ABSTRACT
BACKGROUND: The effects of Helicobacter pylori (H. pylori) infection on metabolic syndrome (MetS) in pregnant women are unclear to date. This study was designed to explore the relationship between H. pylori infection and MetS during pregnancy. METHODS: Pregnant women were enrolled in the prospective cohort study, and their demographic data and metabolic parameters were collected. H. pylori infection was measured using the C13 urea breath test. All enrolled patients were followed up until the last baby was born. Metabolic disorders, including elevated levels of serum triglycerides (TG), high-density lipoprotein (HDL) cholesterol and blood glucose (BG), and adverse pregnancy outcomes, including gestational diabetes mellitus (GDM), preeclampsia, spontaneous preterm birth (SPB), fetal growth restriction (FGR), and uncomplicated pregnancy, were recorded during follow up. RESULTS: There were 320 pregnant women enrolled in this study. They were divided into two groups according to H. pylori infection, and each group was then divided into two subgroups on whether their BMI was more than 24 or not. The results showed that H. pylori infection significantly increased the incidence of MetS as well as other metabolic disorders, especially in pregnant women with high BMI. Multivariable logistic regression analysis showed that risk factors of MetS were high BMI and H. pylori infection. Besides, H. pylori infection increased the incidence of GDM and preeclampsia and potentially reduced the incidence of uncomplicated pregnancy. CONCLUSIONS: H. pylori infection in pregnant women acts as a crucial risk factor of Mets and affects the incidence of several adverse pregnancy outcomes.
ABSTRACT
BACKGROUND: Siderophores are major virulent factors of K. pneumoniae, and their roles are iron chelators in the host. Several studies have shown that iron chelation could result in mitochondrial dysfunction and increase the production of reactive oxygen species (ROS), which further induces cell mitophagy and apoptosis. However, the impacts of siderophores on platelets are still unknown. METHODS: We obtained platelets of healthy volunteers to perform in vitro experiments in our study and treated platelets with different siderophores. Mitophagy related proteins (TOMM20, TIMM23, LC3, and p62), signal proteins (PINK1/Parkin and BNIP3), and apoptosis protein (caspase3) in platelets were analyzed by western blot. The co-localization of mitotracker with LC3-II was analyzed by immunofluorescence assays. The flow cytometer was used to evaluate ROS levels. RESULTS: All four kinds of siderophores (10 µM) secreted by K. pneumoniae increased the expression of LC3 II and reduced the expression of mitochondrial membrane protein, TOMM20, and TIMM23. Immunofluorescence assays revealed that the treatment of enterobactin significantly increased the co-localization of mitotracker with LC3-II. All four kinds of siderophores increased the ROS level in platelets. Mitophagy of platelets was activated through several pathways, including PINK1/Parkin- and BNIP3-dependent pathways. We also proved that siderophores increased the expression of caspase3 in platelets, and the expression of caspase3 significantly decreased after the pathways of mitophagy were blocked. CONCLUSIONS: K. pneumoniae siderophores lead to mitophagy in platelets, and mitophagy further induces apoptosis, which may be a potential treatment of thrombocytopenia in infections.
ABSTRACT
BACKGROUND: To investigate the correlation between Claudin-18 expression and the clinicopathological features and prognosis of gastric cancer. METHODS: A total of 63 patients who underwent gastric cancer surgery from December 2012 to June 2013 were recruited as the research participants. The clinicopathological data and prognostic information of the participants were collected, and expression levels of Claudin-18 in gastric cancer and adjacent tissues were detected by immunohistochemical (IHC) staining. The correlation between Claudin-18 expression and clinicopathological features of gastric cancer patients was analyzed. The Cox regression model was used to analyze the risk factors associated with the prognosis of gastric cancer patients. RESULTS: The expression of Claudin-18 was positive in 35 (55.6%) of the participants' gastric cancer tissues, which was significantly lower than that in the adjacent tissues (51 tissues/81.0%), and the difference was statistically significant (P=0.002). In addition, the IHC staining score of Claudin-18 expression in gastric cancer tissues (1.49±1.69), was significantly lower than that in the adjacent tissues (4.61±1.81), and the difference was statistically significant (P=0.016), The incidence of nerve invasion in patients with low expression of Claudin-18 was significantly higher than that in patients with high expression of Claudin-18 (P=0.038). In addition, univariate Cox regression analysis showed that nerve invasion, Claudin-18 staining score, tumor size, and positive count of lymph nodes were risk factors associated with the survival of gastric cancer patients. Multivariate Cox regression analysis showed that Claudin-18 staining score and tumor size were independent risk factors associated with the survival of gastric cancer patients. The overall survival (OS) of patients with low Claudin-18 staining score or larger tumor size was significantly reduced. CONCLUSIONS: The low expression of Claudin-18 was closely related to nerve invasion in gastric cancer, which indicated the poor clinical prognosis of gastric cancer patients.
ABSTRACT
The epithelial-to-mesenchymal transition (EMT) is a critical step in tumor metastasis. NEDD9 has been shown to be an oncogene in colorectal cancer. However, little is known about the relationship between NEDD9 and EMT in colorectal cancer metastasis. A total of 63 pairs of freshly frozen colorectal cancer tissues and adjacent noncancerous tissues were evaluated for NEDD9 gene expression using quantitative real-time PCR. The expression of NEDD9 and three epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, ß-catenin and vimentin) was examined in 122 colorectal cancers by immunohistochemistry. The expression of NEDD9 was markedly increased in colorectal cancer tissues compared with adjacent noncancerous tissues. The expression level of NEDD9 was positively correlated and TNM stage but not with other clinicopathological features of colorectal tumors. Furthermore, the expression of NEDD9 was strongly associated with the loss of epithelial marker E-cadherin and acquired expression of the mesenchymal markers nuclear ß-catenin and vimentin. These findings suggested that NEDD9 might promote EMT and the progression of colorectal cancer, and thus may be a potential therapeutic target of colorectal cancers.
ABSTRACT
The epithelialtomesenchymal transition (EMT) has been noted as a critical event in the early step of cancer metastasis. Recent studies showed that nuclear transcription factor caudal type homeobox transcription factor 2 (CDX2) is a prognostic factor, which acts as a marker of good outcome in gastric cancer (GC) patients. However, the association between CDX2 expression and EMT has remained to be fully elucidated. The present study reported that forced overexpression of CDX2 in MKN45/CDX2 cells inhibited GCcell growth and proliferation, and attenuated migration and invasion in vitro. Furthermore, MKN45/CDX2 cells exhibited a significant upregulation of Ecadherin protein and a significant downregulation of vimentin protein expression. These results were further supported by in vivo tumorigenicity assays, which showed that CDX2 suppressed gastric tumor xenograft growth and inhibited EMT in nude mice. These results indicated that CDX2 is capable of inhibiting GCcell growth and invasion. CDX2 may participate in the process of EMT of GC cells by regulating the expression of the epithelial and mesenchymal proteins Ecadherin and vimentin.
