-
International Journal of Molecular... Jul 2023Classical swine fever (CSF) and porcine epidemic diarrhea (PED) are highly contagious viral diseases that pose a significant threat to piglets and cause substantial...
Classical swine fever (CSF) and porcine epidemic diarrhea (PED) are highly contagious viral diseases that pose a significant threat to piglets and cause substantial economic losses in the global swine industry. Therefore, the development of a bivalent vaccine capable of targeting both CSF and PED simultaneously is crucial. In this study, we genetically engineered a recombinant classical swine fever virus (rCSFV) expressing the antigenic domains of the porcine epidemic diarrhea virus (PEDV) based on the modified infectious cDNA clone of the vaccine strain C-strain. The S1N and COE domains of PEDV were inserted into C-strain cDNA clone harboring the mutated 136th residue of N and substituted 3'UTR to generate the recombinant chimeric virus vC/SM3'UTR-S1NCOE. To improve the efficacy of the vaccine, we introduced the tissue plasminogen activator signal (tPAs) and CARD domain of the signaling molecule VISA into vC/SM3'UTR-S1NCOE to obtain vC/SM3'UTR-tPAsS1NCOE and vC/SM3'UTR-CARD/tPAsS1NCOE, respectively. We characterized three vaccine candidates in vitro and investigated their immune responses in rabbits and pigs. The N mutant exhibited normal autoprotease activity and mitigated the inhibition of IFN-β induction. The introduction of tPAs and the CARD domain led to the secretory expression of the S1NCOE protein and upregulated IFN-β induction in infected cells. Immunization with recombinant CSFVs expressing secretory S1NCOE resulted in a significantly increased in PEDV-specific antibody production, and coexpression of the CARD domain of VISA upregulated the PEDV-specific IFN-γ level in the serum of vaccinated animals. Notably, vaccination with vC/SM3'UTR-CARD/tPAsS1NCOE conferred protection against virulent CSFV and PEDV challenge in pigs. Collectively, these findings demonstrate that the engineered vC/SM3'UTR-CARD/tPAsS1NCOE is a promising bivalent vaccine candidate against both CSFV and PEDV infections.
Topics: Swine; Animals; Rabbits; Classical Swine Fever; Tissue Plasminogen Activator; Antibodies, Viral; Vaccines, Combined; DNA, Complementary; Coronavirus Infections; Viral Vaccines; Adjuvants, Immunologic; Swine Diseases; Adjuvants, Pharmaceutic; Diarrhea
PubMed: 37569329
DOI: 10.3390/ijms241511954 -
Scientific Reports Mar 2021Spodoptera frugiperda is a pest of economic importance for several crops with resistance reports to Bt crops and pesticides. Eco-friendly Bt biopesticides may be an...
Spodoptera frugiperda is a pest of economic importance for several crops with resistance reports to Bt crops and pesticides. Eco-friendly Bt biopesticides may be an alternative to chemical insecticides due to their selectivity and specificity. However, the efficacy of Bt biopesticides may be influenced by the association with other chemicals, such as adjuvants. This study evaluated the compatibility and toxicity of Bt biopesticides mixed with adjuvants for the control of S. frugiperda. The treatments included the association of Dipel SC and Dipel PM with adjuvants. Compatibility tests were used to evaluate the Bt mixture. Bt suspensions obtained from mixtures of Bt and adjuvants at 10 and 3 × 10 spores/mL were used to evaluate S. frugiperda mortality and distilled water was used as the control. The addition of the adjuvant LI increased growth and sporulation, indicating compatibility with Bt biopesticides. The other adjuvants were toxic to reducing Bt growth and sporulation. Only the mixture of Bt with LI and Bt alone was effective to S. frugiperda. The addition of adjuvants to Bt biopesticide affect the Bt sporulation, growth and mortality.
Topics: Adjuvants, Pharmaceutic; Animals; Bacillus thuringiensis; Bacillus thuringiensis Toxins; Bacterial Proteins; Biological Control Agents; Crop Protection; Crops, Agricultural; Drug Compounding; Endotoxins; Gossypium; Insecticide Resistance; Insecticides; Spodoptera
PubMed: 33674750
DOI: 10.1038/s41598-021-84871-w -
Frontiers in Immunology 2023Traditional emulsion adjuvants are limited in clinical application because of their surfactant dependence. Graphene oxide (GO) has unique amphiphilic properties and...
