Compositional and functional alterations of gut microbiota in patients with stroke.

BACKGROUND AND AIMS: There is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied. METHODS AND RESULTS: We performed a case-control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4-V5 regions), and TMAO was determined via liquid chromatography-tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08-0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study. CONCLUSION: This study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.

[Expression and Significance of Notch1, P21WAF1 and involucrin in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Abnormal expression of Notch1 protein was often found in many kinds of primary tumors, but its correlation with nasopharyngeal carcinoma (NPC) is still unclear. This study was designed to investigate the expression of Notch1 and its downstream proteins P21(WAF1) and Involucrin in NPC, and analyze their correlations with the differentiation of NPC cells. METHODS: The expression of Notch1, P21(WAF1), and Involucrin in 101 specimens of NPC and 20 specimens of chronic inflammatory nasopharyngeal mucosa were detected by SP immunohistochemistry. RESULTS: The positive rates of Notch1, P21(WAF1), and Involucrin were 100%, 90.0%, and 100% in chronic inflammatory nasopharyngeal mucosa, and were 77.2%, 89.1%, and 80.1% in NPC, respectively. The expression of Notch1, P21(WAF1), and Involucrin were significantly suppressed along with descending differentiation of NPC (P=0.000, P=0.026, and P=0.000). The positive rates of Notch1, P21(WAF1), and Involucrin were significantly higher in keratinizing squamous cell carcinoma (KSCC) than in differentiated nonkeratinizing carcinoma (DNKC) and undifferentiated carcinoma (UDC) (P<0.05), and were significantly higher in DNKC than in UDC (P<0.05). The expression of Notch1 in NPC was positively correlated with the expression of P21(WAF1) (r=0.306, P=0.002) and Involucrin (r=0.325, P=0.001). No significant correlation was found between the expression of P21(WAF1) and Involucin. CONCLUSION: The expression of Notch1, P21(WAF1), and Involucrin are closely correlated to the differentiation of NPC cells.