Publications by authors named "Hyo-Jin Kim"

417 Publications

Association between serum uric acid and left ventricular hypertrophy/left ventricular diastolic dysfunction in patients with chronic kidney disease.

PLoS One 2021 6;16(5):e0251333. Epub 2021 May 6.

Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea.

Background: The level of serum uric acid (SUA) has been reported to be associated with left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). However, this association remains unclear in patients with chronic kidney disease (CKD).

Methods: A total of 1025 patients with pre-dialysis CKD with preserved left ventricular systolic function were enrolled in this cross-sectional study. The LVH and LVDD were assessed using two-dimensional echocardiography and tissue Doppler imaging. The associations of LVH/LVDD with clinical and laboratory variables were investigated using univariable and multivariable logistic regression analyses.

Results: In a multivariable analysis, the SUA level was an independent predictor of LVH (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.31-1.50, P < 0.001). In addition, patient age, systolic blood pressure, intact parathyroid hormone levels, and left atrial volume index levels were independent predictors of LVH. The SUA level was also an independent predictor of LVDD (OR: 1.93, 95% CI: 1.53-2.43, P < 0.001). Furthermore, systolic blood pressure and left atrial volume index levels were an independent predictor of LVDD. Receiver-operating characteristic curve analysis showed that the best cutoff values of SUA levels for identifying LVH and LVDD were ≥ 7.5 mg/dL and ≥ 6.3 mg/dL, respectively.

Conclusion: The SUA level was an independent predictor of LVD and LVDD in patients with CKD, suggesting that SUA could be a biomarker for LVH and LVDD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251333PLOS
May 2021

Endothelial Cells Differentiated from Porcine Epiblast Stem Cells.

Cell Reprogram 2021 Apr;23(2):89-98

Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, Republic of Korea.

Pluripotent stem cells (PSCs) have the ability of self-renewal that can retain the characteristics of the mother cell, and of pluripotency that can differentiate into several body types. PSCs typically include embryonic stem cells (ESCs) derived from the inner cell mass of the preimplantation embryo, and epiblast stem cells (EpiSCs) derived from the epiblast of postimplantation embryo. Although PSCs are able to be used by differentiation into endothelial cells as a potential treatment for vascular diseases, human ESCs and induced PSCs (iPSCs) are followed by ethical and safety issues. Pigs are anatomically and physiologically similar to humans. Therefore, the goal of this study was to establish an efficient protocol that differentiates porcine EpiSCs (pEpiSCs) into the endothelial cells for applying the treatment of human vascular diseases. As a result, alkaline phosphatase (AP)-negative (-) pEpiSCs cultured in endothelial cell growth basal medium-2 (EBM-2) differentiation medium in association with 50 ng/mL of vascular endothelial growth factor (VEGF) for 8 days were changed morphologically like the feature of endothelial cells, and expression of pluripotency-associated markers (OCT-3/4, NANOG, SOX2, and C-MYC) in porcine differentiated cells was significantly decreased ( < 0.05). Additionally, when pEpiSCs were cultured in EBM-2 + 50 ng/mL of VEGF, porcine differentiated cells represented a common endothelial cell marker positive (CD31+) but monocytes and lymphocytes marker negative (CD45-). Therefore, these results indicated that pEpiSCs cultured in EBM-2 + 50 ng/mL of VEGF culture condition were efficiently differentiated into endothelial cells for the treatment of blood vessel diseases.
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http://dx.doi.org/10.1089/cell.2020.0088DOI Listing
April 2021

Impact of nutritional index on contrast-associated acute kidney injury and mortality after percutaneous coronary intervention.

Sci Rep 2021 Mar 29;11(1):7123. Epub 2021 Mar 29.

Division of Nephrology, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.

The risk of malnutrition in acute kidney injury and mortality in coronary artery disease patients has not been studied. This study aimed to evaluate whether nutritional status assessed by Onodera's prognostic nutritional index (PNI) was related to percutaneous coronary intervention (PCI) outcomes. A total of 3731 patients who received PCI between January 2010 and December 2018 were included. The relationship between PNI at the time of PCI and the occurrence of contrast-associated acute kidney injury (AKI) and all-cause death was evaluated using logistic regression and Cox proportional hazards models, respectively. AKI occurred in 271 patients (7.3%). A low PNI was independently associated with an increased risk of AKI on multivariate logistic regression analysis (OR 0.96, 95% CI 0.94-0.98, P = 0.001). During the median follow-up of 4.3 years, Kaplan-Meier analysis showed that patients with AKI/low PNI < 47.8 had a higher death rate. After adjusting for various risk factors, a low PNI was a significant risk factor for mortality (HR 0.98, CI 0.96-0.99, P = 0.003). A low level of PNI was associated with increased mortality, especially in the group aged over 70 years and female sex. PNI was closely associated with acute kidney outcomes and patient mortality after PCI.
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http://dx.doi.org/10.1038/s41598-021-86680-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007688PMC
March 2021

Different Seasonal Variations of Potassium in Hemodialysis Patients with High Longitudinal Potassium Levels: A Multicenter Cohort Study Using DialysisNet.

Yonsei Med J 2021 Apr;62(4):315-324

Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

Purpose: To determine seasonal variations in serum potassium levels among hemodialysis patients.

Materials And Methods: This was a multicenter cohort study of patients whounderwent hemodialysis and were registered in DialysisNet at our four associated general hospitals between January and December 2016. Month-to-month potassium variability was quantified as SD/√{n/(n-1)}, and a non-hierarchical method was used to cluster groups according to potassium trajectories. Seasonal variations in potassium levels were analyzed using a cosinor analysis.

Results: The analysis was performed on 279 patients with a mean potassium level of 5.08±0.58 mmol/L. After clustering, 52.3% (n=146) of patients were included in the moderate group (K, 4.6±0.4 mmol/L) and 47.7% (n=133) in the high group (K, 5.6±0.4 mmol/L). The mean potassium level peaked in January in the moderate group (4.83±0.74 mmol/L) and in August in the high group (5.51±0.70 mmol/L). In the high potassium group, potassium levels were significantly higher in summer than in autumn (<0.001) and spring (=0.007). Month-to-month potassium variability was greater in the high group than in the moderate group (0.59±0.19 mmol/L vs. 0.52±0.21 mmol/L, respectively, =0.012). Compared to patients in the first quartile of potassium variability (≤0.395 mmol/L), those with higher variability (2nd-4th quartiles) were 2.8-4.2 fold more likely to be in the high potassium group.

