Potential Signaling Pathways Involved in the Clinical Application of Oxymatrine.

Oxymatrine, an alkaloid component extracted from the roots of Sophora species, has been shown to have antiinflammatory, antifibrosis, and antitumor effects and the ability to protect against myocardial damage, etc. The potential signaling pathways involved in the clinical application of oxymatrine might include the TGF-ß/Smad, toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells, toll-like receptor9/TRAF6, Janus kinase/signal transduction and activator of transcription, phosphatidylinositol-3 kinase/Akt, delta-opioid receptor-arrestinl-Bcl-2, CD40, epidermal growth factor receptor, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathways, and dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine metabolism pathway. In this review, we summarize the recent investigations of the signaling pathways related to oxymatrine to provide clues and references for further studies on its clinical application. Copyright © 2016 John Wiley & Sons, Ltd.

Octreotide for primary moderate to severe acute pancreatitis: a meta-analysis.

BACKGROUND/AIMS: To systematically evaluate the effect and safety of octreotide on primary moderate to severe acute pancreatitis. METHODOLOGY: The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed, EMBASE, Science Citation Index Expanded (SCI-E), and Chinese Biomedicine Database (CBM) were searched in September 2011. Major outcomes contained mortality, incidence rate of complications, rate of surgical intervention, and length of hospital stay. RESULTS: Eleven randomized clinical trials with 720 participants were included and evaluated, only two of which had a high study quality and were combined in meta-analysis. The pool estimate of RR of mortality was 0.88 (95% CI: 0.53, 1.45) and that of incidence rate of complication was 1.08 (95% CI: 0.94, 1.26), both of which had no significant difference. The other two outcomes could not be combined for lack of enough data. CONCLUSIONS: Present evidence does not approve octreotide's benefit in the major outcomes of moderate to severe acute pancreatitis and further randomized controlled trials with high quality and large sample size are required.

Therapy for acute pancreatitis with platelet-activating factor receptor antagonists.

Acute pancreatitis (AP) causes release of platelet-activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participate in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of compounds show significant PAF-RAs, and significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.

Significance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021.

AIM: To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS: Wistar male rats were randomly assigned to the negative control group (NC group), SAP model group (SAP group), and BN52051-remedy group (BN group), and each of the groups was divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n = 10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS: Serum amylase and pathological results showed the that SAP model was successfully prepared, BN52021 was able to decrease serum amylase, and the pathological ratings in BN group at 3 h, 6 h, and 12 h significantly decreased compared with those in the SAP group (8.85 +/- 0.39 vs 5.95 +/- 0.19, 9.15 +/- 0.55 vs 5.55 +/- 0.36, 10.10 +/- 0.65 vs 6.72 +/- 0.30, P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups, which increased gradually in early stage, reached a peak at 3 h (0.71 +/- 0.14 vs 0.54 +/- 0.14, 0.69 +/- 0.13 vs 0.59 +/- 0.04, P < 0.05), and decreased gradually later. There were significant differences at each time point except 1 h and 2 h, when compared with those in the NC group (0.71 +/- 0.14 or 0.69 +/- 0.13 vs 0.47 +/- 0.10, 0.38 +/- 0.08 or 0.59 +/- 0.04 vs 0.47 +/- 0.09, 0.25 +/- 0.07 or 0.29 +/- 0.05 vs 0.46 +/- 0.10, 0.20 +/- 0.06 or 0.20 +/- 0.04 vs 0.43 +/- 0.09, P < 0.05), whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h, when compared with those in the NC group (0.90 +/- 0.02 or 0.80 +/- 0.05 vs 0.48 +/- 0.02, 1.69 +/- 0.06 or 1.58 +/- 0.02 vs 0.48 +/- 0.03, 1.12 +/-0.10 or 0.98 +/- 0.03 vs 0.49 +/- 0.09, 1.04 +/- 0.14 or 0.87 +/- 0.02 vs 0.52 +/- 0.08, 0.97 +/- 0.16 or 0.90 +/- 0.05 vs 0.49 +/- 0.10, P < 0.05), whereas there was no significant difference between the BN group and the SAP group. CONCLUSION: PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.

Effect of BN52021 on NFkappa-Bp65 expression in pancreatic tissues of rats with severe acute pancreatitis.

