-
European Journal of Pharmaceutics and... Jun 2024Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not...
Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not ideal for compliance. The multiple doses could potentially be replaced by sustained or pulsatile release of antigens encapsulated in degradable microparticles (MPs). The efficacy of a vaccine is improved by adding an adjuvant, which can be co-delivered from the particles to enhance immunogenicity. Here, we developed degradable poly-lactic-co-glycolic acid (PLGA) (7-17 kDa) MPs capable of sustained release of ultraviolet killed influenza virus (A/PR/8/34) (kPR8) vaccine and the natural killer T (NKT) cell agonist alpha-galactosylceramide (α-GalCer) and tested their effectiveness at providing long-term protection against influenza virus infection in mice. Multiple formulations were developed for encapsulating the virus and adjuvant separately, and in combination. The MPs exhibited sustained release of both the virus and the adjuvant lasting more than a month. Co-encapsulation significantly increased the encapsulation efficiency (EE) of the vaccine but reduced the release duration. On the other hand, co-encapsulation led to a reduction in EE for the α-GalCer and a change in release profile to a higher initial burst followed by a linear release compared to a low initial burst and slower linear release. The α-GalCer also had considerably longer release duration compared to the vaccine. Mice injected with particle formulations co-encapsulating kPR8 and α-GalCer were protected from a lethal influenza virus infection 30 weeks after vaccination. This study demonstrates that PLGA MP based vaccines are promising for providing effective vaccination and possibly for replacing multiple doses with a single injection.
PubMed: 38876362
DOI: 10.1016/j.ejpb.2024.114365 -
Archives of Dermatological Research Jun 2024Ultraviolet-B (UV-B) radiation overexposure causes function impairment of epidermal stem cells (ESCs). We explored the mechanism of Annexin A1 (ANXA1) ameliorating...
Ultraviolet-B (UV-B) radiation overexposure causes function impairment of epidermal stem cells (ESCs). We explored the mechanism of Annexin A1 (ANXA1) ameliorating UV-B-induced ESC mitochondrial dysfunction/cell injury. ESCs were cultured in vitro and irradiated with different doses of UV-B. Cell viability/ANXA1 protein level were assessed. After oe-ANXA1 transfection, ESCs were treated with oe-ANXA1/UV-B irradiation/CCCP/CCG-1423/3-methyladenine for 12 h. Cell viability/death, and adenosine triphosphate (ATP)/reactive oxygen species (ROS) levels were determined. Mitochondrial membrane potential (MMP) changes/DNA (mtDNA) content/oxygen consumption and RhoA activation were assessed. ROCK1/p-MYPT1/MYPT1/(LC3BII/I)/Beclin-1/p62 protein levels were determined. Mitochondrial morphology was observed. Mito-Tracker Green (MTG) and LC3B levels were determined. UV-B irradiation decreased cell viability/ANXA1 expression in a dose-dependent manner. UV-B-treated ESCs exhibited reduced cell viability/ATP content/MMP level/mitochondrial respiratory control ratio/mtDNA number/RhoA activity/MYPT1 phosphorylation/MTGLC3B cells/(LC3BII/I) and Beclin-1 proteins, increased cell death/ROS/p62/IL-1β/IL-6/TNF-α expression, contracted mitochondrial, disappeared mitochondrial cristae, and increased vacuolar mitochondria, which were averted by ANXA1 overexpression, suggesting that UV-B induced ESC mitochondrial dysfunction/cell injury/inflammation by repressing mitophagy, but ANXA1 promoted mitophagy by activating the RhoA/ROCK1 pathway, thus repressing UV-B's effects. Mitophagy activation ameliorated UV-B-caused ESC mitochondrial dysfunction/cell injury/inflammation. Mitophagy inhibition partly diminished ANXA1-ameliorated UV-B's effects. Conjointly, ANXA1 promoted mitophagy by activating the RhoA/ROCK1 pathway, thereby improving UV-B-induced ESC mitochondrial dysfunction/cell injury.
Topics: Ultraviolet Rays; Mitochondria; Annexin A1; Cell Survival; Stem Cells; Humans; Membrane Potential, Mitochondrial; Reactive Oxygen Species; Epidermal Cells; Cells, Cultured
PubMed: 38874830
DOI: 10.1007/s00403-024-02875-8 -
Frontiers in Oncology 2024We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two...
PURPOSE
We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two courses of intensity modulated radiotherapy (IMRT) to provide more reliable dose-volume data reference to set the temporal lobe tolerance dose for recurrent NPC patients in the future.
