Long Cheng

Effects of treatment with hydrogen sulfide on methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats

Oxidative stress and inflammation play important roles in the progression from simple fatty liver to non‐alcoholic steatohepatitis (NASH). The aim of this work was to investigate whether treatment with hydrogen sulfide (H2S) prevented NASH in rats through abating oxidative stress and suppressing inflammation.

Negative correlation of ITCH E3 ubiquitin ligase and miRNA-106b dictates metastatic progression in pancreatic cancer

Pancreatic cancer is one of the major malignancies and cause for mortality across the world, with recurrence and metastatic progression remaining the single largest cause of pancreatic cancer mortality. Hence it is imperative to develop novel biomarkers of pancreatic cancer prognosis. The E3 ubiquitin ligase ITCH has been previously reported to inhibit the tumor suppressive Hippo signaling by suppressing LATS1/2 in breast cancer and chronic lymphocytic leukemia. However, the role of ITCH in pancreatic cancer progression has not been described. Here we report that ITCH transcript and protein expression mimic metastatic trait in pancreatic cancer patients and cell lines. Loss-of-function studies of ITCH showed that the gene product is responsible for inducing metastasis in vivo. We furthermore show that hsa-miR-106b, which itself is down regulated in metastatic pancreatic cancer, directly interacts and inhibit ITCH expression. ITCH and hsa-miR-106b are thus potential biomarkers for pancreatic cancer prognosis.

Clinical significance of serum triglyceride elevation at early stage of acute biliary pancreatitis

BackgroundPancreatitis induced by hypertriglyceridemia (HTG) has gained much attention. However, very limited numbers of studies have focused on the clinical significance of TG elevation in non-HTG induced pancreatitis, such as acute biliary pancreatitis (ABP). This study aimed to study the clinical significances of triglyceride (TG) elevation in patients with ABP.MethodsWe retrospectively analyzed a total of 426 ABP cases in our research center. According to the highest TG level within 72xa0h of disease onset, the patients were divided into a normal TG group and an elevated TG group. We analyzed the differences between the two groups of patients in aspects such as general information, disease severity, APACHE II (acute physiology and chronic health evaluation II) and Ranson scores, inflammatory cytokines, complications and prognosis.ResultsCompared with the normal TG group, patients in the elevated TG group showed a significantly higher body mass index and were significantly younger. TG elevation at the early stage of ABP was associated with higher risk of severe pancreatitis and organ failures, especially respiratory failure. For patients with severe pancreatitis, those with elevated TG levels were more likely to have a larger area of necrosis, and higher incidence of pancreatic abscess as well as higher mortality (17.78% versus 9.80%, Pu2009<u20090.05).ConclusionsIn ABP patients, TG elevation might participate in the aggravation of pancreatitis and the occurrence of systemic or local complications. Thus, the TG level may serve as an important indicator to determine the prognosis of patients with ABP.

Glycyrrhizin Suppresses the Expressions of HMGB1 and Relieves the Severity of Traumatic Pancreatitis in Rats

Background High mobility group box 1 (HMGB1) plays important roles in a large variety of diseases; glycyrrhizin (GL) is recognized as an HMGB1 inhibitor. However, few studies have focused on whether glycyrrhizin can potentially improve the outcome of traumatic pancreatitis (TP) by inhibiting HMGB1. Methods A total of 60 male Wistar rats were randomly divided into three groups (nu200a=u200a20 in each): Control group, TP group and TP-GL group. Pancreatic trauma was established with a custom-made biological impact machine-III, and GL was administered at 15 minutes after the accomplishment of operation. To determine survival rates during the first 7 days after injury, another 60 rats (nu200a=u200a20 in each) were grouped and treated as mentioned above. At 24 hours of induction of TP, the histopathological changes in pancreas were evaluated and serum amylase levels were tested. Serum tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and HMGB1 were measured using enzyme linked immunosorbent assay. HMGB1 expressions in pancreas were measured using immunohistochemical staining, Western blot and Real-Time PCR analysis. Results Serum levels of HMGB1, TNF-α and IL-6 were increased dramatically in TP group at 24 hours after induction of TP. However, these indicators were reduced significantly by GL administration in TP-GL group comparing with TP group (P<0.05). Meanwhile, survival analysis showed that the seven-day survival rate in TP-GL group was significantly higher than that in TP group (85% versus 65%, P<0.05). GL treatment significantly decreased the pancreatic protein and mRNA expressions of HMGB1 and ameliorated the pancreatic injury in rats with TP. Conclusions Glycyrrhizin might play an important role in improving survival rates and ameliorating pancreatic injury of TP by suppression of the expressions of HMGB1 and other proinflammatory cytokine.

