Shigang Ding

The involvement of Helicobacter pylori thioredoxin-1 in gastric carcinogenesis.

Helicobacter pylori infection is related to the development of gastric diseases. Various virulence factors are responsible for the pathogenic mechanisms of H. pylori infection. Our previous studies using two-dimensional gel electrophoresis showed that H. pylori thioredoxin-1 (Trx1) is overexpressed in gastric carcinomas. Here, we examined whether H. pylori Trx1 is a novel virulence factor associated with gastric tumorigenesis. We found that Trx1 expression in H. pylori isolated from gastric cancer tissues was significantly higher than that from tissues exhibiting gastritis. In the gastric epithelial cell line GES-1, infection of H. pylori with high Trx1 expression significantly induced cell apoptosis, decreased the expression of cyclin D1 and upregulated p21. However, in the gastric cancer cell line BGC823, high Trx1 expression in H. pylori significantly increased cell proliferation, and upregulated cyclin D1. The effects on cell lines were confirmed using the H. pylori Trx1-knockout mutant strain. Our observations indicate that high Trx1 expression in H. pylori is associated with gastric carcinogenesis. In H. pylori, Trx1 likely participates in the pathogenesis of gastric cancer and H. pylori expressing high levels of Trx1 would be expected to be highly pathogenic in gastric diseases in China.

Comparative proteome analysis of Helicobacter pylori clinical strains by two-dimensional gel electrophoresis

ObjectiveTo investigate the pathogenic properties of Helicobacter pylori by comparing the proteome map of H. pylori clinical strains.MethodsTwo wild-type H. pylori strains, YN8 (isolated from biopsy tissue of a gastric cancer patient) and YN14 (isolated from biopsy tissue of a gastritis and duodenal ulcer patient), were used. Proteomic analysis, using a pH range of 3–10 and 5–8, was performed. The individual proteins were identified by quadrupole time-of-flight (Q-TOF) mass spectrometer and protein database search.ResultsVariation in spot patterns directed towards differential protein expression levels was observed between the strains. The gel revealed prominent proteins with several protein “families”. The comparison of protein expressions of the two strains reveals a high variability. Differentially present or absent spots were observed. Nine differentially expressed protein spots identified by Q-TOF included adenosine triphosphate (ATP)-binding protein, disulfide oxidoreductase B (DsbB)-like protein, N utilization substance A (NusA), ATP-dependent protease binding subunit/heat shock protein, hydantoin utilization protein A, seryl-tRNA synthetase, molybdenum ABC transporter ModD, and hypothetical proteins.ConclusionsThis study suggests that H. pylori strains express/repress protein variation, not only in terms of the virulence proteins, but also in terms of physiological proteins, when they infect a human host. The difference of protein expression levels between H. pylori strains isolated from gastric cancer and gastritis may be the initiator of inflammation, and result in the different clinical presentation. In this preliminary study, we report seven differential proteins between strains, with molecule weights from approximately 10 kDa to approximately 40 kDa. Further studies are needed to investigate those proteins and their function associated with H. pylori colonization and adaptation to host environment stress.

Autoimmune metaplastic atrophic gastritis in chinese: a study of 320 patients at a large tertiary medical center

