Non-antibiotic alternative treatments to combat the increasing number of infections caused by multidrug resistant bacteria are urgently needed. In recent years, bacteriophages have reemerged to potentially replace or complement the role of antibiotics, as bacterial viruses have the ability to inactivate pathogens. This study aimed to evaluate the synergy of phage–antibiotic combinations. A Citrobacter amalonaticus isolate was used in this study together with the phage MRM57. Eight different antibiotics with different mechanisms of action were used in combination with the phage to study the impact of the combination treatment on the minimal inhibitory concentrations. We found that antibiotic concentration dependent synergism exists, albeit at different extents, with very low numbers of phages. This demonstrates the use of phages as an adjuvant with a sublethal concentration of antibiotics as an effective therapeutic strategy.

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Background: pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. Methods: the systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. Findings: of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2–2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195–3.556; p-value: 0.09. Interpretation: our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to discover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.

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