Alterations of the salivary microbiota in gastroesophageal reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is among the most prevalent gastrointestinal disorders. The oral microbiota plays an important role in human health and may be altered by the presence of GERD. Here, we aimed to investigate the alterations of salivary microbiota in GERD patients. METHODS: We collected clinical information and salivary samples from 60 individuals. All participants underwent combined pH/impedance monitoring measurement and submitted samples for salivary microbiota sequencing. According to acid exposure time and DeMeester score, participants were divided into two groups: GERD + (Group G) and GERD - (Group C). RESULTS: There was no significant difference in alpha diversity between study groups. Regarding beta diversity, principal coordinate analysis plots indicated that the microbiota composition data of the participants were grouped within partial overlapping clusters. The statistical analysis of the distance matrices was performed using the Adonis test (p = 0.017). Based on linear discriminant analysis effect size, the relative abundances of the phylum Bacteroidetes, class Bacteroidia, order Bacteroidales, family Prevotellaceae, and genus unidentified_Prevotellaceae were enriched in Group G. Compared with Group C, the phylum Actinobacteria, classes unidentified_Actinobacteria and Bacilli, orders Micrococcales and Lactobacillales, families Micrococcaceae and Streptococcaceae, and genuses Rothia and Streptococcus were decreased in Group G. At the genus level, the abundances of Streptococcus and Rothia were negatively correlated with DeMeester score and acid exposure time. CONCLUSIONS: This study revealed alterations of the salivary microbiota in GERD patients, suggesting that acid reflux changes the oral ecosystem.

Inhibitory effects of canagliflozin on pancreatic cancer are mediated via the downregulation of glucose transporter­1 and lactate dehydrogenase A.

Pancreatic cancer is one of the most lethal solid malignancies, with a poor prognosis and a high mortality rate. Pancreatic cancer cells exhibit enhanced glycolysis to maintain their rapid growth. Canagliflozin (CANA) is a sodium­glucose co­transporter 2 inhibitor used for the clinical treatment of diabetes. Recent studies have demonstrated the potential ability of CANA to suppress hepatocellular carcinoma, whereas its therapeutic effects on and mechanisms in pancreatic cancer have rarely been reported. In the present study, the antitumor effects of CANA on pancreatic cancer were investigated. The data obtained indicated that pancreatic cancer growth was effectively suppressed by CANA in a dose­dependent manner, with peak inhibition rates of 54.3 and 57.6% in cultured Capan­1 and PANC­1 cells respectively. The tumor inhibitory rate reached 45.2% in nude mice with PANC­1­derived tumors, suggesting its effective antitumor activity against pancreatic cancer in vitro and/or in vivo. In addition, the combined treatment of Capan­1 and PANC­1 cells with gemcitabine and CANA exhibited a greater efficacy compared with that of treatment with gemcitabine alone. Moreover, glucose uptake and lactate production were decreased, and the mRNA levels of the glycolysis­associated genes, including glucose transporter­1 and lactate dehydrogenase A were decreased, indicating the inhibitory effects caused by the combination treatment on the metabolism of glucose in pancreatic cancer cells. Furthermore, CANA induced apoptosis, notably early apoptosis, and decreased the protein levels of PI3K, p­AKT, p­mTOR and HIF­1α, which indicated that the PI3K/AKT/mTOR signaling pathway was involved in the glycolytic process. These results demonstrated that pancreatic cancer growth was effectively inhibited by CANA via the suppression of glycolysis. This was mediated primarily by the PI3K/AKT/mTOR signaling pathway, revealing the underlying role and potential of this pathway for the clinical treatment of pancreatic cancer. Novel applications for the existing drug CANA can be explored, which could reduce the cost and time required for drug development in the field of drug discovery.

Characterization of a polysaccharide from Eupolyphaga sinensis walker and its effective antitumor activity via lymphocyte activation.

A polysaccharide (ESPS) purified from Eupolyphaga sinensis Walker by ion exchange chromatography and gel chromatography was investigated, including its structure characterization and antitumor activity. The results showed that ESPS was composed of rhamnose, fucose, arabinose, xylose, glucose, and galactose in a molar ratio of 7.4: 3.1: 13.9: 9.3: 39.7: 26.5, with the mean weight (Mw) of 2.14 × 104Da; the main chain of ESPS was mainly composed of → 4) - α - D - Glcp - (1 â†’ and → 3) - ß - D - Galp - (1 →, and the side chains were connected to the main chain through the O-6 atom of glucose and O-4 and O-6 atom of galactose. In addition, ESPS promoted the lymphocyte proliferation and inhibited liver cancer cells growth through enhancing lymphocyte activity in vitro, mainly NK cells. Moreover, ESPS markedly stimulated immunity in H22-bearing mice by increasing the spleen and thymus indices and effectively inhibited H22 cell growth in vivo. These data indicated that ESPS was a polysaccharide component possessing high anti-hepatocellular carcinoma activity, representing a potential immunotherapy candidate for the treatment of liver cancer.

Polysaccharide enhanced NK cell cytotoxicity against pancreatic cancer via TLR4/MAPKs/NF-κB pathway in vitro/vivo.

A polysaccharide isolated from Strongylocentrotus nudus eggs (SEP) reportedly displays immune activity in vivo. Here, its effect and underlying mechanism in the treatment of pancreatic cancer were investigated. SEP obviously inhibited pancreatic cancer growth by activating NK cells in vitro/vivo via TLR4/MAPKs/NF-κB signaling pathway, The tumor inhibitory rate achieved to 44.5% and 50.8% at a dose of 40 mg/kg in Bxpc-3 and SW1990 nude mice, respectively. Moreover, SEP obviously augmented the Gemcitabine (GEM) antitumor effect by upregulating NKG2D, which improved the sensitivity of NK cells targeting to its ligand MICA; meanwhile, the antitumor inhibitory rate was 68.6% in BxPC-3 tumor-bearing mice. Moreover, SEP reversed GEM-induced apoptosis and atrophy in both spleen and bone marrow via suppressing ROS secretion in vivo. These results suggested that pancreatic cancer was effectively inhibited by SEP-enhanced NK cytotoxicity mediated primarily through TLR4/MAPKs/NF-κB signaling pathway, representing a potential immunotherapy candidate for the treatment of pancreatic cancer.