Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma.

BACKGROUND: Phospholipase A2 (PLA2) enzymes are pivotal in various biological processes, such as lipid mediator production, membrane remodeling, bioenergetics, and maintaining the body surface barrier. Notably, these enzymes play a significant role in the development of diverse tumors. AIM: To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma (CCA). METHODS: We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus. The study identified differentially expressed genes between tumor tissues and adjacent normal tissues, with a focus on PLA2G2A and PLA2G12B. Gene Set Enrichment Analysis was utilized to pinpoint associated pathways. Moreover, relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted, and their correlation with the prognosis of CCA was evaluated. RESULTS: PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA, manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals. Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients. Additionally, the study delineated pathways and miRNAs associated with these genes. CONCLUSION: Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA. The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA, and their expression levels are indicative of prognosis, underscoring their potential utility in clinical settings.

Abdominal paracentesis drainage improves outcome of acute pancreatitis complicated with intra-abdominal hypertension in early phase.

BACKGROUND: Intra-abdominal hypertension (IAH) is an important risk factor for organ dysfunction, and it occurs in the early phase of severe acute pancreatitis (SAP). We have reported a novel step-up approach and shown the benefit of performing abdominal paracentesis drainage (APD) ahead of percutaneous catheter drainage (PCD) when treating Patients with SAP with fluid collections. This study aimed to evaluate the efficacy of APD in Patients with SAP complicated with IAH in the early phase. METHODS: In the present study, 206 AP patients complicated with IAH in the early phase were enrolled in hospital between June 2017 and December 2020. The patients were divided into two groups: 109 underwent APD (APD group) and 97 were managed without APD (non-APD group). We retrospectively compared the outcomes of the APD and non-APD groups for IAH treatment. The parameters including mortality, infection, organ failure, inflammatory factors, indications for further interventions, and drainage-related complications were observed. RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the APD group (3.7%) than in the non-APD group (8.2%). Compared with the non-APD group, the intra-abdominal pressure and laboratory parameters of the APD group decreased more rapidly, and the mean number of failed organs was lower. However, there was no significant difference in incidence of infections between the two groups. CONCLUSIONS: Application of APD is beneficial to AP patients. It significantly attenuated inflammation injury, avoided further interventions, and reduced multiple organ failure.

Tissue-Specific Hydrogels Ameliorate Hepatic Ischemia/Reperfusion Injury in Rats by Regulating Macrophage Polarization via TLR4/NF-κB Signaling.

Injectable acellular matrix hydrogels are proven to be potential translational materials to facilitate the repairment in various tissues. However, their potential to repair hepatic ischemia/reperfusion injury (IRI) has not been explored. In this work, we made hepatic acellular matrix (HAM) hydrogels based on the decellularized process and evaluated the biocompatibility and hepatoprotective effects in a rat IRI model. HAM hydrogels supported viability, proliferation, and attachment of hepatocytes in vitro. Treatment with HAM hydrogels significantly attenuated hepatic damage caused by IRI, as evidenced by hepatic biochemistry, histology, and inflammatory responses. Importantly, HAM hydrogels inhibited macrophage M1 (CD68/CCR7) differentiation but promoted M2 (CD68/CD206) differentiation. Additionally, TLR4/NF-κB signaling was found to be involved in the hepatoprotective effect of HAM hydrogels. Collectively, our study reveals that HAM hydrogels ameliorate hepatic IRI by facilitating M2 polarization via TLR4/NF-κB signaling.

Bile Acid Transporters Are Expressed and Heterogeneously Distributed in Rat Bile Ducts.

Background/Aims: Cholangiocytes are capable of reabsorbing bile salts from bile, but the pathophysiological significance of this process is unclear. To this end, we detected the expression and distribution of bile acid transport proteins in cholangiocytes from normal rat liver and analyzed the possible pathophysiological significance. Methods: Bile duct tissues of Sprague-Dawley rats were isolated by enzymatic digestion and mechanical isolation, and then divided into large and small bile duct tissues. Immunohistochemistry, real-time polymerase chain reaction and Western blotting were used to determine the expression of the apical sodium-dependent bile acid transporter (ASBT), ileal bile acid binding protein (IBABP), and basolateral organic solute transporter α (Ostα) in the biliary tract system of rats. Differences in the expression and distribution of these proteins were analyzed. Results: In cholangiocytes, ASBT and IBABP were mainly expressed in cholangiocytes of the large bile ducts, in which the expression of both was significantly higher than that in the small ducts (p<0.05). Ostα was simultaneously expressed in cholangiocytes of both the large and small bile ducts, showing no significant difference in expression between the two groups of bile ducts (p>0.05). Conclusions: Bile acid transporters are expressed and heterogeneously distributed in rat bile ducts, indicating that bile acid reabsorption by cholangiocytes might mainly occur in the large bile ducts. These findings may help explore the physiology of bile ducts and the pathogenesis of various cholangiopathies.

