Publications by authors named "Seul Lee"

306 Publications

Chest CT abnormalities in COVID-19: a systematic review.

Int J Med Sci 2021 1;18(15):3395-3402. Epub 2021 Aug 1.

Department of Pediatrics, Yonsei University College of Medicine, Yonsei-ro 50, Seodaemun-gu, C.P.O Box 8044, Seoul 03722, Republic of Korea.

Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.
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http://dx.doi.org/10.7150/ijms.50568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436104PMC
August 2021

Effects of Oats ( L.) on Inflammation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Nutr 2021 27;8:722866. Epub 2021 Aug 27.

College of Pharmacy, Seoul National University, Seoul, South Korea.

Oat and its compounds have been found to have anti-inflammatory effects. Through this systematic review and meta-analysis, we aimed to determine an evidence-based link between oat consumption and inflammatory markers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. By the end of April 2021, we included randomized controlled trials (RCTs) that investigated the anti-inflammatory effect of oat and oat-related products through screening PubMed, Embase, Web of Science, ClinicalTrial.gov, and CENTRAL. Meta-analysis was conducted with a random-effect model on the standardized mean difference (SMD) of the change scores of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Subgroup analyses were conducted to stratify confounding variables. The risk of bias was evaluated using the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to report the quality of evidence. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021245844). Systematic screening of five databases yielded 4,119 studies, of which 23 RCTs were finally selected. For the four systemic inflammatory markers analyzed, no significant alterations were found after oat consumption. However, oat intake was found to significantly decrease CRP levels in subjects with one or more health complications (SMD: -0.18; 95% CI: -0.36, 0.00; = 0.05; = 10%). Furthermore, IL-6 levels were significantly decreased in subjects with dyslipidemia (SMD = -0.34; 95% CI: -0.59, -0.10; = 0.006; = 0%). These beneficial effects might be attributed to the effects of avenanthramide and β-glucan. Overall evidence supporting the alleviation of inflammatory response by oat intake was poor, calling for future studies including a larger sample size to confirm the findings.
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http://dx.doi.org/10.3389/fnut.2021.722866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429797PMC
August 2021

Farrerol Induces Cancer Cell Death via ERK Activation in SKOV3 Cells and Attenuates TNF-α-Mediated Lipolysis.

Int J Mol Sci 2021 Aug 30;22(17). Epub 2021 Aug 30.

Department of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Korea.

Farrerol (FA) is a flavanone isolated from the Chinese herbal medicine "Man-shan-hong" ( L.). In the present study, FA decreased the viability of SKOV3 cells in a dose- and time-dependent manner, and it induced G2/M cell cycle arrest and cell apoptosis. Cell cycle distribution analysis via flow cytometry showed that FA decreased G1 populations and increased G2/M populations in SKOV3 cells. Additionally, Western blotting confirmed an increase in the expression level of proteins involved in the cell cycle, e.g., CDK and cyclins. FA-induced apoptosis in SKOV3 cells was also investigated using a TUNEL assay, and increased expression levels of proapoptotic factors, including Caspase-3 and poly ADP ribose polymerase (PARP), through the Extracellular signal-regulated kinase (ERK)/MAPK pathway were investigated. Proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1) have been identified as a driver of the pathological mechanisms underlying involuntary weight loss and impaired physical function, i.e., cachexia, during cancer; in the present study, we showed that farrerol attenuates TNF-α-induced lipolysis and increases adipogenic differentiation in 3T3-L1 cells. Thus, farrerol could potentially be used as an anticancer agent or anticachetic drug.
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http://dx.doi.org/10.3390/ijms22179400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430798PMC
August 2021

Author Correction: High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester.

Nat Commun 2021 Sep 3;12(1):5360. Epub 2021 Sep 3.

Department of Chemistry, Seoul National University, Seoul, 08826, Korea.

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http://dx.doi.org/10.1038/s41467-021-25676-3DOI Listing
September 2021

Customized Power Wheelchair Joysticks Made by Three-Dimensional Printing Technology: A Pilot Study on the Environmental Adaptation Effects for Severe Quadriplegia.

Int J Environ Res Public Health 2021 07 13;18(14). Epub 2021 Jul 13.

Department of Mechanical Engineering, Korea National University of Transportation, 50 Daehak-ro, Cungju 380702, Korea.

Background: Power wheelchair joysticks are often available as standardized ready-made products for patients with severe hand dysfunction. However, standardized joysticks have limitations in accommodating the individualized features of hand dysfunctions. Three-dimensional (3D) printing technology has facilitated active research on the development of joysticks that can overcome such limitations.

Methods: Four subjects participated in the study to evaluate driving abilities and satisfaction after using the customized joystick for two weeks. Modified power-mobility indoor driving assessment (PIDA), National Aeronautics and Space Administration task load index (NASA-TLX), and psychosocial impact of assistive devices scale (PIADS; Korean version) were employed for evaluation.

Results: In patients 1-3, the modified PIDA scores had the highest values in the pre-test and post-test. In patient 4, the modified PIDA score had a higher value in the post-test (mean value = 4) compared to the pre-test (mean value = 3.33). In all patients, the modified PIDA time was lower in the post-test compared to the pre-test. The NASA-TLX and PIADS values indicate that greater satisfaction was achieved through the usage of customized joysticks in the post-test.

