Publications by authors named "Eun Young Lee"

694 Publications

The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Interstitial Lung Diseases Using Quantitative HRCT Scores.

J Clin Med 2021 Aug 25;10(17). Epub 2021 Aug 25.

Department of Internal Medicine, Division of Rheumatology, College of Medicine, Seoul National University, Seoul 03080, Korea.

We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 ( = 26) had matched PFT results and prospective cohort 2 ( = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation-the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = -0.433, = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.
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http://dx.doi.org/10.3390/jcm10173812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432030PMC
August 2021

The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Interstitial Lung Diseases Using Quantitative HRCT Scores.

J Clin Med 2021 Aug 25;10(17). Epub 2021 Aug 25.

Department of Internal Medicine, Division of Rheumatology, College of Medicine, Seoul National University, Seoul 03080, Korea.

We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 ( = 26) had matched PFT results and prospective cohort 2 ( = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation-the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = -0.433, = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.
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http://dx.doi.org/10.3390/jcm10173812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432030PMC
August 2021

Tetrahydrocurcumin Ameliorates Kidney Injury and High Systolic Blood Pressure in High-Fat Diet-Induced Type 2 Diabetic Mice.

Endocrinol Metab (Seoul) 2021 Aug 27;36(4):810-822. Epub 2021 Aug 27.

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Background: Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice.

Methods: Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed.

Results: HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P<0.05). Kidney injury in these mice was indicated by an increase in the ratio of albumin to creatinine, glomerular hypertrophy, and the effacement of podocyte foot processes. Expression of intrarenal angiotensin-converting enzyme, angiotensin II type I receptor, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4, and monocyte chemoattractant protein-1 was also markedly increased in HFD-fed mice. HFD-fed mice exhibited elevated SBP that was accompanied by an increase in the wall thickness and vascular cross-sectional area (P<0.05), 12 weeks post-HFD consumption. Treatment with THU (100 mg/kg/day) suppressed intrarenal RAS activation, improved insulin sensitivity, and reduced SBP, thus, attenuating kidney injury in these mice.

Conclusion: THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RAS/nicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.
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http://dx.doi.org/10.3803/EnM.2021.988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419617PMC
August 2021

Ciclesonide Inhaler Treatment for Mild-to-Moderate COVID-19: A Randomized, Open-Label, Phase 2 Trial.

J Clin Med 2021 Aug 12;10(16). Epub 2021 Aug 12.

Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea.

Although some intravenous drugs have been used to treat coronavirus disease 2019 (COVID-19), no effective antiviral agents are currently available in the outpatient setting. We aimed to evaluate the efficacy and adverse events of 14-day ciclesonide treatment vs. standard care for patients with mild-to-moderate COVID-19. A randomized, open-label, multicenter clinical trial of ciclesonide inhalers was conducted in patients with mild-to-moderate COVID-19. Patients were enrolled within 3 days of diagnosis or within 7 days from symptom onset and randomly assigned to receive either ciclesonide (320 µg inhalation twice per day for 14 days) or standard care. The primary endpoint was the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication rate on day 14 from study enrollment. Clinical status was assessed once daily, and serial nasopharyngeal viral load was evaluated by quantitative reverse transcription polymerase chain reaction. There were 35 and 26 patients in the ciclesonide and standard care groups, respectively. The SARS-CoV-2 eradication rate at day 14 was significantly higher in the ciclesonide group ( = 0.021). In multivariate analysis, SARS-CoV-2 negative conversion within 14 days was 12 times more likely in the ciclesonide group (95% confidence interval, 1.187-125.240). Additionally, the clinical failure rate (high-flow nasal oxygen therapy or mechanical ventilation) was significantly lower in the ciclesonide group ( = 0.034). In conclusion, ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and it may inhibit the progression to acute respiratory failure in patients with mild-to-moderate COVID-19. Clinical Trial Registration NCT04330586.
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http://dx.doi.org/10.3390/jcm10163545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396813PMC
August 2021

"A Divine Infection": A Systematic Review on the Roles of Religious Communities During the Early Stage of COVID-19.

J Relig Health 2021 Aug 17. Epub 2021 Aug 17.

School of Kinesiology and Health Studies, Queen's University, KHS 307, 28 Division St, Kingston, ON, K7L 3N6, Canada.

The objective of this systematic review was to summarize the roles that religious communities played during the early stage of COVID-19 pandemic. Seven databases were searched and a total of 58 articles in English published between February 2020 and July 2020 were included in evidence synthesis. The findings of the literature showed diverse influences of religion as a double-edged sword in the context of COVID-19 pandemic. Religious communities have played detrimental and/or beneficial roles as a response to COVID-19 pandemic. A collaborative approach among religious communities, health science, and government is critical to combat COVID-19 crisis and future pandemics/epidemics.
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http://dx.doi.org/10.1007/s10943-021-01364-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370454PMC
August 2021

Acremonamide, a Cyclic Pentadepsipeptide with Wound-Healing Properties Isolated from a Marine-Derived Fungus of the Genus .

J Nat Prod 2021 08 13;84(8):2249-2255. Epub 2021 Aug 13.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, California 92093-0204, United States.

