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1.
NPJ Vaccines ; 9(1): 34, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38360752

ABSTRACT

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

2.
NPJ Vaccines ; 8(1): 167, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37907507

ABSTRACT

We developed a promising mRNA vaccine against severe fever with thrombocytopenia syndrome (SFTS), an infectious disease caused by the SFTS virus that is primarily transmitted through tick bites. Administration of lipid nanoparticle-encapsulated mRNA-Gn successfully induced neutralizing antibodies and T-cell responses in mice. The vaccinated mice were protected against a lethal SFTS virus challenge, suggesting that this mRNA vaccine may be an effective and successful SFTS vaccine candidate.

3.
Chem Sci ; 14(39): 10644-10663, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37829040

ABSTRACT

This perspective paper comprehensively explores recent electrochemical studies on layered transition metal oxides (LTMO) in aqueous media and specifically encompasses two topics: catalysis of the oxygen evolution reaction (OER) and cathodes of aqueous lithium-ion batteries (LiBs). They involve conflicting requirements; OER catalysts aim to facilitate water dissociation, while for cathodes in aqueous LiBs it is essential to suppress water dissociation. The interfacial reactions taking place at the LTMO in these two distinct systems are of particular significance. We show various strategies for designing LTMO materials for each desired aim based on an in-depth understanding of electrochemical interfacial reactions. This paper sheds light on how regulating the LTMO interface can contribute to efficient water splitting and economical energy storage, all with a single material.

4.
Open Vet J ; 13(6): 705-714, 2023 06.
Article in English | MEDLINE | ID: mdl-37545702

ABSTRACT

Background: In the porcine industry, Escherichia coli (E. coli) infections have been causing post-weaning diarrhea (PWD) and edema disease (ED) for many years. It is classified into pathotypes and serotypes in animals according to virulence factors. Serotyping is performed for O, K, H, and F antigens, essential for discriminating pathogenicity and epidemiology. Furthermore, E. coli strains that produce F18 fimbriae are major sources of ED and PWD associated with Shiga-toxin producing E. coli (STEC) expressing F18ab and enterotoxigenic E. coli (ETEC) expressing F18ac, respectively. Aim: To investigate the pathogenicity potential and infection characteristics of experimental infection and confirm the pathological features of the Korean STEC/ETEC strains F18ab and F18ac in piglets. Methods: Three-week-old pigs were randomized into three experimental groups: infected G1 (F18ab), infected G2 (F18ac), and G3 (control). General health status was monitored daily, and pathological changes were evaluated. Results: Diarrhea occurred in all infected piglets. Pathological changes were only observed in the small intestine and regional lymph nodes. In G1, mucosal necrosis, inflammatory cell infiltration with hemorrhagic lesions, and apoptotic cell death in the tunica media of arterioles in the small intestine were observed. In contrast, the mucosa and epithelium appeared almost intact, with no abnormal vessel lesions in G2. Conclusion: Both strains, isolated from pigs in Korea, could be infected and did not spread from the alimentary tract to other organs. The pathological features were quite different among the F18 subtypes. The F18ab strain was more virulent than F18ac, and the virulence characteristics of the F18ac strain were more similar to ETEC than STEC.


Subject(s)
Enterotoxigenic Escherichia coli , Escherichia coli Infections , Shiga-Toxigenic Escherichia coli , Swine Diseases , Animals , Diarrhea/veterinary , Escherichia coli Infections/epidemiology , Escherichia coli Infections/veterinary , Feces , Republic of Korea/epidemiology , Swine , Swine Diseases/epidemiology
5.
JACS Au ; 3(5): 1392-1402, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37234123

