Morphologic characterization of residual DNA methylation in the gastric mucosa after Helicobacter pylori eradication
CANCER MEDICINE
Authors: Tahara, Sayumi; Tahara, Tomomitsu; Tuskamoto, Tetsuya; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Shibata, Tomoyuki; Kuroda, Makoto; Ohmiya, Naoki
Abstract
Residual DNA methylation in the gastric mucosa after Helicobacter pylori (H.pylori) eradication may have a role in gastric carcinogenesis. We examined the association between morphologic features and promoter methylation status of non-neoplastic gastric mucosa especially after H.pylori eradication. A total of 140 gastric specimens from 99 participants who had at least 6months of post-eradication period were examined. The magnifying narrow-band imaging (NBI) endoscopic feature of gastric mucosa was divided into two types: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA, and PRDM5) were examined by bisulfite pyrosequencing. The atrophic type, informative endoscopic features of intestinal metaplasia, demonstrated higher methylation levels in all five genes compared to the restored type (all P<0.0001). In the restored type, methylation levels were significantly lower among the samples with longer post-eradication period (for all genes, P<0.0001), which was not observed in atrophic type (for all genes, P>0.1). Multivariate analysis demonstrated that atrophic type or presence of intestinal held an independent factor for hyper methylation (odds ratio: 24.69, 95% confidence interval: 6.95-87.76, P<0.0001). The atrophic type by the magnifying NBI and presence of intestinal metaplasia are the morphologic characteristics of residual DNA methylation of after H.pylori eradication, regardless of the post-eradication period and it might be considered as the epigenetic irreversible point with H.pylori eradication.
Increased Expression of miR-1 in Fast-Twitch Skeletal Muscle in Response to Resistance Exercise
IRANIAN RED CRESCENT MEDICAL JOURNAL
Authors: Fathi, Mohammad; Gharakhanlou, Reza; Soleimani, Masoud; Rajabi, Hamid
Abstract
Background: The response of microRNA (miR-1), upstream regulators (Myogenic Differentiation 1 (MyoDi) and Myocyte Enhancer Factor 2C (Mef2C)), and a downstream target (Histone Deacetylase 4 (Hdac4)) to an acute bout of Resistance Exercise (RE) in Extensor Digitorum Longus (EDL) and soleus muscles has remained elusive. Objectives: In this experimental study, we investigated the effect of an acute bout of RE on the expression of miR-1, MyoD1, Mef2C, and Hdac4 genes in the slow and fast-twitch muscle of rats. Methods: The current study was conducted at Tarbiat Modares University, Tehran, Iran, in 2017. Fifteen male Wistar rats were randomly divided into two groups, control (n = 5) and RE (n =10). The RE protocol consisted of four sets of five repetitions of climbing a ladder with weights attached to the tails of rats. The soleus and EDL muscles of rats were collected at 3 h (n = 5) and 6 h (n = 5) post-RE. The real-time polymerase chain reaction was used to measure the levels of miR-1, MyoD1, Mef2C, and Hdac4 mRNA expression. Results: The miR-1 expression in EDL muscle was significantly lower at 3 h and 6 h post-exercise in the RE group than in the control group (P < 0.01). The miR-1 expression in soleus muscle was significantly lower at 3 h post-exercise in the RE group than in the control group (P < 0.007) but it was significantly higher at 6 h post-exercise (P < 0.036). The expression of MyoD1, Mef2C, and Hdac4 genes in the EDL muscle was higher in the RE group than in the control group (P < 0.01). The expression of these genes in response to RE had more fluctuations in soleus muscle. Conclusions: It can be concluded that miR-1 expression in extensor digitorum longus and soleus muscles of rats responds to resistance exercise in different manners and this coincides with a change in upstream regulators and downstream target.