Clinicopathologic characteristics and prognostic factors of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study.

OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

Ottowia cancrivicina sp. nov., isolated from human stomach.

A Gram-negative, facultative anaerobic, non-motile and rod-shaped bacterium, designated 10c7w1T, was isolated from a human gastrointestinal tract. Colonies on agar plates were small, circular, smooth and beige. The optimal growth conditions were determined to be 37 °C, pH 7.0-7.5 and 0 % (w/v) NaCl. Comparative analysis of complete 16S rRNA gene sequences revealed that strain 10c7w1T showed the highest sequence similarity of 95.8 % to Ottowia beijingensis MCCC 1A01410T, followed by Ottowia thiooxydans (95.2 %) JCM 11629T. The average amino acid identity values between 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were above 60 % (71.4 and 69.5 %). The average nucleotide identity values between strain 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were 76.9 and 72.5 %, respectively. The dominant fatty acids (≥10 %) were straight chain ones, with summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C16 : 00 being the most abundant. Q-8 was the only respiratory quinone. The major polar lipids of strain 10c7w1T were phosphatidylethanolamine, diphosphatidylglycerol and unknown lipids. The DNA G+C content of strain 10c7w1T was 63.6 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic data, strain 10c7w1T is considered to represent a novel species within the genus Ottowia, for which the name Ottowia cancrivicina sp. nov. is proposed. The type strain is 10c7w1T (=MCCC 1H01399T=KCTC 92200T).

Marinicella marina sp. nov. and Marinicella gelatinilytica sp. nov., isolated from coastal sediment, and genome analysis and habitat distribution of the genus Marinicella.

Three Marinicella strains, X102, S1101T and S6413T, were isolated from sediment samples from different coasts of Weihai, PR China. All strains were Gram-stain-negative, rod-shaped and non-motile. The predominant fatty acids of all strains were iso-C15 : 0 and summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c) and the major polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Strains X102 and S1101T shared 100 % 16S rRNA gene sequence similarity, and strains S1101T/X102 and S6413T had 95.4 % similarity. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains S1101T and X102 were 99.9 and 99.2 %, respectively. Strain S1101T had ANI values of 69.1-72.9% and dDDH values of 17.9-20.5 % to members of the genus Marinicella. Strain S6413T had ANI values of 69.1-77.5% and dDDH values of 17.6-21.5 % to members of the genus Marinicella. The results of phylogenetic and comparative genomic analysis showed that the three strains belong to two novel species in the genus Marinicella, and strains X102 and S1101T represented one novel species, and strain S6413T represented another novel species. The result of BOX-PCR and genomic analysis showed that X102 and S1101T were not the same strain. The phylogenetic analyses and genomic comparisons, combined with phylogenetic, phenotypic and chemotaxonomic features, strongly supported that the three strains should be classified as representing two novel species of the genus Marinicella, for which the names Marinicella marina sp. nov. and Marinicella gelatinilytica sp. nov. are proposed, respectively. The type strains of the two novel species are S1101T (=KCTC 92642T=MCCC 1H01359T) and S6413T (=KCTC 92641T=MCCC 1H01362T), respectively. In addition, all previously described isolates of Marinicella were isolated from marine environments, but our study showed that Marinicella is also distributed in non-/low-saline habitats (e.g. animal gut, soil and indoor surface), which broadened our perception of the environmental distribution of Marinicella.

Tumebacillus lacus sp. nov., isolated from lake water.

A Gram-stain-positive, aerobic, rod-shaped, endospore-forming and motile, by means of peritrichous flagella, bacterium, designated DT12T, was isolated from a lake water sample from Datun Lake of Yunnan Province, PR China. The results of phylogenetic analysis based on 16S rRNA gene sequence and the concatenated alignment of 120 ubiquitous single-copy proteins indicated that the novel strain represented a member of the genus Tumebacillus. The sole quinone was menaquinone-7 and the cell-wall peptidoglycan was type-A1γ. The major fatty acids (>10 %) of the novel strain were iso-C15 : 0 and anteiso-C15 : 0, while the major polar lipids were phosphatidylmonomethylethanolamine, phosphatidylethanolamine and phosphatidylglycerol. The results of phylogenetic analyses combined with phylogenetic, phenotypic and chemotaxonomic features, strongly supported the hypothesis that the strain should be classified as representing a novel species of the genus Tumebacillus, for which the name Tumebacillus lacus sp. nov. is proposed. The type strain is DT12T (=KCTC 33958T= MCCC 1H00320T). The genomic analysis revealed that DT12T has various biosynthetic gene clusters for secondary metabolites, and members of the genus Tumebacillus may represent a promising source of new natural products. Our study also showed that members of the genus Tumebacillus are widely distributed in a variety of habitats throughout the globe, particularly in soils, human-, animal- and plant-associated environments. Members of the genus Tumebacillus may have an important role in the growth and health of humans, plants and animals.

