• BMB Reports
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• 제54권10호
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• pp.528-533
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• 2021

Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1β), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OA-like condition of chondrocytes in vitro. Avn-C restrained IL-1β-mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1β, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1β treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis.

• Journal of Microbiology and Biotechnology
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• 제29권8호
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• pp.1230-1239
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• 2019

Scutellaria baicalensis Georgi has been widely used in China for treatment of various diseases. This study investigated the effect of Scutellaria baicalensis Georgi extracts (SBE) against Coxsackievirus B3 (CVB3)-induced myocarditis in vitro and in vivo. In vitro, Hela cells and primary myocardial cells were infected with CVB3 and treated with SBE ($50-800{\mu}g/ml$) and ribavirin ($200{\mu}M$) for 48 h and then determined by CCK8 assay. Real-time PCR and western blotting assays were performed. In vivo, a myocarditis model was induced in male BALB/c mice by injecting CVB3 suspension intraperitoneally for three times, followed by treatment with SBE (400 and 200 mg/kg) and ribavirin (100 mg/kg) for 28 days. SBE ameliorated the cytotoxicity of CVB3 in Hela cells, especially at $400{\mu}g/ml$ (39.93% vs 65.67%, p < 0.05) without influencing cell growth and also significantly reduced CVB3 replication in primary myocardial cells. The levels of AKT, ERK, and p38 were increased after CVB3 infection. SBE could downregulate the expressions of AKT and p38. In vivo, the mortality rate from CVB3 reached to 66.67%, while 10.00% and 23.33% of this came after 400 and 200 mg/kg SBE treatment, respectively (p < 0.05). The CVB3 replication was obviously reduced after SBE administration from day 5. Similarly, the levels of AKT, ERK, and p38 mRNAs and proteins were increased, and SBE suppressed the expression of AKT and p38. Our study indicates that SBE is a promising potent antiviral agent against CVB3-induced myocarditis by inhibition of virus replication via depressing AKT and p38 expressions.

• 대한한의학회지
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• 제39권4호
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• pp.86-113
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• 2018

Objectives: We examined the effects of a mixed formula consisting of dried pomegranate concentrate powder (PCP) and the aqueous extracts of Eucommiae cortex (EC) and Achyranthis radix (AR) in rats with surgically induced osteoarthritis (OA). Methods: Two weeks after OA-inducing surgery, a PCP:EC:AR 5:4:1 (g/g) combination or single formula was orally administered. Changes in body weight, knee thickness, maximum knee extension angle, bone mineral density of the knee joints, femoral and tibial articular surfaces, and compressive strength of the femoral and tibial articular cartilage (AC) were assessed, along with the prostaglandin E2 level, 5-lipoxygenase, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and chondrogenic gene mRNA expression in the femoral and tibial AC with the synovial membrane (SM). In addition, the number of cleaved poly(ADP-ribose) polymerase, cyclooxygenase and tumor necrosis factor-${\alpha}$-immunoreactive cells in the femoral and tibial AC with SM were monitored, and the rate of cell proliferation was determined with a 5-bromo-2'-deoxyuridine uptake assay. Results : The signs of surgically induced OA in rats were significantly inhibited by both PCP, EC and AR combined and single formulas. In particular, the combination formula-treated OA model rats showed dose-dependent, significantly increased inhibitory activity against all tested criteria compared with single formula-treated rats. Conclusions: Taken together, our results suggest that the combination formula synergistically increased the anti-OA effects of its components through anti-inflammatory and chondrogenic activity in rats with surgically induced OA. In addition, 200, 100 and 50 mg/kg combination formula treatments showed dose-dependent inhibitory activity against all of the tested criteria.

• Clinical and Experimental Pediatrics
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• 제62권3호
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• pp.95-101
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• 2019

Purpose: Increased apoptosis was recently found in the hypertrophied left ventricle of spontaneously hypertensive rats (SHRs). Although the available evidence suggests that apoptosis can be induced in cardiac cells by various insults including pressure overload, cardiac apoptosis appears to result from an exaggerated local production of angiotensin in adult SHRs. Altered expressions of Bcl associated X (Bax), Bcl-2, chemokine receptor (CCR)-2, monocyte chemoattractant protein (MCP)-1, transforming growth factor $(TGF)-{\beta}1$, phosphorylated extracellular signal-regulated kinases (PERK), and connexin 43 proteins, and kallikrein mRNA were investigated to explore the effects of losartan on the SHR model. Methods: Twelve-week-old male rats were grouped as follows: control (C), SHR (hypertension: H), and losartan (L; SHRs were treated with losartan [10 mg/kg/day] for 5 weeks). Western blot and reverse transcription polymerase chain reaction assays were performed. Results: Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA was significantly increased in the H group compared to that in the C group at weeks 3 and 5. Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, and connexin 43 proteins and kallikrein mRNA was significantly decreased after losartan treatment at week 5. PERK protein expression was significantly decreased after losartan treatment at weeks 3 and 5. Bcl-2 protein expression was significantly decreased in the H group compared to that in the C group at weeks 3 and 5. Conclusion: Losartan treatment reduced expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA in SHRs, along with decreased inflammation and apoptosis.

