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Abstract Background Ceramide, a bioactive signaling sphingolipid, has long been implicated in cancer. Members of the ceramide synthase (CerS) family determine the acyl chain lengths of ceramides, with ceramide synthase 4 (CerS4) primarily generating C18–C20-ceramide. Although CerS4 is known to be overexpressed in breast cancer, its role in breast cancer pathogenesis is not well established. Methods To investigate the role of CerS4 in breast cancer, public datasets, including The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE115577 and GSE96058) were analyzed. Furthermore, MCF-7 cells stably overexpressing CerS4 (MCF-7/CerS4) as a model for luminal subtype A (LumA) breast cancer were produced, and doxorubicin (also known as Adriamycin [AD])-resistant MCF-7/ADR cells were generated after prolonged treatment of MCF-7 cells with doxorubicin. Kaplan–Meier survival analysis assessed the clinical significance of CERS4 expression, while Student’s t-tests or Analysis of Variance (ANOVA) compared gene expression and cell viability in different MCF-7 cell lines. Results Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA. Persistent CerS4 overexpression in MCF-7 cells activated multiple cancer-associated pathways, including pathways involving sterol regulatory element–binding protein, nuclear factor kappa B (NF-κB), Akt/mammalian target of rapamycin (mTOR), and β-catenin. Furthermore, MCF-7/CerS4 cells acquired doxorubicin, paclitaxel, and tamoxifen resistance, with concomitant upregulation of ATP-binding cassette (ABC) transporter genes, such as ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2. MCF-7/CerS4 cells were characterized by increased cell migration and epithelial–mesenchymal transition (EMT). Finally, CERS4 knockdown in doxorubicin-resistant MCF-7/ADR cells resulted in reduced activation of cancer-associated pathways (NF-κB, Akt/mTOR, β-catenin, and EMT) and diminished chemoresistance, accompanied by ABCB1 and ABCC1 downregulation. Conclusions Chronic CerS4 overexpression may exert oncogenic effects in breast cancer via alterations in signaling, EMT, and chemoresistance. Therefore, CerS4 may represent an attractive target for anticancer therapy, especially in LumA breast cancer.

Background To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves’ disease (GD) in real-world practice. Methods This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year). Results Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (–84.7 [TSI slope, –198.2 to 8.2] vs. –120.1 [TSI slope, –204.4 to –45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII, P=0.001). Conclusion Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

Objective: To examine the associations between neighborhood resources (i.e., number of restaurants, recreation centers, or social services for seniors and persons with disability per land area) and cognitive decline among a community-dwelling long-term care population and whether they differ by baseline cognition status. Study design: Prospective longitudinal cohort study. Methods: We used a longitudinal dataset that assessed over a two-year period older adults receiving state-funded home- and community-based services in Michigan Metropolitan areas (N = 9,802) and applied nonlinear mixed models with a random intercept with Poisson distribution. Results: Cognitively intact older adults were less likely to experience cognitive decline when they resided in resource-rich neighborhoods, compared to those cognitively intact but living in neighborhoods that lacked resources. But their cognitively impaired or dementia-diagnosed counterparts did not similarly benefit from living in neighborhoods with rich resources. Conclusions: Neighborhood resources may be an important aspect of intervention to mitigate cognitive decline before older adults become cognitively impaired.

Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients’ quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its multi-compound, multi-target herbal medicines (medicinal plants), offers a promising alternative. However, the complexity of these multi-compound traits poses challenges in understanding the overall mechanisms and efficacy of herbal medicines. Here, we demonstrate the efficacy and underlying mechanisms of these multi-compound herbal medicines specifically used for AR at a systemic level. We utilized a modified term frequency–inverse document frequency method to select AR-specific herbs and constructed an herb–compound–target network using reliable databases and computational methods, such as the Quantitative Estimate of Drug-likeness for compound filtering, STITCH database for compound-target interaction prediction (with a high confidence score threshold of 0.7), and DisGeNET and CTD databases for disease-gene association analysis. Through this network, we conducted AR-related targets and pathway analyses, as well as clustering analysis based on target-level information of the herbs. Gene ontology enrichment analysis was conducted using a protein–protein interaction network. Our research identified 14 AR-specific herbs and analyzed whether AR-specific herbs are highly related to previously known AR-related genes and pathways. AR-specific herbs were found to target several genes related to inflammation and AR pathogenesis, such as PTGS2, HRH1, and TBXA2R. Pathway analysis revealed that AR-specific herbs were associated with multiple AR-related pathways, including cytokine signaling, immune response, and allergic inflammation. Additionally, clustering analysis based on target similarity identified three distinct subgroups of AR-specific herbs, corroborated by a protein–protein interaction network. Group 1 herbs were associated with the regulation of inflammatory responses to antigenic stimuli, while Group 2 herbs were related to the detection of chemical stimuli involved in the sensory perception of bitter taste. Group 3 herbs were distinctly associated with antigen processing and presentation and NIK/NF-kappa B signaling. This study decodes the principles of TAM herbal configurations for AR using a network pharmacological approach, providing a holistic understanding of drug effects beyond specific pathways.

