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Objective: To evaluate the effects of Capsosiphon fulvescens (C. fulvescens) ethanolic extract on inflammation in lipopolysaccharide (LPS)-induced RAW296.7 macrophages. Methods: The protective effects of C. fulvescens ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis, including enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis. To examine reactive oxygen species (ROS) production, flow cytometry analysis, and immunofluorescence staining were used. Furthermore, the modulatory effect of C. fulvescens ethanolic extract on NF-κB activation was investigated. Results: C. fulvescens ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix metalloproteinases. In addition, C. fulvescens ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling pathway. Conclusions: C. fulvescens ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 macrophages. C. fulvescens can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

Objective To analyze the changes in muscle mass and quality with time on the paretic and non-paretic sides in subacute stroke patients and identify correlations between the variation of muscle mass and quality and lower limb functions. Methods Thirty hemiplegia patients diagnosed with stroke participated in this study. To evaluate poststroke muscle changes, longitudinal measurement of muscle mass and quality was conducted with bilateral lower limbs. The elastic shear modulus was measured using shear wave elastography and muscle thickness (MT) of rectus femoris, vastus intermedius, vastus lateralis (VL), vastus medialis, tibialis anterior, and gastrocnemius (GCM) muscles. Functional evaluation was performed using Berg Balance Scale (BBS), Five Times Sit to Stand Test (FTSST). Follow-up was performed at discharge. The muscle mass and quality were compared according to time. We analyzed whether muscle quantity and quality were related to function. Results MT demonstrated no significant change with time. The elastic shear modulus increased significantly in the paretic VL and GCM muscles and did not change significantly in the muscles on the non-paretic side. Correlation analysis detected that elastic shear modulus in the VL has a cross-sectional negative relationship between BBS and positive relationship between FTSST. There were significant correlation between variation of FTSST and the variation of the elastic shear modulus in VL. Conclusion Only paretic VL and GCM muscle quality changed in subacute stroke patients and muscle’s property related to lower limb functions. Therefore, the lower extremity requires an approach to muscle quality rather than quantity for subacute stroke patients.

Abstract Pathogenic variants of KCNQ4 cause symmetrical, late-onset, progressive, high-frequency-affected hearing loss, which eventually involves all frequencies with age. To understand the contribution of KCNQ4 variants to hearing loss, we analyzed whole-exome and genome sequencing data from patients with hearing loss and individuals whose hearing phenotypes were unknown. In KCNQ4, we identified seven missense variants and one deletion variant in 9 hearing loss patients and 14 missense variants in the Korean population with an unknown hearing loss phenotype. The p.R420W and p.R447W variants were found in both cohorts. To investigate the effects of these variants on KCNQ4 function, we performed whole-cell patch clamping and examined their expression levels. Except for p.G435Afs*61, all KCNQ4 variants exhibited normal expression patterns similar to those of wild-type KCNQ4. The p.R331Q, p.R331W, p.G435Afs*61, and p.S691G variants, which were identified in patients with hearing loss, showed a potassium (K+) current density lower than or similar to that of p.L47P, a previously reported pathogenic variant. The p.S185W and p.R216H variants shifted the activation voltage to hyperpolarized voltages. The channel activity of the p.S185W, p.R216H, p.V672M, and p.S691G KCNQ4 proteins was rescued by the KCNQ activators retigabine or zinc pyrithione, whereas p.G435Afs*61 KCNQ4 proteins were partially rescued by sodium butyrate, a chemical chaperone. Additionally, the structure of the variants predicted using AlphaFold2 showed impaired pore configurations, as did the patch-clamp data. Our findings suggest that KCNQ4 variants may be overlooked in hearing loss that starts in adulthood. Some of these variants are medically treatable; hence, genetic screening for KCNQ4 is important.

Auranofin is a US Food and Drug Administration (FDA)-approved anti-arthritis medication that functions as a thioredoxin reductase inhibitor. Spermidine, a polyamine present in marine algae, can exert various physiological functions. Herein, we examined the synergistic anticancer activity of auranofin and spermidine in hepatocellular carcinoma (HCC). Combined treatment with auranofin and spermidine suppressed cell viability more efficiently than either treatment alone in HCC Hep3B cells. The isobologram plotted by calculating the half maximal inhibitory concentration (IC50) values of each drug indicated that the two drugs exhibited a synergistic effect. Based on the analysis of annexin V and cell cycle distribution, auranofin and spermidine markedly induced apoptosis in Hep3B cells. Moreover, auranofin and spermidine increased mitochondria-mediated apoptosis by promoting mitochondrial membrane potential (Δψm) loss. Auranofin and spermidine significantly increased reactive oxygen species (ROS) production in Hep3B cells, and the blocking ROS suppressed apoptosis induced by spermidine and auranofin. In addition, auranofin and spermidine reduced the expression of phosphorylated phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), and PI3K inhibitor accelerated auranofin- and spermidine-induced apoptosis. Using ROS scavenger and PI3K inhibitor, we revealed that ROS acts upstream of auranofin- and spermidine-induced apoptosis. Collectively, our study suggests that combination treatment with auranofin and spermidine could afford synergistic anticancer activity via ROS overproduction and reduced PI3K/Akt signaling pathway.

Abstract Background In Canada, Ontario Health Teams (OHTs) are a new model for integrated healthcare. Core to OHTs are family physicians (FPs) and their ability to collaborate with other FPs and healthcare providers. Whereas the factors for intra-organizational collaboration have been well-studied, inter-organizational collaboration between FPs and other healthcare organizations as an integrated care network, are less understood. This paper aims to explore the structural factors, processes, and theoretical frameworks that support FPs’ collaboration for integrated healthcare. Methods A scoping review was undertaken based on Joanna Briggs Institute (JBI) methodology for scoping review and using the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Review (PRISMA_ScR) checklist. A search for academic and relevant grey literature published between 2000–2021 was conducted across databases (MEDLINE, EMBASE, EBSCOhost).Thematic analysis was used to identify the key findings of the selected studies. Results Thirty-two studies were included as eligible for this review. Three structural components were identified as critical to FPs’ successful participation in inter-organizational partnerships: (1) shared vision/values, (2) leadership by FPs, and (3) defined decision-making procedures. Also, three processes were identified: (1) effective communication, (2) a collective sense of motivation for change, and (3) relationships built on trust. Three theoretical frameworks provided insight into collaborative initiatives: (1) Social Identity Approach, (2) framework of interprofessional collaboration, and (3) competing values framework. Conclusion FPs hold unique positions in healthcare and this review is the first to synthesize the best evidence for building collaborations between FPs and other healthcare sectors. These findings will inform collaboration strategies for healthcare integration, including with OHTs.

