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https://www.readbyqxmd.com/read/28655204/trak2-a-novel-regulator-of-abca1-expression-cholesterol-efflux-and-hdl-biogenesis
#1
Nicole J Lake, Rachael L Taylor, Hugh Trahair, K N Harikrishnan, Joanne E Curran, Marcio Almeida, Hemant Kulkarni, Nigora Mukhamedova, Anh Hoang, Hann Low, Andrew J Murphy, Matthew P Johnson, Thomas D Dyer, Michael C Mahaney, Harald H H Göring, Eric K Moses, Dmitri Sviridov, John Blangero, Jeremy B M Jowett, Kiymet Bozaoglu
Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration...
June 26, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28655161/dysfunction-of-pla2g6-and-cyp2c44-associated-network-signals-imminent-carcinogenesis-from-chronic-inflammation-to-hepatocellular-carcinoma
#2
Meiyi Li, Chen Li, Wei-Xin Liu, Conghui Liu, Jingru Cui, Qingrun Li, Hong Ni, Yingcheng Yang, Chaochao Wu, Chunlei Chen, Xing Zhen, Tao Zeng, Mujun Zhao, Lei Chen, Jiarui Wu, Rong Zeng, Luonan Chen
Little is known about how chronic inflammation contributes to the progression of hepatocellular carcinoma (HCC), especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c-myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker (DNB) model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms...
June 26, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28655071/melatonin-rescues-mesenchymal-stem-cells-from-senescence-induced-by-the-uremic-toxin-p-cresol-via-inhibiting-mtor-dependent-autophagy
#3
Seung Pil Yun, Yong-Seok Han, Jun Hee Lee, Sang Min Kim, Sang Hun Lee
p-Cresol, found at high concentrations in the serum of chronic kidney failure patients, is known to cause cell senescence and other complications in different parts of the body. p-Cresol is thought to mediate cytotoxic effects through the induction of autophagy response. However, toxic effects of p-cresol on mesenchymal stem cells have not been elucidated. Thus, we aimed to investigate whether p-cresol induces senescence of mesenchymal stem cells, and whether melatonin can ameliorate abnormal autophagy response caused by p-cresol...
June 27, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28654916/inhibition-of-cox2-enhances-the-chemosensitivity-of-dichloroacetate-in-cervical-cancer-cells
#4
Bo Li, Xinzhe Li, Haojun Xiong, Peng Zhou, Zhenhong Ni, Teng Yang, Yan Zhang, Yijun Zeng, Jintao He, Fan Yang, Nan Zhang, Yuting Wang, Yingru Zheng, Fengtian He
Dichloroacetate (DCA), a traditional mitochondria-targeting agent, has shown promising prospect as a sensitizer in fighting against malignancies including cervical cancer. But it is unclear about the effect of DCA alone on cervical tumor. Moreover, previous reports have demonstrated that the increased cyclooxygenase-2 (COX2) expression is associated with chemoresistance and poor prognosis of cervical cancer. However, it is still unknown whether COX2 can affect the sensitivity of DCA in cervical cancer cells...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654910/microrna16-regulates-glioma-cell-proliferation-apoptosis-and-invasion-by-targeting-wip1-atm-p53-feedback-loop
#5
Xiao-Hong Zhan, Qiu-Yan Xu, Rui Tian, Hong Yan, Min Zhang, Jing Wu, Wei Wang, Jie He
The present study aimed to investigate the role and underlying mechanisms of microRNA16 (miR-16) on proliferation, apoptosis and invasion of glioma cells. The cell models of miR-16 upregulation and Negative control group (NC group) were built. The cell functions of different groups were detected by colony formation assay, transwell chamber assay, proliferation, apoptosis and cycle experiments. The intracranial orthotopic transplantation animal models were built to different groups: miR-16 agomir group, miR-16 antagomir group and their NC group...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654907/knockdown-of-malat1-expression-inhibits-huvec-proliferation-by-upregulation-of-mir-320a-and-downregulation-of-foxm1-expression
#6
Jian-Yong Sun, Zheng-Wei Zhao, Wei-Miao Li, Guang Yang, Peng-Yu Jing, Pei Li, Hai-Zhou Dang, Zhao Chen, Yong-An Zhou, Xiao-Fei Li
