Excessive iodine intake can induce autoimmune thyroiditis (AIT), and the methylation of programmed death receptor 2 (PD-L2) may be involved in the development of iodine-induced AIT. Here, we investigated the immune role of methylation of the susceptibility gene PD-L2 in the occurrence of iodine-induced AIT using the DNA methyltransferase inhibitor Decitabine (Dec) in an experimental autoimmune thyroiditis (EAT) rat model. After injecting Dec intraperitoneally into EAT rats, we performed arsenic-cerium catalytic spectrophotometry, pathological hematoxylin and eosin staining, enzyme-linked immunosorbent assay, quantitative methylation-specific polymerase chain reaction (qMSP), and quantitative real-time polymerase chain reaction (qPCR) to determine the relevant indices. The results showed that compared with the control group, the urinary iodine, thyroid lymphocyte infiltration, thyroglobulin antibody (TgAb), interferon (IFN-γ), and interleukin (IL-23) levels of the EAT rats were significantly increased. The PD-L2 methylation levels were significantly decreased in EAT rats compared to control rats, and the mRNA expression of the PD-L2 was significantly increased. Following Dec intervention, the methylation level of the PD-L2 in rats increased and interferon and interleukin-23 levels decreased, albeit not significantly. However, the mRNA expression of PD-L2 decreased significantly after Dec intervention, and the thyroid function of EAT rats also showed a gradual improvement trend. In summary, hypomethylation of PD-L2 is closely related to the development of iodine-induced AIT. Pro-inflammatory cellular factors are also involved in iodine-induced AIT progression. Although Dec shows promise in the treatment of AIT, further evaluation of its safety is necessary.

2024-11-02·MUTAGENESIS

Determination of global DNA methylation level by methylation-sensitive comet assay in patients with urinary bladder cancer

Article

作者: Onal, Bulent ; Kankaya, Selin ; Kalender, Goktug ; Kocak, Ozer ; Dincer, Yildiz ; Citgez, Sinharib

Abstract:

DNA methylation is an important mechanism in the regulation of gene expression and maintenance of genomic integrity. Aberrant DNA methylation is an early event in carcinogenesis. DNA methyltransferase inhibitors are used to restore aberrant DNA methylation and inhibit tumor growth. Evaluation of DNA methylation level is important for an effective anti-cancer therapy. In the present study, the determination of global DNA methylation levels in patients with urinary bladder cancer was proposed. The methylation-sensitive comet assay determined the global DNA methylation level at the level of single cells. McrBC enzyme, a methylation-sensitive restriction endonuclease, was used for enzymatic digestion to generate additional breaks at methylated sites. % DNA methylation level was significantly higher in patients with bladder cancer compared to the control group. The clinical performance of % DNA methylation analysis by methylation-sensitive comet assay was evaluated by ROC curve. Using the cutoff value of 6.5% DNA methylation, 92% sensitivity, and 42% specificity were obtained. In conclusion, global DNA methylation measured by methylation-sensitive comet assay may be a promising noninvasive biomarker that reduces interventional tests required in the diagnosis and follow-up of urinary bladder cancer.

2024-11-01·Current medicinal chemistry

The Impact of Alcohol-Induced Epigenetic Modifications in the Treatment of Alcohol use Disorders

Review

作者: Ferraguti, Giampiero ; Micangeli, Ginevra ; Ceccanti, Mauro ; Fiore, Marco ; Terracina, Sergio ; Fanfarillo, Francesca ; Fuso, Andrea ; Lucarelli, Marco ; Tarani, Luigi

Alcohol use disorders are responsible for 5.9% of all death annually and 5.1% of the global disease burden. It has been suggested that alcohol abuse can modify gene expression through epigenetic processes, namely DNA and histone methylation, histone acetylation, and microRNA expression. The alcohol influence on epigenetic mechanisms leads to molecular adaptation of a wide number of brain circuits, including the hypothalamus-hypophysis-adrenal axis, the prefrontal cortex, the mesolimbic-dopamine pathways and the endogenous opioid pathways. Epigenetic regulation represents an important level of alcohol-induced molecular adaptation in the brain. It has been demonstrated that acute and chronic alcohol exposure can induce opposite modifications in epigenetic mechanisms: acute alcohol exposure increases histone acetylation, decreases histone methylation and inhibits DNA methyltransferase activity, while chronic alcohol exposure induces hypermethylation of DNA. Some studies investigated the chromatin status during the withdrawal period and the craving period and showed that craving was associated with low methylation status, while the withdrawal period was associated with elevated activity of histone deacetylase and decreased histone acetylation. Given the effects exerted by ethanol consumption on epigenetic mechanisms, chromatin structure modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, might represent a new potential strategy to treat alcohol use disorder. Further investigations on molecular modifications induced by ethanol might be helpful to develop new therapies for alcoholism and drug addiction targeting epigenetic processes.

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