivan, Jun Wang, Maria T Pigott, Neil Docherty, Noreen Boyle, Samuel Kana Lis, John F Gilmer, Carlos Medina
BACKGROUND AND PURPOSE: Matrix metalloproteinase-9 is upregulated in Ulcerative Colitis and implicated in the pathology of the disease. In this study, we have examined the effects of a barbiturate-based MMP inhibitor incorporating a nitric oxide donor/mimetic group (dinitrate-barbiturate) in the intestinal injury induced by dextran sulphate sodium (DSS). EXPERIMENTAL APPROACH: In-vivo experiments were carried out using male Wistar rats given DSS 5% ad libitum in drinking water...
January 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28076753/cd25-targeted-therapy-of-chemotherapy-resistant-leukemic-stem-cells-using-dr5-specific-trail-peptide
#18
Jayaprakasam Madhumathi, Surapally Sridevi, Rama Shanker Verma
Chemotherapy resistant leukemic stem cells (LSCs) are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP) of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81...
January 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28074072/targeting-bet-proteins-improves-the-therapeutic-efficacy-of-bcl-2-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#19
S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe, S Goossens, B C Bornhauser, J-P Bourquin, P Van Vlierberghe
Inhibition of anti-apoptotic BCL-2 has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET bromodomain inhibitor JQ1...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28072841/a-small-insulinomimetic-molecule-also-improves-insulin-sensitivity-in-diabetic-mice
#20
Sandip Mukherjee, Mrittika Chattopadhyay, Sushmita Bhattacharya, Suman Dasgupta, Sahid Hussain, Saitanya K Bharadwaj, Dhrubajyoti Talukdar, Abul Usmani, Bhola S Pradhan, Subeer S Majumdar, Pronobesh Chattopadhyay, Satinath Mukhopadhyay, Tushar K Maity, Mihir K Chaudhuri, Samir Bhattacharya
Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1...
2017: PloS One
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