Superior effect of intraperitoneal vs intravenous IL-17A antibody administration.

<p>Intraperitoneal (A) or intravenous (B) anti-IL-17A antibody administration protected the mice from severe CLP. The CLP mice were intraperitoneally or intravenously given 50 µg of anti-IL-17A antibodies (<i>n</i> = 15), 50 µg of isotype control antibodies (<i>n</i> = 12), or 0.2 mL of PBS 3 h after severe CLP surgery. **<i>P</i><0.01: i.p. anti-IL-17A compared with the CLP group; ^##<i>P</i><0.01: i.p. anti-IL-17A compared with the i.p. isotype group; <i>P</i><0.05: i.v. anti-IL-17A compared with the CLP group.</p

Bacterial clearance after intraperitoneal anti-IL-17A antibody administration.

<p>The mice underwent a sham procedure, CLP, CLP with intraperitoneal anti-IL-17A, or isotype administration (n = 10 for each group). Blood and peritoneal lavage fluid were harvested 24 h after surgery. Mice that received intraperitoneal anti-IL-17A antibodies exhibited a deceased bacterial burden in the blood (A) and peritoneal cavity (B) compared with mice that received isotype antibodies or PBS. **P<0.01.</p

Cytokine levels in plasma and peritoneal lavage fluid after intraperitoneal or intravenous anti-IL-17A antibody blockade.

<p>The mice underwent a sham procedure, CLP, or CLP with intraperitoneal or intravenous anti-IL-17A administration (<i>n</i> = 5 for each group). The levels of TNF-α and IL-6 in the blood (A, B) and peritoneal lavage fluid (C, D) were measured 12 h after surgery. **<i>P</i><0.01, *<i>P</i><0.05.</p

IL-17A concentration in blood and peritoneal lavage fluid after severe CLP.

<p>(A) IL-17A concentration in blood 3, 6, 12, and 24 h after the sham operation and CLP, which peaked at 12 h. (B) IL-17A concentration in peritoneal lavage fluid 3, 6, 12, and 24 h after the sham operation and CLP, which peaked at 6 h. **P<0.01: Compared with CLP 3 h group, IL-17A concentration elevated significantly. ##P<0.01 and #P<0.05: IL-17A concentration elevated significantly in CLP mice than sham group mice on the same time point.</p

MicroRNA-572 Improves Early Post-Operative Cognitive Dysfunction by Down-Regulating Neural Cell Adhesion Molecule 1

<div><p>Post-operative cognitive dysfunction (POCD) is a commonly-seen postoperative complication in elderly patients. However, the underlying mechanisms of POCD remain unclear. miRNAs, which are reported to be involved in the pathogenesis of the nervous system diseases, may also affect POCD. In this study, miRNA microarray technology was used to analyze the circulating miRNA expression profile of POCD patients. Among the altered miRNAs, miR-572 had the greatest decrease, which was also verified <i>in vivo</i> in rat POCD model. Further analysis found that miR-572 could regulate the expression of NCAM1 in the hippocampal neurons and interfering miR-572 expression could facilitate the restoration of cognitive function <i>in vivo.</i> Moreover, clinical correlation analysis found that the miR-572 expression was associated with the incidence of POCD. Collectively, miR-572 is involved in the development and restoration of POCD and it may serve as a biological marker for early diagnosis of POCD.</p></div

Flow cytometric analysis of IL-17A–producing cells in peritoneal fluid after CLP and the percentage of neutrophil granulocytes in peritoneal fluid after intraperitoneal blockade with anti-IL-17A antibodies.

<p>(A) Representative flow cytometric dot plots. (B) Percentage of IL-17A+ -T cells in peritoneal lavage fluid after CLP or sham operation. (C) Percentage of neutrophil granulocytes in peritoneal fluid after blockade of anti-IL-17A in the four groups. The mice underwent a sham procedure, CLP, CLP with intraperitoneal anti-IL-17A or isotype administration (<i>n</i> = 6 for each group). Peritoneal lavage fluid was harvested 24 h after surgery. *<i>P</i><0.05.</p

Correlations between plasma TRAIL level and HLA-DR expression on monocytes in septic patients.

<p>Pearson correlation analysis, r = 0.43, P<0.01.</p

miR-572 expression in the peripheral blood of clinical patients.

<p>A. Real-time quantitative PCR detection of the miR-572 expression levels in the peripheral blood of POCD patients (n = 38) before surgery (Pre), 24 h after surgery (Pos-24h), and 7 days after surgery (Pos-7d). B. Real-time quantitative PCR detection of the miR-572 expression levels in the peripheral blood of non-POCD patients (n = 62) before surgery (Pre), 24 h after surgery (Pos-24h), and 7 days after surgery (Pos-7d). C. Real-time quantitative PCR detection of the miR-572 expression levels in the peripheral blood of POCD patients whose cognitive function was recovered 3 months after surgery (n = 29, Group1) and whose cognitive function was not recovered (n = 9, Group2) 24 h after surgery. D. Real-time quantitative PCR detection of the miR-572 expression levels in the peripheral blood of POCD patients whose cognitive function was recovered 3 months after surgery (n = 29, Group1) and whose cognitive function was not recovered (n = 9, Group2) 7 days after surgery.</p

Targeted regulation of the expression of NCAM by miR-572.

<p>A. Schematics of miR-572 binding to the 3'UTR region of the NCAM1 mRNA (wildtype and mutant) in the dual-luciferase experiment. B. The dual-luciferase assay showed that miR-572 significantly reduced the luciferase activity of plasmids containing the wildtype 3'UTR region of mouse NCAM1 mRNA. C. Overexpression of miR-572 in mouse HT22 cells could significantly reduce the NCAM1 expression at the mRNA and protein levels. D. Inhibition of miR-572 in mouse HT22 cells could significantly promote NCAM1 expression at the mRNA and protein levels. E. Immunohistochemical detection showed that after inhibiting miR-572 expression in the POCD rat brain, the NCAM1 expression was elevated. WT, wildtype; MUT, mutant; NC, negative control.</p

Effects of miR-572 on the cognitive function of the POCD rat model.

<p>A. Detection of miR-572 in rat peripheral blood (left) and in situ hybridization detection of miR-572 expression in the rat hippocampus area. B. Schematics of the water maze routes. C. After surgery, the POCD rats had a longer latency in finding the platform in the water maze test compared to the time needed before surgery. D. Real-time quantitative PCR detection of miR-572 in the peripheral blood of POCD rats and non-POCD rats before and after surgery. In POCD rats, the postoperative miR-572 expression in the peripheral blood was lower than the preoperative level (left), while the non-POCD rats did not show significant changes in the miR-572 expression before and after surgery (right). E. Schematic diagram of the water maze route for the POCD rats after treatment with the miR-572 inhibitor (left). After treatment, the latency of the rats in the water maze test was significantly reduced (middle), whereas the control group showed no significant improvement (right). F. In situ hybridization detection found that after injection of inhibitors, the expression level of miR-572 in the rat hippocampus was decreased. pre, preoperation; pos, postoperation.</p