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https://www.readbyqxmd.com/read/29199464/sperm-rna-elements-as-markers-of-health
#1
Rayanne B Burl, Stephanie Clough, Edward Sendler, Molly Estill, Stephen A Krawetz
Idiopathic infertility, an etiology not identified as part of standard clinical assessment, represents approximately 20% of all infertility cases. Current male infertility diagnosis focuses on the concentration, motility, and morphology of spermatozoa. This is of limited value when predicting birth success and of limited utility when selecting the optimum treatment. At fertilization, spermatozoa provide their genomic contribution, as well as a set of RNAs and proteins that have distinct roles in development...
December 3, 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29174527/genotypic-and-phenotypic-spectrum-of-the-most-common-causative-genes-of-charcot-marie-tooth-disease-in-hungarian-patients
#2
György Máté Milley, Edina Timea Varga, Zoltán Grosz, Csilla Nemes, Zsuzsanna Arányi, Judit Boczán, Péter Diószeghy, Mária Judit Molnár, Anikó Gál
Charcot-Marie-Tooth neuropathy (CMT) is a genetically and clinically heterogeneous group of neuromuscular disorders with an overall prevalence of 1 per 2500. Here we report the first comprehensive genetic epidemiology study of Hungarian CMT patients. 409 CMT1 and 122 CMT2 patients were enrolled and genetic testing of PMP22, GJB1, MPZ, EGR2 and MFN2 genes were performed routinely. NDRG1 and CTDP1 genes were screened only for founder mutations in Roma patients. Causative genetic mutations were identified in 67...
September 8, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29161883/targeting-oncogenic-nf-%C3%AE%C2%BAb-signaling-with-redox-active-agents-for-cancer-treatment
#3
Leyla Fouani, Zaklina Kovacevic, Des R Richardson
<b><i>Significance:</i></b> Nuclear factor kappa B (NF-κB) signaling is essential under physiologically-relevant conditions. However, aberrant activation of this pathway plays a pertinent role in tumorigenesis and contributes to resistance. <b><i>Recent Advances: </i></b>The importance of the NF-κB pathway means that its targeting must be specific to avoid side effects. For many currently used therapeutics and those under development, the ability to generate reactive oxygen species (ROS) is a promising strategy...
November 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29156765/network-directed-cis-mediator-analysis-of-normal-prostate-tissue-expression-profiles-reveals-downstream-regulatory-associations-of-prostate-cancer-susceptibility-loci
#4
Nicholas B Larson, Shannon K McDonnell, Zach Fogarty, Melissa C Larson, John Cheville, Shaun Riska, Saurabh Baheti, Alexandra M Weber, Asha A Nair, Liang Wang, Daniel O'Brien, Jaime Davila, Daniel J Schaid, Stephen N Thibodeau
Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis-acting associations due to study limitations. While trans-eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans-eQTL associations are mediated by cis-regulated genes, such as transcription factors...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137287/n-myc-downstream-regulated-gene-1-promotes-apoptosis-in-colorectal-cancer-via-up-regulating-death-receptor-4
#5
Xian Zhang, Bo Feng, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Meng Pan, Zirui He, Xiongzhi Wangpu, Jing Sun, Xiao Yang
The aim of this study was to evaluate the clinical significance of N-myc downstream-regulated gene 1 (NDRG1) in colorectal cancer (CRC) patients and to explore the mechanisms governing the role of NDRG1 in apoptosis of CRC cells. In the current study, we found that NDRG1 was a prognostic marker of CRC patients. Moreover, NDRG1 expression negatively correlated to tumor size and clinical TNM stage, suggesting that NDRG1 might act as a tumor suppressor by inhibiting proliferation or inducing apoptosis in CRC. Consistently, substantial apoptosis was observed in vitro and in vivo in the presence of NDRG1...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29127096/retention-of-interstitial-genes-between-tmprss2-and-erg-is-associated-with-low-risk-prostate-cancer
#6
Stephen J Murphy, Farhad Kosari, R Jeffrey Karnes, Aqsa Nasir, Sarah H Johnson, Athanasios G Gaitatzes, James B Smadbeck, Laureano J Rangel, George Vasmatzis, John C Cheville
TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between TMPRSS2 and ERG has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of TMPRSS2-ERG fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens...