Enterococcus faecium is a prevalent species found in fermented soybean products, known for its contributions to flavor development and inhibition of pathogenic microorganisms during fermentation. This study aims to provide comprehensive phenotypic and genomic evidence supporting the probiotic characteristics of E. faecium EFEL8600, a bacteriocin-producing strain isolated from Korean soy-meju. Phenotypic analysis revealed that EFEL8600 produced a peptide with inhibitory activity against Listeria monocytogenes, estimated to be 4.6 kDa, corresponding to the size of enterocins P or Q. Furthermore, EFEL8600 exhibited probiotic traits, such as resilience in gastrointestinal conditions, antioxidant and anti-inflammatory activities, and protection of the intestinal barrier. Safety assessments demonstrated no hemolytic and bile salt deconjugation activities. Genomic analysis revealed the presence of several genes associated with probiotic characteristics and bacteriocin production, while few deleterious genes with a low likelihood of expression or transferring were detected. Overall, this study highlights E. faecium EFEL8600 as a potent anti-listeria probiotic strain suitable for use as a starter culture in soymilk fermentation, providing potential health benefits to consumers.

Abstract Background Probiotic starters can improve the flavor profile, texture, and health-promoting properties of fermented foods. Tetragenococcus halophilus is a halophilic lactic acid bacterium that is a candidate starter for high-salt fermented foods. However, the species is known to produce biogenic amines, which are associated with neurotoxicity. Here, we report a probiotic starter strain of T. halophilus, EFEL7002, that is suitable for use in high-salt fermentation. Results EFEL7002 was isolated from Korean meju (fermented soybean) and identified as T. halophilus, with 99.85% similarity. The strain is safe for use in food as it is a non-hemolytic and non-biogenic amine producer. EFEL7002 is tolerant to gastrointestinal conditions and can adhere to Caco-2 cells. This strain showed antioxidant, anti-inflammatory, and protective effects against the human gut epithelial barrier. EFEL7002 grew well in media containing 0–18% NaCl showing maximum cell densities in 6% or 12% NaCl. Conclusions T. halophilus EFEL7002 can be used as a health-promoting probiotic starter culture for various salty fermented foods.

Background: A small number of studies have suggested an association between systemic lupus erythematosus (SLE) and Parkinson’s disease (PD). Objectives: This study aimed to determine the risk of incident PD among Korean patients with SLE. Design: A nationwide retrospective cohort study using the claims database of the National Health Insurance Service of Korea was conducted. Methods: Patients above 40 years of age diagnosed with SLE between 2010 and 2015 were included in the study. The primary outcome of the study was incident PD, defined by registration in the rare intractable diseases program for PD and an ICD-10 code of G20. Subjects were followed until PD diagnosis or the end of 2017. We estimated the cumulative incidence of PD among the SLE cohort and compared this to that in a 1:5 age- and sex-matched control group. Results: Totals of 11,615 SLE cases and 58,075 matched controls were identified. The cumulative incidence rate of PD was 0.7 per 1000 person-years in the SLE cohort. The crude hazard ratio (HR) of incident PD was 1.71 (95% CI: 1.25–2.36) among the SLE cohort compared to the control group. The HR was 1.59 (95% CI: 1.15–2.20) after adjustment for age, sex, income, and baseline comorbidities. Conclusion: This study demonstrated that patients with SLE had an increased risk of incident PD compared to non-SLE controls. Further research is required to determine the mechanism underlying this and to elucidate the precise role of systemic inflammation in the development of PD in patients with SLE.

Abstract Intestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific diagnostic tests to differentiate them. We used a proteomic approach to discover novel diagnostic biomarkers specific to intestinal BD. Colon mucosa tissue samples were obtained from patients with intestinal BD or CD using colonoscopy-guided biopsy of the affected bowel. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Using TMT/LC–MS/MS-based proteomic quantification, we identified 39 proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed higher intensity in the IHC staining of intestinal BD tissues than in CD tissues. The serum MGAM level was higher in intestinal BD patients. Proteomic analysis revealed that some proteins were differentially expressed in patients with intestinal BD compared with those with CD. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker.

Background Metabolic disturbances are modifiable risk factors for dementia. Because the status of metabolic syndrome (MetS) and its components changes over time, we aimed to investigate the association of the cumulative exposure to MetS and its components with the risk of dementia. Methods Adults (n=1,492,776; ≥45-years-old) who received health examinations for 4 consecutive years were identified from a nationwide population-based cohort in Korea. Two exposure-weighted scores were calculated: cumulative number of MetS diagnoses (MetS exposure score, range of 0 to 4) and the composite of its five components (MetS component exposure score, range of 0 to 20). Hazard ratio (HR) and 95% confidence interval (CI) values for dementia were analyzed using the multivariable Cox proportional-hazards model. Results Overall, 47.1% of subjects were diagnosed with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase in the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia with increasing MetS exposure score and MetS component exposure score (each P for trend

Abstract Background Although elevated serum gamma‐glutamyltransferase (GGT) is a known indicator of increased risk of several cancers, the clinical value of repeated measurements of GGT has not been determined. Therefore, we aimed to investigate whether repeatedly elevated serum GGT levels are associated with the risk of respiratory cancer incidence. Methods We included participants who had undergone the Korean Health screening four times during 2009–2012 and had previously undergone four consecutive examinations. Those who were diagnosed with respiratory cancer before the date of examination were excluded. The participants obtained one GGT point if their GGT levels were in the highest quartile (the quartile 4 group). We analyzed the association between GGT points and respiratory cancer incidence by Cox proportional hazard models. Results During mean follow‐up of 6.39 ± 1.2 years, 3,559,109 participants were enrolled. Of them, 8,944 (0.34%) men and 1,484 (0.14%) women were newly diagnosed with respiratory cancer. In multivariate analysis adjusted for confounding factors, male participants with 4 GGT points had a significantly higher hazards of developing respiratory cancer than those with 0 GGT points (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.31–1.48). Among female, participants with the highest points of GGT also had sixfold increased risk of developing laryngeal cancer. However, no significant association was observed between GGT points and lung cancer incidence among women (HR: 0.95; 95% CI: 0.81–1.11). Conclusion Repeatedly elevated serum levels of GGT were associated with a higher risk of respiratory cancer incidence, especially in men. This finding suggests that physicians can identify a person with a higher risk of respiratory cancer through a simple repeated measurement of GGT.

