Background/Aims: Human mutL homolog 1 (MLH1) promoter methylation was reported in gastric cancer (GC). This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. Methods: The combined odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area under the curve (AUC) were analyzed. Results: A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis. MLH1 promoter methylation was significantly higher in GC samples than in gastric adenomas, chronic gastritis, adjacent tissues, normal gastric mucosa, and normal healthy blood samples, but it exhibited a similar frequency in GC vs. intestinal metaplasia and dysplasia samples. MLH1 promoter methylation correlated with age and microsatellite instability (MSI), but it was not associated with gender, H. pylori infection, smoking, drinking behaviors, pathological histology, tumor differentiation, clinical stage, lymph node status, distant metastasis, or overall survival of GC. MLH1 promoter methylation exhibited a poor sensitivity value (< 0.5) in patients with GC compared with adjacent tissues, gastric adenomas, chronic gastritis, normal gastric mucosa, and normal healthy blood samples. The pooled sensitivity, specificity, and AUC of MLH1 promoter methylation in GC with MSI vs. GC with microsatellite stability (MSS) samples were 0.64, 0.96, and 0.90, respectively. Conclusions: Our results suggest that the detection of MLH1 promoter methylation may be a potential prognostic biomarker for GC patients with MSI.

Helicobacter pylori (H. pylori) infection has an important effect on human health as it is an established cause of gastric carcinoma. microRNAs (miRNAs/miRs) are a family of small RNAs with various functions in the control of cellular profiles. However, the effect of miR‑100 in H. pylori infection remains unknown. Healthy volunteers (n=100) and patients with H. pylori infection (n=98) were included in the present study. H. pylori infection was confirmed by urea breath tests. The levels of miR‑100 in gastroscopic biopsy samples and cultured GES‑1 cells were measured by reverse transcription‑quantitative polymerase chain reaction. Furthermore, miR‑100 was overexpressed or inhibited in GES‑1 cells by an miR‑100 mimic or inhibitor, respectively. The expression of cell‑junction proteins and members of the mechanistic target of rapamycin kinase (mTOR) signaling pathway was investigated by western blotting. The results demonstrated that miR‑100 levels were upregulated in infected patients and cultured gastric epithelial cells, compared with the respective controls. Additionally, the expression of epithelial (E)‑cadherin and zona occludens‑1 in the gastric mucosa of infected patients and GES‑1 cells was downregulated. Furthermore, infected gastric epithelial cells exhibited impaired barrier functions, as measured by resistance and permeability tests. Overexpression of miR‑100 inhibited junction protein expression, as well as the activation of the mTOR signaling pathway, while suppression of miR‑100 restored E‑cadherin expression and mTOR signaling. The results of the present study indicate that H. pylori infection may cause dysfunction of the gastric epithelial barrier by increasing miR‑100 levels, which subsequently inhibit mTOR signaling. These results may have potential applications affecting miR‑100 in H. pylori‑related diseases.

Flowering is central to the transformation of plants from vegetative growth to reproductive growth. The circadian clock system enables plants to sense the changes in the external environment and to modify the growth and development process at an appropriate time. Photoperiod-1 (Ppd-1), which is controlled by the output signal of the circadian clock, has played an important role in the wheat “Green Revolution.” In the current study, we systematically studied the relationship between Ppd-1 haplotypes and both wheat yield- and quality-related traits, using genome-wide association analysis and transgenic strategies, and found that highly appropriate haplotypes had been selected in the wheat breeding programs. Genome-wide association analysis showed that Ppd-1 is associated with significant differences in yield-related traits in wheat, including spike length (SL), heading date (HD), plant height (PH), and thousand-grain weight (TGW). Ppd-1-Hapl-A1 showed increased SL by 4.72–5.93%, whereas Ppd-1-Hapl-B1 and Ppd-1-Hapl-D1 displayed earlier HD by 0.58–0.75 and 1.24–2.93%, respectively, decreased PH by 5.64–13.08 and 13.62–27.30%, respectively, and increased TGW by 4.89–10.94 and 11.12–21.45%, respectively. Furthermore, the constitutive expression of the Ppd-D1 gene in rice significantly delayed heading date and resulted in reduced plant height, thousand-grain weight, grain width (GW), and total protein content. With reference to 40years of data from Chinese wheat breeding, it was found that the appropriate haplotypes Ppd-1-Hapl-A1, Ppd-1-Hapl-B1, and Ppd-1-Hapl-D1 had all been subjected to directional selection, and that their distribution frequencies had increased from 26.09, 60.00, and 52.00% in landraces to 42.55, 93.62, and 96.23% in wheat cultivars developed in the 2010s. A Ppd-B1 methylation molecular marker was also developed to assist molecular wheat breeding. This research is of significance for fully exploring the function of the Ppd-1 gene and its genetic resource diversity, to effectively use the most appropriate haplotypes and to improve crop yield and sustainability.

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