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BackgroundCarotid atherosclerosis (CAS) is an important cause of stroke. Although interactions between the gut microbiome and metabolome have been widely investigated with respect to the pathogenesis of cardiovascular diseases, information regarding CAS remains limited.Materials and MethodsWe utilized 16S ribosomal DNA sequencing and untargeted metabolomics to investigate the alterations in the gut microbiota and plasma metabolites of 32 CAS patients and 32 healthy controls. The compositions of the gut microbiota differed significantly between the two groups, and a total of 11 differentially enriched genera were identified. In the metabolomic analysis, 11 and 12 significantly changed metabolites were screened in positive (POS) and negative (NEG) modes, respectively. α-N-Phenylacetyl-L-glutamine was an upregulated metabolite in CAS patients detected in both POS and NEG modes and had the highest | log2(fold change)| in POS mode. In addition, transcriptomic analysis was performed using the GSE43292 dataset.ResultsA total of 132 differentially expressed genes (DEGs) were screened. Among the upregulated DEGs in CAS patients, FABP4 exhibited the highest | log2(fold change)|. Furthermore, FABP4 was positively associated with Acidaminococcus and had the highest Spearman’s correlation coefficient and the most significant p-value among the microbiota–DEG pairs.ConclusionIn this study, we investigated the potential “microbiota–metabolite–gene” regulatory axis that may act on CAS, and our results may help to establish a theoretical basis for further specialized study of this disease.

GBM) is one of the most common aggressive cancers that occurs in the adult brain, and the survival period after initial diagnosis is only 12-15 months. 1 GBM accounts for nearly 70% of all adult brain tumours. 2 Effective treatment for GBM, which is characterized by rapid proliferation ability and highly infiltrative growth, is still lacking. 3 Bortezomib is a selective and reversible proteasome inhibitor that was first developed for the treatment of inflammation and cachexia in the late 90 seconds. 4 Studies using several tumour cells lines from the National Cancer Institute (NCI) confirmed its potency and wide range of anti-tumour effects. 5 Bortezomib was initially approved by US Food and Abstract Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acidbased potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities.In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM.

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