Conclusion: Different seasonal patterns of serum potassium were identified in the moderate and high potassium groups, with potassium levels being significantly higher in the summer season in the high potassium group and in winter for the moderate potassium group.
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http://dx.doi.org/10.3349/ymj.2021.62.4.315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007431PMC
April 2021

Dialysis unit blood pressure two hours after hemodialysis is useful for predicting home blood pressure and ambulatory blood pressure in maintenance hemodialysis patients.

Ther Apher Dial 2021 Mar 27. Epub 2021 Mar 27.

Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.

This study aimed to determine which BP measurement obtained in the HD unit correlated best with home BP and ambulatory BP monitoring (ABPM). We retrospectively analyzed data from 40 patients that received maintenance HD who had available home BP and ABPM data. Dialysis unit BPs were the averages of pre-, 2hr- (2 h after starting HD), and post-HD BP during a 9-month study. Home BP was defined as the average of morning and evening home BPs. Dialysis unit BP and home BP were compared over the 9-month study period. ABPM was performed once for 24 h in the absence of dialysis during the final 2 weeks of the study period and was compared to the 2-week dialysis unit BP and home BP. There was a significant difference between dialysis unit systolic blood pressure (SBP) and home SBP over the 9-month period. No significant difference was observed between the 2hr-HD SBP and home SBP. When analyzing 2 weeks of dialysis unit BP and home BP, including ABPM, SBPs were significantly different (dialysis unit BP > home BP > ABPM; P = 0.009). Consistent with the 9-month study period, no significant difference was observed between 2hr-HD SBP and home SBP (P = 0.809). The difference between 2hr-HD SBP and ambulatory SBP was not significant (P = 0.113). In conclusion, the 2hr-HD SBP might be useful for predicting home BP and ABPM in HD patients.
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http://dx.doi.org/10.1111/1744-9987.13648DOI Listing
March 2021

Ultra-Lightweight, Flexible InGaP/GaAs Tandem Solar Cells with a Dual-Function Encapsulation Layer.

ACS Appl Mater Interfaces 2021 Mar 10;13(11):13248-13253. Epub 2021 Mar 10.

School of Electrical and Electronic Engineering, Yonsei University, 50, Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

Lightweight, flexible solar cells from III-V semiconductors offer new application opportunities for devices that require a power supply, such as cars, drones, satellites, or wearable devices, due to their outstanding efficiency and power-to-weight ratio (specific power). However, the specific power and stability of flexible photovoltaic (PV) devices need to be enhanced for use in such applications because current flexible PV devices are vulnerable to moisture and heat. Here, we develop ultra-lightweight, flexible InGaP/GaAs tandem solar cells with a dual-function encapsulation layer that serves as both a moisture barrier and an antireflection coating for the active device layer. Using a thin polymer film as a substrate and an ultrathin metal as a bonding layer, the total weight of the device is dramatically reduced. Therefore, the specific power of our solar cells is remarkably high with a value of over 5000 W/kg under the AM 1.5G solar spectrum. Additionally, there is no degradation even if the solar cells are exposed to harsh environmental conditions.
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http://dx.doi.org/10.1021/acsami.1c00006DOI Listing
March 2021

OTUD6A Is an Aurora Kinase A-Specific Deubiquitinase.

Int J Mol Sci 2021 Feb 16;22(4). Epub 2021 Feb 16.

Department of Life Sciences, Sogang University, Seoul 04107, Korea.

Aurora kinases are serine/threonine kinases required for cell proliferation and are overexpressed in many human cancers. Targeting Aurora kinases has been a therapeutic strategy in cancer treatment. Here, we attempted to identify a deubiquitinase (DUB) that regulates Aurora kinase A (Aurora-A) protein stability and/or kinase activity as a potential cancer therapeutic target. Through pull-down assays with the human DUB library, we identified OTUD6A as an Aurora-A-specific DUB. OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A. Notably, OTUD6A promotes the protein half-life of Aurora-A and activates Aurora-A by increasing phosphorylation at threonine 288 of Aurora-A. From qPCR screening, we identified and validated that the cancer gene encoding Cyclin-dependent kinases regulatory subunit 2 is the most upregulated cell cycle regulator when OTUD6A is overexpressed. The results suggest that OTUD6A may serve as a therapeutic target in human cancers.
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http://dx.doi.org/10.3390/ijms22041936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919836PMC
February 2021

Epigenetic regulation of TGF-β-induced EMT by JMJD3/KDM6B histone H3K27 demethylase.

Oncogenesis 2021 Feb 26;10(2):17. Epub 2021 Feb 26.

Department of Biochemistry, Kangwon National University, Chuncheon, Gangwon-do, 24341, Republic of Korea.

Transforming growth factor-β (TGF-β) signaling pathways are well-recognized for their role in proliferation and epithelial-mesenchymal transition (EMT) of cancer cells, but much less is understood about their contribution to interactions with other signaling events. Recent studies have indicated that crosstalk between TGF-β and Ras signaling makes a contribution to TGF-β-mediated EMT. Here, we demonstrate that Jumonji domain containing-3 (JMJD3 also called KDM6B) promotes TGF-β-mediated Smad activation and EMT in Ras-activated lung cancer cells. JMJD3 in lung cancer patients was significantly increased and JMJD3 expression in lung tumor tissues was correlated with expression of K-Ras or H-Ras in particular, and its expression was regulated by Ras activity in lung cancer cells. JMJD3 promotes TGF-β-induced Smad activation and EMT in Ras-activated lung cancer cells through the induction of syntenin, a protein that regulates TGF-β receptor activation upon ligand binding. Tissue array and ChIP analysis revealed that JMJD3 epigenetically induces syntenin expression by directly regulating H3K27 methylation levels. Mechanical exploration identified a physical and functional association of JMJD3 with syntenin presiding over the TGF-β in Ras-activated lung cancer cells. Taken together, these findings provide new insight into the mechanisms by which JMJD3 promotes syntenin expression resulting in oncogenic Ras cooperation with TGF-β to promote EMT.
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http://dx.doi.org/10.1038/s41389-021-00307-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910473PMC
February 2021

Median nerve swelling is an independent risk factor of carpal tunnel syndrome in chronic hemodialysis patients.