Long Noncoding RNA NEAT1 Promotes Growth and Metastasis of Cholangiocarcinoma Cells.

Long noncoding RNAs (lncRNAs) are known to play important roles in cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis. We investigated the role of nuclear paraspeckle assembly transcript 1 (NEAT1) lncRNA in promoting CCA. qRT-PCR analysis of patient samples showed that NEAT1 expression was higher in CCA tumors than in matched adjacent nontumor tissue. NEAT1 levels were also higher in CCA cell lines than in a normal biliary epithelium cell line (HIBEpic). NEAT1 knockdown in CCA cell lines using shNEAT1 reduced cell proliferation and colony formation in CCK-8 and colony formation assays, respectively. CCA cells transfected with shNEAT1 also exhibited reduced metastasis and invasiveness in Transwell assays. NEAT1 knockdown cells produced smaller tumors, demonstrating that NEAT1 promotes tumor growth in vivo. Silencing of NEAT1 increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with NEAT1 expression in CCA tissue samples. RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. We postulate that NEAT1 is a potentially useful diagnostic and therapeutic target for CCA.

Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs.

Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell-cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future.

Carbon nanotube-composite hydrogels promote intercalated disc assembly in engineered cardiac tissues through ß1-integrin mediated FAK and RhoA pathway.

Carbon nanotube (CNT)-based hydrogels have been shown to support cardiomyocyte growth and function. However, their role in cellular integrity among cardiomyocytes has not been studied in detail and the mechanisms underlying this process remain unclear. Here, single walled CNTs incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels were utilized to construct cardiac tissues, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, transmission electron microscopy and intracellular calcium transient measurement, the incorporation of CNTs into the scaffolds was observed to markedly enhance the assembly and formation in the cardiac constructs. Importantly, we further explored the underlying mechanism behind these effects through the use of immunohistochemical staining and western blotting. The ß1-integrin-mediated FAK and RhoA signaling pathways were found to be responsible for CNT-induced upregulation of electrical and mechanical junction proteins respectively. Together, our study provides new insights into the facilitative effects of CNTs on ID formation, which has important significance for improving the quality of engineered cardiac tissue and applying them to cardiac regenerative therapies. STATEMENT OF SIGNIFICANCE: Currently, the bottleneck to engineering cardiac tissues (ECTs) for cardiac regeneration is the lack of efficient cellular integrity among adjacent cells, especially the insufficient remodeling of intercalated discs (IDs) in ECTs. Recently, carbon nanotube (CNT) hydrogels provide an advantageous supporting microenvironment and therefore benefit greatly the functional performance of ECTs. Although their beneficial effect in modulating ECT performance is evident, the influence of CNTs on structural integrity of ECTs has not been studied in detail, and the mechanisms underlying the process remain to be determined. Here, we utilized carbon nanotube incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels to construct cardiac tissues, determined the influence of CNTs on intercalated discs (IDs) assembly and formation and explored the underlying mechanisms.

Carbon nanotube-based substrates promote cardiogenesis in brown adipose-derived stem cells via ß1-integrin-dependent TGF-ß1 signaling pathway.

Stem cell-based therapy remains one of the promising approaches for cardiac repair and regeneration. However, its applications are restricted by the limited efficacy of cardiac differentiation. To address this issue, we examined whether carbon nanotubes (CNTs) would provide an instructive extracellular microenvironment to facilitate cardiogenesis in brown adipose-derived stem cells (BASCs) and to elucidate the underlying signaling pathways. In this study, we systematically investigated a series of cellular responses of BASCs due to the incorporation of CNTs into collagen (CNT-Col) substrates that promoted cell adhesion, spreading, and growth. Moreover, we found that CNT-Col substrates remarkably improved the efficiency of BASCs cardiogenesis by using fluorescence staining and quantitative real-time reverse transcription-polymerase chain reaction. Critically, CNTs in the substrates accelerated the maturation of BASCs-derived cardiomyocytes. Furthermore, the underlying mechanism for promotion of BASCs cardiac differentiation by CNTs was determined by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction, and Western blotting assay. It is notable that ß1-integrin-dependent TGF-ß1 signaling pathway modulates the facilitative effect of CNTs in cardiac differentiation of BASCs. Therefore, it is an efficient approach to regulate cardiac differentiation of BASCs by the incorporation of CNTs into the native matrix. Importantly, our findings can not only facilitate the mechanistic understanding of molecular events initiating cardiac differentiation in stem cells, but also offer a potentially safer source for cardiac regenerative medicine.

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.