ABSTRACT

The incompatibility of lithium intercalation electrodes with water has impeded the development of aqueous Li-ion batteries. The key challenge is protons which are generated by water dissociation and deform the electrode structures through intercalation. Distinct from previous approaches utilizing large amounts of electrolyte salts or artificial solid-protective films, we developed liquid-phase protective layers on LiCoO2 (LCO) using a moderate concentration of 0.5∼3 mol kg-1 lithium sulfate. Sulfate ion strengthened the hydrogen-bond network and easily formed ion pairs with Li+, showing strong kosmotropic and hard base characteristics. Our quantum mechanics/molecular mechanics (QM/MM) simulations revealed that sulfate ion paired with Li+ helped stabilize the LCO surface and reduced the density of free water in the interface region below the point of zero charge (PZC) potential. In addition, in situ electrochemical surface-enhanced infrared absorption spectroscopy (SEIRAS) proved the appearance of inner-sphere sulfate complexes above the PZC potential, serving as the protective layers of LCO. The role of anions in stabilizing LCO was correlated with kosmotropic strength (sulfate > nitrate > perchlorate > bistriflimide (TFSI-)) and explained better galvanostatic cyclability in LCO cells.

6.
Immunotherapy ; 15(3): 149-161, 2023 02.
Article in English | MEDLINE | ID: mdl-36748363

ABSTRACT

Aim: Comparing pharmacokinetics and safety of CT-P17 and EU-approved reference adalimumab (EU-adalimumab) in Japan. Materials & methods: Double-blind, parallel-group phase I trial at three hospitals. Healthy Japanese adults were randomized (1:1) to CT-P17 or EU-adalimumab (single 40-mg subcutaneous dose). The primary end point was pharmacokinetic equivalence for area under the concentration-time curve from time zero to infinity and maximum serum concentration. Results: Of the 205 randomized subjects (102 CT-P17, 103 EU-adalimumab), 204 received study drug. CT-P17 and EU-adalimumab were pharmacokinetically equivalent: 90% CIs for geometric least-squares mean ratios were within predefined 80-125% equivalence margins. Secondary pharmacokinetic end points, safety and immunogenicity were similar between the groups. Conclusion: CT-P17 had pharmacokinetics, safety and immunogenicity comparable to EU-adalimumab in healthy Japanese adults.


CT-P17 is a biosimilar that has been determined by the EMA to be highly similar to adalimumab. CT-P17 is approved to treat the same inflammatory conditions as reference adalimumab. CT-P17 is formulated at a high concentration (40 mg/0.4 ml) and may be associated with less injection-site pain than the original lower-concentration formulation of the reference product. In this study, healthy Japanese adults were given a single dose of either CT-P17 or EU-approved reference adalimumab. Pharmacokinetics (drug absorption, distribution, metabolism and excretion), safety and immunogenicity (occurrence of immune response to the drug) were comparable between the two groups. Previous studies with CT-P17 did not take place in Japan. These results support applying the conclusions regarding CT-P17 biosimilarity from other studies to the Japanese population.


Subject(s)
Adalimumab , Biosimilar Pharmaceuticals , East Asian People , Adult , Humans , Adalimumab/pharmacokinetics , Adalimumab/therapeutic use , Area Under Curve , Biosimilar Pharmaceuticals/pharmacokinetics , Biosimilar Pharmaceuticals/therapeutic use , Double-Blind Method , Healthy Volunteers , Therapeutic Equivalency , Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Monoclonal, Humanized/therapeutic use
7.
J Vet Sci ; 23(5): e75, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36174979

