Qingyong Ma

Effect of resveratrol on peritoneal macrophages in rats with severe acute pancreatitis

Abstract.Objective: The literature on resveratrol in severe acute pancreatitis (SAP) is limited though it has been widely studied in infections and trauma. The aim of this study was to investigate the inhibitory effect of resveratrol on inflammatory responses in a rat model of SAP.n Methods: Male Sprague-Dawley (SD) rats were randomly divided into 3 groups: SAP group, resveratrol group and control group. 4.0% sodium taurocholate was injected into the pancreatic duct to induce SAP. In the resveratrol group, resveratrol (10xa0mg/kg) was injected through penal vein 5xa0min after SAP was induced. The peritoneal macrophages of the rats were collected 3, 6 and 12 h after stimulus and then incubated for 24 h. The expression of nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in peritoneal macrophages was measured. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1) and nitric oxide (NO) in culture medium of peritoneal macrophages and serum of rats were evaluated.n Results: Histological examination of pancreas indicated that the damage in the SAP group was more severe than that in the resveratrol group. The expression of NF-κB and iNOS in peritoneal macrophages was significantly higher in the SAP group than in the resveratrol group. The concentrations of TNF-α, IL-1 and NO in culture medium and serum were significantly elevated in the SAP group when compared with the resveratrol group.n Conclusions: The inhibiting effect on the inflammatory response and the decreased expression of TNF-α, IL-1 and NO in peritoneal macrophages suggest resveratrol as a novel anti-inflammatory agent for reducing the severity of SAP.

Clinical Significance of B7-H1 and B7-1 Expressions in Pancreatic Carcinoma

BackgroundCancer cells develop mechanisms to evade immune cells and achieve progression. Aberrant B7-H1 and B7-1 expressions may help pancreatic carcinoma (PC) cells escape immune attack; these molecules can be considered as prognostic markers for patients with PC who have undergone radical resection.MethodsWe recruited 81 patients who had undergone radical surgical resection for PC between 1999 and 2007. To investigate the prognostic factors, we evaluated the B7-H1 and B7-1 protein expressions in the tissue specimens of these 81 patients by immunohistochemistry and analyzed the clinical and pathological features of these specimens.ResultsB7-H1 was expressed mainly in pancreatic islets, and no B7-1 expression was detected in normal pancreatic tissues. B7-H1 and B7-1 expressions were higher in pancreatic carcinoma tissues than in normal pancreatic tissues (Pxa0<xa00.05). B7-H1 and B7-1 significantly correlated with the pathological grade and tumor-node-metastasis (TNM) stage, respectively (Pxa0<xa00.05). Furthermore, B7-1-negative or B7-H1-positive statuses were prognostic indicators of poor disease-specific survival (Pxa0<xa00.05), but only combined B7-1/B7-H1 expression retained the prognostic potential after adjusting by Cox proportional hazards regression models (Pxa0<xa00.05).ConclusionsBoth B7-H1 and B7-1 are expressed in PC; these molecules are important markers for PC progression. Furthermore, combined B7-1/B7-H1 expression can serve as an independent prognostic marker for PC.

Resveratrol ameliorates hepatic injury via the mitochondrial pathway in rats with severe acute pancreatitis

To gain insight into the processes by which severe acute pancreatitis induced apoptosis takes place in the liver, and to observe the protective effect of resveratrol on hepatic injury, a rat model of severe acute pancreatitis was induced by administering 4% sodium taurocholate through the common biliopancreatic duct. Pancreatic and hepatic injury was assessed by histology. Serum ALT (alanine aminotransferase), AST (aspartate aminotransferase) and total bilirubin were determined by reaction rate assay, and the serum levels of TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) were detected by ELISA (enzyme linked immunosorbent assay). We investigated cytochrome c released from mitochondria and used the RT-PCR (reverse transcription PCR), Western blot technique to evaluate Bax, Bcl-2, and caspase-3 expression levels in hepatic tissue over the time course of apoptosis. Changes in hepatic cell mitochondrial membrane potential were observed by confocal laser scanning microscopy. The majority of cytochrome c release occurred early in apoptosis from mitochondria, which undergo gradual hepatic impairment. The released cytochrome c can be reduced by resveratrol through both up-regulation of Bcl-2 and down-regulation of Bax and caspase-3. These data provide substantial evidence that apoptosis is involved in hepatic injury during the severe acute pancreatitis process and that resveratrol can ameliorate the situation, thus protecting liver function in rats with severe acute pancreatitis.