November 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/29118118/n-myc-downstream-regulated-gene-1-restricts-hepatitis-c-virus-propagation-by-regulating-lipid-droplet-biogenesis-and-viral-assembly
#7
Cameron J Schweitzer, Fang Zhang, Audrey Boyer, Kristin Valdez, Maggie Cam, T Jake Liang
Host cells harbor various intrinsic mechanisms to restrict viral infections as a first line of antiviral defense. Viruses have evolved various countermeasures against these antiviral mechanisms. Here we show that N-Myc Downstream-Reguated Gene 1 (NDRG1) limits productive HCV infection by inhibiting viral assembly. Interestingly, HCV infection down-regulates NDRG1 protein and mRNA expression. Loss of NDRG1 increases the size and number of lipid droplets, which are the sites of HCV assembly. HCV suppresses NDRG1 expression by up-regulating MYC, which directly inhibits the transcription of NDRG1 Up-regulation of MYC also leads to reduced expression of NDRG1-specific kinase SGK1, resulting in markedly diminished phosphorylation of NDRG1...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29072693/corrigendum-ndrg1-inhibition-sensitizes-osteosarcoma-cells-to-combretastatin-a-4-through-targeting-autophagy
#8
Hongsheng Wang, Wen Li, Jing Xu, Tao Zhang, Dongqing Zuo, Zifei Zhou, Binhui Lin, Gangyang Wang, Zhuoying Wang, Wei Sun, Mengxiong Sun, Shimin Chang, Zhengdong Cai, Yingqi Hua
This corrects the article DOI: 10.1038/cddis.2017.438.
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29018329/cddo-and-atra-instigate-differentiation-of-imr32-human-neuroblastoma-cells
#9
Namrata Chaudhari, Priti Talwar, Christian Lefebvre D'hellencourt, Palaniyandi Ravanan
Neuroblastoma is the most common solid extra cranial tumor in infants. Improving the clinical outcome of children with aggressive tumors undergoing one of the multiple treatment options has been a major concern. Differentiating neuroblastoma cells holds promise in inducing tumor growth arrest and treating minimal residual disease. In this study, we investigated the effect of partial PPARγ agonist 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) on human neuroblastoma IMR32 cells. Our results demonstrate that treatment with low concentration of CDDO and particularly in combination with all trans retinoic acid (ATRA) induced neurite outgrowth, increased the percentage of more than two neurites bearing cells, and decreased viability in IMR32 cells...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28981455/a-unique-tgfb1-driven-genomic-program-links-astrocytosis-low-grade-inflammation-and-partial-demyelination-in-spinal-cord-periplaques-from-progressive-multiple-sclerosis-patients
#10
Serge Nataf, Marc Barritault, Laurent Pays
We previously reported that, in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses did not allow providing a comprehensive view of molecular events in astrocytes vs. oligodendrocytes. Here, we re-assessed our transcriptomic data and performed co-expression analyses to characterize astrocyte vs...
October 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28906492/ndrg1-inhibition-sensitizes-osteosarcoma-cells-to-combretastatin-a-4-through-targeting-autophagy
#11
Hongsheng Wang, Wen Li, Jing Xu, Tao Zhang, Dongqing Zuo, Zifei Zhou, Binhui Lin, Gangyang Wang, Zhuoying Wang, Wei Sun, Mengxiong Sun, Shimin Chang, Zhengdong Cai, Yingqi Hua
Combretastatin A-4 (CA-4), a tubulin-depolymerizing agent, shows promising antitumor efficacy and has been under several clinical trials in solid tumors for 10 years. Autophagy has an important pro-survival role in cancer therapy, thus targeting autophagy may improve the efficacy of antitumor agents. N-myc downstream-regulated gene 1 (NDRG1) is a significant stress regulatory gene, which mediates cell survival and chemoresistance. Here we reported that CA-4 could induce cell-protective autophagy, and combination treatment of CA-4 and autophagy inhibitor chloroquine (CQ) exerted synergistic cytotoxic effect on human osteosarcoma (OS) cells...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28902413/frequent-genes-in-rare-diseases-panel-based-next-generation-sequencing-to-disclose-causal-mutations-in-hereditary-neuropathies
#12
Maike F Dohrn, Nicola Glöckle, Lejla Mulahasanovic, Corina Heller, Julia Mohr, Christine Bauer, Erik Riesch, Andrea Becker, Florian Battke, Konstanze Hörtnagel, Thorsten Hornemann, Saranya Suriyanarayanan, Markus Blankenburg, Jörg B Schulz, Kristl G Claeys, Burkhard Gess, Istvan Katona, Andreas Ferbert, Debora Vittore, Alexander Grimm, Stefan Wolking, Ludger Schöls, Holger Lerche, G Christoph Korenke, Dirk Fischer, Bertold Schrank, Urania Kotzaeridou, Gerhard Kurlemann, Bianca Dräger, Anja Schirmacher, Peter Young, Beate Schlotter-Weigel, Saskia Biskup
Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11...
December 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28867478/hemidesmosomal-linker-proteins-regulate-cell-motility-invasion-and-tumorigenicity-in-oral-squamous-cell-carcinoma-derived-cells
#13
Pratik Rajeev Chaudhari, Silvania Emlit Charles, Zinia Charlotte D'Souza, Milind Murlidhar Vaidya
BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28865129/effects-of-long-term-hypoxia-in-human-chondrosarcoma-cells
#14
J Piltti, J Bygdell, C J Qu, M J Lammi
The cell-based therapies could be potential methods to treat damaged cartilage tissues. Instead of native hyaline cartilage, the current therapies generate mainly weaker fibrocartilage-type of repair tissue. A correct microenvironment influences the cellular phenotype, and together with external factors it can be used, e.g., to aid the differentiation of mesenchymal stem cells to defined types of differentiated adult cells. In this study, we investigated the effect of long-term exposure to 5% low oxygen atmosphere on human chondrosarcoma HCS-2/8 cells...