Abstract To date, no study has reported the objective metabolic laboratory findings worldwide or the comorbidities for Ménière’s disease (MD) using a population-based design in Asian populations. The aim of this study was to investigate the comorbidities and associated factors for MD using the Korean National Health Insurance Service database. This retrospective population-based study was conducted using a data from the National Sample Cohort database from 2009 to 2015. We only enrolled patients whose records showed a prescription for MD medicine and audiometry findings as well as an appropriate diagnostic code. We also included a matched cohort without MD who were enrolled randomly and matched for sex, age, year of diagnosis, income level, and residential area with the MD group with a ratio of 10:1. We evaluated comorbidities including autoimmune, allergic, metabolic diseases and cancer and the health screening data including general characteristics (height, weight, waist circumference, body mass index, and blood pressure), laboratory findings (fasting glucose, cholesterol, triglyceride, high-density lipoproteintryglyceride (HDL) cholesterol, low-density lipoproteintryglyceride cholesterol, hemoglobin, creatinine, aspartate aminotransferase and alanine aminotransferase, and gamma-glutamyltrans- peptidase (rGT)), and general health behaviors (smoking, alcohol, and exercise) of the MD group, and compared these characteristics with those of the MD-free control group. A total of 2,013 and 20,130 participants were included in the MD and MD-free control groups (1,640 and 15,458 for health screening data). We found the increase in incidence of allergic rhinitis and allergic asthma, decrease in systolic blood pressure, HDL cholesterol, and rGT, and less frequent alcohol consumption and less prevalent smoking in the MD group. No significant differences were observed between the groups in the incidence of autoimmune diseases, and cerebro- and cardiovascular disease as well as health screening data and objective laboratory findings. Inconsistence with published studies, the results of this study suggest that the autoimmunity and metabolic disorder, and skeletal growth might not be associated with the onset of MD. Another well-designed study for other races will be needed to the generalization of this study results.

Objectives: Neighborhood disadvantage may increase the risk of adverse health outcomes among older refugees. Yet few studies rigorously estimate the effects of place-based factors on later-life health, particularly dementia and mortality. Evidence about refugees is especially sparse. Methods: This study leveraged a natural experiment in the form of a Danish policy (1986–1998) that dispersed refugees quasi-randomly across neighborhoods upon arrival. We used longitudinal registers allowing 30 years of follow-up among refugees aged 40+ years upon arrival in Denmark (N = 9,854). Cox models assessed the association between neighborhood disadvantage and risk of dementia and mortality. We examined heterogeneous effects by sex, age, and family size. We also examined associations among non-refugee immigrants and native-born Danes. Results: Neighborhood disadvantage was not associated with dementia in any group. One unit increase in neighborhood disadvantage index (ranges −8 to 5.7) was associated with greater mortality risk among non-refugee immigrants (HR 1.06, 95%CI: 1.02, 1.10) and native-born Danes (HR 1.11, 95%CI: 1.06, 1.17). In contrast, neighborhood disadvantage was associated with lower mortality risk among refugees (HR 0.96, 95%CI: 0.93, 0.99). Neighborhood disadvantage remained negatively associated with mortality risk in subgroups: refugees who are female (on moderate-disadvantage compared to low-disadvantage), aged 60+, and who arrived with families. Discussion: While neighborhood disadvantage was associated with lower mortality risk among refugees, it was associated with greater mortality risk among non-refugee immigrants and native-born Danes, perhaps due to confounding in the latter groups or different place-based experiences by immigration status. Future research is warranted to explain the reasons for contrasting findings.

