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https://www.readbyqxmd.com/read/29803992/rational-development-of-nanomedicines-for-molecular-targeting-in-periodontal-disease
#1
REVIEW
Nikola Geskovski, Simona Dimchevska Sazdovska, Silvana Gjosheva, Rumenka Petkovska, Mirjana Popovska, Liljana Anastasova, Kristina Mladenovska, Katerina Goracinova
Recent advances in understanding the etiology and pathogenesis of periodontal disease and polymicrobial synergy in the dysbiotic oral microbial community endorsed novel therapeutic targets and assured further improvement in periodontal disease treatment. Moreover, understanding of the events at the molecular level inspired the researchers to alleviate the stress from the disease by applying the bottom-up approach and delivering the drugs at the site of action, using nanoscale medicines. This review is focused on promising strategies for rational design of nanopaharmaceuticals for periodontal disease treatment based on novel therapeutic targets and the potential of advanced concepts for inflammation cascade targeting...
May 14, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29678492/hmga1a-induces-alternative-splicing-of-estrogen-receptor-alpha-in-mcf-7-human-breast-cancer-cells
#2
Kenji Ohe, Shinsuke Miyajima, Ichiro Abe, Tomoko Tanaka, Yuriko Hamaguchi, Yoshihiro Harada, Yuta Horita, Yuki Beppu, Fumiaki Ito, Takafumi Yamasaki, Hiroki Terai, Masayoshi Mori, Yusuke Murata, Makito Tanabe, Kenji Ashida, Kunihisa Kobayashi, Munechika Enjoji, Toshihiko Yanase, Nobuhiro Harada, Toshiaki Utsumi, Akila Mayeda
The high-mobility group A protein 1a (HMGA1a) protein is known as an oncogene whose expression level in cancer tissue correlates with the malignant potential, and known as a component of senescence-related structures connecting it to tumor suppressor networks in fibroblasts. HMGA1 protein binds to DNA, but recent studies have shown it exerts novel functions through RNA-binding. Our previous studies have shown that sequence-specific RNA-binding of HMGA1a induces exon-skipping of Presenilin-2 exon 5 in sporadic Alzheimer disease...
April 17, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29668077/jc-and-bk-virus-dna-detection-in-archival-slides-of-urine-cytospin-from-renal-transplant-patients
#3
Patricia Assis, Carlos Eduardo Carvalho, Marcelo Soares Silva, Bruna Ribeiro, Maria da Gloria Carvalho
BACKGROUND: Although identifying cytological viral inclusions (decoy cells) in the urine is relatively easy, distinguishing between Polyomaviruses BKV and JCV is not possible. Few studies have been published regarding JCV detection in kidney transplant recipients. OBJECTIVE: To evaluate the incidence of BKV and JCV DNA in archival slides of urine cytospin material from renal transplant patients. METHODS: A total of 44 urine specimens were evaluated cytologically for the presence of viral inclusions (decoy cells) and by nested polymerase chain reaction to differentiate between JCV and BKV in DNA isolated from archival slides of urine cytospin material...
April 18, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29610464/single-helically-folded-aromatic-oligoamides-that-mimic-the-charge-surface-of-double-stranded-b-dna
#4
Krzysztof Ziach, Céline Chollet, Vincent Parissi, Panchami Prabhakaran, Mathieu Marchivie, Valentina Corvaglia, Partha Pratim Bose, Katta Laxmi-Reddy, Frédéric Godde, Jean-Marie Schmitter, Stéphane Chaignepain, Philippe Pourquier, Ivan Huc
Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein-DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known. Here, we report the design, synthesis and structural characterization of aromatic oligoamides that fold into single helical conformations and display a double helical array of negatively charged residues in positions that match the phosphate moieties in B-DNA...