• The Korean Journal of Pain
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• 제32권1호
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• pp.12-21
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• 2019

Spinal cord contusion injury is one of the most serious nervous system disorders, characterized by high morbidity and disability. To mimic spinal cord contusion in humans, various animal models of spinal contusion injury have been developed. These models have been developed in rats, mice, and monkeys. However, most of these models are developed using rats. Two types of animal models, i.e. bilateral contusion injury and unilateral contusion injury models, are developed using either a weight drop method or impactor method. In the weight drop method, a specific weight or a rod, having a specific weight and diameter, is dropped from a specific height on to the exposed spinal cord. Low intensity injury is produced by dropping a 5 g weight from a height of 8 cm, moderate injury by dropping 10 g weight from a height of 12.5-25 mm, and high intensity injury by dropping a 25 g weight from a height of 50 mm. In the impactor method, injury is produced through an impactor by delivering a specific force to the exposed spinal cord area. Mild injury is produced by delivering $100{\pm}5kdyn$ of force, moderate injury by delivering $200{\pm}10kdyn$ of force, and severe injury by delivering $300{\pm}10kdyn$ of force. The contusion injury produces a significant development of locomotor dysfunction, which is generally evident from the $0-14^{th}$ day of surgery and is at its peak after the $28-56^{th}$ day. The present review discusses different animal models of spinal contusion injury.

• Investigative Magnetic Resonance Imaging
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• 제25권2호
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• pp.118-128
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• 2021

Purpose: To investigate the value of MR textural analysis, including use of diffusion-weighted imaging (DWI) to differentiate malignant from benign soft-tissue tumors on 3T MRI. Materials and Methods: We enrolled 69 patients (25 men, 44 women, ages 18 to 84 years) with pathologically confirmed soft-tissue tumors (29 benign, 40 malignant) who underwent pre-treatment 3T-MRI. We calculated MR texture, including mean, standard deviation (SD), skewness, kurtosis, mean of positive pixels (MPP), and entropy, according to different spatial-scale factors (SSF, 0, 2, 4, 6) on axial T1- and T2-weighted images (T1WI, T2WI), contrast-enhanced T1WI (CE-T1WI), high b-value DWI (800 sec/mm²), and apparent diffusion coefficient (ADC) map. We used the Mann-Whitney U test, logistic regression, and area under the receiver operating characteristic curve (AUC) for statistical analysis. Results: Malignant soft-tissue tumors had significantly lower mean values of DWI, ADC, T2WI and CE-T1WI, MPP of ADC, and CE-T1WI, but significantly higher kurtosis of DWI, T1WI, and CE-T1WI, and entropy of DWI, ADC, and T2WI than did benign tumors (P < 0.050). In multivariate logistic regression, the mean ADC value (SSF, 6) and kurtosis of CE-T1WI (SSF, 4) were independently associated with malignancy (P ≤ 0.009). A multivariate model of MR features worked well for diagnosis of malignant soft-tissue tumors (AUC, 0.909). Conclusion: Accurate diagnosis could be obtained using MR textural analysis with DWI and CE-T1WI in differentiating benign from malignant soft-tissue tumors.

• Journal of Neurogastroenterology and Motility
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• 제25권3호
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• pp.387-393
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• 2019

Background/Aims Delayed gastric emptying (GE) is associated with high morbidity and mortality in subjects with diabetes. The aim of this study is to investigate associations between GE time and the major cardiovascular events (coronary heart diseases and ischemic stroke) in diabetic subjects with upper gastrointestinal (UGI) symptoms. Methods Among 259 subjects with chronic UGI symptoms who underwent gastric emptying study (GES) over 13 years, 122 diabetic subjects without gastric surgery and/or rapid GE were enrolled in this study. We also gathered data about baseline demographics, clinical characteristics, estimated GE half-time (GE T½) and incidence of cardiovascular events following GES. Results The mean age of subjects was 64.0 ± 17.4 years. There were 86 women and 104 subjects with type 2 diabetes. There were 52 (42.6%) subjects with normal GE, 50 (41.0.%) subjects with mild delayed GE, and 20 (16.4%) subjects with marked delayed GE. During follow-up (median, 207 weeks), cardiovascular events occurred in 7 (13.5%) subjects with normal GE, 4 (8.0%) subjects with mild delayed GE and 7 (35.0%) subjects with marked GE (P = 0.015). Univariate analysis showed that GE T½ was significantly associated with incidence of cardiovascular events (crude OR, 1.74; 95% CI, 1.12-2.69; P = 0.014). In a multivariate model, association between GE T½ and incidence of cardiovascular events remained statistically significant after adjustment for baseline characteristics and comorbidities (adjusted OR, 1.94; 95% CI, 1.21-3.12; P = 0.006). Conclusion A delay of GE was associated with an increased incidence of cardiovascular events in diabetic subjects with chronic UGI symptoms.