Conclusions: All patients can improve their power wheelchair driving abilities and achieve greater satisfaction.

Clinical Relevance: Three-dimensional printed customized power wheelchair joysticks can offer enhanced driving abilities and satisfaction to patients with limited hand function owing to severe spinal cord injury.
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http://dx.doi.org/10.3390/ijerph18147464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306002PMC
July 2021

Clinical decision support algorithm based on machine learning to assess the clinical response to anti-programmed death-1 therapy in patients with non-small-cell lung cancer.

Eur J Cancer 2021 Aug 26;153:179-189. Epub 2021 Jun 26.

Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objective: Anti-programmed death (PD)-1 therapy confers sustainable clinical benefits for patients with non-small-cell lung cancer (NSCLC), but only some patients respond to the treatment. Various clinical characteristics, including the PD-ligand 1 (PD-L1) level, are related to the anti-PD-1 response; however, none of these can independently serve as predictive biomarkers. Herein, we established a machine learning (ML)-based clinical decision support algorithm to predict the anti-PD-1 response by comprehensively combining the clinical information.

Materials And Methods: We collected clinical data, including patient characteristics, mutations and laboratory findings, from the electronic medical records of 142 patients with NSCLC treated with anti-PD-1 therapy; these were analysed for the clinical outcome as the discovery set. Nineteen clinically meaningful features were used in supervised ML algorithms, including LightGBM, XGBoost, multilayer neural network, ridge regression and linear discriminant analysis, to predict anti-PD-1 responses. Based on each ML algorithm's prediction performance, the optimal ML was selected and validated in an independent validation set of PD-1 inhibitor-treated patients.

Results: Several factors, including PD-L1 expression, tumour burden and neutrophil-to-lymphocyte ratio, could independently predict the anti-PD-1 response in the discovery set. ML platforms based on the LightGBM algorithm using 19 clinical features showed more significant prediction performance (area under the curve [AUC] 0.788) than on individual clinical features and traditional multivariate logistic regression (AUC 0.759).

Conclusion: Collectively, our LightGBM algorithm offers a clinical decision support model to predict the anti-PD-1 response in patients with NSCLC.
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http://dx.doi.org/10.1016/j.ejca.2021.05.019DOI Listing
August 2021

Monitoring Cerebral Perfusion Changes Using Arterial Spin-Labeling Perfusion MRI after Indirect Revascularization in Children with Moyamoya Disease.

Korean J Radiol 2021 Sep 26;22(9):1537-1546. Epub 2021 May 26.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: To assess the role of arterial spin-labeling (ASL) perfusion MRI in identifying cerebral perfusion changes after indirect revascularization in children with moyamoya disease.

Materials And Methods: We included pre- and postoperative perfusion MRI data of 30 children with moyamoya disease (13 boys and 17 girls; mean age ± standard deviation, 6.3 ± 3.0 years) who underwent indirect revascularization between June 2016 and August 2017. Relative cerebral blood flow (rCBF) and qualitative perfusion scores for arterial transit time (ATT) effects were evaluated in the middle cerebral artery (MCA) territory on ASL perfusion MRI. The rCBF and relative time-to-peak (rTTP) values were also measured using dynamic susceptibility contrast (DSC) perfusion MRI. Each perfusion change on ASL and DSC perfusion MRI was analyzed using the paired test. We analyzed the correlation between perfusion changes on ASL and DSC images using Spearman's correlation coefficient.

Results: The ASL rCBF values improved at both the ganglionic and supraganglionic levels of the MCA territory after surgery ( = 0.040 and = 0.003, respectively). The ATT perfusion scores also improved at both levels ( < 0.001 and < 0.001, respectively). The rCBF and rTTP values on DSC MRI showed significant improvement at both levels of the MCA territory of the operated side (all < 0.05). There was no significant correlation between the improvements in rCBF values on the two perfusion images ( = 0.195, = 0.303); however, there was a correlation between the change in perfusion scores on ASL and rTTP on DSC MRI ( = 0.701, < 0.001).

Conclusion: Recognizing the effects of ATT on ASL perfusion MRI may help monitor cerebral perfusion changes and complement quantitative rCBF assessment using ASL perfusion MRI in patients with moyamoya disease after indirect revascularization.
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http://dx.doi.org/10.3348/kjr.2020.1464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390823PMC
September 2021

Comparison of conventional magnetic resonance imaging and diffusion-weighted imaging in the differentiation of bone plasmacytoma from bone metastasis in the extremities.

Diagn Interv Imaging 2021 Jun 11. Epub 2021 Jun 11.

Department of Radiology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 06591 Seoul, Republic of Korea.

Purpose: To compare conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the differentiation of bone plasmacytoma from bone metastasis in the extremities.

Materials And Methods: A total of 65 patients with 27 bone plasmacytomas (11 men; mean age, 63.6±8.2 [SD] years) and 38 patients with bone metastases (20 men; mean age, 64.1±11.5 [SD] years) were retrospectively included. Plasmacytomas and metastases were compared for size, peritumoral edema, signal intensity (SI), SI pattern, apparent diffusion coefficient (ADC) values and standard deviation (SD) of ADC. Receiver operating characteristic analysis with area under the curve (AUC) was used to calculate sensitivity, specificity, and accuracy of MRI and DWI for the diagnosis of plasmacytoma according to a defined cut-off value.

