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https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#1
Janina-Miriam Noy, Hongxu Lu, Philip Hogg, Jia-Lin Yang, Martina H Stenzel
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anti-cancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition fragmentation chin transfer) polymerization with poly(polyethylene glycol methyl ether methacrylate) (PEGMA) as comonomer and poly(methylmethacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt...
January 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29346133/dexmedetomidine-impairs-diaphragm-function-and-increases-oxidative-stress-but-does-not-aggravate-diaphragmatic-atrophy-in-mechanically-ventilated-rats
#2
Thomas Breuer, Christian Bleilevens, Rolf Rossaint, Gernot Marx, Julian Gehrenkemper, Henning Dierksen, Antoine Delpierre, Joachim Weis, Ghislaine Gayan-Ramirez, Christian S Bruells
BACKGROUND: Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients' mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction. METHODS: Twenty-four rats were separated into three groups (n = 8/group)...
January 18, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29346075/human-papillomavirus-e6-interaction-with-cellular-pdz-domain-proteins-modulates-yap-nuclear-localization
#3
Sydney Webb Strickland, Nicole Brimer, Charles Lyons, Scott B Vande Pol
HPV E6 oncoproteins associate with cellular PDZ proteins. In addition to previously identified cellular PDZ proteins, we found association of the HPV16 E6 PBM with the Dystrophin Glycoprotein Complex, LRCC1, and SLC9A3R2. HPV18 E6 had additional associations when lysates from adenomatous cell lines were used including LRPPRC, RLGAPB, EIF3A, SMC2 and 3, AMOT, AMOTL1, and ARHGEF1; some of these cellular PDZ proteins are implicated in the regulation of the YAP1 transcriptional co-activator. In keratinocytes, nuclear translocation of YAP1 was promoted by the complete HPV-16 genome, or by expression of the individual E6 or E7 oncoproteins; the activity of E6 required an intact PBM at the carboxy-terminus...
January 12, 2018: Virology
https://www.readbyqxmd.com/read/29345557/co-registration-of-cone-beam-ct-and-preoperative-mri-for-improved-accuracy-of-electrode-localization-following-cochlear-implantation
#4
A S Dragovic, A K Stringer, L Campbell, C Shaul, S J O'Leary, R J Briggs
OBJECTIVES: To investigate the clinical usefulness and practicality of co-registration of Cone Beam CT (CBCT) with preoperative Magnetic Resonance Imaging (MRI) for intracochlear localization of electrodes after cochlear implantation. METHODS: Images of 20 adult patients who underwent CBCT after implantation were co-registered with preoperative MRI scans. Time taken for co-registration was recorded. The images were analysed by clinicians of varying levels of expertise to determine electrode position and ease of interpretation...
January 18, 2018: Cochlear Implants International
https://www.readbyqxmd.com/read/29345269/tributyltin-induces-epigenetic-changes-and-decreases-the-expression-of-nuclear-respiratory-factor-1
#5
Saki Hanaoka, Keishi Ishida, Saki Tanaka, Shuichiro Sakamoto, Katsuhiro Okuda, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Tributyltin (TBT), a common organotin environmental pollutant, has been widely used as a component of marine antifouling paints. We previously reported that exposure to TBT inhibits the expression and DNA binding of nuclear respiratory factor-1 (NRF-1) and causes neurotoxicity. In the present study, we focused on the epigenetic effects of TBT and investigated whether TBT decreases NRF-1 expression via epigenetic modifications in SH-SY5Y human neuroblastoma cells. First, we found that exposure to 300 nM TBT decreases NRF-1 expression...
January 18, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29344983/anti-inflammatory-effect-of-4-methylcyclopentadecanonein-rats-submitted-to-ischemic-stroke
#6
Yan Jin, Fang Wei, Xiaoli Dai, Min Qi, Yukui Ma
The present study aimed to investigate the anti-inflammatory effect of 4-methylcyclopentadecanone (4-MCPC) in rats suffering from a cerebral ischemia/ reperfusion (I/R) injury. In this study, the focal cerebral ischemia in rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase (MPO) activity and TNF-α and IL-1β levels in the ischemic cerebral cortex were determined by ELISA, while nuclear translocation of NF-κB p65 subunit and expression of p-IκBα were investigated by western blotting...
January 18, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29344311/gilz-activin-a-as-a-novel-signaling-axis-orchestrating-mesenchymal-stem-cell-and-th17-cell-interplay
#7
Patricia Luz-Crawford, Gabriel Espinosa-Carrasco, Natacha Ipseiz, Rafael Contreras, Gautier Tejedor, Daniel A Medina, Ana-Maria Vega-Letter, Devi Ngo, Eric F Morand, Jérôme Pène, Javier Hernandez, Christian Jorgensen, Farida Djouad
Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce chronic inflammation through the active release of mediators. Recently, we showed that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved in their therapeutic effect by promoting the generation of regulatory T cells. However, the mechanisms underlying this pivotal role of Gilz remain elusive. Methods and Results In this study, we have uncovered evidence that Gilz modulates the phenotype and function of Th1 and Th17 cells likely by upregulating the level of Activin A and NO2 secreted by MSC...
