The ENAH gene, which encodes a member of the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins, is involved in the assembly of actin filaments required for cell adhesion and motility. Recent studies show overexpressed ENAH in several cancer types, and ENAH correlates with tumor invasiveness. This study aimed to investigate the expression and function of ENAH in primary gastric adenocarcinoma, and its prognostic significance. We found significantly increased mRNA (P = 0.0283) and protein (P = 0.0301) expression of ENAH in gastric cancer tissues. ENAH expression markedly associated with tumor size (P < 0.001), T stage (P < 0.001), N stage (P = 0.001), TNM stage (P < 0.001) and prognosis (P < 0.001). Cox regression analyses revealed ENAH expression as an independent predictor of overall survival (P = 0.019). We also analyzed data of 155 gastric cancer cases from The Cancer Genome Atlas (TCGA) and found that ENAH expression significantly correlated with age (P = 0.003), T stage (P = 0.023) and prognosis (P = 0.05). Furthermore, the function of ENAH in cell proliferation, colony formation, cell migration and invasion of gastric cancer cells was analyzed in vitro. Knockdown of ENAH expression suppressed cell proliferation, colony formation, cell migration and invasion in MKN45 cells. Conversely, overexpression of ENAH promoted cell proliferation, cell migration and invasion in MGC803 cells. Our research suggests that ENAH might play promoting functions in carcinogenesis and progression of gastric cancer, and may serve as a valuable prognostic marker for primary gastric adenocarcinoma patients.

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SummaryYoung guinea pigs were fed a semipurified diet low in selenium (Se) and phospholipid. The blood Se and tissue glutathione peroxidase activity were lowered, electrocardiogram and ultrastructure of the myocardium appeared abnormal, and tissue chromolipids were elevated in guinea pigs fed with this basal diet. Diminished changes, however, occurred in groups receiving supplemental Se. Supplementation of Se resulted in maintenance of the normal level of total phospholipid and the ratio between different phospholipids in the cartilage (Acta Pharmacol. Sinica, 5 (1984) 264-267), but in the heart the ratio was improved only when adequate phospholipid (especially endogenous phospholipid) was given simultaneously. Activity of the membrane binding enzyme was slightly restored by Se supplementation. Only when both phospholipid and Se were given sufficiently did the cytochrome oxidase activity in myocardium and CAMP level in plasma increase markedly, even more than that of the control group.

The aim of the current study was to determine the effect of parathyroid hormone (PTH) 1–34 on cartilage degeneration, and the association between PTH 1–34 and factors associated with the Wnt/β-catenin pathway following anterior cruciate ligament and medial meniscectomy-induced osteoarthritis (OA) in rats. A total of 64 Sprague-Dawley rats were randomly divided into the following four groups: Sham-operated rats with normal saline (NS)-treatment (n=16); anterior cruciate ligament transection with partial medial meniscectomy (ACLT + MMx) rats with NS-treatment (n=16); sham-operated rats treated with PTH 1–34 (n=16); and ACLT + MMx rats treated with PTH 1–34 (n=16). PTH (15 µg/kg/day) was administered via subcutaneous injection 5 days per week from the first postoperative day for 2 or 6 weeks. Staining with hematoxylin and eosin and safranin O, and a scoring system modified by Mankin were used to assess the histopathological features of cartilage. The present study detected the expression of PTH 1 receptor (PTH1R), sclerostin, dickkopf Wnt signaling pathway inhibitor 1 (DKK1), β-catenin and runt-related transcription factor 2 (RUNX2) in cartilage by immunohistochemical analysis to determine the association between PTH 1–34 and factors associated with the Wnt/β-catenin pathway. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression levels of PTH1R and β-catenin in cartilage. Histological analysis demonstrated that cartilage degeneration was present post-surgery and gradually increased over time. PTH 1–34 reduced the Mankin scores in ACLT + MMx rats compared with the NS-treated ACLT + MMx rats. Immunohistochemistry and RT-qPCR analysis demonstrated that, in cartilage, PTH 1–34 treatment increased the mRNA expression and protein levels of PTH1R and β-catenin, and decreased protein levels of sclerostin, DKK1 and RUNX2 in ACLT + MMx rats compared with the NS-treated ACLT + MMx group. The present study demonstrated that PTH 1–34 upregulated the Wnt/β-catenin signaling pathway and that PTH1-34 downregulated RUNX2 through an alternative pathway to the Wnt/β-catenin signaling pathway, in a rat model of OA.

Organic nitrates are still widely used in the therapy of patients with ischaemic heart disease because they induce vasorelaxation by releasing nitric oxide (NO) to activate soluble guanylyl cyclase to increase the levels of cyclic guanosine monophosphate in vascular smooth muscle cells. 1,2 However, continuous exposure to nitrate esters can lead to nitrate tolerance. Whether long-term nitrate therapy delays the recovery of cardiac function after acute myocardial infarction (MI) remains unknown.