Cholesterol gallstones and bile host diverse bacterial communities with potential to promote the formation of gallstones.

The prevalence of cholesterol gallstones has increased in recent years. Bacterial infection correlates with the formation of gallstones. We studied the composition and function of bacterial communities in cholesterol gallstones and bile from 22 cholesterol gallstone patients using culture-dependent and culture-independent methods. Altogether fourteen and eight bacterial genera were detected in cholesterol gallstones and bile, respectively. Pseudomonas spp. were the dominant bacteria in both cholesterol gallstones and bile. As judged by diversity indices, hierarchical clustering and principal component analysis, the bacterial communities in gallstones were different from those in bile. The gallstone microbiome was considered more stable than that of bile. The different microbial communities may be partially explained by differences in their habitats. We found that 30% of the culturable strains from cholesterol gallstones secreted ß-glucuronidase and phospholipase A2. Pseudomonas aeruginosa strains showed the highest ß-glucuronidase activity and produced the highest concentration of phospholipase A2, indicating that Ps. aeruginosa may be a major agent in the formation of cholesterol gallstones.

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

BACKGROUND: Pancreatitis 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. METHODS: We retrospectively analyzed a total of 426 ABP cases in our research center. According to the highest TG level within 72 h 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. RESULTS: Compared 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%, P < 0.05). CONCLUSIONS: In 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.

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, >0.6 mM, 6 mL/kg) or normal saline (NS, 6 mL/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-1ß, 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.

Visualization of the omental bursa and its spatial relationships to left subphrenic extraperitoneal spaces by the second Chinese Visible Human model.

PURPOSE: In order to overcome the obstacle that detailed spatial relationships of the omental bursa to its related spaces cannot be displayed clearly by thick-slice sectional anatomical imaging and computed tomography, we designed a new approach to three-dimensional (3D) visualization of the omental bursa. METHODS: By Amira(®) software, we employed thin-slice cross-sectional images of the upper abdomen retrieved from second Chinese Visible Human datasets to display the spatial relationships of the omental bursa to its related spaces, especially to the left subphrenic extraperitoneal spaces. Moreover, these spatial relationships were presented on 3D sections reconstructed from second Chinese Visible Human images and computed tomography images. RESULTS: Of importance, the gastric bare area is located among the superior, inferior, and splenic recesses. The appearance of the foramen bursae omenti majoris is the only pathway communicating between the superior and inferior recesses of the omental bursa, and also is the anatomic landmark between the superior and inferior recesses. The splenic recess is surrounded from behind by the splenic bare area and the gastric bare area. CONCLUSION: As one of the subphrenic spaces, the omental bursa with its related spaces was imaged three-dimensionally using a visualization technique. Familiarity with the anatomic location and spatial relationships of the omental bursa to its related spaces may be beneficial for the differential diagnosis and intervention, improving outcome.

Enhancing HOTAIR/MiR-10b Drives Normal Liver Stem Cells Toward a Tendency to Malignant Transformation Through Inducing Epithelial- to-Mesenchymal Transition.

Previously, other groups and our team consistently have demonstrated that the possible origination of liver cancer stem cells (LCSCs) is the malignant transformation from liver normal stem cells (LNSCs). However, this complex and multi-step process is far from clear due to the accumulation of various gene dysregulations. Because non-coding RNAs (ncRNAs) could regulate multiple genes, a family of genes, and even whole chromosomes, this study further investigated the effect of dysregulated short ncRNA microRNA-10b and long ncRNA HOX transcript antisense RNA (HOTAIR) between LNSCs and LCSCs on phenotype reversion. To clarify the role of ncRNA in malignant transformation of LNSCs, we used lentivirus transduction to enhance the miR-10b and HOTAIR expression levels in our previously isolated rat LNSCs. The malignant abilities of proliferation, invasiveness, and tumorigenesis were observed and compared in cells before and after ncRNAs enhancement. After microRNA-10b and HOTAIR were enhanced separately, several cancer stem cell (CSC)-like traits appeared in these LNSCs, including in vitro-enhanced proliferative capacity, expression of putative LCSC markers, progressive invasive ability, and even in vivo aggravation into and taking the place of normal liver tissue. Furthermore, strengthened expression of these ncRNAs partially degraded E-cadherin in LNSCs, which is one of the classic markers in epithelial-to-mesenchymal transition (EMT). HOTAIR or miR-10b enhanced in LNSCs may drive the LNSCs to a tendency toward malignant transformation. This study partially uncovers the mechanism by which miR-10b or HOTAIR promotes malignant transformation of LNSCs through down-regulating E-cadherin and inducing EMT.

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 (n = 20 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 (n = 20 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.

Retrocrural space involvement on computed tomography as a predictor of mortality and disease severity in acute pancreatitis.