Acremonamide () was isolated from a marine-derived fungus belonging to the genus . The chemical structure of was established using MS, UV, and NMR spectroscopic data analyses. Acremonamide () was found to contain -Me-Phe, -Me-Ala, Val, Phe, and 2-hydroxyisovaleric acid. The absolute configurations of the four aforementioned amino acids were determined through acid hydrolysis followed by the advanced Marfey's method, whereas the absolute configuration of 2-hydroxyisovaleric acid was determined through GC-MS analysis after formation of the -pentafluoropropionylated derivative of the (-)-menthyl ester of 2-hydroxyisovaleric acid. As an intrinsic biological activity, acremonamide () did not exert cytotoxicity to cancer and noncancer cells and increased the migration and invasion. Based on these activities, the wound healing properties of acremonamide () were confirmed and .
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http://dx.doi.org/10.1021/acs.jnatprod.1c00305DOI Listing
August 2021

Dose-dependent and joint associations between screen time, physical activity, and mental wellbeing in adolescents: an international observational study.

Lancet Child Adolesc Health 2021 Aug 9. Epub 2021 Aug 9.

CHEO Research Institute and Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.

Background: Mental wellbeing in adolescents has declined considerably during past decades, making the identification of modifiable risk factors important. Prolonged screen time and insufficient physical activity appear to operate independently and synergistically to increase the risk of poor mental wellbeing in school-aged children. We aimed to examine the gender-stratified dose-dependent and joint associations of screen time and physical activity with mental wellbeing in adolescents.

Methods: We used data from three rounds of Health Behaviour in School-aged Children cross-sectional surveys (2006, 2010, and 2014) from 42 European and North American countries. Survey participants, aged 11 years, 13 years, and 15 years, provided self-reported information by completing an anonymous questionnaire that included items on health indicators and related behaviours. We used the self-reported variables of life satisfaction and psychosomatic complaints as indicators of adolescents' mental wellbeing, combining these with the self-reported discretionary use of screens and engagement in physical activity. We used generalised additive models and multilevel regression modelling to examine the gender-stratified relationships between mental wellbeing and screen time and physical activity.

Findings: Our sample included 577 475 adolescents (mean age 13·60 years, SD 1·64), with 296 542 (51·35%) girls and 280 933 (48·64%) boys. The mean reported life satisfaction score (on a scale of 0-10) was 7·70 (95% CI 7·69-7·71) in boys and 7·48 (7·46-7·50) in girls. Psychosomatic complaints were more common among girls (mean 9·26, 95% CI 9·23-9·28) than boys (6·89, 6·87-6·91). Generalised additive model analyses showed slightly non-linear associations of screen time and physical activity with life satisfaction and psychosomatic complaints for girls and boys. Detrimental associations between screen time and mental wellbeing started when screen time exceeded 1 h per day, whereas increases in physical activity levels were beneficially and monotonically associated with wellbeing. Multilevel modelling showed that screen time levels were negatively associated with life satisfaction and positively associated with psychosomatic complaints in a dose-dependent manner. Physical activity levels were positively associated with life satisfaction and negatively associated with psychosomatic complaints in a dose-dependent manner. Joint associations of screen time-physical activity with mental wellbeing showed that, compared with the least active participants with more than 8 h per day of screen time and no physical activity, most of the other screen time-physical activity groups had considerably higher life satisfaction and lower psychosomatic complaints.

Interpretation: Higher levels of screen time and lower levels of physical activity were associated with lower life satisfaction and higher psychosomatic complaints among adolescents from high-income countries. Public health strategies to promote adolescents' mental wellbeing should aim to decrease screen time and increase physical activity simultaneously.

Funding: None.
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http://dx.doi.org/10.1016/S2352-4642(21)00200-5DOI Listing
August 2021

Dehydrozingerone inhibits renal lipotoxicity in high-fat diet-induced obese mice.

J Cell Mol Med 2021 Sep 12;25(18):8725-8733. Epub 2021 Aug 12.

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Ectopic fat accumulation in the kidneys causes oxidative stress, inflammation and cell death. Dehydrozingerone (DHZ) is a curcumin analog that exhibits antitumour, antioxidant and antidiabetic effects. However, the efficacy of DHZ in diabetic nephropathy (DN) is unknown. Here, we verified the efficacy of DHZ on DN. We divided the experimental animals into three groups: regular diet, 60% high-fat diet (HFD) and HFD with DHZ for 12 weeks. We analysed levels of renal triglycerides and urinary albumin and albumin-creatinine ratio, renal morphological changes and molecular changes via real-time polymerase chain reaction and immunoblotting. Furthermore, high glucose (HG)- or palmitate (PA)-stimulated mouse mesangial cells or mouse podocytes were treated with DHZ for 24 h. As a result, DHZ markedly reduced renal glycerol accumulation and albuminuria excretion through improvement of thickened glomerular basement membrane, podocyte loss and slit diaphragm reduction. In the renal cortex in the HFD group, phospho-AMPK and nephrin expression reduced, whereas arginase 2 and CD68 expression increased; however, these changes were recovered after DHZ administration. Increased reactive oxygen species (ROS) stimulated by HG or PA in podocytes was inhibited by DHZ treatment. Collectively, these findings indicate that DHZ ameliorates DN via inhibits of lipotoxicity-induced inflammation and ROS formation.
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http://dx.doi.org/10.1111/jcmm.16828DOI Listing
September 2021

2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association.

Diabetes Metab J 2021 07 30;45(4):461-481. Epub 2021 Jul 30.

