Publications by authors named "Seunghun Lee"

161 Publications

Estimated Artificial Neural Network Modeling of Maximal Oxygen Uptake Based on Multistage 10-m Shuttle Run Test in Healthy Adults.

Int J Environ Res Public Health 2021 08 12;18(16). Epub 2021 Aug 12.

Taekwondo Research Institute of Kukkiwon, 32 Teheran 7-gil, Gangnam-gu, Seoul 06130, Korea.

We aimed to develop an artificial neural network (ANN) model to estimate the maximal oxygen uptake (VOmax) based on a multistage 10 m shuttle run test (SRT) in healthy adults. For ANN-based VOmax estimation, 118 healthy Korean adults (59 men and 59 women) in their twenties and fifties (38.3 ± 11.8 years, men aged 37.8 ± 12.1 years, and women aged 38.8 ± 11.6 years) participated in this study; data included age, sex, blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP)), waist circumference, hip circumference, waist-to-hip ratio (WHR), body composition (weight, height, body mass index (BMI), percent skeletal muscle, and percent body), 10 m SRT parameters (number of round trips and final speed), and VOmax by graded exercise test (GXT) using a treadmill. The best estimation results (R = 0.8206, adjusted R = 0.7010, root mean square error; RMSE = 3.1301) were obtained in case 3 (using age, sex, height, weight, BMI, waist circumference, hip circumference, WHR, SBP, DBP, number of round trips in 10 m SRT, and final speed in 10 m SRT), while the worst results (R = 0.7765, adjusted R = 0.7206, RMSE = 3.494) were obtained for case 1 (using age, sex, height, weight, BMI, number of round trips in 10 m SRT, and final speed in 10 m SRT). The estimation results of case 2 (using age, sex, height, weight, BMI, waist circumference, hip circumference, WHR, number of round trips in 10 m SRT, and final speed in 10 m SRT) were lower (R = 0.7909, adjusted R = 0.7072, RMSE = 3.3798) than those of case 3 and higher than those of case 1. However, all cases showed high performance (R) in the estimation results. This brief report developed an ANN-based estimation model to predict the VOmax of healthy adults, and the model's performance was confirmed to be excellent.
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http://dx.doi.org/10.3390/ijerph18168510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391137PMC
August 2021

Use of Quantitative Vertebral Bone Marrow Fat Fraction to Assess Disease Activity and Chronicity in Patients with Ankylosing Spondylitis.

Korean J Radiol 2021 Jul 26. Epub 2021 Jul 26.

Departments of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.

Objective: We quantitatively measured the fat fraction (FF) in the vertebrae of patients with ankylosing spondylitis (AS) using magnetic resonance imaging (MRI) and investigated the role of FF as an indicator of both active inflammation and chronicity.

Materials And Methods: A total of 52 patients with AS who underwent spinal MRI were retrospectively evaluated. The FF values of the anterosuperior and anteroinferior corners of the bone marrow in the L1-S1 spine were assessed using the modified Dixon technique. AS activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), AS Disease Activity Score (ASDAS), and serum inflammatory marker levels. AS disease chronicity was assessed by AS disease duration and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Univariable and multivariable regression analyses were conducted to investigate the correlation between FF and other clinical characteristics.

Results: The mean FF ± standard deviation of the total lumbar spine was 43.0% ± 11.3%. At univariable analysis, spinal FF showed significant negative correlation with BASDAI (β = -0.474, = 0.002) and ASDAS with C-reactive protein (ASDAS-CRP; β = -0.478, = 0.002) and a significant positive correlation with AS disease duration (β = 0.440, = 0.001). After adjusting for patient age, sex, and total mSASSS score, spinal FF remained significantly negatively correlated with BASDAI (β = -0.543, < 0.001), ASDAS-CRP (β = -0.568, < 0.001), and ASDAS with erythrocyte sedimentation rate (β = -0.533, = 0.001). Spinal FF was significantly lower in patients with very high disease activity (ASDAS-CRP > 3.5) than in those with only high disease activity (2.1 ≤ ASDAS-CRP ≤ 3.5) ( = 0.010).

Conclusion: Spinal FF may help assess both AS disease activity and chronicity.
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http://dx.doi.org/10.3348/kjr.2020.0953DOI Listing
July 2021

Comprehensive in vitro comparison of cellular and osteogenic response to alternative biomaterials for spinal implants.

Mater Sci Eng C Mater Biol Appl 2021 Aug 10;127:112251. Epub 2021 Jun 10.

ETH Zurich, Institute for Biomechanics, Zurich, Switzerland. Electronic address:

A variety of novel biomaterials are emerging as alternatives to conventional metals and alloys, for use in spinal implants. These promise potential advantages with respect to e.g. elastic modulus compatibility with the host bone, improved radiological imaging or enhanced cellular response to facilitate osseointegration. However, to date there is scarce comparative data on the biological response to many of these biomaterials that would give insights into the relative level of bone formation, resorption inhibition and inflammation. Thus, in this study, we aimed to evaluate and compare the in vitro biological response to standard discs of four alternative biomaterials: polyether ether ketone (PEEK), zirconia toughened alumina (ZTA), silicon nitride (SN) and surface-textured silicon nitride (ST-SN), and the reference titanium alloy Ti6Al4V (TI). Material-specific characteristics of these biomaterials were evaluated, such as surface roughness, wettability, protein adsorption (BSA) and apatite forming capacity in simulated body fluid. The activity of pre-osteoblasts seeded on the discs was characterized, by measuring viability, proliferation, attachment and morphology. Then, the osteogenic differentiation of pre-osteoblasts was compared in vitro from early to late stage by Alizarin Red S staining and real-time PCR analysis. Finally, osteoclast activity and inflammatory response were assessed by real-time PCR analysis. Compared to TI, all other materials generally demonstrated a lower osteoclastic activity and inflammatory response. ZTA and SN showed generally an enhanced osteogenic differentiation and actin length. Overall, we could show that SN and ST-SN showed a higher osteogenic effect than the other reference groups, an inhibitive effect against bone resorption and low inflammation, and the results indicate that silicon nitride has a promising potential to be developed further for spinal implants that require enhanced osseointegration.
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http://dx.doi.org/10.1016/j.msec.2021.112251DOI Listing
August 2021

Erratum to "Optimization of physicochemical properties of pyridone-based EP3 receptor antagonists" [Bioorg. Med. Chem. Lett. 47 (2021) 128172].