Ther Apher Dial 2021 Feb 25. Epub 2021 Feb 25.

Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea.

Carpal tunnel syndrome (CTS) has a wide variety of underlying causes and occurs in association with dialysis. Early diagnosis is essential to prevent permanent nerve damage and functional sequelae. We evaluated the association between CTS and cross-sectional area (CSA) of the median nerve in chronic hemodialysis (HD) patients. Patients with end-stage renal disease on maintenance HD via arteriovenous fistula were enrolled. We divided 43 patients into two groups; patients diagnosed with CTS (n = 19) and patients without CTS (n = 24). The median nerve CSA was measured at the wrist (CSA-W) and forearm (CSA-F) by ultrasonography. Median nerve swelling was assessed by the wrist-to-forearm ratio (WFR). There were no significant differences in the underlying causes of chronic kidney disease and adequacy of dialysis between the two groups (p = NS). The patients with CTS showed significantly higher WFR than the patients without CTS (p = 0.001). Univariate Cox regression analysis revealed that WFR >1.25 (odds ratio, 6.30; 95% confidence interval, 1.44-27.45; p = 0.014) was associated with CTS in HD patients. The factors traditionally associated with CTS such as age, sex, diabetes, vintage of HD, β2-MG, intact PTH, and Kt/V were not associated with CTS. After adjustment for age and sex, we found a strong correlation between CTS and the WFR >1.25 (odds ratio, 10.8; 95% confidence interval, 1.85-62.4; p = 0.008). High WFR was associated with the development of CTS, and median nerve swelling was an independent risk factor of CTS in chronic HD patients.
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http://dx.doi.org/10.1111/1744-9987.13636DOI Listing
February 2021

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously.

Am J Physiol Renal Physiol 2021 04 22;320(4):F559-F568. Epub 2021 Feb 22.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Hypercalciuria is one of the early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal Ca reabsorption. Soluble klotho has been previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose, where sialic acid is located, on TRPV5, rather than cleave it. Here, we report that soluble klotho tethers TRPV5 on the membrane by binding both TRPV5 and galectin-1, thereby protecting membrane TRPV5 from diabetes-induced endocytosis. In the present study, we injected recombinant soluble α-klotho protein (rKL) into and mice for 8 wk and collected urine and kidneys. We administered rKL, AZD4547 [fibroblast growth factor (FGF) receptor type 1 inhibitor], and OTX008 (galectin-1 inhibitor) to cultured mouse distal tubular cells with or without 30 mM high-glucose (HG) exposure. mice showed increased renal Ca excretion and decreased renal TRPV5 expression. rKL treatment reversed this change. In vitro, TRPV5 expression in distal tubular cells decreased under HG conditions, and rKL successfully upregulated TRPV5 with or without FGF23. Also, immunofluorescence showed colocalization of klotho, TRPV5, and galectin-1 in distal tubule cells, suggesting that klotho binds to both TRPV5 and galectin-1. Moreover, when both FGF receptor type 1 and galectin-1 were inhibited, rKL failed to increase TRPV5 under HG conditions. Our results indicate that soluble klotho prevents TRPV5 from degradation and subsequent diabetes-induced endocytosis by anchoring TRPV5 through binding with both TRPV5 and galectin-1. Soluble α-klotho anchors transient receptor potential vanilloid type 5 (TRPV5) on the apical membrane of the distal tubule by binding both TRPV5 and a membrane-abundant protein, galectin-1. This newly discovered mechanism works even when fibroblast growth factor (FGF)23 signaling is inhibited by treatment with FGF receptor type 1 inhibitor. Therefore, we identified how soluble α-klotho increases TRPV5 without FGF23. We confirmed this mechanism by observing that soluble α-klotho fails to enhance TRPV5 when both FGF receptor type 1 and galectin-1 are inhibited.
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http://dx.doi.org/10.1152/ajprenal.00044.2021DOI Listing
April 2021

Analysis of access flow using duplex ultrasonography and the ultrasound dilutional method.

J Vasc Access 2021 Feb 2:1129729821991756. Epub 2021 Feb 2.

Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea.

Background: This study aimed to evaluate the correlation between duplex ultrasonography (DUS) and ultrasound dilution (UD) measurement's results and determine the factors affecting the correlation of the measured values among other clinical factors in patients.

Methods: This cross-sectional study was conducted from April 2020 to May 2020 and included 60 patients who visited our dialysis centre. The flow of the fistula was measured in the proximal brachial artery using DUS. While dialysis was performed on the same day, the access flow was measured using the UD method. The correlation and agreement between the access flows acquired by each measurement method were analysed. Similarly, the correlation was analysed by classifying the groups based on the predisposing factor, and statistically significant factors were observed through comparison.

Results: Both measurements showed a moderate positive correlation ( = 0.60,  < 0.01). The bias (mean of UD-DUS) between the two measurements was about 230 mL/min. When the measurement site of DUS was near the inflow artery and in the same anatomical section, a strong correlation with the measurement value of UD was observed (brachial based fistula:  = 0.85, radial based fistula:  = 0.87). Similarly, for patients without diabetes and those who regularly underwent access surveillance for the dialysis route, strong correlations were observed between the two measurements ( = 0.79 and  = 0.88).

Conclusions: Several factors can influence the correlation between UD and DUS. The findings showed a high correlation for DUS measurement sites within the same anatomical section as the inflow artery, patients without diabetes, and patients undergoing periodic surveillance.
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http://dx.doi.org/10.1177/1129729821991756DOI Listing
February 2021

The complete mitochondrial genome of (Erxleben, 1777), as a model species of Chronic Wasting Disease (CWD).

Mitochondrial DNA B Resour 2020 Jul 2;5(3):2621-2623. Epub 2020 Jul 2.