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

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.
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http://dx.doi.org/10.4093/dmj.2021.0156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369224PMC
July 2021

Hypomethylation of lncRNA H19 as a potential prognostic biomarker for oral squamous cell carcinoma.

Arch Oral Biol 2021 Sep 22;129:105214. Epub 2021 Jul 22.

Department of Oral Pathology, and BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, 50612, Gyeongsangnam-do, Republic of Korea. Electronic address:

Objectives: Dysregulated DNA methylation is common in cancers and is considered one of the most important triggers in cancer development and progression. The expression and promoter methylation status of long non-coding RNA (lncRNA) H19 play a key role in several cancers, but its role is unclear in oral cancer. The aim of this study was to evaluate the potential of lncRNA H19 as a prognostic biomarker for oral cancer.

Designs: The transcript levels and the methylation status of lncRNA H19 in OSCC cell lines and OSCC patient tissues were investigated by quantitative real-time RT-PCR (qRT-PCR) and methylation-specific PCR (MSP). Methylation ratio (%) were calculated from the intensity of the MSP in the gel image and Kaplan-Meier survival analysis of OSCC patient survival was performed for patients grouped according to the lncRNA H19 promoter methylation ratio.

Results: lncRNA H19 was highly expressed and its promoter region was hypomethylated in OSSC cell lines as compared to normal control. Almost all OSCC patients tissues (63 out of 65, 97 %) showed hypomethylation of lncRNA H19 compared to normal oral mucosa tissues. There was a significant correlation between methylation ratio and tumor histopathologic grade. OSCC patients with hypomethylation of lncRNA H19 had a significantly lower 5-year survival rate.

Conclusions: Hypomethylation of lncRNA H19 may serve as a potential prognostic biomarker for oral cancer.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105214DOI Listing
September 2021

Machine learning to predict distal caries in mandibular second molars associated with impacted third molars.

Sci Rep 2021 Jul 29;11(1):15447. Epub 2021 Jul 29.

Department of Oral and Maxillofacial Surgery, Chungbuk National University Hospital, 776, 1Sunhwan-ro, Seowon-gu, Cheongju, Chungbuk, 28644, South Korea.

Impacted mandibular third molars (M3M) are associated with the occurrence of distal caries on the adjacent mandibular second molars (DCM2M). In this study, we aimed to develop and validate five machine learning (ML) models designed to predict the occurrence of DCM2Ms due to the proximity with M3Ms and determine the relative importance of predictive variables for DCM2Ms that are important for clinical decision making. A total of 2642 mandibular second molars adjacent to M3Ms were analyzed and DCM2Ms were identified in 322 cases (12.2%). The models were trained using logistic regression, random forest, support vector machine, artificial neural network, and extreme gradient boosting ML methods and were subsequently validated using testing datasets. The performance of the ML models was significantly superior to that of single predictors. The area under the receiver operating characteristic curve of the machine learning models ranged from 0.88 to 0.89. Six features (sex, age, contact point at the cementoenamel junction, angulation of M3Ms, Winter's classification, and Pell and Gregory classification) were identified as relevant predictors. These prediction models could be used to detect patients at a high risk of developing DCM2M and ultimately contribute to caries prevention and treatment decision-making for impacted M3Ms.
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http://dx.doi.org/10.1038/s41598-021-95024-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322059PMC
July 2021

Clinical Factors Associated with Balance Function in the Early Subacute Phase after Stroke.

Am J Phys Med Rehabil 2021 Jul 27. Epub 2021 Jul 27.

Department of Physical Medicine and Rehabilitation, Korea University College of Medicine, Seoul, Republic of Korea Brain Convergence Research Center, Korea University, Seoul, Republic of Korea Department of Biomedical Sciences, Korea University, Seoul, Republic of Korea.

Objective: To investigate the key factors of balance function in the early subacute phase after stroke.

Design: Ninety-four stroke patients were included. Multiple variables were evaluated, including demographic factors, clinical variables (stroke type; lesion site; Korean Mini-Mental State Examination [MMSE]; motor strength of the hip, knee, and ankle joints; Fugl-Meyer Assessment of lower extremity [FMA-LE]); neurophysiologic variables (amplitude ratio of somatosensory evoked potential [SEP] of the tibial nerves), and laterality index of fractional anisotropy (FA-LI) of the corticospinal tract using diffusion tensor imaging. Balance function was measured using the Berg balance scale (BBS).

Results: The BBS score was significantly negatively correlated with age and FA-LI and positively correlated with MMSE; FMA-LE; motor strength of the affected hip, knee, and ankle joint; and SEP amplitude ratio (p < 0.05). The abnormal SEP group and poor integrity of the corticospinal tract group showed significantly decreased BBS scores. In multivariable logistic regression analysis, age, FMA-LE score, and ankle plantar flexion strength were significantly associated with balance function (odds ratios: 0.919, 1.181, and 15.244, respectively, p < 0.05).

Conclusion: Higher age, severe initial motor impairment, and strength of the affected lower extremity muscles, especially the ankle plantar flexor, are strongly associated with poor balance function early after stroke.
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http://dx.doi.org/10.1097/PHM.0000000000001856DOI Listing
July 2021

Unveiling the genetic variation of severe continuous/mixed-type ossification of the posterior longitudinal ligament by whole-exome sequencing and bioinformatic analysis.

Spine J 2021 Jul 15. Epub 2021 Jul 15.

