Isolinderalactone Resistance to the Liver Injury Induced by Oxaliplatin in Rats Through Inhibiting IL-6/STAT3 Signal Pathway.

BACKGROUND: Oxaliplatin (OXA) is easy to cause sinusoidal obstruction syndrome (SOS), leading to liver injury. Isolinderalactone (ILL), one of the main components of Lindera aggregate, has been reported to have a protecting effect on the liver. However, it is unclear whether ILL has a therapeutic effect on liver injury caused by OXA. This study aims to determine the effect of ILL on the prevention and treatment of OXA-induced liver injury and to provide a basis for the chemotherapy of gastrointestinal tumors. METHODS: Intraperitoneal injection of folinic acid, 5-fluorouracil, and OXA was administered on the SOS rat model for 7 weeks. The indexes of liver function were measured by biochemical kit. The ratio of liver weight to body weight was calculated. The pathological analysis of the liver was scored with the SOS scoring standard, fibrosis was evaluated with a four-point scale. The expression of inflammation factors was detected by Real-Time PCR, and the related indexes of IL-6/STAT3 were examined by Western blot analysis. RESULTS: ILL down-regulated the portal vein pressure and alleviated the abnormal liver function of SOS rats and improved the liver lesions. ILL inhibited the SOS by inhibiting IL-6/STAT3. CONCLUSION: ILL resistance to liver injury through inhibiting IL-6/STAT3 signal pathway.

Curcumin Suppresses Cell Proliferation, Migration, and Invasion Through Modulating miR-21-5p/SOX6 Axis in Hepatocellular Carcinoma.

Background: Curcumin is the major component of turmeric, which has an anticancer property in multiple cancers, including hepatocellular carcinoma (HCC). However, the mechanisms are still largely unclear. This research aims to assess the pharmacological function of curcumin and explore the potential microRNA (miRNA)-mRNA regulatory mechanism in curcumin-mediated HCC progression. Materials and Methods: Hep3B and Huh-7 cells were used for in vitro experiments. Cells were exposed to various doses of curcumin, and transfection was conducted using Lipofectamine 2000. Cell proliferation, migration, and invasion were examined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide or transwell assay. The abundances of miR-21-5p and gender-determining region Y-related high-mobility group box 6 (SOX6) were examined using quantitative real-time polymerase chain reaction or Western blot. The relationship between miR-21-5p and SOX6 was analyzed through luciferase reporter analysis. Results: Curcumin repressed HCC cell proliferation, migration, and invasion. miR-21-5p level was decreased in curcumin-treated cells, and miR-21-5p overexpression reversed curcumin-mediated inhibition of HCC progression. SOX6 was targeted through miR-21-5p, and SOX6 restoration attenuated miR-21-5p-induced promotion of HCC progression. Moreover, curcumin exposure increased SOX6 expression through regulating miR-21-5p, and knockdown of SOX6 overturned curcumin-modulated suppression of HCC progression. Conclusions: Curcumin repressed proliferation, migration, and invasion of HCC cells by regulating miR-21-5p and SOX6, indicating the promisingly pharmacological effect of curcumin in HCC.

Effects of miR-489 targeting on SOX4 gene on proliferation and apoptosis of human hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma is one of the most common malignant tumors found all over the globe. Despite advances in surgery and chemotherapy, the five-year survival rate of patients with hepatocellular carcinoma is still low. It is known that the proliferation of hepatocellular carcinoma cells is closely related to the occurrence, development and prognosis of hepatocellular carcinoma. The present work investigates the expression of microRNA-489 (miR-489) in human hepatocellular carcinoma cells and its effect on the biological behavior of human hepatocellular carcinoma cells. METHODS: The expression of miR-489 by fluorescence quantitative PCR detection in 30 patients with hepatoblastoma of liver cancer tissues and adjacent tissues was studied. Also, the determination of hepatoblastoma in four cell lines with different metastatic potential (HR8348, HCT116, HT29 and HEPG2) and the expression of miR-489 during miR-489 simulation process was studied. MTT assay, flow cytometry and Western blot analysis were performed to know the cell proliferation to detect the changes in cell cycle, apoptosis of cells, and SOX4 gene expression respectively. RESULTS: RT-PCR results showed that the cells compared with pre-cancerous tissue, the expression level of miR-489 in hepatocellular carcinoma tissues than in adjacent tissue significantly decreased (P<0.05), and with liver cancer cell metastasis increased (P<0.05); analogue transfection constructed miR-489 overexpressing HEPG2 cell line by microRNA. MTT results showed that miR-489 can inhibit the proliferation of HEPG2 cells, the differences were statistically significant (P<0.05); flow cytometry results showed that miR-489 mimics was transfected into HEPG2 cells at 48 hours had no significant effect on cell cycle distribution (P > 0.05); but miR-489 expression could induce apoptosis, compared with the control group, the apoptosis of miR-489 mimics was significantly increased and the difference was statistically significant (P < 0.05). CONCLUSION: In conclusion, miR-489 can significantly inhibit the occurrence and development of hepatocellular carcinoma cells. The mechanism may be down regulated by the expression of SOX4 and inhibit cell proliferation. Further this study showed that the tumor cells SOX4 gene as a regulatory factor target the genes of miR-489 in hepatocellular carcinoma.

Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis.

The aim of the present study was to investigate the effects of hepatic blood inflow on liver function, liver ultrastructure and the regeneration of future liver remnant (FLR) following major hepatectomy in rats with liver cirrhosis. A rat model of cirrhosis was established through intraperitoneal injection of carbon tetrachloride for 8 consecutive weeks. Extensive liver resection and different blood inflow models by portal vein (PV) and/or hepatic artery (HA) stenosis were conducted on the cirrhosis rats. Animal models were constructed as follows: Control (group A), low-flow PV + high-flow HA (group B), low-flow PV + low-flow HA (group C), high-flow PV + high-flow HA (group D) and high-flow PV + low-flow HA (group E). Hepatic blood inflow was detected by laser speckle contrast analysis, liver function and pathological changes were analyzed, Masson staining was used to identify the fibrosis of the liver and Periodic acid-Schiff staining was used to identify glycogen synthesis and hepatocyte function. The liver cell ultrastructure was evaluated by transmission electron microscopy, and the expression of Ki-67 in hepatocytes and the weight of the FLR were recorded to determine the regeneration of the FLR. Five days after major hepatectomy and liver blood inflow modulation, pathological examination of the livers from groups B and C revealed less congestion and less extensive hepatocellular injury. The serum alanine aminotransferase level of group B at 1, 3 and 5 days after hepatectomy and blood inflow modulation was 460.9±31.7, 331.0±22.0 and 285.6±15.8 U/l, respectively (control group: 676.9±41.7, 574.9±28.0 and 436.1±32.7 U/l, respectively; P<0.05); the total bilirubin of group B at 1, 3 and 5 days was 20.4±1.5, 16.1±1.0 and 13.5±0.6 µmol/l, respectively (control group: 30.3±1.4, 26.5±0.8 and 22.1±1.2 µmol/l, respectively; P<0.05). The size of the endoplasmic reticulum in the low-flow PV groups increased significantly and the mitochondrial swelling was alleviated. The positive rate of Ki-67 in the hepatocytes of groups B, C and D was 23.9±3.6, 15.7±2.3 and 12.9±2.4%, respectively (control group: 10.1±2.1%, P<0.05), and the positive rate of Ki-67 in group E was 6.1±1.4% (compared with that of the control group, P<0.05). The remnant liver weight of group B was 15.4±1.0 g (compared with that of the control group, P<0.05). Therefore, decreased portal blood flow combined with increased hepatic arterial blood flow alleviated the congestion in the liver following major hepatectomy in cirrhotic rats, improved the pathological status and liver function, increased the expression of Ki-67 and promoted liver regeneration.

Differences between images of large adenoma and protruding type of gallbladder carcinoma.

The aim of this study was to investigate the differences between images of large adenoma of the gallbladder and the protruding type carcinoma of the gallbladder. A retrospective study was performed on 130 patients who underwent cholecystectomy or biopsy for gallbladder polypoid lesions larger than 10 mm; among them, 20 patients were malignant and 110 patients were benign. Patients' details including ultrasonography (US), computed tomography (CT) and magnetic resonance (MR) findings were analyzed. All patients whose lesions were >15 mm by US, had CT or MR scans to further determine the nature of the lesion; two patients who were suspected to have a malignant lesion due to their large tumor size were benign by histological examination. Distinct differences were found between large adenoma and protruding type of gallbladder carcinoma. There were distinct differences between adenomas and the protruding type gallbladder cancers, and there was a pathological basis for the differences. Benign tumors had a more homogeneous texture, had spaces between the tumor and the gallbladder wall and a relatively normal configuration of the gallbladder wall. Based on these findings, certain lesions could be definitively diagnosed as benign adenomas and could help in treatment strategy.

Mechanisms of blunt liver trauma patterns: An analysis of 53 cases.

Blunt liver trauma is the most dangerous and the second most frequent solid organ trauma that occurs in the abdominal cavity. Management of this life-threatening situation remains a significant challenge. The present study identified that the patterns of blunt liver trauma were closely correlated with the characteristics of the blunt force. Illustrations of findings from this study have been included in the hope that they may aid surgeons in improving the management of this emergency. In total, 53 cases of blunt liver trauma that underwent laparotomy in the First Affiliated Hospital of Wenzhou Medical College between 1999 and 2009 were retrospectively studied. The cause of the injury, the direction and site of the blunt force, surgical records and CT films were carefully studied to obtain information on the patterns and severity of the liver injury and the correlation with blunt forces. Trauma in the right lobe of the liver was mainly caused by acceleration, deceleration and compression of the liver, while in the left lobe of the liver, acceleration was the main cause of the trauma. Liver lacerations were always located close to the attachment sites of the ligaments which bore the majority of the shearing stress. The characteristics of the blunt force play a key role in the different patterns of blunt liver trauma. A thorough understanding of the mechanisms of blunt liver trauma may aid doctors in the management of patients with this condition.