Results: On conventional MRI, plasmacytomas showed less peritumoral edema (22% vs. 71%; P<0.001), were more often hyperintense on T1-weighted image (48% vs. 18%; P=0.022) and more homogeneous on T2-weighted image (78% vs. 26%; P<0.001) and contrast-enhanced T1-weighted images (70% vs. 25%; P=0.001) than bone metastases. Mean ADC value and SD of ADC were significantly lower in bone plasmacytomas (760.1±196.9 [SD] μm/s and 161.5±62.7 [SD], respectively) than in bone metastases (1214.2±382.6 [SD] μm/s and 277.0±110.3 [SD], respectively) (P<0.001). Using an ADC value≤908.3μm/s, DWI yielded 88% sensitivity and 78% specificity for the diagnosis of plasmacytoma. ADC value yielded best area under the curve (AUC=0.913), followed by SD of ADC (AUC=0.814) and homogeneity on T2-weighted images (AUC=0.757). The combination of conventional MRI and DWI (AUC=0.894) showed improved diagnostic performance over conventional MRI alone (AUC= 0.843) for discriminating between plasmacytoma and metastasis.

Conclusion: Conventional MRI in combination with DWI can be useful to discriminate between bone plasmacytoma and bone metastasis in the extremities.
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http://dx.doi.org/10.1016/j.diii.2021.05.009DOI Listing
June 2021

Enhancement of the Antiobesity and Antioxidant Effect of Purple Sweet Potato Extracts and Enhancement of the Effects by Fermentation.

Antioxidants (Basel) 2021 May 31;10(6). Epub 2021 May 31.

Department of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Korea.

The browning of white adipocytes, which transforms energy-storing white adipocytes to heat-producing beige adipocytes, is considered a strategy against metabolic diseases. Several dietary compounds, such as anthocyanins, flavonoids, and phenolic acids, induce a brown adipocyte-like phenotype in white adipocytes. In this study, we demonstrated that purple sweet potato (Ipomoea batatas) extract (PSP) exhibited potent radical scavenging activity. In addition, PSP was found to contain large amounts of phenolic, flavonoid, and anthocyanin compounds; the amount of these compounds was affected by fermentation. Functionally, PSP-induced adipose browning in high-fat-diet (HFD)-induced obese mice. The administration of PSP significantly suppressed the body weight gain and abnormal expansion of white adipose tissues in the obese mice. The expression of adipose browning-related genes was higher in the inguinal white adipose tissues from the PSP-treated mice than those in the HFD-fed mice. Moreover, PSP-treated 3T3-L1 adipocytes formed multilocular lipid droplets, similar to those formed in the 3T3-L1 adipocytes treated with a browning induction cocktail. The PSP-treated cells had an increased expression level of mitochondria and lipolysis-related genes. The browning effects of PSP were enhanced by fermentation with Lactobacillus. This study, to our knowledge, is the first to identify a new mechanism to increase the antiobesity effects of PSP by inducing adipocyte browning of adipocytes.
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http://dx.doi.org/10.3390/antiox10060888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229661PMC
May 2021

Agricultural nitrogen and phosphorus balances of Korea and Japan: Highest nutrient surplus among OECD member countries.

Environ Pollut 2021 Oct 12;286:117353. Epub 2021 May 12.

Division of Applied Life Science (BK 21+ Program), Gyeongsang National University, 501 Jinju-daero, Jinju, 52828, Republic of Korea; Institute of Agriculture and Life Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, 52828, Republic of Korea. Electronic address:

Excessive nutrient balance is a very crucial issue for environmental hazards. The constant addition of high-amounts of nutrient sources in agricultural production generates negative environmental conditions in Korea and Japan yet to be resolved. Therefore, it is obligatory to comprehend the nutrient (nitrogen (N) and phosphorus (P)) balance that is assessed by the difference between nutrient input and output in the soil surface in Korea and Japan. Among 34 Economic Co-operation and Development (OECD) countries, Korea and Japan had the highest N and P balances and thus both countries are primarily responsible for severe environmental pollution via nutrient release. The cultivable land area in both countries has constantly decreased during 1990-2017 at approximately 20 and 15% in Korea and Japan, respectively. Even N and P use efficiency sharply decreased with increasing N and P balance in both targeted countries. Japanese P balance, Korean N and P balances were decreased after the mid-1990s whereas, Japanese N balance almost unchanged for the last 28 years. Unlike chemical fertilizer input, Korean manure input level significantly increased from 78 kg N ha in 1990 to 157 kg N ha in 2017. Japanese manure input level was higher than that of chemical fertilizer without any big change for the last 28 years. The lion share of high N and P balance in both countries could generate from manure inputs, therefore, the number of livestock and their produced debris need to be used with more cautious for the reduction of national N and P surpluses at a benchmark level. These findings ensure to make a more environment friendly policy that can further reduce nutrient balance as well as improve soil health.
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http://dx.doi.org/10.1016/j.envpol.2021.117353DOI Listing
October 2021

Endothelial angiogenic activity and adipose angiogenesis is controlled by extracellular matrix protein TGFBI.

Sci Rep 2021 May 6;11(1):9644. Epub 2021 May 6.

Department of Food Science and Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea.

