Activation Of α7 Nicotinic Acetylcholine Receptors Prevents Monosodium Iodoacetate-Induced Osteoarthritis In Rats

Background/Aims: Although some evidence suggests that the prevalence of osteoarthritis (OA) is lower in smokers compared to nonsmokers, the mechanisms of nicotine-induced protection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) appears to be a critical mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells. The inhibition of secreted inflammatory molecules and the subsequent inflammatory processes have been proposed as a novel strategy for the treatment of OA. The objective of the present study was to determine whether nicotine-induced protection in a monosodium iodoacetate (MIA) rat model of OA occurs via α7-nAChR-mediated inhibition of chondrocytes. Methods: Both in vivo (MIA) and in vitro (MIA; Interleukin-1β, IL-1β) models of OA were used to investigate the roles and the possible mechanisms whereby α7-nAChRs protect against knee joint degradation. Multiple experimental approaches, including macroscopic, histological analysis, chondrocyte cell cultures, confocal microscopy, and western blotting, were employed to elucidate the mechanisms of α7-nAChR-mediated protection. Results: Systemic administration of nicotine alleviated MIA-induced joint degradation. The protective effects of nicotine were abolished by administration of the α7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured rat chondrocytes, pretreatment with nicotine suppressed both p38, extracellular regulated kinase (Erk) 1/2 and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPK) phosphorylation and phosphorylated nuclear factor-kappa B (NF-κB) p65 activation induced by MIA- or IL-1β, and these effects were also reversed by MLA. Conclusion: Taken together, our results suggest that activation α7-nAChRs is an important mechanism underlying the protective effects of nicotine

T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related to mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection but did mediate antibody-dependent enhancement in vitro, though this did not have an adverse impact on survival. This study suggests that the SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue to develop a novel bivalent vaccine against both ZIKV and JEV. KEY POINTS: • JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice. • T cell immunity rather than antibody mediated the cross-protection. • It provides important information in terms of ZIKV prevention or precaution

Cross-Protection Against Four Serotypes of Dengue Virus in Mice Conferred by a Zika DNA Vaccine

Both Zika virus (ZIKV) and four serotypes of dengue virus (DENV1–4) are antigenically related mosquito-borne flaviviruses that co-circulate in overlapping geographic distributions. The considerable amino acid sequence homology and structural similarities between ZIKV and DENV1–4 may be responsible for the complicated immunological cross-reactivity observed for these viruses. Thus, a successful Zika vaccine needs to not only confer protection from ZIKV infection but must also be safe during secondary exposures with other flavivirus, especially DENVs. In this study, we used a Zika DNA vaccine candidate (pV-ZME) expressing the ZIKV premembrane and envelop proteins to immunize BALB/c mice and evaluated the potential cross-reactive immune responses to DENV1–4. We observed that three doses of the pV-ZME vaccine elicited the production of cross-reactive antibodies, cytokines and CD8+ T cell responses and generated cross-protection against DENV1–4. Our results demonstrate a novel approach for design and development of safe Zika and/or dengue vaccines

Vaccination With a Single Consensus Envelope Protein Ectodomain Sequence Administered in a Heterologous Regimen Induces Tetravalent Immune Responses and Protection Against Dengue Viruses in Mice

The development of a safe and effective tetravalent dengue vaccine that elicits protection against all dengue virus (DENV) serotypes is urgently needed. The consensus sequence of the ectodomain of envelope (E) protein of DENV (cE80) has been examined as an immunogen previously. In the current study, a cE80 DNA (D) vaccine was constructed and evaluated in conjunction with the cE80 protein (P) vaccine to examine whether both vaccines used together can further improve the immune responses. The cE80 DNA vaccine was administrated using either a homologous (DNA alone, DDD) or heterologous (DNA prime-protein boost: DDP or DPP) regimen, and evaluated for immunogenicity and protective efficacy in mice. Among the three DNA-based immunization regimens tested, DDP immunization is the optimal immunization regimen that elicited the greatest systemic immune response and conferred protection against all four DENV serotypes. This work provides innovative ideas for the development of consensus E-based dengue vaccines and the testing of optimal immunization regimens

Suppressive Effects on the Immune Response and Protective Immunity to a JEV DNA Vaccine by Co-administration of a GM-CSF-Expressing Plasmid in Mice

