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https://www.readbyqxmd.com/read/29244790/lentivirus-mediated-silencing-of-the-ptc1-and-ptc2-genes-promotes-recovery-from-spinal-cord-injury-by-activating-the-hedgehog-signaling-pathway-in-a-rat-model
#1
Ya-Dong Zhang, Zhong-Sheng Zhu, Dong Zhang, Zhen Zhang, Bin Ma, Shi-Chang Zhao, Feng Xue
This study aimed to investigate the effect of Patched-1 (PTC1) and PTC2 silencing in a rat model, on Hedgehog (Hh) pathway-mediated recovery from spinal cord injury (SCI). An analytical emphasis on the relationship between the sonic hedgehog (Shh) pathway and nerve regeneration was explored. A total of 126 rats were divided into normal, sham, SCI, negative control (NC), PTC1-RNAi, PTC2-RNAi and PTC1/PTC2-RNAi groups. The Basso, Beattie and Bresnahan (BBB) scale was employed to assess hind limb motor function...
December 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29244184/accumulation-of-long-term-transcriptionally-active-integrated-retroviral-vectors-in-active-promoters-and-enhancers
#2
Filip Šenigl, Dalibor Miklík, Miroslav Auxt, Jirí Hejnar
Most retroviruses preferentially integrate into certain genomic locations and, as a result, their genome-wide integration patterns are non-random. We investigate the epigenetic landscape of integrated retroviral vectors and correlate it with the long-term stability of proviral transcription. Retroviral vectors derived from the avian sarcoma/leukosis virus expressing the GFP reporter were used to transduce the human myeloid lymphoblastoma cell line K562. Because of efficient silencing of avian retrovirus in mammalian cells, only ∼3% of established clones displayed stable proviral expression...
December 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29243047/role-of-%C3%AE-catenin-in-cisplatin-resistance-relapse-and-prognosis-of-head-and-neck-squamous-cell-carcinoma
#3
Souvick Roy, Madhabananda Kar, Shomereeta Roy, Arka Saha, Swatishree Padhi, Birendranath Banerjee
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of β-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis. METHODS: In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess β-catenin expression in the cut margin and tumor areas of each sample...
December 14, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29243000/rna-interference-based-therapy-and-its-delivery-systems
#4
Xiuhui Chen, Lingegowda S Mangala, Cristian Rodriguez-Aguayo, Xianchao Kong, Gabriel Lopez-Berestein, Anil K Sood
RNA interference (RNAi) is considered a highly specific approach for gene silencing and holds tremendous potential for treatment of various pathologic conditions such as cardiovascular diseases, viral infections, and cancer. Although gene silencing approaches such as RNAi are widely used in preclinical models, the clinical application of RNAi is challenging primarily because of the difficulty in achieving successful systemic delivery. Effective delivery systems are essential to enable the full therapeutic potential of RNAi...
December 14, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29242551/ezh2-phosphorylation-state-determines-its-capacity-to-maintain-cd8-t-memory-precursors-for-antitumor-immunity
#5
Shan He, Yongnian Liu, Lijun Meng, Hongxing Sun, Ying Wang, Yun Ji, Janaki Purushe, Pan Chen, Changhong Li, Jozef Madzo, Jean-Pierre Issa, Jonathan Soboloff, Ran Reshef, Bethany Moore, Luca Gattinoni, Yi Zhang
Memory T cells sustain effector T-cell production while self-renewing in reaction to persistent antigen; yet, excessive expansion reduces memory potential and impairs antitumor immunity. Epigenetic mechanisms are thought to be important for balancing effector and memory differentiation; however, the epigenetic regulator(s) underpinning this process remains unknown. Herein, we show that the histone methyltransferase Ezh2 controls CD8+ T memory precursor formation and antitumor activity. Ezh2 activates Id3 while silencing Id2, Prdm1 and Eomes, promoting the expansion of memory precursor cells and their differentiation into functional memory cells...