Several studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis. In the present study, we demonstrated that transforming growth factor-beta induced (TGFBI) suppresses angiogenesis stimulated by adipocyte-conditioned medium (Ad-CM), both in vitro and in vivo. TGFBI knockout (KO) mice exhibited increased numbers of blood vessels in adipose tissue, and blood vessels from these mice showed enhanced infiltration into Matrigel containing Ad-CM. The treatment of Ad-CM-stimulated SVEC-10 endothelial cells with TGFBI protein reduced migration and tube-forming activity. TGFBI protein suppressed the activation of the Src and extracellular signaling-related kinase signaling pathways of these SVEC-10 endothelial cells. Our findings indicated that TGFBI inhibited adipose angiogenesis by suppressing the activation of Src and ERK signaling pathways, possibly because of the stimulation of the angiogenic activity of endothelial cells.
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http://dx.doi.org/10.1038/s41598-021-88959-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102489PMC
May 2021

Production of value-added aromatics from wasted COVID-19 mask via catalytic pyrolysis.

Environ Pollut 2021 Aug 1;283:117060. Epub 2021 Apr 1.

School of Environmental Engineering, University of Seoul, Seoul, 02504, Republic of Korea. Electronic address:

In this study, wasted mask is chosen as a pyrolysis feedstock whose generation has incredibly increased these days due to COVID-19. We suggest a way to produce value-added chemicals (e.g., aromatic compounds) from the mask with high amounts through catalytic fast pyrolysis (CFP). To this end, the effects of zeolite catalyst properties on the upgradation efficiency of pyrolytic products produced from pyrolysis of wasted mask were investigated. The compositions and yields of pyrolytic gases and oils were characterized as functions of pyrolysis temperature and the type of zeolite catalyst (HBeta, HY, and HZSM-5), including the mesoporous catalyst of Al-MCM-41. The mask was pyrolyzed in a fixed bed reactor, and the pyrolysis gases evolved in the reactor was routed to a secondary reactor inside which the zeolite catalyst was loaded. It was chosen 550 °C as the CFP temperature to compare the catalyst performance for the production of benzene, toluene, ethylbenzene, and xylene (BTEX) because this temperature gave the highest oil yield (80.7 wt%) during the non-catalytic pyrolysis process. The large pore zeolite group of HBeta and HY led to 134% and 67% higher BTEX concentrations than HZSM-5, respectively, likely because they had larger pores, higher surface areas, and higher acid site density than the HZSM-5. This is the first report of the effect of zeolite characteristics on BTEX production via CFP.
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http://dx.doi.org/10.1016/j.envpol.2021.117060DOI Listing
August 2021

The usefulness of noninvasive liver stiffness assessment using shear-wave elastography for predicting liver fibrosis in children.

BMC Med Imaging 2021 Apr 12;21(1):68. Epub 2021 Apr 12.

Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: Pediatric patients with liver disease require noninvasive monitoring to evaluate the risk of fibrosis progression. This study aimed to identify the significant factors affecting liver stiffness values using two-dimensional shear-wave elastography (2D-SWE), and determine whether liver stiffness can predict the fibrosis stage of various childhood liver diseases.

Methods: This study included 30 children (22 boys and 8 girls; mean age, 5.1 ± 6.1 years; range, 7 days-17.9 years) who had undergone biochemical evaluation, 2D-SWE examination, histopathologic analysis of fibrosis grade (F0 to F3), assessment of necroinflammatory activity, and steatosis grading between August 2016 and March 2020. The liver stiffness from 2D-SWE was compared between fibrosis stages using Kruskal-Wallis analysis. Factors that significantly affected liver stiffness were evaluated using univariate and multivariate linear regression analyses. The diagnostic performance was determined from the area under the receiver operating curve (AUC) values of 2D-SWE liver stiffness.

Results: Liver stiffness at the F0-1, F2, and F3 stages were 7.9, 13.2, and 21.7 kPa, respectively (P < 0.001). Both fibrosis stage and necroinflammatory grade were significantly associated with liver stiffness (P < 0.001 and P = 0.021, respectively). However, in patients with alanine aminotransferase (ALT) levels below 200 IU/L, the only factor affecting liver stiffness was fibrosis stage (P = 0.030). The liver stiffness value could distinguish significant fibrosis (≥ F2) with an AUC of 0.950 (cutoff value, 11.3 kPa) and severe fibrosis (F3 stage) with an AUC of 0.924 (cutoff value, 18.1 kPa). The 2D-SWE values for differentiating significant fibrosis were 10.5 kPa (≥ F2) and 18.1 kPa (F3) in patients with ALT levels below 200 IU/L.

Conclusion: The liver stiffness values on 2D-SWE can be affected by both fibrosis and necroinflammatory grade and can provide excellent diagnostic performance in evaluating the fibrosis stage in various pediatric liver diseases. However, clinicians should be mindful of potential confounders, such as necroinflammatory activity or transaminase level, when performing 2D-SWE measurements for liver fibrosis staging.
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http://dx.doi.org/10.1186/s12880-021-00601-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040233PMC
April 2021

Impact of an Acute Care Surgery Model on the Management of Acute Appendicitis in South Korea: A Retrospective Cohort Study.

Emerg Med Int 2021 26;2021:5522523. Epub 2021 Mar 26.

Division of Acute Care Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Background: The acute care surgery (ACS) system is a new model for the prompt management of diseases that require rapid treatment in patients with acute abdomen. This study compared the outcomes and characteristics of the ACS system and traditional on-call system (TROS) for acute appendicitis in South Korea.