BACKGROUND: Because computed tomography (CT) has advantages for visualizing the manifestation of necrosis and local complications, a series of scoring systems based on CT manifestations have been developed for assessing the clinical outcomes of acute pancreatitis (AP), including the CT severity index (CTSI), modified CTSI, etc. Despite the internationally accepted CTSI having been successfully used to predict the overall mortality and disease severity of AP, recent literature has revealed the limitations of the CTSI. Using the Delphi method, we establish a new scoring system based on retrocrural space involvement (RCSI), and compared its effectiveness at evaluating the mortality and severity of AP with that of the CTSI. METHODS: We reviewed CT images of 257 patients with AP taken within 3-5 days of admission in 2012. The RCSI scoring system, which includes assessment of infectious conditions involving the retrocrural space and the adjacent pleural cavity, was established using the Delphi method. Two radiologists independently assessed the RCSI and CTSI scores. The predictive points of the RCSI and CTSI scoring systems in evaluating the mortality and severity of AP were estimated using receiver operating characteristic (ROC) curves. PRINCIPAL FINDINGS: The RCSI score can accurately predict the mortality and disease severity. The area under the ROC curve for the RCSI versus CTSI score was 0.962±0.011 versus 0.900±0.021 for predicting the mortality, and 0.888±0.025 versus 0.904±0.020 for predicting the severity of AP. Applying ROC analysis to our data showed that a RCSI score of 4 was the best cutoff value, above which mortality could be identified. CONCLUSION: The Delphi method was innovatively adopted to establish a scoring system to predict the clinical outcome of AP. The RCSI scoring system can predict the mortality of AP better than the CTSI system, and the severity of AP equally as well.

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

BACKGROUND AND AIM: 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 (H2 S) prevented NASH in rats through abating oxidative stress and suppressing inflammation. METHODS: A methionine-choline-deficient (MCD) diet rat model was prepared. Rats were divided into three experimental groups and fed for 8 weeks as follows: (i) control rats; (ii) MCD-diet-fed rats; (iii) MCD-diet-fed rats treated with NaHS (intraperitoneal injection of 0.1 mL/kg/day of 0.28 mol/L NaHS, a donor of H2 S). RESULTS: MCD diet impaired hepatic H2 S biosynthesis in rats. Treatment with H2 S prevented MCD-diet-induced NASH, as evidenced by hematoxylin and eosin staining, reduced apoptosis and activities of alanine aminotransferase and aspartate aminotransferase, and attenuated hepatic fat accumulation in rats. Treatment with H2 S abated MCD-diet-induced oxidative stress through reducing cytochrome p4502E1 expression, enhancing heme oxygenase-1 expression, and suppressing mitochondrial reactive oxygen species formation, and suppressed MCD-diet-induced inflammation through suppressing activated nuclear factor κB signaling and reducing interleukin-6 and tumor necrosis factor α expressions. In addition, treatment of MCD-diet fed rats with H2 S had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers. CONCLUSIONS: Treatment with H2 S prevented NASH induced by MCD diet in rats possibly through abating oxidative stress and suppressing inflammation.

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-ß. 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.

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

BACKGROUND: Annular 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 PRESENTATION: The 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), and was discharged in a good condition. CONCLUSION: AP 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.

The naïve effector cells of collagen type I during acute experimental pancreatitis are acinar cells and not pancreatic stellate cells.

OBJECTIVE: The purpose of this study was to investigate the expression of collagen type I and the mRNA level of its regulatory factor, TGF-ß1, in tissue samples of acute pancreatitis and to determine the significance of collagen type I in predisposition to pancreatic fibrosis during acute pancreatitis. METHODS: Sprague-Dawley rats were divided into an experimental group (30 rats) and a control group (12 rats). The rats in the experimental group were intraperitoneally injected with cerulein to induce acute pancreatitis. The distribution and expression of collagen type I in the pancreatic tissues were examined by immunohistochemical staining. The mRNA level of TGF-ß1 was determined by real-time polymerase chain reaction (PCR). RESULTS: (1) Collagen type I was localized in the cytoplasm of pancreatic acinar cells. With pancreatitis progressed, strong positive staining for collagen type I covered whole pancreatic lobules, whereas, the islet tissue, interlobular area, and pancreatic necrotic area were negative for collagen type I. (2) The level of TGF-ß1 mRNA in rats from the experimental group increased gradually the establishment of acute pancreatitis, and was significantly higher than that in the control group at every time point. CONCLUSIONS: (1) During acute pancreatitis, pancreatic acinar cells, not pancreatic stellate cells as traditionally believed, were the naïve effector cells of collagen type I. (2) TGF-ß1 played a key role in regulating collagen I expression during acute pancreatitis.