AIM: To investigate dynamic changes and significance of expression of NF-kappaBp65 in pancreatic tissues of rats with severe acute pancreatitis (SAP), as well as BN52021 effects. METHODS: Wistar male rats were randomly divided into negative control group (NC group, n=60), SAP-model group (SAP group, n=60), and BN52021-treated group (BN group, n=60), and each of the above groups was respectively divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n=10). By RT-PCR and Western blot, NF-kappaBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively. RESULTS: The expression of NF-kappaBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and higher in BN groups than SAP group at 1 h (P<0.05). The NF-kappaBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h (P<0.01), and 2 h, 12 h, and 24 h (P<0.05), higher in BN groups than NC groups at all time points (P<0.05), and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h (P<0.05). CONCLUSION: The expression of NF-kappaBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAP. BN52021 exerts therapeutic effects through reducing the expression level of NF-kappaBp65 protein in the early stage of SAP.

Pharmacological action and mechanisms of ginkgolide B.

OBJECTIVE: To review the recent research progress in pharmacological actions and mechanisms of ginkgolide B. Data sources Information included in this article was identified by searching of PUBMED (1987 - 2006) online resources using the key terms "ginkgolide B", "platelet activating factor", and "pharmacological". Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. RESULTS: The key issues related to the pharmacological actions and mechanisms of ginkgolide B were summarized. The ginkgolide B possesses a number of beneficial effects such as anti-inflammatory, anti-allergic, antioxidant, and neuroprotective effects. Meantime, their mechaniams were discussed. CONCLUSIONS: The Ginkgolide B is the most potent antagonist of platelet activating factor (PAF) and exhibits therapeutic action in a variety of diseases mainly by the PAF receptor.

Mechanisms of regulation and function of G-protein-coupled receptor kinases.

G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated form of G-protein-coupled receptor (GPCR) to affect receptor phosphorylation and to initiate profound impairment of receptor signaling, or desensitization. GPCR forms the largest family of cell surface receptors, and defects in GRK function have the potential consequence to affect GPCR-stimulated biological responses in many pathological situations.

Role of platelet-activating factor in the pathogenesis of acute pancreatitis.

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides with diverse pathological and physiological effects. This bioactive phospholipid mediates processes as diverse as wound healing, physiological inflammation, angiogenesis, apoptosis, reproduction and long-term potentiation. PAF acts by binding to a specific G protein-coupled receptor to activate multiple intracellular signaling pathways. Since most cells both synthesize and release PAF and express PAF receptors, PAF has potent biological actions in a broad range of cell types and tissues. Inappropriate activation of this signaling pathway is associated with many diseases in which inflammation is thought to be one of the underlying features. Acute pancreatitis (AP) is a common inflammatory disease. The onset of AP is pancreatic autodigestion mediated by abnormal activation of pancreatic enzyme caused by multiple agents, which subsequently induce pancreatic and systemic inflammatory reactions. A number of experimental pancreatitis and clinical trials indicate that PAF does play a critical role in the pathogenesis of AP. Administration of PAF receptor antagonist can significantly reduce local and systemic events that occur in AP. This review focuses on the aspects that are more relevant to the pathogenesis of AP.

Bibliometric analysis of top 100 cited articles in nonalcoholic fatty liver disease research.

AIM: To identify and assess the research situation of top 100 cited articles in nonalcoholic fatty liver disease (NAFLD). METHODS: The global scientific research articles in the Science Citation Index-Expanded relevant to NAFLD were retrieved and listed according to their citation times from the most to the least. The 100 most frequently cited original articles were selected to systematically evaluate their bibliometric parameters including times cited, publication year, journals, subject categories, and the highly related concepts of NAFLD, which reflected the history and current situation, publication distribution of leading countries and institutes as well as the research hotspots of NAFLD. RESULTS: Top 100 cited articles in NAFLD were published from 1965 to 2015 with a citation ranging of 227 to 2151 times since publication, in which the United States was the most predominant country and Mayo Clin was the most productive institution. The majority of the top 100 cited articles were concentrated in SCI subject category of Gastroenterology and Hepatology. Hepatology and Gastroenterology is the top journal that published over half 100 top-cited articles. The significant peak of top cited articles present in the first half of the 2000s while the highest mean number of citation presents in first half of the 1980s. In addition, concepts related to pathology characteristics, epidemiology and medicalization, metabolic syndrome and its combination of symptoms including insulin resistance, biomarkers of lipid metabolism and obesity are listed as the highly related concepts. CONCLUSION: The 100 top-cited articles marked with the leading countries, institutions, journals, hotspots and development trend in NAFLD field that could provide the foundation for further investigations.

Global publication trends and research hotspots of nonalcoholic fatty liver disease: a bibliometric analysis and systematic review.

With the globally increasing prevalence, nonalcoholic fatty liver disease (NAFLD) becomes the predominant cause of chronic liver disease. A global look at the publication trends and the research hotspots of NAFLD are urgently needed to assess the situation of NAFLD research. The global scientific research in the Science Citation Index-Expanded covered articles relevant to NAFLD was retrieved and its bibliometric parameters and research hotspots of NAFLD were systematically evaluated. To sum up, 6356 articles were published in 994 different journals covering 93 SCI subject categories during 1986-2013, in which English was the most predominant language used. Starting from the late 1980s, the publication on NAFLD grew slowly and entered into a highly developing period in the 21st century, especially in the last decade. Besides hepatic steatosis, metabolic syndrome and its combination of symptoms such as obesity, insulin resistance are listed as the top frequent keywords. Bibliometric results suggest that the obviously rapid growth of the articles in recent years appears to be associated with the accelerating incidence of NAFLD and its cofactors such as metabolic syndrome. In addition, epidemiology focusing on comparing different regions and population is attracting ever-growing attention. Meantime, pathology plays an important role in NAFLD research.

Potential role of NADPH oxidase in pathogenesis of pancreatitis.

Studies have demonstrated that reactive oxygen species (ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase (NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules (lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis.

Prevention effect of allopurinol on post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of prospective randomized controlled trials.

BACKGROUND: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs) have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP). However, these results remained controversial. OBJECTIVE: To conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP. METHODS: Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ2 test with the significance set P<0.10 or I2>50%. RESULTS: Six RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986) and 9.9%(98/988) respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39-1.42) with significant heterogeneity (I2 = 70.4%, P = 0.005). When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (Imoderate2 = 82.3%, Pmoderate = 0.018). Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (Imild2 = 62.8%, Pmild = 0.068). CONCLUSION: The prophylactic use of allopurinol in different dosages and administration time had no effect in preventing incidence and severity of PEP.

Roles of BN52021 in platelet-activating factor pathway in inflammatory MS1 cells.

AIM: To determine the effects of BN52021 on platelet-activating factor receptor (PAFR) signaling molecules under lipopolysaccharide (LPS)-induced inflammatory conditions in MS1 cells. METHODS: MS1 cells (a mouse pancreatic islet endothelial cell line) were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mmol/L glutamine and 100 µg/mL penicillin/streptomycin in 5% CO2 at 37 °C. After growth to confluency in media, the cells were processed for subsequent studies. The MS1 cells received 0, 0.1, 1 and 10 µg/mL LPS in this experiment. The viability/proliferation of the cells induced by LPS was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Apoptosis and necrosis of the cells under the inflammatory condition described previously were observed using Hoechst 33342-propidium iodide staining. Adenylate cyclase (AC), phospholipase A2 (PLA2), phospholipase Cß (PLCß), protein tyrosine kinase (PTK), G protein-coupled receptor kinases (GRK) and p38-mitogen-activated protein kinase (p38 MAPK) mRNA in the PAFR signaling pathway were measured by real-time polymerase chain reaction. The protein expression level of phosphorylated AC (p-AC), phosphorylated PLA2 (p-PLA2), phosphorylated PTK (p-PTK), phosphorylated p38 MAPK (p-p38 MAPK), PLCß and GRK was measured using Western blotting analysis. RESULTS: The activity of MS1 cells incubated with different concentrations of LPS for 6 h decreased significantly in the 1 µg/mL LPS group (0.49 ± 0.10 vs 0.67 ± 0.13, P < 0.05) and 10 µg/mL LPS group (0.44 ± 0.10 vs 0.67 ± 0.13, P < 0.001), but not in 0.1 µg/mL group. When the incubation time was extended to 12 h (0.33 ± 0.05, 0.32 ± 0.03 and 0.25 ± 0.03 vs 0.69 ± 0.01) and 24 h (0.31 ± 0.01, 0.29 ± 0.03 and 0.25 ± 0.01 vs 0.63 ± 0.01), MS1 cell activity decreased in all LPS concentration groups compared with the blank control (P < 0.001). BN52021 significantly improved the cell activity when its concentration reached 50 µmol/L compared with the group that received LPS treatment alone, which was consistent with the results obtained from fluorescence staining. The mRNAs levels of AC (4.02 ± 0.14 vs 1.00 ± 0.13), GRK (2.63 ± 0.03 vs 1.00 ± 0.12), p38 MAPK (3.87 ± 0.07 vs 1.00 ± 0.17), PLA2 (3.31 ± 0.12 vs 1.00 ± 0.12), PLCß (2.09 ± 0.08 vs 1.00 ± 0.06) and PTK (1.85 ± 0.07 vs 1.00 ± 0.11) were up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up-regulated mRNAs including AC (2.35 ± 0.13 vs 3.87 ± 0.08), GRK (1.17 ± 0.14 vs 2.65 ± 0.12), p38 MAPK (1.48 ± 0.18 vs 4.30 ± 0.07), PLCß (1.69 ± 0.10 vs 2.41 ± 0.13) and PLA2 (1.87 ± 0.11 vs 2.96 ± 0.08) were significantly suppressed by BN52021 except for that of PTK. The level of p-AC (1.11 ± 0.12 vs 0.65 ± 0.08), GRK (0.83 ± 0.07 vs 0.50 ± 0.03), PLCß (0.83 ± 0.16 vs 0.50 ± 0.10) and p-p38 MAPK (0.74 ± 0.10 vs 0.38 ± 0.05) was up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up-regulated proteins, including p-AC (0.65 ± 0.15 vs 1.06 ± 0.14), GRK (0.47 ± 0.10 vs 0.80 ± 0.06), PLCß (0.47 ± 0.04 vs 0.80 ± 0.19) and p-p38 MAPK (0.30 ± 0.10 vs 0.97 ± 0.05), was significantly suppressed by BN52021, but p-PLA2 and p-PTK protein level were not suppressed. CONCLUSION: BN52021 could effectively inhibit LPS-induced inflammation by down-regulating the mRNA and protein levels of AC, GRK, p38 MAPK, PLA2 and PLCß in the PAFR signaling pathway.