ABSTRACT

BACKGROUND: Since 2013, the number of requests for diagnosis for horses based on neurological symptoms has increased rapidly in South Korea. The affected horses have commonly exhibited symptoms of acute seasonal hindlimb ataxia. A previous study from 2015-2016 identified Setaria digitata as the causative agent. OBJECTIVES: This study is an epidemiological investigation to find out risk factors related to the rapid increase in hindlimb ataxia of horses due to aberrant parasites in South Korea. METHODS: An epidemiological investigation was conducted on 155 cohabiting horses in 41 horse ranches where the disease occurred. The surrounding environment was investigated at the disease-causing horse ranches (n = 41) and 20, randomly selected, non-infected ranches. RESULTS: Hindlimb ataxia was confirmed in nine cohabiting horses; this was presumed to be caused by ectopic parasitism. Environments that mosquitoes inhabit, such as paddy fields within 2 km and less than 0.5 km from a river, had the greatest association with disease occurrence. CONCLUSIONS: Most horse ranches in South Korea are situated in favorable environments for mosquitoes. Moreover, the number of mosquitoes in the country has increased since 2013 due to climate change. Additional research is required; however, these data show that it is necessary to establish guidelines for the use of anthelmintic agents based on local factors in South Korea and disinfection of the environment to prevent disease outbreaks.


Subject(s)
Ataxia , Horse Diseases , Animals , Ataxia/veterinary , Disease Outbreaks/veterinary , Hindlimb , Horse Diseases/epidemiology , Horses , Republic of Korea/epidemiology
8.
Front Mol Biosci ; 9: 821137, 2022.
Article in English | MEDLINE | ID: mdl-35281271

ABSTRACT

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. In the context of viral infections, small non-coding RNAs (sncRNAs) are known to play important roles in regulating the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we found that sncRNA profiles in human nasopharyngeal swabs (NPS) samples are significantly impacted by SARS-CoV-2. Among impacted sncRNAs, tRFs are the most significantly affected and most of them are derived from the 5'-end of tRNAs (tRF5). Such a change was also observed in SARS-CoV-2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several small virus-derived ncRNAs (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3'-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

9.
BMC Complement Med Ther ; 22(1): 6, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-34983480

ABSTRACT

BACKGROUND: Quercus acuta Thunb. (Fagaceae) or Japanese evergreen oak is cultivated as an ornamental plant in South Korea, China, Japan, and Taiwan and used in traditional medicine. The acorn or fruit of Quercus acuta Thunb. (QAF) is the main ingredient of acorn jelly, a traditional food in Korea. Its leaf was recently shown to have potent xanthine oxidase inhibitory and anti-hyperuricemic activities; however, there have been no studies on the biological activity of QAF extracts. Solar ultraviolet light triggers photoaging of the skin, which increases the production of reactive oxygen species (ROS) and expression of matrix metalloproteinase (MMPs), and destroys collagen fibers, consequently inducing wrinkle formation. The aim of this study was to investigate the effect of water extracts of QAF against UVB-induced skin photoaging and to elucidate the underlying molecular mechanisms in human keratinocytes (HaCaT). METHODS: In this study, we used HPLC to identify the major active components of QAF water extracts. Anti-photoaging effects of QAF extracts were evaluated by analyzing ROS procollagen type I in UVB-irradiated HaCaT keratinocytes. Antiradical activity was determined using 2,2-diphenyl-1-picrylhydrazyl and 2,20-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) assays. The expression of MMP-1 was tested by western blotting and ELISA kits. QAF effects on phosphorylation of the MAPK (p38, JNK, and ERK) pathway and transcription factor AP-1, which enhances the expression of MMPs, were analyzed by western blots. RESULTS: We identified two major active components in QAF water extracts, gallotannic acid and ellagic acid. The QAF aqueous extracts recovered UVB-induced cell toxicity and reduced oxidative stress by inhibiting intracellular ROS generation in HaCaT cells. QAF rescued UVB-induced collagen degradation by suppressing MMP-1 expression. The anti-photoaging activities of QAF were associated with the inhibition of UVB-induced phosphorylation of extracellular signal-regulated kinase (ERK) and activator protein 1 (AP-1). Our findings indicated that QAF prevents UVB-induced skin damage due to collagen degradation and MMP-1 activation via inactivation of the ERK/AP-1 signaling pathway. Overall, this study strongly suggests that QAF exerts anti-skin-aging effects and is a potential natural biomaterial that inhibits UVB-induced photoaging. CONCLUSION: These results show that QAF water extract effectively prevents skin photoaging by enhancing collagen deposition and inhibiting MMP-1 via the ERK/AP-1 signaling pathway.