BACKGROUND
Traditional emulsion adjuvants are limited in clinical application because of their surfactant dependence. Graphene oxide (GO) has unique amphiphilic properties and therefore has potential to be used as a surfactant substitute to stabilize Pickering emulsions.
METHODS
In this study, GO-stabilized Pickering emulsion (GPE) was prepared and used as an adjuvant to facilitate an enhanced immune response to the () Pgp3 recombinant vaccine. Firstly, GPE was prepared by optimizing the sonication conditions, pH, salinity, GO concentration, and water/oil ratio. GPE with small-size droplets was characterized and chosen as the candidate. Subsequently, controlled-release antigen delivery by GPE was explored. Cellular uptake behaviors, M1 polarization, and cytokine stimulation by GPE + Pgp3 was considered in terms of the production of macrophages. Finally, GPE's adjuvant effect was evaluated by vaccination with Pgp3 recombinant in BALB/c mouse models.
RESULTS
GPE with the smallest droplet sizes was prepared by sonication under 163 W for 2 min at 1 mg/mL GO in natural salinity with a pH of 2 when the water/oil ratio was 10:1 (w/w). The optimized average GPE droplet size was 1.8 μm and the zeta potential was -25.0 ± 1.3 mv. GPE delivered antigens by adsorption onto the droplet surface, demonstrating the controlled release of antigens both and . In addition, GPE promoted antigen uptake, which stimulated proinflammatory tumor necrosis factor alpha (TNF-α), enhancing the M1 polarization of macrophages . Macrophage recruitment was also significantly promoted by GPE at the injection site. In the GPE + Pgp3 treatment group, higher levels of immunoglobin (IgG), immunoglobin G1 (IgG1), immunoglobin G2a (IgG2a) sera, and immunoglobin A (IgA) were detected in vaginal fluid, and higher levels of IFN-γ and IL-2 secretion were stimulated, than in the Pgp3 group, showing a significant type 1 T helper (Th1)-type cellular immune response. challenging showed that GPE enhanced Pgp3's immunoprotection through its advanced clearance of bacterial burden and alleviation of chronic pathological damage in the genital tract.
CONCLUSION
This study enabled the rational design of small-size GPE, shedding light on antigen adsorption and control release, macrophage uptake, polarization and recruitment, which enhanced augmented humoral and cellular immunity and ameliorated chlamydial-induced tissue damage in the genital tract.
Topics: Female; Animals; Mice; Antigens, Bacterial; Chlamydia trachomatis; Emulsions; Chlamydia Infections; Adjuvants, Immunologic; Vaccines, Synthetic; Adjuvants, Pharmaceutic; Water; Surface-Active Agents
PubMed: 37143655
DOI: 10.3389/fimmu.2023.1148253 -
PeerJ 2023Currently, the utilization of unmanned aerial vehicles (UAVs) for spraying pesticides is a prevalent issue in Asian countries. Improving the pesticide efficiency of UAV...
Currently, the utilization of unmanned aerial vehicles (UAVs) for spraying pesticides is a prevalent issue in Asian countries. Improving the pesticide efficiency of UAV spraying is a major challenge for researchers. One of the factors that affect the efficiency is the wetting property of the spraying solutions on crop leaves. Tank-mix adjuvants, which can modify the wetting ability of the solutions, are often used for foliar application. However, different types and concentrations of tank-mix adjuvants may have different impacts on the wetting properties of droplets. In this article, we investigated the effects of four tank-mix adjuvants, Beidatong (BDT), Velezia Pro (VP), Nongjianfei (NJF), and Lieying (LY), on the dynamic contact angle (CA) values of droplets on the adaxial surface of wheat leaves. We measured the dynamic CA values of various concentrations of each adjuvant solution and determined the optimal concentrations based on the CA values, droplet spreading time, and cost. The results showed that adding any of the four adjuvants decreased the CA values, but the patterns of decrease varied among them. The CAs of BDT and VP solutions decreased slowly during the observation time (0-8.13 s), while those of NJF and LY solutions decreased rapidly throughout the observation period. According to the dynamic CA values of different concentrations, the optimal concentrations of BDT, VP, NJF, and LY for wheat field application were 12%, 16%, 6‰, and 0.3‰, respectively. Alkoxy-modified polytrisiloxane adjuvant (LY) could be recommended as an appropriate tank-mix adjuvant for wheat field application, considering spreading efficiency and cost. This study provides theoretical and practical guidance for selecting and optimizing tank-mix adjuvants for UAV spraying.