Mechanism and dose-effect of Ginkgolide B on severe acute pancreatitis of rats.

AIM: To determine the optimal dosage and mechanism of Ginkgolide B (BN52021) on severe acute pancreatitis (SAP) of rats. METHODS: Seventy male Wistar rats were randomly divided into seven groups (10 for each group). Sham-operation group (SO), SAP model group (SAP), dimethyl sulfoxide (DMSO) contrast group (DMSO), and groups treated with 2.5 mg/kg BN52021 (BN1), 5 mg/kg BN52021 (BN2), 10 mg/kg BN52021 (BN3), and 20 µg/kg Sandostatin (SS). The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely into the common bilio-pancreatic duct. The rats of SO, DMSO and BN52021 were injected with 0.9% NaCl, 0.5% DMSO and BN52021 through femoral vein 15 min after the operation. The SS group was injected with Sandostatin subcutaneously. All rats were anaesthetized at 6 h after operation, and venous blood was collected to determine the levels of serum amylase and phospholipase A2 (PLA2), and pancreas tissue was harvested and stained. RESULTS: There was no significant difference between the SAP and DMSO groups in serum amylase level, PLA2, ascites and pathologic score, but significant difference was found in SAP/DMSO groups compared with those in SO group (P < 0.05) and the levels of serum amylase, PLA2, ascites, and pathologic score were lower in the BN1, BN2, BN3 and SS groups than in the SAP and DMSO groups (P < 0.05). However, among BN1, BN2, BN3 and SS groups, BN2 had the best effect in decreasing the levels of serum amylase and PLA2 (P < 0.05). Expression of platelet activating factor (PAF) receptor (PAFR) mRNA and protein showed no significant difference between the SAP and DMSO groups, or among BN1, BN2, BN3 and SS groups, but there was remarkable difference between SAP/DMSO group and SO group (P < 0.05), and expression of PAFR mRNA and protein was higher in the BN1, BN2, BN3 and SS groups than in the SAP and DMSO groups (P < 0.05). PAFR expression was observed in the nucleus and cytoplasm of pancreatic islet cells in Wistar rats by immunohistochemistry. CONCLUSION: By iv injection, 5 mg/kg of BN52021 is the optimal dosage for SAP rats. BN52021 may inhibit the interaction/binding of PAF with PAFR.

[Effects of neuroactive steroid allopregnanolone on the damage of cortical neurons].