Department of Neurosurgery, Seoul National University Hospital, Seoul; Department of Neurosurgery, Seoul National University College of Medicine; Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, The Republic of Korea. Electronic address:

Background Context: Ossification of the posterior longitudinal ligament (OPLL) in the cervical spine is known as a rare, complex genetic disease, its complexity being partly because OPLL is diagnosed by radiological findings regardless of clinical or genetic evaluations. Although many genes associated with susceptibility have been reported, the exact causative genes are still unknown.

Purpose: We performed an analysis using next-generation sequencing and including only patients with a clear involved phenotype.

Study Design/setting: This was a case control study.

Patient Sample: A total of 74 patients with severe OPLL and 26 healthy controls were included.

Outcome Measures: Causal single-nucleotide variant (SNV), gene-wise variant burden (GVB), and related pathway METHOD: We consecutively included the severe OPLL patients with continuous-/mixed-type and an occupying ratio of ≥ 40%, and performed whole-exome sequencing (WES) and bioinformatic analysis. Then, a validation test was performed for candidate variations. Participants were divided into 4 groups (rapidly-growing OPLL, growing rate ≥ 2.5%/y; slow-growing, < 2.5%/y; uncertain; and control).

Results: WES was performed on samples from 74 patients with OPLL (rapidly-growing, 33 patients; slow-growing, 37; and uncertain, 4) with 26 healthy controls. Analysis of 100 participants identified a newly implicated SNV and 4candidate genes based on GVB. The GVB of CYP4B1 showed a more deleterious score in the OPLL than the control group. Comparison between the rapidly growing OPLL and control groups revealed seven newly identified SNVs. We found significant association for 2 rare missense variants; rs121502220 (odds ratio [OR] = infinite; minor allele frequency [MAF] = 0.034) in NLRP1 and rs13980628 (OR= infinite; MAF = 0.032) in SSH2. The 3 genes are associated with inflammation control and arthritis, and SSH2 and NLRP1 are also related to vitamin D modulation.

Conclusions: Identification of unique variants in novel genes such as CYP4B1 gene may induce the development of OPLL. In subgroup analysis, NLRP1 and SSH2 genes coding inflammation molecules may related with rapidly-growing OPLL.
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http://dx.doi.org/10.1016/j.spinee.2021.07.005DOI Listing
July 2021

Clinical characteristics of non-radiographic axial spondyloarthritis: Results of the Korean Nonradiographic Axial SPondyloArthritis (KONASPA) data.

Int J Rheum Dis 2021 Sep 11;24(9):1137-1147. Epub 2021 Jul 11.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Aim: To evaluate clinical characteristics and natural history of non-radiographic axial spondyloarthritis (nr-axSpA) using KOrean Nonradiographic Axial SPondyloArthritis (KONASPA) data.

Methods: Data were collected from 11 centers in South Korea. A total of 278 patients with nr-axSpA from January 2018 to July 2020 were included. Demographic data, clinical features, comorbidities, disease activity, medications, and laboratory results were collected.

Results: Mean age at symptom onset was 28.2 ± 14.2 years. Of 278 patients, 152 (54.7%) were male. Mean Bath Ankylosing Spondylitis Disease Activity Index at diagnosis was 3.5 ± 2.1. Dyslipidemia was the most common comorbidity (8.4%), followed by hypertension (6.1%). Mean age at diagnosis of nr-axSpA was older in female patients than in male patients (31.8 ± 15.8 years vs 24.9 ± 12.0 years, P < 0.001). Enthesitis and uveitis were more frequently found in female patients than in male patients. Thirty-one (11.1%) participants with nr-axSpA progressed to ankylosing spondylitis. The median follow-up duration was 48 months. In multivariable Cox regression analysis, age at symptom onset (hazard ratio [HR] 0.93, 95% confidence interval (CI) 0.88-0.97, P = 0.006), body mass index (BMI) (HR 1.24, 95% CI 1.06-1.44, P = 0.005) and sacroiliitis grade (HR 1.86, 95% CI 1.19-2.92, P = 0.006) were associated with progression to ankylosing spondylitis.

Conclusions: Results of nationwide data revealed that women with nr-axSpA showed a late disease onset and more extra-articular manifestations than men. Young age at symptom onset, high BMI, and presence of radiographic sacroiliitis at diagnosis were risk factors for progression to AS.
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http://dx.doi.org/10.1111/1756-185X.14175DOI Listing
September 2021

A phenomenological study on the experiences of patient transfer from the intensive care unit to general wards.

PLoS One 2021 7;16(7):e0254316. Epub 2021 Jul 7.

College of Nursing Research Institute of Nursing Science, Ajou University, Suwon, South Korea.

Objectives: This study aimed to derive an in-depth understanding of the transfer experience of intensive care unit (ICU) patients in South Korea through a phenomenological analysis.

Methods: Participants were 15 adult patients who were admitted to a medical or surgical ICU at a university hospital for more than 48 hours before being transferred to a general ward. Data were collected three to five days after their transfer to the general ward from January to December 2017 through individual in-depth interviews and were analyzed using Colaizzi's phenomenological data analysis method, phenomenological reduction, intersubjective reduction, and hermeneutic circle. Data analysis yielded eight themes and four theme clusters related to the unique experiences of domestic ICU patients in the process of transfer to the general ward.

Results: The four main themes of the patients' transfer experiences were "hope amid despair," "gratitude for being alive," "recovery from suffering," and "seeking a return to normality."