RESVERATROL AMELIORATES LUNG INJURY VIA INHIBITION OF APOPTOSIS IN RATS WITH SEVERE ACUTE PANCREATITIS

The objective of this study was to evaluate the protective effects of resveratrol on lung injury in rats with severe acute pancreatitis. Ninety-six male Sprague-Dawley rats were randomly classified into 4 equal groups (n = 24): control, model, resveratrol-treated, and dexamethasone-treated. The rats were evaluated at 3, 6, and 12 hours after induction of pancreatitis. The following were assessed: PaO2by arterial blood gas analysis; pancreatic and lung injury by histology; and ultrastructure of lung tissue by transmission electron microscopy. The authors investigated mitochondrial cytochrome c release and evaluated the Bax, Bcl-2, and caspase-3 expression levels in lung tissue over the time course of apoptosis. Changes in lung cell mitochondrial membrane potential were evaluated by confocal laser scanning microscopy. In the model group, lung congestion, edema, inflammatory-cell infiltration, mitochondrial swelling, and cell apoptosis were apparent. In the resveratrol and dexamethasone groups, the morphological changes of the lungs were alleviated. The expression level of Bcl-2 was significantly higher and those of Bax, caspase-3, and cytochrome c were significantly lesser in the resveratrol group than in the model group. Apoptosis is involved in lung injury associated with severe acute pancreatitis, and resveratrol can ameliorate this injury, thus protecting lung function in rats with severe acute pancreatitis.

CacyBP/SIP Expression is Involved in the Clinical Progression of Breast Cancer

ObjectiveCalcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) is a target protein of the S100A6, which is a member of the S100 family. It has been shown that CacyBP/SIP plays important roles in cell cycle progression, differentiation, and carcinogenesis. The purpose of this study was to explore the correlation of CacyBP/SIP expression and clinical significance in breast cancer.MethodsImmunohistochemistry was performed to detect the CacyBP/SIP expression in 79 pairs of breast cancer tissues and adjacent nontumor tissues. Western blot analysis and semiquantitative RT-PCR were used to measure CacyBP/SIP protein and mRNA levels in three pairs of fresh breast cancer tissues and adjacent nontumor tissues. The clinical data were collected by telephone follow-up for 5xa0years.ResultsCacyBP/SIP mRNA and protein levels in breast cancer tissues were significantly higher compared with adjacent nontumor tissues. Poor cellular differentiation, lymph node invasion, and clinicopathological staging in breast cancer were associated with CacyBP/SIP expression. Other factors, such as age, menses, and tumor size, were not related to CacyBP/SIP expression. The up-regulation of CacyBP/SIP expression also was shown to increase recurrence and metastasis of breast cancer and to correlate with short overall survival rate.ConclusionsCacyBP/SIP expression is evident in more advanced clinical progression of breast cancer, and it might be a biomarker for poor prognosis and a potential therapeutic target in breast cancer.

Blockade of hedgehog signaling pathway as a therapeutic strategy for pancreatic cancer

Recent studies have demonstrated that pancreatic adenocarcinoma cells require hedgehog (HH) signaling for proliferation and survival. Mutations in the smoothened (SMOH) gene and loss-of-function mutations in the patched (PTCH) gene, which are involved in the HH signaling pathway, may cause pancreatic tumors. Since HH signaling pathway may contribute to the induction and maintenance of pancreatic tumors, the use of HH pathway inhibitors for targeting the pancreatic cancer might represent a novel therapeutic approach to advanced pancreatic carcinoma. Among the HH inhibitors, cyclopamine inhibits HH signaling through direct interaction with SMOH and retards the growth of cancer cells by inhibiting stem cells. Novel therapies that target the HH signaling pathway should become one of the more effective treatments for pancreatic cancer, which cannot be cured with current therapies.

Resveratrol Ameliorates the Deleterious Effect of Severe Acute Pancreatitis

Resveratrol (RES) is a traditional Chinese herbal medicine having anti-inflammatory properties. We sought to explore the role of RES in intestinal injury during severe acute pancreatitis (SAP) in a rat model study. For this purpose, RES-treated and sham-operated (SO) SAP rat models were established, and SAP was induced in rats by injecting 4% sodium taurocholate into the biliary-pancreatic duct. In the RES group, RES was infused intravenously immediately after the SAP induction in rats; SO group served as controls. Histopathological analysis, determination of tissue levels of superoxide dismutase (SOD) and malondialdehyde (MDA) and serum levels of TNF-α as well as ICAM-1 and VCAM-1 expression were carried out at 3, 6, and 12xa0h following SAP induction. The data show that following SAP induction, SOD levels decreased and MDA levels increased along with ICAM-1 and VCAM-1 expression in the intestine. Serum TNF-α levels increased in the SAP group. Importantly, RES treatment significantly reversed all the pathological changes. In conclusion, this study confirmed the anti-inflammatory properties of RES and demonstrated the prevention of injury to the intestinal barrier in the rat SAP model.

