Temporal alterations in pericytes at the acute phase of ischemia/reperfusion in the mouse brain

Pericytes,as the mural cells surrounding the microvasculature,play a critical role in the regulation of microcirculation;however,how these cells respond to ischemic stroke remains unclear.To determine the temporal alterations in pericytes after ischemia/reperfusion,we used the 1-hour middle cerebral artery occlusion model,which was examined at 2,12,and 24 hours after reperfusion.Our results showed that in the reperfused regions,the cerebral blood flow decreased and the infarct volume increased with time.Furthermore,the pericytes in the infarct regions contracted and acted on the vascular endothelial cells within 24 hours after reperfusion.These effects may result in incomplete microcirculation reperfusion and a gradual worsening trend with time in the acute phase.These findings provide strong evidence for explaining the“no-reflow”phenomenon that occurs after recanalization in clinical practice.

急性重症溃疡性结肠炎的治疗

急性重症溃疡性结肠炎(acute severe ulcerative colitis,ASUC)是一种医疗紧急情况,有危及生命的风险.随着近年来溃疡性结肠炎发病率的不断上升,临床上ASUC也愈发常见.目前激素仍是主要治疗手段,激素治疗3 d后应评估疗效,疗效欠佳时及时转换为英夫利昔单抗或环孢素抢救治疗,内科治疗效果欠佳或发生严重并发症时,可选择结肠切除术.本综述阐述了目前ASUC常用治疗方案,有助于临床医疗决策的制定,改善患者预后,并提高患者生活质量.

The association between disruption of the circadian rhythm and aggravation of colitis in mice

Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation.The circadian rhythmcontrols cell proliferation and energy metabolism.However,the role of circadian genes in inflammatory bowel disease is largely unknown.The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism.Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days,whereas those in the control group were not.Subsequently,half of the mice in the control and jet-lagged groups were given dextran sodium sulfate(DSS)to induce colitis.Mice in each group were euthanized at zeitgeber time(ZT)0,ZT4,ZT8,ZT12,ZT16,and ZT20.To investigate the effects of jet lag on the mice,colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes(Bmal1,Clock,Per1,Per2,Cry1,Cry2,and Nr1d1).We analysed the mitochondrial morphology,adenosine triphosphate(ATP)levels,and the expression of dynamin-related protein 1(Drp1)and ser637-phosphorylated(p)-Drp1,which are closely related to ATP production.We further investigated the effect of PER2 knockdown in the colon epithelial cells(CCD 841 CoN)by measuring ATP and cell proliferation levels.Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice,altered the mitochondrial morphology of the colon specimens,decreased the expression of p-Drp1,reduced ATP production,and exacerbated inflammatory responses in mice with DSS-induced colitis.Additionally,silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation.Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis.