Deregulation of Toll-like receptor 4 (TLR4) is closely associated with the progression of various types of cancers, but its role in pancreatic carcinogenesis is unclear. This study aimed to ...investigate the role of TLR4 in the angiogenesis of pancreatic cancer and the underlying molecular mechanisms.
The culture supernatant (conditioned medium) of PANC-1 cells after appropriate treatment was used for the treatment of HUVECs. The proliferation, migration and tube formation of HUVECs were assessed by MTT, Transwell and Matrigel, respectively. In pancreatic cancer tissues, TLR4, VEGF and CD31 were upregulated as determined by immunohistochemistry and the expression of TLR4 and VEGF was positively correlated with microvessel density as detected by CD31 staining. Activation of TLR4 signaling by LPS in PANC-1 cells resulted in increased VEGF and phosphorylation of AKT, which were abolished by TLR4 silencing with siRNA and PI3K/AKT signaling inhibitor LY294002.
The conditioned medium from PANC-1 cells treated with LY294002 or transfected with TRL4 siRNA reduced the proliferation, migration and tube formation of HUVECs. In contrast, the conditioned medium from PANC-1 cells treated with LPS stimulated the proliferation, migration and tube formation of HUVECs, which was however significantly inhibited by pretreatment of PANC-1 cells with LY294002 or transfection with TRL4 siRNA.
Our findings suggest TLR4 may promote angiogenesis in pancreatic cancer by activating the PI3K/AKT signaling pathway to induce VEGF expression.
Inflammation, apoptosis and oxidative stress contribute to the development of severe acute pancreatitis-associated acute lung injury (SAP-ALI). Currently, there is no curative treatment for SAP-ALI ...in the clinic. This study investigated the potential therapeutic role and mechanisms of colchicine in a rat model of SAP-ALI.
Male Sprague-Dawley rats were randomized and administrated intragastrically with vehicle saline or colchicine (0.5 mg/kg/day) for seven days, followed by injecting sodium taurocholate to induce SAP-ALI. Together with a healthy control group of rats, their pancreatic and lung tissues and plasma samples were collected for histology, enzyme-linked immunosorbent assay (ELISA), immunoblot, immunohistochemistry, and immunofluorescence.
Compared with the sham controls, the SAP group of rats with vehicle saline treatment displayed severe damages, inflammation with many neutrophil and macrophage infiltrates in pancreatic and lung tissues, accompanied by elevated levels of plasma interleukin-1β (IL-1β), IL-6 and tumor necrosis factor (TNF)-α, which were significantly mitigated in colchicine-treated SAP + COL group of rats. Furthermore, colchicine treatment significantly attenuated nuclear factor kappa-B (NF-κB)-p65, signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) phosphorylation, reduced inducible nitric oxide synthase (iNOS) and 4-Hydroxynonenal expression, ROS production and cell apoptosis by decreasing caspase-3 cleavage, Bax expression, but increasing Bcl-2, nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in pancreatic and lung tissues, relative to the SAP group of rats.
Colchicine treatment significantly mitigated the severity of SAP-ALI by inhibiting inflammation, oxidative stress and cell apoptosis in rats.
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•Inflammation, apoptosis and oxidative stress play critical roles in severe acute pancreatitis (SAP).•Colchicine (COL) mitigates severe acute pancreatitis-associated lung injury (SAP-ALI) in rats model.•Colchicine limits inflammation, apoptosis and oxidative stress in SAP-ALI.
Complications of peptic ulcer disease (PUD) are common in China. Population-based estimates of the prevalence of PUD are needed to quantify and characterize the population at risk of these ...complications.
As part of a large epidemiological study, 3,600 randomly selected residents of Shanghai (aged 18-80 years) were asked to undergo endoscopy and to provide blood samples for Helicobacter pylori serology. All participants also completed a general information questionnaire and Chinese versions of the reflux disease questionnaire (RDQ) and Rome II questionnaire. Associations between PUD and other factors were analyzed using a multiple logistic regression model.
In total, 3,153 individuals (87.6%) completed the survey. All underwent blood tests, and 1,030 patients (32.7%) agreed to undergo endoscopy. Results from 1,022 patients were suitable for analysis. In all, 176 participants (17.2%) had PUD (62 with gastric ulcer; 136 with duodenal ulcer). The prevalence of H. pylori infection was 73.3% in the total population and 92.6% among those with PUD. H. pylori infection was associated with the presence of PUD (odds ratio (OR), 6.77; 95% confidence interval (CI), 2.85-16.10). The majority (72.2%) of individuals with PUD had none of the upper gastrointestinal symptoms assessed by the RDQ. PUD was not significantly associated with symptom-defined gastroesophageal reflux disease (GERD) (OR, 0.80; 95% CI, 0.32-2.03), reflux esophagitis (OR, 1.46; 95% CI, 0.76-2.79) or dyspepsia (OR, 1.69; 95% CI, 0.94-3.04).
