11. 乙醇脱氢酶同工酶--乙醇脱氢酶IV作为幽门螺杆菌感染的潜在标记物
幽门螺杆菌感染与胃黏膜中乙醇脱氢酶(ADH)活性的降低相关。胃黏膜ADH活性的降低程度取决于炎症和黏膜损伤的严重程度。这种损伤可能导致胃黏膜乙醇脱氢酶进一步释放,最终导致幽门螺旋杆菌感染患者血清中ADH活性增加。对140幽门螺旋杆菌感染病例进行分析。研究结果显示幽门螺旋杆菌感染患者血清中总ADH以及ADH IV活性显著增加，提示ADH IV可以作为幽门螺杆菌感染的潜在标记物。
Arch Med Sci. 2014 Oct 27;10(5):951-5. doi: 10.5114/aoms.2014.46215. Epub 2014 Oct 23.
The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate marker of Helicobacter pylori infection.
Jelski W, Laniewska-Dunaj M, Strumnik A, Szmitkowski M.
Abstract
INTRODUCTION:
Helicobacter pylori infection is associated with decreased alcohol dehydrogenase (ADH) activity in the gastric mucosa. The decrease in gastric ADH activity depends on the severity of inflammation and mucosal injury. This damage can be a reason of the release of enzyme from gastric mucosa and leads to the increase of the ADH activity in the sera of patients with H. pylori infection.
MATERIAL AND METHODS:
Serum samples were taken from 140 patients with H. pylori infection. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde. For the measurement of the activity of class I and II isoenzymes we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate.
RESULTS:
The activity of ADH IV in the serum of patients with H. pylori infection increased about 42% (7.86 mU/l) in the comparison to the control level (4.52 mU/l). Total activity of ADH was 1105 mU/l in patients group and 682 mU/l in control. The diagnostic sensitivity for ADH IV was 88%, specificity 90%, positive and negative predictive values were 91% and 84% respectively. Area under ROC curve for ADH IV was 0.84.
CONCLUSIONS:
Helicobacter pylori infection of gastric mucosa is reflected in the serum by significant increase of class IV and total ADH activity. The results suggest a potential role for ADH IV as a marker of H.pylori infection.
12利用MicroRNA网络分析法识别在胃癌癌前病变中的关键微小RNAs及基因
为了寻找胃癌的早期治疗及预防的潜在靶点,利用microRNA 基因表达谱对10例幽门螺杆菌相关胃炎标本及10例胃肠上皮化生样本进行筛查。实验结果提示RAB22A, SOX4, IKZF2, PLAG1, and BTBD7这5个基因可能可作为调节胃癌进展的靶向基因。
Genet Mol Res. 2014 Oct 27;13(4):8695-703. doi: 10.4238/2014.October.27.10.
MicroRNA network analysis identifies key associated with precancerous lesions of gastric cancer.
Wang XW1, Wu Y2, Wang D1, Qin ZF3.
Author information
Abstract
To identify potential targets for the early treatment and prevention of gastric cancer, microRNA (miRNA) expression profiles of precancerous lesions of gastric cancer were investigated.The miRNA microarray dataset GSE24839 was downloaded from Gene Expression Omnibus (GEO) and included 10 Helicobacter pylori-related gastritis samples and 10 gastric intestinal metaplasia samples. Differentially expressed miRNAs (DEMs) were screened using the Student t-test; P < 0.05 was considered to be statistically significant. Co-expression networks of total miRNAs and DEMs were constructed based on the Pearson correlation coefficient for the two diseases. Target genes of the DEMs were retrieved using miRecords and pathway-enrichment analysis was performed using a hypergeometric test. A total of 20 DEMs were obtained for H.pylori-related gastritis and gastric intestinal metaplasia samples, including 12 up-regulated and 8 down-regulated miRNAs. The identified DEMs appear to play key roles in gastric cancer, as the average degree of the DEM sub-network was higher than that of the total miRNA co-expression network. Furthermore, target genes for 6 DEMs (hsa-miR-106b, hsa-miR-193a-3p, hsa-miR-204, hsa-miR-30e, hsa-miR-519d, and hsa-miR-524-5p) are in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including signal transduction, cell growth and death, and transport and catabolism. Among the target genes, 5 (RAB22A, SOX4, IKZF2, PLAG1, and BTBD7) were of interest because they can be simultaneously regulated by several DEMs. These findings suggest that these genes may be targets for modulating gastric cancer progression.