Subject(s)
Extracellular Signal-Regulated MAP Kinases/pharmacology , Keratinocytes/drug effects , Quercus/metabolism , Signal Transduction , Skin Aging/drug effects , Transcription Factor AP-1/pharmacology , Ultraviolet Rays/adverse effects , Humans , Plant Extracts/pharmacology
10.
Perspect Psychiatr Care ; 58(4): 1959-1966, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34961939

ABSTRACT

PURPOSE: To investigate the influence of grit on academic burnout, clinical practice burnout, and job-seeking stress in nursing students. DESIGN AND METHODS: The participants were 302 nursing students. Data were collected from May to August 2019 using structured questionnaires for this descriptive study. FINDINGS: A statistically significant, negative correlation was found between grit and academic burnout, clinical practice burnout, and job-seeking stress (p < 0.001). The high-grit group revealed lower probability of burnout and stress scores than the low-grit group: odds ratio (OR) = 6.051, OR = 3.621, OR = 3.302, respectively (p < 0.001). PRACTICE IMPLICATIONS: Grit can help reduce academic burnout, clinical practice burnout, and job-seeking stress for nursing students.


Subject(s)
Burnout, Professional , Occupational Stress , Students, Nursing , Humans , Surveys and Questionnaires
11.
Chem Rev ; 122(5): 5165-5208, 2022 03 09.
Article in English | MEDLINE | ID: mdl-34767350

ABSTRACT

Smart materials can respond to stimuli and adapt their responses based on external cues from their environments. Such behavior requires a way to transport energy efficiently and then convert it for use in applications such as actuation, sensing, or signaling. Ultrasound can carry energy safely and with low losses through complex and opaque media. It can be localized to small regions of space and couple to systems over a wide range of time scales. However, the same characteristics that allow ultrasound to propagate efficiently through materials make it difficult to convert acoustic energy into other useful forms. Recent work across diverse fields has begun to address this challenge, demonstrating ultrasonic effects that provide control over physical and chemical systems with surprisingly high specificity. Here, we review recent progress in ultrasound-matter interactions, focusing on effects that can be incorporated as components in smart materials. These techniques build on fundamental phenomena such as cavitation, microstreaming, scattering, and acoustic radiation forces to enable capabilities such as actuation, sensing, payload delivery, and the initiation of chemical or biological processes. The diversity of emerging techniques holds great promise for a wide range of smart capabilities supported by ultrasound and poses interesting questions for further investigations.


Subject(s)
Smart Materials
12.
Microorganisms ; 11(1)2022 Dec 30.
Article in English | MEDLINE | ID: mdl-36677388

ABSTRACT

Downer cow can be caused by muscular paralysis, neurological damage, metabolic disorder, and/or the complication of microbial infection. However, downer cow with unknown etiology is issued because of the non-detection of its bacterial etiological agent. In this study, differences in the bacterial community in brain tissues between downer cattle with unknown etiology and healthy slaughtered cattle are investigated. Bacterial diversity and representative genera between downer and normal cattle were significantly different (p < 0.05). There are significant differences in representative genera of downer and normal cattle, especially the significance, fold change, and area under the receiver operating characteristic curve score (p < 0.05). Furthermore, the prediction of functional genes in brain microbiota between the downer and normal cattle revealed differences in the cluster of orthologous gene categories, such as lipid transport and metabolism, secondary metabolite biosynthesis, and signal transduction (p < 0.05). This study revealed a significant difference in microbiota between the downer and normal cattle. Thus, we demonstrate that representative genera from downer cattle through 16S rRNA gene amplicon sequencing and microbiota analysis have the potential as candidates for bacterial etiological agents for downer cow.

