Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. Here, we generated a conditional replication-competent adenovirus (CRCA), designated Ad-hTERT-E1a-Apoptin, and investigated the effectiveness of the CRCA a gene therapy agent for further clinical trials.</p> <p>Results</p> <p>The observation that infection with Ad-hTERT-E1a-Apoptin significantly inhibited growth of the melanoma cells, protecting normal human epidermal melanocytes from growth inhibition confirmed cancer cell selective adenoviral replication, growth inhibition, and apoptosis induction of this therapeutic approach. The <it>in vivo </it>assays performed by using C57BL/6 mice containing established primary or metastatic tumors expanded the <it>in vitro </it>studies. When treated with Ad-hTERT-E1a-Apoptin, the subcutaneous primary tumor volume reduction was not only observed in intratumoral injection group but in systemic delivery mice. In the lung metastasis model, Ad-hTERT-E1a-Apoptin effectively suppressed pulmonary metastatic lesions. Furthermore, treatment of primary and metastatic models with Ad-hTERT-E1a-Apoptin increased mice survival.</p> <p>Conclusions</p> <p>These data further reinforce the previously research showing that an adenovirus expressing Apoptin is more effective and advocate the potential applications of Ad-hTERT-E1a-Apoptin in the treatment of neoplastic diseases in future clinical trials.</p

Comprehensive Mapping of Common Immunodominant Epitopes in the West Nile Virus Nonstructural Protein 1 Recognized by Avian Antibody Responses

West Nile virus (WNV) is a mosquito-borne flavivirus that primarily infects birds but occasionally infects humans and horses. Certain species of birds, including crows, house sparrows, geese, blue jays and ravens, are considered highly susceptible hosts to WNV. The nonstructural protein 1 (NS1) of WNV can elicit protective immune responses, including NS1-reactive antibodies, during infection of animals. The antigenicity of NS1 suggests that NS1-reactive antibodies could provide a basis for serological diagnostic reagents. To further define serological reagents for diagnostic use, the antigenic sites in NS1 that are targeted by host immune responses need to be identified and the potential diagnostic value of individual antigenic sites also needs to be defined. The present study describes comprehensive mapping of common immunodominant linear B-cell epitopes in the WNV NS1 using avian WNV NS1 antisera. We screened antisera from chickens, ducks and geese immunized with purified NS1 for reactivity against 35 partially overlapping peptides covering the entire WNV NS1. This study identified twelve, nine and six peptide epitopes recognized by chicken, duck and goose antibody responses, respectively. Three epitopes (NS1-3, 14 and 24) were recognized by antibodies elicited by immunization in all three avian species tested. We also found that NS1-3 and 24 were WNV-specific epitopes, whereas the NS1-14 epitope was conserved among the Japanese encephalitis virus (JEV) serocomplex viruses based on the reactivity of avian WNV NS1 antisera against polypeptides derived from the NS1 sequences of viruses of the JEV serocomplex. Further analysis showed that the three common polypeptide epitopes were not recognized by antibodies in Avian Influenza Virus (AIV), Newcastle Disease Virus (NDV), Duck Plague Virus (DPV) and Goose Parvovirus (GPV) antisera. The knowledge and reagents generated in this study have potential applications in differential diagnostic approaches and subunit vaccines development for WNV and other viruses of the JEV serocomplex

Advances in the applications of polymer biomaterials for in vitro follicle culture

The ovarian reserve (OR) indicates ovarian function by representing the quantity and quality of ovarian follicles, and it gradually decreases with increasing age. With the prolongation of women’s lives, the protection provided by estrogen is lost for decades in postmenopausal women, and the related cardiovascular and cerebrovascular diseases, osteoporosis, and decreased immunity are the main risk factors affecting women’s quality of life and longevity. Pharmacologic hormone replacement therapy (PHRT) has been controversial, and the construction of artificial ovary (AO) has attracted increasing attention. The most critical step of AO generation is the establishment of an in vitro culture (IVC) system to support the development of isolated follicles. This article mainly compares the advantages and disadvantages of different polymer biomaterials for use in follicle IVC, provides theoretical support for the development and construction of the follicle IVC system using natural biological materials, and provides a theoretical basis for establishing mature AO technology