METHODS AND MATERIALS
Recurrent NPC patients were randomly divided into training data set and validation data set in a ratio of 2:1, All the temporal lobes (TLs) were re-contoured as R/L structures and named separately in the MIM system. The dose distribution of the initial IMRT plan was deformed into the second course planning CT via MIM software to get the deformed dose. Equivalent dose of TLs in 2Gy fractions was calculated via linear quadratic model, using an α/β=3 for temporal lobes. NTCP model that correlated the irradiated volume of the temporal lobe and? the clinical variables were evaluated in a multivariate prediction model using AUC analysis.
RESULTS
From Jan. 2010 to Dec. 2020, 78 patients were enrolled into our study. Among which 26 (33.3%) developed TLI. The most important factors affecting TLI was the sum-dose d1.5cc of TL, while the possible clinical factors did not reach statistically significant differences in multivariate analysis. According to NTCP model, the TD5 and TD50 EQD2 dose of sum-dose d1.5cc were 65.26Gy (46.72-80.69Gy) and 125.25Gy (89.51-152.18Gy), respectively. For the accumulated EQD2 dose, the area under ROC shadow was 0.8702 (0.7577-0.9828) in model validation, p<0.001.
CONCLUSION
In this study, a NTCP model of temporal lobe injury after a second course of IMRT for recurrent nasopharyngeal carcinoma was established. TD5 and TD50 doses of temporal lobe injury after re-RT were obtained according to the model, and the model was verified by validation set data.
PubMed: 38873258
DOI: 10.3389/fonc.2024.1394111 -
Dental Materials : Official Publication... Jun 2024To investigate the transdentinal effects of surface reaction-type pre-reacted glass-ionomer (S-PRG) fillers on odontoblast-like cells.
OBJECTIVES
To investigate the transdentinal effects of surface reaction-type pre-reacted glass-ionomer (S-PRG) fillers on odontoblast-like cells.
METHODS
An eluate of S-PRG fillers was obtained by dissolving the particles in distilled water (1:1 m/v). Dentin discs with similar permeability were mounted into artificial pulp chambers and MDPC-23 cells were seeded on their pulpal surface. The occlusal surface was treated with (n = 10): ultrapure water (negative control - NC), hydrogen peroxide (positive control - PC), S-PRG eluate exposure for 1 min (S-PRG 1 min), or S-PRG filler eluate exposure for 30 min (S-PRG 30 min). After 24 h, cell viability (alamarBlue) and morphology (SEM) were evaluated. The extract obtained from transdentinal diffusion was applied to MDPC-23 pre-cultured in plates for another 24 h to evaluate viability (alamarBlue, 1, 3, and 7 days), gene expression of Col1a1, Alpl, Dspp, and Dmp1 (RT-qPCR, 1 and 7 days), and mineralization (Alizarin Red, 7 days). Data were analyzed with ANOVA (α = 5 %).
RESULTS
While S-PRG 1 min did not differ from NC, S-PRG 30 min reduced 17.9 % viability of cells from discs. S-PRG treatments resulted in low cell detaching from dentin, and the remaining cells exhibited typical morphology or minor cytoplasmic contraction. S-PRG 30 min slightly increased cell viability (6 %) 1 day after contact with the extract. S-PRG treatments upregulated the expression of the investigated genes, especially after 1 day. S-PRG 30 min stimulated mineralization activity by 39.7 %.
CONCLUSIONS
S-PRG filler eluate does not cause transdentinal cytotoxicity on odontoblast-like cells, and long-term exposure can stimulate their dentinogenic-related mineralization activity.
SIGNIFICANCE
The transdentinal elution of ions from S-PRG fillers is not expected to be harmful to the dental pulp and may exert bioactive effects by inducing dentin matrix deposition through the metabolism of underlying odontoblasts.
PubMed: 38871524
DOI: 10.1016/j.dental.2024.06.002 -
Clinical Oral Investigations Jun 2024The purpose of this study is to evaluate the bond strength of different computer-aided design / computer-aided manufacturing (CAD/CAM) hybrid ceramic materials following...
OBJECTIVES
The purpose of this study is to evaluate the bond strength of different computer-aided design / computer-aided manufacturing (CAD/CAM) hybrid ceramic materials following different pretreatments.
METHODS
A total of 306 CAD/CAM hybrid material specimens were manufactured, n = 102 for each material (VarseoSmile Crown [VSCP] by 3D-printing; Vita Enamic [VE] and Grandio Blocs [GB] by milling). Each material was randomly divided into six groups regarding different pretreatment strategies: control, silane, sandblasting (50 μm aluminum oxide particles), sandblasting + silane, etching (9% hydrofluorics acid), etching + silane. Subsequently, surface roughness (Ra) values, surface free energy (SFE) were measured. Each specimen was bonded with a dual-cured adhesive composite. Half of the specimens were subjected to thermocycling (5000 cycles, 5-55 °C). The shear bond strength (SBS) test was performed. Data were analyzed by using a two-way analysis of variance, independent t-test, and Mann-Whitney-U-test (α = 0.05).