13幽门螺杆菌是动脉粥样硬化的感染性危险因素?
大量研究表明，幽门螺旋杆菌感染与某些发病机制以持续、低度系统性炎症为特征的胃外疾病有关。近期，幽门螺旋杆菌感染与动脉粥样硬化及其并发症临床之间的关系备受关注。动脉粥样硬化是一种多因素的疾病,传统的风险因素只能解释50%的病因。因此,寻找动脉粥样硬化的危险因素是十分重要的。本文从流行病学与病原学的角度寻找幽门螺旋杆菌的感染与动脉粥样硬化发生发展间的关系。
J Atheroscler Thromb. 2014 Oct 24. [Epub ahead of print]
Helicobacter pylori-An Infectious Risk Factor for Atherosclerosis?
Author information
Abstract
Accumulating evidence implicates Helicobacter pylori (H. pylori) infection in the pathogenesis of certain diseases localized outside the stomach, particularly those characterized by persistent and low-grade systematic inflammation. Recently, the role of H. pylori infection in the development of atherosclerosis and its clinical complications has received attention. Atherosclerosis is a high-cost disease, and acute events resulting from this condition rank first among morbidity and mortality statistics in most industrialized countries. Atherosclerosis is a multifactorial disorder, and traditional risk factors explain only 50% of its etiology. Therefore, identifying new risk factors for atherosclerosis is necessary. Serological studies indicate that chronic H. pylori infection, especially that with more virulent strains, may predispose patients to the onset of atherosclerosis and related adverse clinical events, and PCR studies have detected H. pylori DNA in atherosclerotic plaques, although this finding remains controversial. If this association were to be confirmed, its importance to public health would be substantial, as the eradication of H. pylori is more straightforward and less costly than the long-term treatment of other risk factors. This review investigates the potential relationship between H. pylori infection and atherosclerosis from both epidemiological and pathogenic perspectives and characterizes the potential mechanisms underlying this correlation.
14病例对照研究：幽门螺杆菌感染、非甾体类抗炎药、小剂量阿司匹林、抗高血压药物引起消化性溃疡出血的风险
截至目前，在幽门螺杆菌感染率高的亚洲地区，仍不明确抗凝或抗高血压药物等是否为消化性溃疡出血的危险因素。本研究旨在评估抗血栓形成的药物、血管紧张素II受体拮抗剂、血管紧张素转换酶(ACE)抑制剂、钙通道阻滞剂、α受体阻断剂、β受体阻断剂消化性溃疡出血引起风险。研究结果显示饮酒、消化性溃疡病史、幽门螺旋杆菌感染、非甾体类抗炎药的使用以及小剂量阿司匹林均为消化性溃疡出血的独立危险因素，但是一旦幽门螺旋杆菌得到根除或使用PPIs、H2RA可降低出血的风险
J Gastroenterol Hepatol. 2014 Oct 22. doi: 10.1111/jgh.12805. [Epub ahead of print]
Risk of peptic ulcer bleeding associated with Helicobacter pylori infection, NSAIDs, low-dose aspirin, and antihypertensive drugs: A case-control study.
Nagata N1, Niikura R, Sekine K, Sakurai T, Shimbo T, Kishida Y, Tanaka S, Aoki T, Okubo H, Watanabe K, Yokoi C,Akiyama J, Yanase M, Mizokami M, Uemura N.
Author information
Abstract
BACKGROUND:
The associations between antithrombotic or antihypertensive drugs and peptic ulcer bleeding (PUB) remain unknown, particularly in Asia, where Helicobacter pylori infection is prevalent. This study aims to evaluate the risks of PUB from antithrombotic drugs, angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, α-blockers, and β-blockers.
METHODS:
This prospective hospital-based case-control study included 230 patients with endoscopically verified PUB and 920 age- and sex-matched controls (1:4) without bleeding on screening endoscopy. Adjusted odds ratios (AOR) for the risk of PUB were determined by conditional logistic regression analysis.