Regulation of cancer angiogenesis could be a useful strategy in cancer therapy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA), and can induce cancer cell proliferation, while lncRNAs, generally are able to act as microRNA (miRNA) sponges. The latter is a type of competitive endogenous RNA (ceRNA) that regulates expression of the targeting miRNAs and protein-coding genes. This study investigated the proliferative role of MALAT1 in human umbilical vein endothelial cells (HUVECs) and the underlying molecular events...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654903/synergistic-suppression-of-t-8-21-positive-leukemia-cell-growth-by-combining-oridonin-and-mapk1-erk2-inhibitors
#7
Pavel Spirin, Timofey Lebedev, Natalia Orlova, Alexey Morozov, Nadezhda Poymenova, Sergey E Dmitriev, Anton Buzdin, Carol Stocking, Kovalchuk Olga, Prassolov Vladimir
One of the most common chromosomal translocations in acute myeloid leukemia is t(8;21)(q22;q22), which results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO. Therefore, this oncoprotein is considered to be a pertinent and promising target for treating t(8;21) leukemia. Previously, we have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell survival and determined that the protein ERK2 can mediate activation of most of these pathways...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654888/mek-inhibition-enhances-efficacy-of-bacillus-calmette-gu%C3%A3-rin-on-bladder-cancer-cells-by-reducing-release-of-toll-like-receptor-2-activated-antimicrobial-peptides
#8
Young Mi Whang, Su Bin Jin, Serk In Park, In Ho Chang
Bacillus Calmette-Guérin (BCG) is one of the standard treatment options for non-muscle-invasive bladder cancer. The details of the biological defense mechanisms against BCG remain unclear. Here, we investigated whether BCG-induced release of antimicrobial peptides (AMPs; e.g., human β-defensin-2, -3, and cathelicidin) is involved with mitogen-activated protein kinase (MAPK) pathways, and investigated the enhanced anticancer effect of BCG through the down-regulation of Toll-like receptors (TLRs) and MAPK pathways in bladder cancer cells...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654887/glucose-oxidase-initiated-cascade-catalysis-for-sensitive-impedimetric-aptasensor-based-on-metal-organic-frameworks-functionalized-with-pt-nanoparticles-and-hemin-g-quadruplex-as-mimicking-peroxidases
#9
Xingxing Zhou, Shijing Guo, Jiaxi Gao, Jianmin Zhao, Shuyan Xue, Wenju Xu
Based on cascade catalysis amplification driven by glucose oxidase (GOx), a sensitive electrochemical impedimetric aptasensor for protein (carcinoembryonic antigen, CEA as tested model) was proposed by using Cu-based metal-organic frameworks functionalized with Pt nanoparticles, aptamer, hemin and GOx (Pt@CuMOFs-hGq-GOx). CEA aptamer loaded onto Pt@CuMOFs was bound with hemin to form hemin@G-quadruplex (hGq) with mimicking peroxidase activity. Through sandwich-type reaction of target CEA and CEA aptamers (Apt1 and Apt2), the obtained Pt@CuMOFs-hGq-GOx as signal transduction probes (STPs) was captured to the modified electrode interface...
June 20, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28654884/specific-and-selective-probes-for-staphylococcus-aureus-from-phage-displayed-random-peptide-libraries
#10
Laura M De Plano, Santina Carnazza, Grazia M L Messina, Maria Giovanna Rizzo, Giovanni Marletta, Salvatore P P Guglielmino
Staphylococcus aureus is a major human pathogen causing health care-associated and community-associated infections. Early diagnosis is essential to prevent disease progression and to reduce complications that can be serious. In this study, we selected, from a 9-mer phage peptide library, a phage clone displaying peptide capable of specific binding to S. aureus cell surface, namely St.au9IVS5 (sequence peptide RVRSAPSSS).The ability of the isolated phage clone to interact specifically with S. aureus and the efficacy of its bacteria-binding properties were established by using enzyme linked immune-sorbent assay (ELISA)...