13.
Viruses ; 15(1)2022 12 24.
Article in English | MEDLINE | ID: mdl-36680097

ABSTRACT

tRNA-derived RNA fragments (tRFs) are a recently discovered family of small noncoding RNAs (sncRNAs). We previously reported that respiratory syncytial virus (RSV) infection induces functional tRFs, which are derived from a limited subset of parent tRNAs, in airway epithelial cells. Such induction is also observed in nasopharyngeal wash samples from RSV patients and correlates to RSV genome copies, suggesting a clinical significance of tRFs in RSV infection. This work also investigates whether the modification of parent tRNAs is changed by RSV to induce tRFs, using one of the most inducible tRFs as a model. We discovered that RSV infection changed the methylation modification of adenine at position 57 in tRNA glutamic acid, with a codon of CTC (tRNA-GluCTC), and the change is essential for its cleavage. AlkB homolog 1, a previously reported tRNA demethylase, appears to remove methyladenine from tRNA-GluCTC, prompting the subsequent production of tRFs from the 5'-end of tRNA-GluCTC, a regulator of RSV replication. This study demonstrates for the first time the importance of post-transcriptional modification of tRNAs in tRF biogenesis following RSV infection, providing critical insights for antiviral strategy development.


Subject(s)
RNA, Small Untranslated , Respiratory Syncytial Virus Infections , Humans , Respiratory Syncytial Virus Infections/genetics , RNA, Transfer/genetics , RNA, Small Untranslated/genetics , Epithelial Cells
14.
Front Immunol ; 12: 757758, 2021.
Article in English | MEDLINE | ID: mdl-34733289

ABSTRACT

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children. It is also a significant contributor to upper respiratory tract infections, therefore, a major cause for visits to the pediatrician. High morbidity and mortality are associated with high-risk populations including premature infants, the elderly, and the immunocompromised. However, no effective and specific treatment is available. Recently, we discovered that an exchange protein directly activated by cyclic AMP 2 (EPAC2) can serve as a potential therapeutic target for RSV. In both lower and upper epithelial cells, EPAC2 promotes RSV replication and pro-inflammatory cytokine/chemokine induction. However, the overall role of EPAC2 in the pulmonary responses to RSV has not been investigated. Herein, we found that EPAC2-deficient mice (KO) or mice treated with an EPAC2-specific inhibitor showed a significant decrease in body weight loss, airway hyperresponsiveness, and pulmonary inflammation, compared with wild-type (WT) or vehicle-treated mice. Overall, this study demonstrates the critical contribution of the EPAC2-mediated pathway to airway diseases in experimental RSV infection, suggesting the possibility to target EPAC2 as a promising treatment modality for RSV.


Subject(s)
Guanine Nucleotide Exchange Factors/physiology , Respiratory Syncytial Virus Infections/physiopathology , Airway Obstruction/etiology , Animals , Cyclic AMP/physiology , Cytokines/biosynthesis , Cytokines/genetics , Granulocyte Colony-Stimulating Factor/biosynthesis , Granulocyte Colony-Stimulating Factor/genetics , Guanine Nucleotide Exchange Factors/antagonists & inhibitors , Guanine Nucleotide Exchange Factors/deficiency , Inflammation , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Respiratory Hypersensitivity/etiology , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Viruses/physiology , Specific Pathogen-Free Organisms , Virus Replication , Weight Loss
15.
Healthcare (Basel) ; 9(9)2021 Sep 03.
Article in English | MEDLINE | ID: mdl-34574931

ABSTRACT

The purpose of this study was to investigate the relationship between nursing students' acceptance intention of a smart device, information literacy, and problem-solving confidence to explore the factors that may improve nursing students' problem-solving confidence. Data were collected from 450 nursing students between July and August 2019 in two cities in Korea. The results showed that there is a positive correlation between problem-solving confidence and acceptance intention (r = 0.353, p < 0.001) and between problem-solving confidence and information literacy (r = 0.501, p < 0.001). Further, participants with high acceptance intention of a smart device and information literacy scores had significantly higher problem-solving confidence (t = 5.447, p < 0.001; t = 10.072, p < 0.001) than participants with low acceptance intention. In addition, in the logistic regression the odds ratio between the acceptance intention of a smart device, information literacy, and problem-solving confidence groups was odds ratio 2.071 (p < 0.001, CI: 1.412-3.037) and odd ratio 4.966 (p < 0.001, CI: 3.298-7.477). To improve nursing students' problem-solving confidence, educational strategies should be developed to build information experience and information utilization capabilities.