Bioorg Med Chem Lett 2021 Sep 1;47:128232. Epub 2021 Jul 1.

Discovery Sciences, Discovery Chemistry, Janssen Research & Development, LLC, 1400 McKean Road, Box 776, Spring House, PA 19477, United States.

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http://dx.doi.org/10.1016/j.bmcl.2021.128232DOI Listing
September 2021

Effectiveness of bazedoxifene in preventing glucocorticoid-induced bone loss in rheumatoid arthritis patients.

Arthritis Res Ther 2021 07 2;23(1):176. Epub 2021 Jul 2.

Hanyang University Hospital for Rheumatic Diseases, 222-1 wangsimni-ro, Seongdong-gu, Seoul, 04763, South Korea.

Objective: To evaluate the effectiveness of bazedoxifene in preventing bone loss in patients with rheumatoid arthritis (RA) receiving low-dose glucocorticoids (GCs).

Methods: In this randomized, controlled, open-label study, we assigned postmenopausal women with osteopenia who had been receiving low-dose GCs for RA to two groups: a group receiving bazedoxifene (20 mg/day) with elemental calcium 1200 mg and vitamin D 800 IU daily (bazedoxifene group) and a group receiving the same doses of calcium and vitamin D only (control group). As primary outcome, bone mineral density (BMD) change in the lumbar spine (L-spine) from baseline to 48 weeks was assessed. Changes in BMD in the femur, trabecular bone score, bone turnover markers, and development of fracture were assessed as secondary outcomes. For intention-to-treat analysis, 20 completed data sets were created by applying multiple imputations by chained equations.

Results: A total of 114 patients (57 patients in each group) were recruited. A significant increase in L-spine BMD (0.015 g/cm, P = 0.007) was observed in the bazedoxifene group, and the increase was significantly higher than in the control group (0.013, 95% CI 0.0003-0.026, P = 0.047). Reductions in bone turnover markers in the bazedoxifene group were significantly greater than in the control group. Only one fracture was observed in the bazedoxifene group, while four fractures developed in the control group.

Conclusion: In postmenopausal patients with RA receiving low-dose GCs, bazedoxifene improved BMD and reduced bone turnover markers. However, the change in BMD did not exceed the least significant change.

Trial Registration: ClinicalTrials.gov, NCT02602704 .
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http://dx.doi.org/10.1186/s13075-021-02564-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252248PMC
July 2021

Preliminary Validation of a Continuum Model for Dimple Patterns on Polyethylene Naphthalate via Ar Ion Beam Sputtering.

Polymers (Basel) 2021 Jun 10;13(12). Epub 2021 Jun 10.

Department of Nano-Bio Convergence, Korea Institute of Materials Science, 797 Changwondae-ro, Changwon 51508, Korea.

This work reports the self-organization of dimple nanostructures on a polyethylene naphthalate (PEN) surface where an Ar ion beam was irradiated at an ion energy of 600 eV. The peak-to-peak roughness and diameter of dimple nanostructures were 29.1~53.4 nm and 63.4~77.6 nm, respectively. The electron energy loss spectrum at the peaks and troughs of dimples showed similar C=C, C=O, and O=CH bonding statuses. In addition, wide-angle X-ray scattering showed that Ar ion beam irradiation did not induce crystallization of the PEN surface. That meant that the self-organization on the PEN surface could be due to the ion-induced surface instability of the amorphous layer and not due to the partial crystallinity differences of the peaks and valleys. A nonlinear continuum model described surface instability due to Ar ion-induced sputtering. The Kuramoto-Sivashinsky model reproduced the dimple morphologies numerically, which was similar to the experimentally observed dimple patterns. This preliminary validation showed the possibility that the continuum equation used for metal and semiconductor surfaces could be applied to polymer surfaces where ion beam sputtering occurred.
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http://dx.doi.org/10.3390/polym13121932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230451PMC
June 2021

Biomechanics of subtrochanteric fracture fixation using short cephalomedullary nails: A finite element analysis.

PLoS One 2021 1;16(7):e0253862. Epub 2021 Jul 1.

Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital, Hallym University School of Medicine, Anyang, South Korea.

A finite element analysis was performed to evaluate the stresses around nails and cortical bones in subtrochanteric (ST) fracture models fixed using short cephalomedullary nails (CMNs). A total 96 finite element models (FEMs) were simulated on a transverse ST fracture at eight levels with three different fracture gaps and two different distal locking screw configurations in both normal and osteoporotic bone. All FEMs were fixed using CMNs 200 mm in length. Two distal locking screws showed a wider safe range than 1 distal screw in both normal and osteoporotic bone at fracture gaps ≤ 3 mm. In normal bone FEMs fixed even with two distal locking screws, peak von Mises stresses (PVMSs) in cortical bone and nail constructs reached or exceeded 90% of the yield strength at fracture levels 50 mm and 0 and 50 mm, respectively, at all fracture gaps. In osteoporotic bone FEMs, PVMSs in cortical bone and nail constructs reached or exceeded 90% of the yield strength at fracture levels 50 mm and 0 and 50 mm, respectively, at a 1-mm fracture gap. However, at fracture gaps ≥ 2 mm, PVMSs in cortical bone reached or exceeded 90% of the yield strength at fracture levels ≥ 35 mm. PVMSs in nail showed the same results as 1-mm fracture gaps. PVMSs increased and safe range reduced, as the fracture gap increased. Short CMNs (200 mm in length) with two distal screws may be considered suitable for the fixation of ST transverse fractures at fracture levels 10 to 40 mm below the lesser trochanter in normal bone and 10 to 30 mm in osteoporotic bone, respectively, under the assumptions of anatomical reduction at fracture gap ≤ 3 mm. However, the fracture gap should be shortened to the minimum to reduce the risk of refracture and fixation failure, especially in osteoporotic fractures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253862PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248632PMC
July 2021

Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice.