RESULTS:
In multivariate analysis, alcohol consumption (AOR, 2.2; p<0.001), history of peptic ulcer (AOR, 4.8; p<0.001), H. pylori infection (AOR, 2.1; P<0.001), comorbidity index (AOR, 1.1; p=0.089), non-steroidal anti-inflammatory drugs (NSAIDs) (AOR, 2.0; P=0.025) and low-dose aspirin (AOR, 2.8; P=0.003) increased the risk of PUB, whereas H. pylori-eradication (AOR, 0.03; P<0.001), proton pump inhibitors (PPIs) (AOR, 0.1; P<0.001) and histamine 2-receptor antagonists (H2RA) (AOR, 0.1; P<0.001) reduced it. No significant interactions were observed between H. pylori infection and NSAIDs use for PUB (P=0.913). ARBs (P=0.564), ACE inhibitors (P=0.213), calcium channel blockers (P=0.215), α-blockers (P=0.810), and β-blockers (P=0.864) were not associated with PUB.
CONCLUSIONS:
We found that alcohol consumption, history of peptic ulcer, H. pylori infection, NSAIDs use, and low-dose aspirin use were independent risk factors for PUB, whereas H. pylori-eradication, PPIs use, and H2RA use reduced its risk. Interactions between H. pylori and NSAIDs use in PUB were not observed. No antihypertensive drug was associated with PUB.
This article is protected by copyright. All rights reserved.
15巨噬细胞释放的细胞因子BAFF在幽门螺旋杆菌感染性慢性胃炎中引发Th17 响应
BAFF是一种重要的细胞因子，可影响固有免疫细胞及适应性免疫细胞的活性。它促进Th17细胞在自身免疫性疾病的进展。本研究旨在探索在幽门螺旋杆菌感染性慢性胃炎中BAFF对Th17的影响。
研究结果显示，确实存在幽门螺旋杆菌感染患者体内确实存在依赖幽门螺旋杆菌的BAFF/Th17反应链。此外，本研究还发现，BAFF既可通过影响固有免疫细胞分泌Th17前体来间接诱导Th17反应活动，还可通过影响变异T细胞直接接到Th17反应活动。
J Immunol. 2014 Oct 22. pii: 1302865. [Epub ahead of print]
Cytokine BAFF Released by Helicobacter pylori-Infected Macrophages Triggers the Th17 Response in Human Chronic Gastritis.
Munari F1, Fassan M2, Capitani N3, Codolo G1, Vila-Caballer M1, Pizzi M4, Rugge M4, Della Bella C5, Troilo A5,D'Elios S5, Baldari CT6, D'Elios MM7, de Bernard M8.
Author information
Abstract
BAFF is a crucial cytokine that affects the activity of both innate and adaptive immune cells. It promotes the expansion of Th17 cells in autoimmune disorders. With this study, we investigated the BAFF/Th17 responses in Helicobacter pylori-induced gastritis in humans. Our results show that the mucosa from Helicobacter+patients with chronic gastritis is enriched in IL-17 and BAFF, whereas the two cytokines are weakly expressed in Helicobacter- patients with chronic gastritis; moreover, the expression of both BAFF and IL-17 decreases after bacteria eradication. We demonstrate that BAFF accumulates in macrophages in vivo and that it is produced by monocyte-derived macrophages in vitro, after Helicobacter stimulation. Application of BAFF on monocytes triggers the accumulation of reactive oxygen species that are crucial for the release of pro-Th17 cytokines, such as IL-23, IL-1β, and TGF-β. Moreover, BAFF directly promotes the differentiation of Th17 cells. In conclusion, our results support the notion that an axis BAFF/Th17 exists in chronic gastritis of Helicobacter+ patients and that its presence strictly depends on the bacterium. Moreover, we demonstrated that BAFF is able to drive Th17 responses both indirectly, by creating a pro-Th17 cytokine milieu through the involvement of innate immune cells, and directly, via the differentiation of T cells toward the specific profile. The results obtained in this study are of great interest for Helicobacter-related diseases and the development of novel therapeutic strategies based on the inhibition of the BAFF/IL-17 response.
16 幽门螺杆菌外炎性蛋白的核酸菌蜕疫苗能够提高C57BL/6小鼠的免疫保护力
该项研究探索了新的研发抗HP感染疫苗的方法。并在小鼠中做了评估实验。
Vaccine. 2014 Oct 21;32(46):6054-60. doi: 10.1016/j.vaccine.2014.09.014. Epub 2014 Sep 16.
