Objective To explore the protective effect of resveratrol (RSV) on intestine barrier injury induced by hemorrhagic shock and its mechanism in rats.Methods According to random number table method,sixty-four SPF grade male Sprague-Dawley (SD) rats were divided into four groups:Sham operation group (only the catheters were indwelled in arterial and venous passages after anesthesia),hemorrhagic shock model group (model group,the catheters were indwelled in arterial and venous passages after anesthesia,and 0.3 mL solvent was administrated after hemorrhagic shock),RSV group (the catheters were indwelled in arterial and venous passages after anesthesia,15 mg/kg RSV was administered after hemorrhagic shock),superoxide dismutase 2 (SOD2) specific inhibitor,2-Methoxyoestradiol (2-ME) group (on the basic treatment of RSV group,0.1 mmol/L 2-ME was administered).The hemorrhagic shock model was reproduced by femoral artery bleeding.After drug administration,all rats were divided into two parts.One part was used for observations on 24-hour survival rate and survival time,while in the other part,2 hours after the hemorrhagic shock,the blood was collected for determination of the content of serum D-lactic acid,and afterward the rats were executed to obtain small intestine tissues for the examination of histopathological changes and Chiu's score.Moreover,differences of expression levels of tight junction proteins (Occludin,Claudin,ZO-1) of small intestine tissue and the oxidative stress related indexes SOD2 activity and reduced glutathione (GSH),oxidized glutathione (GSSH),malonaldehyde (MDA) contents were compared among the groups.Results Compared with the sham group,the model group demonstrated decreased survival rate,SOD2 activity,GSH content,GSH/GSSH ratio,reduced survival time,significantly increased serum D-lactic acid activity,Chiu's score and MDA content,and decreased expressions of tight junction proteins in small intestine tissue.Compared with model group,the RSV group showed significant increased survival rate [75.0％ (6/8) vs.37.5％ (3/8)] and prolonged survival time (hours:21.0±4.3 vs.10.4±5.8,P ＜ 0.05),significantly decreased serum D-lactic acid (μg/L:380.18 ± 70.59 vs.500.88 ± 97.53) and Chiu's score (1.75 ± 0.71 vs.4.00± 0.53) in small intestine (both P ＜ 0.05),obviously increased expressions of tight junction proteins,SOD2 activity,GSH and GSH/GSSG [Occludin (gray value):0.89 ± 0.10 vs.0.43 ± 0.77,Claudin (gray value):0.78±0.06 vs.0.33 ± 0.05,ZO-1 (gray value):0.83 ± 0.06 vs.0.34 ± 0.07,all P ＜ 0.05],and the elevated SOD2 activity (kU/L:0.85 ± 0.12 vs.0.51 ± 0.11,P ＜ 0.05],as well as increased GSH content and GSH/GSSG ratio [GSH (μmol/L):7.25±1.01 vs.3.86±0.54,GSH/GSSG:6.39± 1.14 vs.1.56±0.25,both P ＜ 0.05] in the small intestine,and markedly reduced MDA content (ng/g:5.00± 1.31 vs.8.63±0.92,P ＜ 0.05).Compared with RSV group,the 2-ME group demonstrated significantly decreased survival rate [50.0％ (4/8) vs.75.0％ (6/8)] and further shorter survival time (hours:12.2 ± 5.7 vs.21.0±4.3),increased serum D-lactic acid (μg/L:463.88 ± 60.16 vs.380.18 ± 70.59),obviously elevated Chiu's score (3.13 ± 0.99 vs.1.75±0.71,P ＜ 0.05),decreased expressions of tight junction proteins [Occludin (gray value):0.55±0.04 vs.0.89±0.10,Claudin (gray value):0.38±0.05 vs.0.78±0.06,ZO-1 (gray value):0.41±0.04 vs.0.83±0.06,all P ＜ 0.05];moreover,the activity of SOD2,GSH content,GSH/GSSG ratio were greatly reduced [SOD2 activity (kU/L):0.58 ± 0.13 vs.0.85 ± 0.12,GSH (μmol/L):4.49 ± 0.52 vs.7.25 ± 1.01,GSH/GSSG:1.57 ± 0.39 vs.6.39 ± 1.14,all P ＜ 0.05],and increased MDA content (ng/g:6.25 ± 1.04 vs.5.00 ± 1.31,P ＜ 0.05).The small intestine tissue was basically normal in Sham group,and no significant pathological changes were seen;in the model group,the small intestine epithelial mierovilli were collapsed and the mucosal barrier was destroyed obviously;in the RSV group the damages of small intestine microvilli and barrier were markedly alleviated;in 2-ME group the pathological changes were more evident compared with those in the RSV group.Conclusion RSV can improve intestinal barrier injury following hemorrhagic shock in rats;its mechanism may be related to SOD2 activation.

