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The aim of the present study was to investigate the significance of cell apoptosis, the phosphoinositide-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, and the 5' adenosine monophosphate-activated protein kinase (AMPK)‑mTOR pathways in the process of diabetic gastroparesis. Changes in gastric smooth muscle cells of diabetic rats with induced gastroparesis were examined. The diabetic rat model was established by dividing animals into a normal control group and diabetic model groups examined at 2, 4 and 6 weeks. Diabetic gastroparesis was evaluated by examining the rates of gastric residual pigment, whereas flow cytometry was used to detect the apoptosis of gastric smooth muscle cells. The expression levels of PI3K and phosphorylated (p‑) AKT, AMPK, mTOR, tuberous sclerosis complex 2, p70 ribosomal S6 kinase, and eukaryotic translation initiation factor 4‑binding protein 1 were determined in gastric muscles using western blot analysis. Diabetic gastroparesis was confirmed in models at 6 weeks. The apoptosis of gastric smooth muscle cells gradually increased in all diabetic groups, and significant changes were observed in key proteins involved in PI3K‑AKT‑mTOR and AMPK‑mTOR signaling. The results indicated that apoptosis was important in the occurrence of diabetic gastroparesis, and the PI3K‑AKT‑mTOR and AMPK‑mTOR pathways were activated during the apoptotic processes, but were incapable of regulating apoptosis.

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The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression. Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffinembedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting. Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells. Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.

Although the presence of C-type natriuretic peptide (CNP) in gastrointestinal tract has been demonstrated, the effect of CNP on interstitial cells of Cajal (ICC), pacemaker cells in gastrointestinal tract, is still unclear. This study was designed to investigate the effect of CNP on pacemaker currents of ICC and possible mechanisms. We used immunocytochemistry techniques to exhibit natriuretic peptide receptors (NPR) and recorded membrane currents by using whole-cell patch clamp technique on cultured ICC. Our experiment showed that NPR-A and NPR-B were expressed in ICC from murine small intestine. Whole cell recordings further showed that the amplitude of pacemaker currents in intestinal small networks of ICC was 322+/-22pA and the frequency was 16.25+/-0.95Hz. CNP significantly reduced the amplitude of pacemaker currents in small networks of ICC in a dose-dependent manner, and the amplitude was inhibited by 23.95%, 61.76% and 81.67%, the amplitude values in 329+/-28.0pA, 311.2+/-14.8pA and 295+/-26.5pA before treatment with CNP and 237.9+/-27.5pA, 119.6+/-18.5pA and 57.2+/-13.5pA after treatment with 0.01 micromolxL(-1), 0.1 micromolxL(-1) and 1pmolxL(-1) CNP, respectively. The frequencies of pacemaker currents were also significantly reduced from 16.25+/-0.95Hz of control to 13+/-0.9Hz, 12+/-0.8Hz and 3+/-0.2Hz by 0.01micromolxL 1, 0.1micromolxL(-1) and 1 micromol x L(-1) CNP, respectively. CNP also inhibited the amplitude of pacemaker currents in single ICC. The inhibitory effect of CNP was mimicked by 8-Br-cGMP, a membrane permeable cGMP analogue, which suggests that CNP could inhibit pacemaker currents via NPR-B-particulate guanylate cyclase (pGC)-cGMP signal pathway.