Downregulation of miR­7 and miR­153 is involved in Helicobacter pylori CagA induced gastric carcinogenesis and progression.

Helicobacter pylori (H. pylori) infection plays a pivotal role in the development of gastric cancer (GC). However, the association between aberrant microRNAs (miRNAs/miRs) expression and H. pylori­induced GC remains poorly understood. The present study reported that repeated infection of H. pylori caused the oncogenicity of GES­1 cells in BALB/c Nude mice. miRNA sequencing revealed that both miR­7 and miR­153 were significantly decreased in the cytotoxin­associated gene A (CagA) positive GC tissues and this was further confirmed in a chronic infection model of GES­1/HP cells. Further biological function experiments and in vivo experiments validated that miR­7 and miR­153 can promote apoptosis and autophagy, inhibit proliferation and inflammatory response in GES­1/HP cells. All the associations between miR­7/miR­153 and their potential targets were revealed via bioinformatics prediction and dual­luciferase reporter assay. Particularly, downregulation of both miR­7 and miR­153 obtained an improved sensitivity and specificity in diagnosing H. pylori (CagA+)­induced GC. The present study identified that the combination of miR­7 and miR­153 may be regarded as novel therapeutic targets in H. pylori CagA (+)­associated GC.

Helicobacter pylori and gastric microbiota homeostasis: progress and prospects.

Helicobacter pylori, a Gram-negative microaerobic bacteria belonging to the phylum Proteobacteria, can colonize in the stomach and duodenum, and cause a series of gastrointestinal diseases such as gastritis, gastric ulcer and even gastric cancer. At present, the high diversity of the microorganisms in the stomach has been confirmed with culture-independent methods; some researchers have also studied the stomach microbiota composition at different stages of H. pylori carcinogenesis. Here, we mainly review the possible role of H. pylori-mediated microbiota changes in the occurrence and development of gastric cancer to provide new ideas for preventing H. pylori infection and regulating microecological imbalance.

Huntingtin-associated protein 1 is a potential tumor suppressor for gastric cancer.

BACKGROUND: Gastric cancer is heterogeneous cancer and the causes of this disease are complex. New diagnostic and therapeutic targets are urgently needed to explore. Huntingtin-associated protein 1 (HAP1) is directly related to Huntington's disease (HD). However, patients with Huntington's disease have a lower incidence of cancer. Therefore, we are committed to studying the correlation between HAP1 and gastric carcinogenesis and development. METHODS AND RESULTS: Immunohistochemical staining, western blot analysis, and RT-qPCR were conducted to explore the localization and expression of HAP1 in gastric cancer. To study the biological significance of HAP1, we overexpressed HAP1 in both MKN28 and AGS cell lines by lentivirus infection. To explore the role of HAP1 in cell proliferation, the cells counting assay, EdU incorporation assay, and colony formation assay were carried out. We performed the wound healing assay and transwell assay to study the cell migration and invasion. To further investigate whether HAP1 could regulate gastric cancer cell death during glucose deprivation, Annexin V-FITC/PI staining was performed. In our study, we elucidated that HAP1 was downregulated in gastric cancer. What's more, overexpressing HAP1 inhibited cell proliferation, cell migration and invasion, and triggered apoptosis during glucose deprivation. More importantly, the antitumor properties and mechanisms of HAP1 have been elucidated further in gastric cancer. CONCLUSIONS: Taken together, the available evidence implies that HAP1 may serve as a potential tumor suppressor, making it a significant target in preventing and treating gastric cancer. This research provides a theoretical basis for the early diagnosis, clinical targeted therapy, and prognosis evaluation of gastric cancer.

Comparison of Drug-Coated Balloons to Bare Metal Stents in the Treatment of Symptomatic Vertebral Artery-Origin Stenosis: A Prospective Randomized Trial.