Methods: This single-center, retrospective study included all patients (aged ≥18 years) who underwent surgery for acute appendicitis in 2016 and 2018. The TROS and ACS system were used for the 2016 and 2018 groups, respectively. We retrospectively obtained data on each patient from the electrical medical records. The independent samples -test and Mann-Whitney -test were used for continuous and nonnormally distributed data, respectively.

Results: In total, 126 patients were included. The time taken to get from the emergency room admission to the operating room, operation times, and postoperative complication rates were similar between both groups. However, the length of the hospital stay was shorter in the ACS group than in the TROS group (4.3 ± 3.2 days vs. 7.2 ± 9.6 days, =0.039).

Conclusions: Since the introduction of the ACS system, the length of hospital stay for surgical patients has decreased. This may be due to the application of an integrated medical procedure, such as a new clinical pathway, rather than differences in the surgical techniques.
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http://dx.doi.org/10.1155/2021/5522523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018862PMC
March 2021

D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism.

Cells 2021 03 31;10(4). Epub 2021 Mar 31.

New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbok-ro, Dong gu, Daegu 41061, Korea.

The presence of brown adipocytes within white adipose tissue is associated with phenotypes that exhibit improved metabolism and proper body weight maintenance. Therefore, a variety of dietary agents that facilitate the browning of white adipocytes have been investigated. In this study, we screened a natural product library comprising 133 compounds with the potential to promote the browning of white adipocytes, and found that D-mannitol induces the browning of 3T3-L1 adipocytes by enhancing the expression of brown fat-specific genes and proteins, and upregulating lipid metabolism markers. D-mannitol also increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 (ACC), suggesting a possible role in lipolysis and fat oxidation. Moreover, an increase in the expression of genes associated with D-mannitol-induced browning was strongly correlated with the activation of the β3-adrenergic receptor as well as AMPK, protein kinase A (PKA), and PPARγ coactivator 1α (PGC1α). D-mannitol effectively reduced the body weight of mice fed a high-fat diet, and increased the expression of β1-oxidation and energy expenditure markers, such as Cidea, carnitine palmityl transferase 1 (CPT1), uncoupling protein 1 (UCP1), PGC1α, and acyl-coenzyme A oxidase (ACOX1) in the inguinal white adipose tissue. Our findings suggest that D-mannitol plays a dual regulatory role by inducing the generation of a brown fat-like phenotype and enhancing lipid metabolism. These results indicate that D-mannitol can function as an anti-obesity supplement.
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http://dx.doi.org/10.3390/cells10040768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066535PMC
March 2021

Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic.

Int J Environ Res Public Health 2021 03 23;18(6). Epub 2021 Mar 23.

Department of Child Development and Family Studies, College of Human Ecology, Seoul National University, Seoul 08826, Korea.

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey ( = 1236) and the 2019 Korean Children and Youth Well-being Index Survey ( = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic.
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http://dx.doi.org/10.3390/ijerph18063324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004811PMC
March 2021

Effects of Dietary Inclusion Level of Microwave-Dried and Press-Defatted Black Soldier Fly () Larvae Meal on Carcass Traits and Meat Quality in Broilers.

Animals (Basel) 2021 Mar 2;11(3). Epub 2021 Mar 2.

Animal Nutrition & Physiology Team, Rural Development Administration, National Institute of Animal Science, Wanju 55365, Korea.

Limited information is available regarding the use of microwave-dried larvae meal (HILM) as a dietary protein source for broiler diets. Therefore, we investigated the effects of microwave-dried HILM on carcass traits, meat quality, fatty acid (FA) profiles of abdominal fat and meat, and heavy metal residues of the meat in broilers. A total of 126 male broilers were randomly assigned to three dietary treatment groups (6 replicates and 7 birds/pen): a control diet and two experimental diets in which soybean meal was replaced with 25 or 50% HILM. The broilers were slaughtered at 35 days; the carcasses were weighed, and breast and leg meats were excised from 12 birds per treatment (2 birds/pen) for meat analysis. The breast meat quality and proximate composition showed satisfactory results. For the higher HILM diet, the content of saturated FA in the abdominal fat was increased and that of polyunsaturated FA was decreased ( < 0.001); the FA profile of leg meat did not significantly differ between groups. The concentrations of undesirable heavy metals in the HILM and leg meat were below permissible levels. However, the carcass weight was decreased ( < 0.001) in the 50% HILM group. Microwave-dried HILM is a potential ingredient for broiler diets, with up to 25% substitution showing no detrimental effects on carcass traits, meat quality, FA profiles, and heavy metal residues in the meat.
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http://dx.doi.org/10.3390/ani11030665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999917PMC
March 2021

Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease.

Gastroenterology 2021 Jun 5;160(7):2340-2353. Epub 2021 Mar 5.

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. Electronic address:

Background & Aims: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD).

Methods: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (C), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%.

Results: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for C of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching.

Conclusions: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.
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http://dx.doi.org/10.1053/j.gastro.2021.02.068DOI Listing
June 2021

Pollen grains as a low-cost, green, alternative sorbent for hydrophilic solid-phase extraction.