World J Gastroenterol 2021 Jun;27(23):3342-3356

Department of Gastroenterology, Kosin University College of Medicine, Busan 49267, South Korea.

Background: Inflammatory bowel diseases (IBD) is related to uncontrolled immune response. Currently, there is no successful treatment for significant improvement in IBD. Stem cells display their therapeutic effects through their repopulating capacity or secreting factors.

Aim: To investigate the effects of conditioned mouse adipose-derived stem cells (mADSCs) secretome on colitis-induced mice.

Methods: mADSCs were isolated from adipose tissue of C57BL/6 mice. Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides (LPS, 1 μg/mL) for 24 h. Acute colitis was induced by 2% dextran sulfate sodium (DSS) drinking water for 7 d and then normal drinking water for 4 d. The mice were treated with normal culture medium (NM group), conditioned mADSCs secretome (CM group) or mADSCs (SC group). The length of colon and histopatholgy of colon tissues were evaluated. The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin (IL)-6 levels were determined.

Results: The isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment. The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines, colony-stimulating factors and inflammatory cytokines. The loss of body weight and reduction in colon length were ameliorated in the CM group. The conditioned mADSCs secretome reduced the histological score in colon tissue. The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group, respectively. The elevation of serum IL-6 levels was also ameliorated in the CM group. These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced mice.

Conclusion: Conditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis, and may be more effective than stem cells themselves in the regeneration of colon tissue.
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http://dx.doi.org/10.3748/wjg.v27.i23.3342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218368PMC
June 2021

Optimization of physicochemical properties of pyridone-based EP3 receptor antagonists.

Bioorg Med Chem Lett 2021 Sep 6;47:128172. Epub 2021 Jun 6.

Discovery Sciences, Discovery Chemistry, Janssen Research & Development, LLC, 1400 McKean Road, Box 776, Spring House, PA 19477, United States.

A novel series of pyridone-based EP3 receptor antagonists was optimized for good physical properties and oral bioavailability in rodents. The lead compounds 3h, 3l and 4d displayed good in vitro profiles, moderate to good metabolic stability and good rodent PK profiles with low clearance, high oral exposure and acceptable half-life.
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http://dx.doi.org/10.1016/j.bmcl.2021.128172DOI Listing
September 2021

Addition of lactoferrin and substance P in a chitin/PLGA-CaSO hydrogel for regeneration of calvarial bone defects.

Mater Sci Eng C Mater Biol Appl 2021 Jul 6;126:112172. Epub 2021 May 6.

Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi-682041, India. Electronic address:

Calcium-based injectable hydrogels with various bioactive active molecules possess a great potential for bone regeneration. Herein, we have synthesized a chitin-PLGA-calcium sulfate hydrogel (CSG) containing bioactive molecules - lactoferrin (LF) and substance P (SP). SEM and XRD analysis revealed that CS crystal growth was altered with the addition of LF. Rheological measurements indicated that the injectability of the hydrogels was maintained after the addition of LF, however, there was a reduction in storage modulus after LF addition. The addition of LF increased stem cell proliferation whereas, SP enhanced the cell migration. Osteogenic gene expression revealed that LF concentration at 25 μg/mg of CSG was optimal for a favourable outcome. To this optimized LF containing CSG, SP was incorporated and 0.05 μg/mg was found to be most effective (CSG-L3S2) in vitro studies. Further, the μ-CT and histological studies confirmed that CSG-L3S2 showed enhanced bone regeneration compared to the controls in critical-sized calvarial defect of mice. Thus the results indicate that a combination of the chemotactic agent (SP), pleiotropic growth protein (LF), and CS in the chitin-PLGA hydrogel could be a promising approach for non-load bearing bone defects.
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http://dx.doi.org/10.1016/j.msec.2021.112172DOI Listing
July 2021

GRK Inhibition Potentiates Glucagon-Like Peptide-1 Action.

Front Endocrinol (Lausanne) 2021 14;12:652628. Epub 2021 May 14.

Cardiovascular and Metabolic Disease Research, Janssen Research & Development, Spring House, PA, United States.

The glucagon-like peptide-1 receptor (GLP-1R) is a G-protein-coupled receptor (GPCR) whose activation results in suppression of food intake and improvement of glucose metabolism. Several receptor interacting proteins regulate the signaling of GLP-1R such as G protein-coupled receptor kinases (GRK) and β-arrestins. Here we evaluated the physiological and pharmacological impact of GRK inhibition on GLP-1R activity leveraging small molecule inhibitors of GRK2 and GRK3. We demonstrated that inhibition of GRK: i) inhibited GLP-1-mediated β-arrestin recruitment, ii) enhanced GLP-1-induced insulin secretion in isolated islets and iii) has additive effect with dipeptidyl peptidase 4 in mediating suppression of glucose excursion in mice. These findings highlight the importance of GRK to modulate GLP-1R function and . GRK inhibition is a potential therapeutic approach to enhance endogenous and pharmacologically stimulated GLP-1R signaling.
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http://dx.doi.org/10.3389/fendo.2021.652628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160450PMC
May 2021

Lactobacillus rhamnosus HDB1258 modulates gut microbiota-mediated immune response in mice with or without lipopolysaccharide-induced systemic inflammation.