Foreign Animal Disease Research Division, Animal and Plant Quarantine Agency (APQA), OIE Reference Laboratory for CWD, Gimcheon, Korea.

(Erxleben, 1777) has been used as a model species of Chronic Wasting Disease (CWD). We completed the mitochondrial genome of , susceptible to the CWD. Its length is 16,428 bp, identical to the previous mitochondrial genome of , and 37 genes (13 protein-coding genes, two rRNAs, and 22 tRNAs) were identified. It may reflect the extreme decrease of tule elk population in 1870s and CWD is not related to genetic elements on mitochondrial genome. Phylogenetic trees show that our mitochondrial genome is clustered with the previously sequenced mitochondrial genome of .
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http://dx.doi.org/10.1080/23802359.2020.1780983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782213PMC
July 2020

The first complete mitogenome of (Merriam, 1905).

Mitochondrial DNA B Resour 2020 Jun 2;5(3):2294-2296. Epub 2020 Jun 2.

OIE Reference Laboratory for CWD, Foreign Animal Disease Research Division, Animal and Plant Quarantine Agency (APQA), Gimcheon, Gyeongsangbukdo, Korea.

(Merriam, 1905) is one of the subspecies of elk distributed only in California, USA. We completed the first mitogenome of . Its length is 16,428 bp, which is in middle among 24 available mitogenomes. It contains 37 genes (13 protein-coding genes, 2 rRNAs, and 22 tRNAs). Phylogenetic trees show that was clustered with some subspecies of . Number of inter-subspecific variations between and are relatively small in comparison to intraspecific variations of insect and fish mitogenomes and plant chloroplast genomes.
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http://dx.doi.org/10.1080/23802359.2020.1772689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782940PMC
June 2020

Salinomycin suppresses TGF-β1-induced EMT by down-regulating MMP-2 and MMP-9 via the AMPK/SIRT1 pathway in non-small cell lung cancer.

Int J Med Sci 2021 1;18(3):715-726. Epub 2021 Jan 1.

Department of Internal Medicine, Wonkwang University, School of Medicine, Iksan, Jeonbuk 54538, Republic of Korea.

Salinomycin (Sal) is a recently identified anti-tumor drug for treating several types of solid tumor; however, its effects on the migratory and invasive properties of non-small cell lung cancer (NSCLC) remain unclear. This study investigated the inhibitory effect underlying mechanisms of Salon transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) and cell migration. Sal solidly blocked cell migration and invasion enhancement by TGF-β1-induced EMT, through recovering E-cadherin loss and suppressing mesenchymal markers induction, as well as TGF-β1-mediated AMPK/SIRT signaling activity upregulation. The pharmacologic inhibition or knockdown of AMPK or SIRT1 can act synergistically with Sal to inhibit TGF-β1-induced MMP-2 and MMP-9. In contrast, AMPK or SIRT1 upregulation can protect against TGF-β1-induced MMP-2 and MMP-9 inhibition by Sal. Next we demonstrated that the MMP-2 and MMP-9 knockdown can act synergistically with Sal to inhibit TGF-β1-induced EMT. Moreover, treatment of PMA of MMP activator increased TGF-β1-induced MMP-2 and MMP-9, even with Sal. Our results demonstrate that Sal suppresses TGF-β1-induced EMT by downregulating MMP-2 and MMP-9 through the AMPK/SIRT pathway, thereby inhibiting lung cancer cell migration and invasion.
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http://dx.doi.org/10.7150/ijms.50080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797542PMC
January 2021

Experimental oral transmission of chronic wasting disease to sika deer ().

Prion 2020 12;14(1):271-277

National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency , Ottawa, Canada.

Chronic wasting disease (CWD) affects a broad array of cervid species and continues to be detected in an expanding geographic range. Initially introduced into the Republic of Korea through the importation of CWD-infected elk (), additional cases of CWD were subsequently detected in farmed Korean elk and sika deer (). Wild and farmed sika deer are found in many regions of Asia, North America, and Europe, although natural transmission to this species has not been detected outside of the Republic of Korea. In this study, the oral transmission of CWD to sika deer was investigated using material from CWD-affected elk. Pathological prion (PrP) immunoreactivity was detected in oropharyngeal lymphoid tissues of one sika deer at 3.9 months post-inoculation (mpi) and was more widely distributed in a second sika deer examined at 10.9 mpi. The remaining four sika deer progressed to clinical disease between 21 and 24 mpi. Analysis of PrP tissue distribution in clinical sika deer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, and the gastrointestinal tract. Prion protein gene () sequences of these sika deer were identical and consistent with those reported in natural sika deer populations. These findings demonstrate the efficient oral transmission of CWD from elk to sika deer.
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http://dx.doi.org/10.1080/19336896.2020.1857038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734081PMC
December 2020

Airway Management with Dexmedetomidine and High-Flow Nasal Cannula in a Patient with Deep Neck Infection.

Int Med Case Rep J 2020 2;13:679-683. Epub 2020 Dec 2.

Department of Anesthesiology and Pain Medicine, Inje University Seoul Paik Hospital, Seoul, Korea.

Retropharyngeal deep neck infection sometimes necessitates securing of the airway and surgery for drainage. Airway management in patients with deep neck infection is challenging for anesthesiologists. A 56-year-old woman diagnosed with deep neck infection was admitted for incision and drainage. In the first operation for incision and drainage, indirect videolaryngoscope was utilized to confirm the airway before tracheal intubation, and the patient was intubated successfully. In the second operation for wound closure, dexmedetomidine administration and high-flow nasal cannulation were used during monitored anesthesia care throughout a subsequent procedure. The outcome in the present case suggests that indirect videolaryngoscope, dexmedetomidine, and high-flow nasal cannula can facilitate effective management during surgery in patients with retropharyngeal deep neck space infection.
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http://dx.doi.org/10.2147/IMCRJ.S276018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719301PMC
December 2020

Comparative study of the effects of diosmin and diosmetin on fat accumulation, dyslipidemia, and glucose intolerance in mice fed a high-fat high-sucrose diet.

Food Sci Nutr 2020 Nov 20;8(11):5976-5984. Epub 2020 Sep 20.