Conclusion: Our findings expand the realistic and holistic understanding from the patient's perspective. This study's findings can contribute to the development of appropriate nursing interventions that can support preparation and adaptation to the transfer of ICU patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254316PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263304PMC
July 2021

Urinary exosomal microRNA profiling in type 2 diabetes patients taking dipeptidyl peptidase-4 inhibitor compared with sulfonylurea.

Kidney Res Clin Pract 2021 Jul 7. Epub 2021 Jul 7.

Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group).

Methods: This was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction.

Results: Twenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.01; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index.

Conclusion: There was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.
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http://dx.doi.org/10.23876/j.krcp.21.015DOI Listing
July 2021

Tetrahydrocurcumin Ameliorates Skin Inflammation by Modulating Autophagy in High-Fat Diet-Induced Obese Mice.

Biomed Res Int 2021 14;2021:6621027. Epub 2021 Jun 14.

Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Republic of Korea.

Obesity can induce chronic low-grade inflammation via oxidative stress. Tetrahydrocurcumin (THC) is a major curcumin metabolite with anti-inflammatory and antioxidant effects, but little is known about its effects on the skin of obese individuals. Thus, the aim of this study was to investigate the effects of THC on inflammatory cytokine production, oxidative stress, and autophagy in the skin of mice with high-fat diet- (HFD-) induced obesity. Eight-week-old C57BL/6J mice were fed a regular diet, HFD (60% of total calories from fat), or HFD supplemented with THC (100 mg/kg/day orally) for 12 weeks. We measured their body weights during the experimental period. After 12-week treatments, we performed western blotting and real-time polymerase chain reaction analyses on skin samples to evaluate the expression of inflammatory cytokines, oxidative stress markers, and autophagy markers. We observed higher tumor necrosis factor- (TNF-), NADPH oxidase 2 (Nox2), Nox4, and phosphorylated p65 levels; lower nuclear factor erythroid 2-related factor 2 (Nrf2) expression; and higher light chain 3 (LC3), autophagy-related 5 (Atg5), and Beclin 1 expression in the skin of HFD mice compared to the corresponding levels in the skin of mice fed with regular diet. THC administration decreased TNF-, Nox2, Nox4, and phosphorylated p65 levels and activated the Nrf2 pathway. Interestingly, THC administration suppressed the expression of the autophagy markers LC3, Atg5, and Beclin 1. Overall, HFD-fed mice exhibited an elevation in inflammation, oxidative stress, and autophagy in their skin. THC ameliorated obesity-related skin pathology, and therefore, it is a potential therapeutic agent for obesity-related inflammatory skin diseases.
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http://dx.doi.org/10.1155/2021/6621027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219437PMC
June 2021

Vascular Calcification as a Novel Risk Factor for Kidney Function Deterioration in the Nonelderly.

J Am Heart Assoc 2021 Jul 19;10(13):e019300. Epub 2021 Jun 19.

Department of Internal Medicine Soonchunhyang University Cheonan Hospital Cheonan Korea.

Background The relationship between vascular calcification and chronic kidney disease is well known. However, whether vascular calcification affects renal function deterioration remains unclear. We investigated whether kidney function deteriorated more rapidly in individuals with higher vascular calcification indicated by the coronary artery calcium score (CACS). Methods and Results Individuals with a normal estimated glomerular filtration rate (>60 mL/min per 1.73 m) who underwent cardiac computed tomography in our institution (a tertiary teaching hospital in Cheonan, Korea) from January 2010 to July 2012 were retrospectively reviewed. All participants were aged 20 to 65 years. Among 739 patients, 447, 175, and 117 had CACSs of 0, 1 to 99, and ≥100 units, respectively. The participants were followed for 7.8 (interquartile range, 5.5-8.8) years. The adjusted annual estimated glomerular filtration rates declined more rapidly in patients in the CACS ≥100 group compared with those in the CACS 0 group (adjusted-β, -0.40; 95% CI, -0.80 to -0.03) when estimated using a linear mixed model. The adjusted hazard ratio in the CACS ≥100 group for Kidney Disease: Improving Global Outcomes criteria (a drop in estimated glomerular filtration rate category accompanied by a 25% or greater drop in estimated glomerular filtration rate) was 2.52 (1.13-5.61). After propensity score matching, more prevalent renal outcomes (13.2%) were observed in patients with a CACS of ≥100 compared with those with a CACS of 0 (1.9%), with statistical significance (=0.004). Conclusions Our results showed that renal function declined more rapidly in patients with higher CACSs, suggesting that vascular calcification might be associated with chronic kidney disease progression.
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http://dx.doi.org/10.1161/JAHA.120.019300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403323PMC
July 2021

Association of first, second, and third-line bDMARDs and tsDMARD with drug survival among seropositive rheumatoid arthritis patients: Cohort study in A real world setting.

Semin Arthritis Rheum 2021 Aug 7;51(4):685-691. Epub 2021 Jun 7.

Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea. Electronic address:

Objectives: To determine the association of first, second, and third-line biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among seropositive rheumatoid arthritis (RA) patients.

Methods: The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date.

Results: Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46-0.68), tofacitinib (aHR 0.27, 95% CI 0.18-0.42), or abatacept (aHR 0.83, 95% CI 0.69-0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25-0.55), tofacitinib (aHR 0.23, 95% CI 0.15-0.37), or abatacept (aHR 0.54, 95% CI 0.35-0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16-0.62) or tofacitinib (aHR 0.35, 95% CI 0.19-0.63) was associated with lower drug failure risk compared to third TNFi users.

