VMP1 promotes exosome secretion and enhances 5-FU resistance in colon cancer cells.

BACKGROUND: Drug resistance of colon cancer cells is the key to affect the efficacy of colon cancer chemotherapy and lead to chemotherapy failure. Recent studies have found that exosomes play an important role in chemoresistance of colon cancer, while the expression of VMP1 may be involved in exosome secretion. METHOD: Drug sensitivity of colon cancer cells was detected by MTT. VMP1 expression levels were detected by qPCR and western blot. Expression of VMP1 was silenced in SW620 and HT-29 cell lines. Exosomes were isolated by ultracentrifugation, the particle size and concentration of exosomes were analyzed by NTA, and the morphology of exosomes was investigated by transmission electron microscopy. Exosome marker protein expression was detected by Western blot. The effect of exosomes on 5-FU sensitivity in SW620 and HT-29 cells was examined by MTT and western blot. RESULTS: VMP1 presented high expression in SW620 and HT-29 cells, their VMP1 gene and protein levels were significantly higher than those in SW480 and HCT116 cells, they were less sensitive to 5-FU, and exosome secretion was significantly reduced in SW620 and HT-29 cells after silencing of VMP1. Importantly, addition of exosomes to cells after silencing of VMP1 re-improved drug resistance. Co-incubation of exosomes secreted from SW620 and HT-29 cells with homologous cells significantly increased cell viability after 5-FU (50 µM) treatment, and increased the expression levels of the resistance protein ABCC1 and the anti-apoptotic protein Bcl-2. CONCLUSION: High expression of VMP1 in colon cancer cells is able to promote exosome secretion, which mediates the acquisition of more drug-resistant properties by cancer cells.

Effect of Evidence-Based Pharmacy Care on Satisfaction and Cognition in Patients with Non-Valvular Atrial Fibrillation Taking Rivaroxaban.

PURPOSE: We aimed to determine the effects of using evidence-based pharmacy care on satisfaction and cognition among patients with non-valvular atrial fibrillation (NVAF) and taking rivaroxaban. PATIENTS AND METHODS: Between July 2018 and June 2019, 200 consecutive hospitalized patients taking oral rivaroxaban, who were diagnosed with NVAF and registered in the hospital information management system, were randomly assigned to a control group (n=100) and a study group (n=100) in a single-blind manner. The control group received pharmaceutical care based on the general pharmaceutical care model whereas the study group received care based on an evidence-based pharmaceutical care model. Patients' satisfaction and cognition were evaluated regularly using questionnaires. The follow-up time was 1 year. We compared differences in satisfaction and cognition between the two groups after pharmaceutical-related care administered by clinical pharmacists. RESULTS: The study group had higher satisfaction scores than the control group after the EBP intervention (14.58±0.88 vs.13.81±1.01, p<0.01); cognition scores were also higher in the study group (22.58±2.19 vs 20.80±3.02, p<0.01) after the intervention. In the study group, satisfaction was increased from a score of 10.15±1.33 before the EBP intervention. Cognition also increased after the intervention in the study group, from a score of 9.88±4.09 pre-intervention. In the control group, satisfaction was 10.04±1.29 before the traditional pharmaceutical care intervention, smaller than the 13.81±1.01 after the intervention (p<0.01). Cognition in the control group was 9.83±3.51 before traditional pharmaceutical care, smaller than the 20.80±3.02 after the intervention (p<0.01). CONCLUSION: The care model based on evidence-based pharmacy care can improve patient satisfaction and cognition, providing more comprehensive safety and efficacy of subsequent medication.

Biodegradation of bis(2-hydroxyethyl) terephthalate by a newly isolated Enterobacter sp. HY1 and characterization of its esterase properties.

Bis(2-hydroxyethyl) terephthalate (BHET) is an important compound produced from poly(ethylene terephthalate) (PET) cleavage. It was selected as the representative substance for the study of PET degradation. A bacterial strain HY1 that could degrade BHET was isolated and identified as Enterobacter sp. The optimal temperature and pH for BHET biodegradation were determined to be 30°C and 8.0, respectively. The half-life of degradation was 70.20 h at an initial BHET concentration of 1,000 mg/L. The results of metabolites' analysis by liquid chromatograph-mass spectrometer revealed that BHET was first converted to mono-(2-hydroxyethyl) terephthalate (MHET) and then to terephthalic acid. Furthermore, an esterase-encoding gene, estB, was cloned from strain HY1, and the expressed enzyme EstB was characterized. The esterase has a molecular mass of approximately 25.13 kDa, with an isoelectric point of 4.68. Its optimal pH and temperature were pH 8.0 and 40°C, respectively. The analysis of the enzymatic products showed that EstB could hydrolyze one ester bond of BHET to MHET. To the best of authors' knowledge, this is the first report on the biodegradation characteristics of BHET by a member of the Enterobacter genus.