Mesenchymal stem cells improve intestinal integrity during severe acute pancreatitis.

Severe acute pancreatitis (SAP) is an acute inflammatory disease of the pancreas that involves various distant tissues and organs. This study aimed to investigate post-tissue injury repair by mesenchymal stem cells (MSCs) in a rat model of SAP. A total of 54 pathogen-free adult male SD rats were randomly assigned to the groups SAP, SAP + MSCs and sham-operated (SO). SAP was induced by 4% sodium taurocholate, and MSCs were injected via the dorsal penile vein 1 h later. The amylase activity, and tumor necrosis factor (TNF)-α and diamine oxidase (DAO) levels were measured with an enzyme-linked immunosorbent assay (ELISA), while the expression of aquaporin (AQP)-1 was evaluated by immunohistochemical staining. The pathological score of intestinal tissues was also compared among groups. Marked improvement in intestinal necrosis, villi shedding and infiltration of inflammatory cells was observed in the SAP + MSCs group compared to the SAP and SO groups. Amylase, TNF-α, and DAO levels were significantly increased in the SAP + MSCs group. The intestinal expression of AQP-1 was increased at 12 and 24 h post-MSC transplantation compared to the SO group. Rats of the SAP + MSCs group displayed higher pathological scores compared to the SAP group at all time points. Overall, these data showed that MSCs can inhibit systemic inflammation and reduce TNF-α release in a rat model of SAP-induced intestinal injury, suggesting that MSCs exert protective effects on the intestinal barrier during SAP.

"Fast track" rehabilitation after gastric cancer resection: experience with 80 consecutive cases.

BACKGROUND: To evaluate the safety, efficacy and outcomes of fast-track rehabilitation applied to gastric cancer proximal, distal and total gastrectomy. METHODS: Eighty consecutive patients undergoing gastric cancer resection performed by a single surgeon, received perioperative multimodal rehabilitation. Demographic and operative data, gastrointestinal function, postoperative hospital stays, surgical and general complications and mortality were assessed prospectively. RESULTS: Of the 80 patients (mean age 56.3 years), 10 (12.5%) received proximal subtotal gastrectomy (Billroth I), 38 (47.5%) received distal (Billroth II), and 32 (40%) received total gastrectomy (Roux-en-Y). Mean operative time was 104.9 minutes and intraoperative blood loss was 281.9 ml. Time to first flatus was 2.8 ± 0.5 postoperative days. Patients were discharged at a mean of 5.3 ± 2.2 postoperative days; 30-day readmission rate was 3.8%. In-hospital mortality was 0%; general and surgical complications were both 5%. CONCLUSIONS: Fast-track multimodal rehabilitation is feasible and safe in patients undergoing gastric cancer resection and may reduce time to first flatus and postoperative hospital stays.

[Correlation of methylation of CpG island in cystathionine beta synthase promoter and clinicopathological features in colorectal cancer].

OBJECTIVE: To explore the association between methylation of cystathionine-beta-synthase (CBS) promoter and clinicopathological features in colorectal cancer. METHODS: Bisulfate sequencing PCR, real-time RT-PCR, and immunohistochemistry were used to investigate the methylation of CpG island in CBS promoter of 95 sporadic colorectal cancers. Software SPSS PASW Statistics was used to analyze the data of the hypermethylation levels in the malignant tissues and the correlation with pathological parameters and clinical outcome. RESULTS: Methylation levels in tumor tissue of patients [(64.9 ± 14.3)%]with colorectal cancer were significantly higher than that in normal tissues[(27.5 ± 13.1)%, P < 0.001]. The CBS mRNA levels in the hypomethylation group (7.22 ± 1.91) were significantly higher than that in the hypermethylation group (2.78 ± 1.12, P < 0.01). Univariate analysis showed that age, pT stage, pN stage, liver metastases, pTNM stage, and CBS hypermethylation level significantly correlated with the survival and recurrence rates of colorectal cancer patients (All P < 0.05). Multivariate analysis showed that CBS hypermethylation level and liver metastasis were independent factors significantly correlated with the recurrence rate and overall survival of the patients (All P < 0.05). CONCLUSIONS: Our study indicates that methylation of CpG island in CBS promoter is correlated with the occurrence and progression of colorectal cancer and plays a role in its tumorigenesis. It might serve as a useful marker for early diagnosis, targeted therapy and prediction of prognosis in colorectal cancer.

Protective effect of transplanted bone marrow-derived mesenchymal stem cells on pancreatitis-associated lung injury in rats.

Severe acute pancreatitis (SAP) is initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, leading to self-digestion and inflammatory responses in pancreatic ductal cells, thus giving rise to systemic inflammatory response syndrome (SIRS). The most common and serious SIRS is pancreatitis-associated lung injury, and inflammatory mediators play an important role in its pathogenesis. Bone marrow-derived mesenchymal stem cells (MSCs) are differentiated into alveolar endothelial cells to replace the damaged alveolar endothelial cells and inhibit inflammatory response in the injured lung tissues. In this study, we aimed to investigate the therapeutic effect of bone marrow-derived MSCs in rats with pancreatitis-associated lung injury. Experimental SAP was induced by a retrograde injection of 5% sodium taurocholate into the biliopancreatic duct of 75 male Sprague-Dawley rats, which were divided into the SAP group (n=25), the MSC group (n=25) and the sham-operated group (n=25) to explore the pathology and function of lung tissues and the regulation of inflammatory mediators. Pulmonary edema was estimated by measuring water content in the lung tissues. Pulmonary myeloperoxidase (MPO) activity was detected using spectrophotometry. Serum amylase was detected using the Automatic Biochemistry Analyzer. Tumor necrosis factor-α (TNF-α) and substance P (SP) mRNA levels were determined by quantitative reverse transcriptase-polymerase chain reaction. Our results showed that serum amylase activity was significantly decreased in the MSC group compared to the SAP group. Pulmonary edema was significantly diminished (p<0.05) in the MSC group compared to the SAP group. Typical acute lung injury was observed in the SAP group, and the pathological changes were mild in the MSC group. The expression of TNF-α and SP mRNA in lung tissue was diminished in the MSC group compared to the SAP group. In conclusion, MSC transplantation attenuates pulmonary edema and inflammation, and reduces the mRNA expression of TNF-α and SP in pancreatitis-associated lung injury.

Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis.

AIM: To investigate the role and potential mechanisms of bone marrow mesenchymal stem cells (MSCs) in severe acute peritonitis (SAP). METHODS: Pancreatic acinar cells from Sprague Dawley rats were randomly divided into three groups: non-sodium deoxycholate (SDOC) group (non-SODC group), SDOC group, and a MSCs intervention group (i.e., a co-culture system of MSCs and pancreatic acinar cells + SDOC). The cell survival rate, the concentration of malonaldehyde (MDA), the density of superoxide dismutase (SOD), serum amylase (AMS) secretion rate and lactate dehydrogenase (LDH) leakage rate were detected at various time points. In a separate study, Sprague Dawley rats were randomly divided into either an SAP group or an SAP + MSCs group. Serum AMS, MDA and SOD, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α levels, intestinal mucosa injury scores and proliferating cells of small intestinal mucosa were measured at various time points after injecting either MSCs or saline into rats. In both studies, the protective effect of MSCs was evaluated. RESULTS: In vitro, The cell survival rate of pancreatic acinar cells and the density of SOD were significantly reduced, and the concentration of MDA, AMS secretion rate and LDH leakage rate were significantly increased in the SDOC group compared with the MSCs intervention group and the Non-SDOC group at each time point. In vivo, Serum AMS, IL-6, TNF-α and MAD level in the SAP + MSCs group were lower than the SAP group; however serum IL-10 level was higher than the SAP group. Serum SOD level was higher than the SAP group at each time point, whereas a significant between-group difference in SOD level was only noted after 24 h. Intestinal mucosa injury scores was significantly reduced and the proliferating cells of small intestinal mucosa became obvious after injecting MSCs. CONCLUSION: MSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium, promote the proliferation of enteric epithelium and repair of the mucosa, attenuate systemic inflammation in rats with SAP.

[The protective effects of bifidobacterial adhesin on ischemic reperfusion injury of intestine in rats].

OBJECTIVE: To investigate the protection effect of bifidobacterial adhesin for intestine ischemia/reperfusion (I/R) injury on gut barrier function in rat. METHODS: Seventy-two male SD rats were randomly divided into sham operation group (n = 24), I/R model group (n = 24) and pretreatment group of bifidobacterial adhesin (pretreatment group, n = 24). Six rats were anatomized at 6 h, 1 d, 4 d and 7d after inducing I/R model in each group, respectively. The pathological changes of the terminal ilea and the blood levels of TNFα, IL-6, IL-10, diamine oxidase (DAO), and the activity and content of D-lactic acid were observed. RESULTS: The blood levels of TNFα, IL-6, DAO and D-lactic acid in I/R model group were significantly higher than sham operation group at all time points (P < 0.05), while the blood level of IL-10 was no significantly change. The activity of IL-6 and DAO in pretreatment group was significantly lower than I/R model group at all time points (P < 0.05), the blood level of TNFα in pretreatment group was significantly lower than I/R model group at 1 d, the blood level of D-lactic was significantly lower than I/R model group at 4 d and 7 d (P < 0.05). Intestinal pathological damages were obviously milder in pretreatment group than I/R model group at all time points (Chiu's pathological scores: 6 h, 3.22 ± 0.22 vs 3.57 ± 0.20; 1 d, 3.77 ± 0.13 vs 3.90 ± 0.12; 4 d, 2.93 ± 0.23 vs 3.07 ± 0.21; 7 d, 2.10 ± 0.30 vs 2.22 ± 0.17, all P < 0.05). CONCLUSION: The pretreatment of bifidobacterial adhesin could protect the intestinal mucosa from I/R injury, and alleviate intestinal ischemic reperfusion injury.

Effect of parenteral nutrition with L-arginine supplementation on postoperative immune function in patients with colorectal cancer.

OBJECTIVE: To study the effects of parenteral nutrition (PN) supplemented with L-arginine on the immune function of patients with colorectal cancer after operation. METHODS: Forty randomly chosen patients with colorectal cancer were enrolled in this study, who received either standard PN or PN supplemented with 20 g/d L-arginine for 7 d after surgical removal of the tumors. Tests of the immune function (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), interleukin-2R, natural killer cells, C3, C4, CH50, IgA, IgM, IgG) were performed preoperatively and at different time periods postoperatively. RESULTS: Data analysis with ANOVA demonstrated immune suppression in the patients before operation, and the condition was improved (as evidenced by increased CD4(+),CD4(+)/CD8(+), natural killer cells and interleukin-2R levels) in L-arginine group as compared with the results in the control group at days 4 and 7 (P<0.05). CONCLUSION: Arginine can improve the immune function in patients with colorectal cancer after operation and enhance PN effect.