Abstract We evaluated the impacts of lifestyle behaviors, namely smoking, alcohol consumption, and physical activity, on the development of new-onset AF in patients with DM. Using the Korean Nationwide database, we identified subjects diagnosed with type 2 DM and without previous history of AF between 2009 and 2012. Self-reported lifestyle behaviors were analyzed. Among 2,551,036 included subjects, AF was newly diagnosed in 73,988 patients (median follow-up 7.1 years). Both ex-smokers (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02–1.07) and current smokers (HR 1.06, 95% CI 1.03–1.08) demonstrated a higher risk of AF than never smokers. Patients with moderate (15–29 g/day) (HR 1.12, 95% CI 1.09–1.15) and heavy (≥ 30 g/day) (HR 1.24, 95% CI 1.21–1.28) alcohol consumption exhibited an increased risk of AF, while subjects with mild alcohol consumption (

Background Evidence regarding the association between variabilities in obesity measures and health outcomes is limited. We aimed to examine the association between variabilities in obesity measures and cardiovascular outcomes and all-cause mortality. Methods We identified 4,244,460 individuals who underwent health examination conducted by the Korean National Health Insurance Service during 2012, with ≥3 anthropometric measurements between 2009 and 2012. Variabilities in body weight (BW) and waist circumference (WC) were assessed using four indices including variability independent of the mean (VIM). We performed multivariable Cox proportional hazards regression analyses. Results During follow-up of 4.4 years, 16,095, 18,957, and 30,200 cases of myocardial infarction (MI), stroke, and all-cause mortality were recorded. Compared to individuals with the lowest quartiles, incrementally higher risks of study outcomes and those of stroke and all-cause mortality were observed among individuals in higher quartiles of VIM for BW and VIM for WC, respectively. The multivariable adjusted hazard ratios and 95% confidence intervals comparing the highest versus lowest quartile groups of VIM for BW were 1.17 (1.12 to 1.22) for MI, 1.20 (1.16 to 1.25) for stroke, and 1.66 (1.60 to 1.71) for all-cause mortality; 1.07 (1.03 to 1.12) for stroke and 1.29 (1.25 to 1.33) for all-cause mortality regarding VIM for WC. These associations were similar with respect to the other indices for variability. Conclusion This study revealed positive associations between variabilities in BW and WC and cardiovascular outcomes and all-cause mortality. Our findings suggest that variabilities in obesity measures are associated with adverse health outcomes in the general population.

Abstract Aims/Introduction We investigated the risk of incident type 2 diabetes according to the cumulative exposure to obesity or metabolic syndrome (MetS) during annual or biennial health examinations. Materials and Methods The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this retrospective longitudinal study. The risk for type 2 diabetes was analyzed according to the cumulative exposure to obesity and MetS among individuals who underwent four health examinations from 2009 to 2012 or 2013 (n = 2,851,745). Results During examinations, 28.56 and 17.86% of the total participants showed fluctuations in metabolic health state and obesity, respectively. During a mean 5.01 years of follow up, 98,950 new type 2 diabetes cases developed. The risk for type 2 diabetes increased with the increase in exposure to MetS (hazard ratio [HR] 2.92, 95% confidence interval [CI] 2.86–2.99; HR 4.96, 95% CI 4.85–5.08; HR 7.46, 95% CI 7.30–7.63; HR 12.24, 95% CI 12.00–12.49 in groups with number of exposures one to four, respectively) and obesity (HR 1.60, 95% CI 1.56–1.65; HR 1.87, 95% CI 1.81–1.92; HR 2.25, 95% CI 2.19–2.31; HR 3.46, 95% CI 3.41–3.51 in groups with number of exposures one to four, respectively), showing a more detrimental effect of cumulative exposure to MetS, when compared with the exposure to obesity. Conclusions Metabolic health and obesity fluctuated within a relatively short period of 4–5 years. Although the impact was much greater for MetS than for obesity, the cumulative duration of both obesity and MetS was associated with an increased risk of type 2 diabetes in a dose‐response manner. Therefore, continuously maintaining metabolic health and normal weight is crucial to prevent incident type 2 diabetes.

Abstract Background Metabolic syndrome (MetS) status changes over time, but few studies have investigated the relationship between the extent or duration of exposure to MetS and the risk of cardiovascular disease (CVD). We investigated the cumulative effects of MetS and its components on the risk of myocardial infarction (MI) and stroke. Methods From the Korean National Health Insurance database, 2,644,851 people who received annual health examinations from 2010 to 2013 were recruited. Exposure-weighted scores for MetS during this 4-year period were calculated in two ways: cumulative number of MetS diagnoses (MetS exposure score, range: 0–4) and the composite of its five components (MetS component exposure score, range: 0–20). The multivariable Cox proportional-hazards model was used to assess CVD risk according to the exposure-weighted scores for MetS. Results MetS was identified at least once in 37.6% and persistent MetS in 8.2% of subjects. During the follow-up (median, 4.4 years), 10,522 cases of MI (0.4%) and 10,524 cases of stoke (0.4%) occurred. The risk of MI and stroke increased gradually with increasing exposure scores of MetS and its components (each P for trend

Abstract Background Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. Results All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17). Conclusion We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.

Abstract Background We aimed to investigate the hazard of hospitalization for heart failure (hHF) according to the transitions in metabolic health and obesity status. Methods The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this nationwide, longitudinal, population-based study. The hazard of hHF was analyzed according to the eight groups stratified by stability in metabolic health and transition in obesity status among initially metabolically healthy adults who underwent two cycles of health examinations in 2009–2010 and 2013–2014 (N = 7,148,763). Results During two examinations, 48.43% of the initially metabolically healthy obese (MHO) individuals and 20.94% of the initially metabolically healthy non-obese (MHNO) individuals showed changes in their metabolic health and obesity status. During a mean follow-up of 3.70 years, 3151 individuals were hospitalized for HF. When stable MHNO individuals were set as the reference, transition to metabolically unhealthy phenotype was associated with an increased hazard of hHF; the hazard ratio (HR) and 95% confidence interval (CI) in the individuals who transformed from MHO to metabolically unhealthy non-obese was 2.033 (1.579–2.616). The constant MHO group had a 17.3% increased hazard of hHF compared with the stable MHNO group [HR (95% CI) 1.173 (1.039–1.325)]. Individuals who shifted from MHO to MHNO showed a 34.3% lower hazard of hHF compared with those who maintained the MHO category [HR (95% CI) 0.657 (0.508–0.849)]. Conclusion Dynamic changes in metabolic health and obesity status were observed during a relatively short interval of 3–5 years. Loss of metabolic health was significantly associated with an increased hazard of hHF. Even if metabolic health was maintained, persistent obesity remained as a risk factor for hHF, and transition from MHO to MHNO had a protective effect against hHF. Therefore, the prevention and control of obesity while maintaining metabolic health would be crucial in preventing hHF.

