Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE2, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE2 signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.
Background Patients with rectal cancer are usually at advanced stage with or beyond serosa invasion in China. Severe complications after laparoscopic rectal surgery leads to prolonged hospitalization and high medical cost. This study aimed to explore risk factors for severe complications after laparoscopic surgery of T3 or T4 rectal cancer. Material/Methods A total of 287 patients diagnosed with T3 or T4 rectal cancer were enrolled from the Department of Gastrointestinal Surgery of Anhui Provincial Hospital from February 2012 to February 2017. Univariate analysis and multivariable logistic regression model were used to analyze the risk factors for severe complications (Clavien-Dindo grade ≥III) after laparoscopic surgery. Results Eighteen patients (6.25%) had severe complications; 15 patients were categorized as Clavien-Dindo grade III, and 3 patients were categorized as Clavien-Dindo grade IV. Univariate analysis showed that male gender, high preoperative white blood cells (WBC), diabetes mellitus, pulmonary dysfunction, and tumor distance from anus were associated with increased risk of severe complications after laparoscopic surgery for rectal cancer. Multivariate analysis showed that preoperative WBC ≥6.9×10 9 /L (OR=5.54 (1.58–19.45), P =0.008), diabetes mellitus (OR=13.07 (3.31–51.67), P =0.000) and pulmonary dysfunction (OR=7.75 (1.69–35.63), P =0.008) were independent risk factors for postoperative severe complications. Conclusions Preoperative high white blood cells, diabetes mellitus and pulmonary dysfunction were independent risk factors for severe complications after laparoscopic surgery for T3 or T4 rectal cancer.
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