Sepsis,life-threatening organ dysfunction caused by a dysregulated host response to infection,is a major public health concern.To date,the mechanism of sepsis is not completely understood,which is still a huge task ahead of numerous clinical and laboratory researchers.Recently,increasing evidences show that deacetylase sirtuins play an important role in sepsis and the function of sirtuins are varied in different stages of sepsis.More importantly,the mechanism of sirutins is not fully understood.The sirtuins family is composed by sirtuin 1-7 members.Among them,sirtuin 1 is widely reported.In addition to sirtuin 1,other members of sirtuins are also involved in the regulation of inflammation or metabolism signaling following sepsis.Of note,the sirtuins may interact with each other and form a precious control mechanism.Herein,we tried to summarize the recent paper from PubMed,to explain the possible mechanism of distinct role of sirtuin 1/2,to generalize the downstream effects of sirtuin 3 action,and to describe the interactions among sirtuins members on sepsis,which might be helpful for our future research and potential clinical applications.

Objective To explore the changes and significane of USP20 and HIF-α expression in breast cancer.Methods Following transfection of shRNA-USP20 lentivirus into breast cancer MDA-MB-231 cells,the gene and protein expression levels of USP20 were detected using fluorescence quantitative PCR and Western Blot.Subsequently,the overexpression of USP20 was observed to determine its effect on HIF-α expression.Similarly,siRNA-USP20 was used to knock down USP20 in breast cancer MDA-MB-231 cells,followed by detection of gene and protein expression levels using fluorescence quantitative PCR and Western Blot.The subsequent changes in HIF-α expression were then examined.Rusults The positive expression rates of USP20 and HIF-α in breast cancer tissues were 69.6%and 46.83%,respectively,while they were negatively expressed in the adjacent normal tissues,with statistically significant differences(P＜0.01).The positive expressions of USP20 and HIF-α were predomi-nantly observed in the cytoplasm of breast cancer tissue,with a smaller amount present in the nucleus.There was a significant positive correlation between USP20 and HIF-α in breast cancer.Following transfection of shRNA-USP20 lentivirus into MDA-MB-231 cells,both the protein and gene expression levels of USP20 significantly increased(P＜0.01).Over-expression of USP20 did not affect HIF-α mRNA levels but led to a significant increase in HIF-α protein expression(P＜0.01).Conversely,siRNA-USP20 interference resulted in a significant decrease in both the protein and gene expression levels of USP20(P＜0.01),without affecting HIF-α mRNA levels;however,it caused a notable reduction in HIF-α protein expression(P＜0.01).Conclusion The expression of USP20 exhib-ited a significant positive correlation with HIF-α in breast cancer.Overexpression of USP20 led to a substantial increase in HIF-α protein expression,while knock-down of the USP20 gene resulted in a significant decrease in HIF-α protein levels.Therefore,it can be inferred that USP20 may exert its influence on the development of breast cancer through modulation of HIF-α expression,thereby providing crucial experimental evidence for clinical treat-ment,prognosis,and further investigations.