May 2018: Nature Chemistry
https://www.readbyqxmd.com/read/29552282/identification-and-preclinical-evaluation-of-the-small-molecule-nsc745887-for-treating-glioblastomas-via-suppressing-dcr3-associated-signaling-pathways
#5
Li-Yun Fann, Ying Chen, Da-Chen Chu, Shao-Ju Weng, Heng-Cheng Chu, Alexander T H Wu, Jiann-Fong Lee, Ahmed Atef Ahmed Ali, Tsung-Chih Chen, Hsu-Shan Huang, Kuo-Hsing Ma
The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29538618/nimbus-a-design-driven-analyses-suite-for-amplicon-based-ngs-data
#6
R W W Brouwer, M C G N van den Hout, C E M Kockx, E Brosens, B Eussen, A de Klein, F Sleutels, W F J van IJcken
Motivation: PCR-based DNA enrichment followed by massively parallel sequencing is a straightforward and cost effective method to sequence genes up to high depth. The full potential of amplicon based sequencing assays is currently not achieved as analysis methods do not take into account the source amplicons of the detected variants. Tracking the source amplicons has the potential to identify systematic biases, enhance variant calling and improve the designs of future assays. Results: We present Nimbus, a software suite for the analysis of amplicon based sequencing data...
March 10, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29511732/adenovirus-mediated-delivery-of-decoy-hyper-binding-sites-targeting-oncogenic-hmga1-reduces-pancreatic-and-liver-cancer-cell-viability
#7
Faizule Hassan, Shuisong Ni, Tyler C Arnett, Melanie C McKell, Michael A Kennedy
High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition...
March 30, 2018: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29464201/prediction-of-early-bk-virus-infection-in-kidney-transplant-recipients-by-the-number-of-cells-with-intranuclear-inclusion-bodies-decoy-cells
#8
Yoshiteru Yamada, Tomohiro Tsuchiya, Isao Inagaki, Mitsuru Seishima, Takashi Deguchi
Background: BK virus (BKV) is the cause of nephropathy. Because BKV nephropathy can progress to graft loss, early diagnosis of BKV infection is very important. In this study, we aimed to investigate the utility of quantifying cells with intranuclear inclusion bodies (decoy cells) in urinary sediment for the screening and monitoring of BKV infection in renal transplant recipients at our hospital. Methods: This was a retrospective single-center study. Urine sediment examination was performed at each outpatient visit, and the number of decoy cells was measured in the whole microscopic field...
February 2018: Transplantation Direct
https://www.readbyqxmd.com/read/29440232/non-coding-rnas-long-non-coding-rnas-and-micrornas-in-endocrine-related-cancers
#9
REVIEW
Carolyn M Klinge
The human genome is 'pervasively transcribed' leading to a complex array of non-coding RNAs (ncRNAs) that far outnumber coding mRNAs. ncRNAs have regulatory roles in transcription and post-transcriptional processes as well numerous cellular functions that remain to be fully described. Best characterized of the 'expanding universe' of ncRNAs are the ~22 nucleotide microRNAs (miRNAs) that base-pair to target mRNA's 3' untranslated region within the RNA-induced silencing complex (RISC) and block translation and may stimulate mRNA transcript degradation...