Large villous adenoma of gallbladder: A case report.

INTRODUCTION: Adenomas of the biliary tract are uncommon. Gallbladder adenomas are generally smaller than 20mm in size and can be classified histologically as tubular, papillary, or tubulopapillary. Villous adenoma of gallbladder is extremely rare and is considered as a premalignant condition that eventually progresses to adenocarcinoma via the adenoma-carcinoma sequence. PRESENTATION OF CASE: The clinical data including images, surgical specimen and pathological results of this gallbladder adenoma larger than 50mm were analyzed. This huge gallbladder adenoma had unique imaging appearance, and the pathological examination revealed the lesion to be villous adenoma with mild to moderate dysplasia. DISCUSSION: This rare huge villous adenoma of gallbladder had unique images and pathological appearance different from that of huge tubular adenoma of gallbladder and that of adenocarcinoma. CONCLUSION: Large villous adenoma of gallbladder is a rare disease with unique imaging appearance and pathological characteristics.

A novel canine model of portal vein stenosis plus thioacetamide administration-induced cirrhotic portal hypertension with hypersplenism.

Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism.

Spontaneous rupture of the left common iliac vein.

A 63-year-old woman was admitted because she presented with acute lower abdominal pain and left leg pain without any history of trauma. Lower extremity venous duplex ultrasound demonstrated deep vein thrombosis in the left lower extremity. Computed tomography scan revealed high-density, irregular clumps in the pelvic region and a soft-tissue mass shadow in the right lower abdomen. Emergency laparotomy revealed a 1.5-cm longitudinal tear in the left common iliac vein. The vein was repaired primarily and the postoperative course was uneventful.

A canine portal hypertension model induced by intra-portal administration of Sephadex microsphere.

BACKGROUND AND AIM: Big animal models of portal hypertension are important for the research into this disease. The aim of this study was to establish a canine portal hypertension model by intra-portal administration of microspheres. METHODS: Sixteen mongrel dogs were assigned to control group and experimental group randomly. The catheterization of portal vein was performed by laparotomy and the outer end of the catheter was fixed subcutaneously in the abdominal wall. The dogs of the experimental group were given intra-portal injections of microspheres at a five-day interval, six times in total. Portal hemodynamics, blood cell counting, liver and renal function test, portography, gastroscopy, liver, spleen and lung histological examination were taken to evaluate the model. RESULTS: 1, 2, 3 and 4 months after initial injection of microspheres, portal venous pressure rose from baseline 8.7 +/- 0.7 mmHg to 24.3 +/- 1.6, 20.6 +/- 2.1, 19.0 +/- 1.8 and 17.7 +/- 2.0 mmHg, respectively (P < 0.01). The diameter of portal vein increased from 7.6 +/- 0.3 to 8.6 +/- 0.3 mm, calculated portal resistance increased from 0.46 +/- 0.06 to 1.06 +/- 0.20 (mmHg/mL/min/kg body weight); velocity of portal blood flow decreased from 35.1 +/- 1.7 to 26.1 +/- 2.4 cm/s (P < 0.01, respectively). The animals of experimental group developed marked splenomegaly and profuse portosystemic collateral circulations with normal liver and renal function. CONCLUSION: Repeated intra-portal administration of microspheres can induce stable and reproducible chronic portal hypertension in dogs with normal liver and renal functions. This model can meet multiple demands of both basic and clinical research of portal hypertension.

A modified canine model of portal hypertension with hypersplenism.

OBJECTIVE: The aim of this study was to develop and describe an experimental canine model of portal hypertension with hypersplenism. MATERIAL AND METHODS: Twenty-five dogs were used randomly divided into three groups: group I (control group, n = 5), group II (PVS, n = 10) and group III (PVS + SVS, n = 10). Portal vein stenosis (PVS) was performed in dogs of group II; in group III dogs the model was first prepared by PVS and additional splenic vein stenosis 3 weeks later (PVS + SVS). Portal vein pressure (PVP), length of spleen and fluctuation of hematocyte counts were measured and recorded at the appointed times. Surgery permitted visual verification of portosystemic collateral circulation. Histopathological variation of the spleen and condition of the bone marrow hyperplasia were examined to confirm the development of hypersplenism. RESULT: Both group II and group III developed prehepatic portal hypertension; group III also presented satisfactory hypersplenism compared to the control group and group II, as documented at surgery and by hematologic and pathologic examination. CONCLUSIONS: Based on this study, the modified model of portal hypertension (by PVS + SVS) appears appropriate when studying the relationship between hypersplenism and hemodynamics in portal hypertension. It is also likely to be useful in studying the influence of diseased spleen in the treatment of portal hypertension.