Objective:To explore the expression and clinical significance of S100A8 and S100A9 in Helicobacter pylori ( H. pylori) associated gastritis. Methods:A total of 101 patients with chronic gastritis diagnosed in the First Hospital of Shanxi Medical University from October 2018 to May 2019 were selected. The expression levels of S100A8 and S100A9 in the gastric mucosa tissues of 101 patients with chronic gastritis were determined by immunohistochemistry (in absorbance), and the mRNA expression levels of S100 A8 and S100 A9 in the gastric mucosa tissues of 48 patients were detected by reverse transcription-polymerase chain reaction. And the results combined with pathological diagnosis of routine staining and clinical H. pylori infection data were analyzed. Mann-Whitney U test, Kruskal-Wallis H test and Spearman rank correlation were used for statistical analysis. Results:Among 101 patients, there were 59 cases of chronic atrophic gastritis (CAG group) and 42 cases of chronic non-atrophic gastritis (NAG group); 59 cases were H. pylori positive ( H. pylori positive group) and 42 cases were H. pylori negative ( H. pylori negative group). There were statistically significant differences in the expression levels of S100A8 and S100A9 between CAG group and NAG group (0.10, 0.07 to 0.13 vs. 0.09, 0.06 to 0.10 and 0.13, 0.08 to 0.15 vs. 0.09, 0.07 to 0.10, respectively), and between H. pylori positive group and H. pylori negative group (0.11, 0.10 to 0.13 vs. 0.07, 0.06 to 0.08 and 0.13, 0.10 to 0.15 vs. 0.07, 0.07 to 0.08, respectively) ( U=754.00, 602.00, 5.00 and 40.00, all P<0.01). There were statistically significant differences in the expression levels of S100A8 and S100A9 between H. pylori positive patients (34 cases) and H. pylori negative patients (25 cases) in CAG group (0.13, 0.11 to 0.14 vs. 0.07, 0.07 to 0.08 and 0.15, 0.14 to 0.16 vs. 0.08, 0.08 to 0.09, respectively), similarly, there were significant differences in the expression levels of S100A8 and S100A9 between H. pylori positive patients (25 cases) and H. pylori negative patients (17 cases) in NAG group (0.10, 0.09 to 0.10 vs. 0.06, 0.05 to 0.07 and 0.10, 0.10 to 0.11 vs. 0.07, 0.06 to 0.07, respectively) ( U=1.00, 0.00, 0.00 and 0.00, all P<0.01). The results indicated that the expression levels of S100A8 and S100A9 were high in H. pylori positive patients in CAG group, the expression levels of S100A8 and S100A9 were low in H. pylori negative patients in NAG group, and the differences were statistically significant ( H=84.78 and 89.64, both P<0.01). There were statistically significant differences in the expression of S100 A8 and S100 A9 at mRNA level between CAG group (24 cases) and NAG group (24 cases) (0.12, 0.06 to 1.31 vs. 0.05, 0.03 to 0.08; 0.19, 0.03 to 0.43 vs. 0.03, 0.01 to 0.09), and the expression of S100 A8 and S100 A9 at mRNA level was significant between H. pylori positive patients (24 cases) and H. pylori negative patients (24 patients) (0.45, 0.10 to 1.90 vs. 0.05, 0.03 to 0.08 and 0.36, 0.24 to 0.81 vs. 0.03, 0.01 to 0.04) ( U=55.00, 74.00, 19.00 and 2.00, all P<0.05). There were statistically significant differences in the expression of S100 A8 and S100 A9 at mRNA level between H. pylori positive patients (12 cases) and H. pylori negative patients (12 cases) of CAG group (0.85, 0.27 to 2.28 vs. 0.06, 0.03 to 0.09 and 0.39, 0.25 to 0.87 vs. 0.03, 0.02 to 0.05), and the expression of S100 A8 and S100 A9 at mRNA level was significant between H. pylori positive patients (12 cases) and H. pylori negative patients (12 cases) of NAG group (0.09, 0.05 to 0.28 vs. 0.04, 0.03 to 0.07 and 0.20, 0.09 to 0.65 vs. 0.01, 0.01 to 0.03) ( U=5.00, 2.00, 0.00 and 0.00, all P<0.01). The results showed that the expression of S100 A8 and S100 A9 at mRNA level was high in H. pylori positive patients in CAG group, the expression of S100 A8 and S100 A9 at mRNA level was low in H. pylori negative patients in NAG group, and the differences were statistically significant ( H=20.43 and 24.15, both P<0.01). The expression levels of S100A8 and S100A9 were positively correlated at both protein level and mRNA level ( r=0.899 and 0.903, both P<0.01). Conclusions:S100A8 and S100A9 may involve in the inflammation process of H. pylori-infected gastric mucosa and promote the proliferation of gastric epithelial cells, which may be one of mechanisms of intrinsic glands reduction and CAG genesis. S100A8 and S100A9 are expected to be potential biomarkers for diagnosis and follow-up and potential targets for treatmert of CAG.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.