Hongren Wang

Protection against Helicobacter pylori infection in BALB/c mice by oral administration of multi-epitope vaccine of CTB-UreI-UreB

Chronic gastric infection by the Gram-negative bacterium Helicobacter pylori (H. pylori) is strongly associated with gastritis, gastric ulcer and the development of distal gastric carcinoma and gastric mucosal lymphoma in humans. Antibiotic treatment of H. pylori is becoming less effective because of increasing antibiotic resistance; other treatment approaches such as specifically targeted methods, etc. to destroy this organism would be beneficial. An epitope vaccine is a promising option for protection against H. pylori infection. In this study, a multi-epitope vaccine was constructed by linking cholera toxin B subunit (CTB), two antigenic fragments of H. pylori urease I subunit (UreI20-29, UreI98-107) and four antigenic fragments of H. pylori urease B subunit (UreB12-23, UreB229-251, UreB327-400, UreB515-561), resulting in the recombinant CTB-UreI-UreB (BIB). Its protective effect against H. pylori infection was evaluated in BALB/c mice. Significant protection against H. pylori challenge was achieved in BALB/c mice immunized with BIB (15/18, 83.3%), rIB plus rCTB (6/18, 33.3%) and rIB (2/18, 11.1%) separately, while no protective effect was found in the mice immunized with either adjuvant rCTB alone or PBS. The induction of significant protection against H. pylori is possibly mediated by specific serum IgA and mucosal sIgA antibodies, and a mixed Th1/Th2/Th17 cells response. This multi-epitope vaccine might be a promising vaccine candidate that helps to control H. pylori infection.

Expressions and dimerization affinities of three highly identical APETALA3 genes in Brassica napus

Three highly identical cDNA clones of APETALA3 (AP3) gene, BnAP3-2, BnAP3-3 and BnAP3-4 were isolated from Brassica napus L. by RT-PCR. The sequence analysis showed that all the three AP3 cDNAs contained a complete open reading frame. Their nucleotide sequences had 91–97 % similarity and their predicted amino acid sequences shared 93–98 % identity. Real-time quantitative RT-PCR result showed that all the three BnAP3 genes were expressed at the transcriptional level in petals as well as stamens. Among the three BnAP3 genes, BnAP3-3 was expressed at the highest level and BnAP3-2 was expressed at the lowest level in petals. The transcription level of BnAP3-3 was 1.59 times than that of BnAP3-2. The transcription levels of BnAP3-2, BnAP3-3 and BnAP3-4 in stamen were 7.75, 5.11 and 3.88 times than those in petal, respectively. The yeast two-hybrid assays results showed that all the three BnAP3 proteins could form strong heterodimers with BnPI, and obviously different dimerization affinities among the three proteins to BnPI were observed. The ratio of the affinity of BnAP3-2, BnAP3-3 and BnAP3-4 to BnPI-1 was 1.27:1:1.62. Although the three BnAP3 genes were highly identical, the differences of their expression and affinity of protein interaction might reflect some functional divergence.

Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials

Background Integrase strand transfer inhibitors (INSTIs) are a novel class of anti-HIV agents that show high activity in inhibiting HIV-1 replication. Currently, licensed INSTIs include raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG); these drugs have played a critical role in AIDS therapy, serving as additional weapons in the arsenal for treating patients infected with HIV-1. To date, long-term data regarding clinical experience with INSTI use and the emergence of resistance remain scarce. However, the literature is likely now sufficiently comprehensive to warrant a meta-analysis of resistance to INSTIs. Methods Our team implemented a manuscript retrieval protocol using Medical Subject Headings (MeSH) via the Web of Science, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases. We screened the literature based on inclusion and exclusion criteria and then performed a quality analysis and evaluation using RevMan software, Stata software, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). We also performed a subgroup analysis. Finally, we calculated resistance rates and risk ratios (RRs) for the three types of drugs. Results We identified 26 references via the database search. A meta-analysis of the RAL data revealed that the resistance rate was 3.9% (95% CI = 2.9%-4.9%) for the selected randomized controlled trials (RCTs). However, the RAL resistance rate reached 40.9% (95% CI = 8.8%-72.9%) for the selected observational studies (OBSs). The rates of resistance to RAL that were associated with HIV subtypes A, B, and C as well as with more complex subtypes were 0.1% (95% CI = -0.7%-0.9%), 2.5% (95% CI = 0.5%-4.5%), 4.6% (95% CI = 2.7%-6.6%) and 2.2% (95% CI = 0.7%-3.7%), respectively. The rates of resistance to EVG and DTG were 1.2% (95% CI = 0.2%-2.2%) and 0.1% (95% CI = -0.2%-0.5%), respectively. Furthermore, we found that the RRs for antiviral resistance were 0.414 (95% CI = 0.210–0.816) between DTG and RAL and 0.499 (95% CI = 0.255–0.977) between EVG and RAL. When RAL was separately co-administered with nuclear nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs), the rates of resistance to RAL were 0.2% (95% CI = -0.1%-0.5%) and 0.2% (95% CI = -0.2%-0.6%), respectively. The ten major integrase mutations (including N155H, Y143C/R, Q148H/R, Y143Y/H, L74L/M, E92Q, E138E/A, Y143C, Q148Q and Y143S) can reduce the sensitivity of RAL and EVG. The resistance of DTG is mainly shown in 13 integrase mutations (including T97T/A, E138E/D, V151V/I, N155H, Q148, Y143C/H/R, T66A and E92Q). Conclusions Our results reveal that the DTG resistance rate was lower than the RAL resistance rate in a head-to-head comparison. Moreover, we confirmed that the EVG resistance rate was lower than the RAL resistance rate. In addition, our results revealed that the resistance rate of RAL was lower than that of efavirenz. The rates of resistance to RAL, EVG and DTG were specifically 3.9%, 1.2% and 0.1%, respectively. Compared with other types of antiviral drugs, the rates of resistance to INSTIs are generally lower. Unfortunately, the EVG and DTG resistance rates could not be compared because of a lack of data.