April 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29433938/b-cell-lymphoma-immunotherapy-using-tlr9-targeted-oligonucleotide-stat3-inhibitors
#10
Xingli Zhao, Zhuoran Zhang, Dayson Moreira, Yu-Lin Su, Haejung Won, Tomasz Adamus, Zhenyuan Dong, Yong Liang, Hongwei H Yin, Piotr Swiderski, Raju K Pillai, Larry Kwak, Stephen Forman, Marcin Kortylewski
Growing evidence links the aggressiveness of non-Hodgkin's lymphoma, especially the activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCLs) to Toll-like receptor 9 (TLR9)/MyD88 and STAT3 transcription factor signaling. Here, we describe a dual-function molecule consisting of a clinically relevant TLR9 agonist (CpG7909) and a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). The CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29409936/epigenetic-regulation-by-cpg-methylation-splits-strong-from-retarded-ifn%C3%AE-induced-il-18bp-in-epithelial-versus-monocytic-cells
#11
Malte Bachmann, Josef Pfeilschifter, Heiko Mühl
Interferon (IFN)-γ-inducing interleukin (IL)-18 is a crucial inflammatory cytokine systemically provided by monocytes. It is counteracted by IL-18 binding protein (IL-18BP), a decoy receptor that displays IFNγ-inducibility thus curbing inflammation by negative feedback. Since IL18BP inducibility is pronounced in human epithelial cells but diminished in monocytes, differential IL18BP regulation was investigated herein in both types of cells. Interestingly, DNA-demethylating 5-aza-2'-deoxycytidine enhanced IFNγ-induced IL-18BP only in monocytic but not in epithelial cells...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29291159/dual-radiosensitization-and-anti-stat3-anti-proliferative-strategy-based-on-delivery-of-gold-nanoparticle-oligonucleotide-nanoconstructs-to-head-and-neck-cancer-cells
#12
Surong Zhang, Suresh Gupta, Thomas J Fitzgerald, Alexei A Bogdanov
Constitutively activated signal transducer and activator of transcription 3 (STAT3) factor is an important therapeutic target in head and neck cancer (HNC). Despite early promising results, a reliable systemic delivery system for STAT3- targeted oligonucleotide (ODN) drugs is still needed for future clinical translation of anti-STAT3 therapies. We engineered and tested a novel ODN duplex/gold nanoparticle (AuNP)-based system carrying a therapeutic STAT3 decoy (STAT3d) payload. This strategy is two-pronged because of the additive STAT3 antagonism and radiosensitizing properties of AuNP...
2018: Nanotheranostics
https://www.readbyqxmd.com/read/29228714/unique-expression-signatures-of-circular-rnas-in-response-to-dna-tumor-virus-sv40-infection
#13
Jiandong Shi, Ningzhu Hu, Jianfang Li, Zhaoping Zeng, Ling Mo, Jing Sun, Meini Wu, Yunzhang Hu
Circular RNAs (circRNAs), identified as a class of widely expressed endogenous regulatory RNAs, are involved in diverse physiological and pathological processes. However, their role in viral pathogenesis and cellular antiviral response remains unexplored. In this study, a potent DNA tumor virus, simian virus 40 (SV40), was used as a model to investigate the viral influences on cellular circRNA transcriptome. Using RNA-seq, 15,241 putative circRNAs were identified de novo from 5,057 parental genes in monkey kidney-derived Vero cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215015/malaria-parasite-dna-harbouring-vesicles-activate-cytosolic-immune-sensors
#14
Xavier Sisquella, Yifat Ofir-Birin, Matthew A Pimentel, Lesley Cheng, Paula Abou Karam, Natália G Sampaio, Jocelyn Sietsma Penington, Dympna Connolly, Tal Giladi, Benjamin J Scicluna, Robyn A Sharples, Andreea Waltmann, Dror Avni, Eli Schwartz, Louis Schofield, Ziv Porat, Diana S Hansen, Anthony T Papenfuss, Emily M Eriksson, Motti Gerlic, Andrew F Hill, Andrew G Bowie, Neta Regev-Rudzki
STING is an innate immune cytosolic adaptor for DNA sensors that engage malaria parasite (Plasmodium falciparum) or other pathogen DNA. As P. falciparum infects red blood cells and not leukocytes, how parasite DNA reaches such host cytosolic DNA sensors in immune cells is unclear. Here we show that malaria parasites inside red blood cells can engage host cytosolic innate immune cell receptors from a distance by secreting extracellular vesicles (EV) containing parasitic small RNA and genomic DNA. Upon internalization of DNA-harboring EVs by human monocytes, P...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29064575/dna-detection-of-jc-and-bk-virus-in-archival-urine-cytospin-slides
#15
Patricia G de Assis, Carlos Eduardo de Souza Carvalho, Marcelo Soares da Mota E Silva, Maria da Gloria da Costa Carvalho
To identify decoy cells, cytological examination was performed in urine cytospin slides. Decoy cells are related to Polyomaviruses (JC virus [JCV] and BK virus [BKV]), which are recognized worldwide due to potential infection and morbidity in kidney transplant recipients. Cytologically, it is difficult to evaluate the cytopathic effect of JCV and BKV in urine of patients with urothelial neoplasia. For this reason, there is a need for molecular approaches. To evaluate the incidence of BKV and JCV DNA in archival slides of urine cytospin material with benign and malignant characteristics...