Anal Methods 2021 03;13(10):1295-1301

College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

Many natural products have demonstrated functionality as novel, green sorbents for organic compounds. However, only limited reports exist on the use of such green materials as solid-phase extraction (SPE) sorbents for select organic acids. In this study, we employed pollen grains as a hydrophilic sorbent and investigated the influence of various extraction parameters using a series of experimental designs. The chemical structure and surface properties of the prepared sorbent were investigated by Fourier-transform infrared spectroscopy and scanning electron microscopy. The Plackett-Burman design was used to experimentally screen for parameters that significantly influenced the extraction performance. Three selected parameters were then statistically optimized by applying a central composite design combined with a response surface methodology. Phenolic acid residues were determined and quantified using high performance liquid chromatography with ultraviolet detection; a mass spectrometric detector in the selected ion monitoring mode was also used for identification. As a practical example, phenolic acids in the soil were successfully separated by the developed pollen sorbent. These results therefore indicate that pollen grains can be considered as a sustainable, green, and safe alternative to bare silica for extraction and separation applications.
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http://dx.doi.org/10.1039/d1ay00044fDOI Listing
March 2021

Crystal Structure and Regiospecificity of Catechol -Methyltransferase from .

J Agric Food Chem 2021 Mar 17;69(8):2531-2538. Epub 2021 Feb 17.

School of Life Sciences, KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.

Catechol -methyltransferase (COMT) is an enzyme that transfers a methyl group to the catechol-derivative substrates using -adenosyl-l-methionine (SAM) and Mg. We report the biochemical and structural analysis of COMT from (COMT). COMT showed the highest activity with Mg, although the enzyme also showed a significant level of activity with Cu and Zn. COMT structures complexed with SAH and Mg elucidated how the enzyme stabilized the cosubstrate and the metal ion and revealed that the region near the SAM binding site undergoes conformational changes upon the binding of the cosubstrate and the metal ion. We also identified the catechol binding pocket of the enzyme and explained a broad substrate specificity of the bacterial enzyme and its ability to accommodate the catechol derivatives. In addition, we developed the COMT and COMT variants that showed both enhanced activities and regiospecificity for the production of the para-forms. Our study provides a structural basis for regiospecificity of COMT, which is related with the conformational change upon binding of SAM and Mg.
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http://dx.doi.org/10.1021/acs.jafc.0c07621DOI Listing
March 2021

Comparison of the Effectiveness of Three Lumbosacral Orthoses on Early Spine Surgery Patients: A Prospective Cohort Study.

Ann Rehabil Med 2021 Feb 9;45(1):24-32. Epub 2021 Feb 9.

Center of Prosthetics and Orthotics, Veterans Health Service Medical Center, Seoul, Korea.

Objective: To compare the convenience and effectiveness of the existing lumbosacral orthoses (LSO) (classic LSO and Cybertech) and a newly developed LSO (V-LSO) by analyzing postoperative data.

Methods: This prospective cohort study was performed from May 2019 to November 2019 and enrolled and analyzed 88 patients with degenerative lumbar spine disease scheduled for elective lumbar surgery. Three types of LSO that were provided according to the time of patient registration were applied for 6 weeks. Patients were randomized into the classic LSO group (n=31), Cybertech group (n=26), and V-LSO group (n=31). All patients were assessed using the Oswestry Disability Index (ODI) preoperatively and underwent plain lumbar radiography (anteroposterior and lateral views) 10 days postoperatively. Lumbar lordosis (LS angle) and frontal imbalance were measured with and without LSO. At the sixth postoperative week, a follow-up assessment with the ODI and orthosis questionnaire was conducted.

Results: No significant differences were found among the three groups in terms of the LS angle, frontal imbalance, ODI, and orthosis questionnaire results. When the change in the LS angle and frontal imbalance toward the reference value was defined as a positive change with and without LSO, the rate of positive change was significantly different in the V-LSO group (LS angle: 41.94% vs. 61.54% vs. 83.87%; p=0.003).

Conclusion: The newly developed LSO showed no difference regarding its effectiveness and compliance when compared with the existing LSO, but it was more effective in correcting lumbar lordosis.
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http://dx.doi.org/10.5535/arm.20158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960949PMC
February 2021

Global Studies of Using Fecal Biomarkers in Predicting Relapse in Inflammatory Bowel Disease.

Front Med (Lausanne) 2020 17;7:580803. Epub 2020 Dec 17.

Department of General Surgery and Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract mainly comprising two forms including Crohn's disease (CD) and ulcerative colitis (UC). IBD is a lifelong relapsing remitting disease and relapses occur at random patterns which are unpredictable. Fecal biomarkers have been increasingly used to assess disease activity in IBD due to their positive correlations with intestinal inflammation. Recent studies have also assessed the use of fecal biomarkers in predicting relapse and post-operative recurrence. This review provides information from global studies of using fecal calprotectin, lactoferrin and S100A12 to predict relapse in IBD. Strategies for further studies and the use of these fecal biomarkers for personalized management in IBD are also discussed.
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http://dx.doi.org/10.3389/fmed.2020.580803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773777PMC
December 2020

Modeling takeover time based on non-driving-related task attributes in highly automated driving.

Appl Ergon 2021 Apr 18;92:103343. Epub 2020 Dec 18.