RESULTS
Material type (p = 0.001), pretreatment strategy (p < 0.001), and the interaction (p < 0.001) all had significant effects on Ra value. However, only etching on VSCP and VE surface increased SFE value significantly. Regarding SBS value, no significant difference was found among the three materials (p = 0.937), while the pretreatment strategy significantly influenced SBS (p < 0.05). Etching on VSCP specimens showed the lowest mean value among all groups, while sandblasting and silane result in higher SBS for all test materials.
CONCLUSIONS
The bond strength of CAD/CAM hybrid ceramic materials for milling and 3D-printing was comparable. Sandblasting and silane coupling were suitable for both millable and printable materials, while hydrofluoric etching should not be recommended for CAD/CAM hybrid ceramic materials.
CLINICAL RELEVANCE
Since comparable evidence between 3D-printable and millable CAD/CAM dental hybrid materials is scarce, the present study gives clear guidance for pretreatment planning on different materials.
Topics: Surface Properties; Computer-Aided Design; Dental Bonding; Crowns; Materials Testing; Dental Stress Analysis; Shear Strength; Ceramics; Silanes; Dental Materials; Dental Etching; Dental Porcelain; In Vitro Techniques; Humans
PubMed: 38869697
DOI: 10.1007/s00784-024-05767-3 -
Dalton Transactions (Cambridge, England... Jun 2024We investigated the possibility of synthesizing Co nanoparticles in CoZrH/AlO(OH)/Al ceramic-metal catalysts and controlling the catalytic properties of these...
We investigated the possibility of synthesizing Co nanoparticles in CoZrH/AlO(OH)/Al ceramic-metal catalysts and controlling the catalytic properties of these nanoparticles in syngas conversion by changing the Co/Zr ratio. The CoZr nanocomposites were obtained from metal powders by mechanochemical activation in a high-energy mill under an argon atmosphere, followed by treatment with hydrogen at high pressure and room temperature. Ceramic-metal catalysts were prepared by mixing the corresponding CoZrH powder nanocomposite (30 wt%) with powdered aluminum (70 wt%), hydrothermal treatment of the mixture and subsequent calcination. The materials were characterized with a set of physicochemical methods: powder X-ray diffraction, scanning electron microscopy, Co internal field nuclear magnetic resonance spectroscopy, and temperature programmed reduction. Catalytic studies were performed in a laboratory fixed-bed flow reactor at 2 MPA and 210-270 °C. It is shown that the activity in syngas conversion to C hydrocarbons and selectivity to methane and C-C hydrocarbons depend on the Co/Zr ratio. Thus, with an increase in the zirconium content in the samples, the interaction of metal cobalt with metal zirconium improves in the process of mechanical activation and subsequent treatment with hydrogen. The destruction of the agglomerates of crystallites of metallic cobalt in the form of β-Co (Co) occurs as well as their transformation to α-Co (Co) particles active in the syngas conversion to C hydrocarbons. This can explain the highest specific yield of C hydrocarbons on a cermet with the lowest Co/Zr ratio.
PubMed: 38869457
DOI: 10.1039/d4dt00960f -
Journal of Virology Jun 2024Alpha herpesvirus (α-HV) particles enter their hosts from mucosal surfaces and efficiently maintain fast transport in peripheral nervous system (PNS) axons to establish...
Alpha herpesvirus (α-HV) particles enter their hosts from mucosal surfaces and efficiently maintain fast transport in peripheral nervous system (PNS) axons to establish infections in the peripheral ganglia. The path from axons to distant neuronal nuclei is challenging to dissect due to the difficulty of monitoring early events in a dispersed neuron culture model. We have established well-controlled, reproducible, and reactivateable latent infections in compartmented rodent neurons by infecting physically isolated axons with a small number of viral particles. This system not only recapitulates the physiological infection route but also facilitates independent treatment of isolated cell bodies or axons. Consequently, this system enables study not only of the stimuli that promote reactivation but also the factors that regulate the initial switch from productive to latent infection. Adeno-associated virus (AAV)-mediated expression of herpes simplex-1 (HSV-1) VP16 alone in neuronal cell bodies enabled the escape from silencing of incoming pseudorabies virus (PRV) genomes. Furthermore, the expression of HSV VP16 alone reactivated a latent PRV infection in this system. Surprisingly, the expression of PRV VP16 protein supported neither PRV escape from silencing nor reactivation. We compared transcription transactivation activity of both VP16 proteins in primary neurons by RNA sequencing and found that these homolog viral proteins produce different gene expression profiles. AAV-transduced HSV VP16 specifically induced the expression of proto-oncogenes including c-Jun and Pim2. In addition, HSV VP16 induces phosphorylation of c-Jun in neurons, and when this activity is inhibited, escape of PRV silencing is dramatically reduced.IMPORTANCEDuring latency, alpha herpesvirus genomes are silenced yet retain the capacity to reactivate. Currently, host and viral protein interactions that determine the establishment of latency, induce escape from genome silencing or reactivation are not completely understood. By using a compartmented neuronal culture model of latency, we investigated the effect of the viral transcriptional activator, VP16 on pseudorabies virus (PRV) escape from genome silencing. This model recapitulates the physiological infection route and enables the study of the stimuli that regulate the initial switch from a latent to productive infection. We investigated the neuronal transcriptional activation profiles of two homolog VP16 proteins (encoded by HSV-1 or PRV) and found distinct gene activation signatures leading to diverse infection outcomes. This study contributes to understanding of how alpha herpesvirus proteins modulate neuronal gene expression leading to the initiation of a productive or a latent infection.