March 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/28968978/decoy-receptor-1-dcr1-promoter-hypermethylation-and-response-to-irinotecan-in-metastatic-colorectal-cancer
#16
Linda J W Bosch, Geert Trooskens, Petur Snaebjornsson, Veerle M H Coupé, Sandra Mongera, Josien C Haan, Susan D Richman, Miriam Koopman, Jolien Tol, Tim de Meyer, Joost Louwagie, Luc Dehaspe, Nicole C T van Grieken, Bauke Ylstra, Henk M W Verheul, Manon van Engeland, Iris D Nagtegaal, James G Herman, Philip Quirke, Matthew T Seymour, Cornelis J A Punt, Wim van Criekinge, Beatriz Carvalho, Gerrit A Meijer
Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI))...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28928124/emerging-mechanisms-of-long-noncoding-rna-function-during-normal-and-malignant-hematopoiesis
#17
REVIEW
Juan R Alvarez-Dominguez, Harvey F Lodish
Long noncoding RNAs (lncRNAs) are increasingly recognized as vital components of gene programs controlling cell differentiation and function. Central to their functions is an ability to act as scaffolds or as decoys that recruit or sequester effector proteins from their DNA, RNA, or protein targets. lncRNA-modulated effectors include regulators of transcription, chromatin organization, RNA processing, and translation, such that lncRNAs can influence gene expression at multiple levels. Here we review the current understanding of how lncRNAs help coordinate gene expression to modulate cell fate in the hematopoietic system...
November 2, 2017: Blood
https://www.readbyqxmd.com/read/28903493/editor-s-highlight-formulation-and-toxicology-evaluation-of-the-intrathecal-ayx1-dna-decoy-in-sprague-dawley-rats
#18
Julien Mamet, David C Yeomans, Tony L Yaksh, Donald C Manning, Scott Harris
The longevity of pain after surgery is debilitating and limits the recovery of patients. AYX1 is a double-stranded, unprotected, 23 base-pair oligonucleotide designed to reduce acute post-surgical pain and prevent its chronification with a single intrathecal perioperative dose. AYX1 mimics the DNA sequence normally bound by EGR1 on chromosomes, a transcription factor transiently induced in the dorsal root ganglia-spinal cord network following a noxious input. AYX1 binds to EGR1 and prevents it from launching waves of gene regulation that are necessary to maintain pain over time...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28878400/thiamine-antagonists-trigger-p53-dependent-apoptosis-in-differentiated-sh-sy5y-cells
#19
Sergiy Chornyy, Yulia Parkhomenko, Nataliya Chorna
Accumulating evidences suggest that p53 is a key coordinator of cellular events triggered by oxidative stress often associated with the impairment in thiamine metabolism and its functions. However, there are limited data regarding the pursuant feedback between p53 transactivation and thiamine homeostasis. Impairment in thiamine metabolism can be induced experimentally via interference with the thiamine uptake and/or inhibition of the thiamin pyrophosphate-dependent enzymes using thiamine antagonists - amprolium (AM), oxythiamine (OT) or pyrithiamine (PT)...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865342/inclusion-of-oligonucleotide-antimicrobials-in-biocompatible-cationic-liposomes-a-structural-study
#20
Marianna Mamusa, Francesco Barbero, Costanza Montis, Laura Cutillo, Ana Gonzalez-Paredes, Debora Berti
HYPOTHESIS: Transcription factor decoys (TFD) are short oligonucleotides designed to block essential genetic pathways in bacteria and defeat resistant infections. TFD protection in biological fluids and their delivery to the site of infection require formulation in appropriate delivery systems. In this work, we build on a classical phosphatidylcholine/phosphatidylethanolamine (POPC/DOPE) scaffold to design TFD-loaded cationic liposomes by combining the DNA-complexing abilities of a bolaamphiphile, (1,1'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride (12-bis-THA), with the biocompatible cationic lipid ethyl-phosphatidylcholine (DPePC)...
August 24, 2017: Journal of Colloid and Interface Science
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