Conclusion: First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third-line use of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among seropositive RA patients.
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http://dx.doi.org/10.1016/j.semarthrit.2021.06.002DOI Listing
August 2021

Operationalization of intersectionality in physical activity and sport research: A systematic scoping review.

SSM Popul Health 2021 Jun 30;14:100808. Epub 2021 Apr 30.

School of Kinesiology and Health Studies, Queen's University, SKHS Building 28 Division Street, Kingston, ON K7L 3N6, Canada.

Participation in and opportunities for physical activity (PA) and sports (PA inclusively hereafter) are known to vary across individuals with different social positions. Intersectionality theory may help us to better understand the complex processes of multiple interlocking systems of oppression and privilege shaped by intersections of individuals' social categories. The objectives of this systematic scoping review were (1) to summarize the findings of articles examining PA claimed operationalization of intersectionality and (2) to identify the scope and gaps pertaining to the operationalization of intersectionality in PA research. A search was conducted in September 2019 in seven electronic databases (e.g., SPORTDiscus, Scopus, Web of Science) for relevant research articles written in English. Key search terms included "intersectionality" AND "physical activity" OR "sport". Database searches, data screening and extraction, and narrative synthesis were conducted between September 2019 and May 2020. Of 16564 articles identified, 45 articles were included in this review. The majority of included articles used qualitative methods (n = 41), with two quantitative and two mixed-methods articles. The most frequently observed intersectional social position was sex/gender + race/ethnicity (n = 11), followed by sex/gender + race/ethnicity + sexuality (n = 6) and sex/gender + race/ethnicity + religion (n = 6). Most qualitative studies (n = 38) explicitly claimed operationalization of intersectionality as a key theoretical framework, and over half of these studies (n = 27) implicitly used intra-categorical intersectionality. Two quantitative studies were identified which examined a number of intersections simultaneously using inter-categorical intersectionality. Complex processes of individual and social-structural level factors that drive inequalities in PA opportunities and participation could be better elucidated with the operationalization of intersectionality theory. Intersectionality theory may serve as a useful framework in both qualitative and quantitative investigations. Advancement in quantitative intersectionality is critical in order to produce knowledge that could inform more inclusive PA promotion efforts.
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http://dx.doi.org/10.1016/j.ssmph.2021.100808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182115PMC
June 2021

The 'freedom' to pollute? An ecological analysis of neoliberal capitalist ideology, climate culpability, lifestyle factors, and population health risk in 124 countries.

Can J Public Health 2021 Jun 11. Epub 2021 Jun 11.

School of Kinesiology and Health Studies, Queen's University, 28 Division St., Kingston, ON, K7L 3N6, Canada.

Objectives: This ecological study examined the relationship between neoliberal capitalist ideology (hereafter, neoliberal ideology) and non-communicable diseases (NCD) mortality in 124 countries, focusing on the degree to which climate culpability and physical inactivity are implicated in explaining that relationship.

Methods: The economic freedom of the world index of the Fraser Institute (representing neoliberal ideology), CO emissions (metric tons/capita) from the World Bank (representing climate culpability), and the World Health Organization's age-adjusted physical inactivity and NCD mortality data were used. Covariates included gross domestic product (GDP)/capita, the country-level prevalence of obesity (n = 123), tobacco smoking (n = 111), and alcohol consumption (n = 61).

Results: Neoliberal ideology was associated with NCD mortality after controlling for GDP/capita, physical inactivity, and obesity, and this association was most pronounced in less culpable countries. The association between neoliberal ideology and NCD mortality remained statistically significant even after further controlling for tobacco smoking and alcohol consumption. Neoliberal ideology was associated with NCD mortality, after controlling for GDP, climate culpability, and tobacco smoking, regardless of physical inactivity. When alcohol consumption was introduced, physical inactivity moderated the association between neoliberal ideology and NCD mortality.

Conclusion: Neoliberal ideology was consistently associated with NCD mortality. Also, NCD mortality appears to be most severe in countries that are less culpable for global climate change. Our findings offer preliminary evidence-based support for a shift in thinking toward the fundamental determinants of health and calls for an upstream shift in climate change mitigation interventions to improve population health through the creation of equitable global political and economic systems.
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http://dx.doi.org/10.17269/s41997-021-00530-7DOI Listing
June 2021

Fighting the uphill battle to cure type 1 diabetes.

J Diabetes Investig 2021 Sep 22;12(9):1542-1544. Epub 2021 Jul 22.

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.

Three complementary approaches for type 1 diabetes. Immunotherapy targets the pathogenic immune cells or inflammatory cytokines to revert type 1 diabetes. An artificial pancreas delivers insulin automatically using continuous glucose monitoring, a controlling algorithm, and an insulin pump. Beta cell replacement therapy varies depending on the cell sources: allogeneic, or xenogeneic islet; beta-like cells derived from ESCs or iPSCs.
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http://dx.doi.org/10.1111/jdi.13613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409888PMC
September 2021

Effect of Renamezin upon attenuation of renal function decline in pre-dialysis chronic kidney disease patients: 24-week prospective observational cohort study.

PLoS One 2021 7;16(6):e0252186. Epub 2021 Jun 7.

Department of Internal Medicine, Kangnam Sacred Heart Hospital, Seoul, Korea.

