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Endoplasmic reticulum (ER) is one of the most important cell organelles in the body, regulating protein synthesis, folding and aggregation. Endoplasmic reticulum stress (ERS) is a particular subcellular pathological process involving an imbalance of homeostasis and ER disorder. In the early stage of ERS, cells show a protective unfolded protein response that changes the cellular transcriptional and translational programs to alleviate the process. Therefore, a certain degree of ERS can activate the protective adaptation of cells, whereas sustained severe ERS triggers an apoptotic signal and leads to apoptosis. Acute pancreatitis is a disease caused by trypsin digestion of the pancreas, although the pathogenesis is not completely understood. However, a close association has been suggested between pancreatitis and ERS. This article reviewed relevant research advances and discussed the effect of ERS on the development and progression of acute pancreatitis., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Aim: To assess the value of plasma melatonin in predicting acute pancreatitis when combined with the acute physiology and chronic health evaluation II (APACHEII) and bedside index for severity in acute pancreatitis (BISAP) scoring systems., Methods: APACHEII and BISAP scores were calculated for 55 patients with acute physiology (AP) in the first 24 h of admission to the hospital. Additionally, morning (6:00 AM) serum melatonin concentrations were measured on the first day after admission. According to the diagnosis and treatment guidelines for acute pancreatitis in China, 42 patients suffered mild AP (MAP). The other 13 patients developed severe AP (SAP). A total of 45 healthy volunteers were used in this study as controls. The ability of melatonin and the APACHEII and BISAP scoring systems to predict SAP was evaluated using a receiver operating characteristic (ROC) curve. The optimal melatonin cutoff concentration for SAP patients, based on the ROC curve, was used to classify the patients into either a high concentration group (34 cases) or a low concentration group (21 cases). Differences in the incidence of high scores, according to the APACHEII and BISAP scoring systems, were compared between the two groups., Results: The MAP patients had increased melatonin levels compared to the SAP (38.34 ng/L vs 26.77 ng/L) (P = 0.021) and control patients (38.34 ng/L vs 30.73 ng/L) (P = 0.003). There was no significant difference inmelatoninconcentrations between the SAP group and the control group. The accuracy of determining SAP based on the melatonin level, the APACHEII score and the BISAP score was 0.758, 0.872, and 0.906, respectively, according to the ROC curve. A melatonin concentration ≤ 28.74 ng/L was associated with an increased risk of developing SAP. The incidence of high scores (≥ 3) using the BISAP system was significantly higher in patients with low melatonin concentration (≤ 28.74 ng/L) compared to patients with high melatonin concentration (> 28.74 ng/L) (42.9% vs 14.7%, P = 0.02). The incidence of high APACHEII scores (≥ 10) between the two groups was not significantly different., Conclusion: The melatonin concentration is closely related to the severity of AP and the BISAP score. Therefore, we can evaluate the severity of disease by measuring the levels of serum melatonin.

Objective: To explore the effects of intraperitoneal injection of mesenchymal stem cells (MSC) on intestinal barrier in serve acute pancreatitis (SAP) rats., Methods: MSC were harvested and cultured from femurs of one male SD rat. And 30 female SD rats were divided into 3 groups: control group (n = 6), SAP group (n = 12) and MSC transplantation group (n = 12). SAP was induced by intraperitoneal injection of L-arginine (2 g/kg) twice in SAP and MSC groups. In MSC group, the third-generation MSC (5×10(6)) were injected intraperitoneally once daily for 3 days. All rats were sacrificed after 72 h. The histomorphologic alternations of small intestine were measured to evaluate the therapeutic effect of MSC transplantation. Reverse transcription (RT)-PCR were used to identify the expression of TNF-α mRNA and IL-1β mRNA in small intestine and pancreas. Small intestine and pancreatic samples were examined for the engraftment of donor-derived MSC by Y chromosome in situ hybridization analysis., Results: Compared with SAP group, histomorphologic alternations of small intestine significantly lower in MSC group (4.17 ± 0.28 vs 3.00 ± 0.33, P < 0.05). The relative expression quantity of TNF-α mRNA and IL-1β mRNA in pancreas were both significant higher in SAP and MSC groups than those in control group (3.10 ± 0.73 and 1.92 ± 0.37 vs 0.51 ± 0.24, 4.60 ± 0.59 and 2.43 ± 0.39 vs 1.15 ± 0.18, all P < 0.05). Compared with SAP group, the expression quantity of TNF-α mRNA and IL-1β mRNA in pancreas significantly lower in MSC group (both P < 0.05). The relative expression quantity of TNF-α mRNA and IL-1β mRNA in small intestine were both significant higher in SAP and MSC groups than those in control group (2.73 ± 0.91 and 1.55 ± 0.48 vs 0.62 ± 0.20, 5.20 ± 0.94 and 2.10 ± 0.34 vs 0.99 ± 0.10, all P < 0.05). The expressions of TNF-α mRNA and IL-1β mRNA in MSC group were lower than those in SAP group (both P < 0.05). Sry gene was not detected in pancreatic and intestinal tissue of MSC-treated rats., Conclusions: Syngraft MSC exert protective effects on pancreas and small intestine injury. And their beneficial effects are primarily mediated via indirect actions but not by their differentiation into target cells.