The prevalence of endoscopically confirmed PUD in this Shanghai population (17.2%) is substantially higher than in Western populations (4.1%). The majority of individuals with PUD were asymptomatic.
Altered gene methylation, regulated by DNA methyltransferases (DNMT) 1, 3a and 3b, contributes to tumorigenesis. However, the role of DNMT in pancreatic ductal adenocarcinoma (PDAC) remains unknown.
...Expression of DNMT 1, 3a and 3b was detected in 88 Pancreatic ductal adenocarcinoma (PDAC) and 10 normal tissue samples by immunohistochemistry. Changes in cell viability, cell cycle distribution, and apoptosis of PDAC cell lines (Panc-1 and SW1990) were assessed after transfection with DNMT1 and 3b siRNA. Levels of CDKN1A, Bcl-2 and Bax mRNA were assessed by qRT-PCR, and methylation of the Bax gene promoter was assayed by methylation-specific PCR (MSP).
DNMT1, 3a and 3b proteins were expressed in 46.6%, 23.9%, and 77.3% of PDAC tissues, respectively, but were not expressed in normal pancreatic tissues. There was a co-presence of DNMT3a and DNMT3b expression and an association of DNMT1 expression with alcohol consumption and poor overall survival. Moreover, knockdown of DNMT1 and DNMT3b expression significantly inhibited PDAC cell viability, decreased S-phase but increased G1-phase of the cell cycle, and induced apoptosis. Molecularly, expression of CDKN1A and Bax mRNA was upregulated, and the Bax gene promoter was demethylated. However, a synergistic effect of combined DNMT1 and 3b knockdown was not observed.
Expression of DNMT1, 3a and 3b proteins is increased in PDAC tissues, and DNMT1 expression is associated with poor prognosis of patients. Knockdown of DNMT1 and 3b expression arrests tumor cells at the G1 phase of the cell cycle and induces apoptosis. The data suggest that DNMT knockdown may be a novel treatment strategy for PDAC.
Abstract
Objective.
Gastroesophageal reflux disease (GERD) is thought to be less prevalent in China than in Western countries. However, essential population-based endoscopy data are lacking for this ...country.
Material and methods.
As part of a wider study, 3600 individuals selected randomly from the Shanghai region were asked to undergo endoscopy. Participants completed a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire. When sufficient numbers were available, associations were assessed using multiple logistic regression or the Wilcoxon rank-sum test.
Results.
Of 3153 (87.6%) individuals who completed the survey, 1030 (32.7%) agreed to endoscopy and 1029 endoscopies were suitable for analysis. Symptom-defined GERD was more prevalent in the endoscopy group (4.7%) than in the non-endoscopy group (1.7%). Prevalence estimates were 6.4% for reflux esophagitis, 1.8% for endoscopically suspected esophageal metaplasia and 0.7% for hiatus hernia. Reflux esophagitis was more prevalent in patients with symptom-defined GERD than in those without (12.5% 6/48 vs. 6.1% 60/981), and was significantly associated with reflux symptoms of any frequency or severity (OR = 2.10, 95% CI 1.13-3.89) and with negative Helicobacter pylori infection (OR = 0.44, 95% CI 0.25-0.80). Only 28.8% of participants with reflux esophagitis had heartburn and/or regurgitation symptoms. Epigastric burning was significantly more severe and frequent in participants with reflux esophagitis than in those without (p = 0.05).
Conclusions.
Reflux esophagitis is less prevalent in China than reported in Western countries. Further work is needed to establish why reflux esophagitis appears less symptomatic in China than in Western countries.
To investigate the diagnostic value of liquid-based cytology test (LCT) in pancreatic lesions sampled by ultrasound-guided fine needle aspiration (EUS-FNA).
A retrospective analysis of 556 cases of ...LCT smears sampled by EUS-FNA of pancreatic lesions was performed, and 164 cases had histologic diagnosis with subsequent surgical resection or biopsy and immunohistochemistry. The accuracy of the cytologic diagnosis was assessed using the histologic diagnosis as the gold standard. The discrepant cases were reviewed to identify sources of errors.