December 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29242529/decitabine-a-dna-demethylating-agent-promotes-differentiation-via-notch1-signaling-and-alters-immune-related-pathways-in-muscle-invasive-bladder-cancer
#6
Swathi Ramakrishnan, Qiang Hu, Nithya Krishnan, Dan Wang, Evelyn Smit, Victoria Granger, Monika Rak, Kristopher Attwood, Candace Johnson, Carl Morrison, Roberto Pili, Gurkamal Chatta, Khurshid Guru, Geraldine Gueron, Lacey McNally, Jianmin Wang, Anna Woloszynska-Read
Aberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation...
December 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29242407/central-role-of-the-p53-pathway-in-the-noncoding-rna-response-to-oxidative-stress
#7
Paola Fuschi, Matteo Carrara, Christine Voellenkle, Jose Manuel Garcia-Manteiga, Paolo Righini, Biagina Maimone, Elena Sangalli, Francesco Villa, Claudia Specchia, Mario Picozza, Giovanni Nano, Carlo Gaetano, Gaia Spinetti, Annibale A Puca, Alessandra Magenta, Fabio Martelli
Oxidative stress plays a fundamental role in many conditions. Specifically, redox imbalance inhibits endothelial cell (EC) growth, inducing cell death and senescence. We used global transcriptome profiling to investigate the involvement of noncoding-RNAs in these phenotypes. By RNA-sequencing, transcriptome changes were analyzed in human ECs exposed to H2O2, highlighting a pivotal role of p53-signaling. Bioinformatic analysis and validation in p53-silenced ECs, identified several p53-targets among both mRNAs and long noncoding-RNAs (lncRNAs), including MALAT1 and NEAT1...
December 12, 2017: Aging
https://www.readbyqxmd.com/read/29242288/a-role-for-mono-methylation-of-histone-h3-k27-in-gene-activity-in-drosophila
#8
Liangjun Wang, Preeti Joshi, Ellen L Miller, LeeAnn Higgins, Matthew Slattery, Jeffrey A Simon
Polycomb repressive complex 2 (PRC2) is a conserved chromatin-modifying enzyme that methylates histone H3 on lysine-27 (K27).  PRC2 can add one, two, or three methyl groups and the fully methylated product, H3-K27me3, is a hallmark of Polycomb-silenced chromatin.  Less is known about functions of K27me1 and K27me2 and the dynamics of flux through these states.  These modifications could serve mainly as intermediates to produce K27me3 or they could each convey distinct epigenetic information.  To investigate this, we engineered a variant of Drosophila melanogaster PRC2 which is converted into a mono-methyltransferase...
December 14, 2017: Genetics
https://www.readbyqxmd.com/read/29242101/epigenetic-silencing-of-evl-mir-342-in-multiple-myeloma
#9
Zhenhai Li, Kwan Yeung Wong, Godfrey Chi-Fung Chan, Wee-Joo Chng, Chor Sang Chim
miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in multiple cancers. As the promoter region of its host gene, EVL, is embedded in a CpG island, we postulated that miR-342-3p is an intronic miRNA co-regulated with its host gene by promoter DNA methylation in multiple myeloma (MM). By methylation-specific polymerase chain reaction, verified by quantitative bisulfite pyrosequencing, methylation of EVL/miR-342 was absent in all healthy controls (n = 10) and 12 of 15 (80%) human myeloma cell lines (HMCLs), but partially methylated in 3 of 15 (20%) HMCLs, including KMS-12-PE, OCI-MY5, and RPMI-8226R...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29241545/the-germline-linker-histone-dbigh1-and-the-translational-regulator-bam-form-a-repressor-loop-essential-for-male-germ-stem-cell-differentiation
#10
Albert Carbonell, Salvador Pérez-Montero, Paula Climent-Cantó, Oscar Reina, Fernando Azorín
Drosophila spermatogenesis constitutes a paradigmatic system to study maintenance, proliferation, and differentiation of adult stem cell lineages. Each Drosophila testis contains 6-12 germ stem cells (GSCs) that divide asymmetrically to produce gonialblast cells that undergo four transit-amplifying (TA) spermatogonial divisions before entering spermatocyte differentiation. Mechanisms governing these crucial transitions are not fully understood. Here, we report the essential role of the germline linker histone dBigH1 during early spermatogenesis...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241539/functional-and-molecular-characterization-of-mechanoinsensitive-silent-nociceptors