Department of Industrial Engineering, Yonsei University, Seoul, Republic of Korea. Electronic address:

This study aims to investigate the effects of non-driving-related tasks (NDRTs) on the transition of control in highly automated driving (HAD) by investigating the effects of NDRT physical, visual, and cognitive attributes during transition of control. A conceptual model of the takeover process is proposed by dividing this process into motor and mental reactions. A laboratory experiment was conducted to evaluate the effects of each NDRT attribute on the corresponding stage of the process of taking over control. A prediction model was developed using the results of multiple linear regression analysis. Additionally, a validation experiment with nine NDRTs and a baseline condition was conducted to determine the extent to which the developed model explains the takeover time for each NDRT condition. The results showed that the timing aspects of the transition of control in HAD largely consist of participant motor reactions that are affected by the physical attributes of NDRTs.
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http://dx.doi.org/10.1016/j.apergo.2020.103343DOI Listing
April 2021

Fibrinolysis with Lower Dose Urokinase in Patients with Complicated Parapneumonic Effusion.

Tuberc Respir Dis (Seoul) 2021 Apr 17;84(2):134-139. Epub 2020 Dec 17.

Pulmonology Division, Department of Internal Medicine, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.

Background: Intrapleural urokinase is one of the most widely used fibrinolytic agents in the treatment of complicated parapneumonic effusion (CPPE). However, little research has been performed on the optimal urokinase dosage. The aim of this study was to evaluate the treatment efficacy of half dose urokinase compared with conventional dose urokinase.

Methods: We retrospectively enrolled 92 patients with CPPE or empyema who underwent intrapleural urokinase treatment at two tertiary hospitals. Patients received antibiotics, chest tube drainage, and other treatments as part of routine care. The primary outcome was the treatment success rate in the half dose urokinase group (50,000 IU daily for maximal 6 days) and the conventional dose urokinase group (100,000 IU daily). Treatment success was defined as clinical and radiological improvements without surgical treatment or re-admission within one month.

Results: Forty-four patients received half dose urokinase, whereas 48 patients were treated with conventional dose urokinase. Both groups were relatively well matched at baseline, excluding higher serum white blood cell count and higher empyema prevalence in the half dose urokinase group. The treatment success rate was not different between the two groups (p=0.048). There were no differences in the rate of in-hospital death and surgical treatment, hospitalization duration, and indwelling catheter duration. In the multivariate analysis, urokinase dose was not a predictor of treatment success.

Conclusion: Half dose intrapleural urokinase is equally effective conventional dose urokinase in treating patients with CPPE or empyema.
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http://dx.doi.org/10.4046/trd.2020.0018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010421PMC
April 2021

Metabolomics Analysis of the Beef Samples with Different Meat Qualities and Tastes.

Food Sci Anim Resour 2020 Nov 1;40(6):924-937. Epub 2020 Nov 1.

Animal Nutrition & Physiology Team, National Institute of Animal Science, Wanju 55365, Korea.

The purpose of this study was to investigate the meat metabolite profiles related to differences in beef quality attributes (i.e., high-marbled and low-marbled groups) using nuclear magnetic resonance (NMR) spectroscopy. The beef of different marbling scores showed significant differences in water content and fat content. High-marbled meat had mainly higher taste compounds than low-marbled meat. Metabolite analysis showed differences between two marbling groups based on partial least square discriminant analysis (PLS-DA). Metabolites identified by PLS-DA, such as N,N-dimethylglycine, creatine, lactate, carnosine, carnitine, sn-glycero-3-phosphocholine, betaine, glycine, glucose, alanine, tryptophan, methionine, taurine, tyrosine, could be directly linked to marbling groups. Metabolites from variable importance in projection plots were identified and estimated high sensitivity as candidate markers for beef quality attributes. These potential markers were involved in beef taste-related pathways including carbohydrate and amino acid metabolism. Among these metabolites, carnosine, creatine, glucose, and lactate had significantly higher in high-marbled meat compared to low-marbled meat (p<0.05). Therefore, these results will provide an important understanding of the roles of taste-related metabolites in beef quality attributes. Our findings suggest that metabolomics analysis of taste compounds and meat quality may be a powerful method for the discovery of novel biomarkers underlying the quality of beef products.
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http://dx.doi.org/10.5851/kosfa.2020.e59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713764PMC
November 2020

Diagnostic Performance of a New Convolutional Neural Network Algorithm for Detecting Developmental Dysplasia of the Hip on Anteroposterior Radiographs.

Korean J Radiol 2021 04 26;22(4):612-623. Epub 2020 Nov 26.

Department of Radiology, Pusan National University Yangsan Hospital, Yangsan, Korea.

Objective: To evaluate the diagnostic performance of a deep learning algorithm for the automated detection of developmental dysplasia of the hip (DDH) on anteroposterior (AP) radiographs.

Materials And Methods: Of 2601 hip AP radiographs, 5076 cropped unilateral hip joint images were used to construct a dataset that was further divided into training (80%), validation (10%), or test sets (10%). Three radiologists were asked to label the hip images as normal or DDH. To investigate the diagnostic performance of the deep learning algorithm, we calculated the receiver operating characteristics (ROC), precision-recall curve (PRC) plots, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) and compared them with the performance of radiologists with different levels of experience.

