Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes

BACKGROUND: An effective vaccine and new therapeutic methods for hepatitis C virus (HCV) are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI). Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens. RESULTS: A recombinant replication-defective adenovirus serotype 5 (rAd5) vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1-746 amino acid HCV 1b subtype). Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m.), intranasal injection (i.n.), or intradermal injection (i.d.) and boosted using a different combination of injection routes. CMI was evaluated via IFN-γ ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2) was elicited and remained at a high level for a long period (16 weeks post-vaccination) in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross-protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a) vaccinia virus. CONCLUSIONS: Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates

CircZNF652 accelerates the proliferation and migration of primary lung carcinoma cells by downregulating miR-766

Purpose: To explore the biological functions and molecular mechanism of circZNF652 involvement in primary lung carcinoma.Methods: CircZNF652 levels in primary lung carcinoma cases and controls were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Its prognostic value in primary lung carcinoma was examined by depicting it with Kaplan-Meier curves. The biological functions of circZNF652 in regulating proliferative and migratory capacities in A549 and SPC-A-1 cells were analyzed from the curves. Interaction between circZNF652 and its downstream gene, miR-766, wasassessed, and their co-regulation on primary lung carcinoma was determined by rescue experiments.Results: CircZNF652 was abnormally and significantly upregulated in primary lung carcinoma cases (p< 0.05), resulting in a poor prognosis. The knockdown effect of circZNF652 attenuated the proliferative and migratory capacities of A549 and SPC-A-1 cells, and downregulated epithelial-mesenchymal transition (EMT)-associated genes. CircZNF652 bound and negatively regulated miR-766, a keydownstream gene involved in circZNF652-induced aggravation of primary lung carcinoma.Conclusion: CircZNF652 serves as an oncogene, triggering the aggravation of primary lung carcinoma by negatively regulating miR-766. The results of this study may provide new insights into the treatment of lung carcinoma

The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization

Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with “tree-in-bud” form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV

Targeting Histone Reader ENL with PROTAC Degrader

ENL is a histone reader that is part of the super elongation complex and is primarily involved in chromatin and gene expression regulation. ENL has also been found to play an essential role in the progression of a spectrum of acute myeloid leukemia (AML). Some hotspot mutations of its reader module, the YEATS domain, have been found to be oncogenic. For this reason, we explored the efficacy of a newly developed ENL PROTAC degrader in its ability to degrade wild-type and mutant ENL protein and suppress oncogene expression in cancer cells

Expressions of CXCL12/CXCR4 in Oral Premalignant and Malignant Lesions

Objective. The chemokine receptor CXCR4 and its ligand CXCL12 have been suggested to play important roles in the initiation or progression of cancers. The goal of the present study was to investigate alterations of CXCL12/CXCR4 in oral premalignant lesions and oral squamous cell carcinoma (OSCC). Methods. In 13 normal oral epithelia, 24 dysplastic oral leukoplakia (OLK), and 40 OSCC specimens, expressions of CXCL12 and CXCR4 were evaluated by immunohistochemistry. Results. CXCR4 was expressed in 37.5% of OLK and 60% of OSCC. CXCL12 was detected in 50% of OLK and 62.5% of OSCC. In OLK, CXCR4 positive ratio showed no significant difference from normal epithelia, but the CXCL12 positive ratio was significantly higher. Significant relationship between CXCL12 and CXCR4 was found both in OLK and OSCC. Conclusion. Our results indicated that CXCL12/CXCR4 axis may play roles from early steps of oral malignant transformation and contribute to the progress of oral carcinogenesis

Growth of Human Colorectal Cancer SW1116 Cells Is Inhibited by Cytokine-Induced Killer Cells

Previous reports have suggested that treatment with cytokine-induced killer (CIK) cells may benefit patients with various types of tumor. The aim of this study was to evaluate the antitumor effects of CIK cells against the colorectal cancer line SW1116 in vitro and in vivo. CIK cells were generated routinely from peripheral blood mononuclear cells of healthy human donors, and the number of CD3+CD56+ cells was expanded more than 1300-fold after 14-day culture. At an effector : target cell ratio of 50 : 1, the percentage lysis of SW1116 cells reached 68% in the presence of CIK cells, Experimental mice injected with SW1116 cells subcutaneously were divided randomly into four groups: untreated, 5-fluorouracil (5-FU)-treated, CIK-consecutive treated (injected once/day) and CIK-interval treated (injected once every 5 days). CIK cells were injected abdominally five times in total. Compared with the untreated group, xenograft growth was inhibited greatly by CIK treatment, to nearly the same extent as with 5-FU treatment. We demonstrated that the necrotic area in the tumor xenograft was markedly larger in the CIK-treated groups than in the other groups. These findings suggest that CIK-based immunotherapy may represent an effective choice for patients with colorectal cancer

Variation on gut microbiota diversity of endangered red pandas (Ailurus fulgens) living in captivity acrosss geographical latitudes

The gut microbiome plays important roles in metabolic and immune system related to the health of host. This study applied non-invasive sampling and 16S rDNA high-throughput sequencing to study the gut microbiota structure of red pandas (Ailurus fulgens) for the first time under different geographical latitudes in captivity. The results showed that the two predominant phyla Firmicutes (59.30%) and Proteobacteria (38.58%) constituted 97.88% of the total microbiota in all the fecal samples from north group (red pandas from Tianjin Zoo and Jinan Zoo) and south group (red pandas from Nanjing Hongshan Forest Zoo). The relative abundance of Cyanobacteria in north group was significantly higher than that in south group. At the genus level, Escherichia-Shigella (24.82%) and Clostridium_sensu_stricto_1 (23.00%) were common dominant genera. The relative abundance of norank_f__norank_o__Chloroplast, Terrisporobacter and Anaeroplasma from south group was significantly higher than that of north group. Alpha and Beta analysis consistently showed significant differences between north group and south group, however, the main functions of intestinal microbiota were basically the same, which play an important role in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in different environments, and amino acid biosynthesis. The variations in gut microbiota between the northern and southern populations of the same species, both kept in captivity, which are primarily driven by significant differences in climate and diet. These findings provide a deeper understanding of the gut microbiota in red pandas and have important implications for their conservation, particularly in optimizing diet and environmental conditions in captivity

Effects of Intravitreal Ranibizumab Injection on Chinese Patients with Wet Age-Related Macular Degeneration: 5-Year Follow-Up Results

Purpose. To observe the effect of intravitreal ranibizumab injection on wet age-related macular degeneration (wAMD) over 5 years in Chinese patients. Methods. Thirty-seven patients who were diagnosed with wAMD in our hospital from June 2007 to June 2014 were retrospectively reviewed. The PRN regimen and the treatment and extend regimen were applied. Best corrected visual acuity (BCVA), number of ranibizumab injections, and changes in the choroidal neovascularization (CNV) lesion over 5 years were analyzed. Results. The mean BCVA measured by the ETDRS chart at baseline was 47.4 and 5 years after the treatment it was 34.89 letters, which was significantly different (p=0.013). Fourteen eyes (37.8%) had improved visual acuity after 5 years. The number of injections in 5 years was 11.53, and most of the injections were in the first two years. Seventeen (45.9%) cases developed fibrous lesions, and 2 (5.4%) cases had atrophic lesions after 5 years. The fibrosis/atrophy was significantly correlated with the injection numbers (Pearson, r=0.663, and p=0.000). Conclusion. Most of the patients can maintain visual acuity treated by ranibizumab in the first 3 years. After 5 years, some patients can still improve or maintain visual acuity. Fibrous scarring of the lesion is the main reason for a decrease in vision of wAMD patients