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https://www.readbyqxmd.com/read/28629051/novel-biomimetic-composite-material-for-potentiometric-screening-of-acetylcholine-a-neurotransmitter-in-alzheimer-s-disease
#1
Ana S Sacramento, Felismina T C Moreira, Joana L Guerreiro, Ana P Tavares, M Goreti F Sales
This work describes a novel approach to produce an antibody-like biomimetic material. It includes preparing composite imprinted material never presented before, with highly conductive support nanostructures and assembling a high conductivity polymeric layer at low temperature. Overall, such highly conductive material may enhance the final features of electrically-based devices. Acetylcholine (ACh) was selected as target analyte, a neurotransmitter of importance in Alzheimer's disease. Potentiometric transduction was preferred, allowing quick responses and future adaptation to point-of-care requirements...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28624794/knockdown-of-hdac1-expression-suppresses-invasion-and-induces-apoptosis-in-glioma-cells
#2
Xiao-Qiang Wang, Hong-Min Bai, Shi-Ting Li, Hui Sun, Ling-Zhao Min, Bang-Bao Tao, Jun Zhong, Bin Li
Glioma is the most common malignant tumor of the central nervous system, with a low survival rate of five years worldwide. Although high expression and prognostic value of histone deacetylase 1 (HDAC1) have been recently reported in various types of human tumors, the molecular mechanism underlying the biological function of HDAC1 in glioma is still unclear. We found that HDAC1 was elevated in glioma tissues and cell lines. HDAC1 expression was closely related with pathological grade and overall survival of patients with gliomas...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618955/oridonin-synergizes-with-nutlin-3-in-osteosarcoma-cells-by-modulating-the-levels-of-multiple-bcl-2-family-proteins
#3
Xiao-Hui Wang, Shu-Feng Zhang, Jun-Tao Bao, Fu-Yun Liu
The small-molecule inhibitors of p53-murine double minute 2 interaction, such as Nutlin-3, are effective against cancers bearing wild-type p53. However, murine double minute 2 inhibitors often are unable to completely eliminate solid tumor cells. To address this issue, we investigated the anticancer effects of Nutlin-3 in combination with Oridonin in osteosarcoma cells. We found that Oridonin at sub-toxic concentrations synergistically enhanced Nutlin-3-mediated cell viability inhibition in wild-type p53 U2OS and SJSA-1, but not in p53-mutant MNNG/HOS and in null-p53 Saos-2 osteosarcoma cell lines...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617441/concomitant-epigenetic-targeting-of-lsd1-and-hdac-synergistically-induces-mitochondrial-apoptosis-in-rhabdomyosarcoma-cells
#4
Tinka Haydn, Eric Metzger, Roland Schuele, Simone Fulda
The lysine-specific demethylase 1 (LSD1) is overexpressed in several cancers including rhabdomyosarcoma (RMS). However, little is yet known about whether or not LSD1 may serve as therapeutic target in RMS. We therefore investigated the potential of LSD1 inhibitors alone or in combination with other epigenetic modifiers such as histone deacetylase (HDAC) inhibitors. Here, we identify a synergistic interaction of LSD1 inhibitors (i.e., GSK690, Ex917) and HDAC inhibitors (i.e., JNJ-26481585, SAHA) to induce cell death in RMS cells...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28615521/ier3ip1-deficiency-leads-to-increased-%C3%AE-cell-death-and-decreased-%C3%AE-cell-proliferation
#5
Juan Sun, Decheng Ren
Mutations in the gene for Immediate Early Response 3 Interacting Protein 1 (IER3IP1) cause permanent neonatal diabetes mellitus in human. The mechanisms involved have not been determined and the role of IER3IP1 in β-cell survival has not been characterized. In order to determine if there is a molecular link between IER3IP1 deficiency and β-cell survival and proliferation, we knocked down Ier3ip1 gene expression in mouse MIN6 insulinoma cells. IER3IP1 suppression induced apoptotic cell death which was associated with an increase in Bim and a decrease in Bcl-xL...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613881/radical-reactions-affecting-polar-groups-in-threonine-peptide-ions
#6
Huong T H Nguyen, Prokopis C Andrikopoulos, Daniel Bim, Lubomir Rulisek, Andy Dang, Frantisek Turecek
Peptide cation-radicals containing the threonine residue undergo radical-induced dissociations upon collisional activation and photon absorption in the 210-400 nm range. Peptide cation-radicals containing a radical defect at the N-terminal residue, [●Ala-Thr-Ala-Arg+H]+, were generated by electron transfer dissociation of peptide dications and characterized by UV-VIS photodissociation action spectroscopy combined with time-dependent density functional theory (TD-DFT) calculations of absorption spectra, including thermal vibronic band broadening...