OBJECTIVE: To investigate the protective mechanism of neuroactive steroid allopregnanolone on N-methyl-D-aspartate (NMDA) induced toxicity in primary mouse cortical neurons. METHODS: Primary cultured mouse cortical neurons were subjected to allopregnanolone, the expression of beta-aminobutyric acid receptor beta2 subunit (beta2-GABA-R) mRNAs was detected by RT-PCR and Akt phosphorylation was assayed by Western blot using Akt-phosphoserine 473-specific antibody. After the cultured mouse cortical neurons were pretreated with or without allopregnanolone prior to treatment with NMDA , DNA isolated was analyzed by agarose gel electrophoresis and proteins collected were analyzed by Western blot with anti-cleaved-PARP, anti-cleaved caspase-3, and anti-cleaved caspase-9 antibodies. RESULTS: When cultured mouse cortical neurons were exposed to allopregnanolone both the expression of beta2-GABA-R mRNAs and Akt phosphorylation increased. Allopregnanolone inhibited the NMDA-induced apoptosis and decreased the level of active-PARP, active-caspase-3 and active-caspase-9 notably at a final concentration of 5 x 10(6) mol/L. CONCLUSION: Pretreatment with allopregnanolone may be neuroprotective on NMDA-induced neuronal cells apoptosis by increasing beta2-GABA-R expression and Akt phosphorylation.

Silencing of the hPOT1 gene by RNA inference promotes apoptosis and inhibits proliferation and aggressive phenotype of gastric cancer cells, likely through up-regulating PinX1 expression.

BACKGROUND: The human protection of telomeres 1 (hPOT1) protein, a single-strand telomeric DNA binding protein, plays an important role in telomere protection and telomere length regulation. However, its effect on invasion of gastric cancer remains unclear. AIMS: To explore the role of hPOT1 in the proliferation and invasion of gastric cancer cells. METHODS: The gastric expression of hPOT1 was examined in normal gastric mucosa (n=25), intestinal metaplasia (n=20), gastric dysplasia (n=20) and gastric cancer (n=150) by immunohistochemistry. The mean optical density (MOD) of the immunostaining was determined by semi-quantitative image analysis. The role of hPOT1 in the cell proliferation, apoptosis and invasion of gastric cancer 7901 cells was determined by means of the RNA interference (RNAi) of hPOT1 mRNA. The effects of hPOT1 RNAi on the expression of hPinX1 and hTERT were detected with western blotting. RESULTS: The hPOT1 MOD was progressively increased from the normal mucosa to intestinal metaplasia, dysplasia, and gastric cancer. An increased hPOT1 expression significantly correlated with tumour serosal invasion, node metastasis and advanced stage. Transfection of hPOT1 siRNA into SGC-7901 cells led to a decrease in cell proliferation, colony formation and invasion, and also an increase of apoptosis. An up-regulation of hPinX1 and down-regulation of hTERT were found in gastric cancer cells with hPOT1 siRNA. CONCLUSIONS: Increased hPOT1 expression is associated with an advanced tumour stage. hPOT1 RNAi inhibits proliferation and invasion, and induces apoptosis of gastric cancer cells. The effects of hPOT1 RNAi seem to be functionally linked to up-regulation of PinX1 and down-regulation of hTERT.

[Effect of ginkgolide B on plasma levels of interleukin-12 and PAF in severe acute pancreatitis in rats].

AIM: To observe the levels of interleukin-12 (IL-12) and platelet activating factor (PAF) in severe acute pancreatitis (SAP) in rats and the efficacy of Ginkgolide B (BN52021) in treating SAP. METHODS: Wistar rats were randomly divided into 3 groups: model group (SAP), treatment group (BN) and negative control group (NC). SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in Wistar rats. NC rats only receive abdominal incision. In groups of SAP and NC rats received the femoral vein injection of isotonic Na chloride 15 minutes after induction of SAP; in BN group,rats received BN52021 instead. After operation rats were sacrificed at 1, 6 and 12 hour for plasma IL-12 and PAF determined with ELISA. RESULTS: An increase of IL-12 in group BN was observed VS group SAP or group NC at 1 h stage (p = 0.011, P < 0.01). At 6 h or 12 h stage,an increase of IL-12 in group SAP was observed VS group NC (P < 0.01, P < 0.05). The plasma level of PAF in group SAP or group BN was increased significantly at 1 h time stage VS group NC (P < 0.001). At 6 h or 12 h stage, a decrease of PAF in group BN or group NC was observed VS group SAP (P < 0.05, P < 0.01). CONCLUSION: It confirmed that the plasma level of cytokine IL-12 in SAP group was decreased significantly in early stage and it witnessed a remarkable increase of cytokine PAF. The plasma level of IL-12 was increased in early stage but PAF was decreased in rats treatment by BN52021 which inhibited the development of SAP.