Results: The area under the ROC plot generated by the deep learning algorithm and radiologists was 0.988 and 0.988-0.919, respectively. The area under the PRC plot generated by the deep learning algorithm and radiologists was 0.973 and 0.618-0.958, respectively. The sensitivity, specificity, PPV, and NPV of the proposed deep learning algorithm were 98.0, 98.1, 84.5, and 99.8%, respectively. There was no significant difference in the diagnosis of DDH by the algorithm and the radiologist with experience in pediatric radiology ( = 0.180). However, the proposed model showed higher sensitivity, specificity, and PPV, compared to the radiologist without experience in pediatric radiology ( < 0.001).

Conclusion: The proposed deep learning algorithm provided an accurate diagnosis of DDH on hip radiographs, which was comparable to the diagnosis by an experienced radiologist.
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http://dx.doi.org/10.3348/kjr.2020.0051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005351PMC
April 2021

Brown Algae Exert Anti-Oxidative and Anti-AdipogenicEffects on 3T3-L1 Adipocytes by Downregulating PPARγ.

Medicina (Kaunas) 2020 Nov 24;56(12). Epub 2020 Nov 24.

School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Korea.

, belonging to the family Sargassaceae, has been reported to have various biological effects such as anti-tyrosinase activity and anti-inflammation. However, the anti-obesity effect of has not yet been reported. The effects of extract (SME) on 3T3-L1 adipocytes were screened by3-(4,5)-dimethylthiazo-2-yl-2,5-diphenyltetrazolium bromide (MTT), Oil red O staining, western blot, and Real-time reverse transcription polymerase chain reaction analyses. : Here, we show that SME had potent 2,2'-azinobis-3-ehtlbezothiazoline-6-sulfonic acid radical decolorization (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity with half maximal inhibitory concentration (IC50) value of 0.2868 ± 0.011 mg/mL and 0.2941 ± 0.014 mg/mL, respectively. In addition, SME significantly suppressed lipid accumulation and differentiation of 3T3-L1 preadipocytes, as shown by Oil Red O staining results. SME attenuated the expression of adipogenic- and lipogenic-related genes such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα), CCAAT-enhancer-binding protein delta (C/EBPδ), adiponectin, adipose triglyceride lipase (ATGL), fatty acid synthase (FAS), hormone-sensitive lipase (HSL), and lipoprotein lipase (LPL). These findings suggest that SME may have therapeutic implications for developing a new anti-obesity agent.
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http://dx.doi.org/10.3390/medicina56120634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760913PMC
November 2020

Neurotrophic isoindolinones from the fruiting bodies of Hericium erinaceus.

Bioorg Med Chem Lett 2021 01 25;31:127714. Epub 2020 Nov 25.

College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea. Electronic address:

Four compounds, hericerin (1), isohericerinol A (2), N-de-phenylethyl isohericerin (3) and corallocin A (4) were isolated from the fruiting bodies of Hericium erinaceus, a lion's mane mushroom (Hericiaceae). Among them, isohericerinol A (2) was newly reported in nature. Further investigation of the neurotrophic effect of isolated compounds demonstrated that isohericerinol A (2) strongly increased the nerve growth factor (NGF) production in C6 glioma cells followed by corallocin A (4) and hericerin (1). Increased NGF production by these compounds promoted the neurite outgrowth in N2a neuronal cells. Western blot analysis also showed the increased protein expression of NGF, brain-derived neurotrophic factor (BDNF) and synaptophysin (SYP) in C6-N2a cells. Taken together, our present study characterized the neurotrophic constituents of H. erinaceus, which may support the potential use of memory improvement.
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http://dx.doi.org/10.1016/j.bmcl.2020.127714DOI Listing
January 2021

Dual conformational recognition by Z-DNA binding protein is important for the B-Z transition process.

Nucleic Acids Res 2020 12;48(22):12957-12971

Department of Biological Sciences, Seoul National University, Seoul 08826, Korea.

Left-handed Z-DNA is radically different from the most common right-handed B-DNA and can be stabilized by interactions with the Zα domain, which is found in a group of proteins, such as human ADAR1 and viral E3L proteins. It is well-known that most Zα domains bind to Z-DNA in a conformation-specific manner and induce rapid B-Z transition in physiological conditions. Although many structural and biochemical studies have identified the detailed interactions between the Zα domain and Z-DNA, little is known about the molecular basis of the B-Z transition process. In this study, we successfully converted the B-Z transition-defective Zα domain, vvZαE3L, into a B-Z converter by improving B-DNA binding ability, suggesting that B-DNA binding is involved in the B-Z transition. In addition, we engineered the canonical B-DNA binding protein GH5 into a Zα-like protein having both Z-DNA binding and B-Z transition activities by introducing Z-DNA interacting residues. Crystal structures of these mutants of vvZαE3L and GH5 complexed with Z-DNA confirmed the significance of conserved Z-DNA binding interactions. Altogether, our results provide molecular insight into how Zα domains obtain unusual conformational specificity and induce the B-Z transition.
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http://dx.doi.org/10.1093/nar/gkaa1115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736808PMC
December 2020

Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial.

Rheumatology (Oxford) 2021 05;60(5):2277-2287

Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.

Objective: To assess non-inferiority of s.c. to i.v. CT-P13 in RA.

Methods: Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46-54) then PFS (W56-64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: -0.6).

Results: Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS.

Conclusion: CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients.

Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.
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http://dx.doi.org/10.1093/rheumatology/keaa580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121438PMC
May 2021
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