OBJECTIVE: We sought to compare the angiographic and clinical outcomes of drug-coated balloon (DCB) with distal embolic protection devices (EPDs) versus bare metal stent (BMS) without EPD in the treatment of symptomatic vertebral artery origin stenosis (VAOS). METHODS: Between January 2017 and December 2018, a prospective randomized trial was conducted involving 95 patients with symptomatic VAOS randomly assigned to treatment with DCB + EPD (n = 49) or BMS without EPD (n = 46). Target vessel restenosis (RS) >50% detected by computed tomography angiography was the primary endpoint. Technical success, clinical success, and signal intensity abnormalities on diffusion-weighted imaging within 3 days after operation were compared. RESULTS: The 30-day technical success rate was 93.9% for DCB group versus 95.7% for the BMS group (P = 0.094). Diffusion-weighted imaging within 3 days postoperative showed asymptomatic embolization in 2 (4.1%) patients in the DCB group and 9 (19.6%) patients in the BMS group (P = 0.004). At a mean 16-month follow-up, the clinical success rate was 89.8% for the DCB group versus 91.3% (42/46) for the BMS group (P = 0.125). The RS was seen in 5/49 (10.2%) in the DCB group and 6/46 (13.0%) in the BMS group (P = 0.082). Target vessel revascularization was performed in 4 (8.7%) BMS group versus 3 (6.1%) in the DCB group (P = 0.091). CONCLUSIONS: DCB with EPD in the treatment of symptomatic VAOS is technically feasible and safe and significantly reduced thromboembolic events on imaging when compared with BMS without EPD. There was no significant difference between the 2 groups in the rate of RS during 12 months after surgery.

Ostreibacterium oceani gen. nov., sp. nov., isolated from oyster, and description of Ostreibacteriaceae fam. nov.

A novel Gram-stain-negative, short rod-shaped, facultatively anaerobic, non-motile, non-gliding, oxidase-positive and catalase-negative bacterium, designated ML27T, was isolated from oyster homogenate in Rushan, Weihai, PR China. Growth occurred at 20-33 °C (optimum, 30 °C), at pH 7.0-9.0 (optimum, pH 7.5-8.0) and in the presence of 1-6 % (w/v) NaCl (optimum, 3 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ML27T was 90.7 % similar to Suttonella ornithocola DSM 18249T, 89.2 % to Suttonella indologenes JCM 1478T and 88.2 % to Cardiobacterium hominis DSM 8339T; similarities to other species were less than 90 %. The average amino acid identity between strain ML27T, S. indologenes JCM 1478T, S. ornithocola DSM 18249T, C. hominis DSM 8339T and Dichelobacter nodosus ATCC 25549T were 46.23, 45.86, 45.54 and 45.84 %, respectively. Phylogenomic tree and phylogenetic analyses based on 16S rRNA gene sequences showed that the isolate formed a novel family-level clade in the order Cardiobacteriales. The sole respiratory quinone was ubiquinone-7 (Q-7). The dominant cellular fatty acids were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c; 46.3 %), C16 : 0 (17.8 %) and summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c; 13.5 %). The DNA G+C content of strain ML27T was 45.6 mol%. Polar lipids included phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and one unidentified lipid. Comparative analyses of 16S rRNA gene sequences, genomic distinctiveness and characterization indicated that strain ML27T represents a novel species of a new genus within a novel family of the order Cardiobacteriales, for which the name Ostreibacterium oceani gen. nov., sp. nov. is proposed. The type strain of Ostreibacterium oceani is ML27T (=MCCC 1H00372T=KCTC 72155T). In addition, a novel family, Ostreibacteriaceae fam. nov., is proposed to accommodate the genus Ostreibacterium.

Sulfitobacter algicola sp. nov., isolated from green algae.