BMC Microbiol 2021 05 13;21(1):146. Epub 2021 May 13.

Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, South Korea.

Background: Gut microbiota closely communicate in the immune system to maintain a balanced immune homeostasis in the gastrointestinal tract of the host. Oral administration of probiotics modulates gut microbiota composition. In the present study, we isolated Lactobacillus rhamnosus HDB1258, which induced tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression in macrophages, from the feces of breastfeeding infants and examined how HDB1258 could regulate the homeostatic immune response in mice with or without lipopolysaccharide (LPS)-induced systemic inflammation.

Results: Oral administration of HDB1258 significantly increased splenic NK cell cytotoxicity, peritoneal macrophage phagocytosis, splenic and colonic TNF-α expression, TNF-α to IL-10 expression ratio, and fecal IgA level in control mice, while Th1 and Treg cell differentiation was not affected in the spleen. However, HDB1258 treatment significantly suppressed peritoneal macrophage phagocytosis and blood prostaglandin E2 level in mice with LPS-induced systemic inflammation. Its treatment increased LPS-suppressed ratios of Treg to Th1 cell population, Foxp3 to T-bet expression, and IL-10 to TNF-α expression. Oral administration of HDB1258 significantly decreased LPS-induced colon shortening, myeloperoxidase activity and NF-κB/CD11c cell population in the colon, while the ratio of IL-10 to TNF-α expression increased. Moreover, HDB1258 treatment shifted gut microbiota composition in mice with and without LPS-induced systemic inflammation: it increased the Cyanobacteria and PAC000664_g (belonging to Bacteroidetes) populations and reduced Deferribacteres and EU622763_s group (belonging to Bacteroidetes) populations. In particular, PAC001066_g and PAC001072_s populations were negatively correlated with the ratio of IL-10 to TNF-α expression in the colon, while the PAC001070_s group population was positively correlated.

Conclusions: Oral administered HDB1258 may enhance the immune response by activating innate immunity including to macrophage phagocytosis and NK cell cytotoxicity in the healthy host and suppress systemic inflammation in the host with inflammation by the modulation of gut microbiota and IL-10 to TNF-α expression ratio in immune cells.
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http://dx.doi.org/10.1186/s12866-021-02192-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120827PMC
May 2021

A Biomimetic Macroporous Hybrid Scaffold with Sustained Drug Delivery for Enhanced Bone Regeneration.

Biomacromolecules 2021 06 10;22(6):2460-2471. Epub 2021 May 10.

Institute for Biomechanics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.

Bone regeneration is a highly complex physiological process regulated by several factors. In particular, bone-mimicking extracellular matrix and available osteogenic growth factors such as bone morphogenetic protein (BMP) have been regarded as key contributors for bone regeneration. In this study, we developed a biomimetic hybrid scaffold (CEGH) with sustained release of BMP-2 that would result in enhanced bone formation. This hybrid scaffold, composed of BMP-2-loaded cryoelectrospun poly(ε-caprolactone) (PCL) (CE) surrounded by a macroporous gelatin/heparin cryogel (GH), is designed to overcome the drawbacks of the relatively weak mechanical properties of cryogels and poor biocompatibility and hydrophobicity of electrospun PCL. The GH component of the hybrid scaffold provides a hydrophilic surface to improve the biological response of the cells, while the CE component increases the mechanical strength of the scaffold to provide enhanced mechanical support for the defect area and a stable environment for osteogenic differentiation. After analyzing characteristics of the hybrid scaffold such as hydrophilicity, pore difference, mechanical properties, and surface charge, we confirmed that the hybrid scaffold shows enhanced cell proliferation rate and apatite formation in simulated body fluid. Then, we evaluated drug release kinetics of CEGH and confirmed the sustained release of BMP-2. Finally, the enhanced osteogenic differentiation of CEGH with sustained release of BMP-2 was confirmed by Alizarin Red S staining and real-time PCR analysis.
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http://dx.doi.org/10.1021/acs.biomac.1c00241DOI Listing
June 2021

Copper-Coated Polypropylene Filter Face Mask with SARS-CoV-2 Antiviral Ability.

Polymers (Basel) 2021 Apr 22;13(9). Epub 2021 Apr 22.

Department of Nano-Bio Convergence, Korea Institute of Materials Science, 797 Changwondae-ro, Changwon 51508, Korea.

Face masks will be used to prevent pandemic recurrence and outbreaks of mutant SARS-CoV-2 strains until mass immunity is confirmed. The polypropylene (PP) filter is a representative disposable mask material that traps virus-containing bioaerosols, preventing secondary transmission. In this study, a copper thin film (20 nm) was deposited via vacuum coating on a spunbond PP filter surrounding a KF94 face mask to provide additional protection and lower the risk of secondary transmission. Film adhesion was improved using oxygen ion beam pretreatment, resulting in cuprous oxide formation on the PP fiber without structural deformation. The copper-coated mask exhibited filtration efficiencies of 95.1 ± 1.32% and 91.6 ± 0.83% for NaCl and paraffin oil particles, respectively. SARS-CoV-2 inactivation was evaluated by transferring virus-containing media onto the copper-coated PP filters and subsequently adding Vero cells. Infection was verified using real-time polymerase chain reaction and immunochemical staining. Vero cells added after contact with the copper-coated mask did not express the RNA-dependent RNA polymerase and envelope genes of SARS-CoV-2. The SARS-CoV-2 nucleocapsid immunofluorescence results indicated a reduction in the amount of virus of more than 75%. Therefore, copper-coated antiviral PP filters could be key materials in personal protective equipment, as well as in air-conditioning systems.
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http://dx.doi.org/10.3390/polym13091367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122733PMC
April 2021

Discovery of a Novel Series of Pyridone-Based EP3 Antagonists for the Treatment of Type 2 Diabetes.