Korea Food Research Institute Wanju-gun Republic of Korea.

This study compared the effects of diosmin and its aglycone, diosmetin, on body weight, liver fat, serum cholesterol, and glucose intolerance in male C57BL/6 mice fed a high-fat high-sucrose (HFHS) diet for 12 weeks. The mice were divided into four groups that received the following diets: normal diet (ND), HFHS diet, HFHS diet with 0.5% diosmin, and HFHS diet with 0.5% diosmetin. The body weight increased significantly in the HFHS diet group but decreased significantly in the HFHS diet with 0.5% diosmin group. The diosmin and diosmetin treatment inhibited fat accumulation in liver and epididymal tissues, and improved glucose intolerance by lowering glucose levels during a glucose tolerance test; these effects were greater in the diosmin group than those in the diosmetin group. Furthermore, only diosmin significantly ameliorated dyslipidemia, by reducing TC and LDL-C levels, while diosmetin had little effect on these parameters. Taken together, the results showed that diosmin and diosmetin can prevent fat accumulation and glucose intolerance; however, diosmin was more effective and also showed an antidyslipidemic effect.
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http://dx.doi.org/10.1002/fsn3.1883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684606PMC
November 2020

[Endotracheal tube cuff pressure increases in patients undergoing shoulder arthroscopy: a single cohort study].

Rev Bras Anestesiol 2020 Nov-Dec;70(6):583-587. Epub 2020 Nov 18.

Inje University Seoul Paik Hospital, Department of Anesthesiology and Pain Medicine, Seoul, Coreia. Electronic address:

Background And Objectives: Several airway complications can occur during shoulder arthroscopy including airway obstruction, pleural puncture, and subcutaneous emphysema. It was hypothesized that the irrigation fluid used during a shoulder arthroscopic procedure might increase the cuff pressure of the endotracheal tube, which can cause edema and ischemic damage to the endotracheal mucosa. Therefore, this study aimed to evaluate the relationship between irrigation fluid and endotracheal tube cuff pressures.

Methods: Forty patients aged 20 to 70 years with an American Society of Anesthesiologists (ASA) score I or II, scheduled for elective arthroscopic shoulder surgery under general anesthesia, participated in our study. We recorded endotracheal tube cuff pressures and neck circumferences every hour from the start of the operation. We also recorded the total duration of the anesthesia, operation, and the total volume of fluid used for irrigation.

Results: A positive correlation was shown between endotracheal tube cuff pressures and the amount of irrigation fluid (r = 0.385, 95% CI 0.084 to 0.62, p = 0.0141). The endotracheal tube cuff pressure significantly increased at 2 and 3hours after starting the operation (p = 0.0368 and p = 0.0245, respectively). However, neck circumference showed no significant difference.

Conclusions: Endotracheal tube cuff pressures increased with operation time and with increased volumes of irrigation fluid used in patients who underwent shoulder arthroscopy. We recommend close monitoring of endotracheal tube cuff pressures during shoulder arthroscopy, especially during long operations using a large amount of irrigation fluid, to prevent complications caused by raised cuff pressures.
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http://dx.doi.org/10.1016/j.bjan.2020.04.021DOI Listing
November 2020

Expert-level segmentation using deep learning for volumetry of polycystic kidney and liver.

Investig Clin Urol 2020 11;61(6):555-564

Department of Urology, Hallym University Sacred Heart Hospital, Hallym University Collge of Medicine, Anyang, Korea.

Purpose: Volumetry is used in polycystic kidney and liver diseases (PKLDs), including autosomal dominant polycystic kidney disease (ADPKD), to assess disease progression and drug efficiency. However, since no rapid and accurate method for volumetry has been developed, volumetry has not yet been established in clinical practice, hindering the development of therapies for PKLD. This study presents an artificial intelligence (AI)-based volumetry method for PKLD.

Materials And Methods: The performance of AI was first evaluated in comparison with ground-truth (GT). We trained a V-net-based convolutional neural network on 175 ADPKD computed tomography (CT) segmentations, which served as the GT and were agreed upon by 3 experts using images from 214 patients analyzed with volumetry. The dice similarity coefficient (DSC), interobserver correlation coefficient (ICC), and Bland-Altman plots of 39 GT and AI segmentations in the validation set were compared. Next, the performance of AI on the segmentation of 50 random CT images was compared with that of 11 PKLD specialists based on the resulting DSC and ICC.

Results: The DSC and ICC of the AI were 0.961 and 0.999729, respectively. The error rate was within 3% for approximately 95% of the CT scans (error<1%, 46.2%; 1%≤error<3%, 48.7%). Compared with the specialists, AI showed moderate performance. Furthermore, an outlier in our results confirmed that even PKLD specialists can make mistakes in volumetry.

Conclusions: PKLD volumetry using AI was fast and accurate. AI performed comparably to human specialists, suggesting its use may be practical in clinical settings.
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http://dx.doi.org/10.4111/icu.20200086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606119PMC
November 2020

Evaluation of assembly methods combining long-reads and short-reads to obtain sp. R4 high-quality complete genome.

3 Biotech 2020 Nov 19;10(11):480. Epub 2020 Oct 19.

Unit of Polar Genomics, Korea Polar Research Institute (KOPRI), Inchon, 21990 Republic of Korea.

We sequenced the sp. R4 using Oxford Nanopore Technology (ONT), single molecule real-time (SMRT) technology from Pacific Biosciences (PacBio), and Illumina technologies to investigate the application of nanopore reads in de novo sequencing of bacterial genomes. We compared the differences in both genome sequences between genome assemblies using nanopore and PacBio reads and focused on the difference in the prediction of coding sequences. The results indicated that for more accurate predictions of open reading frames, contigs in the assemblies using only PacBio reads also needed to be corrected using short reads with high-quality bases, and repeat regions in genomes did not affect the increase of mispredicted coding sequences via genome polishing significantly. In assemblies using only nanopore reads, genome polishing was essential, but many repeat regions in genomes might increase the number of mispredicted coding sequences via genome polishing. The hybrid assembly combining the long reads and short reads represents the best result for coding sequence predictions in genome assemblies using nanopore reads.
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http://dx.doi.org/10.1007/s13205-020-02474-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573059PMC
November 2020

Reliability of pre-operative diffusion tensor imaging parameter measurements of the cervical spine in patients with cervical spondylotic myelopathy.