Involvement of a membrane potassium channel in heparan sulphate-induced activation of macrophages

Increasing evidence has demonstrated that Toll‐like receptor 4 (TLR4) ‐mediated systemic inflammatory response syndrome accompanied by multiple organ failure, is one of the most common causes of death in patients with severe acute pancreatitis. Recent reports have revealed that heparan sulphate (HS) proteoglycan, a component of extracellular matrices, potentiates the activation of intracellular pro‐inflammatory responses via TLR4, contributing to the aggravation of acute pancreatitis. However, little is known about the participants in the HS/TLR4‐mediated inflammatory cascades. Our previous work provided a clue that a membrane potassium channel (MaxiK) is responsible for HS‐induced production of inflammatory cytokines. Therefore, in this report we attempted to reveal the roles of MaxiK in the activation of macrophages stimulated by HS. Our results showed that incubation of RAW264.7 cells with HS up‐regulated MaxiK and TLR4 expression levels. HS could also activate MaxiK channels to promote the efflux of potassium ions from cells, as measured by the elevated activity of caspase‐1, whereas this was significantly abolished by treatment with paxilline, a specific blocker of the MaxiK channel. Moreover, it was found that paxilline substantially inhibited HS‐induced activation of several different transcription factors in macrophages, including nuclear factor‐κB, p38 and interferon regulatory factor‐3, followed by decreased production of tumour necrosis factor‐α and interferon‐β. Taken together, our investigation provides evidence that the HS/TLR4‐mediated intracellular inflammatory cascade depends on the activation of MaxiK, which may offer an important opportunity for a new approach in therapeutic strategies of severe acute pancreatitis.

The Role of Exogenous Hydrogen Sulfide in Free Fatty Acids Induced Inflammation in Macrophages

Background: This study aimed to investigate whether exogenous hydrogen sulfide (H2S) can protect the RAW264.7 macrophages against the inflammation induced by free fatty acids (FFA) by blunting NLRP3 inflammasome activation via a specific TLR4/NF-κB pathway. Methods: RAW264.7 macrophages were exposed to increasing concentrations of FFA for up to 3 days to induce FFA-induced inflammation. The cells were pretreated with NaHS (a donor of H2S) before exposure to FFA. Cell viability, cell apoptosis, TLR4, NF-κB, NLRP3 inflammasome, IL-1β, IL-18 and cleaved caspase-3 expression were measured by a combination of MTT assay, ELISA, and immunoblotting. Results: H2S attenuated FFA-induced cell apoptosis, and reduced the expression of NLRP3, ASC, pro-caspase-1, caspase-1, IL- 1β, IL-18 and caspase-3. In addition, H2S inhibited the FFA-induced activation of TLR4 and NF-κB. Furthermore, NLRP3 inflammasome activation was regulated by the TLR4 and NF-κB pathway. Conclusion: The present study demonstrated for the first time that H2S appears to suppress FFA-induced macrophage inflammation and apoptosis by inhibiting the TLR4/ NF-κB pathway and its downstream NLRP3 inflammasome activation. Thus H2S might possess potential in the treatment of diseases resulting from FFA overload like insulin resistance and type diabetes.

Progressive balloon dilatation following hepaticojejunostomy improves outcome of bile duct stricture after iatrogenic biliary injury

BackgroundIatrogenic biliary stricture (IBS) is a disastrous complication of cholecystectomy. Although the endoscopic treatments are well accepted as initial attempts for IBS, surgical hepaticojejunostomy (HJ) is often necessary for a considerable proportion of patients. However, the anastomotic stricture after HJ also occurs.MethodsIn the present study, a new procedure, progressive balloon dilation following HJ (HJPBD), was designed and utilized in the IBS treatment. We retrospectively compared HJPBD with the traditional HJ in term of the outcomes when used for IBS treatment.ResultsBetween January 1997 and December 2009, 112 patients with IBS attributed to cholecystectomy enrolled in our hospital were treated with surgical reconstruction with either HJ (n=58) or HJPBD (n=54). Of the 58 patients in HJ group, 48 patients (82.8%) had a successful outcome, while 52 out of 54 patients (96.3%) in HJPBD group achieved success. The successful surgical reconstruction rates were significantly different between these two groups, with a further improved outcome in patient undergone progressive balloon dilation following HJ. Additionally, 8 of the 10 failure cases in HJ group were successfully rescued by HJPBD procedure.ConclusionsOur findings suggest that the new procedure of HJPBD could be successfully applied to IBS patients, and significantly improve the outcome of IBS reconstruction.