Topics: Triticum; Pesticides; Wettability; Adjuvants, Pharmaceutic; Adjuvants, Immunologic; Plant Leaves
PubMed: 38025725
DOI: 10.7717/peerj.16464 -
Pain Research & Management 2022In patients with postherpetic neuralgia (PHN), the effectiveness of epidural block and the benefits of adjuvant hypertonic saline (HS) have not been fully determined.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In patients with postherpetic neuralgia (PHN), the effectiveness of epidural block and the benefits of adjuvant hypertonic saline (HS) have not been fully determined. Therefore, we investigated these issues in this study.
METHODS
At a tertiary medical center's single pain clinic in Seoul, Republic of Korea, patients complaining of PHN even after 4 months of herpes zoster onset were enrolled and randomly assigned to either the HS or normal saline (NS) group. After epidural block with adjuvant HS or NS administration according to each protocol, outcomes were assessed at baseline and one and three months after the intervention. The primary outcome was pain intensity on the numerical rating scale (NRS). The secondary outcomes were the insomnia severity index (ISI), the medication quantification scale (MQS), and the global perceived effect of satisfaction (GPES).
RESULTS
Thirty-six patients (NS: 17, HS: 19) were included in the intention-to-treat analysis. The estimated pain intensity decreased in both groups at one and three months after the procedure ( < 0.001), without a significant group difference. The estimated ISI and MQS were not significantly different at 1 month compared with baseline but significantly decreased at 3 months in each group ( < 0.001 and < 0.001, respectively), without group differences. In addition, there was no difference between the groups on the GPES scale at one and three months after the procedure.
CONCLUSIONS
Epidural steroid injection may have the advantages of short-term pain relief, improved sleep quality, and decreased medication usage in patients with PHN. In addition, adjuvant HS administration with epidural steroid injection did not show beneficial effects in patients with PHN. Further studies are needed to clarify the potential effectiveness of HS in treating neuropathic pain such as PHN. This trial is registered with KCT0002845.
Topics: Humans; Saline Solution; Neuralgia, Postherpetic; Adjuvants, Pharmaceutic; Anesthesia, Epidural; Steroids
PubMed: 36451915
DOI: 10.1155/2022/8081443 -
Scientific Reports Mar 2024To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment...
To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment (RRD). This retrospective and comparative study included patients who underwent SB with PR (n = 88) or SB alone (n = 161) for primary RRD. The primary anatomical success rate for SB with PR was 81.8%, whereas that for SB alone was 80.7% (P = 0.836). Among patients who achieved primary anatomical success, those in the SB with PR group showed postoperative epiretinal membrane (ERM) formation more frequently than those in the SB alone group (11 of 72 [15.3%] vs. 6 of 130 [4.6%]) (P = 0.009). The mean time to subretinal fluid absorption was not significantly different between the SB with PR and SB alone groups (11.2 ± 6.2 vs. 11.4 ± 5.8 months, P = 0.881). In the SB with PR group, retinal detachment involving ≥ three quadrants was a significant risk factor for surgical failure (hazard ratio, 3.04; P = 0.041). Adjuvant pneumatic retinopexy does not provide additional benefit in improving the surgical outcomes of SB for primary RRD repair.
Topics: Humans; Scleral Buckling; Retinal Detachment; Retrospective Studies; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 38438557
DOI: 10.1038/s41598-024-55999-2 -
International Journal of Molecular... Dec 2023Previous studies have shown that the in vivo administration of soil-derived bacteria with anti-inflammatory and immunoregulatory properties, such as NCTC 11659, can...