Abstract Background Bodyweight variability is a risk factor for atrial fibrillation (AF). We aimed to examine the relationship between bodyweight variability and the risk of AF in patients with type 2 diabetes mellitus (DM), and whether this relationship was affected by baseline body mass index (BMI), weight change, or advanced diabetic stage. Methods A nationwide population-based cohort of 670,797 patients with type 2 DM from the Korean National Health Insurance Service database without a history of AF and with ≥ 3 measurements of bodyweight over a 5-year period were followed up for AF development. Intra-individual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quintile with the highest variability with the lower four quintiles as reference. Results During a median of 7.0 years of follow-up, 22,019 patients (3.3%) newly developed AF. After multivariate adjustment, those in the highest quintile of bodyweight variability showed a higher risk of incident AF (HR 1.16, 95% CI 1.12–1.20) compared to those in the lower 4 quintiles with reference bodyweight variability, irrespective of baseline BMI group and direction of overall weight change. This association was greater in magnitude in subjects with lower BMI, those on insulin, and those with a DM duration of greater than 5 years. In sensitivity analyses, high bodyweight variability was consistently associated with AF development using other indices of variability and adjusting for glycemic variability. Conclusions High variability in bodyweight was associated with AF development, independently of traditional cardiovascular risk factors and baseline BMI. This association was stronger in underweight patients and with advanced diabetic stage. Weight fluctuation may interfere with the beneficial effects of weight loss and should be avoided when possible in weight control regimens for DM patients.

Abstract This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.

Lactiplantibacillus plantarum PMO 08 has been used as a probiotic starter culture for plant-based fermented beverages, with various health-promoting effects such as cholesterol-lowering and anti-inflammatory activities. This study aimed to analyze the genome sequence of Lp. plantarum PMO 08 and identify its safety and probiotic characteristics at the genomic level. For this, complete genome sequencing was conducted to investigate the genes associated with risk and probiotic characteristics by using Pacbio combined with Illumina HiSeq. This bacterial strain has one circular chromosome of 3,247,789 bp with 44.5% G + C content and two plasmids of 50,296 bp with 39.0% G + C content and 19,592 bp with 40.5% G + C content. Orthologous average nucleotide identity analysis showed that PMO 08 belongs to the Lp. plantarum group with 99.14% similarity to Lp. plantarum WCFS1. No deleterious genes were determined in the virulence factor analysis, and no hemolysin activity or secondary bile salt synthesis were detected in vitro test. In the case of antibiotic resistance analysis, PMO 08 was resistant to ampicillin in vitro test, but these genes were not transferable. In addition, the strain showed same carbohydrate utilization with Lp. plantarum WCFS1, except for mannopyranoside, which only our strain can metabolize. The strain also harbors a gene for inositol monophosphatase family protein related with phytate hydrolysis and have several genes for metabolizing various carbohydrate which were rich in plant environment. Furthermore, in probiotic characteristics several genes involved in phenotypes such as acid/bile tolerance, adhesion ability, and oxidative stress response were detected in genome analysis. This study demonstrates that Lp. plantarum PMO 08 harbors several probiotic-related genes (with no deleterious genes) and is a suitable probiotic starter for plant-based fermentation.

Loss of immunity is an important cause in the pathology of infectious disease. This study investigates the effect of Litsea japonica fruit extract (LJFE) as a potential functional food on immunity and hematopoietic function in immunosuppressed BALB/c mice. Immunity-stimulating activity was observed in mice supplemented with LJFE at low (25 mg/kg), medium (50 mg/kg), and high (100 mg/kg) dosage for seven days after administration of cyclophosphamide. LJFE treatment significantly improved spleen injury score (p < 0.001) and body weight (p < 0.02) by approximately two-fold with a high dosage of LJFE (100 mg/kg). Spleen-derived lymphocyte analysis demonstrated that the numbers of clusters of differentiation (CD)4+ and CD8+ T-cells were notably increased by approximately two-fold (p < 0.001) with a high dosage of LJFE (100 mg/kg). In mouse splenocytes differentiated into T- and B-lymphocytes, LJFE significantly induced proliferation up to approximately 90% of control for T- (p < 0.001) and B-lymphocytes (p < 0.01) with a high dosage of LJFE (100 mg/kg). Furthermore, LJFE significantly recovered the numbers of white blood cells, red blood cells, and platelets. Enzyme-linked immunosorbent assay revealed that serum levels of immune-related cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-2, and interferon (IFN)-γ, were notably Increased. In addition, serum levels of immunoglobulin (Ig) A, IgM, and IgG were restored by LJFE treatment. This study provides a reference to use L. japonica as a functional food ingredient to improve immunity and hematological function in humans.

BackgroundMetabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals.MethodsWe analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO.ResultsDuring the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged

Abstract Background Previous studies reported that stature is inversely related to the risk of cardiovascular disease. However, there is limited evidence on the association between height and lipid profiles. We aimed to examine the association of height with total cholesterol and hypercholesterolemia based on the nationally representative dataset of Korean adults. Methods The data of 13,701 adults aged ≥19 years who participated in the Korea National Health and Nutrition Examination Survey (2013–2015) were used in this nationwide population-based cross-sectional study. Hypercholesterolemia was defined as a serum total cholesterol level ≥ 240 mg/dL or use of lipid-lowering medications. Multivariable linear regression and logistic regression analyses were used to examine the association of height with mean total cholesterol level and odds ratios (ORs) of hypercholesterolemia. Results Approximately 17% of participants had hypercholesterolemia. Mean total cholesterol levels decreased in the higher quartile (Q) groups of height after adjusting for confounding variables including age, sex, body mass index, smoking status, alcohol consumption, physical activity, income, educational level, hypertension, and diabetes mellitus (P for trend = 0.035). After adjusting for these potential confounding variables, the adjusted ORs of hypercholesterolemia were significantly lower in the Q3 and Q4 groups than in the Q1 group; ORs decreased in the higher quartile groups of height (OR: 0.83, 95% confidence interval: 0.71–0.99 in Q3; 0.81, 0.69–0.95 in Q4, P for trend = 0.007). The association between height (Q4 vs. Q1–Q3) and hypercholesterolemia was stronger in men or individuals without hypertension or diabetes than in women or individuals with such diseases. Conclusions Height is inversely associated with total cholesterol level and odds of hypercholesterolemia among Korean adults. Childhood environment related to short stature may be associated with hypercholesterolemia and cardiovascular health in adulthood.

