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Xiao-Dong Li, Xin-Rui Zhang, Zhi-Hao Li, Yang Yang, Duo Zhang, Heng Zheng, Shu-Ying Dong, Juan Chen, Xian-Dong Zeng
BACKGROUND: Dendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 (MMP-13), a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs). The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis...
March 20, 2017: Chinese Medical Journal
Jalal Babaie, Mohammad Sayyah, Pezhman Fard-Esfahani, Majid Golkar, Kourosh Gharagozli
Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One-third of world's population is infected with Toxoplasma gondii (T. gondii). This intracellular parasite has high tendency to excitable cells including neurons. We assessed seizure susceptibility and involvement of dopaminergic system in male mice with acute and chronic T. gondii infection. Mice were infected by intraperitoneal injection of T. gondii cysts. Acute and chronic stages of infection were determined by quantification of SAG1/BAG1 transcripts and level of repetitive REP-529 sequence in the brain of mice by real-time PCR...
March 7, 2017: Journal of Neuroscience Research
Dong-Pyo Hong, Joshua B Radke, Michael W White
The Toxoplasma biology that underlies human chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite stage. We investigated the roles of two alkaline-stress-induced ApiAP2 transcription factors, AP2IV-3 and AP2IX-9, in bradyzoite development. These factors were expressed in two overlapping waves during bradyzoite development, with AP2IX-9 increasing expression earlier than AP2IV-3, which peaked as AP2IX-9 expression was declining. Disruption of the AP2IX-9 gene enhanced, while deletion of AP2IV-3 gene decreased, tissue cyst formation, demonstrating that these factors have opposite functions in bradyzoite development...
January 2017: MSphere
Iikki Donner, Riku Katainen, Tomas Tanskanen, Eevi Kaasinen, Mervi Aavikko, Kristian Ovaska, Miia Artama, Eero Pukkala, Lauri A Aaltonen
Esophageal cancer is common worldwide, and often fatal. The major histological subtype is esophageal squamous cell carcinoma (ESCC). ESCC shows familial aggregation and high heritability. Mutations in RHBDF2 cause tylosis, a very rare disorder characterized by high life-time risk of ESCC, but no other well-established predisposition genes have been identified. To identify candidate susceptibility variants for ESCC we utilized the Population Information System and the Finnish cancer registry to find study materials by clustering ESCC patients by family name at birth and municipality at birth...
February 6, 2017: Genes, Chromosomes & Cancer
Christine Hantouche, Brittany Williamson, William C Valinsky, Joshua Solomon, Alvin Shrier, Jason C Young
Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity...
February 10, 2017: Journal of Biological Chemistry
Marina Gonçalves Diniz, Alessandra Pires Duarte, Rolando A Villacis, Bruna V A Guimarães, Luiz Cláudio Pires Duarte, Sílvia R Rogatto, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes
BACKGROUND: Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors. METHODS: We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status...
September 28, 2016: Journal of Oral Pathology & Medicine
Ugur Serbes, Ozlem D Ozsoylemez, Gul Ozcan
We aim to determine the regulation of apoptosis by paclitaxel-induced and understand cancer dynamics to treatment targets for HeLa cells by identifying decrease/increase genes expression on HeLa cells. In this study, the anti-tumor effects of Paclitaxel (PAC) on HeLa cells have been studied in order to determine the cellular and molecular mechanisms of these effects. PAC has been applied to HeLa cells in 6 different doses (3, 7.5, 15, 30, 60, 120 nM) for 48 hours and the IC50 dose MTT method, has been determined with apoptic index (AI) DAPI...
2016: Current Pharmaceutical Biotechnology
Yifeng Sun, Likun Hou, Yu Yang, Huikang Xie, Yang Yang, Zhigang Li, Heng Zhao, Wen Gao, Bo Su
BACKGROUND: In this study, we investigated the contribution of a gene expression-based signature (composed of BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, SH3BGR) to survival prediction for early-stage lung adenocarcinoma categorized by the new International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) classification. We also aimed to verify whether gene signature improves the risk discrimination of IASLC/ATS/ERS classification in early-stage lung adenocarcinoma...
