Sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative colitis.

BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing. AIM: To investigate the role of SIRT1 in intestinal epithelial cells (IECs) in UC and further explore the underlying mechanisms. METHODS: We developed a coculture model using macrophages and Caco-2 cells. After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide (NAM), the expression of occludin and zona occludens 1 (ZO-1) was assessed by Western blot analysis. Annexin V-APC/7-AAD assays were performed to evaluate Caco-2 apoptosis. Dextran sodium sulfate (DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 d. Transferase-mediated dUTP nick-end labeling (TUNEL) assays were conducted to assess apoptosis in colon tissues. The expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western blot. RESULTS: SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis, whereas NAM administration caused the opposite effects. DSS-induced colitis mice treated with SRT1720 had a lower disease activity index (P < 0.01), histological score (P < 0.001), inflammatory cytokine levels (P < 0.01), and apoptotic cell rate (P < 0.01), while exposure to NAM caused the opposite effects. Moreover, SIRT1 activation reduced the expression levels of GRP78, CHOP, cleaved caspase-12, cleaved caspase-9, and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated mice. CONCLUSION: SIRT1 activation reduces apoptosis of IECs via the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and caspase-12. SIRT1 activation may be a potential therapeutic strategy for UC.

Pre-existing cirrhosis is associated with increased mortality of traumatic patients: analysis of cases from a trauma center in east China.

AIM: To determine the impact of cirrhosis on trauma patients and define the factors predicting death. METHODS: The data on patients admitted to the trauma center from January 2000-2005 were studied retrospectively. The clinical variables were recorded and compared to identify the factors differentiating cirrhotic trauma survivors from non survivors. Child's classification criteria were derived from the reviewed charts of cirrhotic trauma patients to evaluate their predictive value in cirrhotic trauma. Trauma registry was also used to generate a trauma control group by matching for age, sex, abbreviated injury score (AIS) over the same period of time. The outcome variables compared were mortality rate, time of ICU and hospital stay. Results were expressed as mean +/- SD. These data were analyzed by SPSS.11.0 statistical software. Univariate analysis was performed to identify significant medical factors for survivor and non survivors subjected to chi-square test. Fisher's exact test and Student's t test were performed to determine the statistical difference between cirrhotic and control groups. P < 0.05 was considered statistically significant. RESULTS: Poor prognosis of traum patients was associated with one or more of the following findings: ascitcs, yperbilirubinemia (more than 2 mg/dL), hypoalbuminemia (less than 3.5 mg/dL), and prolonged prothrombin time (more than 12.5 s). Although Child's classification was used to predict the outcome in cirrhotic patients undergoing portacaval shunt procedures, no significant difference was found in mortality rate as a function of Child's classification. CONCLUSION: Cirrhosis is associated with a higher mortality, a longer time of ICU and hospital stay of trauma patients. It seems that treatment of trauma patients with pre-existing severe liver disease is a challenge to surgeons.

Can albumin administration relieve lung injury in trauma/hemorrhagic shock?

AIM: To study the effect of albumin administration on lung injury in trauma/hemorrhagic shock (T/HS). METHODS: Sixty experimental animals were randomly divided into three groups: rats undergoing laparotomy without shock (T/SS); rats with T/HS and resuscitation with blood plus twice the volume of shed blood as Ringer's lactate (RL), and rats with T/HS and resuscitation with blood plus additional 3 mL of 50 g/L human albumin. Expression of polymorphonuclear neutrophil (PMN) CD11b/CD18, intercellular adhesion molecule-1 (ICAM-1) of jugular vein blood and the severity of lung injuries [determined mainly by measuring activity of lung tissue myeloperoxidase (MPO) and lung injury score (LIS)] were measured after a 3-h recovery period. RESULTS: All three groups showed a significant difference in the expressions of CD11b/CD18, ICAM-1, and severity of lung injury. The expressions of CD11b/CD18 in T/SS group, T/HS + RL group, T/HS + albumin group were 17.76% +/- 2.11%, 31.25% +/- 3.48%, 20.36% +/- 3.21%, respectively (F = 6.25, P < 0.05). The expressions of ICAM-1 (U/mL) in T/SS group, T/HS + RL group, T/HS + albumin group were 258.76 +/- 98.23, 356.23 +/- 65.6, 301.01 +/- 63.21, respectively (F = 5.86, P < 0.05). The expressions of MPO (U/g) in T/SS group, T/HS + RL group, T/HS + albumin group were 2.53 +/- 0.11, 4.63 +/- 1.31, 4.26 +/- 1.12, respectively (F = 6.26, P < 0.05). Moreover, LIS in T/HS + RL group, T/HS + albumin group was 2.62 +/- 0.23, 1.25 +/- 0.24, respectively. The expressions of CD11b/CD18, ICAM-1 and MPO in T/HS + RL group were significantly increased compared to T/SS group (P = 0.025, P = 0.036, P = 0.028, respectively). However, administration of 3 mL of 50 g/L albumin significantly down-regulated the expressions of CD11b/CD18, ICAM-1 and lung injury index (MPO and LIS) when compared with the T/HS + RL rats (P = 0.035, P = 0.046, P = 0.038, P = 0.012, respectively). CONCLUSION: The infusion of albumin during resuscitation period can protect lung from injury and decrease the expressions of CD11b/CD18, ICAM-1 in T/HS rats.

Protective effect of albumin on lungs injury in traumatic/hemorrhagic shock rats.