Background Identifying predictive markers for future atherosclerotic cardiovascular diseases may be helpful to motivate young adults to promote healthy lifestyle. We sought to determine the association between persistently elevated low‐density lipoprotein‐cholesterol (LDL‐C) and/or triglyceride levels and the atherosclerotic cardiovascular diseases risks in young adults. Methods and Results We conducted a nationwide population‐based cohort study of 1 887 853 statin‐naive adults aged 20 to 39 years, with LDL‐C

Triggering receptor expressed on myeloid cell-1 (TREM-1) signaling is expressed on neutrophils and monocytes that is necessary for the successful antimicrobial response and resolution of inflammation in the gut. In this study, we determined the effect of an anti-TREM-1 agonistic antibody (α-TREM-1) on colitis and identify its underlying mechanism of action. Administration of α-TREM-1 alleviated colitis in mice and resolved dysbiosis, which required TLR4/Myd88 signaling. α-TREM-1 increased the production of neutrophil extracellular traps and interleukin-22 by CD177+ neutrophils, which led to pathogen clearance and protection of the intestinal barrier. TREM-1 activation using an α-TREM-1 antibody protects against colitis by rebalancing the microbiota and protecting the epithelium against the immune response as well as modulates the function of neutrophils and macrophages. These results highlight the importance of the TREM-1 pathway in intestinal homeostasis and suggest that α-TREM-1 treatment may be an effective therapeutic strategy for inflammatory bowel disease.

AimsNon-alcoholic fatty liver disease (NAFLD) has a dynamic disease course, therefore repeated measurements of NAFLD status could have benefits rather than single one. The aim of this study was to investigate the effects of persistent NAFLD on the incidence of myocardial infarction (MI) and stroke and all-cause mortality by using repeated measurement of fatty liver index (FLI).MethodsAbout 3 million subjects who had undergone the health screening four times from 2009 until 2013 were included. NAFLD was defined as an FLI ≥60. FLI points were defined as the number of times participants meeting the criteria of NAFLD (0–4). Outcomes included all-cause mortality, MI, and stroke.ResultsThe higher the FLI points, the higher the risk of all-cause mortality, MI, and stroke (P for trend

Background Although occult hemoglobin in feces is universally valued as a screening tool for colorectal cancer (CRC), only few studies investigated the clinical meaning of fecal immunochemical test (FIT) in other diseases. We evaluated the clinical utility of FIT in patients with cardiovascular diseases (namely, ischemic stroke and myocardial infarction [MI]). Methods and Results Using the National Health Insurance database, participants (aged >50 years) with CRC screening records from 2009 to 2012 were screened and followed up. Subjects with a history of cardiovascular diseases and CRC were excluded. Ischemic stroke, MI, and other comorbidities were defined by International Classification of Diseases, Tenth Revision (ICD‐10), codes. Age, sex, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, and body mass index were adjusted in a multivariate analysis. A total of 6 277 446 subjects were eligible for analysis. During the mean 6.79 years of follow‐up, 168 570 participants developed ischemic stroke, 105 983 developed MI, and 11 253 deaths were observed. A multivariate‐adjusted model revealed that the risk of ischemic stroke was higher in the FIT‐positive population (adjusted hazard ratio [HR], 1.09; 95% CI, 1.07–1.11). Similarly, FIT‐positive subjects were at an increased risk of MI (adjusted HR, 1.09; 95% CI, 1.06–1.12). Moreover, increased all‐cause mortality was observed in the FIT‐positive population (adjusted HR, 1.15; 95% CI, 1.07–1.23). The increased risk remained consistent in the stratified analysis on anemia and CRC status. Conclusions Positive FIT findings were associated with ischemic stroke, MI, and mortality. Occult blood in feces may offer more clinical information than its well‐known conventional role in CRC screening.

This study aimed to evaluate the effect of a horse-riding simulator (HRS) with virtual reality (VR) on gross motor function, balance control, and body composition in children with spastic cerebral palsy (CP). Seventeen preschool and school-aged children with spastic CP were included; 10 children in the intervention group (HRS group) received 30 min of HRS with VR training twice a week for a total of 16 sessions in addition to conventional physiotherapy. Seven children in the control group were instructed to perform home-based aerobic exercises twice a week for 8 weeks in addition to conventional physiotherapy. Gross motor function measure (GMFM) and body composition were evaluated before the first session and after the last session. Before and after the 2-month intervention, Pediatric Balance Scale and Timed Up and Go test were evaluated for the HRS group. GMFM scores and body composition changed significantly in the HRS group (p < 0.05). However, no significant differences were observed in the control group. Changes in the GMFM total scores, GMFM dimension D scores, and skeletal muscle mass significantly differed between the HRS and control groups (p < 0.05). HRS with VR may be an effective adjunctive therapeutic approach for the rehabilitation of children with CP.

ObjectiveVariability in estimated glomerular filtration rate (eGFR) has been associated with adverse outcomes in patients with diabetes or chronic kidney disease (CKD). However, no previous study has explored the relationship between eGFR variability and type 2 diabetes incidence.Research design and methodsIn this nationwide, longitudinal, cohort study, we investigated the association between eGFR variability and type 2 diabetes risk using the Korean National Health Insurance Service datasets from 2002 to 2017. eGFR variability was calculated using the variability independent of the mean (eGFR-VIM), coefficient of variation (eGFR-CV), standard deviation (eGFR-SD) and average real variability (eGFR-ARV).ResultsWithin 7 673 905.58 person-years of follow-up (mean follow-up: 3.19 years; n=2 402 668), 11 981 cases of incident type 2 diabetes were reported. The HRs and 95% CIs for incident type 2 diabetes increased according to advance in quartiles of eGFR-VIM (HR (95% CI): Q2, 1.068 (1.009 to 1.130); Q3, 1.077 (1.018 to 1.138); Q4, 1.203 (1.139 to 1.270)) even after adjusting for confounding factors including mean eGFR and mean fasting plasma glucose levels. The subgroup analyses according to risk factors as well as analyses using eGFR-CV, eGFR-SD and eGFR-ARV showed consistent results. The association between increased eGFR variability and type 2 diabetes risk was more prominent in men, individuals with dyslipidemia and those with CKD as shown in the subgroup analysis (p for interaction

Lactobacillus plantarum has been identified as a probiotic bacterium owing to its role in immune regulation and maintenance of intestinal permeability. Here, we investigated the anti-colitic effects and mechanism of L. plantarum CBT LP3 (LP3). This in vivo study was performed using dextran sodium sulfate (DSS) to induce colitis in mice. Mice were randomly divided into three groups: a control supplied with normal drinking water, a DSS-treated group followed by oral administration of vehicle, and a DSS-treated group gavaged with LP3 daily for 7 days following DSS administration. An analysis of macrophages and T cell subsets harvesting from peritonium cavity cells and splenocytes was performed using a flow cytometric assay. Gene expression and cytokine profiles were measured using quantitative reverse transcriptase polymerase chain reaction. The administration of LP3 significantly attenuated disease activity and histolopathology compared to control. LP3 had anti-inflammatory effects, with increased induction of regulatory T cells and type 2 helper T cells in splenocytes and restoration of goblet cells accompanied by suppression of proinflammatory cytokine expressions. These findings suggest that L. plantarum CBT LP3 can be used as a potent immunomodulator, which has significant implications for IBD treatment.

Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensorineural hearing loss were selected for exome sequencing. Mutational alleles in MYO7A were identified according to ACMG guidelines. Segregation analysis was performed to examine whether pathogenic variants segregated with affected status of families. All identified pathogenic variants were evaluated for a phenotype–genotype correlation. MYO7A variants were detected in 4.7% of post-lingual families, and 12 of 14 families were multiplex. Five potentially pathogenic missense variants were identified. Fourteen variants causing autosomal dominant deafness were clustered in motor and MyTH4 domains of MYO7A protein. Missense variants in the motor domain caused late onset of hearing loss with ascending tendency. A severe audiological phenotype was apparent in individuals carrying tail domain variants. We report two new pathogenic variants responsible for DFNA11 in the Korean ADHL population. Dominant pathogenic variants of MYO7A occur frequently in motor and MyTH4 domains. Audiological differences among individuals correspond to specific domains which contain the variants. Therefore, appropriate rehabilitation is needed, particularly for patients with late-onset familial hearing loss.

Air pollutants, especially ambient fine particulate matter2.5, may contribute to various ocular surface disorders, including dry eye disease, keratitis and conjunctivitis. A natural polyamine spermidine has a protective effect on the retina and optic nerve; however, no study has been conducted on the application of spermidine in particulate matter2.5-induced dry eye disease. In the present study, we investigated the effect of spermidine eye drops in topically exposed particulate matter2.5-induced dry eye models of Sprague-Dawley rats, by hematological, biochemical and histological evaluation. Spermidine eye drops attenuated the particulate matter2.5 exposure-induced reduction of tear secretion and corneal epithelial damage. Furthermore, spermidine protected against conjunctival goblet cell loss and retinal ganglion cell loss induced by particulate matter2.5. Additionally, spermidine markedly prevented particulate matter2.5-induced infiltration of cluster of differentiation3+ and cluster of differentiation4+ T lymphocytes and F4/80+ macrophages on lacrimal gland. Moreover, over expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 and interleukin-17 in the lacrimal gland and cornea. Meanwhile, the levels of serum total cholesterol and low-density lipoprotein cholesterol were markedly increased by topical exposure to particulate matter2.5, but this change in the lipid profile was decreased by spermidine. Taken together, spermidine may have protective effects against particulate matter2.5-induced dry eye symptoms via stabilization of the tear film and suppression of inflammation and may in part contribute to improving retinal function and lipid metabolism disorder.

The horse riding simulator (HRS) reportedly has a beneficial effect on motor function and balance in children with cerebral palsy (CP). However, by itself, the HRS is not a sufficient source of challenge and motivation for children. To address this issue, we combined the HRS with virtual reality (VR) to promote somatosensory stimulation and motivation. Sixteen children (ages: 5–17 years) with CP and presenting Gross Motor Function Classification System (GMFCS) levels I–IV were enrolled in the study. Using a head-mounted display and controllers, interventions were carried out over 30-min periods (two rides lasting 12 min each, along with a six-min rest period) twice a week over a period of eight weeks (16 sessions in aggregate). The Pediatric Balance Scale (PBS), Gross Motor Function measure (GMFM)-88, and GMFM-66 scores of each participant were measured before and after the interventions. Statistically significant improvements were observed in the PBS, GMFM-66, the total GMFM-88 scores, and those corresponding to dimensions D and E of GMFM-88 after the intervention (p < 0.05). This study demonstrates that VR-incorporated HRS is effective in improving motor function and balance in children with CP and that its incorporation in conventional PT programs could yield beneficial results.

Ferulic acid (FA), a ubiquitous natural phenolic component found in many plants and fruits, has a wide range of biomedical applications. However, action mechanism of FA involved in lipid accumulation remains unclear. In this study, lipid accumulation and changes in expression levels of genes and proteins associated with adipocyte differentiation were investigated. Oil red O staining and glycerol accumulation assay revealed that FA decreased lipid accumulation in cells. FA downregulated expression levels of C/EBP-β, C/EBP-α, PPAR-γ, and SREBP-1, but upregulated expression levels of p38MAPK, p44/42 (Erk 1/2), and AMPK-α phosphorylation in 3T3-L1 cells. FA effects on high fat diet-induced (HFD) obese mice were also investigated. FA lowered HFD-induced body weight gain of obese mice without affecting regular food intake. FA reduced serum levels of total cholesterol and triglycerides in HFD obese mice. Similar to results of in vitro study, FA inhibited adipogenesis and lipid accumulation via downregulating PPAR-γ while upregulating p38MAPK, p44/42 (Erk 1/2), and AMPK-α phosphorylation in Swiss albino mice.

Abstract Interleukin 33 (IL-33) that signals through the ST2 receptor has emerged as a critical modulator in several inflammatory disorders, including inflammatory bowel disease (IBD). However, the precise mechanisms by which IL-33 modulates IBD are controversial. The aim of this study was thus to clarify the role of IL-33 in IBD. The plasma levels of IL-33 were significantly decreased, but soluble ST2 levels were increased in patients with IBD compared to healthy individuals. Moreover, IL-33 restored goblet cell numbers and induced macrophage switching from the M1 to the M2 phenotype. These effects were sufficient to ameliorate colitis in dextran sodium sulfate, trinitrobenzene sulfonic acid, and peritoneal cavity cell transfer models. IL-33 facilitated goblet cell restoration via modulating macrophages toward the M2 phenotype. In addition, wound healing was significantly faster in IL-33-treated human monocyte-derived macrophages than in control cells, which could be attributed to increased polarisation into M2 macrophages. We found that patients with IBD show decreased serum levels of IL-33 compared with healthy individuals and that IL-33 can attenuate colitis and aid tissue repair in mice. The mechanism by which IL-33 exerts these effects appears to involve the stimulation of differentiation of goblet cells and M2 macrophages.