June 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28602396/mycoplasma-fermentans-deacetylase-promotes-mammalian-cell-stress-tolerance
#7
Qingzhou Cheng, Lijuan Wu, Rongfu Tu, Jun Wu, Wenqian Kang, Tong Su, Runlei Du, Wenbin Liu
Mycoplasma fermentans is a pathogenic bacterium that infects humans and has potential pathogenic roles in respiratory, genital and rheumatoid diseases. NAD(+)-dependent deacetylase is involved in a wide range of pathophysiological processes and our studies have demonstrated that expression of mycoplasmal deacetylase in mammalian cells inhibits proliferation but promotes anti-starvation stress tolerance. Furthermore, mycoplasmal deacetylase is involved in cellular anti-oxidation, which correlates with changes in the proapoptotic proteins BIK, p21 and BIM...
August 2017: Microbiological Research
https://www.readbyqxmd.com/read/28596542/leukocyte-bim-deficiency-does-not-impact-atherogenesis-in-ldlr-mice-despite-a-pronounced-induction-of-autoimmune-inflammation
#8
Lieve Temmerman, Marijke M Westra, Ilze Bot, Bart J M van Vlijmen, Niek Van Bree, Martine Bot, Kim L L Habets, Tom G H Keulers, Johan van der Vlag, Thomas G Cotter, Theo J C van Berkel, Erik A L Biessen
Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim (-/-) or wild type bone marrow transplanted ldlr (-/-) mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28590526/gas-phase-fragmentation-of-1-adamantylbisimidazolium-salts-and-their-complexes-with-cucurbit-7-uril-studied-using-selectively-2-h-labeled-guest-molecules
#9
Andrea Čablová, Michal Rouchal, Barbora Hanulíková, Jan Vícha, Lenka Dastychová, Zdeňka Prucková, Robert Vícha
RATIONALE: Bisimidazolium salts (BIMs) represent an interesting family of ditopic ligands that are used in the construction of supramolecular systems with hosts based on cyclodextrins or cucurbit[n]urils. Understanding the fragmentation mechanism of individual BIMs and how this mechanism changes after complexation with cucurbit[n]urils can bring new insight into the intrinsic host-guest relationship, thereby allowing utilization of mass spectrometry to describe binding behavior. METHODS: Selectively (2) H-labeled bisimidazolium salts were prepared and fully characterized by spectroscopic methods...
June 7, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28584208/establishment-of-a-novel-method-for-screening-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-mutations-in-lung-cancer
#10
Hong-Xia Tian, Xu-Chao Zhang, Zhen Wang, Jin-Ji Yang, Wei-Bang Guo, Zhi-Hong Chen, Yi-Long Wu
BACKGROUND: Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28582840/bim-may-be-a-poor-prognostic-biomarker-in-breast-cancer-patients-especially-in-those-with-luminal-a-tumors
#11
Yusufu Maimaiti, Lingling Dong, Aikebaier Aili, Tao Huang, Kelimu Abudureyimu
BACKGROUND: Bcl-2 interacting mediator of cell death (Bim) appears to have contradictory roles in cancer. It is uncertain whether Bim show prognostic significance in patients with breast cancer. OBJECTIVE: To investigate the correlation between Bim expression and clinicopathological characteristics of breast cancer and to evaluate Bim's effect on overall survival (OS). METHODS: We used immunohistochemistry (IHC) technique to detect the expression of Bim via tissue microarray in 275 breast cancer samples, Kaplan-Meier analysis to perform survival analysis, and Cox proportional hazards regression model to explore the risk factors of breast cancer...