2016: OncoTargets and Therapy
M A Zaimy, A Jebali, B Bazrafshan, S Mehrtashfar, S Shabani, A Tavakoli, S H Hekmatimoghaddam, A Sarli, H Azizi, P Izadi, B Kazemi, A Shojaei, A Abdalaian, J Tavakkoly-Bazzaz
The aim of this study was to evaluate an engineered nanostructure to silence five important oncogenes, including BAG1, MDM2, Bcl-2, BIRC5 (survivin) and XIAP, in acute myeloid leukemia subtype 2 (AML-M2). The smart nanostructures were functionalized gold nanoparticles (FGNs) containing five antisense oligonucleotides (AOs) and one anti-CD33(+)/CD34(+) aptamer. First, the best AO for each gene was selected with the OligoWalk online software, and then different arrangements of AOs were evaluated with the RNAstructure software...
September 2016: Cancer Gene Therapy
Jennifer N Rauch, Erik R P Zuiderweg, Jason E Gestwicki
Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70. The release of nucleotide is known to be mediated by interactions between the conserved BAG domain and the Hsc70 NBD...
September 16, 2016: Journal of Biological Chemistry
Christian Behl
Human BAG (Bcl-2-associated athanogene) proteins form a family of antiapoptotic proteins that currently consists of six members (BAG1-6) all sharing the BAG protein domain from which the name arises. Via this domain, BAG proteins bind to the heat shock protein 70 (Hsp70), thereby acting as a co-chaperone regulating the activity of Hsp70. In addition to their antiapoptotic activity, all human BAG proteins have distinct functions in health and disease, and BAG3 in particular is the focus of many investigations...
August 2016: Trends in Pharmacological Sciences
Theresa A Koleck, Yvette P Conley
Research is beginning to suggest that the presence and/or severity of symptoms reported by breast cancer survivors may be associated with disease-related factors of cancer. In this article, we present a novel approach to the identification and prioritization of biologically plausible candidate genes to investigate relationships between genomic variation and symptom variability in breast cancer survivors. Cognitive dysfunction is utilized as a representative breast cancer survivor symptom to elucidate the conceptualization of and justification for our cellular, disease-based approach to address symptom variability in cancer survivors...
2016: Breast Cancer: Targets and Therapy
Nezar Noor Al-Hebshi, Shiyong Li, Akram Thabet Nasher, Maged El-Setouhy, Rashad Alsanosi, Jan Blancato, Christopher Loffredo
The study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty archival OSCC samples, 15 of which with a history of shammah exposure, were whole-exome sequenced at an average depth of 127×. Somatic mutations were identified using a novel, matched controls-independent filtration algorithm. CODEX and Exomedepth coupled with a novel, Database of Genomic Variant-based filter were employed to call somatic gene-copy number variations...
July 15, 2016: International Journal of Cancer. Journal International du Cancer
Xiangzhi Li, Di Chen, Qianqian Hua, Yujing Wan, Lina Zheng, Yangyang Liu, Jiaxin Lin, Changwang Pan, Xin Hu, Feng Tan
Autophagy process in Toxoplasma gondii plays a vital role in regulating parasite survival or death. Thus, once having an understanding of certain effects of autophagy on the transformation of tachyzoite to bradyzoite this will allow us to elucidate the function of autophagy during parasite development. Herein, we used three TgAtg proteins involved in Atg8 conjugation system, TgAtg3, TgAtg7 and TgAtg8 to evaluate the autophagy level in tachyzoite and bradyzoite of Toxoplasma in vitro based on Pru TgAtg7-HA transgenic strains...
April 2016: Parasitology
Yadi Wang, Minwen Ha, Jingsong Liu, Ping Li, Wenlu Zhang, Xuan Zhang
The present study aimed to address the pharmacogenetic role of BAG1 in platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) and in cultured human lung adenocarcinoma A549 cells. A total of 108 NSCLC patients (stages I-IIIA) were treated with a standard chemotherapy regimen of cisplatin plus vinorelbine. Additionally, in vitro cultured A549 cells were treated with cisplatin in the presence or absence of tunicamycin. Cell proliferation was determined by MTT assay and protein levels were assessed via western blot analysis...
