•Immunization with MERS spike protein nanoparticles induced only Th2-biased response.•Heterologous prime-boost immunization induced both Th1 and Th2-biased responses.•Our vaccination strategy showed ...the protective effect against MERS-CoV.
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime–boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime–boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime–boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime–boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime–boost regimens did not. Thus, heterologous prime–boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime–boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.
The goal of the present study focused on the adverse reaction of contrast medium (CM) via the induction of inflammatory molecules in human umbilical vein endothelial cells (HUVECs). Ultravist-induced ...monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) gene expression was markedly increased in interleukin-4 (IL-4)-pretreated HUVECs in a time- and dose-dependent manner and was paralleled by concomitant production of MCP-1 and VCAM-1 proteins. MCP-1 and VCAM-1 gene expression by Ultravist in combination with IL-4 was mediated by the c-Jun N-terminal kinases (JNK1/2) signaling pathway. IL-4-pretreated Ultravist-stimulated HUVECs showed greatly increased migration and adhesion of THP-1 cells. Cell migration was decreased by treatment of CCR2 antagonist, and cell adhesion was also decreased by VCAM-1 blocking antibody. Furthermore, when tested in vivo under similar conditions, MCP-1 protein was significantly increased in Ultravist combined with IL-4-injected mice. Taken together, our findings suggest that MCP-1 blocking may be crucial in preventing the endothelial dysfunction induced by contrast medium in patients with inflammatory disease and atherosclerosis.
The high prevalence of cartilage diseases and limited treatment options create a significant biomedical burden. Due to the inability of cartilage to regenerate itself, introducing chondrocyte ...progenitor cells to the affected site is of significant interest in cartilage regenerative therapies. Tissue engineering approaches using human mesenchymal stem cells (MSCs) are promising due to their chondrogenic potential, but a comprehensive understanding of the mechanisms governing the fate of MSCs is required for precise therapeutic applications in cartilage regeneration. TGF-β is known to induce chondrogenesis by activating SMAD signaling pathway and upregulating chondrogenic genes such as SOX9; however, the epigenetic regulation of TGF-β-mediated chondrogenesis is not understood. In this report, we found that TGF-β dramatically induced the expression of KDM4B in MSCs. When KDM4B was overexpressed, chondrogenic differentiation was significantly enhanced while KDM4B depletion by shRNA led to a significant reduction in chondrogenic potential. Mechanistically, upon TGF-β stimulation, KDM4B was recruited to the SOX9 promoter, removed the silencing H3K9me3 marks, and activated the transcription of SOX9. Furthermore, KDM4B depletion reduced the occupancy of SMAD3 in the SOX9 promoter, suggesting that KDM4B is required for SMAD-dependent coactivation of SOX9. Our results demonstrate the critical role of KDM4B in the epigenetic regulation of TGF-β-mediated chondrogenic differentiation of MSCs. Since histone demethylases are chemically modifiable, KDM4B may be a novel therapeutic target in cartilage regenerative therapy.
Background and Purpose. Traditional medicine (TM) has been widely used in China (including the Taiwan region), Korea, and Japan. The purposes of this paper are to summarize the basic data on TM ...systems in these three countries and to compare them in terms of overall policy, education, and insurance. Methods. Government websites, national statistics, and authoritative papers from each country were fully searched. Further data were gathered by TM experts from each country. Results. China and Korea showed similar patterns in TM systems, whereas Japan showed different patterns. In China and Korea, TM was practiced in a dual system with conventional medicine (CM), and TM education was 6-year training programs on average for TM doctors, and acupuncture, moxibustion, and cupping were completely insured. Whereas, CM was dominant in Japan, and TM was practiced by each health care worker who has received different TM education respectively, and main TM therapies were partially insured. Conclusions. TM was developed similarly or somewhat differently based on differences in cultural background and national policies in East Asia. We cautiously propose that this study could contribute to the development of TM and also be used for reference in complementary and alternative medicine systems.
