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Neural precursor cell Expressed‚Developmentally Down-regulated protein 4 (NEDD4-1‚ also known as NEDD4 in some papers) is a tumor-related protein that has attracted much attention in recent years. It belongs to the E3 HECT (homologous to E6 associated protein C terminus) ubiquitin ligase‚ which could ubiquitinate various proteins that are subsequently degraded in lysosomes or proteasomes‚ or mediate their nuclear-cytoplasmic translocation‚ or indirectly affect various signaling pathways of different malignant tumors. With the deepening of a large number of tumor-related experiments‚ it has been found that NEDD4-1 can affect the biological behavior of tumors by regulating cell cycle‚ invasion and metastasis of cancer cells‚ antagonize drug resistance and many other pathways. In digestive system tumors‚ NEDD4-1 mainly promotes the proliferation‚ invasion and migration of hepatocellular carcinoma through multiple pathways such as PTEN/ PI3K/ Akt‚ TGF-β‚ Hippo and LDLRAD4. In pancreatic cancer‚ NEDD4-1 acted as an oncogene in the PI3K/ Akt signaling pathway‚ but acted as a tumor suppressor gene in the Myc-Sirt2 signaling circuit. In gastric and colorectal cancer‚ the NEDD4-1-related signaling pathways are different from other digestive system tumors. NEDD4-1 promotes gastric cancer progression and metastasis (via the EGFR signaling pathway) and inhibits colorectal cancer tumor growth (via the Wnt signaling pathway) independently of the PTEN/ PI3K/ Akt pathway. NEDD4-1 has become a hot research direction for therapeutic purposes. In this paper‚ we summarize the functions‚ signaling pathways and potential inhibitors of NEDD4-1 in different digestive system tumors‚ and discuss the relationship between NEDD4-1 and different signaling pathways‚ aiming to provide important reference data for cancer therapy.
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OBJECTIVE@#To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP).@*METHODS@#AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HP, Group C with HP, Group D with HP and CWNAE, and Group E with HP and CWNAE. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and tumor invasion assays, examinations of morphology and ultramicroscopic structures, quantitative real-time polymerase chain reaction and Western blots were performed to measure the effects and uncover the mechanisms behind these effects of HP and CWNAE on the epithelial-mesenchymal transition (EMT) of AGS cells.@*RESULTS@#The 10% inhibitory concentration of CWNAE against AGS cells after a 48 h incubation was 19.73±1.30 μg/mL. More AGS cells were elongated after co-culturing with HP than after culturing with HP. In tumor invasion assays, HP significantly enhanced the invasiveness of AGS cells compared to the other experimental groups (all P value <0.05), and this effect was inhibited by CWNAE. Treatment with CWNAE normalized tight junctions and reduced the number of pseudopodia of AGS cells co-cultured with HP. HP up-regulated zincfinger ebox binding homeobox 1 (ZEB1) in AGS cells after co-culturing for 24 h. Expression of caudal type homeobox transcription factor (CDX-2) and claudin-2 was significantly increased by HP (P<0.05), but not by HP.@*CONCLUSION@#HP promoted the invasiveness of AGS cells through up-regulation of ZEB1 transcription and claudin-2 and CDX-2 expression. CWNAE inhibited these effects of HP on AGS cells by down-regulating ZEB1 transcription, and CDX-2 and claudin-2 expression.
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Objective To determine the prevalence of post traumatic stress disorder (PTSD) in the army officers and soldiers (AOSs),and identify its relationship with functional gastrointestinal disorders (FGIDs).Methods PTSD and FGIDs were diagnosed based on the PTSD checklist--civilian (PCL-C) and Rome Ⅲ Modular Questionnaire respectively,the overlaps of PTSD and FGIDs and their correlation were diagnosed.The correlation of PTSD with traumatic and stressful events was investigated using Trauma History and Stressful Event Screening Questionnaire.The coexistence and relationship of PTSD and FGIDs were analyzed.Results Of 927 AOSs,33 were diagnosed with PTSD.The prevalence of PTSD was 3.56％.FGIDs were identified in 435 subjects and the incidence of FGIDs was 46.93％.Among 33 AOSs with PTSD,28 were diagnosed as having FGIDs and the prevalence of FGIDs was 84.85％,which was significantly higher than that of non-PTSD group (45.53％,P＜0.05).Moreover,the FGIDs group had a higher prevalence of PTSD,compared with the non-FGID group (6.43％ vs.1.02％,P＜0.05).Cyclic vomiting syndrome (CVS,33.33％),unspecified functional bowel disorder (24.24％),functional bloating (18.18％) and functional anorectal pain (18.18％) were the four most frequent FGIDs in PTSD AOSs.Multiple regression analysis showed PTSD was the risk factor for CVS (OR=9.118),functional anorectal pain (OR=3.373),functional bloating (OR=4.772),irritable bowel syndrome (OR=3.438),rumination syndrome (OR=16.033),functional vomiting (OR=10.329),functional dysphagia (OR=9.891)(P＜0.05).CVS (OR=4.063),the number of traumatic (OR=1.159) and stress events (OR=1.401) were the risk factors for PTSD in AOSs (P＜0.05).Conclusions PTSD and FGID interact as risk factor each other.The prevalence of PTSD differs significantly in different FGIDs.CVS is the most frequent FGID in PTSD AOSs and risk factor for PTSD,which deserves more concerns.
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<p><b>OBJECTIVE</b>To study the role of nuclear factor (NF)-kappaB pathway with p38MAPK in Curcuma wenyujin diterpenoid compound C (CDCC) fighting against inflammation and inducing gastric cancer cell apoptosis by stimulating gastric cell SGC7901 with tumor necrosis factor-alpha (TNF-alpha).</p><p><b>METHODS</b>Human umbilical vein endothelial cells (HUVECs) and human gastric cancer SGC-7901 cells were in vitro acted by CDCC in different concentrations at different time points. Their growth inhibition ratios were measured by MTT assay. The apoptosis rate of gastric cancer cells was detected by Annexin V-FITC/PI double staining. Nuclear translocation of p65 was detected by cell immunofluorescence. Expression levels of p38MAPK/P-p38MAPK, p65/P-p65, and Caspase 3/P-Caspase 3 were measured by Western blot.</p><p><b>RESULTS</b>CDCC had significant inhibitory effect on the proliferation of SGC-7901. It also could effectively induce the apoptosis of gastric cancer cell SGC-7901. It also could reduce nuclear translocation of p65 in gastric cancer cell SGC-7901. Results of Western blot indicated that expression levels of p38MAPK and p65 were reduced and the expression level of Caspase-3 was elevated along with increased concentrations of CDCC (P<0.05).</p><p><b>CONCLUSION</b>Apoptosis executive protein Caspase 3 activated by regulating p65 via p38MAPK might be one of possible mechanisms for CDCC fighting against inflammation and gastric cancer.</p>