Macrophage inhibitory cytokine 1 (MIC-1), which is overproduced in various human cancers and associated with cachexia, acts on the hypothalamus to suppress appetite and reduce body weight. We investigated the mechanisms through which MIC-1 affects bile acid metabolism and gallstone formation, which are poorly understood. Over 6 weeks, male C57BL/6 mice fed either standard chow or a lithogenic diet were intraperitoneally injected with phosphate-buffered saline (PBS) or MIC-1 (200 μg/kg/week). Among lithogenic diet-fed mice, MIC-1 treatment resulted in increased gallstone formation compared with PBS treatment. Compared with PBS treatment, MIC-1 treatment decreased hepatic cholesterol and bile acid levels and reduced expression of HMG-CoA reductase (HMGCR), the master cholesterol metabolism regulator sterol regulatory element-binding protein 2, cholesterol 7α-hydroxylase (CYP7A1), mitochondrial sterol 27-hydroxylase, and oxysterol 7α-hydroxylase. Compared with PBS treatment, MIC-1 treatment had no effect on small heterodimer partner, farnesoid X receptor, or pregnane X receptor expression, and extracellular signal-related kinase and c-Jun N-terminal kinase phosphorylation decreased, suggesting that these factors do not contribute to the MIC-1-induced reduction in CYP7A1 expression. Compared with PBS treatment, MIC-1 treatment increased AMP-activated protein kinase (AMPK) phosphorylation. Treatment with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) reduced CYP7A1 and HMGCR expression, whereas the AMPK inhibitor Compound C reversed MIC-1-induced reductions in CYP7A1 and HMGCR expression. Furthermore, in MIC-1-treated mice, total biliary cholesterol levels increased together with increased ATP-binding cassette subfamily G (ABCG)5 and ABCG8 expression. Compared with PBS treatment, MIC-1 treatment did not affect expression of liver X receptors α and β, liver receptor homolog 1, hepatocyte nuclear factor 4α, or NR1I3 (also known as constitutive androstane receptor), which are upstream of ABCG5/8; however, MIC-1 treatment increased ABCG5/8 expression and promoter activities. Our study indicates that MIC-1 influences gallstone formation by increasing AMPK phosphorylation, reducing CYP7A1 and HMGCR expression, and increasing ABCG5 and ABCG8 expression.

Hail has long caused extensive damage and economic loss in places inhabited by humans. Climate change is expected to lead to different types of damage due to the geographic characteristics of each continent. Under changing environment, hail is becoming increasingly unstable and is causing damage that is difficult to repair, making it essential to study the occurrence of hail and hail-damage. Hail formation has been studied at the micro- and macrophysical scales as well as thermal and dynamical scales. Hail forms in various sizes, and the scale of damage varies with size. Hail precipitation occurs suddenly and is localized, making it is difficult to observe and predict. Nonetheless, techniques to measure and forecast hail precipitation are improving in accuracy. Hail-damage management and financial compensation systems are used to mitigate the severe economic losses caused by hail fallen in rural and urban areas. This review most comprehensively considers hail research, focusing on the mechanisms, observation and prediction methods, damage, social compensation systems for hail damage, and hail-disaster prevention, suggesting future study directions briefly.

Abstract The association between weather-related variables or seasons and the development of Bell’s palsy (BP) is controversial. This study aimed to evaluate the incidence and clinical characteristics of BP and assess the effects of meteorological factors on seasonal and monthly incidence. This retrospective population-based study used data from the Korean Health Insurance claims database (NHICD) from 2010 to 2018, in which annual, seasonal, and monthly incidence rates and age and sex distributions were calculated. A multivariate linear regression and autoregressive integrated moving average (ARIMA) model was used to determine the association between the seasonal and monthly incidence of BP and meteorological factors, including average wind speed, temperature, relative humidity, and atmospheric pressure. We also conducted a scoping review of the literature on epidemiological and seasonality studies of BP in the past 30 years and summarized them in a table for easy comparison with other studies. In this study, the incidence rate of BP increased over 9 years (from 12.86 to 19.92 per 100,000 persons) and was the highest in patients in their 60s (31.6/100,000 persons). The seasonal incidence of BP was the highest in autumn and showed a significant difference compared with spring (coefficient − 0.318, p = 0.003) and summer (coefficient − 0.463, p