As the Korean society is aging rapidly, the issues on physical, social, economic, and mental disabilities of single-person households aged 65 years or older has also increased. This study aimed to ...investigate the nutrition-related dietary conditions of elderly people living alone and determine their dietary behavior by calculating the nutrition quotient for elderly (NQ-E). One hundred and three elderly people living alone who were basic living recipients were recruited from six senior welfare centers in Seoul, and the data were collected using a questionnaire from 19 July 2016 to 17 August 2016, with a 1:1 in-depth interview using the modified version of the NQ-E questionnaire. The data were analyzed using SPSS 27.0 for Mac (IBM Corp., Armonk, NY, USA); a p value of <0.05 was considered significant. The nutrition-related dietary conditions of the elderly living alone were limited, and many of them received support from the government, which helped improve their diet. The nutrition quotient score of the elderly living alone was 50.14, which was lower than the NQ-E mean score (57.6) of the Korean elderly and the NQ-E (62 points), which is the top 25% of the national survey subjects according to the criteria value presented by the Korean Nutrition Society. Elderly people living alone often have poor dietary habits and nutritional status. The NQ-E presented in this study can be used to evaluate the dietary conditions of the elderly and is expected to be used as an indicator for developing community programs for health promotion and evaluating their effectiveness.
We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive ...delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE.
Melatonin is an endogenous indoleamine that plays a significant role in various physiological processes, including the sleep-wake cycle, anxiety, immunity, and circadian rhythms. However, it is ...important to clarify that melatonin does not directly control circadian rhythms. Circadian rhythms are primarily synchronized by light, which acts on the suprachiasmatic nucleus (SCN) and subsequently regulates melatonin production. This light-mediated synchronization of circadian rhythms is essential for maintaining the alignment of the body with the light-dark cycle. In this study, we investigated the efficacy of melatonin administration during different times of the day or night and explored its neuroprotective effects. Furthermore, we aimed to apply these findings to rodent models of dementia, aging, and neuro-inflammation for potential therapeutic applications. Our study uncovered novel evidence suggesting the involvement of RNA-binding motif protein (RBM)-47 and Nrf2 in the signaling pathways associated with melatonin administration during both day and night. We examined the role of RBM47 in Nrf2 activity through siRNA or CRISPR-mediated knockdown experiments using hippocampal neuronal cells and lentivirus injections in mice. In 5xFAD/aging/neuroinflammatory mouse models, antioxidant effects were enhanced when melatonin was administered during the day compared to nighttime administration. Furthermore, mRNA analysis and molecular biology experiments revealed the differential expression of RBM47 depending on the timing of melatonin administration. These findings suggest that a decrease in RBM47 expression may improve the antioxidant defense system in the hippocampus. Consequently, administering melatonin during the day rather than at night may present a plausible therapeutic strategy as an antioxidant.
Display omitted
•RBM-47 and Nrf2 are involved in melatonin administration-associated pathways.•Daytime administration of melatonin increases antioxidant effects in mouse models.•RBM47 is differentially expressed depending on the time of melatonin administration.•Decreased RBM47 expression may improve the antioxidant defense system.•Melatonin administration during the day may serve as a therapeutic strategy.
Display omitted
•Polyhydroxyalkanoate (PHA) is a promising alternative to petrochemical-based plastics.•The incorporation of monomers such as 3HP, 3HHx, 4HV, 4HB, 5HV, and 6HHx in P(3HB) shows ...amorphous and elastomer properties.•Lignocellulosic biomass, Levulinic acid, Glycerol and Waste oil can be utilized as feedstocks for sustainable and inexpensive PHA production.•Metabolic engineering can contribute to the expansion of the PHA portfolio from renewable resources.