A novel Gram-stain-negative, aerobic, non-flagellated, non-motile, oval-rod-shaped and light pink to light tawny-pigmented bacterial strain (designated 1151T) were isolated from marine green algae obtained from the coastal seawater of Weihai, China. Strain 1151T was found to grow at 15-37 °C (optimum, 33 °C), pH 7.0-9.5 (optimum, 7.5-8.5) and in the presence of 1-6% (w/v) NaCl (optimum, 3%). Cells were oxidase-positive and catalase-positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 1151T was a member of the genus Sulfitobacter and exhibited the hightest sequence similarity to Sulfitobacter indolifex DSM 14862T (96.6%), followed by the sequence similarity to Sulfitobacter aestuarii hydD52T (96.5%) and Sulfitobacter profundi SAORIC-263T (96.5%). The average nucleotide identity and digital DDH values between strain 1151T and Sulfitobacter indolifex DSM 14862T were 69.9% and 20.9%, respectively. The average amino acid identity between strain 1151T and Sulfitobacter pontiacus DSM 10014T (type strain of the type species) was 62.3%. Q-10 was detected as the sole respiratory quinone. The dominant cellular fatty acids were sum feature 8 (C18: 1ω7c; 44.1%), C20: 1ω7c (29.7%) and C18: 0 (11.7%). The DNA G + C content of strain 1151T was 51.8 mol%. The polar lipids included phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and three unidentified lipids (L1, L2 and L3). Based on the phylogenetic and phenotypic characteristics, strain 1151T is considered to represent a novel species of the genus Sulfitobacter, for which the name Sulfitobacter algicola sp. nov. is proposed. The type strain is 1151T (= KCTC 72513T = MCCC 1H00384T).

Acute and chronic infection of H. pylori caused the difference in apoptosis of gastric epithelial cells.

Helicobacter pylori (H. pylori) is one of the most important pathogenic bacteria associated with various gastrointestinal diseases. At present, its apoptotic or antiapoptotic mechanism on gastric epithelial cells remains unknown and needs further illustrated. In this study, acute infection model (H. pylori and GES-1 cells were co-cultured for 24 h at a multiplicity of infection MOI of 100:1) and chronic infection model (GES-1 cells were infected repeatedly every 24 h at a multiplicity of infection MOI of 100:1 for approximately 8 weeks) were established, respectively. the chronic H. pylori infected GES-1 cells underwent a typically morphological change and Western Blot results showed that there was slight decrease in expression of E-cadherin, and obvious increase in expression of Vimentin. Apoptosis of these two models were analyzed by flow cytometry compared with the control cells, meanwhile, apoptosis associated markers (Bcl-xL, Bcl-2, Bax, etc) were detected by Western blot, additional in clinical H. pylori-positive gastric cancer tissues. Results showed that compared with the control cells, acute infection of H. pylori significantly accelerated the apoptosis of GES-1, increased the expression of Bax and Cleaved caspase-3, down-regulated expression of Bcl-xL and Bcl-2. Moreover, an opposite result was found in chronic infection of model and clinical gastric cancer tissues, and enhanced expression of NF-κB p65. Taken together, these findings suggest that H. pylori infection plays differential effects on apoptosis of gastric epithelial cells.

Randomized control trial comparing the titanium osteosynthesis and the biodegradable osteosynthesis in mandibulotomy access.

BACKGROUND: The clinical degradation rate and strength of biodegradable implant exposed to postoperative radiotherapy (PORT) are unknown. METHODS: A prospective randomized control trial of 40 consecutive mandibulotomy patients randomly divided into titanium and biodegradable cohorts. All patients received PORT. The following parameters were compared: maximal mouth opening, occlusal force, center of force trajectory, occlusal status, radiographic evidence of bony union, mandibular function impairment questionnaire (MFIQ), overall satisfaction score, and complication rates. RESULTS: Both the mandibular function and occlusal status parameter of the biodegradable and the titanium groups were not significantly difference. Biodegradable cohort showed better MFIQ scores (P = .08) and overall satisfaction scores (P = .64) but was not statistically significant. Of note, 40% of patients in the titanium cohort complained of plate palpability/cold intolerance and required plate removal (P = .02); 10% of patients in the titanium cohort developed osteoradionecrosis. CONCLUSION: Biodegradable osteosynthesis is as reliable as titanium osteosynthesis for mandibulotomy fixation. PORT did not increase the complication rate in the biodegradable group.

The type IV secretion system in Helicobacter pylori.

Helicobacter pylori (H. pylori) has an essential role in the pathogenesis of gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. The severity of the host inflammatory responses against the bacteria have been straightly associated with a special bacterial virulence factor, the cag pathogenicity island, which is a type IV secretion system (T4SS) to deliver CagA into the host cells. Besides cag-T4SS, the chromosomes of H. pylori can encode another three T4SSs, including comB, tfs3 and tfs4. In this review, we systematically reviewed the four T4SSs of H. pylori and explored their roles in the pathogenesis of gastroduodenal diseases. The information summarized in this review might provide valuable insights into the pathogenic mechanism for H. pylori.