2018: Theranostics
https://www.readbyqxmd.com/read/29344294/cardiomyocyte-restricted-low-density-lipoprotein-receptor-related-protein-6-lrp6-deletion-leads-to-lethal-dilated-cardiomyopathy-partly-through-drp1-signaling
#8
Zhidan Chen, Yang Li, Ying Wang, Juying Qian, Hong Ma, Xiang Wang, Guoliang Jiang, Ming Liu, Yanpeng An, Leilei Ma, Le Kang, Jianguo Jia, Chunjie Yang, Guoping Zhang, Ying Chen, Wei Gao, Mingqiang Fu, Zheyong Huang, Huiru Tang, Yichun Zhu, Junbo Ge, Hui Gong, Yunzeng Zou
Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group...
2018: Theranostics
https://www.readbyqxmd.com/read/29344131/a-novel-variant-translocation-1-9-p22-q34-resulting-in-a-dek-nup214-fusion-gene-in-a-patient-with-acute-myeloid-leukemia-a-case-report
#9
Qishan Hao, Qi Zhang, Chengwen Li, Shuning Wei, Qinghua Li, Yang Song, Yingchang Mi
The present case report describes a 46-year-old female patient diagnosed with M4 acute myeloid leukemia (AML), accompanied with a t(1;9)(p22;q34) chromosomal abnormality. Transcriptome sequencing identified a DEK proto-oncogene (DEK)/nucleoporin (NUP)214 fusion gene, which results from the t(6;9)(p23;q34) chromosomal translocation. Polymerase chain reaction analysis and fluorescence in situ hybridization were used to verify the existence of the DEK/NUP214 fusion gene. Few patients with AML with the t(6;9)(p23;q34) chromosomal translocation have been reported to have other chromosomal or karyotype changes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344112/zgdhu-1-for-cancer-therapy
#10
Jinlin Liu, Liannv Qiu, Jun Xia, Sufeng Chen, Xiping Yu, Yonglie Zhou
N,N'-di-(m-methylphenyl)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) is a novel tetrazine derivative that was initially designed and produced by Professor W.X. Hu, and which has been reported by our group to exhibit antitumor activity. Accumulating evidence suggests that the anticancer mechanisms of ZGDHu-1 may be involved indifferent biological activities, particularly in acute myeloid leukemia (AML) cells. At a high concentration, ZGDHu-1 has been demonstrated to inhibit the proliferation of the leukemia cells by arresting the cell cycle at the G2/M phase, and by inducing cell apoptosis via inducing the accumulation of reactive oxygen species, the translocation of phosphatidylserine across the plasma membrane and the loss of mitochondrial membrane potential...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344090/overexpression-of-the-proneural-transcription-factor-ascl1-in-chronic-lymphocytic-leukemia-with-a-t-12-14-q23-2-q32-3
#11
Theodora Malli, Melanie Rammer, Sabrina Haslinger, Jonathan Burghofer, Sonja Burgstaller, Hans-Christian Boesmueller, Renate Marschon, Wolfgang Kranewitter, Martin Erdel, Sabine Deutschbauer, Gerald Webersinke
Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis by deregulating the expression of the IGH-partner genes. Identification of these genes and investigation of the downstream effects of their deregulation can reveal disease-causing mechanisms. Case presentation: We report on the molecular characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29344006/histone-deacetylase-2-hdac2-attenuates-lipopolysaccharide-lps-induced-inflammation-by-regulating-pai-1-expression
#12
Wen-Feng Fang, Yu-Mu Chen, Chiung-Yu Lin, Hui-Lin Huang, Hua Yeh, Ya-Ting Chang, Kuo-Tung Huang, Meng-Chih Lin
Background: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, and is primarily characterized by an uncontrolled systemic inflammatory response. In the present study, we developed an effective adjunct therapy mediated by a novel mechanism, to attenuate overt inflammation. LPS-treated macrophages were adopted as an in vitro model of endotoxin-induced inflammation during sepsis. Experiments were carried out using primary mouse peritoneal macrophages and the murine macrophage cell line RAW264...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29343880/novel-application-of-loop-mediated-isothermal-amplification-for-rapid-detection-of-gene-translocation
#13
Ibu Matsuzaki, Hideto Iguchi, Yurina Mikasa, Hiromu Morishita, Katsuya Okuda, Keita Nakaguchi, Yuki Mori, Yoshifumi Iwahashi, Kenji Warigaya, Masakazu Fujimoto, Fumiyoshi Kojima, Shin-Ichi Murata
Identification of fusion genes in cancer is essential for pathological diagnosis and clinical therapy. Although methods for detection of fusion genes, such as fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (PCR), have been developed in last two decades, these methods are not ideal for detection of these genetic alterations owing to their high cost and time-consuming procedures. In this study, we developed novel application for detection of gene translocations using loop-mediated isothermal amplification (LAMP)...