The satisfactory rate for EUS-FNA was 96.0%(534/556). The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 87.7%(128/146), 13/16, 97.7%(128/131), 41.9%(13/31) and 87.0%(141/162) respectively. The diagnostic accuracy was lower in cystic lesions than that in solid lesions. The LCT sensitivities of adenocarcinoma, lymphoma and neuroendocrine tumors were higher than those of cystic tumors and mesenchymal tumors. False
Transparent conductive oxide (TCO) films are widely used as electrodes in photovoltaic devices, such as perovskite solar cells and heterojunction solar cells. However, in the conventional physical ...vapor deposition process, there may be ion bombardment damage to the underlayer coatings, and high deposition temperature also have an adverse effect on perovskite and amorphous silicon layers during TCO deposition. Herein, reactive plasma deposition was effectively utilized for cerium-doped indium oxide (ICO) film as an ultra-transparent electrode. The effects of plasma gun current and the oxygen ratio on the optical and electrical properties, and also on the structure of the ICO films, were investigated. With an industry-scale reactive plasma deposition tool, an outcome of 140-nm ICO film can be achieved within 50 s, which represents a good throughput with the average growth rate of 2.8 nm/s. When the working current was 165 A and the oxygen ratio was 12%, the average transmittance of ICO films reached the highest value (93.09%) in the wavelength range of 400–1200 nm. The average transmittance in the visible wavelength range was 94.23%. The peak transmittance was up to 99.67% at 515 nm, and the corresponding resistivity was 4.68 × 10
−4
Ω cm.
Background and Aim: Helicobacter pylori infection remains common in East Asia, though its prevalence is decreasing in Western countries. H. pylori‐related atrophic gastritis (AG) may reduce the ...likelihood of gastroesophageal reflux disease (GERD). We investigated the prevalence of H. pylori infection and AG and their association with endoscopic findings and symptom‐defined GERD in Shanghai.
Methods: A representative random sample of 3600 Shanghai residents aged 18–80 years was invited to complete a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire, to provide blood samples for H. pylori serology and pepsinogen (PG) I/II assay (to detect AG, defined as PGI < 70 µg/L and/or PGI/PGII < 7), and to undergo endoscopy. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multivariate logistic regression.
Results: A total of 1022 Shanghai residents underwent endoscopy and were valid for inclusion in the study. Of these, 71.7% tested positive for H. pylori, 63.8% had AG and 30.5% had moderate/severe AG (PGI < 50 µg/L and/or PGI/PGII < 5). Helicobacter pylori infection was equally common in all age groups. Severity of AG increased with age in women. Reflux esophagitis was inversely associated with AG (OR, 0.23 CI, 0.09–0.55 for moderate/severe AG compared with no H. pylori or gastritis). However, symptom‐defined GERD showed no clear association with AG.
Conclusions: Helicobacter pylori infection and AG are very common in Shanghai, and the infection is acquired early in life. Atrophic gastritis is inversely associated with reflux esophagitis but is not significantly associated with symptom‐defined GERD.
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication following ERCP and the mechanism is not fully understood. This study evaluated the ...changes in the inflammatory response, cellular apoptosis, and tight junction integrity in a rat model of pancreatitis to explore the underlying mechanism.
PEP was induced in rats by retrograde biliopancreatic ductal infusion of contrast agents or saline. Pancreatic tissues were harvested and evaluated by histopathologic, immunohistochemical, immunofluorescence, and Western blot analyses. In addition, amylase and proinflammatory cytokines in plasma were quantified by ELISA assay.
PEP rats developed more severe acute pancreatitis than the sham group after injection of the contrast agent or isotonic saline. PEP rats exhibited increased tissue damage, plasma amylase, proinflammatory cytokines, necrosis, inflammatory infiltrates, apoptosis, and tight junction disruption. At the molecular level, contrast agent and isotonic saline-injected PEP rats demonstrated elevated NF-κB p65 and STAT3 pathways activation, altered expression and activation of apoptosis-related proteins, and suppressed expression of tight junction molecules. However, the contrast agent concentration had no effect on these changes.
In models of acute pancreatitis induced using contrast agent and hydrostatic pressure, the contrast agent and high hydrostatic pressure easily induced the inflammatory response, apoptosis, and tight junction disruption. It is noteworthy that no significant difference in damaged pancreatic acinar cells was observed with different concentrations of the contrast agent.
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