WITHDRAWN: A Randomized Controlled Trial Comparing Between Titanium Osteosynthesis and Biodegradable Osteosynthesis in Access Mandibulotomy for Oral Malignancy.

Available online April 7, 2018. This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Post-operative hemimaxillectomy rehabilitation using prostheses supported by zygoma implants and remaining natural teeth.

OBJECTIVES:: This study aimed to evaluate the stability of prostheses supported by zygoma implants and remaining teeth for subjects who had undergone hemi-maxillectomy. METHODS:: Ten patients were included in the study. Oral rehabilitation was performed using a temporary prosthesis that was supported by remaining teeth for the first three months. Then, a zygoma implant was placed to provide support for a final prosthesis in addition to the remaining teeth. Each prosthesis was tailor-made according to biomechanical three-dimensional finite element analysis results. The patients were assessed using the prosthesis functioning scale of the Memorial Sloan-Kettering Cancer Center. In addition, retention and bite force were recorded for both the temporary prosthesis and the final prosthesis. RESULTS:: The mean bite force of the prosthetic first molar was increased to 69.2 N. The mean retentive force increased to 13.5 N after zygoma implant insertion. The bite force on the prosthetic first molar was improved to 229.3 N. CONCLUSION:: Bite force increased significantly with the support of a zygoma implant. The use of zygoma implants in the restoration of maxillary defects improved functional outcome and patient satisfaction.

Post-operative hemimaxillectomy rehabilitation using prostheses supported by zygoma implants and remaining natural teeth

OBJECTIVES: This study aimed to evaluate the stability of prostheses supported by zygoma implants and remaining teeth for subjects who had undergone hemi-maxillectomy. METHODS: Ten patients were included in the study. Oral rehabilitation was performed using a temporary prosthesis that was supported by remaining teeth for the first three months. Then, a zygoma implant was placed to provide support for a final prosthesis in addition to the remaining teeth. Each prosthesis was tailor-made according to biomechanical three-dimensional finite element analysis results. The patients were assessed using the prosthesis functioning scale of the Memorial Sloan-Kettering Cancer Center. In addition, retention and bite force were recorded for both the temporary prosthesis and the final prosthesis. RESULTS: The mean bite force of the prosthetic first molar was increased to 69.2 N. The mean retentive force increased to 13.5 N after zygoma implant insertion. The bite force on the prosthetic first molar was improved to 229.3 N. CONCLUSION: Bite force increased significantly with the support of a zygoma implant. The use of zygoma implants in the restoration of maxillary defects improved functional outcome and patient satisfaction.

Biological function of hpsh4590 localized in the plasticity zone of Helicobacter pylori.

The aim of this study was to determine the biological function of hpsh4590 in Helicobacter pylori. After Hpsh4590 was expressed using a prokaryotic expression system, the cytotoxic effects and IL-8 production of Hpsh4590 were analyzed by co-culturing with GES-1 cells. Meanwhile, the antibody of rHpsh4590, produced by immunizing rabbit, was used for localization and protein interaction studies. Hpsh4590 fusion protein was expressed successfully in Escherichia coli Rosetta (DE3), and the polyclonal antibody was produced at high titers. The MTT assay showed that the inhibition ratio of GES-1 cells cultured with 0.1 µg/mL rHpsh4590 (3.02% ± 0.02%) was significantly lower than that of 20 µg/mL rHpsh4590 (57.57% ± 0.03%, p < 0.01), while DAPI staining showed the cytotoxic effects of rHpsh4590 for GES-1 cells. The up-regulation of cleaved caspase-3 and cleaved PARP was observed after GES-1 cells co-cultured with rHpsh4590 by Western blot. Co-culturing of GES-1 cells with rHpsh0459 (20 µg/mL) led to significant production of IL-8 at 12 h(1097.74 ± 212.37 pg/mL) and 24 h (1379.55 ± 209.58 pg/mL) then at 6 h(134.68 ± 14.64 pg/mL, p < 0.01). These observations suggest that the cytotoxicity of Hpsh4590 occurred in a concentration dependent manner, which is related with IL-8 secretion from gastric mucosal epithelial cells. Hpsh4590 was found localized in the membrane and the periplasm of H. pylori, interacted with zinc finger protein and methionine ABC transporter ATP-binding protein, and potentially regulates DNA uptake or transfer.