May 12, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28581873/budget-impact-model-in-moderate-to-severe-psoriasis-vulgaris-assessing-effects-of-calcipotriene-and-betamethasone-dipropionate-foam-on-per-patient-standard-of-care-costs
#12
Carl V Asche, Minchul Kim, Steven R Feldman, Panagiotis Zografos, Minyi Lu
AIMS: To develop a budget impact model (BIM) for estimating the financial impact of formulary adoption and uptake of calcipotriene and betamethasone dipropionate (C/BD) foam (0.005%/0.064%) on the costs of biologics for treating moderate-to-severe psoriasis vulgaris in a hypothetical US healthcare plan with 1 million members. METHODS: This BIM incorporated epidemiologic data, market uptake assumptions, and drug utilization costs, simulating the treatment mix for patients who are candidates for biologics before (Scenario #1) and after (Scenario #2) the introduction of C/BD foam...
June 19, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28580175/differential-cytokine-withdrawal-induced-death-sensitivity-of-effector-t-cells-derived-from-distinct-human-cd8-memory-subsets
#13
Sasha E Larsen, Kelsey Voss, Eric D Laing, Andrew L Snow
CD8(+) central memory (CM) and effector memory (EM) T-cell subsets exhibit well-established differences in proliferative and protective capacity after infectious challenge. However, their relative sensitivity to apoptosis has been largely overlooked, despite the importance of programmed cell death in regulating effector T-cell homeostasis. Here we demonstrate that primary human effector T cells derived from the CD8(+) EM subset exhibit significantly higher sensitivity to cytokine withdrawal-induced cell death (CWID), a critical intrinsic apoptosis program responsible for culling cells once an infection is cleared and interleukin-2 (IL-2) levels diminish...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28573865/intrinsic-bond-energies-from-a-bonds-in-molecules-neural-network
#14
Kun Yao, John E Herr, Seth N Brown, John Parkhill
Neural networks are being used to make new types of empirical chemical models as inexpensive as force fields, but with accuracy similar to the ab initio methods used to build them. In this work, we present a neural network that predicts the energies of molecules as a sum of intrinsic bond energies. The network learns the total energies of the popular GDB9 database to a competitive MAE of 0.94 kcal/mol on molecules outside of its training set, is naturally linearly scaling, and applicable to molecules consisting of thousands of bonds...
June 15, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28566428/rational-combination-therapy-with-parp-and-mek-inhibitors-capitalizes-on-therapeutic-liabilities-in-ras-mutant-cancers
#15
Chaoyang Sun, Yong Fang, Jun Yin, Jian Chen, Zhenlin Ju, Dong Zhang, Xiaohua Chen, Christopher P Vellano, Kang Jin Jeong, Patrick Kwok-Shing Ng, Agda Karina B Eterovic, Neil H Bhola, Yiling Lu, Shannon N Westin, Jennifer R Grandis, Shiaw-Yih Lin, Kenneth L Scott, Guang Peng, Joan Brugge, Gordon B Mills
Mutant RAS has remained recalcitrant to targeted therapy efforts. We demonstrate that combined treatment with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors and mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors evokes unanticipated, synergistic cytotoxic effects in vitro and in vivo in multiple RAS mutant tumor models across tumor lineages where RAS mutations are prevalent. The effects of PARP and MEK inhibitor combinations are independent of BRCA1/2 and p53 mutation status, suggesting that the synergistic activity is likely to be generalizable...