16.
Front Vet Sci ; 8: 673820, 2021.
Article in English | MEDLINE | ID: mdl-34422940

ABSTRACT

In South Korea, domestic cattle, pigs, and goats were subjected to mandatory foot-and-mouth disease (FMD) vaccination and year-round serosurveillance since 2011. In 2020, approximately USD 95 million was spent solely for FMD vaccine purchase for 59 million livestock, and 1.25 million samples were tested to estimate the population immunity and demonstrate the absence of virus circulation. As the FMD vaccination program was revised in 2018, the post-vaccination monitoring (PVM) was designed to evaluate the effectiveness of the vaccine program of three vaccines approved for routine use. To this end, monitoring post-vaccination immunity has been conducted by collecting 35,626 serum samples at 28 days post-vaccination following regular national vaccinations, which were carried out in April and in October in 2020. The design of the serological test for PVM was specially targeted at particular livestock groups, including dairy cattle, goats, and beef cattle aged 6-12 months, which were generally estimated to have a low expected seroprevalence. The risk factors had also been identified, considering the increased likelihood of infection in a particular location, herd size, and husbandry system applied in a targeted sample collection. Serum sample collection and SP-O and NSP antibody tests were performed by local veterinary laboratories using commercially available ELISAs. The current FMD vaccination program, which was performed twice a year following the regimen of primary vaccination and boost, resulted in over 80% population immunity. The seroprevalence monitored after the vaccination in fall was higher than the one studied in spring except in pigs. It was demonstrated that the seroprevalence of risk-based targeted samples ranged from 93.8 to 100% in cattle, 63.2 to 100% in pigs, and 20.0 to 100% in goats. Of note is the area near the North Korean borders which showed a relatively low seroprevalence among the targeted regions, and no NSP sero-positive reactor was detected in this region. When subpopulation immunity at the individual level was assessed, the seroprevalence in young cattle stock was slightly lower (95.8%) than that of adults (98.4%). In conclusion, the FMD vaccination campaign has been successfully implemented in Korea, and the PVM can be a supplementary program for massive routine surveillance in terms of providing timely information needed both to estimate population immunity and to properly target "risk-based surveillance."

17.
Viruses ; 13(6)2021 06 21.
Article in English | MEDLINE | ID: mdl-34205489

ABSTRACT

The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC-EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies.


Subject(s)
Adenoviridae/physiology , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Metapneumovirus/physiology , Respiratory Syncytial Virus, Human/physiology , Virus Replication , A549 Cells , Cell Line , Chemokines/immunology , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Epithelial Cells/drug effects , Epithelial Cells/virology , Guanine Nucleotide Exchange Factors/antagonists & inhibitors , HEK293 Cells , Humans , Quinolines/pharmacology
18.
Ann Biomed Eng ; 49(9): 2412-2420, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34002287

ABSTRACT

Bladder cancer (BC) is the main disease in the urinary tract with a high recurrence rate and it is diagnosed by cystoscopy (CY). To train the CY procedures, a realistic bladder phantom with correct anatomy and physiological properties is highly required. Here, we report a soft bladder phantom (FlexBlad) that mimics many important features of a human bladder. Under filling, it shows a large volume expansion of more than 300% with a tunable compliance in the range of 12.2 ± 2.8 - 32.7 ± 5.4 mL cmH2O-1 by engineering the thickness of the bladder wall. By 3D printing and multi-step molding, detailed anatomical structures are represented on the inner bladder wall, including sub-millimeter blood vessels and reconfigurable bladder tumors. Endoscopic inspection and tumor biopsy were successfully performed. A multi-center study was carried out, where two groups of urologists with different experience levels executed consecutive CYs in the phantom and filled in questionnaires. The learning curves reveal that the FlexBlad has a positive effect in the endourological training across different skill levels. The statistical results validate the usability of the phantom as a valuable educational tool, and the dynamic feature expands its use as a versatile endoscopic training platform.