OBJECTIVE: To determine the effect of albumin administration on lung injury in traumatic/hemorrhagic shock (T/HS) rats. METHODS: Forty-eight adult Sprague-Dawley rats were divided into three groups randomly (n=16 in each group): Group A, Group B, Group C. In Group A, rats underwent laparotomy without shock. In Group B, rats undergoing T/HS were resuscitated with their blood plus lactated Ringer's (twice the volume of shed blood). In Group C, rats undergoing T/HS were resuscitated with their shed blood plus additional 3 ml of 5% human albumin. The expression of polymorphonuclear neutrophils CD18/CD11b in jugular vein blood was evaluated. The main lung injury indexes (the activity of myeloperoxidase and lung injury score) were measured. RESULTS: Significant differences of the expression of CD18/11b and the severity degree of lung injury were founded between the three groups. (P<0.05). The expression of CD18/CD11b and the main lung injury indexes in Group B and Group C increased significantly compared with those in Group A (P<0.05). At the same time, the expression of CD18/CD11b and the main lung injury indexes in Group C decreased dramatically, compared those in Group B (P<0.05). CONCLUSIONS: The infusion of albumin during resuscitation period can protect lungs from injury and decrease the expression of CD18/CD11b in T/HS rats.

Liver fibrosis caused by choledocholith to regress after biliary drainage.

AIM: To study the correlation between liver fibrosis severity and biliary drainage in patients with choledocholith. METHODS: A follow-up study on seven patients with liver fibrosis due to choledocholith was made. The data, including biochemical tests (aspartate aminotransferase, alanine aminotransferase) and liver histological features before and after biliary drainage, were collected and studied. The fibrosis severity was scored on a scale from 0 to 3, with 0 denoting none, 1 portal and periportal fibrosis, 2 the presence of numerous fiber septa, and 3 cirrhosis. The average liver fibrosis severity scores of the first and second biopsy were compared with statistical method. RESULTS: The first, second liver fibrosis severity scores of these seven patients were 2,1; 2,1; 1,0; 1,1; 2,1; 2,1; 1,0 respectively. The results showed that the average liver fibrosis severity score of the second liver biopsy decreased significantly compared with the first liver biopsy (n = 7, t = 4.25, P<0.05). CONCLUSION: Liver fibrosis due to choledocholith may regress after biliary drainage.

Regression of liver fibrosis after biliary drainage in patients with choledocholith: a preliminary report.

BACKGROUND: Choledocholith is prevalent in some Asian countries and may lead to liver fibrosis and portal vein hypertension. Biliary drainage is an effective treatment for choledocholith. The aim of this study was to assess the impact of biliary drainage on liver fibrosis due to choledocholith. METHODS: Eight patients with liver fibrosis caused by choledocholith were followed up by biochemical tests (aspartate aminotransferase, alanine aminotransferase) and liver biopsy before and after biliary drainage, respectively. The severity of the fibrosis was scored on a scale from 0 to 3 (0: denoting none; 1: portal and periportal fibrosis; 2: the presence of numerous fiber septa; and 3: cirrhosis). The results were analyzed statistically. RESULTS: The severity scores of liver fibrosis in the 8 patients were 2,1; 2,1; 1,0; 1,1; 2,1; 1,1; 2,1; 1,0 before and after biliary drainage, respectively. The results showed that the average severity of liver fibrosis decreased significantly after biliary drainage (n=8, t=4.573, P=0.003). CONCLUSION: Liver fibrosis due to choledocholith may regress after biliary drainage.

Effects of intestinal lymph on expression of neutrophil adhesion factors and lung injury after trauma-induced shock.

AIM: To study how intestinal lymph after trauma-induced shock (TIS) interferes with expression of neutrophil adhesion factors (CD11b and CD18) and causes lung injury. METHODS: Thirty-two adult healthy Sprague-Dawley rats were randomly divided into four experimental groups. Groups 1 and 2 included rats with TIS caused by hitting the mid-upper part of both side femoral bones with a 2,500 kg raw- iron, and with or without ligation of mesenteric lymph duct. Groups 3 and 4 included rats with sham-TIS and with or without ligation of mesenteric lymph duct. Expression of neutrophil CD18 and CD11b in at 1 and 3 h after a 90-min TIS/sham-TIS was evaluated. These rats were killed at 3 h after TIS/sham-TIS, and lungs were taken immediately. The main lung injury indexes (the MPO activity and lung injury score) were measured. RESULTS: The expressions of CD18 and CD11b at 1 and 3 h after a 90-min TIS and the main lung injury indexes were significantly increased compared with those in the sham-TIS groups (P<0.05). Moreover, at 1 and 3 h after TIS, the expressions of CD18 (32.12+/-1.25 and 33.46+/-0.98) and CD11b (29.56+/-1.35 and 30.56+/-1.85) were significantly decreased in rats with ligation of mesenteric lymph duct, compared with those (52.3+/-1.12 and 50.21+/-1.25, and 42.24+/-1.24 and 42.81+/-1.12, respectively) in those without the ligation (all P<0.05). The main lung injury indexes in rats with TIS with ligation of mesenteric lymph duct (0.96+/-0.12 and 6.54+/-0.35) were also significantly decreased, compared with those (1.56+/-0.21 and 9.56+/-0.23) in rats with TIS without the ligation (both P<0.05). However, there was no significant difference in expressions of CD18 and CD11b and the main lung injury indexes between the two sham-TIS groups. CONCLUSION: Previous ligation of mesenteric lymph ducts prevents or alleviates the up-regulated expression of PMN CD18 and CD11b and the lung injury induced by TIS. Our findings also indicate that neutrophil adhesion molecule activation and lung injury during TIS appear to be caused by some factors that are released or produced by post-ischemic intestine through the mesenteric lymph pathway.