Annular pancreas concurrent with pancreaticobiliary maljunction presented with symptoms until adult age: case report with comparative data on pediatric cases

BackgroundAnnular pancreas (AP) concurrent with pancreaticobiliary maljunction (PBMJ), an unusual coexisted congenital anomaly, often presented symptoms and subjected surgical treatment at the early age of life. We reported the first adult case of concurrent AP with PBMJ presented with symptoms until his twenties, and performed a literature review to analyze the clinicopathological features of such cases comparing with its pediatric counterpart.Case presentationThe main clinical features of this case were abdominal pain and increased levels of plasma amylase as well as liver function test. A complete type of annular pancreas with duodenal stenosis was found, and dilated common bile duct with high confluence of pancreaticobiliary ducts was also observed. Meanwhile, extremely high levels of bile amylase were detected both in common bile duct and gallbladder. The patient received duodenojejunostomy (side-to-side anastomosis) as well as choledochojejunostomy (Roux-en-Y anastomosis), adnd was discharged in a good condition.ConclusionAP concurrent with PBMJ usually presents as duodenal obstruction in infancy, while manifests as pancreatitis in adulthood. Careful long-term follow-up is required for children with AP considering its association with PBMJ which would induce various intractable pathologic conditions in the biliary tract and pancreas.

Hydrogen-Rich Saline Protects against Ischemia/Reperfusion Injury in Grafts after Pancreas Transplantations by Reducing Oxidative Stress in Rats

Purpose. This study aimed to investigate the therapeutic potential of hydrogen-rich saline on pancreatic ischemia/reperfusion (I/R) injury in rats. Methods. Eighty heterotopic pancreas transplantations (HPT) were performed in syngenic rats. The receptors were randomized blindly into the following three groups: the HPT group and two groups that underwent transplantation and administration of hydrogen-rich saline (HS, >0.6u2009mM, 6u2009mL/kg) or normal saline (NS, 6u2009mL/kg) via the tail vein at the beginning of reperfusion (HPT + HS group, HPT + NS group). Samples from the pancreas and blood were taken at 12 hours after reperfusion. The protective effects of hydrogen-rich saline against I/R injury were evaluated by determining the changes in histopathology and measuring serological parameters, oxidative stress-associated molecules, and proinflammatory cytokines. Results. Administration of hydrogen-rich saline produced notable protection against pancreatic I/R injury in rats. Histopathological improvements and recovery of impaired pancreatic function were observed. In addition, TNF-α, IL-1β, and IL-6 were reduced markedly in the HPT + HS group. Additionally, there were noticeable inhibitory effects on the pancreatic malondialdehyde level and considerable recruitment of SOD and GPx, which are antioxidants. Conclusion. Hydrogen-rich saline treatment significantly attenuated the severity of pancreatic I/R injury in rats, possibly by reducing oxidative stress and inflammation.

Outcome benefit of abdominal paracentesis drainage for severe acute pancreatitis patients with serum triglyceride elevation by decreasing serum lipid metabolites

BackgroundOur previous reports demonstrated that abdominal paracentesis drainage (APD) exerts a beneficial effect on severe acute pancreatitis (SAP) patients. However, the underlying mechanisms for this effectiveness are not well understood.MethodsA retrospective cohort of 132 consecutive non-hypertriglyceridemia (HTG)-induced SAP patients with triglyceride (TG) elevation and pancreatitis-associated ascitic fluid (PAAF) was recruited from May 2010 to May 2015 and included in this study. The patients were divided into two groups: the APD group (nu2009=u200968) and the non-APD group (nu2009=u200964). The monitored parameters mainly included mortality, hospital stay, the incidence of further intervention, levels of serum lipid metabolites and inflammatory factors, parameters related to organ failure and infections, and severity scores.ResultsThe demographic data and severity scores were comparable between the two groups. Compared with the non-APD group, the primary outcomes (including mortality, hospital stay and the incidence of percutaneous catheter drainage) in the APD group were improved. The serum levels of lipid metabolites were significantly lower in the APD group after 2xa0weeks of treatment than in the non-APD group. Logistic regression analysis indicated that the decreased extent of free fatty acid (FFA)(odds ratio, 1.435; Pu2009=u20090.015) was a predictor of clinical improvement after 2xa0weeks of treatment.ConclusionTreatment with APD benefits non-HTG-induced SAP patients with serum TG elevation by decreasing serum levels of FFA.