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Radon-induced demethylation of Cdk2 CpG island in the rat lung
Cheng Wu,Qiu Chen,Jian Tong,Xin Xie,Fengmei Cui,Yang Jiao,Dandan Qi,Jihua Nie,Tom K. Hei,Qisheng Jiang 한국유전학회 2014 Genes & Genomics Vol.36 No.6
Radon exposure has been linked to lung carcinogenesisin both human and animal studies. The identificationof sequential changes in DNA methylation duringtumour progression and the elucidation of their interplaywith genetic changes will broaden our molecular understandingof this disease. Rats were exposed to 120 or 400working level months (WLM) of radon, lung pathologicalchanges were examined by haematoxylin and eosin staining,lung single cell suspension cell cycles were detected byflow cytometry, lung cell cycle regulated gene (Cdkn2a,P53, Cdk4/2, Mdm4/2 and Rb1 genes) expression wasquantified by real-time PCR and methylation of CpG islandsin the promoters of cell cycle-regulated genes were detectedby bisulfite sequencing PCR. The alveolar walls of rat lungsafter exposured to radon exhibited papillae and the lungbronchial epithelial cells stained positively for proliferatingcell nuclear antigen. The bronchial epithelial cells displayedsome hyperplasia after challenged by 400 WLM of radon. Moreover, G1 arrest decreased; Rb1, Mdm2/4, and Cdk2/4expression decreased and Cdk2 was demethylated at thesecond and sixth CpG loci from base pairs 3092704 to3092953 of chromosome 7. Cdk2 demethylation may beapplicable as a biomarker of early lung damage that wasinduced by radon and other environmental carcinogens.
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Jing Ma,Suhe Dong,Hongtao Lu,Zhongmin Chen,Huijie Yu,Xuejun Sun,Renjun Peng,Wei Li,Sinian Wang,Qisheng Jiang,Fengsheng Li,Li Ma 한국생체재료학회 2022 생체재료학회지 Vol.26 No.2
Objective: This study aimed to reveal the protective effect of hydrogen storage nanomaterial MgH2 on radiationinduced male fertility impairment. Methods: The characterization of MgH2 were analyzed by scanning electron microscopy (SEM) and particle size analyzer. The safety of MgH2 were evaluated in vivo and in vitro. The radioprotective effect of MgH2 on the reproductive system were analyzed in mice, including sperm quality, genetic effect, spermatogenesis, and hormone secretion. ESR, flow cytometry and western blotting assay were used to reveal the underlying mechanisms. Results: MgH2 had an irregular spherical morphology and a particle size of approximately 463.2 nm, and the content of Mg reached 71.46%. MgH2 was safe and nontoxic in mice and cells. After irradiation, MgH2 treatment significantly protected testicular structure, increased sperm density, improved sperm motility, reduced deformity rates, and reduced the genetic toxicity. Particularly, the sperm motility were consistent with those in MH mice and human semen samples. Furthermore, MgH2 treatment could maintain hormone secretion and testicular spermatogenesis, especially the generation of Sertoli cells, spermatogonia and round sperm cells. In vitro, MgH2 eliminated the [·OH], suppressed the irradiation-induced increase in ROS production, and effectively alleviated the increase in MDA contents. Moreover, MgH2 significantly ameliorated apoptosis in testes and cells and reversed the G2/M phase cell cycle arrest induced by irradiation. In addition, MgH2 inhibited the activation of radiation-induced inflammation and pyroptosis. Conclusion: MgH2 improved irradiation-induced male fertility impairment by eliminating hydroxyl free radicals.
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Han, Qianqian,Yang, Pishan,Wu, Yuwei,Meng, Shu,Sui, Lei,Zhang, Lan,Yu, Liming,Tang, Yin,Jiang, Hua,Xuan, Dongying,Kaplan, David L.,Kim, Sung Hoon,Tu, Qisheng,Chen, Jake Mary Ann Liebert 2015 Tissue engineering. Part A Vol.21 No.15
<P>Epigenetic regulation of gene expression is a central mechanism that governs cell stemness, determination, commitment, and differentiation. It has been recently found that PHF8, a major H4K20/H3K9 demethylase, plays a critical role in craniofacial and bone development. In this study, we hypothesize that PHF8 promotes osteoblastogenesis by epigenetically regulating the expression of a nuclear matrix protein, special AT-rich sequence-binding protein 2 (SATB2) that plays pivotal roles in skeletal patterning and osteoblast differentiation. Our results showed that expression levels of PHF8 and SATB2 in preosteoblasts and bone marrow stromal cells (BMSCs) increased simultaneously during osteogenic induction. Overexpressing PHF8 in these cells upregulated the expression of SATB2, Runx2, osterix, and bone matrix proteins. Conversely, knockdown of PHF8 reduced the expression of these genes. Furthermore, ChIP assays confirmed that PHF8 specifically bound to the transcription start site (TSS) of the SATB2 promoter, and the expression of H3K9me1 at the TSS region of SATB2 decreased in PHF8 overexpressed group. Implantation of the BMSCs overexpressing PHF8 with silk protein scaffolds promoted bone regeneration in critical-sized defects in mouse calvaria. Taken together, our results demonstrated that PHF8 epigenetically modulates SATB2 activity, triggering BMSCs osteogenic differentiation and facilitating bone formation and regeneration in biodegradable silk scaffolds.</P>
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