ACS Med Chem Lett 2021 Mar 26;12(3):451-458. Epub 2021 Feb 26.

Discovery Chemistry, Cardiovascular and Metabolic Research, Janssen Research & Development, LLC, 1400 McKean Roads, Box 776, Spring House, Pennsylvania 19477, United States.

A novel series of pyridones were discovered as potent EP3 antagonists. Optimization guided by EP3 binding and functional assays as well as by eADME and PK profiling led to multiple compounds with good physical properties, excellent oral bioavailability, and a clean in vitro safety profile. Compound was identified as a lead compound as evidenced by the reversal of sulprostone-induced suppression of glucose-stimulated insulin secretion in INS 1E β-cells in vitro and in a rat ivGTT model in vivo. A glutathione adduction liability was eliminated by replacing the naphthalene of structure with the indazole ring of structure .
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http://dx.doi.org/10.1021/acsmedchemlett.0c00667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957929PMC
March 2021

Low BASDAI score alone is not a good predictor of anti-tumor necrosis factor treatment efficacy in ankylosing spondylitis: a retrospective cohort study.

BMC Musculoskelet Disord 2021 Feb 4;22(1):140. Epub 2021 Feb 4.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Background: The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated.

Methods: We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores (< 4) and available ASDAS-C-reactive protein (CRP) data after 3 months of first-line anti-TNF treatment. Patients were grouped into high-ASDAS (≥ 2.1) and low-ASDAS (< 2.1) groups according to the ASDAS-CRP after 3 months of anti-TNF treatment. Their characteristics were compared. And survival analyses were carried out using Kaplan-Meier curves and log-rank test with the event being discontinuation of anti-TNF treatment due to lack/loss of efficacy.

Results: Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011).

Conclusions: A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.
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http://dx.doi.org/10.1186/s12891-020-03941-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860220PMC
February 2021

Fiber-Optic Localized Surface Plasmon Resonance Sensors Based on Nanomaterials.

Sensors (Basel) 2021 Jan 26;21(3). Epub 2021 Jan 26.

Departments of Congo-Mechatronics Engineering, Pusan National University, Busan 46241, Korea.

Applying fiber-optics on surface plasmon resonance (SPR) sensors is aimed at practical usability over conventional SPR sensors. Recently, field localization techniques using nanostructures or nanoparticles have been investigated on optical fibers for further sensitivity enhancement and significant target selectivity. In this review article, we explored varied recent research approaches of fiber-optics based localized surface plasmon resonance (LSPR) sensors. The article contains interesting experimental results using fiber-optic LSPR sensors for three different application categories: (1) chemical reactions measurements, (2) physical properties measurements, and (3) biological events monitoring. In addition, novel techniques which can create synergy combined with fiber-optic LSPR sensors were introduced. The review article suggests fiber-optic LSPR sensors have lots of potential for measurements of varied targets with high sensitivity. Moreover, the previous results show that the sensitivity enhancements which can be applied with creative varied plasmonic nanomaterials make it possible to detect minute changes including quick chemical reactions and tiny molecular activities.
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http://dx.doi.org/10.3390/s21030819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865415PMC
January 2021

Partially Digested Osteoblast Cell Line-Derived Extracellular Matrix Induces Rapid Mineralization and Osteogenesis.

ACS Biomater Sci Eng 2021 03 1;7(3):1134-1146. Epub 2021 Feb 1.

School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

An extracellular matrix (ECM) utilized as a biomaterial can be obtained from organs of living organisms. Therefore, it has some limitations in its supply because of insufficient organs. Furthermore, therapeutic efficacy of ECMs varies depending on factors such as donor's health condition and age. For this reason, ECMs obtained from a cell line could be a good alternative because they can be produced under a controlled environment with uniform quality. Thus, the purpose of this study was to investigate the potential of the MC3T3-E1 cell line-derived ECM as bone graft. The optimized decellularization process was developed to separate the ECM from MC3T3-E1, osteoblast cell line, using Trypsin-EDTA and Triton X-100. The decellularized ECM was partially digested using pepsin. Also, human bone marrow-derived mesenchymal stem cells induced faster osteogenesis on the ECM-coated surface than on the collagen-coated surface. Partially digested ECM fragments were embedded on the polyethylene glycol scaffold without additional chemical modification or crosslinking. Micro-computed tomography and histological analysis results showed that the ECM in the scaffold promoted actual bone regeneration after in vivo implantation to a mouse calvarial defect model. This study suggests that the bone-specific ECM derived from the cell line can replace the ECM from organs for application in tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01349DOI Listing
March 2021

Combinatorial effect of nano whitlockite/nano bioglass with FGF-18 in an injectable hydrogel for craniofacial bone regeneration.

Biomater Sci 2021 Apr 19;9(7):2439-2453. Epub 2021 Jan 19.

Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi-682041, India.