Helicobacter pylori outer inflammatory protein DNA vaccine-loaded bacterial ghost enhances immune protective efficacy in C57BL/6 mice.
Author information
Abstract
Helicobacter pylori (H. pylori) infection is associated with incidents of gastrointestinal diseases in half of the human population. However, management of its infection remains a challenge. Hence, it is necessary to develop an efficient vaccine to fight against this pathogen. In the present study, a novel vaccine based on the production of attenuated Salmonella typhimurium bacterial ghost (SL7207-BG), delivering H. pylori outer inflammatory protein gene (oipA) encoded DNA vaccine was developed, and the efficiency was evaluated in C57BL/6 mice. Significant higher levels of IgG2a/IgG1 antibodies and IFN-γ/IL-4 cytokines were detected after mice were oral administered with oipA DNA vaccine loaded SL7207-BG, indicating that a mixed Th1/Th2 immune response was elicited. When challenged with infective doses H. pylori strain SS1, the ghost based vaccine was capable of reducing bacterium colonization in the vaccinated mice. In addition, codon-optimized oipA plasmid loaded SL7207-BG significantly eliminates H. pylori colonization density in mice model. Thus, it has been demonstrated that this novel bacterial ghost based DNA vaccine could be used as a promising vaccine candidate for the control of H. pylori infection.
Copyright © 2014 Elsevier Ltd. All rights reserved.
17. 对日本儿童和青少年的发炎牙髓标本进行幽门螺杆菌DNA的检测
口腔感染被人为是儿童期HP感染的一个传播途径。已有很多研究报道利用不同PCR方法检测口腔标本中HP的DNA，其检出率亦不同。在该研究中，研究者构建了一个新的PCR幽门螺杆菌检测系统，并用它来分析口腔标本。结果显示在牙髓标本中可以检测到HP，而在唾液中为阴性。提示牙髓的根管可能是HP贮存的场所。
J Med Microbiol. 2014 Oct 20. pii: jmm.0.079491-0. doi: 10.1099/jmm.0.079491-0. [Epub ahead of print]
Detection of Helicobacter pylori DNA in inflamed dental pulp specimens from Japanese children and adolescents.
Ogaya Y1, Nomura R2, Watanabe Y3, Nakano K1.
Author information
Abstract
The oral cavity has been implicated as a source of Helicobacter pylori infection in childhood. Various PCR methods have been used to detect H. pylori DNA in oral specimens with various detection rates reported. Such disparity in detection rates complicates the estimation of the true infectious rate of H. pylori in the oral cavity. In the present study, we constructed a novel PCR system for H. pylori detection and used it to analyze oral specimens. Firstly, the nucleotide alignments of genes commonly used for H. pylori detection were compared using complete genome information for 48 strains registered in the GenBank database. Candidate primer sets with an estimated amplification size of approximately 300-400 bp were selected, and the specificity and sensitivity of the detection system using each primer set evaluated. Five sets of primers targeting urea were considered appropriate, of which a single primer set was chosen for inclusion in the PCR system. The sensitivity of the system was considered appropriate and its detection limit established as 1-10 cells per reaction. The novel PCR system was used to examine H. pylori distribution in oral specimens (40 inflamed pulp tissues, 40 saliva samples) collected from Japanese children, adolescents, and young adults. PCR analysis revealed that the detection rate of H. pylori in inflamed pulp was 15%, whereas no positive reaction was found in any of the saliva specimens. Taken together, our novel PCR system was found to be reliable for detecting H. pylori. The results obtained showed that H. pylori was detected in inflamed pulp but not saliva specimens, indicating that an infected root canal may be a reservoir for H. pylori.
Copyright © 2014, the Society for General Microbiology.
18. 对使用过氧化氢酶单克隆抗体来检测粪便标本中幽门螺杆菌方法在儿童和成人人群中应用的评价
找到无创检测HP的合适方法意义重大。该研究对151例粪便样本应用过氧化氢酶单克隆抗体法进行了HP的检测。结果证明非常有效，而且特异性较高。
J Med Microbiol. 2014 Oct 20. pii: jmm.0.077370-0. doi: 10.1099/jmm.0.077370-0. [Epub ahead of print]
Evaluation of a stool antigen test using a monoclonal antibody for native catalase for diagnosis of Helicobacter pylori infection in children and adults.
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