HP promotes neutrophil inflammatory activation by regulating PFKFB2 in the glycolytic metabolism of sepsis

by Song Chen, Qian Zhang, Liyan Sun, Wei Song, Tao Zhang, Weidong Song, Jian Wan

Background

Sepsis, described as an inflammatory reaction to an infection, is a very social health problem with high mortality. This study aims to explore the new mechanism in the progression of sepsis.

Methods

We downloaded the GSE69528 dataset to screen differentially expressed genes (DEGs) for WGCNA, in which the key module was identified and analyzed by DMNC algorithm, expression verification and ROC curve analysis to identify the hub gene. Furthermore, the hub gene was analyzed by immunoassay, and the potential mechanism of hub gene in neutrophils was investigated by in vitro experiments.

Results

The turquoise module was the key module for sepsis in WGCNA on 94 DEGs. The top 20 genes of DMNC network were verified in GSE69528 and GSE9960, and 10 significant genes were obtained for ROC analysis. Based on the ROC curves, HP was considered the hub gene in sepsis, and its expression difference in sepsis and control groups was substantially significant. Further, it was demonstrated the knockdown of HP and PFKFB3 could suppress glycolysis and inflammatory cytokine levels in dHL-60 cell treated with LPS.

Conclusion

In conclusion, HP is identified as a potential diagnostic indicator for sepsis patients, and HP promotes neutrophil inflammatory activation by regulating PFKFB2 in the glycolytic metabolism of sepsis confirmed by in vitro experiments. These will help us deepen the molecular mechanism of sepsis.

The mediation and interaction of the obesity index between moderate-vigorous recreational physical activity and hypertension

by Bingqian Du, Yuting Li, Yun Xia, Shan Wu, Yuan Wei, Zhihao Wang, Shupei Wang, Jiao Guo, Qing Zhu, Tianran Shen, Qingsong Chen

Previous studies showed that physical activity (PA) is concerned with hypertension (HTN). However, the mediation and interaction role of the obesity index: body mass index (BMI), waist-hip ratio (WHR), body fat rate (BFR) and visceral fat index (VFI) between PA and HTN has never been studied. Therefore, the purpose of this study was to assess the mediation and interaction of the obesity index between moderate-vigorous recreational physical activity (MVRPA) and HTN. We conducted a cross-sectional study of 4710 individuals aged 41 or older in Torch Development Zone, Zhongshan City. The mediation and interaction of the obesity index were evaluated by a four-way decomposition. 48.07% of participants had HTN among these groups. In the adjusted linear regression model, MVRPA was significantly correlated with WHR (β±SE = -0.005±0.002; POR) = 1.35), 95% (confidence interval (CI) = 1.17–1.56), insufficient MVRPA increased the risk of developing HTN. Furthermore, there were associations between BMI, WHR, BFR, VFI and HTN where the adjusted ORs and 95% CIs were 1.11 (1.09–1.13), 6.23 (2.61–14.90), 1.04 (1.03–1.06), 1.07 (1.06–1.09), respectively. The mediation analyses suggested that the impact of MVRPA on HTN risk may partly be explained by changes in obesity index, with a pure indirect mediation of WHR between MVRPA and HTN (P