MOESM2 of The chimeric multi-domain proteins mediating specific DNA transfer for hepatocellular carcinoma treatment

Additional file 2: Figure S2. The schematic representation of plasmid chimera and fusion protein transfection into human HepG-2 cells

Retinal regionalization and heterogeneity of butterfly eyes

The regional characteristics of the eyes of butterflies from different families have been surveyed using epi-illumination microscopy, utilizing the eyeshine visible due to the tapetum situated proximally to the rhabdom. All butterflies studied have a high spatial acuity in the frontal region. The facet diameter varies slightly across the eye, and the interommatidial angle and the eye parameter p are especially large dorsally. Whereas the ommatidial lattice is generally highly regular, the eyeshine colours distinctly depend on the species. Sometimes the eyeshine is locally uniform, but often it is heterogeneous. It is hypothesized that the regional characteristics as well as the local heterogeneity are adaptations that optimize spectral discrimination

Autophagy Activated by Bluetongue Virus Infection Plays a Positive Role in Its Replication

Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. Despite extensive study in recent decades, the interplay between BTV and host cells is not clearly understood. Autophagy as a cellular adaptive response plays a part in many viral infections. In our study, we found that BTV1 infection triggers the complete autophagic process in host cells, as demonstrated by the appearance of obvious double-membrane autophagosome-like vesicles, GFP-LC3 dots accumulation, the conversion of LC3-I to LC3-II and increased levels of autophagic flux in BSR cells (baby hamster kidney cell clones) and primary lamb lingual epithelial cells upon BTV1 infection. Moreover, the results of a UV-inactivated BTV1 infection assay suggested that the induction of autophagy was dependent on BTV1 replication. Therefore, we investigated the role of autophagy in BTV1 replication. The inhibition of autophagy by pharmacological inhibitors (3-MA, CQ) and RNA interference (siBeclin1) significantly decreased viral protein synthesis and virus yields. In contrast, treating BSR cells with rapamycin, an inducer of autophagy, promoted viral protein expression and the production of infectious BTV1. These findings lead us to conclude that autophagy is activated by BTV1 and contributes to its replication, and provide novel insights into BTV-host interactions

Thickness dependent properties of ultrathin perovskite nanosheets with Ruddlesden–Popper-like atomic stackings

Ruddlesden-Popper perovskites possess a rich variety of multiple phases due to their mixed organic cations and variable layer numbers. However, the direct observation of these phases and their optical performance in ultrathin nanosheets, have rarely been reported. Here we demonstrate, through a one-pot CVD synthesis method to incorporate MA(+) and NMA(+) cations into PbI2 simultaneously, that the stackings of Ruddlesden-Popper phases with a distribution of a number of layers n can be produced within a single perovskite nanosheet. As featured by the micro-, time-resolved and temperature-dependent photoluminescence measurements, the optical properties are highly dependent on the nanosheet thickness.The work was financially supported by the National Key R&D Program of China (Grant No. 2020YFA0308900), the National Natural Science Foundation of China (Grant No. 92064010, 61801210, 91833302), the Natural Science Foundation of Jiangsu Province (Grant No. BK20180686), the China postdoctoral Science Foundation (2020M683555), the funding for "Distinguished professors" and "High-level talents in six industries" of Jiangsu Province (Grant No. XYDXX-021), the Fundamental Research Funds for the Central Universities, the Key Research and Development Program of Shaanxi Province (2020GXLH-Z-020, 2020GXLH-Z-027) and the start-up foundation of Northwestern Polytechnical University and Nanjing Tech University

Assessment of the specificity of common avian immunodominant epitopes by ELISA using polypeptides derived from homologous regions of viruses from JEV serocomplex viruses.

<p>Chicken, duck and goose antisera immunized with WNV NS1 protein were tested for reactivity against three corresponding polypeptides from other JEV serocomplex viruses by ELISA to identify serotype- and group-specific B cell epitopes. For each polypeptide, the left panel displays the results of ELISA evaluating antibody binding to the JEV serocomplex peptides. Each bar indicates antisera reactivity as determined by the mean absorbance. The right panel depicts the sequence alignments used to identify corresponding polypeptides from representative strains of associated flavivirus isolates. The sequences from DENV1-4 and YFV are shown for comparison.</p