Objectives Although the coating of surface sealants to dental composite resin may potentially reduce bacterial adhesion, there seems to be little information regarding this issue. This preliminary in vitro study investigated the adhesion of Streptococcus mutans (S. mutans) on the dental composite resins coated with three commercial surface sealants. Materials and Methods Composite resin (Filtek Z250) discs (8 mm in diameter, 1 mm in thickness) were fabricated in a mold covered with a Mylar strip (control). In group PoGo, the surfaces were polished with PoGo. In groups PS, OG, and FP, the surfaces polished with PoGo were coated with the corresponding surface sealants (PermaSeal, PS; OptiGuard, OG; Fortify Plus, FP). The surfaces of the materials and S. mutans cells were characterized by various methods. S. mutans adhesion to the surfaces was quantitatively evaluated using flow cytometry (n = 9). Results Group OG achieved the lowest water contact angle among all groups tested (p < 0.001). The cell surface of S. mutans tested showed hydrophobic characteristics. Group PoGo exhibited the greatest bacterial adhesion among all groups tested (p < 0.001). The sealant-coated groups showed statistically similar (groups PS and FP, p > 0.05) or significantly lower (group OG, p < 0.001) bacterial adhesion when compared with the control group. Conclusions The application of the surface sealants significantly reduced S. mutans adhesion to the composite resin polished with the PoGo.

Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid and generally found in the bark of birch trees (Betula sp.). Although several studies have been reported that BA has diverse biological activities, including anti-tumor effects, the underlying anti-cancer mechanism in bladder cancer cells is still lacking. Therefore, this study aims to investigate the anti-proliferative effect of BA in human bladder cancer cell lines T-24, UMUC-3, and 5637, and identify the underlying mechanism. Our results showed that BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest. Furthermore, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c. In addition, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway. BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9. However, pre-treatment of pan-caspase inhibitor markedly suppressed BA-induced apoptosis. Meanwhile, BA did not affect the levels of intracellular reactive oxygen species (ROS), indicating BA-mediated apoptosis was ROS-independent. Furthermore, we found that BA suppressed the wound healing and invasion ability, and decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells. Taken together, this is the first study showing that BA suppresses the proliferation of human bladder cancer cells, which is due to induction of apoptosis, necrosis, and cell cycle arrest, and decrease of migration and invasion. Furthermore, BA-induced apoptosis is regulated by caspase-dependent and ROS-independent pathways, and these results provide the underlying anti-proliferative molecular mechanism of BA in human bladder cancer cells.

Urban particulate matter (UPM) is recognized as a grave public health problem worldwide. Although a few studies have linked UPM to ocular surface diseases, few studies have reported on retinal dysfunction. Thus, the aim of the present study was to evaluate the influence of UPM on the retina and identify the main mechanism of UPM toxicity. In this study, we found that UPM significantly induced cytotoxicity with morphological changes in ARPE-19 human retinal pigment epithelial (RPE) cells and increased necrosis and autophagy but not apoptosis. Furthermore, UPM significantly increased G2/M arrest and simultaneously induced alterations in cell cycle regulators. In addition, DNA damage and mitochondrial dysfunction were remarkably enhanced by UPM. However, the pretreatment with the potent reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) effectively suppressed UPM-mediated cytotoxicity, necrosis, autophagy, and cell cycle arrest. Moreover, NAC markedly restored UPM-induced DNA damage and mitochondrial dysfunction. Meanwhile, UPM increased the expression of mitophagy-regulated proteins, but NAC had no effect on mitophagy. Taken together, although further studies are needed to identify the role of mitophagy in UPM-induced RPE injury, the present study provides the first evidence that ROS-mediated cellular damage through necrosis and autophagy is one of the mechanisms of UPM-induced retinal disorders.

Background and objectives: Hyperuricemia is one of the well-known cardiovascular risk factors. There is a growing interest in the association between hyperuricemia and arrhythmia. We used the representative sample data of Korean population to study the association between hyperuricemia and heart rate irregularity (HRI) that reflects total arrhythmia. Materials and Methods: We performed weighted multivariate logistic regression analysis to assess the association between hyperuricemia and HRI. Results: Of the 10,827 subjects, 1308 (13.2%) had hyperuricemia and 130 (1%) had HRI. In the presence of hyperuricemia, HRI was three times higher than that in the absence of hyperuricemia (OR 2.98, 95% CI 1.71–5.18). The risk of HRI was highest in subjects with both hypertension and hyperuricemia. In the subgroup analysis, the association of hyperuricemia with HRI was most pronounced in the smoker group. Conclusions: Hyperuricemia was highly correlated with HRI in adult Korean representative sample data. Hyperuricemia was associated with a nearly tripled risk for HRI. Hypertension has a synergistic effect with hyperuricemia on HRI. Further research is warranted to clarify the relationship between hyperuricemia and arrhythmia and its mechanism.

Bone growth during childhood and puberty determines an adult’s final stature. Although several prior studies have reported that fermented oyster (FO) consisting of a high amount of gamma aminobutyric acid can be attributed to bone health, there is no research on the efficacy of FO on growth regulation and the proximal tibial growth plate. Therefore, in this study, we investigated the effect of FO oral administration on hepatic and serum growth regulator levels and the development of the proximal tibial growth plate in young Sprague-Dawley rats. Both oral administration of FO (FO 100, 100 mg/kg FO and FO 200, 200 mg/kg FO) and subcutaneous injection of recombinant human growth hormone (rhGH, 200 μg/kg of rhGH) for two weeks showed no toxicity. Circulating levels of growth hormone (GH) significantly increased in the FO 200 group. The expression and secretion of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were enhanced by FO administration. FO administration promoted the expression of bone morphogenic proteins IGF-1 and IGFBP-3 in the proximal tibial growth plate. This positive effect of FO resulted in incremental growth of the entire plate length by expanding the proliferating and hypertrophic zones in the proximal tibial growth plate. Collectively, our results suggested that oral administration of FO is beneficial for bone health, which may ultimately result in increased height.

Synthetic drugs are commonly used to cure various human ailments at present. However, the uses of synthetic drugs are strictly regulated because of their adverse effects. Thus, naturally occurring molecules may be more suitable for curing disease without unfavorable effects. Therefore, we investigated phenyllactic acid (PLA) from Lactobacillus plantarum with respect to its effects on adipogenic genes and their protein expression in 3T3-L1 pre-adipocytes by qPCR and western blot techniques. PLA enhanced differentiation and lipid accumulation in 3T3-L1 cells at the concentrations of 25, 50, and 100 μM. Maximum differentiation and lipid accumulation were observed at a concentration of 100 μM of PLA, as compared with control adipocytes (p < 0.05). The mRNA and protein expression of PPAR-γ2, C/EBP‑α, adiponectin, fatty acid synthase (FAS), and SREBP-1 were increased by PLA treatment as compared with control adipocytes (p < 0.05). PLA stimulates PPAR-γ mRNA expression in a concentration dependent manner, but this expression was lesser than agonist (2.83 ± 0.014 fold) of PPAR-γ2. Moreover, PLA supplementation enhances glucose uptake in 3T3-L1 pre-adipocytes (11.81 ± 0.17 mM) compared to control adipocytes, but this glucose uptake was lesser than that induced by troglitazone (13.75 ± 0.95 mM) and insulin treatment (15.49 ± 0.20 mM). Hence, we conclude that PLA treatment enhances adipocyte differentiation and glucose uptake via activation of PPAR-γ2, and PLA may thus be the potential candidate for preventing Type 2 Diabetes Mellitus (T2DM).