Functional regeneration of bone defects, especially critical-sized, in the craniofacial region remains a major clinical challenge that needs intervention. To address this, the present work focuses on the development of an injectable chitin-PLGA hydrogel (CG) containing bioglass nanoparticles (nBG) or whitlockite nanoparticles (nWH) with FGF-18, and compares the osteogenic and neo-bone formation potential against commercially available hydroxyapatite nanoparticles (nHAP) with FGF-18 fortified CG hydrogel in the critical-sized defect region. The developed CG was injectable and the incorporation of bio-ceramics didn't affect the injectability. Sustained release of FGF-18 was achieved in bio-ceramic containing CG hydrogel systems, while CG hydrogel alone displayed rapid release. In addition, the nBG or nWH containing CG hydrogel groups showed in vitro angiogenic potential. Furthermore, ALP activity, BMP-2 quantification and osteogenic gene expression assays were conducted to ascertain the osteogenic differentiation potential of the hydrogels. In the combination groups, CGnWHF (nWH + FGF-18 containing CG) showed highest osteogenic potential with a synergistic effect, compared to all other groups studied. In vivo bone regeneration studies displayed near-complete bone regeneration for CGnWHF, where its BV/TV% was the highest (synergistic effect) compared to CGnBGF (nBG + FGF-18 in CG) and nHAP with FGF-18 (additive effect) after 8 weeks of implantation. Thus, the use of CGnWHF in irregular craniofacial bone defects could be an attractive option.
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http://dx.doi.org/10.1039/d0bm01496fDOI Listing
April 2021

Efficacy and Safety of Intra-articular Sacroiliac Glucocorticoid Injections in Ankylosing Spondylitis.

J Clin Rheumatol 2020 Dec 8. Epub 2020 Dec 8.

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

Background/aims: To assess the efficacy and safety of intra-articular sacroiliac glucocorticoid injection in ankylosing spondylitis (AS).

Methods: Patients with AS undergoing fluoroscopy-guided intra-articular sacroiliac glucocorticoid injection were enrolled between 2012 and 2018. Efficacy was assessed by numeric pain rating scale, acute phase reactants, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index, and Ankylosing Spondylitis Disease Activity Score (ASDAS). Patients who started biologics within 3 months despite the intervention were compared with those not starting biologics, hence: the nonbiologic group.

Results: A total of 96 patients were treated, with a total of 107 injections. After intervention, there were significant decreases in numeric pain rating scale (7.8 ± 1.8 vs. 3.3 ± 2.2, p < 0.001) and acute phase reactants level (erythrocyte sedimentation rate [ESR] 23.0 mm/h [10.0-47.0 mm/h] vs. 13.0 mm/h [4.0-27.0 mm/h], p < 0.001; C-reactive protein [CRP] 1.0 mg/dL [0.2-2.7 mg/dL] vs. 0.2 mg/dL [0.2-0.9 mg/dL], p < 0.001). Disease activity scores also decreased for BASDAI (6.2 ± 1.8 vs. 4.5 ± 2.5, p = 0.001), Bath Ankylosing Spondylitis Functional Index (5.5 [4.1-7.0] vs. 1.8 [0.5-4.1], p = 0.001), ASDAS-CRP (2.9 ± 1.0 vs. 2.3 ± 1.3, p = 0.046), and ASDAS-ESR (3.7 ± 1.1 vs. 2.4 ± 1.3, p < 0.001). However, 12 patients (12.5%) started biologics within 3 months. These patients showed higher ESR (91.0 mm/h [IQR 21.0-113.0 mm/h] vs. 21.5 mm/h [IQR 9.5-43.0 mm/h], p = 0.010), CRP (8.0 mg/dL [IQR 1.11-17.1 mg/dL] vs. 0.8 mg/dL [IQR 0.2-1.8 mg/dL], p = 0.002), BASDAI (7.4 ± 1.2 vs. 5.9 ± 1.8, p = 0.027), and ASDAS-CRP (4.0 ± 0.5 vs. 2.8 ± 1.0, p = 0.004) than the nonbiologic group. There was no serious adverse event.

Conclusions: Intra-articular sacroiliac glucocorticoid injection can be a safe and effective treatment option for active sacroiliitis in AS.
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http://dx.doi.org/10.1097/RHU.0000000000001584DOI Listing
December 2020

Conventional disease-modifying antirheumatic drugs therapy may not slow spinal radiographic progression in ankylosing spondylitis: results from an 18-year longitudinal dataset.

Ther Adv Musculoskelet Dis 2020 28;12:1759720X20975912. Epub 2020 Nov 28.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.

Objectives: The clinical benefit of conventional disease-modifying antirheumatic drugs (cDMARDs) for treating ankylosing spondylitis (AS) is generally limited to improvements in peripheral arthritis. However, cDMARDs could be conditionally considered as alternatives to established drugs for improving axial manifestations in exceptional circumstances. However, there are few studies of the impact of cDMARDs on radiographic progression outcomes. Therefore, we investigated the effectiveness of cDMARDs on radiographic progression in AS.

Methods: Among 1280 AS patients at a single hospital from 2000 to 2018, 301 who had been treated with sulfasalazine (SSZ) or methotrexate (MTX) were enrolled. For each patient, the entire follow-up period was split into 1-year intervals. Each interval was classified as either an "on-cDMARD" interval, which was a period of treatment with SSZ alone, MTX alone, or a combination of SSZ and MTX, or an "off-cDMARD" interval, which was a period without cDMARD treatment. Radiographic progression was scored using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The relationship between cDMARD use and radiographic progression within the intervals, defined as the rate of mSASSS progression, was investigated using linear models with adjustment for potential confounding covariates and for clustering among observations from the same patient.

Results: The 732 on-cDMARD intervals and 1027 off-cDMARD intervals were obtained from enrolled patients. In multivariable regression analysis, there was no significant association between cDMARDs and the rate of mSASSS progression (β = -0.081,  = 0.418). The mean adjusted mSASSS change per year was 0.610 from on-cDMARD intervals and 0.691 from off-cDMARD intervals.

Conclusion: Treatment with cDMARDs may not reduce radiographic progression in AS patients.
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http://dx.doi.org/10.1177/1759720X20975912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705797PMC
November 2020

Moxifloxacin based fluorescence imaging of intestinal goblet cells.

Biomed Opt Express 2020 Oct 23;11(10):5814-5825. Epub 2020 Sep 23.

Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, South Korea.