Aim: To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury., Methods: Seventy-two male Sprague-Dawley rats were randomly divided into three groups: the sham operation (SO), severe acute pancreatitis (SAP), and melatonin treatment (MT) groups. Acute pancreatitis was induced by infusion of 1 mL/kg of sodium taurocholate (4% solution) into the biliopancreatic duct. Melatonin (50 mg/kg) was administered 30 min before pancreatitis was induced, and the severity of pancreatic and pulmonary injuries was evaluated 1, 4 and 8 h after induction. Serum samples were collected to measure amylase activities, and lung tissues were removed to measure levels of mRNAs encoding interleukin 22 (IL-22) and T helper cell 22 (Th22), as well as levels of IL-22., Results: At each time point, levels of mRNAs encoding IL-22 and Th22 were significantly higher (P < 0.001) in the MT group than in the SAP group (0.526 ± 0.143 vs 0.156 ± 0.027, respectively, here and throughout, after 1 h; 0.489 ± 0.150 vs 0.113 ± 0.014 after 4 h; 0.524 ± 0.168 vs 0.069 ± 0.013 after 8 h, 0.378 ± 0.134 vs 0.122 ± 0.015 after 1 h; 0.205 ± 0.041 vs 0.076 ± 0.019 after 4 h; 0.302 ± 0.108 vs 0.045 ± 0.013 after 8 h, respectively) and significantly lower (P < 0.001) in the SAP group than in the SO group (0.156 ± 0.027 vs 1.000 ± 0.010 after 1 h; 0.113 ± 0.014 vs 1.041 ± 0.235 after 4 h; 0.069 ± 0.013 vs 1.110 ± 0.213 after 8 h, 0.122 ± 0.015 vs 1.000 ± 0.188 after 1 h; 0.076 ± 0.019 vs 0.899 ± 0.125 after 4 h; 0.045 ± 0.013 vs 0.991 ± 0.222 after 8 h, respectively). The mean pathological scores for pancreatic tissues in the MT group were significantly higher (P < 0.01) than those for samples in the SO group (1.088 ± 0.187 vs 0.488 ± 0.183 after 1 h; 2.450 ± 0.212 vs 0.469 ± 0.242 after 4 h; 4.994 ± 0.184 vs 0.513 ± 0.210 after 8 h), but were significantly lower (P < 0.01) than those for samples in the SAP group at each time point (1.088 ± 0.187 vs 1.969 ± 0.290 after 1 h; 2.450 ± 0.212 vs 3.344 ± 0.386 after 4 h; 4.994 ± 0.184 vs 6.981 ± 0.301 after 8 h). The severity of SAP increased significantly (P < 0.01) over time in the SAP group (1.088 ± 0.187 vs 2.450 ± 0.212 between 1 h and 4 h after inducing pancreatitis; and 2.450 ± 0.212 vs 4.994 ± 0.184 between 4 and 8 h after inducing pancreatitis)., Conclusion: Melatonin protects rats against acute pancreatitis-associated lung injury, probably through the upregulation of IL-22 and Th22, which increases the innate immunity of tissue cells and enhances their regeneration.