Residential racial segregation in the U.S. has been hypothesized as a fundamental cause driving health disparities across racial groups. Potential mechanisms include economic and social marginalization, subsequent constrained opportunities, and high stress. Yet evidence on residential segregation's association with health among Black and White children—particularly longitudinally—is sparse. This study aims to address this gap. We used data from the Panel Study of Income Dynamics (PSID), a national longitudinal study of U.S. households, analyzing information on 1,251 Black and 1,427 White children who participated in the Child Development Supplement (CDS) at least twice (survey waves 1997, 2002, 2007, 2014). We fit individual fixed-effects models to estimate the within-person association of neighborhood-level residential segregation, measured with local Getis-Ord G* statistics, with three outcomes (general health, weight status, and behavioral problems). We examined heterogeneous effects by age and sex. We also examined associations between health and childhood segregation trajectories, i.e., the pattern of children's residential segregation exposures from birth through when their health outcomes were measured, providing additional insight on dynamic experiences of segregation. In fixed effects models, among Black children, higher segregation was associated with worse self-rated health, especially for Black children who were older (aged 11–17 years). In trajectory models, among White children, moving out of highly segregated neighborhoods was associated with a lower probability of poor self-rated health, while moving into those neighborhoods or back and forth between neighborhood types were both associated with increased behavioral problems. Our findings highlight the importance of early-life residential segregation in shaping persistent racial health disparities, as well as the costs of segregation for all children living in highly segregated neighborhoods.

BackgroundCardiovascular disease (CVD) disproportionately affects Black adults in the United States. This is increasingly acknowledged to be due to inequitable distribution of health-promoting resources. One potential contributor is inequities in educational opportunities, although it is unclear what aspects of education are most salient. School racial segregation may affect cardiovascular health by increasing stress, constraining socioeconomic opportunities, and altering health behaviors. We investigated the association between school segregation and Black adults' CVD risk.Methods and findingsWe leveraged a natural experiment created by quasi-random (i.e., arbitrary) timing of local court decisions since 1991 that released school districts from court-ordered desegregation. We used the Panel Study of Income Dynamics (PSID) (1991 to 2017), linked with district-level school segregation measures and desegregation court order status. The sample included 1,053 Black participants who ever resided in school districts that were under a court desegregation order in 1991. The exposure was mean school segregation during observed schooling years. Outcomes included several adult CVD risk factors and outcomes. We fitted standard ordinary least squares (OLS) multivariable linear regression models, then conducted instrumental variables (IV) analysis, using the proportion of schooling years spent in districts that had been released from court-ordered desegregation as an instrument. We adjusted for individual- and district-level preexposure confounders, birth year, and state fixed effects. In standard linear models, school segregation was associated with a lower probability of good self-rated health (-0.05 percentage points per SD of the segregation index; 95% CI: -0.08, -0.03; p < 0.001) and a higher probability of binge drinking (0.04 percentage points; 95% CI: 0.002, 0.07; p = 0.04) and heart disease (0.01 percentage points; 95% CI: 0.002, 0.15; p = 0.007). IV analyses also found that school segregation was associated with a lower probability of good self-rated health (-0.09 percentage points; 95% CI: -0.17, -0.02, p = 0.02) and a higher probability of binge drinking (0.17 percentage points; 95% CI: 0.04, 0.30, p = 0.008). For IV estimates, only binge drinking was robust to adjustments for multiple hypothesis testing. Limitations included self-reported outcomes and potential residual confounding and exposure misclassification.ConclusionsSchool segregation exposure in childhood may have longstanding impacts on Black adults' cardiovascular health. Future research should replicate these analyses in larger samples and explore potential mechanisms. Given the recent rise in school segregation, this study has implications for policies and programs to address racial inequities in CVD.