September 2, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28861610/inhibitors-of-the-proteasome-stimulate-the-epithelial-sodium-channel-enac-through-sgk1-and-mimic-the-effect-of-aldosterone
#15
Morag K Mansley, Christoph Korbmacher, Marko Bertog
The epithelial sodium channel (ENaC) marks the tightly regulated, rate-limiting step of sodium re-absorption in the aldosterone-sensitive distal nephron (ASDN). Stimulation of ENaC activity by aldosterone involves the serum and glucocorticoid-induced kinase 1 (SGK1) and is mediated via complex mechanisms including inhibition of channel retrieval. Retrieved channels may be recycled or degraded, e.g. by the proteasomal pathway. The aim of the present study was to investigate whether inhibitors of the proteasome affect ENaC activity and surface expression, and to explore a possible involvement of SGK1...
August 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28803608/identification-of-simvastatin-regulated-targets-associated-with-jnk-activation-in-du145-human-prostate-cancer-cell-death-signaling
#16
Eun Joo Jung, Ky Hyun Chung, Choong Won Kim
The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways...
September 2017: BMB Reports
https://www.readbyqxmd.com/read/28776325/identification-and-functional-characterization-of-two-missense-mutations-in-ndrg1-associated-with-charcot-marie-tooth-disease-type-4d
#17
Li-Xi Li, Gong-Lu Liu, Zhi-Jun Liu, Cong Lu, Zhi-Ying Wu
Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal-recessive demyelinating form of CMT characterized by a severe distal motor and sensory neuropathy. NDRG1 is the causative gene for CMT4D. To date, only four mutations in NDRG1 -c.442C>T (p.Arg148*), c.739delC (p.His247Thrfs*74), c.538-1G>A, and duplication of exons 6-8-have been described in CMT4D patients. Here, using targeted next-generation sequencing examination, we identified for the first time two homozygous missense variants in NDRG1, c...
November 2017: Human Mutation
https://www.readbyqxmd.com/read/28775290/ndrg1-promotes-adipocyte-differentiation-and-sustains-their-function
#18
Kai Cai, Rabih El-Merahbi, Mona Loeffler, Alexander E Mayer, Grzegorz Sumara
Adipocytes play a central role in maintaining metabolic homeostasis in the body. Differentiation of adipocyte precursor cells requires the transcriptional activity of peroxisome proliferator-activated receptor-γ (Pparγ) and CCAAT/enhancer binding proteins (C/Ebps). Transcriptional activity is regulated by signaling modules activated by a plethora of hormones and nutrients. Mechanistic target of rapamacin complexes (mTORC) 1 and 2 are central for the coordination of hormonal and nutritional inputs in cells and are essential for adipogenesis...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775238/n-myc-downstream-regulated-gene-1-promotes-apoptosis-in-colorectal-cancer-via-up-regulating-death-receptor-4
#19
Xian Zhang, Bo Feng, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Meng Pan, Zirui He, Xiongzhi Wangpu, Jing Sun, Xiao Yang
The aim of this study was to evaluate the clinical significance of N-myc downstream-regulated gene 1 (NDRG1) in colorectal cancer (CRC) patients and to explore the mechanisms governing the role of NDRG1 in apoptosis of CRC cells. In the current study, we found that NDRG1 was a prognostic marker of CRC patients. Moreover, NDRG1 expression negatively correlated to tumor size and clinical TNM stage, suggesting that NDRG1 might act as a tumor suppressor by inhibiting proliferation or inducing apoptosis in CRC. Consistently, substantial apoptosis was observed in vitro and in vivo in the presence of NDRG1...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701735/quantitative-proteomics-reveal-the-anti-tumour-mechanism-of-the-carbohydrate-recognition-domain-of-galectin-3-in-hepatocellular-carcinoma
#20
Mingchao Wang, Fang Tian, Wantao Ying, Xiaohong Qian
Hepatocellular carcinoma (HCC) is a serious threat to human health. The carbohydrate recognition domain of Galectin-3 (Gal3C) has been reported to be an anti-tumour molecule. In this study, we aim to explore effects of Gal3C in HCC and its possible molecular mechanism with quantitative proteomics approach. We found that rGal3C stimulation could inhibit cell viability, migration and invasion of HepG2. After rGal3C stimulating, 190 proteins were differentially expressed. Eighty up-regulated proteins located mainly in extracellular exosome and involved in cell adhesion and metabolism, and 110 down-regulated proteins located in mitochondria and extracellular exosome, and related to processes of metabolism and oxidation-reduction...
July 12, 2017: Scientific Reports
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