Renamezin® is a modified capsule-type oral spherical adsorptive carbon which lowers indoxyl sulfate levels in patients with advanced chronic kidney disease (CKD). This 24-week prospective observational cohort study was performed to evaluate the effect of Renamezin® upon attenuation of renal function decline. A total of 1,149 adult patients with baseline serum creatinine 2.0-5.0 mg/dL were enrolled from 22 tertiary hospital in Korea from April 2016 to September 2018. Among them, a total of 686 patients completed the study and were included in the intention-to-treat analysis. A total of 1,061 patients were included in the safety analysis. The mean age was 63.5 years and male patients were predominant (63.6%). Most of the patients (76.8%) demonstrated high compliance with study drug (6g per day). After 24 week of treatment, serum creatinine was increased from 2.86±0.72 mg/dL to 3.06±1.15 mg/dL (p<0.001), but estimated glomerular filtration rate was not changed significantly during observation period (22.3±6.8 mL/min/1.73m2 to 22.1±9.1 mL/min/1.73m2, p = 0.243). Patients with age over 65 years old and those under good systolic blood pressure control <130 mmHg were most likely to get benefit from Renamezin® treatment to preserve renal function. A total of 98 (9.2%) patients out of 1,061 safety population experienced 134 adverse events, of which gastrointestinal disorders were the most common. There were no serious treatment-related adverse events. Renamezin® can be used safely to attenuate renal function decline in moderately advanced CKD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252186PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183994PMC
June 2021

Excessively Enlarged Mitochondria in the Kidneys of Diabetic Nephropathy.

Antioxidants (Basel) 2021 May 7;10(5). Epub 2021 May 7.

Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea.

Diabetic nephropathy (DN) is the most serious complication of diabetes and a leading cause of kidney failure and mortality in patients with diabetes. However, the exact pathogenic mechanisms involved are poorly understood. Impaired mitochondrial function and accumulation of damaged mitochondria due to increased imbalance in mitochondrial dynamics are known to be involved in the development and progression of DN. Accumulating evidence suggests that aberrant mitochondrial fission is involved in the progression of DN. Conversely, studies linking excessively enlarged mitochondria to DN pathogenesis are emerging. In this review, we summarize the current concepts of imbalanced mitochondrial dynamics and their molecular aspects in various experimental models of DN. We discuss the recent evidence of enlarged mitochondria in the kidneys of DN and examine the possibility of a therapeutic application targeting mitochondrial dynamics in DN.
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http://dx.doi.org/10.3390/antiox10050741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151708PMC
May 2021

Personalized Type 2 Diabetes Management Using a Mobile Application Integrated with Electronic Medical Records: An Ongoing Randomized Controlled Trial.

Int J Environ Res Public Health 2021 05 16;18(10). Epub 2021 May 16.

Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Korea.

Controlling type 2 diabetes (T2DM) requires a comprehensive approach including patient education, self-monitoring of blood glucose, individualized behavioral strategies, and frequent contact with healthcare professionals (HCPs). We aimed to compare the efficacy of a personalized lifestyle intervention based on a mobile phone application with regular care in participants with T2DM. This is an ongoing randomized controlled open-label parallel-group trial with a target accrual of 282 participants, of which 181 have been enrolled to date. Participants are randomly assigned to one of three groups: (1) regular care; (2) mobile diabetes management; or (3) mobile diabetes management with HCP feedback. The mobile application is enabled to integrate with both electronic medical records (EMR) and a web-based diabetes management system for HCPs. It can send customized messages based on participants' responses to lifestyle questionnaires administered at the baseline. The intervention period is 26 weeks followed by observation for 26 weeks. We evaluate the intervention's features in order to assess its clinical utility and efficacy and compare outcomes with regular care considering relevant clinical factors, such as age, baseline HbA1c, etc. We expect our study to provide new evidence in support of customized mobile application tools for the management of T2DM.
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http://dx.doi.org/10.3390/ijerph18105300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155840PMC
May 2021

Climate change, 24-hour movement behaviors, and health: a mini umbrella review.

Glob Health Res Policy 2021 04 29;6(1):15. Epub 2021 Apr 29.

School of Kinesiology and Health Studies, Queen's University, KHS 307, 28 Division St, Kingston, ON, K7L3N6, Canada.

Background: The worsening climate change and alarming prevalence of communicable and non-communicable diseases continue to threat human life and existence. Accumulating evidence suggests that favorable patterns of 24-h movement behaviors, high physical activity, low sedentary behavior, and adequate sleep, may positively contribute to achieving dual benefits of climate change mitigation and disease prevention. The purposes of this mini umbrella review were to summarize the most up-to-date, high-level evidence exploring the relationships between climate change, 24-h movement behaviors, and health and elaborate on the mechanisms linking the three variables of interest.

Methods: A systematic search of electronic databases was performed in PubMed and Google Scholar during March-October 2020. Inclusion criteria were: (1) systematic review; (2) reviewed relationships between climate change and movement behaviors and/or health in any directions; (3) written in English; (4) published in 2010-2020. Narrative synthesis was conducted to highlight the main relationships observed and address the current state of knowledge and priorities for future research. In order to illustrate the potential mechanisms between climate change, movement behaviors, and health, the main results from included systematic reviews were summarized and a conceptual framework was developed for future research.

