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The aim of this study was to investigate the association between the susceptibility of severe oral mucositis (OM) in Chinese nasopharyngeal carcinoma (NPC) patients treated with radiotherapy and single nucleotide polymorphisms (SNPs) across the whole genome. SNPs were screened in a total of 24 patients with NPC and an additional 6 were subjected to mRNA expression analysis. Patients were subdivided into CTC 0-2 (CTC toxicity grade 0, 1, and 2) and CTC 3+ (CTC toxicity grade 3 and above) groups according to their CTC (common toxicity criteria) scores. The GTEx dataset was used to performed eQTL analyses and in-vitro functional assays were performed for eQTL-associated genes. Our data identified 7 functional SNPs associated with the development of OM. We observed that rs11081899-A, located in the 5′-UTR of the ZNF24 gene, was significantly correlated with a higher risk of severe mucositis (OR = 14.631, 95% CI = 2.61-105.46, p = 1.2 × 10−4), and positively associated with ZNF24 mRNA expression (p = 4.1 × 10−6) from GTEx dataset. In addition, high ZNF24 mRNA expression was associated with severe OM in patients with NPC (p = 0.02). Further functional assays revealed that ZNF24 knockdown reduced p65 expression and suppressed TNF-α-induced NF-κB activation and pro-inflammatory cytokines release. These findings suggested that rs11081899-A may be a genetic susceptibility factor for radiation-induced OM in patients with NPC, although its value in clinical application needs to be further verified in a large cohort. Also, we suggested that downregulation of ZNF24 may attenuate the development of mucositis by suppressing NF-κB activation.
genetic polymorphism, nasopharyngeal carcinoma, radiotherapy, oral mucositis, ZNF24
Predictive single nucleotide polymorphism markers for acute oral mucositis in patients with nasopharyngeal carcinoma treated with radiotherapy
Ziyu Le,1,3 Xiaoshuang Niu,1,3 Ying Chen,4 Xiaomin Ou,1,3 Guoqi Zhao,4 Qi Liu,4 Wenzhi Tu,4 Chaosu Hu,1,3 Lin Kong,1,3 and Yong Liu2,3
2017 Sep 8
This report describes the complete nucleotide sequence of the genome of herpesvirus saimiri, the prototype of gammaherpesvirus subgroup 2 (rhadinoviruses). The unique low-G + C-content DNA region has 112,930 bp with an average base composition of 34.5% G + C and is flanked by about 35 noncoding high-G + C-content DNA repeats of 1,444 bp (70.8% G + C) in tandem orientation. We identified 76 major open reading frames and a set of seven U-RNA genes for a total of 83 potential genes. The genes are closely arranged, with only a few regions of sizable noncoding sequences. For 60 of the predicted proteins, homologous sequences are found in other herpesviruses. Genes conserved between herpesvirus saimiri and Epstein-Barr virus (gammaherpesvirus subgroup 1) show that their genomes are generally collinear, although conserved gene blocks are separated by unique genes that appear to determine the particular phenotype of these viruses. Several deduced protein sequences of herpesvirus saimiri without counterparts in most of the other sequenced herpesviruses exhibited significant homology with cellular proteins of known function. These include thymidylate synthase, dihydrofolate reductase, complement control proteins, the cell surface antigen CD59, cyclins, and G protein-coupled receptors. Searching for functional protein motifs revealed that the virus may encode a cytosine-specific methylase and a tyrosine-specific protein kinase. Several herpesvirus saimiri genes are potential candidates to cooperate with the gene for saimiri transformation-associated protein of subgroup A (STP-A) in T-lymphocyte growth stimulation.
Primary structure of the herpesvirus saimiri genome
J C Albrecht, J Nicholas, D Biller, K R Cameron, B Biesinger, C Newman, S Wittmann, M A Craxton, H Coleman, B Fleckenstein
The solid-state structures of two metal-pyridine-sulfate compounds, namely catena-poly[[tetrakis(pyridine-κN)iron(II)]-μ-sulfato-κ2 O:O′], [Fe(SO4)(C5H5N)4]n, (1), and catena-poly[[tetrakis(pyridine-κN)cobalt(II)]-μ-sulfato-κ2 O:O′-[tetrakis(pyridine-κN)cobalt(II)]-μ-sulfato-κ3 O,O′:O′′-[tris(pyridine-κN)cobalt(II)]-μ-sulfato-κ2 O:O′], [Co3(SO4)3(C5H5N)11]n, (2), are reported. The iron compound (1) displays a polymeric structure, with infinite chains of FeII atoms adopting octahedral N4O2 coordination environments that involve four pyridine ligands and two bridging sulfate ligands. The cobalt compound (2) displays a polymeric structure, with infinite chains of CoII atoms. Two of the three Co centers have an octahedral N4O2 coordination environment that involves four pyridine ligands and two bridging sulfate ligands. The third Co center has an octahedral N3O3 coordination environment that involves three pyridine ligands, and two bridging sulfate ligands with one sulfate chelating the cobalt atom.
crystal structure, pyridine, sulfate, transition metals, crystal field theory, coordination chemistry
The crystal structures of iron and cobalt pyridine (py)-sulfates, [Fe(SO4)(py)4]n and [Co3(SO4)3(py)11]n
Duyen N. K. Pham,a Mrittika Roy,a Ava Kreider-Mueller,a James A. Golen,a and David R. Mankea,*
2018 Jun 1;