Trypsin is the culprit of multiple organ injury with severe acute pancreatitis

The consistently high proportion of early deaths in patients with severe acute pancreatitis (SAP) has been associated mainly with the development of multiple organ dysfunction syndromes (MODS). So far, scholars believed that the main reasons of MODS with SAP are systemic microcirculation dysfunction and inflammatory mediator induced cascading effect on the basis of pancreas digesting itself. However, there is some special pathological phenomenon in the process of SAP which could not be explained by current theories. First, it has been evident that the pancreatic tissue bleeding and necrosis is special pathological change in pancreas autodigestive effect from digestive enzymes such as trypsin in SAP. However, we found that the liver, the lung, the intestine, the brain and the kidney have the same pathological changes in experimental animal models of SAP. Secondly, unlike the general inflammatory response, a significantly amount of bloody ascites and pleural effusion was often in patients with SAP and in experimental SAP animal models. It indicates that the vascular permeability significantly increased leading to the red blood cells extravasation. Thirdly, apart from dual blood supply, liver bears a strong compensatory function. However, liver has the highest incidence of injury in SAP when compared with other organs. In addition, we found a very interesting phenomenon after reading texts and clinical records. From the pancreatic venous drainage from the point of view, the farther the organ from the pancreas, the lower injury incidence rate observed. How to explain these mysteries? We postulate that the trypsin is the culprit of multiple organs dysfunction in SAP. The activated trypsin destroy the pancreas itself, causing pancreatic tissue bleeding and necrosis, at the same time, through venous flow it flow into the blood circulation and destroy the vascular endothelial barrier, leading to highly increased vascular permeability. So, a large number of bloody exudates leakages from the vessels, resulting in patients early circulatory disorders, multiple organ bleeding, bloody pleural effusion and ascites. This pathological change is the most apparent in the liver because the liver is the first organ to receive the pancreatic venous flow having the highest concentration of trypsin. Thus, if the quantity of trypsin decreases in blood, its ability to damage other organs also shows a trend of gradually reducing. These mysteries can be explained by this hypothesis and might help us to understand more clearly about the mechanism of SAP-associated MODS.

An evaluation of the diagnostic value of CA19-9 and CEA levels in patients with pancreatic cancer

Abstract Objective The use of a combination of tumor markers may be an important tool in the early diagnosis of pancreatic cancer, which is the key to improving prognosis. The study aim was to investigate the diagnostic value of carbohydrate antigen 19-9(CA 19-9) and carcinoembryonic antigen(CEA) levels in patients with pancreatic cancer. Methods An immunoradiometric assay was used to homochronously measure the serum CA19-9 and CEA levels in 78 pancreatic cancer cases and 64 healthy examinees in hospital. The normal reference values were CA19-9(0-39 U/ml) and CEA(0-3.4 ng/ml). Results Mean serum CA19-9 and CEA levels in patients with pancreatic cancer(406.55 ± 60.18 U/ml, 12.43 ± 1.25 ng/ml) were significantly higher(P Conclusion The combined detection of CA19-9 and CEA could overcome the deficiency of using single marker detection by improving the sensitivity to diagnose pancreatic cancer. At the same time, CA19-9 and CEA detection could be used to assess mesenteric artery invasion and the metastasis of lymphatics and distant organs in pancreatic cancer.

Relationship of Fibronectin and CD44v6 Expression with Invasive Growth and Metastasis of Liver Cancer

Fibronectin and CD44v6 are involved in tumor invasion and metastasis. We examined fibronectin and CD44v6 expression in normal liver and liver cancer by immunohistochemistry. Fibronectin expression was identified in 37.5% of liver cancer specimens. Well-differentiated tumors and expansive growth were associated with continuous periacinar, or cytoplasmic and periacinar fibronectin expression; poorly differentiated and invasive tumors showed interrupted periacinar or vascular mesenchymal fibronectin expression. CD44v6 expression was absent in controls but was observed in 67.5% of liver cancers. Increased CD44v6 expression was more common with poor clinical tumor characteristics. FN and CD44v6 are potential markers for determining liver cancer invasion and metastasis.