Background: The aim of this study was to investigate the superiority of the effects of manual acupuncture (MA), electroacupuncture (EA), or transcutaneous electrical nerve stimulation (TENS) on chronic consecutive tinnitus. Methods: Forty-five patients with chronic consecutive tinnitus were allocated into an MA, an EA, or a TENS group at a 1:1:1 ratio. The corresponding patients were treated with MA, EA, or TENS twice a week for 10 sessions (5 weeks). The primary outcome was a change in the tinnitus handicap inventory (THI), and the secondary outcomes were loudness and annoyance of tinnitus, pure-tone audiometry (PTA), and the speech discrimination test. The outcome measures were obtained at baseline, visit 5 (week 3), visit 10 (week 5), and visit 11 (follow-up 4 weeks). Results: Of the 45 participants, 37 (82.22%) completed the study. There was no difference in the THI score change among the groups at any point. However, the number of participants who had reduced scores of more than 10 points was higher in the EA group than in the TENS or MA groups (p = 0.037, Fisher's exact test). There was no significant difference in the loudness and annoyance of tinnitus, PTA, and speech discrimination test findings among the groups. Conclusion: Among the MA, EA, and TENS groups, there was no significant difference in the effects on the treatment of chronic consecutive tinnitus. However, EA could respond to more patients. Trial registration: Registered on October 21, 2016 (KCT0002117 by CRIS).

This paper proposes a new network model for the building evacuation problem considering congestion levels and provides a mixed integer linear programming (MILP) model and an efficient heuristic algorithm solving the problem. Constructing an optimization model with several congestion levels, we introduce a new network called the multi-class time-expanded (MCTE) network having several exclusive arcs connecting the same tail and head nodes. The MCTE networks make both the MILP model and the heuristic algorithm reflect a realistic situation in congested networks. Considering MCTE networks makes the problem difficult to solve, which motivates us to develop an efficient heuristic algorithm. We test our heuristic algorithm using several real-world networks such as a multiplex cinema, a subway station, and a large-size complex shopping mall in addition to an artificial network for clear comparison between the proposed algorithm and the MILP approaches. The results indicate that the proposed algorithm runs fast and produces a near-optimal solution compared with those from MILP models with a commercial solver.

Abstract Background Transcutaneous electrical nerve stimulation (TENS) involves a neuromodulatory effect using electrical stimulation and has been widely used due to its safety and convenience. It has been used for treating tinnitus for decades. Acupuncture has also been used for tinnitus and several research studies have shown that acupuncture can improve a certain kind of tinnitus by stimulating the somatosensory system. Moreover, several studies have shown the efficacy of electroacupuncture, which is a combination of acupuncture and electrical stimulation, for tinnitus. However, the comparative effectiveness of TENS, manual acupuncture, and electroacupuncture for the treatment of tinnitus has not been determined previously. Herein, we design a randomized, non-blind clinical trial to investigate and compare the effects and safety of TENS, manual acupuncture, and electroacupuncture for tinnitus. Methods After screening, 45 patients are randomly assigned to three groups: (1) patients in the TENS group are treated at four sites (tender points of masseter and the sternocleidomastoid muscle, in front of tragus, and mastoid process); (2) the manual acupuncture group patients are treated at 11 acupoints (TE21, SI19, GB2, TE22, ST7, TE17, GB20 of tinnitus affected side, and GB20, TE05, KI3 of both sides); (3) electroacupuncture group patients are treated by using acupuncture as in the manual acupuncture group and electrical stimulation at TE21, SI19, TE17, and GB20. Patients are treated for ten sessions, twice a week. The primary outcome measurement is the change of Tinnitus Handicap Inventory (THI) score between visit 1 and visit 10. The secondary outcome measurements are the response rate of THI, change in visual analogue scale associated with the loudness and annoyance of tinnitus, pure-tone audiometry and speech discrimination, and changes in parameters of heart rate variability. Discussion The purpose of this study is to compare the effect of TENS, manual acupuncture, and electroacupuncture in the auricular area on tinnitus. If the specific treatment shows a significant effect compared to other treatments, it could have potential for use in clinical practice as a primary treatment. Trial registration Clinical Research Information Service (CRIS), KCT0002117. Registered October 21, 2016. Retrospectively registered.