Goblet cells (GCs) in the intestine are specialized epithelial cells that secrete mucins to form the protective mucous layer. GCs are important in maintaining intestinal homeostasis, and the alteration of GCs is observed in inflammatory bowel diseases (IBDs) and neoplastic lesions. In the Barrett's esophagus, the presence of GCs is used as a marker of specialized intestinal metaplasia. Various endomicroscopic imaging methods have been used for imaging intestinal GCs, but high-speed and high-contrast GC imaging has been still difficult. In this study, we developed a high-contrast endoscopic GC imaging method: fluorescence endomicroscopy using moxifloxacin as a GC labeling agent. Moxifloxacin based fluorescence imaging of GCs was verified by using two-photon microscopy (TPM) in the normal mouse colon. Label-free TPM, which could visualize GCs in a negative contrast, was used as the reference. High-speed GC imaging was demonstrated by using confocal microscopy and endomicroscopy in the normal mouse colon. Confocal microscopy was applied to dextran sulfate sodium (DSS) induced colitis mouse models for the detection of GC depletion. Moxifloxacin based GC imaging was demonstrated not only by 3D microscopies but also by wide-field fluorescence microscopy, and intestinal GCs in the superficial region were imaged. Moxifloxacin based endomicroscopy has a potential for the application to human subjects by using FDA approved moxifloxacin.
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http://dx.doi.org/10.1364/BOE.402350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587268PMC
October 2020

Long-Term Non Anesthetic Preclinical Study Available Extra-Cranial Brain Activator (ECBA) System for the Future Minimally Invasive Human Neuro Modulation.

IEEE Trans Biomed Circuits Syst 2020 12 31;14(6):1393-1406. Epub 2020 Dec 31.

In recent years, electroceuticals have been spotlighted as an emerging treatment for various severe chronic brain diseases, owing to their intrinsic advantage of electrical interaction with the brain, which is the most electrically active organ. However, the majority of research has verified only the short-term efficacy through acute studies in laboratory tests owing to the lack of a reliable miniaturized platform for long-term animal studies. The construction of a sufficient integrated system for such a platform is extremely difficult because it requires multi-disciplinary work using state-of-the-art technologies in a wide range of fields. In this study, we propose a complete system of an implantable platform for long-term preclinical brain studies. Our proposed system, the extra-cranial brain activator (ECBA), consists of a titanium-packaged implantable module and a helmet-type base station that powers the module wirelessly. The ECBA can also be controlled by a remote handheld device. Using the ECBA, we performed a long-term non-anesthetic study with multiple canine subjects, and the resulting PET-CT scans demonstrated remarkable enhancement in brain activity relating to memory and sensory skills. Furthermore, the histological analysis and high-temperature aging test confirmed the reliability of the system for up to 31 months. Hence, the proposed ECBA system is expected to lead a new paradigm of human neuromodulation studies in the near future.
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http://dx.doi.org/10.1109/TBCAS.2020.3034444DOI Listing
December 2020

SERS imaging-based aptasensor for ultrasensitive and reproducible detection of influenza virus A.

Biosens Bioelectron 2020 Nov 4;167:112496. Epub 2020 Aug 4.

Department of Chemistry, Chung-Ang University, Seoul 06974, South Korea. Electronic address:

Surface-enhanced Raman scattering (SERS)-based aptasensors display high sensitivity for influenza A/H1N1 virus detection but improved signal reproducibility is required. Therefore, in this study, we fabricated a three-dimensional (3D) nano-popcorn plasmonic substrate using the surface energy difference between a perfluorodecanethiol (PFDT) spacer and the Au layer. This energy difference led to Au nanoparticle self-assembly; neighboring nanoparticles then created multiple hotspots on the substrate. The localized surface plasmon effects at the hot spots dramatically enhanced the incident field. Quantitative evaluation of A/H1N1 virus was achieved using the decrease of Raman peak intensity resulting from the release of Cy3-labeled aptamer DNAs from nano-popcorn substrate surfaces via the interaction between the aptamer DNA and A/H1N1 virus. The use of a Raman imaging technique involving the fast mapping of all pixel points enabled the reproducible quantification of A/H1N1 virus on nano-popcorn substrates. Average ensemble effects obtained by averaging all randomly distributed hot spots mapped on the substrate made it possible to reliably quantify target viruses. The SERS-based imaging aptasensor platform proposed in this work overcomes the issues inherent in conventional approaches (the time-consuming and labor-intensiveness of RT-PCR and low sensitivity and quantitative analysis limits of lateral flow assay kits). Our SERS-based assay for detecting A/H1N1 virus had an estimated limit of detection of 97 PFU mL (approximately three orders of magnitude more sensitive than that determined by the enzyme-linked immunosorbent assay) and the approximate assay time was estimated to be 20 min. Thus, this approach provides an ultrasensitive, reliable platform for detecting viral pathogens.
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http://dx.doi.org/10.1016/j.bios.2020.112496DOI Listing
November 2020

Classification of femur fracture in pelvic X-ray images using meta-learned deep neural network.

Sci Rep 2020 08 13;10(1):13694. Epub 2020 Aug 13.

Department of Orthopedic Surgery, College of Medicine, Hanyang University, Seoul, Korea.

In the medical field, various studies using artificial intelligence (AI) techniques have been attempted. Numerous attempts have been made to diagnose and classify diseases using image data. However, different forms of fracture exist, and inaccurate results have been confirmed depending on condition at the time of imaging, which is problematic. To overcome this limitation, we present an encoder-decoder structured neural network that utilizes radiology reports as ancillary information at training. This is a type of meta-learning method used to generate sufficiently adequate features for classification. The proposed model learns representation for classification from X-ray images and radiology reports simultaneously. When using a dataset of only 459 cases for algorithm training, the model achieved a favorable performance in a test dataset containing 227 cases (classification accuracy of 86.78% and classification F1 score of 0.867 for fracture or normal classification). This finding demonstrates the potential for deep learning to improve performance and accelerate application of AI in clinical practice.
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http://dx.doi.org/10.1038/s41598-020-70660-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426947PMC
August 2020

Sequential growth factor releasing double cryogel system for enhanced bone regeneration.