As a potential cytokine adjuvant of DNA vaccines, granulocyte-macrophage colony–stimulating factor (GM-CSF) has received considerable attention due to its essential role in the recruitment of antigen-presenting cells, differentiation and maturation of dendritic cells. However, in our recent study of a Japanese encephalitis virus (JEV) DNA vaccine, co-inoculation of a GM-CSF plasmid dramatically suppressed the specific IgG response and resulted in decreased protection against JEV challenge. It is known that GM-CSF has been used in clinic to treat neutropenia for repopulating myeloid cells, and as an adjuvant in vaccine studies; it has shown various effects on the immune response. Therefore, in this study, we characterized the suppressive effects on the immune response to a JEV DNA vaccine by the co-administration of the GM-CSF-expressing plasmid and clarified the underlying mechanisms of the suppression in mice. Our results demonstrated that co-immunization with GM-CSF caused a substantial dampening of the vaccine-induced antibody responses. The suppressive effect was dose- and timing-dependent and likely related to the immunogenicity of the antigen. The suppression was associated with the induction of immature dendritic cells and the expansion of regulatory T cells but not myeloid-derived suppressor cells. Collectively, our findings not only provide valuable information for the application of GM-CSF in clinic and using as a vaccine adjuvant but also offer further insight into the understanding of the complex roles of GM-CSF

An Automatic Accurate High-Resolution Satellite Image Retrieval Method

With the growing number of high-resolution satellite images, the traditional image retrieval method has become a bottleneck in the massive application of high-resolution satellite images because of the low degree of automation. However, there are few studies on the automation of satellite image retrieval. This paper presents an automatic high-resolution satellite image accurate retrieval method based on effective coverage (EC) information, which is used to replace the artificial screening stage in traditional satellite image retrieval tasks. In this method, first, we use a convolutional neural network to extract the EC of each satellite image; then, we use an effective coverage grid set (ECGS) to represent the ECs of all satellite images in the library; finally, the satellite image accurate retrieval algorithm is proposed to complete the process of screening images. The performance evaluation of the method is implemented in three regions: Wuhan, Yanling, and Tangjiashan Lake. The large number of experiments shows that our proposed method can automatically retrieve high-resolution satellite images and significantly improve efficiency

Limonene, the compound in essential oil of nutmeg displayed antioxidant effect in sunflower oil during the deep-frying of Chinese Maye

The deep-frying process for plenty of fried products using vegetable oils needs safe and effective antioxidants. In the present exploration, the nutmeg essential oil (NEO) was employed as a potential antioxidant for sunflower oil during the deep-frying of Chinese Maye at 180°C for 30 hr. In the comparative study, the additions for NEO at 0.12 g/kg, TBHQ at 0.12 g/kg, BHA at 0.08 g/kg, and BHT at 0.08 g/kg to sunflower oil were able to obviously improve its oxidative stability during the deep-frying process, and their antioxidant effects were in the relative order: TBHQ at 0.12 g/kg > NEO at 0.12 g/kg > BHA at 0.08 g/kg > BHT at 0.08 g/kg (p < .05). Besides, NEO at 0.12 g/kg could markedly ameliorate the sensory properties including flavor, taste, crispness, and overall acceptability of the fried products, Chinese Maye (p < .05 or p < .01). In addition, using antioxidant activity-guided fractionation, three active compounds including limonene, terpinolene, and geranyl acetate were isolated from NEO. Among them, limonene was demonstrated to not only significantly increase the oxidative stability of sunflower oil in the deep-frying process, but also significantly increase the sensory properties of the fried products, Chinese Maye (p < .05 or p < .01). Consequently, limonene could be employed as antioxidants in sunflower oil for the deep-frying of Chinese Maye, and the sunflower oil flavored by NEO could be used as frying oils for its oxidative stability and unique flavor

An enhanced oil recovery technique by targeted delivery ASP flooding

Aiming at the problem of the loss of the ASP flooding near the injection wells, this paper gives a new idea to enhance oil recovery called “Technique of Targeted Delivery”, which combines the radial horizontal well with ultra-short radius drilled by high pressure water jet with the ASP flooding, the horizontal wells work as the “Target channel” transport the ternary composite system to the remaining oil enrichment area directly, to avoid the loss of the ternary composite system near the injection wells. The plate homogeneous experiment and numerical simulation show that the technique can significantly improve the sweep efficiency and the effect of the oil displacement, and greatly improve the oil recovery rate. The optimal flooding parameters of the target transport technique are: the right angle target, the length of the channel is about 15% of the well distance and the injection volume of the ternary composite system is 0.4 PV. Under such conditions, this technique can enhance recovery by 48.87% and 22.04% respectively, compared with the water flooding and conventional ASP flooding. The target transport technique solves the problem of high loss of chemical agent in near-wellbore area during the ASP flooding, and compensates for the high cost of ASP flooding and the limitation of application, and has a broad application prospect. Key words: ASP flooding, targeted delivery, plate model, parameter optimization, enhanced oil recover