#11
Vincenzo Prato, Francisco J Taberner, James R F Hockley, Gerard Callejo, Alice Arcourt, Bassim Tazir, Leonie Hammer, Paulina Schad, Paul A Heppenstall, Ewan S Smith, Stefan G Lechner
Mechanical and thermal hyperalgesia (pain hypersensitivity) are cardinal signs of inflammation. Although the mechanism underlying thermal hyperalgesia is well understood, the cellular and molecular basis of mechanical hyperalgesia is poorly described. Here, we have identified a subset of peptidergic C-fiber nociceptors that are insensitive to noxious mechanical stimuli under normal conditions but become sensitized to such stimuli when exposed to the inflammatory mediator nerve growth factor (NGF). Strikingly, NGF did not affect mechanosensitivity of other nociceptors...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241530/atp-citrate-lyase-regulates-myofiber-differentiation-and-increases-regeneration-by-altering-histone-acetylation
#12
Suman Das, Frederic Morvan, Giulio Morozzi, Benjamin Jourde, Giulia C Minetti, Peter Kahle, Helene Rivet, Pascale Brebbia, Gauthier Toussaint, David J Glass, Mara Fornaro
ATP citrate lyase (ACL) plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. We report here that ACL silencing impairs myoblast and satellite cell (SC) differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD. Conversely, overexpression of ACL enhances MYOD levels and promotes myogenesis. Myogenesis is dependent on transcriptional but also other mechanisms. We show that ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241219/yap-inhibits-the-apoptosis-and-migration-of-human-rectal-cancer-cells-via-suppression-of-jnk-drp1-mitochondrial-fission-htra2-omi-pathways
#13
Haijun Li, Fucheng He, Xin Zhao, Yuan Zhang, Xi Chu, Chunlan Hua, Yunhui Qu, Yu Duan, Liang Ming
BACKGROUND/AIMS: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo-Yap pathway in human rectal cancer tumorigenesis and metastasis. METHODS: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29241100/the-effect-of-spatial-auditory-landmarks-on-ambulation
#14
Adham M Karim, Kavelin Rumalla, Laurie A King, Timothy E Hullar
The maintenance of balance and posture is a result of the collaborative efforts of vestibular, proprioceptive, and visual sensory inputs, but a fourth neural input, audition, may also improve balance. Here, we tested the hypothesis that auditory inputs function as environmental spatial landmarks whose effectiveness depends on sound localization ability during ambulation. Eight blindfolded normal young subjects performed the Fukuda-Unterberger test in three auditory conditions: silence, white noise played through headphones (head-referenced condition), and white noise played through a loudspeaker placed directly in front at 135 centimeters away from the ear at ear height (earth-referenced condition)...
December 5, 2017: Gait & Posture
https://www.readbyqxmd.com/read/29241071/insights-on-ornithine-decarboxylase-silencing-as-a-potential-strategy-for-targeting-retinoblastoma
#15
Sivashanmugam Muthukumaran, Renganathan Bhuvanasundar, Vetrivel Umashankar, K N Sulochana
Ornithine Decarboxylase (ODC) is a key enzyme involved in polyamine synthesis and is reported to be up regulated in several cancers. However, the effect of ODC gene silencing in retinoblastoma is to be understood for utilization in therapeutic applications. Hence, in this study, a novel siRNA (small interference RNA) targeting ODC was designed and validated in Human Y79 retinoblastoma cells for its effects on intracellular polyamine levels, Matrix Metalloproteinase 2 & 9 activity and Cell cycle. The designed siRNA showed efficient silencing of ODC mRNA expression and protein levels in Y79 cells...
