Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide, and it is the second leading cause of cancer-related mortality. Aquaporin 9 (AQP9) is an essential aquaporin in the liver and located in the basolateral membrane of hepatocytes, but its roles on HCC has not been completely elucidated. This study investigated the regulatory functions of AQP9 in the pathogenesis of HCC. The expression levels of AQP9 were significantly down-regulated in HCC tissues and cells, which was also correlated with tumor size and number, TNM stage, five-year survival rate, lymphatic and distal metastasis within the patients. Furthermore, overexpressed AQP9 suppressed the proliferation, migration and invasion of HCC cells. The levels of PCNA, E-cad, N-cad, α-SMA, DVL2, GSK-3β, cyclinD1 and β-catenin in HCC cells were reduced by overexpressed AQP9, while cell apoptosis was remarkably enhanced. Additionally, following the treatment with Wnt/β-catenin signaling inhibitor (XAV939), the proliferative activity of HCC cells was significantly inhibited; PCNA and EMT-related markers were down-regulated; migration and invasion of cells were notably suppressed; cell apoptotic rate was decreased. Vice versa, after the cells were treated with Wnt/β-catenin inducer (SKL2001), the effects caused by overexpressed AQP9 were abrogated. In vivo studies indicated that tumor volume and weight were remarkably decreased in AQP9 overexpression group, where the levels of Wnt/β-catenin signaling- and EMT-associated molecules were also reduced. Taken together, our results suggested that overexpressed AQP9 could inhibit growth and metastasis of HCC cells via Wnt/β-catenin pathway. AQP9 may be a promising therapeutic target for the treatment of patients with HCC.

Background: Proton pump inhibitors (PPIs) are commonly used in the treatment of acid-related diseases; however, the association between the use of PPIs and potential risk of hypomagnesemia is controversial. Methods: In the present study, databases including PubMed, EMBASE, MEDLINE, PsycINFO, CINAHL, the Cochrane Library, and 4 Chinese databases were searched since the inception until April 2018. Previous observational studies on the incidence of hypomagnesemia in individuals exposed to PPIs were included. Results: This systematic review involved 15 studies including 129,347 participants, and the sample size varied from 52 to 95,205. Meta-analysis of 14 studies indicated that the use of PPIs increased the risk of hypomagnesemia [RR, 1.44, 95% CI, 1.13–1.76; I², 85.2%]. Subgroup analysis revealed that the use of PPI was not associated with the incidence of hypomagnesemia in outpatients [RR, 1.49; 95% CI, 0.83–2.14; I², 41.4%] and hospitalized patients [RR, 1.05; 95% CI, 0.81–1.29; I², 62.1%], respectively. The use of PPIs was not related to the risk of hypomagnesemia based on the cut-off values of 1.8 mg/dL [RR, 1.73; 95% CI, 0.87–2.58; I², 65.2%], 1.7 mg/dL [RR, 1.48; 95% CI, 0.90–2.06; I², 87.6%], and 1.6 mg/dL [RR, 0.98; 95% CI, 0.69–1.27; I², 67.9%]. Conclusion: The association between the exposure to PPI and the incidence of hypomagnesemia remained unclear. Due to the remarkable heterogeneity in previous studies, a definitive conclusion could not be drawn. Further research should be conducted to investigate the relationship between the use of individual PPI and potential risk of hypomagnesemia, and a dose-response analysis may be required.

Immune regulation plays a crucial role in human health and disease. Inflammatory bowel disease (IBD) is a chronic relapse bowel disease with an increasing incidence worldwide. Clinical treatments for IBD are limited and inefficient. However, the pathogenesis of immune-mediated IBD remains unclear. This review describes the activation of innate and adaptive immune functions by intestinal immune cells to regulate intestinal immune balance and maintain intestinal mucosal integrity. Changes in susceptible genes, autophagy, energy metabolism, and other factors interact in a complex manner with the immune system, eventually leading to intestinal immune imbalance and the onset of IBD. These events indicate that intestinal immune imbalance is an alarm for IBD development, further opening new possibilities for the unprecedented development of immunotherapy for IBD.

Aquaporins (AQPs) are highly conserved small transmembrane proteins, which are responsible for the water transport across the cell membrane. AQPs are abundantly expressed in numerous types of cells such as epithelial and endothelial cells. The expression of AQP-1, -3, -4, -5, -8 and -9 were found in the digestive system, where these six AQP isoforms serve essential roles including mediating the transmembrane water transport and regulating the secretion of gastrointestinal (GI) fluids, consequently facilitating the digestion and absorption of GI contents. In addition, the expression levels of AQPs are controlled by various factors, and AQPs can stimulate numerous signaling pathways; however, aberrant expression of AQPs in the GI tracts are associated with the initiation and development of numerous diseases. Thus, this review provides an overview of the expression and functions of AQPs in the digestive system.