Abstracts Background In a former meta-analysis review, acupuncture was considered a potentially effective treatment for dry eye syndrome (DES), but there were heterogeneities among the outcomes. We updated the meta-analysis and conducted subgroup analysis to reduce the heterogeneity and suggest the most effective acupuncture method based on clinical trials. Methods We searched for randomized controlled trials (RCTs) in 10 databases (MEDLINE, EMBASE, CENTAL, AMED, SCOPUS, CNKI, Wangfang database, Oriental Medicine Advanced Searching Integrated System (OASIS), Koreamed, J-stage) and searched by hand to compare the effects of acupuncture and artificial tears (AT). We also conducted subgroup analysis by (1) method of intervention (acupuncture only or acupuncture plus AT), (2) intervention frequency (less than 3 times a week or more than 3 times a week), (3) period of treatment (less than 4 weeks or more than 4 weeks), and (4) acupoints (BL1, BL2, ST1, ST2, TE23, Ex-HN5). The Bucher method was used for subgroup comparisons. Results Nineteen studies with 1126 patients were included. Significant improvements on the Schirmer test (weighted mean difference[WMD], 2.14; 95% confidence interval[CI], 0.93 to 3.34; p = 0.0005) and break up time (BUT) (WMD, 0.98; 95% CI, 0.79 to 1.18; p

Abstract Background In this study, silk fibroin (SF) composite hydrogels containing hydroxyapatite (HAP) nanoparticles (NPs) for bone tissue engineering were fabricated using gamma-ray (γ-ray) irradiation treatment. During the irradiation, the HAP dispersed SF solution was changed to the chemically crosslinked SF hydrogel. Methods Distribution of HAP NPs in the SF hydrogel was examined by SEM imagery and energy dispersive X-ray spectrophotometry, and the crystalline structure of SF composite hydrogels was also confirmed by X-ray diffractometry. An optimum preparation condition of the SF/HAP composite hydrogels was determined with various HAP contents. For evaluation of the osteogenic differentiation of human mesenchymal stem cells (hMSCs), alkaline phosphatase activity (ALP), HAP nucleation in SBF and in vitro calcium accumulation were measured. Results The results revealed that compared with the pure SF hydrogels, the SF/HAP composite hydrogels improved osteogenic differentiation. Conclusion This paper demonstrates the great potential of the SF/HAP composite hydrogels in terms of the production of the bone tissue engineering scaffolds for which osteogenesis is required.

Background: The present study investigated the effect of ginseng berry hot water extract (GBx) on blood flow via the regulation of lipid metabolites and blood coagulation in rats fed a high-fat diet (HFD). Methods: Sixty rats were divided into five groups in descending order of body weight. Except for the control group, the other four groups were fed a HFD containing 45% kcal from fat for 11 wk without GBx. GBx groups were then additionally treated by gastric gavage with GBx dissolved in distilled water at 50 (GBx 50) mg/kg, 100 (GBx 100) mg/kg, or 150 (GBx 150) mg/kg body weight for 6 wk along with the HFD. To investigate the effects of GBx on rats fed a HFD, biochemical metabolite, blood coagulation assay, and histological analysis were performed. Results: In the experiments to measure the serum levels of leptin and apolipoprotein B/A, GBx treatment attenuated the HFD-induced increases in these metabolites (p

Abstract Background The aims of this study were to identify the clinical significances of the size of metastatic lymph node (mLN) and LN ratio (LNR) and to attempt to create a risk stratification for papillary thyroid carcinoma (PTC) patients. Methods We investigated the 435 PTC patients who underwent radioactive iodine (RAI) ablation treatment following thyroid surgery. The patients were classified into two groups (micrometastasis (pN1mic) ≤ 0.2 cm and macrometastasis (pN1mac) > 0.2 cm) and were stratified into the following three risk groups: group I (pN1mic, LNR ≤ 0.5); group II (pN1mic, LNR > 0.5 or pN1mac, LNR ≤ 0.5); and group III (pN1mac with LNR > 0.5). And then we investigated the association of the classified groups and variable clinicopathologic factors. Results The clinical characteristics such as large tumor size, extrathyroidal extension, higher T stage, and greater number of mLN or LNR were significantly associated with pN1mac. The mean stimulated thyroglobulin levels were increased with the patient risk groups (p = 0.02). The recurrence-free survivals were significantly different between the stratified groups (p = 0.001). Conclusions The patient groups I, II, and III may be referred to as low-, intermediate-, and high-risk groups. Clinicians should consider the possibility of recurrence, and the decisions about the application of RAI ablation based on the size of mLN and the patient’s risk groups.

