a-quantitative-dot-blot-assay-for-aav-titration-its-use-for

A Quantitative Dot Blot Assay for AAV Titration and Its Use for Functional Assessment of the Adeno-associated Virus Assembly-activating Proteins

While adeno-associated virus (AAV) is widely accepted as an attractive vector for gene therapy, it also serves as a model virus for understanding virus ...

in-vitro-cellular-activity-evaluation-nanoemulsion-vaccine-adjuvant

In Vitro Cellular Activity Evaluation of the Nanoemulsion Vaccine Adjuvant Ophiopogonin D

As a principal ingredient of vaccines, adjuvants can directly induce or enhance the powerful, widespread, innate, and adaptive immune responses associated ...

preparation-characteristics-toxicity-efficacy-evaluation-nasal-self

Preparation, Characteristics, Toxicity, and Efficacy Evaluation of the Nasal Self-Assembled Nanoemulsion Tumor Vaccine In Vitro and In Vivo

Epitope peptides have attracted widespread attention in the field of tumor vaccines because of their safety, high specificity, and convenient production; ...

Oregon Health & Science University

Third Military Medical University of Chinese PLA

Multi-drug resistant MRSA (methicillin-resistant Staphylococcus aureus) is a global problem for human health, especially skin burn wound patients. Therefore, we estimated the antibacterial and anti-biofilm activity of a chlorhexidine acetate nanoemulsion (CNE) by previously ourselves designed against skin burn wound MRSA infections. Compared with its water solution (CHX), CNE showed a better and faster action against MRSA both in vitro and in vivo. Importantly, CNE was more effective at inhibiting biofilm formation and clearing the biofilm. We also found that the cell walls and membranes of MRSA were severely disrupted after treatment with CNE. Moreover, the relative electrical conductivity and the leakage of alkaline phosphates, K(+), Mg(2+), DNA and protein obviously increased because the cell wall and membrane were damaged. These data show that novel CNE is a promising potential antimicrobial candidate, especially for skin burn wound MRSA infections.

Enhanced efficacy and anti-biofilm activity of novel nanoemulsions against skin burn wound multi-drug resistant MRSA infections.

Rett syndrome (RTT) is a debilitating neurological disorder caused by mutations in the gene encoding the transcription factor Methyl CpG Binding Protein 2 (MECP2). A distinct disorder results from  gene duplication, suggesting that therapeutic approaches must restore close to normal levels of MECP2. Here, we apply the approach of site-directed RNA editing to repair, at the mRNA level, a disease-causing guanosine to adenosine (G > A) mutation in the mouse MeCP2 DNA binding domain. To mediate repair, we exploit the catalytic domain of Adenosine Deaminase Acting on RNA (ADAR2) that deaminates A to inosine (I) residues that are subsequently translated as G. We fuse the ADAR2 domain, tagged with a nuclear localization signal, to an RNA binding peptide from bacteriophage lambda. In cultured neurons from mice that harbor an RTT patient G > A mutation and express engineered ADAR2, along with an appropriate RNA guide to target the enzyme, 72% of  mRNA is repaired. Levels of MeCP2 protein are also increased significantly. Importantly, as in wild-type neurons, the repaired MeCP2 protein is enriched in heterochromatic foci, reflecting restoration of normal MeCP2 binding to methylated DNA. This successful use of site-directed RNA editing to repair an endogenous mRNA and restore protein function opens the door to future in vivo applications to treat RTT and other diseases.

Site-directed RNA repair of endogenous Mecp2 RNA in neurons.

As an ingredient of vaccines, adjuvants are indispensable for enhancing and directly inducing robust and extensive adaptive immune responses associated with vaccine antigens. In this study, we initially determined that a new molecular immunopotentiator, ophiopogonin D (OP-D), enhanced the antibody response to antigen. Because OP-D has certain disadvantages, including poor solubility, we next encapsulated OP-D in a nanoemulsion adjuvant (nanoemulsion-encapsulated OP-D, NOD) using low-energy emulsification methods. The NOD thus produced was small, with an average size of 76.45 nm, and exhibited good distribution (PdI value 0.16), significantly increasing the solubility of OP-D. Furthermore, NOD exhibited reduced cellular toxicity and acute toxicity. Our results showed that a fusion antigen of MRSA (HlaHIsdB) formulated with NOD significantly improved humoral and cellular immune responses compared to those observed in the antigen/OP-D and antigen/AlPO groups. Compared with antigen/OP-D, the antigen formulated with NOD more effectively promoted antigen uptake by dendritic cells (DCs) and the activation of antigen-presenting cells (APCs). Moreover, the NOD-formulated antigen had ideal protective efficacy in a MRSA sepsis model by inducing more potent antibody responses and a Th1/Th17-biased CD4 T cell immune response. Therefore, these results suggest that NOD is a promising and robust adjuvant platform for a MRSA vaccine.