Abstract Objectives: Autoimmune metaplastic atrophic gastritis (AMAG) is an uncommon disease worldwide and may predispose to gastric carcinoid tumors or adenocarcinomas. The aims of this study were to outline the clinical characteristics of Chinese AMAG patients, including demographic pattern, hematologic features, and gastroscopic and histopathologic findings. Patients and methods: A total of 320 Chinese patients with AMAG, from January 2007 to December 2014, were reviewed in a regional hospital of China. Results: Of the 320 AMAG patients, the mean age was 60.6 ± 12.3 years [range 26–86; 206 (64.4%) women]. The coarse annual detection rate was 0.9%. Anemia was present in only 19.3% patients (53/275) and 3.5% (11/315) AMAG patients also had primary biliary cirrhosis. One hundred and thirty-six had endoscopically identifiable lesions. These lesions consisted of 130 polypoid lesions (63 hyperplastic polyps, 2 oxyntic mucosa pseudopolyps, 2 intestinal-type gastric adenomas, 2 fundic gland polyps, 5 concurrent polyps, 14 well-differentiated neuroendocrine neoplasms, 7 submucosal tumors and 35 chronic gastritis), 6 adenocarcinomas. The detection rate of atrophy and intestinal metaplasia in antral mucosa were 47.2 and 37.5%, respectively. Conclusions: AMAG is more frequent than expected in China and display a female predominance, accompanied with other autoimmune disorders. AMAG should be paid more attention by clinicians through a multidisciplinary team approach.

Haemophagocytic lymphohistiocytosis in inflammatory bowel disease with virus infection

Patients with inflammatory bowel disease (IBD) are at risk of developing haemophagocytic lymphohistiocytosis (HLH) because of chronic systemic inflammation as well as exposure to immunosuppressive medications. The two main causes of HLH in IBD patients are infection with cytomegalovirus and Epstein-Barr virus. Patients with Crohns disease are more susceptible to HLH than those with ulcerative colitis. The majority of cases are seen in people receiving an immunosuppressive regimen that included thiopurines.

Clinical Applicability of Various Treatment Approaches for Upper Gastrointestinal Submucosal Tumors

Submucosal tumor (SMT) is a disease that is commonly discovered during endoscopic examination. With advances in endoscopic ultrasonography (EUS) technology, this technique has become the primary screening method for the diagnosis of upper gastrointestinal SMTs. The present study summarized the clinical data of patients who were examined and diagnosed with upper gastrointestinal SMTs by EUS, underwent endoscopic therapy or surgical treatment, and received final pathological results in our hospital between January 2011 and September 2014. Our results show that endoscopic therapy has become the main approach for the treatment of upper gastrointestinal SMTs with the development and maturation of endoscopic technology in recent years. Our conclusion suggests that the selection of endoscopic methods, such as endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and peroral submucosal tunneling endoscopic resection (STER), under the guidance of EUS is safe and effective for the treatment of upper gastrointestinal SMTs.

Expression of three essential antioxidants of Helicobacter pylori in clinical isolates

Objective: Helicobacter pylori maintains long-term persistence in the host and combats oxidative stress via many antioxidant proteins, which are expected to be relevant to bacterial-associated gastric diseases. We aimed to investigate the expression of three essential antioxidants in H. pylori strains isolated from patients with different clinical outcomes. Methods: Forty H. pylori strains were isolated from endoscopic biopsy specimens of gastric mucosa from 13 patients with gastric cancer, 13 with peptic ulcer, and 14 with gastritis. The expression of thioredoxin 1 (Trx1), arginase (RocF), and alkyl hydroperoxide reductase (AhpC) in H. pylori was measured by real-time PCR. Comparisons among multiple sample sets were analyzed using a one-way ANOVA test. Pearson’s correlation test was used to assess relationships among multiple continuous variables. Results: Trx1 expression of H. pylori in gastric cancer and peptic ulcer tissues was higher than that in tissues with gastritis. RocF expression of H. pylori in gastric cancer tissues was higher than that in tissues exhibiting peptic ulcer and gastritis. However, we did not find any differences in AhpC expression in samples from patients with different clinical outcomes. The expression of Trx1 and RocF had a positive, linear correlation. The expression of Trx1 and AhpC had a positive correlation without a linear trend. We found no correlation between the expression of RocF and AhpC. Conclusions: Our observations indicate that the expression of Trx1 and RocF in H. pylori might be related to gastric carcinogenesis. In H. pylori, the expression of members of the antioxidant system may be correlated and relevant to gastric cancer.