June 17, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28654796/srpx2-an-independent-prognostic-marker-promotes-cell-migration-and-invasion-in-hepatocellular-carcinoma
#11
Xiaobo Lin, Weiping Chang, Yuan Wang, Ming Tian, Zhaoxiang Yu
Sushi repeat-containing protein X-linked 2 (SRPX2), a novel chondroitin sulfate proteoglycan, is overexpressed in human cancer. Recent studies have reported that SRPX2 overexpression is observed in gastrointestinal cancer, and promotes migration and invasion of cancer cells. While, the clinical significance and biological function of SRPX2 remain rarely known in hepatocellular carcinoma (HCC). Here, we found that the levels of SRPX2 in HCC tissues were notably overexpressed compared to non-cancerous specimens...
June 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28654764/deep-proteome-profiling-reveals-common-prevalence-of-mzb1-positive-plasma-b-cells-in-human-lung-and-skin-fibrosis
#12
Herbert B Schiller, Christoph H Mayr, Gabriela Leuschner, Maximilian Strunz, Claudia Staab-Weijnitz, Stefan Preisendörfer, Beate Eckes, Pia Moinzadeh, Thomas Krieg, David A Schwartz, Rudolf A Hatz, Jürgen Behr, Matthias Mann, Oliver Eickelberg
RATIONALE: Analyzing the molecular heterogeneity of different forms of organ fibrosis may reveal common and specific factors and thus identify potential future therapeutic targets. OBJECTIVES: We sought to use proteome-wide profiling of human tissue fibrosis to (1) identify common and specific signatures across endstage interstitial lung disease (ILD) cases, (2) characterize ILD subgroups in an unbiased fashion, and (3) identify common and specific features of lung and skin fibrosis...
June 27, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28654754/potential-strategies-to-target-protein-protein-interactions-in-the-dna-damage-response-and-repair-pathways
#13
Naoaki Fujii
This review article discusses some insights about generating novel mechanistic inhibitors of the DNA damage response and repair (DDR) pathways by focusing on protein-protein interactions (PPIs) of the key DDR components. General requirements for PPI strategies, such as selecting the target PPI site on the basis of its functionality, are discussed first. Next, based on functional rationale and biochemical feasibility to identify a PPI inhibitor, 26 PPIs in DDR pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specifically discussed for inhibitor discovery to benefit cancer therapies using a DNA-damaging agent...
June 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28654752/in-silico-prediction-of-the-toxic-potential-of-lupeol
#14
Manuel Antonio Ruiz-Rodríguez, Angelo Vedani, Ana Lidia Flores-Mireles, Manuel Humberto Chairez-Ramirez, Jose Alberto Gallegos-Infante, Ruben F Gonzalez-Laredo
Lupeol is a natural triterpenoid found in many plant species such as mango. This compound is the principal active component of many traditional herbal medicines. In the past decade, a considerable number of publications dealt with lupeol and its analogues due to the interest in their pharmacological activities against cancer, inflammation, arthritis, diabetes, and heart disease. To identify further potential applications of lupeol and its analogues, it is necessary to investigate their mechanisms of action, particularly, their interaction with off-target proteins that may trigger adverse effects or toxicity...
June 27, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28654729/signor-a-database-of-causal-relationships-between-biological-entities-a-short-guide-to-searching-and-browsing
#15
Prisca Lo Surdo, Alberto Calderone, Gianni Cesareni, Livia Perfetto
SIGNOR (http://signor.uniroma2.it), the SIGnaling Network Open Resource, is a database designed to store experimentally validated causal interactions, i.e., interactions where a source entity has a regulatory effect (up-regulation, down-regulation, etc.) on a second target entity. SIGNOR acts both as a source of signaling information and a support for data analysis, modeling, and prediction. A user-friendly interface features the ability to search entries for any given protein or group of proteins and to display their interactions graphically in a network view...