Sci Rep 2020 10 15;10(1):17410. Epub 2020 Oct 15.

Department of Radiology, Seoul National University Bundang Hospital, 166, Gumi-ro, Bundang-gu, Seongnam-si, 463-707, Gyeonggi-do, Korea.

The present study assessed test-retest and inter-observer reliability of diffusion tensor imaging (DTI) in cervical spondylotic myelopathy (CSM), as well as the agreement among measurement methods. A total 34 patients (12 men, 22 women; mean age, 58.7 [range 45-79] years) who underwent surgical decompression for CSM, with pre-operative DTI scans available, were retrospectively enrolled. Four observers independently measured fractional anisotropy (FA) values twice, using three different measurement methods. Test-retest and inter-observer reliability was assessed using intraclass correlation coefficients (ICCs). Overall, inter-observer agreements varied according to spinal cord level and the measurement methods used, and ranged from poor to excellent agreement (ICC = 0.374-0.821), with relatively less agreement for the sagittal region of interest (ROI) method. The radiology resident and neuro-radiologist group showed excellent test-retest reliability at almost every spinal cord level (ICC = 0.887-0.997), but inter-observer agreements varied from fair to good (ICC = 0.404-0.747). Despite excellent test-retest reliability of the ROI measurements, FA measurements in patients with CSM varied widely in terms of inter-observer reliability. Therefore, DTI parameter data should be interpreted carefully when applied clinically.
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http://dx.doi.org/10.1038/s41598-020-74624-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566607PMC
October 2020

Reinforced-hydrogel encapsulated hMSCs towards brain injury treatment by trans-septal approach.

Biomaterials 2021 Jan 30;266:120413. Epub 2020 Sep 30.

Nano-Bio Regenerative Medical Institute, College of Medicine, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do, 24252, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, School of Medicine, Hallym University, Chuncheon, 24253, Republic of Korea. Electronic address:

Encapsulated stem cells in various biomaterials have become a potentially promising cell transplantation strategy in the treatment of various neurologic disorders. However, there is no ideal cell delivery material and method for clinical application in brain diseases. Here we show silk fibroin (SF)-based hydrogel encapsulated engineered human mesenchymal stem cells (hMSCs) to overproduce brain-derived neurotrophic factor (BDNF) (BDNF-hMSC) is an effective approach to treat brain injury through trans-septal cell transplantation in the rat model. In this study, we observed SF induced sustained BDNF production by BDNF-hMSC both in 2D (9.367 ± 1.969 ng/ml) and 3D (7.319 ± 0.1025 ng/ml) culture conditions for 3 days. Through immunohistochemistry using α-tubulin, BDNF-hMSCs showed a significant increased average neurite length of co-cultured neuro 2a (N2a) cells, suggested that BDNF-hMSCs induced neurogenesis in vitro. Encapsulated BDNF-hMSC, pre-labeled with the red fluorescent dye PKH-26, exhibited intense fluorescence up to 14 days trans-septal transplantation, indicated excellent viability of the transplanted cells. Compared to the vehicle-treated, encapsulated BDNF- hMSC demonstrated significantly increased BDNF level both in the sham-operated and injured hippocampus (Hip) through immunoblot analysis after 7 days implantation. Transplantation of the encapsulated BDNF-hMSC promoted neurological functional recovery via significantly reduced neuronal death in the Hip 7 days post-injury. Using magnetic resonance imaging (MRI) analysis, we demonstrated that encapsulated BDNF-hMSC reduced lesion area significantly at 14 and 21 days in the damaged brain following trans-septal implantation. This stem cell transplantation approach represents a critical set up towards brain injury treatment for clinical application.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120413DOI Listing
January 2021

Piceatannol reduces resistance to statins in hypercholesterolemia by reducing PCSK9 expression through p300 acetyltransferase inhibition.

Pharmacol Res 2020 11 28;161:105205. Epub 2020 Sep 28.

Korea Food Research Institute, Jeollabuk-do, 55365, Republic of Korea; Department of Food Biotechnology, Korea University of Science & Technology, Daejeon, 34113, Republic of Korea. Electronic address:

The purpose of this study was to investigate the role of piceatannol (PT) in statin (rosuvastatin and simvastatin) resistance and tolerance and its association with PCSK9 expression via its p300 inhibitory (p300i) activity. An in vitro study was performed using HepG2 cells that were exposed to statins (rosuvastatin or simvastatin) with or without PT in delipidated serum (DLPS) medium. In the statin exposed conditions, PCSK9 expression was reduced following PT treatment when compared to HepG2 cells w/o PT treatment. Furthermore, no significant difference was observed in the expression of the transcription factors SREBP2 and HNF1α, which regulate PCSK9 expression. This resulted in low density lipoprotein receptor (LDLR) stabilization and reduced cellular cholesterol levels. This indicates that PT epigenetically controls statin-induced PCSK9 expression. Interestingly, PT attenuated p300 histone acetyltransferase (HAT) activity. Moreover, simulation of PT-p300 binding suggested that PT inhibits p300 as PT could be docked in the p300 HAT domain. Furthermore, inhibition of p300 HAT activity using C-646, a selective p300 inhibitor, or through an siRNA system effectively reduced PCSK9 induction upon statin exposure in HepG2 cells. The chromatin immunoprecipitation (ChIP) assays revealed that PT blocked the recruitment of p300 to the PCSK9 promoter region. In summary, PT attenuated statin-induced PCSK9 expression by inhibiting p300 HAT activity. Finally, co-administration of simvastatin and PT for 10 weeks further reduced plasma low-density lipoprotein-cholesterol (LDL-C) levels and stabilized the hepatic LDLR protein level compared with those resulting from single treatment of simvastatin in a high-fat diet-induced hypercholesterolemia mouse model. Our findings indicate that PT is a new nutraceutical candidate to reduce the statin resistance and tolerance that occurs in patients with hypercholesterolemia.
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http://dx.doi.org/10.1016/j.phrs.2020.105205DOI Listing
November 2020

Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing.