An immunopotentiator, ophiopogonin D, encapsulated in a nanoemulsion as a robust adjuvant to improve vaccine efficacy.

Methicillin-resistant  (MRSA) is one of the most predominant and fatal pathogens at wound infection sites. MRSA is difficult to treat because of its antibiotic resistance and ability to form biofilms at the wound site.

Chitosan-polyvinyl alcohol nanoscale liquid film-forming system facilitates MRSA-infected wound healing by enhancing antibacterial and antibiofilm properties.

This study aimed to improve the solubility, reduce the side effects and enhance the efficacy of gambogic acid against acute myeloid leukemia in vitro and in vivo. This oil-in-water nanoemulsion (average size 17.20 ± 0.11 nm, zeta potential 4.17 ± 0.82 mV) containing Tween-80, glycol, squalene and gambogic acid with improving 4000 times solubility was prepared by pseudoternary phase diagrams. We found that this nanoemulsion successfully encapsulated gambogic acid; it was stable and showed an obvious delayed release effect for the drug in three different phosphate-buffered saline (pH = 2.0, 5.8 and 7.4). The half inhibiting concentration (IC) of this nanoemulsion (480.7 μg/mL and 408 μg/mL) were 1.67 times and 1.98 times higher than those of its water solution (287 μg/mL and 206 μg/mL) after acting on the toxicity standard cell line (L929 line) for 24 h and 48 h, respectively. Importantly, acute injection toxicity indicated that the half lethal dose (LD) of this nanoemulsion (23.25 mg/kg, 95% LD, 21.7-25.16 mg/kg) was 1.26 times higher than that of its water solution (18.59 mg/kg, 95% LD, 16.84-20.53 mg/kg). Compared with its suspension, the bioavailability of this nanoemulsion was 318.2%. Furthermore, this nanoemulsion had a better efficacy against the acute myeloid leukemia in vitro and in vivo by improving the time and percent of survival (MV4-11 engrafts mice) and reducing half inhibiting concentration values in acute myeloid leukemia such as Jurket, HL-60 and MV4-11 cells. Our studies suggested that this nanoemulsion may be a promising therapeutic medicine for acute myeloid leukemia.

Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo.

Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immunodominant HpaA epitope peptide (HpaA 154-171, P22, MEGVLIPAGFIKVTILEP) in conjunction with a CpG adjuvant decreased bacterial colonization in H. pylori-infected mice. However, to confer more robust and effective protection against H. pylori infection, an optimized delivery system is needed to enhance the P22-specific memory T cell response.

Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori.

ArticleTotal : 3	Year
Publication title Cited by 3	2018
Publication title Cited by 2	2022
Publication title Cited by 1	2022

Article	Year
Enhanced efficacy and anti-biofilm activity of novel nanoemulsions against skin burn wound multi-drug resistant MRSA infections. Nanomedicine : nanotechnology, biology, and medicine\| PubMed ID: 26961464	2016
Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 29078406	2017
An immunopotentiator, ophiopogonin D, encapsulated in a nanoemulsion as a robust adjuvant to improve vaccine efficacy. Acta biomaterialia\| PubMed ID: 30031164	2018
Chitosan-polyvinyl alcohol nanoscale liquid film-forming system facilitates MRSA-infected wound healing by enhancing antibacterial and antibiofilm properties. International journal of nanomedicine\| PubMed ID: 30214202	2018
Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences\| PubMed ID: 30296572	2018
Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori. Journal of nanobiotechnology\| PubMed ID: 30660182	2019

Zhen Song

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