Results: Based on the evidence from eight systematic reviews published in the past decade, multi-directional (i.e., uni-, bi-, or U-shaped) links were observed between climate change and varying human health outcomes. However, little is understood about the association between climate change and 24-h movement behaviors. Two reviews suggested the negative impact of climate change on sleep and bi-directional relationships between climate change and physical activity/sport. One review included two studies suggesting the unfavorable impact of climate change on sedentary behavior; however, the evidence was limited. Finally, no reviews examined the mechanisms by which climate change, movement behaviors, and health impact one another. Based on the findings of this mini umbrella review, a conceptual framework is proposed that could guide future work to unpack mechanisms between climate change, movement behaviors, and health.

Conclusions: This mini umbrella review highlights the importance of better understanding the mechanisms between climate change, movement behaviors, and health in developing effective mitigation and adaptation strategies to climate change, while paying close attention to vulnerable countries/communities/population groups.
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http://dx.doi.org/10.1186/s41256-021-00198-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082629PMC
April 2021

Chemical Structure and Biological Activities of Secondary Metabolites from L.

Molecules 2021 Apr 13;26(8). Epub 2021 Apr 13.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Korea.

L. is a halophyte that grows in salt marshes and muddy seashores, which is widely used both as traditional medicine and as an edible vegetable. This salt-tolerant plant is a source of diverse secondary metabolites with several therapeutic properties, including antioxidant, antidiabetic, cytotoxic, anti-inflammatory, and anti-obesity effects. Therefore, this review summarizes the chemical structure and biological activities of secondary metabolites isolated from L.
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http://dx.doi.org/10.3390/molecules26082252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069253PMC
April 2021

Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy.

Biomedicines 2021 Apr 22;9(5). Epub 2021 Apr 22.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.
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http://dx.doi.org/10.3390/biomedicines9050457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146473PMC
April 2021

3'-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation.

Front Pharmacol 2021 12;12:609817. Epub 2021 Apr 12.

Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea.

Osteoarthritis (OA) is a major degenerative joint disease. Oxidative stress and inflammation play key roles in the pathogenesis of OA. 3'-Sialyllactose (3'-SL) is derived from human milk and is known to regulate a variety of biological functions related to immune homeostasis. This study aimed to investigate the therapeutic mechanisms of 3'-SL in interleukin-1β (IL-1β)-treated SW1353 chondrocytic cells. 3'-SL potently suppressed IL-1β-induced oxidative stress by increasing the levels of enzymatic antioxidants. 3'-SL significantly reversed the IL-1β mediated expression levels of reactive oxygen species in IL-1β-stimulated chondrocytic cells. In addition, 3'-SL could reverse the increased levels of inflammatory markers such as nitrite, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2, IL-1β, and IL-6 in IL-1β-stimulated chondrocytic cells. Moreover, 3'-SL significantly inhibited the apoptotic process, as indicated by the downregulation of the pro-apoptotic protein Bax, upregulation of the anti-apoptotic protein Bcl-2 expression, and significant reduction in the number of TUNEL-positive cells in the IL-1β-treated chondrocytic cells. Furthermore, 3'-SL reversed cartilage destruction by decreasing the release of matrix metalloproteinases (MMP), such as MMP1, MMP3, and MMP13. In contrast, 3'-SL significantly increased the expression levels of matrix synthesis proteins, such as collagen II and aggrecan, in IL-1β-treated chondrocytic cells. 3'-SL dramatically suppressed the activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways, which are related to the pathogenesis of OA. Taken together, our data suggest that 3'-SL alleviates IL-1β-induced OA pathogenesis via inhibition of activated MAPK and PI3K/AKT/NF-κB signaling cascades with the downregulation of oxidative stress and inflammation. Therefore, 3'-SL has the potential to be used as a natural compound for OA therapy owing to its ability to activate the antioxidant defense system and suppress inflammatory responses.
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http://dx.doi.org/10.3389/fphar.2021.609817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072478PMC
April 2021

Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy.

PLoS One 2021 23;16(4):e0250666. Epub 2021 Apr 23.

Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

The anti-aging gene, klotho, has been identified as a multi-functional humoral factor and is implicated in multiple biological processes. However, the effects of klotho on podocyte injury in diabetic nephropathy are poorly understood. Thus, the current study aims to investigate the renoprotective effects of klotho against podocyte injury in diabetic nephropathy. We examined lipid accumulation and klotho expression in the kidneys of diabetic patients and animals. We stimulated cultured mouse podocytes with palmitate to induce lipotoxicity-mediated podocyte injury with or without recombinant klotho. Klotho level was decreased in podocytes of lipid-accumulated obese diabetic kidneys and palmitate-treated mouse podocytes. Palmitate-treated podocytes showed increased apoptosis, intracellular ROS, ER stress, inflammation, and fibrosis, and these were significantly attenuated by klotho administration. Klotho treatment restored palmitate-induced downregulation of the antioxidant molecules, Nrf2, Keap1, and SOD1. Klotho inhibited the phosphorylation of FOXO3a, promoted its nuclear translocation, and then upregulated MnSOD expression. In addition, klotho administration attenuated palmitate-induced cytoskeleton changes, decreased nephrin expression, and increased TRPC6 expression, eventually improving podocyte albumin permeability. These results suggest that klotho administration prevents palmitate-induced functional and morphological podocyte injuries, and this may indicate that klotho is a potential therapeutic agent for the treatment of podocyte injury in obese diabetic nephropathy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250666PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064606PMC
April 2021
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