Deoxycholic Acid Could Induce Apoptosis and Trigger Gastric Carcinogenesis on Gastric Epithelial Cells by Quantitative Proteomic Analysis

Background. Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids. Bile reflux has been generally considered to be associated with intestinal metaplasia and gastric cancer. However, the pathogenic mechanisms of the effects of bile acids on gastric mucosa are still unknown. Methods. To explore the mechanisms by which bile acids induce gastric mucosal lesions, we examined cell apoptosis in the gastric epithelial cell line GES-1 and investigated the changes in protein profiles of GES-1 cells in response to a bile acid deoxycholic acid using a proteomics approach. Changes in the profiles of the differently expressed proteins were analyzed using the DAVID and STRING programs. Results. We found apoptosis was significantly induced in GES-1 cells by deoxycholic acid. Using liquid chromatographic/tandem mass spectrometric (LC-MS/MS) methods, 134 upregulated proteins and 214 downregulated proteins were identified in the bile acid treated GES-1 cells. Bioinformatics analysis revealed the interactions and signaling networks of these differentially expressed proteins. Conclusion. These findings may improve the understanding of the molecular mechanisms underlying the pathogenicity of bile acids on gastric mucosa.

Features of patients with inflammatory bowel diseases who develop hemophagocytic lymphohistiocytosis

Dear Editor: Hemophagocytic lymphohistiocytosis (HLH) is a serious hyperinflammatory condition that develops sporadically in patients undergoing treatment for inflammatory bowel disease (IBD). We collected data from a patient who developed HLH while undergoing treatment for IBD, as well as from 21 other cases through a literature search.We summarized clinical data, laboratory test results, imaging findings, and information on treatments and outcomes, and compared with the general IBD patients in two hospitals. Altogether, 16 papers were collected.Most patients (20/22) were less than 45 years old, the male to female ratio was 12:10, and Crohn’s disease (CD):ulcerative colitis (UC) was 18:4. As for immunosuppressive regimen, nine patients were under thiopurines in monotherapy, in combination with steroids (n=4) and infliximab (n=4); three patients was on steroids monotherapy and one patient in combination with infliximab. Effectiveness of the immunosuppressive regimen was described in nine patients, and among these, eight had a positive clinical response. The interval from prescription of immunosuppressive regimen to the onset of HLH was 4 months to 6 years. Of the 22 patients who developed HLH, 12 (54.5 %) had cytomegalovirus virus (CMV) infection and 8 (36.4 %) had Epstein-Barr virus (EBV) infection. One case had acute pancreatitis and toxic megacolon, the other had no cause identified. (Virological tests were not mentioned in these two cases). Five patients died; three from EBV infection, one from CMV infection and one from an unknown cause. The most common symptoms of HLH were fever (22/22), fatigue (9/22) and abdominal pain (7/22). There were also some flu-like symptoms, such as sore throat (5/22), cough (5/22), rhinorrhoea (3/22), headache (3/22) and myalgia (2/22). Six patients presented with severe hematochezia. On chest X-ray, six patients had multiple bilateral alveolar opacities. Ultrasonography showed splenomegaly and/or hepatomegaly in 13 patients, enlargement of lymph nodes in seven patients, and multiple hypoechoenic nodules of the spleen or liver in two patients. Hemophagocytosis was observed on bone marrow aspiration in 11 patients. Other abnormities included respiratory failure in three patients, coagulopathy or DIC in eight patients. The data source of the control group was a two-institutional cohort of patients with IBD from January, 2013 to December, 2014. Eighty-seven patients with IBD were enrolled in the control group. We compared the proportion of CD patients, viral infection rate, mortality, and usage of immunosuppressive agents including thiopurines between HLH group and the control group. Comparing with the control group, the prevalence of EBVand CMVwere higher in HLH group than those in control group (P=0.000 and P=0.001, respectively); proportion of CD patients was higher in HLH group than that in * Y. Li leeeyuan@aliyun.com