Subject(s)
Phantoms, Imaging , Urinary Bladder/diagnostic imaging , Adult , Aged , Cystoscopy , Humans , Middle Aged , Printing, Three-Dimensional , Tomography, X-Ray Computed , Urinary Bladder Neoplasms/diagnostic imaging
19.
Pathogens ; 10(4)2021 Apr 02.
Article in English | MEDLINE | ID: mdl-33918404

ABSTRACT

Equine herpesvirus-1 (EHV-1) is an important pathogen in horses. It affects horses worldwide and causes substantial economic losses. In this study, for the first time, we characterized EHV-1 isolates from South Korea at the molecular level. We then aimed to determine the genetic divergences of these isolates by comparing them to sequences in databases. In total, 338 horse samples were collected, and 12 EHV-1 were isolated. We performed ORF30, ORF33, ORF68, and ORF34 genetic analysis and carried out multi-locus sequence typing (MLST) of 12 isolated EHV-1. All isolated viruses were confirmed as non-neuropathogenic type, showing N752 of ORF30 and highly conserved ORF33 (99.7-100%). Isolates were unclassified using ORF68 analysis because of a 118 bp deletion in nucleotide sequence 701-818. Seven EHV-1 isolates (16Q4, 19R166-1, 19R166-6, 19/10/15-2, 19/10/15-4, 19/10/18-2, 19/10/22-1) belonged to group 1, clade 10, based on ORF34 and MLST analysis. The remaining 5 EHV-1 isolates (15Q25-1, 15D59, 16Q5, 16Q40, 18D99) belonged to group 7, clade 6, based on ORF34 and MLST analysis.

20.
J Vet Med Sci ; 83(5): 869-875, 2021 Jun 02.
Article in English | MEDLINE | ID: mdl-33775991

ABSTRACT

This study was performed to examine and clarify the cause of hindlimb ataxia and neuropathy seen in the South Korean horse population. Fifty horses diagnosed with hindlimb ataxia and neuropathy were referred for this study. Neurological examination was performed on 47 horses while necropsy was performed in all 50 animals. The occurrence of neurological diseases increased rapidly in the summer and 47 out of 50 horses were referred after the end of July. The incidence of neurological diseases started from the southern part of Korea in July and proceeded northward in August and September. Although there was no correlation with age, Thoroughbred and Warmblood horses showed a higher incidence rate than Halla and Jeju horses. The incidence rate was 5 times higher in geldings than in mares and stallions. Of the 20 cases, 16 were diagnosed with eosinophilic meningoencephalomyelitis in 2015. The most common lesions observed in 2016 were parasitic meningoencephalomyelitis (10 cases, 33%) and eosinophilic meningomyelitis (7 cases, 23%). Histopathological analysis of the brain and spinal cord revealed nematodes of approximately 100-200 µm in diameter, microcavitation and infiltrates of eosinophils, and brown pigmented macrophage infiltrates. The nematodes were identified as Setaria digitata via DNA sequencing, performed subsequent to polymerase chain reaction using DNA isolated from formalin-fixed paraffin-embedded tissue sections of the spinal cord. These results show that aberrant migration of Setaria digitata larva in the brain and spinal cord was a major cause for neurological signs in horses.


Subject(s)
Encephalomyelitis , Horse Diseases , Setaria Nematode , Animals , Ataxia/veterinary , Encephalomyelitis/veterinary , Female , Horse Diseases/epidemiology , Horses , Male , Republic of Korea/epidemiology
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