December 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29240261/mitochondrial-dysfunction-rad51-and-ku80-proteolysis-promote-apoptotic-effects-of-dinaciclib-in-bcl-xl-silenced-cells
#16
Daniel R Premkumar, Esther P Jane, Swetha Thambireddy, Philip A Sutera, Jonathon M Cavaleri, Ian F Pollack
In the present study, we investigated the effect of CDK inhibitors (ribociclib, palbociclib, seliciclib, AZD5438 and dinaciclib) on malignant human glioma cells for cell viability, apoptosis, oxidative stress and mitochondrial function using various assays. None of the CDK inhibitors induced cell death at a clinically relevant concentration. However, low nanomolar concentrations of dinaciclib showed higher cytotoxic activity against Bcl-xL silenced cells in a time- and concentration-dependent manner. This effect was not seen with other CDK inhibitors...
December 14, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29239839/the-formin-diaph1-is-a-key-modulator-of-myocardial-ischemia-reperfusion-injury
#17
Karen M O'Shea, Radha Ananthakrishnan, Qing Li, Nosirudeen Quadri, Devi Thiagarajan, Gopalkrishna Sreejit, Lingjie Wang, Hylde Zirpoli, Juan Francisco Aranda, Arthur S Alberts, Ann Marie Schmidt, Ravichandran Ramasamy
The biochemical, ionic, and signaling changes that occur within cardiomyocytes subjected to ischemia are exacerbated by reperfusion; however, the precise mechanisms mediating myocardial ischemia/reperfusion (I/R) injury have not been fully elucidated. The receptor for advanced glycation end-products (RAGE) regulates the cellular response to cardiac tissue damage in I/R, an effect potentially mediated by the binding of the RAGE cytoplasmic domain to the diaphanous-related formin, DIAPH1. The aim of this study was to investigate the role of DIAPH1 in the physiological response to experimental myocardial I/R in mice...
November 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29239821/long-noncoding-rna-fezf1-as1-indicates-a-poor-prognosis-of-gastric-cancer-and-promotes-tumorigenesis-via-activation-of-wnt-signaling-pathway
#18
Xiaoli Wu, Peichen Zhang, Hua Zhu, Shi Li, Xiangjian Chen, Lingyan Shi
Long non-coding RNAs (lncRNAs) have been demonstrated that it plays very important role in development and progression of carcinomas. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been proved to be implicated in tumor initiation and progression of various cancers, recently. Nevertheless, the biological function and clinical significance of lncRNA FEZF1-AS1 in gastric cancer (GC) are not clear enough. Here, we concentrated on the association of FEZF1-AS1 expression and clinicopathological factors in GC tissues and cells...
November 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29239313/regulation-of-neuronal-survival-by-dna-methyltransferases
#19
REVIEW
Judit Symmank, Geraldine Zimmer
The limited regenerative capacity of neuronal cells requires tight orchestration of cell death and survival regulation in the context of longevity, age-associated diseases as well as during the development of the nervous system. Subordinate to genetic networks epigenetic mechanisms like DNA methylation and histone modifications are involved in the regulation of neuronal development, function and aging. DNA methylation by DNA methyltransferases (DNMTs), mostly correlated with gene silencing, is a dynamic and reversible process...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29238763/modalities-to-enumerate-circulating-tumor-cells-in-the-bloodstream-for-cancer-prognosis-and-to-monitor-the-response-to-the-therapy
#20
G Romano
Certain malignant cells may detach from the primary tumor and enter the vascular system, forming so-called circulating tumor cells (CTCs). Clusters of malignant cells associated with other cell types can also be observed in the peripheral blood of oncological patients. Such cell clusters are termed circulating tumor microemboli (CTM). The isolation and quantification of CTCs and/or CTM from blood samples allow for an accurate prognosis of the clinical course of the disease and to monitor the response to therapy...
September 2017: Drugs of Today
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