Previous studies have shown that the in vivo administration of soil-derived bacteria with anti-inflammatory and immunoregulatory properties, such as NCTC 11659, can prevent a stress-induced shift toward an inflammatory M1 microglial immunophenotype and microglial priming in the central nervous system (CNS). It remains unclear whether NCTC 11659 can act directly on microglia to mediate these effects. This study was designed to determine the effects of NCTC 11659 on the polarization of naïve BV-2 cells, a murine microglial cell line, and BV-2 cells subsequently challenged with lipopolysaccharide (LPS). Briefly, murine BV-2 cells were exposed to 100 µg/mL whole-cell, heat-killed NCTC 11659 or sterile borate-buffered saline (BBS) vehicle, followed, 24 h later, by exposure to 0.250 µg/mL LPS ( 0111: B4; = 3) in cell culture media vehicle (CMV) or a CMV control condition. Twenty-four hours after the LPS or CMV challenge, cells were harvested to isolate total RNA. An analysis using the NanoString platform revealed that, by itself, NCTC 11659 had an "adjuvant-like" effect, while exposure to LPS increased the expression of mRNAs encoding proinflammatory cytokines, chemokine ligands, the component of complement, and components of inflammasome signaling such as . Among LPS-challenged cells, NCTC 11659 had limited effects on differential gene expression using a threshold of 1.5-fold change. A subset of genes was assessed using real-time reverse transcription polymerase chain reaction (real-time RT-PCR), including , , , , , and . Based on the analysis using real-time RT-PCR, NCTC 11659 by itself again induced "adjuvant-like" effects, increasing the expression of , , and while decreasing the expression of . LPS by itself increased the expression of , , , , and while decreasing the expression of . Among LPS-challenged cells, NCTC 11659 enhanced LPS-induced increases in the expression of and , consistent with microglial priming. In contrast, among LPS-challenged cells, although NCTC 11659 did not fully prevent the effects of LPS relative to vehicle-treated control conditions, it increased mRNA expression, suggesting that NCTC 11659 induces an atypical microglial phenotype. Thus, NCTC 11659 acutely (within 48 h) induced immune-activating and microglial-priming effects when applied directly to murine BV-2 microglial cells, in contrast to its long-term anti-inflammatory and immunoregulatory effects observed on the CNS when whole-cell, heat-killed preparations of NCTC 11659 were given peripherally in vivo.
Topics: Animals; Mice; Microglia; Lipopolysaccharides; NLR Family, Pyrin Domain-Containing 3 Protein; Interleukin-6; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Anti-Inflammatory Agents; Cytomegalovirus Infections; Mycobacteriaceae
PubMed: 38203645
DOI: 10.3390/ijms25010474 -
Critical Care Medicine Sep 2018To employ metabolomics-based pathway and network analyses to evaluate the cerebrospinal fluid metabolome after severe traumatic brain injury in children and the capacity... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To employ metabolomics-based pathway and network analyses to evaluate the cerebrospinal fluid metabolome after severe traumatic brain injury in children and the capacity of combination therapy with probenecid and N-acetylcysteine to impact glutathione-related and other pathways and networks, relative to placebo treatment.
DESIGN
Analysis of cerebrospinal fluid obtained from children enrolled in an Institutional Review Board-approved, randomized, placebo-controlled trial of a combination of probenecid and N-acetylcysteine after severe traumatic brain injury (Trial Registration NCT01322009).
SETTING
Thirty-six-bed PICU in a university-affiliated children's hospital.
PATIENTS AND SUBJECTS
Twelve children 2-18 years old after severe traumatic brain injury and five age-matched control subjects.
INTERVENTION
Probenecid (25 mg/kg) and N-acetylcysteine (140 mg/kg) or placebo administered via naso/orogastric tube.
MEASUREMENTS AND MAIN RESULTS
The cerebrospinal fluid metabolome was analyzed in samples from traumatic brain injury patients 24 hours after the first dose of drugs or placebo and control subjects. Feature detection, retention time, alignment, annotation, and principal component analysis and statistical analysis were conducted using XCMS-online. The software "mummichog" was used for pathway and network analyses. A two-component principal component analysis revealed clustering of each of the groups, with distinct metabolomics signatures. Several novel pathways with plausible mechanistic involvement in traumatic brain injury were identified. A combination of metabolomics and pathway/network analyses showed that seven glutathione-centered pathways and two networks were enriched in the cerebrospinal fluid of traumatic brain injury patients treated with probenecid and N-acetylcysteine versus placebo-treated patients. Several additional pathways/networks consisting of components that are known substrates of probenecid-inhibitable transporters were also identified, providing additional mechanistic validation.
CONCLUSIONS
This proof-of-concept neuropharmacometabolomics assessment reveals alterations in known and previously unidentified metabolic pathways and supports therapeutic target engagement of the combination of probenecid and N-acetylcysteine treatment after severe traumatic brain injury in children.