Digital gene expression analysis in mice lung with coinfection of influenza and streptococcus pneumoniae

Influenza A virus (IAV) and Streptococcus pneumoniae (SP) are two major upper respiratory tract pathogens that can also cause infection in polarized bronchial epithelial cells to exacerbate disease in coinfected individuals which may result in significant morbidity. However, the underlying molecular mechanism is poorly understood. Here, we employed BALB/c ByJ mice inflected with SP, IAV, IAV followed by SP (IAV+SP) and PBS (Control) as models to survey the global gene expression using digital gene expression (DGE) profiling. We attempt to gain insights into the underlying genetic basis of this synergy at the expression level. Gene expression profiles were obtain using the Illimina/Hisseq sequencing technique, and further analyzed by enrichment analysis of Gene Ontology (GO) and Pathway function. The hematoxylin-eosin (HE) staining revealed different tissue changes in groups during which IAV+SP group showed the most severe cell apoptosis. Compared with Control, a total of 2731, 3221 and 3946 differentially expressed genes (DEGs) were detected in SP, IAV and IAV+SP respectively. Besides, sixty-two GO terms were identified by Gene Ontology functional enrichment analysis, such as cell killing, biological regulation, response to stimulus, signaling, biological adhesion, enzyme regulator activity, receptor regulator activity and translation regulator activity. Pathway significant enrichment analysis indicated the dysregulation of multiple pathways, including apoptosis pathway. Among these, five selected genes were further verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). This study shows that infection with SP, IAV or IAV+SP induces apoptosis with different degrees which might provide insights into the molecular mechanisms to facilitate further research.

Role of Autophagy and Apoptosis in the Postinfluenza Bacterial Pneumonia

The risk of influenza A virus (IAV) is more likely caused by secondary bacterial infections. During the past decades, a great amount of studies have been conducted on increased morbidity from secondary bacterial infections following influenza and provide an increasing number of explanations for the mechanisms underlying the infections. In this paper, we first review the recent research progress that IAV infection increased susceptibility to bacterial infection. We then propose an assumption that autophagy and apoptosis manipulation are beneficial to antagonize post-IAV bacterial infection and discuss the clinical significance.

Polymorphisms of TGFβ1T+869C and C-509T with Lung Cancer Risk: A Meta-analysis.

BACKGROUND Lung cancer is the most common malignancy worldwide. A better understanding of the mechanisms may contribute to early diagnosis and establishment of new therapeutic targets. OBJECTIVES A meta-analysis was performed to investigate the association of transforming growth factor-beta 1 (TGFβ1) T+869C and C-509T polymorphisms with lung cancer susceptibility. MATERIAL AND METHODS Relevant studies were identified through PubMed, Medline, Embase and CNKI databases. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were employed to assess these associations in a fixedor random-effects model. RESULTS For the TGFβ1 T+869C polymorphism, 5 published case-control studies with 1167 cases and 1365 controls were included. Overall, no significant association was found between the TGFβ1 T+869C polymorphism and lung cancer susceptibility under any genetic models in the total population (p > 0.05). A subgroup analysis by ethnicity showed no significant association among the Asian population as well, while a significant association was observed in Caucasian descendants. For the TGFβ1 C-509T polymorphism, 4 studies were considered, including 1029 cases and 1133 controls. However, this polymorphism also did not increase the risk of lung cancer in all genetic comparison models. CONCLUSIONS This meta-analysis suggests that TGFβ1 T+869C and C-509T polymorphisms may not contribute to lung cancer risk in the total population, while the T+869C polymorphism may increase the risk of lung cancer in the Caucasian population. However, many studies are still required to evaluate these associations in large populations.