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Xia Dong Zhiting Sun Jie Liang Hai Wang Dunwan Zhu Xigang Leng Chun Wang Deling Kong Feng Lv 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(4):1087-1098
Accurate and efficient antigen delivery is crucial for inducing a strong and long-term immune response. A visible protein nanovaccine made from antigen could provide a novel and promising technology for secure and efficient delivery of the antigen with imaging visualization. In this study, a functional nanovaccine based on genipin crosslinked ovalbumin (OVA) fluorescent nanoparticles with chitosan (CS-OVA-NPs) was developed. The nanovaccine can carry abundant antigens by self-crosslinking without additional carriers. The fluorescence imaging technique was applied to monitor and reveal the process of antigen delivery in vivo based on the fluorescence of genipin with a non-invasive and real-time manner. This functional OVA nanovaccine can enhance the uptake of OVA in Dendritic Cells (DCs) and further promote DCs to maturate in vitro. In vivo study further indicated CS-OVA-NPs could trigger antigen-specific immune responses, which demonstrated that this fluorescent nanovaccine provided a novel design approach for accurate and efficient vaccine delivery. 相似文献
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Ling Ding Chenfei Zhu Fei Yu Pengkai Wu Gang Chen Aftab Ullah Kaikai Wang Minjie Sun Jing Li David Oupický 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(6):1765-1776
This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF. 相似文献
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Yi-Chin Chang Kuang-Che Kuo Wu Sun Jiun-Nong Lin Chung-Hsu Lai Chen-Hsiang Lee 《Journal of microbiology, immunology, and infection》2019,52(5):769-778
BackgroundThis study aimed to offer key features to differentiate scrub typhus (ST) and murine typhus (MT) at the early stage of the diseases and provide clinicoepidemiologic characteristics of ST and MT in southern Taiwan, a region where both diseases are endemic. Comparison of doxycycline treatment efficacy between the two diseases by matching disease severity and delayed treatment had never been investigated.MethodsWe reviewed the medical records of cases of ST and MT in four hospitals in southern Taiwan. Propensity-score matching was used to analyze the defervescence curves between patients with doxycycline-treated ST and MT by log-rank test.ResultsBetween 2004 and 2016, 265 ST and 63 MT cases were diagnosed. The number of cases of ST was significantly related to temperature (Rs = 0.77) and rainfall (Rs = 0.63). Island area exposure, arthropod bite, eschar, and lymphadenopathy were only recorded in ST patients. Multivariate analysis revealed that mountainous area exposure (odds ratio [OR], 11.0; 95% confidence interval [CI], 4.4–27.2) was an independent predictor for ST, while contact with rats (OR, 8.4; 95% CI, 3.3–21.3) was that for MT. After propensity-score matching, there was no difference in defervescence curves between these two rickettsioses treated with doxycycline (p = 0.24).ConclusionIn the present study, island area exposure, arthropod bite, eschar, and lymphadenopathy were unique manifestations of ST. Mountainous area exposure is a predictive factor for ST, while contact with rats predicted MT. There was no difference in defervescence time between these two rickettsioses after doxycycline treatment. 相似文献
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Cytosine base editors (CBEs) and adenine base editors (ABEs), which are generally composed of an engineered deaminase and a catalytically impaired CRISPR‐Cas9 variant, are new favorite tools for single base substitution in cells and organisms. In this review, we summarize the principle of base‐editing systems and elaborate on the evolution of different platforms of CBEs and ABEs, including their deaminase, Cas9 variants, and editing outcomes. Moreover, we highlight their applications in mouse and human cells and discuss the challenges and prospects of base editors. The ABE‐ and CBE systems have been used in gene silencing, pathogenic gene correction, and functional genetic screening. Single base editing is becoming a new promising genetic tool in biomedical research and gene therapy. 相似文献
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Deciphering the potential of noncoding loci to influence gene regulation has been the subject of intense research, with important implications in understanding genetic underpinnings of human diseases. Massively parallel reporter assays (MPRAs) can measure regulatory activity of thousands of DNA sequences and their variants in a single experiment. With increasing number of publically available MPRA data sets, one can now develop data‐driven models which, given a DNA sequence, predict its regulatory activity. Here, we performed a comprehensive meta‐analysis of several MPRA data sets in a variety of cellular contexts. We first applied an ensemble of methods to predict MPRA output in each context and observed that the most predictive features are consistent across data sets. We then demonstrate that predictive models trained in one cellular context can be used to predict MPRA output in another, with loss of accuracy attributed to cell‐type‐specific features. Finally, we show that our approach achieves top performance in the Fifth Critical Assessment of Genome Interpretation “Regulation Saturation” Challenge for predicting effects of single‐nucleotide variants. Overall, our analysis provides insights into how MPRA data can be leveraged to highlight functional regulatory regions throughout the genome and can guide effective design of future experiments by better prioritizing regions of interest. 相似文献
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The neurofibromatosis type 1 (NF1) tumor suppressor gene is one of the most frequently mutated genes in human tumors. Research on the NF1 proteins has been partially hindered by the difficulties in cloning and propagating the full‐length coding cDNAs. We have now established a condition for propagating the natural open reading frames (ORFs) and have assembled the ORFs for human NF1 type 1 and 2 isoforms. Furthermore, we were able to eliminate the cDNA cloning toxicity by introducing a mini‐intron. These NF1 minigenes were expressed similarly to the intronless version and could be used to purify full‐length NF1 proteins. The NF1 isoforms expressed from the minigenes showed Ras‐GAP activity in vivo and in vitro, while the type 1 was more potent. Our constructs expand currently available full‐length NF1 constructs and should be valuable tools in expediting the understanding of NF1, particularly the isoform‐specific functions and regulation. 相似文献
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