PubMed: 38869285
DOI: 10.1128/jvi.00561-24 -
Allergy Jun 2024The updated World Health Organization (WHO) air quality guideline recommends an annual mean concentration of fine particulate matter (PM2.5) not exceeding 5 or...
Comprehensive analysis of resilience of human airway epithelial barrier against short-term PM2.5 inorganic dust exposure using in vitro microfluidic chip and ex vivo human airway models.
BACKGROUND AND OBJECTIVE
The updated World Health Organization (WHO) air quality guideline recommends an annual mean concentration of fine particulate matter (PM2.5) not exceeding 5 or 15 μg/m in the short-term (24 h) for no more than 3-4 days annually. However, more than 90% of the global population is currently exposed to daily concentrations surpassing these limits, especially during extreme weather conditions and due to transboundary dust transport influenced by climate change. Herein, the effect of respirable
METHODS
Silica particles at an average size of 1 μm, referred to as
RESULTS
In the AEB-on-a-chip platform, short-term exposure to 800 μg/mL PM2.5 disrupted AEB integrity via increasing barrier permeability, decreasing cell adhesion-barrier markers such as ZO-1, Vinculin, ACE2, and CD31, impaired cell viability and increased the expression levels of proinflammatory markers; IFNs, IL-6, IL-1s, TNF-α, CD68, CD80, and Inos, mostly under dynamic conditions. Besides, decreased tissue viability, impaired tissue integrity via decreasing of Vinculin, ACE2, β-catenin, and E-cadherin, and also proinflammatory response with elevated CD68, IL-1α, IL-6, IFN-Ɣ, Inos, and CD80 markers, were observed after PM2.5 exposure in ex vivo tissue.
CONCLUSION
The duration and concentration of PM2.5 that can be exposed during extreme weather conditions and natural events aligns with our exposure model (0-800 μg/mL 72 h). At this level of exposure, the resilience of the epithelial barrier is demonstrated by both AEB-on-a-chip platform emulating dynamic forces in the body and ex vivo bronchial biopsy slices. Lung-on-a-chip models will serve as reliable exposure models in this context.
PubMed: 38868934
DOI: 10.1111/all.16179 -
Scientific Reports Jun 2024The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation...
The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; and immediately prior to the euthanasia of moribund (preterminal) animals). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. The primary objective was to determine if the radiation-induced expression of specific proteins could serve as an early predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a complex temporal response in which some features exhibit upregulation while others trend downward. These statistically significantly altered features varied from pre-irradiation levels by as much as tenfold. Specifically, we found the expression of integrin alpha and thrombospondin correlated in peripheral blood with the preterminal stage. The differential expression of these proteins implicates dysregulation of biological processes such as hemostasis, inflammation, and immune response that could be leveraged for mitigating radiation-induced adverse effects.
Topics: Animals; Macaca mulatta; Gamma Rays; Male; Proteomics; Biomarkers; Whole-Body Irradiation; Acute Radiation Syndrome; Blood Proteins; Proteome
PubMed: 38866887
DOI: 10.1038/s41598-024-64316-w -
Journal of Environmental Radioactivity Jun 2024Fertilizers play a key role in increasing crop yield per unit land answering the growing demand for food production. However, excessive or improper use of fertilizers...
Fertilizers play a key role in increasing crop yield per unit land answering the growing demand for food production. However, excessive or improper use of fertilizers can lead to several environmental issues including soil contamination. One of the known contaminants attributed to fertilizers are radionuclides. The goal of this study was to determine the concentration of thorium isotopes in several types of commonly used fertilizers produced in Poland. The methodology included the use of an alternative tracer (namely Th) to evaluate chemical recovery. The correctness of the proposed method was confirmed by analyzing certified reference materials. The obtained results showed that the activity concentration of Th was ranged from <0.34 Bq kg for nitrogenous fertilizer up to 97 ± 22 Bq kg for pure phosphate fertilizer.
PubMed: 38865831
DOI: 10.1016/j.jenvrad.2024.107480