June 27, 2017: Current Protocols in Bioinformatics
https://www.readbyqxmd.com/read/28654706/differential-effects-of-heat-shock-protein-90-and-serine-1179-phosphorylation-on-endothelial-nitric-oxide-synthase-activity-and-on-its-cofactors
#16
Yuanzhuo Chen, Bojie Jiang, Yugang Zhuang, Hu Peng, Weiguo Chen
Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. Previous studies showed that bovine eNOS serine 1179 (Serine 1177 for human eNOS) phosphorylation enhanced NO synthesis. Meanwhile, heat shock protein 90 (Hsp90) plays a critical role in maintenance of eNOS structure and function. However, the regulatory difference and importance between Serine 1179 phosphorylation and Hsp90 on eNOS activity have not been evaluated. In current studies, S1179D eNOS was employed to mimic phospho-eNOS and exhibited markedly increased enzyme activity than wild type eNOS (WT eNOS)...
2017: PloS One
https://www.readbyqxmd.com/read/28654641/biological-effects-of-the-hypomagnetic-field-an-analytical-review-of-experiments-and-theories
#17
Vladimir N Binhi, Frank S Prato
During interplanetary flights in the near future, a human organism will be exposed to prolonged periods of a hypomagnetic field that is 10,000 times weaker than that of Earth's. Attenuation of the geomagnetic field occurs in buildings with steel walls and in buildings with steel reinforcement. It cannot be ruled out also that a zero magnetic field might be interesting in biomedical studies and therapy. Further research in the area of hypomagnetic field effects, as shown in this article, is capable of shedding light on a fundamental problem in biophysics-the problem of primary magnetoreception...
2017: PloS One
https://www.readbyqxmd.com/read/28654435/myasthenia-gravis-new-developments-in-research-and-treatment
#18
Amelia Evoli
PURPOSE OF REVIEW: Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than as a single disease. This review summarizes recent advances in pathophysiology which confirm the disease heterogeneity, and may help find disease-targeted and patient-targeted therapies. RECENT FINDINGS: Antibodies to the acetylcholine receptor, the muscle-specific tyrosine kinase and the lipoprotein receptor protein 4, characterize disease subtypes with distinct clinical traits and immune-pathogenic mechanisms...
June 24, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28654422/parp1-expression-and-its-correlation-with-survival-is-tumour-molecular-subtype-dependent-in-glioblastoma
#19
Balázs Murnyák, Mahan C Kouhsari, Rotem Hershkovitch, Bernadette Kálmán, György Marko-Varga, Álmos Klekner, Tibor Hortobágyi
Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1's expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1's associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654419/affimers-proteins-are-versatile-and-renewable-affinity-reagents
#20
Christian Tiede, Robert Bedford, Sophie J Heseltine, Gina Smith, Imeshi Wijetunga, Rebecca Ross, Danah AlQallaf, Ashley Pe Roberts, Alexander Balls, Alistair Curd, Ruth E Hughes, Heather Martin, Sarah R Needham, Laura C Zanetti-Domingues, Yashar Sadigh, Thomas P Peacock, Anna A Tang, Naomi Gibson, Hannah Kyle, Geoffrey W Platt, Nicola Ingram, Thomas Taylor, Louise P Coletta, Iain Manfield, Margaret Knowles, Sandra Bell, Filomena Esteves, Azhar Maqbool, Raj K Prasad, Mark Drinkhill, Robin S Bon, Vikesh Patel, Sarah A Goodchild, Marisa Martin-Fernandez, Ray J Owens, Joanne E Nettleship, Michael E Webb, Michael Harrison, Jonathan D Lippiat, Sreenivasan Ponnambalam, Michelle Peckham, Alastair Smith, Paul Ko Ferrigno, Matt Johnson, Michael J McPherson, Darren Charles Tomlinson
Molecular recognition reagents are key tools for understanding biological processes and are used universally by scientists to study protein expression, localisation and interactions. Antibodies remain the most widely used of such reagents and many show excellent performance, although some are poorly characterised or have stability or batch variability issues, supporting the use of alternative binding proteins as complementary reagents for many applications. Here we report on the use of Affimer proteins as research reagents...
June 27, 2017: ELife
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