December 26, 2017: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/29343861/sensing-native-protein-solution-structures-using-a-solid-state-nanopore-unraveling-the-states-of-vegf
#14
Nitinun Varongchayakul, Diana Huttner, Mark W Grinstaff, Amit Meller
Monitoring individual proteins in solution while simultaneously obtaining tertiary and quaternary structural information is challenging. In this study, translocation of the vascular endothelial growth factor (VEGF) protein through a solid-state nanopore (ssNP) produces distinct ion-current blockade amplitude levels and durations likely corresponding to monomer, dimer, and higher oligomeric states. Upon changing from a non-reducing to a reducing condition, ion-current blockage events from the monomeric state dominate, consistent with the expected reduction of the two inter-chain VEGF disulfide bonds...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343851/ndrg2-facilitates-colorectal-cancer-differentiation-through-the-regulation-of-skp2-p21-p27-axis
#15
Liangliang Shen, Xuan Qu, Huichen Li, Chunsheng Xu, Mengying Wei, Qinhao Wang, Yi Ru, Bei Liu, Yuqiao Xu, Kai Li, Junbi Hu, Lifeng Wang, Yongzheng Ma, Mengyang Li, Xiaofeng Lai, Lei Gao, Kaichun Wu, Libo Yao, Jianyong Zheng, Jian Zhang
Poorly differentiated colorectal cancers (CRCs) are more aggressive and lack targeted therapies. We and others previously reported the predominant role of tumor-suppressor NDRG2 in promoting CRC differentiation, but the underlying mechanism is largely unknown. Herein, we demonstrate that NDRG2 induction of CRC cell differentiation is dependent on the repression of E3 ligase Skp2 activity. In patients and Ndrg2 knockout mice, NDRG2 and Skp2 are negatively correlated and associated with cell differentiation stage...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29343624/inhalation-of-peptide-loaded-nanoparticles-improves-heart-failure
#16
Michele Miragoli, Paola Ceriotti, Michele Iafisco, Marco Vacchiano, Nicolò Salvarani, Alessio Alogna, Pierluigi Carullo, Gloria Belén Ramirez-Rodríguez, Tatiana Patrício, Lorenzo Degli Esposti, Francesca Rossi, Francesca Ravanetti, Silvana Pinelli, Rossella Alinovi, Marco Erreni, Stefano Rossi, Gianluigi Condorelli, Heiner Post, Anna Tampieri, Daniele Catalucci
Peptides are highly selective and efficacious for the treatment of cardiovascular and other diseases. However, it is currently not possible to administer peptides for cardiac-targeting therapy via a noninvasive procedure, thus representing scientific and technological challenges. We demonstrate that inhalation of small (<50 nm in diameter) biocompatible and biodegradable calcium phosphate nanoparticles (CaPs) allows for rapid translocation of CaPs from the pulmonary tree to the bloodstream and to the myocardium, where their cargo is quickly released...
January 17, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#17
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343555/antagonism-of-integrin-cd11b-affords-protection-against-endotoxin-shock-and-polymicrobial-sepsis-via-attenuation-of-hmgb1-nucleocytoplasmic-translocation-and-extracellular-release
#18
Huiting Zhou, Yanhong Li, Huan Gui, He Zhao, Ming Wu, Gang Li, Yiping Li, Zhenjiang Bai, Zhimin Yin, H Paul Redmond, Jian Wang, Jiang Huai Wang, Zhihui Zhao
High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a critical role in sepsis by acting as a key "late-phase" inflammatory mediator. Integrin CD11b is essential for inflammatory cell activation and migration, thus mediating inflammatory responses. However, it is unclear whether CD11b participates in the development of sepsis. In this study, we report that CD11b contributes to LPS-induced endotoxin shock and microbial sepsis, as antagonism of CD11b with the CD11b blocking Ab or CD11b inhibitor Gu-4 protects mice against LPS- and microbial sepsis-related lethality, which is associated with significantly diminished serum HMGB1 levels...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29343547/molecular-pathways-for-immune-recognition-of-preproinsulin-signal-peptide-in-type-1-diabetes
#19
Deborah Kronenberg-Versteeg, Martin Eichmann, Mark A Russell, Arnoud de Ru, Beate Hehn, Norkhairin Yusuf, Peter A van Veelen, Sarah J Richardson, Noel G Morgan, Marius K Lemberg, Mark Peakman
The signal peptide region of preproinsulin (PPI) contains epitopes targeted by human leucocyte antigen-A (HLA-A)-restricted (HLA-A0201, A2402) cytotoxic T-cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended PPI epitope discovery to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles revealing that 4/6 alleles present epitopes derived from the signal peptide region. During co-translational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical, proteasome-directed pathway...
January 17, 2018: Diabetes
https://www.readbyqxmd.com/read/29343501/sequential-bmp7-tgf-%C3%AE-1-signaling-and-microbiota-instruct-mucosal-langerhans-cell-differentiation
#20
Tal Capucha, Noam Koren, Maria Nassar, Oded Heyman, Tsipora Nir, Maayan Levy, Gili Zilberman-Schapira, Katya Zelentova, Luba Eli-Berchoer, Martin Zenke, Thomas Hieronymus, Asaf Wilensky, Herve Bercovier, Eran Elinav, Björn E Clausen, Avi-Hai Hovav
Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction...
January 17, 2018: Journal of Experimental Medicine
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