Petrochemical-based plastics cause environmental pollution and threaten humans and ecosystems. Polyhydroxyalkanoate (PHA) is considered a promising alternative to nondegradable plastics since it is eco-friendly and biodegradable polymer having similar properties to conventional plastics. PHA’s material properties are generally determined by composition and type of monomers in PHA. PHA can be designed in tailor-made manner for their suitable application areas. Among many monomers in PHAs, ω-hydroxalkanoates such as 3-hydroxypropionate (3HP), 4-hydroxybutyrate (4HB), 5-hydroxyvalerate (5HV), and 6-hydroxyhexanoate (6HHx) and medium-chain-length 3-hydroxyalkanoate such as 3-hydroxyhexanoate (3HHx) and 4-hydroxyvalerate (4HV), have been examined as potential monomers able to confer amorphous and elastomer properties when these are incorporated as comonomer in poly(3-hydroxybutyrate) copolymer that has 3HB as main monomer along with comonomers in different monomer fraction. Herein, recent advances in production of PHAs designed to have amorphous and elastomeric properties from renewable sources such as lignocellulose, levulinic acid, crude glycerol, and waste oil are discussed.
20-hydroxyecdysone (20E), a steroidal prohormone, is secreted from the prothoracic glands. While 20E has been shown to have neuroprotective effects in Parkinson's disease (PD) models in vitro, its ...effects have not yet been examined in vivo. We sought to assess the behavioral and mechanistic effects of 20E on MPTP-induced toxicity in mice. To this end, we used behavioral tests, stereological analyses of dopaminergic neurons by tyrosine hydroxylase immunohistochemistry, and assessments of apoptotic mechanisms, focusing on Nrf2 signaling through Western blotting and ELISA assays. A 20E treatment protected against MPTP-induced motor incoordination, postural imbalance, and bradykinesia, and significantly reduced dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) and the striatum (ST). It also attenuated dopamine deficiency in the ST, modulated levels of antioxidative enzymes superoxide dismutase, catalase, and glutathione in the SNpc, increased the Bcl-2/Bax ratio, and inhibited cytosolic cytochrome c release and caspase-9, -7, and -3 activity in the SNpc. These results indicated that 20E inhibited the apoptotic cascade. Furthermore, the attenuation of MPTP neurotoxicity was associated with inhibited cleaved-caspase signaling pathways, along with upregulated Nrf2 pathways in the SNpc, suggesting that 20E mitigates MPTP-induced neurotoxicity via mitochondria-mediated apoptosis by modulating anti-oxidative activities. Our results suggest that 20E can inhibit MPTP-induced behavioral and neurotoxic effects in mice. This lays the foundation for further research on 20E as a potential target for therapeutic use.
Display omitted
•The effects of 20-hydroxyecdysone in Parkinson's disease were assessed.•20E can inhibit MPTP-induced behavioral and neurotoxic effects.•20E may be a potential therapeutic target.
Multi‐valued logic (MVL) computing, which uses more than three logical states, is a promising future technology for handling huge amounts of data in the forthcoming “big data” era. The feasibility of ...MVL computing depends on the development of new concept devices/circuits beyond the complementary metal oxide semiconductor (CMOS) technology. This is because many CMOS devices are required to implement basic MVL functions, such as multilevel NOT, AND, and OR. In this study, a novel MVL device is reported with a complementarily controllable potential well, featuring the negative differential transconductance (NDT) phenomenon. This NDT device implemented on the WS2–graphene–WSe2 van der Waals heterostructure is evolved to a double‐NDT device operating on the basis of two consecutive NDT phenomena via structural engineering and parallel device configuration. This double‐NDT device is intensively analyzed via atomic force microscopy, kelvin probe force microscopy, Raman spectroscopy, and temperature‐dependent electrical measurement to gain a detailed understanding of its operating mechanism. Finally, the operation of a quaternary inverter configured with the double‐peak NDT device and a p‐channel transistor through Cadence circuit simulation is theoretically demonstrated.
The negative differential transconductance (NDT) device is implemented on the WS2–graphene–WSe2 van der Waals heterostructure. This NDT device is then expanded to the double peak NDT device by connecting two different NDT devices (type‐1 and type‐2) in parallel. A quaternary inverter configured with a double peak NDT device and a p‐channel transistor operates with four stable logic states.
PDF