Topics: Acetylcysteine; Adjuvants, Pharmaceutic; Adolescent; Brain Injuries, Traumatic; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Humans; Injury Severity Score; Metabolomics; Probenecid
PubMed: 29742587
DOI: 10.1097/CCM.0000000000003203 -
Frontiers in Immunology 2022With the development of laser technology in the 1960s, a technique was developed to inject intradermal vaccines immediately after irradiating the skin with laser light...
With the development of laser technology in the 1960s, a technique was developed to inject intradermal vaccines immediately after irradiating the skin with laser light to elicit an adjuvant effect, referred to as "laser adjuvant." We have been investigating the mechanism of laser adjuvant in influenza mouse models using noninvasive continuous-wave (CW) near-infrared (NIR) light mainly at a wavelength of 1064 nm, and have shown that the production of reactive-oxygen-species (ROS) in the skin and mast cells in the skin tissue plays an important role in the laser adjuvant effect. The new wavelength of 1270 nm NIR light is characterized by its ability to elicit the same vaccine adjuvant effect as other wavelengths at a lower energy, and may be suitable for clinical applications. In this study, we investigated the physiological activity of CW1270 nm NIR light in mast cells, its biological activity on mouse skin, and the durability of the vaccine adjuvant effect in influenza vaccine mouse models. We show that irradiation of mast cells with 1270 nm NIR light produced ROS and ATP, and irradiation of isolated mitochondria also produced ATP. In mouse skin, the relative expression levels of chemokine mRNAs, such as and , were increased by irradiation with 1270 and 1064 nm NIR light at minimum safe irradiance. However, the relative expression of was increased at 1064 nm, but not at 1270 nm. Serum anti-influenza IgG antibody titers increased early after immunization with 1064 nm, whereas with 1270 nm, there was not only an early response of antibody production but also persistence of antibody titers over the medium- to long-term. Thus, to our knowledge, we show for the first time that 1270 nm NIR light induces ROS and ATP production in mitochondria as photoreceptors, initiating a cascade of laser adjuvant effects for intradermal vaccines. Additionally, we demonstrate that there are wavelength-specific variations in the mechanisms and effects of laser adjuvants. In conclusion, CW1270 nm NIR light is expected to be clinically applicable as a novel laser adjuvant that is equivalent or superior to 1064 nm NIR light, because it can be operated at low energy and has a wavelength-specific adjuvant effect with medium- to long-lasting antibody titer.
Topics: Animals; Mice; Adjuvants, Vaccine; Reactive Oxygen Species; Infrared Rays; Influenza Vaccines; Adjuvants, Immunologic; Mitochondria; Adjuvants, Pharmaceutic; Adenosine Triphosphate
PubMed: 36439134
DOI: 10.3389/fimmu.2022.1028733 -
BioMed Research International 2014Cardiac surgery patients are now more risky in terms of age, comorbidities, and the need for complex procedures. It brings about reperfusion injury, which leads to... (Review)
Review
Cardiac surgery patients are now more risky in terms of age, comorbidities, and the need for complex procedures. It brings about reperfusion injury, which leads to dysfunction and/or loss of part of the myocardium. These groups of patients have a higher incidence of postoperative complications and mortality. One way of augmenting intraoperative myocardial protection is the phenomenon of myocardial conditioning, elicited with brief nonlethal episodes of ischaemia-reperfusion. In addition, drugs are being tested that mimic ischaemic conditioning. Such cardioprotective techniques are mainly focused on reperfusion injury, a complex response of the organism to the restoration of coronary blood flow in ischaemic tissue, which can lead to cell death. Extensive research over the last three decades has revealed the basic mechanisms of reperfusion injury and myocardial conditioning, suggesting its therapeutic potential. But despite the enormous efforts that have been expended in preclinical studies, almost all cardioprotective therapies have failed in the third phase of clinical trials. One reason is that evolutionary young cellular mechanisms of protection against oxygen handling are not very robust. Ischaemic conditioning, which is among these, is also limited by this. At present, the prevailing belief is that such options of treatment exist, but their full employment will not occur until subquestions and methodological issues with the transfer into clinical practice have been resolved.
Topics: Adjuvants, Pharmaceutic; Cardiac Surgical Procedures; Cardiotonic Agents; Clinical Trials as Topic; Humans; Ischemic Postconditioning; Treatment Outcome
PubMed: 25215293
DOI: 10.1155/2014/808096