Biomaterials 2020 10 10;257:120223. Epub 2020 Jul 10.

Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea; School of Chemical and Biological Engineering, The Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea; BioMAX/N-Bio Institute, Institute of BioEngineering, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Bone regeneration is a complicated physiological process regulated by several growth factors. In particular, vascular endothelial growth factor (VEGF) and bone morphogenetic protein-4 (BMP-4) are regarded as key factors that induce bone regeneration by angiogenesis and osteogenesis. In this study, we developed a double cryogel system (DC) composed of gelatin/chitosan cryogel (GC) surrounded by gelatin/heparin cryogel (GH) for dual drug delivery with different release kinetics. VEGF was loaded in GH (outer layer of DC) for the initial release of VEGF to induce angiogenesis and provide blood supply in the defect area, while BMP-4 was loaded in GC (inner layer of DC) that leads to sustained release for continuous osteogenic induction. After analyzing characteristics of the double cryogel system such as porosity, degradation rate, swelling ratio, and mechanical properties, we evaluated release kinetics of VEGF (initial release) and BMP-4 (sustained-release) by ELISA. Then, the timely release of VEGF and BMP from DC synergistically induced in vitro osteogenic differentiation as confirmed by alkaline phosphatase staining, Alizarin Red S staining, and real-time PCR analysis. Finally, a critical-sized cranial defect model confirmed the enhanced bone regeneration as a result of dual release growth factor mechanisms.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120223DOI Listing
October 2020

Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence.

Ann Rheum Dis 2020 10 13;79(10):1327-1332. Epub 2020 Jul 13.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea

Objectives: Tumour necrosis factor inhibitors (TNFis) have been suggested to slow radiographic progression in patients with ankylosing spondylitis. However, limitations such as variations in disease activity, complex drug administration and short follow-up duration make it difficult to determine the effect of TNFis on radiographic progression. The aim of the study was to investigate whether long-term treatment with TNFis can reduce radiographic progression in patients with ankylosing spondylitis using 18-year longitudinal real-world data.

Methods: This retrospective study was conducted between January 2001 and December 2018 at a single centre. Among the 1280 patients whose electronic medical records were reviewed, data of 595 patients exposed to TNFis at least once were included. Among them, time intervals of TNFi exposure or non-exposure were determined in 338 patients ('on the TNFis' or 'off the TNFis' intervals, respectively). The difference in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change rate between 'on the TNFis' and 'off the TNFis' intervals was investigated.

Results: We obtained 2364 intervals of 338 patients (1281 'on the TNFis' and 1083 'off the TNFis' intervals). In the marginal structural model for inverse probability of treatment weighting, the change rate of mSASSS significantly decreased with the use of TNFis (β=-0.112, p=0.004), and the adjusted mSASSS changes were 0.848 and 0.960 per year during 'on the TNFis' and 'off the TNFis' intervals, respectively.

Conclusion: Compared with treatment without TNFis, treatment with TNFis slowed radiologic progression significantly.
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http://dx.doi.org/10.1136/annrheumdis-2019-216741DOI Listing
October 2020

The prevalence of fabella and its association with the osteoarthritic severity of the knee in Korea.

Clin Rheumatol 2020 Dec 18;39(12):3625-3629. Epub 2020 Jun 18.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

The clinical relevance of the fabella, a sesamoid bone, has recently been investigated. Although many studies have documented the prevalence of the fabella, few large-scale studies have been conducted in an Asian, especially Korean, population. We conducted a retrospective survey of Koreans to determine the prevalence and distribution of the fabella and its association with osteoarthritic severity of the knee. From June 2016 to August 2017, a total of 2243 people who visited a rheumatology clinic for musculoskeletal evaluation was consecutively recruited. A total of 2126 subjects (1634 females and 492 males) was finally registered and analysed. Anteroposterior and lateral radiographs of both knees were analysed for presence, number and distribution of fabellae and Kellgren-Lawrence grade. The prevalence of the fabella was 57.2% (57.5% for females, 56.1% for males). Among subjects with a fabella, 21.2% had a unilateral distribution, and 78.8% had a bilateral distribution. The number of fabella was correlated with increasing age (r = 0.169, p < 0.001). In the group of subjects with a fabella, the Kellgren-Lawrence grade was significantly higher than in the group without a fabella (2.64 ± 1.38 vs. 1.89 ± 1.54, p < 0.001). The prevalence of fabella in Koreans was relatively high compared with the findings of previous studies, irrespective of the country studied or methodology used. The number of fabellae tended to increase with age. The osteoarthritic severity of the knee appeared worse in the group with a fabella. Key Points • The radiographical prevalence rate of fabella in Korea was about 58%, higher than the previous results. • The prevalence of fabella increased as the age of the subject increased regardless of gender. • The association between fabella and osteoarthritis is strongly suspected because the osteoarthritic changes in the knee of the subjects with fabella are significantly higher than in the subjects without fabella.
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http://dx.doi.org/10.1007/s10067-020-05078-4DOI Listing
December 2020

Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis.

Arthritis Res Ther 2020 05 24;22(1):121. Epub 2020 May 24.

Hanyang University Institute for Rheumatology Research, Seoul, Republic of Korea.

Background: Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood.

Methods: In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients.

Results: In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro.

Conclusions: Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.
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http://dx.doi.org/10.1186/s13075-020-02217-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245802PMC
May 2020
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