Oncol Lett 2020 Nov 8;20(5):205. Epub 2020 Sep 8.

Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea.

Extranodal marginal zone lymphoma is a type of low-grade B-cell lymphoma that can be classified as a mucosal-associated lymphoid tissue (MALT) lymphoma. Recently, second-generation or next-generation sequencing (NGS), which allows simultaneous sequencing of hundreds to billions of DNA strands, has been a focus of attention and is rapidly being adopted in various fields. In the present study, paraffin-embedded tissue samples of gastric MALT lymphoma (n=1) and small intestine MALT lymphoma (n=4) were selected, and DNA was extracted from the tissue samples. After performing quality control, NGS was performed using HemaSCAN™, a custom panel of 426 genes, including essential blood cancer genes. NGS revealed single nucleotide variations (SNVs), short insertions and deletions (InDels) and copy number variations (CNVs). These genomic variants were reported as annotated, known or novel variants. An annotated variant, an erb-b2 receptor tyrosine kinase 2 gene amplification, was observed in one patient. Known and novel variants, including SNVs of SET binding protein 6 (SETBP6), Runt-related transcription factor 1 and Kelch-like ECH-associated protein 1 genes, InDel of the marker of proliferation Ki-67 gene, and CNVs of the zinc finger protein 703 and NOTCH1 genes, were observed in ≥2 patients. Additionally, InDels with frameshift mutations were identified in the B-cell lymphoma/leukemia 10, DEAD-box helicase 3 X-linked, forkhead box O3 and mucin 2, oligomeric mucus/gel-forming genes in one patient. Since few NGS studies have been performed on MALT lymphoma, the current results were unable to determine if the different mutations that were identified are 'actionable' (that is, potentially responsive to a targeted therapy) Further studies are required to determine the associations between genetic mutations and the development of MALT lymphoma.
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http://dx.doi.org/10.3892/ol.2020.12068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491050PMC
November 2020

Autoimmune hepatitis in a patient with immunoglobulin A nephropathy: A case report.

World J Clin Cases 2020 Sep;8(17):3828-3834

Division of Nephrology, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea.

Background: Immunoglobulin A nephropathy (IgAN) is the most commonly encountered glomerular disease in Asian countries. It has a broad clinical presentation, and it is frequently associated with other conditions. Chronic liver disease is well recognized as the leading cause of secondary IgAN. However, cases of IgAN associated with autoimmune hepatitis (AIH) have seldom been reported.

Case Summary: A 63-year-old Korean woman was admitted to Pusan National University Hospital for an evaluation of abdominal pain and elevated liver enzymes. Two weeks prior, she had presented to our hospital with proteinuria of approximately 1350 mg/d and hematuria and was diagnosed with IgAN. Autoimmune profiles were highly positive for antinuclear antibodies, and symptoms related to portal hypertension including ascites and peripheral edema were present. A diagnosis of AIH was made according to the simplified scoring system of the International Autoimmune Hepatitis Group. Despite immunosuppression with prednisolone and azathioprine, rapid deterioration of liver function led to end-stage liver disease. After a living-donor liver transplantation, liver function gradually improved, and she had maintained stable liver and kidney function at the six months follow-up.

Conclusion: Cases of secondary IgAN with chronic liver disease have been frequently reported in the literature but are rarely associated with AIH. We encountered an IgAN patient with concurrent progressive liver failure due to AIH.
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http://dx.doi.org/10.12998/wjcc.v8.i17.3828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479551PMC
September 2020

Gonad dose assessment in paediatric kidney nuclear medicine test using Monte Carlo simulation.

J Radiat Res 2020 Nov;61(6):895-902

Dongnam Institute of Radiological & Medical Sciences, (46033) 40, Jwadong-gil, Jangan-eup, Gijang-gun, Busan, Republic of Korea.

In this study, we evaluated the effect of radiation dose on gonads during paediatric kidney nuclear medicine tests. Using Monte Carlo simulations, the distribution and effects of radiation were physically evaluated by displaying the distribution path of the source in the human body over time. In particular, the evaluation of doses in children, who are sensitive to radiation during nuclear medicine tests that use internal exposure among several types of medical exposures, was conducted to obtain data for the management of medical exposures. Our results indicated that under normal kidney function, the dose received by the target kidney was 0.430 mGy/mCi, which is ~6% higher than the dose suggested by the International Commission on Radiation Protection (ICRP). Furthermore, when kidney function was compromised, the dose estimated was 0.726 mGy/mCi, which is ~2% lower than the dose suggested by the ICRP. In the male and female gonads, namely the testicles and ovaries, the doses received were 0.359 mGy/mCi and 0.394 mGy/mCi, respectively, under normal kidney function. Similarly, under abnormal kidney function, the doses ranged from 0.187 to 0.353 mGy/mCi and 0.238 to 0.388 mGy/mCi in the male and female gonads, respectively.
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http://dx.doi.org/10.1093/jrr/rraa080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674698PMC
November 2020

Tunable Dielectric and Thermal Properties of Oxide Dielectrics via Substrate Biasing in Plasma-Enhanced Atomic Layer Deposition.

ACS Appl Mater Interfaces 2020 Oct 24;12(40):44912-44918. Epub 2020 Sep 24.

Division of Mechanical Systems Engineering, Sookmyung Women's University, Seoul 04310, South Korea.