May 31, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28554727/testosterone-modulates-foxo3a-and-p53-related-genes-to-protect-c2c12-skeletal-muscle-cells-against-apoptosis
#16
Lucía Pronsato, Lorena Milanesi, Andrea Vasconsuelo, Anabela La Colla
The loss of muscle mass and strength with aging, sarcopenia, is a prevalent condition among the elderly, associated with skeletal muscle dysfunction and enhanced muscle cell apoptosis. We have previously demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells, at different levels: morphological, biochemical and molecular. Since we have observed that testosterone reduces p-p53 and maintains the inactive state of FoxO3a transcription factor, induced by H2O2, we analyzed if the hormone was exerting its antiapoptotic effect at transcriptional level, by modulating pro and antiapoptotic genes associated to them...
May 26, 2017: Steroids
https://www.readbyqxmd.com/read/28554130/betulinic-acid-derivative-b10-inhibits-glioma-cell-proliferation-through-suppression-of-sirt1-acetylation-of-foxo3a-and-upregulation-of-bim-puma
#17
Longwei Huo, Xiaobin Bai, Yafei Wang, Maode Wang
Glioma is the most common primary malignant tumor of the central nervous system. B10 is a new glycosylated derivative of betulinic acid with enhanced cytotoxic activity. The present study was designed to explore the molecular mechanism underlying the anticancer effect of B10 in glioma cells. 25-50μM B10 resulted in a significant decrease of cell viability and BrdU incorporation. 25-50mg/kg B10 significantly reduced the implanted tumor weight and volume in nude mice. Activation of apoptosis was found in glioma cells when the cells were exposed to B10, as evidenced by increased number of TUNEL-stained cells, increased caspase 3 and 9 activities, and Bax and cleaved PARP expression...
May 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28553951/post-translational-control-of-t-cell-development-by-the-escrt-protein-chmp5
#18
Stanley Adoro, Kwang Hwan Park, Sarah E Bettigole, Raphael Lis, Hee Rae Shin, Heewon Seo, Ju Han Kim, Klaus-Peter Knobeloch, Jae-Hyuck Shim, Laurie H Glimcher
The acquisition of a protective vertebrate immune system hinges on the efficient generation of a diverse but self-tolerant repertoire of T cells by the thymus through mechanisms that remain incompletely resolved. Here we identified the endosomal-sorting-complex-required-for-transport (ESCRT) protein CHMP5, known to be required for the formation of multivesicular bodies, as a key sensor of thresholds for signaling via the T cell antigen receptor (TCR) that was essential for T cell development. CHMP5 enabled positive selection by promoting post-selection thymocyte survival in part through stabilization of the pro-survival protein Bcl-2...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28553347/mitomycin-c-induces-apoptosis-in-human-epidural-scar-fibroblasts-after-surgical-decompression-for-spinal-cord-injury
#19
Tao Sui, Da-Wei Ge, Lei Yang, Jian Tang, Xiao-Jian Cao, Ying-Bin Ge
Numerous studies have shown that topical application of mitomycin C after surgical decompression effectively reduces scar adhesion. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of mitomycin C on the proliferation and apoptosis of human epidural scar fibroblasts. Human epidural scar fibroblasts were treated with various concentrations of mitomycin C (1, 5, 10, 20, 40 μg/mL) for 12, 24 and 48 hours. Mitomycin C suppressed the growth of these cells in a dose- and time-dependent manner...
April 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28552963/bim-expression-in-endothelial-cells-and-pericytes-is-essential-for-regression-of-the-fetal-ocular-vasculature
#20
Shoujian Wang, Ismail S Zaitoun, Ryan P Johnson, Nasim Jamali, Zafer Gurel, Catherine M Wintheiser, Andreas Strasser, Volkhard Lindner, Nader Sheibani, Christine M Sorenson
Apoptosis plays a central role in developmental and pathological angiogenesis and vessel regression. Bim is a pro-apoptotic Bcl-2 family member that plays a prominent role in both developmental and pathological ocular vessel regression, and neovascularization. Endothelial cells (EC) and pericytes (PC) each play unique roles during vascular development, maintenance and regression. We recently showed that germline deletion of Bim results in persistent hyaloid vasculature, increased retinal vascular density and prevents retinal vessel regression in response to hyperoxia...
2017: PloS One
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