• Imaging Science in Dentistry
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• 제51권1호
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• pp.1-7
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• 2021

Purpose: The aim of this study was to assess artifacts generated in cone-beam computed tomography (CBCT) of 3 types of dental implants using 3 metal artifact reduction (MAR) algorithm conditions (pre-acquisition MAR, post-acquisition MAR, and no MAR), and 2 peak kilovoltage (kVp) settings. Materials and Methods: Titanium-zirconium, titanium, and zirconium alloy implants were placed in a dry mandible. CBCT images were acquired using 84 and 90 kVp and at normal resolution for all 3 MAR conditions. The images were analyzed using ImageJ software (National Institutes of Health, Bethesda, MD) to calculate the intensity of artifacts for each combination of material and settings. A 3-factor analysis of variance model with up to 3-way interactions was used to determine whether there was a statistically significant difference in the mean intensity of artifacts associated with each factor. Results: The analysis of all 3 MAR conditions showed that using no MAR resulted in substantially more severe artifacts than either of the 2 MAR algorithms for the 3 implant materials; however, there were no significant differences between pre- and post-acquisition MAR. The 90 kVp setting generated less intense artifacts on average than the 84 kVp setting. The titanium-zirconium alloy generated significantly less intense artifacts than zirconium. Titanium generated artifacts at an intermediate level relative to the other 2 implant materials, but was not statistically significantly different from either. Conclusion: This in vitro study suggests that artifacts can be minimized by using a titanium-zirconium alloy at the 90 kVp setting, with either MAR setting.

• Genomics & Informatics
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• 제20권1호
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• pp.11.1-11.20
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• 2022

Vibrio harveyi belongs to the Vibrio genus that causes vibriosis in marine and aquatic fish species through double-stranded DNA virus replication. In humans, around 12 Vibrio species can cause gastroenteritis (gastrointestinal illness). A large amount of virus particles can be found in the cytoplasm of infected cells, which may cause death. Despite these devastating complications, there is still no cure or vaccine for the virus. As a result, we used an immunoinformatics approach to develop a multi-epitope vaccine against most pathogenic hemolysin gene of V. harveyi. The immunodominant T- and B-cell epitopes were identified using the hemolysin protein. We developed a vaccine employing three possible epitopes: cytotoxic T-lymphocytes, helper T-lymphocytes, and linear B-lymphocyte epitopes, after thorough testing. The vaccine was developed to be antigenic, immunogenic, and non-allergenic, as well as having a better solubility. Molecular dynamics simulation revealed significant structural stiffness and binding stability. In addition, the immunological simulation generated by computer revealed that the vaccination might elicit immune reactions in the actual life after injection. Finally, using Escherichia coli K12 as a model, codon optimization yielded ideal GC content and a higher codon adaptation index value, which was then included in the cloning vector pET2+ (a). Altogether, our experiment implies that the proposed peptide vaccine might be a good option for vibriosis prophylaxis.

• Archives of Plastic Surgery
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• 제49권1호
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• pp.121-126
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• 2022

Background Although they may not replace standard training methods that use surgical microscopes, smartphones equipped with high-resolution screens and high-definition cameras are an attractive alternative for practicing microsurgical skills. They are ubiquitous, simple to operate, and inexpensive. This study compared anastomoses of chicken femoral vessels using a smartphone camera versus a standard operative microscope. Methods Forty anastomoses of non-living chicken femoral vessels were divided into four groups. A resident and an experienced microsurgeon performed anastomoses of femoral chicken vessels with 8-0 and 10-0 sutures, using a smartphone camera and a surgical microscope. The time to complete the anastomosis and the number of anastomosis errors were compared using the Mann-Whitney U test. Results The time taken to perform an anastomosis by the experienced microsurgeon was significantly longer when using the smartphone (median: 32.5 minutes vs. 20 minutes, P<0.001). The resident completed the anastomoses with both types of equipment without a significant difference in the operative times. When using a smartphone, the operation times were not significantly different between the resident and the experienced microsurgeon (P=0.238). The resident showed non-significant differences in operation time and the number of errors when using a smartphone or an operative microscope (P=1.000 and P=0.065, respectively). Conclusions Microsurgical practice with non-living chicken femoral vessels can be performed with a smartphone, though it can take longer than with an operative microscope for experienced microsurgeons. The resident may also experience frustration and tend to make more anastomosis errors when using a smartphone versus an operative microscope.