Helicobacter pylori virulence factors in development of gastric carcinoma.

Helicobacter pylori plays a vital role in the pathogenesis of gastric carcinoma. However, only a relatively small proportion of individuals infected with H. pylori develop gastric carcinoma. Differences in the incidence of gastric carcinoma among infected individuals can be explained, at least partly, by the different genotypes of H. pylori virulence factors. Thus far, many virulence factors of H. pylori, such as Cag PAI, VacA, OMPs and DupA, have been reported to be involved in the development of gastric cancer. The risk of developing gastric cancer during H. pylori infection is affected by specific host-microbe interactions that are independent of H. pylori virulence factors. In this review, we discuss virulence factors of H. pylori and their role in the development of gastric carcinoma that will provide further understanding of the biological interactions of H. pylori with the host.

Identification of Novel Inflammatory Cytokines and Contribution of Keratinocyte-Derived Chemokine to Inflammation in Response to Vibrio vulnificus Infection in Mice.

Currently, only tumor necrosis factor alpha (TNF-α) and interleukin family cytokines have been found to be elicited in Vibrio vulnificus (V. vulnificus)-infected animal models and humans. However, multiple other cytokines are also involved in the immune and inflammatory responses to foreign microorganism infection. Antibody array technology, unlike traditional enzyme-linked immunosorbent assay (ELISA), is able to detect multiple cytokines at one time. Therefore, in this study, we examined the proinflammatory cytokine profile in the serum and liver homogenate samples of bacterial-infected mice using antibody array technology. We identified nine novel cytokines in response to V. vulnificus infection in mice. We found that keratinocyte-derived chemokine (KC) was the most elevated cytokine and demonstrated that KC played a very important role in the V. vulnificus infection-elicited inflammatory response in mice, as evidenced by the fact that the blocking of KC by anti-KC antibody reduced hepatic injury in vivo and that KC induced by V. vulnificus infection in AML-12 cells chemoattracted neutrophils. Our findings implicate that KC may serve as a novel diagnostic biomarker and a possible therapeutic target for V. vulnificus infection.

Helicobacter pylori with the Intact dupA Cluster is more Virulent than the Strains with the Incomplete dupA Cluster.

The duodenal ulcer promoting gene (dupA), located in the plasticity region of Helicobacter pylori (H. pylori), is predicted to form a type IV secretory system (T4SS) with vir genes around dupA. In the study, we investigated the association between the dupA cluster status and the virulence of H. pylori in a littoral region of Northeast China. Two hundred and sixty-two H. pylori strains isolated from the chronic gastritis were examined to evaluate the dupA cluster status, cag PAI genes and vacA genotype using PCR and Western blot. Histopathologic evaluations of biopsy specimens were performed to analysis the association between the dupA cluster and the inflammatory response. IL-8 productions in gastric mucosa and from GES-1 cells co-cultured with H. pylori were measured, respectively, to analysis the association between the dupA cluster status and IL-8 production. We found that gastric mucosal inflammatory cell infiltration was significantly higher in patients with dupA-positive H. pylori, including H. pylori with complete dupA cluster (2.71 ± 0.79) and incomplete dupA cluster (2.09 ± 0.61) than in patients with dupA-negative strain (1.73 ± 0.60, p < 0.01), whereas no significant difference in the gastric mucosal atrophy was found according to the status of dupA cluster. Gastric mucosal IL-8 levels were higher in the complete dupA cluster group than in other groups (p < 0.01), and IL-8 production from GES-1 cells was also significantly higher in strains with a complete dupA cluster (1527.9 ± 180.0 pg/ml) than in those with an incomplete dupA cluster (1229.4 ± 75.3 pg/ml, p < 0.01) or those with dupA negative (1201.9 ± 92.3 pg/ml, p < 0.01). In conclusion, the complete dupA cluster in H. pylori is associated with inflammatory cell infiltration and IL-8 secretion, and H. pylori strain with a complete dupA cluster seems to be more virulent than other strains with the incomplete dupA cluster or dupA negative.