February 2016: Oncology Letters
Aline Ketefian, Michelle R Jones, Ronald M Krauss, Yii-Der I Chen, Richard S Legro, Ricardo Azziz, Mark O Goodarzi
OBJECTIVE: To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS). DESIGN: Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms (SNPs) in eight genes for AR chaperones and co-chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. Single-nucleotide polymorphisms were tested for association with PCOS status and with androgenic and metabolic parameters...
February 2016: Fertility and Sterility
Paola Rusmini, Maria Josefa Polanco, Riccardo Cristofani, Maria Elena Cicardi, Marco Meroni, Mariarita Galbiati, Margherita Piccolella, Elio Messi, Elisa Giorgetti, Andrew P Lieberman, Carmelo Milioto, Anna Rocchi, Tanya Aggarwal, Maria Pennuto, Valeria Crippa, Angelo Poletti
Spinal and bulbar muscular atrophy (SBMA) is characterized by loss of motoneurons and sensory neurons, accompanied by atrophy of muscle cells. SBMA is due to an androgen receptor containing a polyglutamine tract (ARpolyQ) that misfolds and aggregates, thereby perturbing the protein quality control (PQC) system. Using SBMA AR113Q mice we analyzed proteotoxic stress-induced alterations of HSPB8-mediated PQC machinery promoting clearance of misfolded proteins by autophagy. In muscle of symptomatic AR113Q male mice, we found expression upregulation of Pax-7, myogenin, E2-ubiquitin ligase UBE2Q1 and acetylcholine receptor (AchR), but not of MyoD, and of two E3-ligases (MuRF-1 and Cullin3)...
October 22, 2015: Scientific Reports
Andreas Matthäus Bader, Kristin Klose, Karen Bieback, Dirk Korinth, Maria Schneider, Martina Seifert, Yeong-Hoon Choi, Andreas Kurtz, Volkmar Falk, Christof Stamm
Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone marrow-derived multipotent mesenchymal stromal cells (MSCs) upon transplantation in ischemic tissue. Given the interest in clinical applications of umbilical cord blood-derived MSCs, we developed a specific hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro by subjecting them to hypoxia and nutrient deprivation with or without preceding hypoxic preconditioning...
2015: PloS One
Pablo Winzer, Joachim Müller, Adriana Aguado-Martínez, Mahbubur Rahman, Vreni Balmer, Vera Manser, Luis Miguel Ortega-Mora, Kayode K Ojo, Erkang Fan, Dustin J Maly, Wesley C Van Voorhis, Andrew Hemphill
We report on the in vitro effects of the bumped kinase inhibitor 1294 (BKI-1294) in cultures of virulent Neospora caninum isolates Nc-Liverpool (Nc-Liv) and Nc-Spain7 and in two strains of Toxoplasma gondii (RH and ME49), all grown in human foreskin fibroblasts. In these parasites, BKI-1294 acted with 50% inhibitory concentrations (IC50s) ranging from 20 nM (T. gondii RH) to 360 nM (N. caninum Nc-Liv), and exposure of intracellular stages to 1294 led to the nondisjunction of newly formed tachyzoites, resulting in the formation of multinucleated complexes similar to complexes previously observed in BKI-1294-treated N...
October 2015: Antimicrobial Agents and Chemotherapy
Neil Patel, Amanda Crider, Chirayu D Pandya, Anthony O Ahmed, Anilkumar Pillai
Although stress has been implicated in the pathophysiology of autistic spectrum disorder (ASD), it is not known whether glucocorticoid receptor (GR) levels are altered in the brain of subjects with ASD. The messenger RNA (mRNA) levels of GR isoforms (GRα, GRβ, GRγ, and GRP), mineralocorticoid receptor (MR), GR co-chaperones (FKBP5, PTGES3, and BAG1), and inflammatory cytokines (IL-6, IL-1β, and IFN-γ) were examined in the postmortem middle frontal gyrus tissues of 13 ASD and 13 age-matched controls by qRT-PCR...
May 2016: Molecular Neurobiology
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