Frontiers in antibiotic alternatives for Clostridioides difficile infection

Clostridioides difficile(C.difficile)is a gram-positive,anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea.Humans are naturally resistant to C.difficile infection(CDI)owing to the protection provided by healthy gut microbiota.When the gut microbiota is disturbed,C.difficile can colonize,produce toxins,and manifest clinical symptoms,ranging from asymptomatic diarrhea and colitis to death.Despite the steady-if not risingprevalence of CDI,it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic era.C.difficile is naturally resistant to most of the currently used antibiotics as it uses multiple resistance mechanisms.Therefore,current CDI treatment regimens are extremely limited to only a few antibiotics,which include vancomycin,fidaxomicin,and metronidazole.Therefore,one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat CDI.In this Frontier article,we collectively summarize recent advances in alternative treatment approaches for CDI.Over the past few years,several studies have reported on natural product-derived compounds,drug repurposing,highthroughput library screening,phage therapy,and fecal microbiota transplantation.We also include an update on vaccine development,pre-and probiotics for CDI,and toxin antidote approaches.These measures tackle CDI at every stage of disease pathology via multiple mechanisms.We also discuss the gaps and concerns in these developments.The next epidemic of CDI is not a matter of if but a matter of when.Therefore,being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.

Dysregulation of microRNA in cholangiocarcinoma identified through a meta-analysis of microRNA profiling

BACKGROUND In the past decades,the potential of microRNA(miRNA)in cancer diagnostics and prognostics has gained a lot of interests.In this study,a meta-analysis was conducted upon the pooled miRNA microarray data of cholangiocarcinoma(CCA).AIM To identify differentially expressed(DE)miRNAs and perform functional analyses in order to gain insights to understanding miRNA-target interactions involved in tumorigenesis pathways of CCA.METHODS Raw data from 8 CCA miRNA microarray datasets,consisting of 443 samples in total,were integrated and statistically analyzed to identify DE miRNAs via comparison of levels of miRNA expression between CCA and normal bile duct samples using t-tests(P<0.001).The 10-fold cross validation was performed in order to increase the robustness of the t-test results.Our data showed 70 up-regulated and 48 down-regulated miRNAs in CCA. GeneOntology and pathway enrichment analyses revealed that mRNA targets of DEmiRNAs were significantly involved in several biological processes. The mostprominent dysregulated pathways included phosphatidylinositol-3 kinases/Akt,mitogen-activated protein kinase and Ras signaling pathways.CONCLUSIONDE miRNAs found in our meta-analysis revealed dysregulation in major cancerpathways involved in the development of CCA. These results indicated thenecessity of understanding the miRNA-target interactions and the significance ofdysregulated miRNAs in terms of diagnostics and prognostics of cancers.