The ability to control the properties of dielectric thin films on demand is of fundamental interest in nanoscale devices. Here, we modulate plasma characteristics at the surface of a substrate to tune both dielectric constant and thermal conductivity of amorphous thin films grown using plasma-enhanced atomic layer deposition. Specifically, we apply a substrate bias ranging from 0 to ∼117 V and demonstrate the systematic tunability of various material parameters of AlO. As a function of the substrate bias, we find a nonmonotonical evolution of intrinsic properties, including density, dielectric constant, and thermal conductivity. A key observation is that the maximum values in dielectric constant and effective thermal conductivity emerge at different substrate biases. The impact of density on both thermal conductivity and dielectric constant is further examined using a differential effective medium theory and the Clausius-Mossotti model, respectively. We find that the peak value in the dielectric constant deviates from the Clausius-Mossotti model, indicating the change of oxygen fraction in our thin films as a function of substrate bias. This finding suggests that the increased local strength of plasma sheath not only enhances material density but also controls the dynamics of microstructural defect formation beyond what is possible with conventional approaches. Based on our experimental observations and modeling, we further build a phenomenological relation between dielectric constant and thermal conductivity. Our results pave invaluable avenues for optimizing dielectric thin films at the atomic scale for a wide range of applications in nanoelectronics and energy devices.
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http://dx.doi.org/10.1021/acsami.0c11086DOI Listing
October 2020

Sargassum horneri (Turner) C. Agardh containing polyphenols attenuates particulate matter-induced inflammatory response by blocking TLR-mediated MYD88-dependent MAPK signaling pathway in MLE-12 cells.

J Ethnopharmacol 2021 Jan 4;265:113340. Epub 2020 Sep 4.

Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju, 63243, Republic of Korea; Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Sargassum horneri (Turner) C. Agardh (S. horneri), an edible brown marine algae, is known to have immunomodulatory effects and has been used in oriental medicine to treat inflammatory diseases. It is well known that ambient particulate matter (PM) is closely related to increased respiratory diseases inducing lung inflammation.

Aim: Considering the use of Sargassum horneri in traditional medicine to treat inflammatory diseases, we hypothesized and investigated the use of Sargassum horneri containing polyphenols against PM-induced inflammatory responses.

Materials And Methods: In this study, we evaluated the impact of PM (majority <2.5 μm in diameter) on deep bronchial penetration ability upon inhalation and a therapeutic approach to mitigate its harmful effects using an ethanol extract of Sargassum horneri, an edible brown algae, containing polyphenols on a type II alveolar epithelial cell line, MLE-12.

Results: PM triggered mRNA expression of toll-like receptors (TLRs) TLR2/4/7, and those TLRs were significantly attenuated by Sargassum horneri extract (SHE). SHE further attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase 1/2 (Erk1/2), and c-Jun NH (2)-terminal kinase (JNK), which were also activated in PM-exposed cells. Altogether, SHE subdued the PM-induced mRNA expression of pro-inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6) and lung epithelial cell derived-chemokines (IL-8, monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL5)). SHE also suppressed the mRNA expression of PM-induced pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33. Furthermore, we showed that SHE suppressed the MAPK-dependent signaling pathway by attenuating receptor-associated factor (TRAF) 6 activation of proteins MyD88 and TNF.

Conclusion: Taking all the data together, we suggest that the anti-inflammatory potential of SHE on PM-exposed MLE-12 cells is mediated by the inhibition of PM-triggered downstream signaling along the TLR2/4/7-MyD88-TRAF6 axis of MAPK signaling.
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http://dx.doi.org/10.1016/j.jep.2020.113340DOI Listing
January 2021

Subclinical sacroiliitis detected by abdominopelvic computed tomography in Korean patients with Crohn's disease.

Korean J Intern Med 2021 Mar 22. Epub 2021 Mar 22.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aims: Sacroiliitis is a frequent extraintestinal manifestation of inflammatory bowel diseases (IBDs). This study aimed to assess the prevalence of sacroiliitis using a validated screening tool based on abdominopelvic computed tomography (APCT) in Korean patients with Crohn's disease (CD) and examine potential associations between clinical characteristics and sacroiliitis.

Methods: One hundred five patients with CD undergoing APCT for any indication at an IBD clinic were matched 1:1 for age and sex with 105 controls without underlying chronic illnesses. Using a validated APCT screening tool that defines sacroiliitis as either ankylosis or a total erosion score (TES) ≥ 3, all computed tomography scans were assessed by two independent, blinded radiologists. We compared the prevalence of sacroiliitis between CD patients and controls and clinical characteristics between CD patients with and without sacroiliitis.

Results: The prevalence of sacroiliitis was significantly higher in CD patients than in controls (13.3% vs. 4.8%, p = 0.030). All subjects with sacroiliitis had a TES ≥ 3, but no ankylosis. The assessment of sacroiliitis in APCT showed excellent interreader reliability (Cohen's kappa = 0.933 for presence of sacroiliitis). Sacroiliitis in CD patients was bilateral and asymptomatic. There were no significant associations between sacroiliitis and any demographic data or clinical characteristics in these patients.

Conclusions: The prevalence of APCT-detected sacroiliitis in CD patients was higher than that in controls, but the condition was asymptomatic. The clinical significance of asymptomatic sacroiliitis in Korean CD patients remains unclear.
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http://dx.doi.org/10.3904/kjim.2020.199DOI Listing
March 2021

Butein Synergizes with Statin to Upregulate Low-Density Lipoprotein Receptor Through -Mediated PCSK9 Inhibition in HepG2 Cells.

J Med Food 2020 Oct 24;23(10):1102-1108. Epub 2020 Aug 24.

Korea Food Research Institute, Wanju-Gun, Korea.

Downregulation of the low-density lipoprotein (LDL) receptor (LDLR) can lead to hypercholesterolemia and related conditions, including cardiovascular diseases. Statins are a class of LDL cholesterol-lowering agents and are best-selling medications for patients at high risk of developing cardiovascular diseases. Indeed, statins upregulate LDLR and proprotein convertase subtilisin/kexin type 9a (PCSK9), leading to LDLR lysosomal degradation, which interferes with the attenuation of hypercholesterolemia. In the present study, butein was found to decrease extracellular PCSK9 levels by reducing its mRNA expression, which was attributable to butein-mediated downregulation of in HepG2 cells. Butein-mediated PCSK9 inhibition further reversed LDLR protein synthesis inhibition, which possibly occurred through butein-mediated inhibition of LDLR degradation. When treated as a combination of butein and a statin, butein reduced statin-mediated enhancement of PCSK9 protein expression. This resulted in a synergistic enhancement of LDLR protein expression, whereas butein alone marginally increased LDLR protein expression. These findings suggest that butein, a novel PCSK9 inhibitor, may be a potential alternative or adjunct to statin treatment.
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http://dx.doi.org/10.1089/jmf.2020.4761DOI Listing
October 2020