We aimed to investigate the antioxidant and acetylcholinesterase inhibitory activities of the anthocyanin rich extract of grape skin. Grape skin anthocyanin (GSA) neutralized free radicals in different test systems, such as 2,-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, to form complexes with Fe2+ preventing 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced erythrocyte hemolysis and oxidative DNA damage. Moreover, GSA decreased reactive oxygen species (ROS) generation in isolated mitochondria thus inhibiting 2',-7'-dichlorofluorescin (DCFH) oxidation. In an in vivo study, female BALB/c mice were administered GSA, at 12.5, 25, and 50 mg per kg per day orally for 30 consecutive days. Herein, we demonstrate that GSA administration significantly elevated the level of antioxidant enzymes in mice sera, livers, and brains. Furthermore, GSA inhibited acetylcholinesterase (AChE) in the in vitro assay with an IC50 value of 363.61 µg/mL. Therefore, GSA could be an excellent source of antioxidants and its inhibition of cholinesterase is of interest with regard to neurodegenerative disorders such as Alzheimer’s disease.

Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on germinated brown rice (GBR) in the present study and the antioxidant and anti-inflammatory activities of the IO grown on germinated brown rice (IOGBR) extracts were evaluated extensively and compared with those for IO and GBR. IOGBR showed highest antioxidant activities with scavenging total intracellular ROS and MDA levels as well as increasing the antioxidant enzymes activity in the H2O2-stimulated mice liver. It also exhibited best inflammatory activities by suppressing the proinflammatory mediators such as NO, PGE2, iNOS, COX-2, TNF-α, IL-1β, and IL-6 in an LPS-stimulated RAW 264.7 cell line. This study provides a comparative approach to find out an excellent natural source of antioxidants and anti-inflammatory agent as a dietary supplement.

Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors.

House dust mites (HDMs) induce allergic diseases such as asthma. Neutrophil apoptosis is an important process of innate immunity, and its dysregulation is associated with asthma. In this study, we examined the effects of HDM on constitutive apoptosis of normal and asthmatic neutrophils. Extract of Dermatophagoides pteronissinus (DP) inhibited neutrophil apoptosis, but Dermatophagoides farinae extract had no effect. Anti-apoptotic signaling mediated by DP involves in TLR4, Lyn, PI3K, Akt, ERK, and NF-κB in normal neutrophils. DP delayed cleavage of procaspase 9 and procaspase 3 and the decrease in Mcl-1 expression. Supernatant collected from DP-treated normal neutrophils inhibited the constitutive apoptosis of normal neutrophils, and S100A8 and S100A9 were identified as anti-apoptotic proteins in the supernatant. S100A8 and S100A9 transduced the anti-apoptotic signal via TLR4, Lyn, PI3K, Akt, ERK, and NF-κB. DP also suppressed asthmatic neutrophil apoptosis and induced secretion of S100A8 and S100A9, which delayed the constitutive apoptosis. The anti-apoptotic effects of DP, S100A8 and S100A9 in asthmatic neutrophils are associated with TLR4, Lyn, PI3K, Akt, ERK, and NF-κB. The concentrations of S100A8 and S100A9 were significantly elevated in asthmatic bronchoalveolar lavage fluid (BALF) when compared to normal BALF (p

The aim of the study was to isolate and characterize the lactic acid bacteria (LAB) from animal manure. Among the thirty LAB strains, four strains, namely, KCC-25, KCC-26, KCC-27, and KCC-28, showed good cell growth and antifungal activity and were selected for further characterization. Biochemical and physiology properties of strains confirmed that the strains are related to the Lactobacillus sp.; further, the 16S rRNA sequencing confirmed 99.99% sequence similarity towards Lactobacillus plantarum. The strains exhibited susceptibility against commonly used antibiotics with negative hemolytic property. Strains KCC-25, KCC-26, KCC-27, and KCC-28 showed strong antifungal activity against Aspergillus fumigatus, Penicillium chrysogenum, Penicillium roqueforti, Botrytis elliptica, and Fusarium oxysporum, respectively. Fermentation studies noted that the strains were able to produce significant amount of lactic, acetic, and succinic acids. Further, the production of extracellular proteolytic and glycolytic enzymes, survival under low pH, bile salts, and gastric juice together with positive bile salt hydrolase (Bsh) activity, cholesterol lowering, cell surface hydrophobicity, and aggregation properties were the strains advantages. Thus, KCC-25, KCC-26, KCC-27, and KCC-28 could have the survival ability in the harsh condition of the digestive system in the gastrointestinal tract. In conclusion, novel L. plantarum KCC-25, KCC-26, KCC-27, and KCC-28 could be considered as potential antimicrobial probiotic strains.

Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-cancer, anti-inflammatory, antioxidant, and neuroprotective activity. This study aims to investigate the anti-diabetic activity of S. serratifolium and its major constituents through inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, and ONOO−-mediated albumin nitration. S. serratifolium ethanolic extract and fractions exhibited broad PTP1B and α-glucosidase inhibitory activity (IC50, 1.83~7.04 and 3.16~24.16 µg/mL for PTP1B and α-glucosidase, respectively). In an attempt to identify bioactive compounds, three plastoquinones (sargahydroquinoic acid, sargachromenol and sargaquinoic acid) were isolated from the active n-hexane fraction of S. serratifolium. All three plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the IC50 range of 5.14–14.15 µM, while sargachromenol and sargaquinoic acid showed dose-dependent inhibitory activity against α-glucosidase (IC50 42.41 ± 3.09 and 96.17 ± 3.48 µM, respectively). In the kinetic study of PTP1B enzyme inhibition, sargahydroquinoic acid and sargaquinoic acid led to mixed-type inhibition, whereas sargachromenol displayed noncompetitive-type inhibition. Moreover, plastoquinones dose-dependently inhibited ONOO−-mediated albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B and α-glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the prevention and treatment of type 2 diabetes.