BACKGROUND:Westernized diet and nutritional metabolism are important in acne pathogenesis, especially in adult patients. However, clinical and basic data are lacking. Pattern identification (PI) is a tool that results in a diagnostic conclusion based on a cluster of concurrent symptoms and signs in traditional medicine. Acne can be classified by PI. However, whether the metabolomic profile differs according to the PI of acne is unknown. Metabolomic data would help clarify the pathogenesis of acne. METHODS:We conducted a cross-sectional study involving 40 healthy controls and 60 subjects with acne. We evaluated androgens, serum lipids, essential amino acids, nonessential amino acids, other amino acids, and pro-inflammatory cytokines of all subjects and compared the metabolomic profiles between acne subjects and healthy controls, and in subgroups according to gender, age, severity, and PI. RESULTS:Dehydroepiandrosterone sulfate and serum fatty acids were significantly higher in female subjects, adolescents, and those with disharmony of the thoroughfare and conception vessels. The total essential and nonessential amino acids were significantly lower in the overall, female, adult, severe, and phlegm-stasis group. The latter group exhibited elevated serum levels of interleukin-1β and -6. CONCLUSIONS:This is the first study to investigate serum lipids, amino acids, and cytokines in subjects with acne. We analyzed the differences between metabolomic profiles to determine the diagnostic value of PI. Prospective studies with more patients are needed to confirm the characteristics of each PI and lipidomic data will enrich knowledge concerning lipid mechanism.

Normal body tissue or lesion characteristics in T1 images have been evaluated; however, how external parameters effect the change in signal intensity by gadolinium-based contrast agent remains unknown. We investigated how contrast enhancement changed according to echo time (TE) in 3.0T magnetic resonance (MR) T1 imaging and determined the optimal settings for TE in contrast-enhanced T1 imaging. Since there are no guidelines regarding parameters for T1 enhancement when using MR-contrast agents, we analyzed results from varying TEs (between 25 and 7 msec) in both a phantom and clinical study. We obtained the following results: contrast percentage of fat to saline increased from 740.0–1003.6%, response start point increased from 30–90 mmol, max peak signal intensity increased from 1771–2425 a.u., max peak point increased from 2–4 mmol, enhancement percentage of the max peak signal intensity (MPSI) to saline increased from 1671.0–2065.2%, the average of SI on each mol as TE increased from 600.8–996.6 a.u., the average of SI as TE on each molar concentration increased from 378–845 a.u., the AEPSS increased from 44.3–140.3%, and the AEPSC increased from 224.3–647.8%. We confirmed that TE can affect contrast enhancement, and the lowest TE has faster and higher effects on contrast enhancement.

Ultraviolet A (UVA) irradiation is responsible for a variety of changes in cell biology. The purpose of this study was to investigate effects of aspartic acid on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Furthermore, we elucidated the UVA-antagonizing mechanisms of aspartic acid. The results of this study showed that aspartic acid attenuated the UVA-induced reduction of the proliferative potential and stemness of hAMSCs, as evidenced by increased proliferative activity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and upregulation of stemness-related genes OCT4, NANOG, and SOX2 in response to the aspartic acid treatment. UVA-induced reduction in the mRNA level of hypoxia-inducible factor (HIF)-1α was also significantly recovered by aspartic acid. In addition, the antagonizing effects of aspartic acid against the UVA effects were found to be mediated by reduced production of PGE2 through the inhibition of JNK and p42/44 MAPK. Taken together, these findings show that aspartic acid improves reduced stemness of hAMSCs induced by UVA and its effects are mediated by upregulation of HIF-1α via the inhibition of PGE2-cAMP signaling. In addition, aspartic acid may be used as an antagonizing agent to mitigate the effects of UVA.

An aqueous solution was successfully prepared using a low-molecular-weight chitosan oligomer and FITC, and its structural and fluorescent properties were observed by using 1H NMR, 13C NMR, FT-IR, XRD, UV-Vis, and PL spectrometry. Its application as a metal ion sensor was also evaluated. The fluorescence in the water-soluble chitosan oligomer was a result of the carbamato anion (NHCOO-), and a synthesized FITC-labeled chitosan oligomer exhibited an effective detection effect for copper ion as well as energy transfer by the ion near FITC that caused a fluorescence decrease (quenching). The chitosan oligomer was confirmed to be applicable as a selective and sensitive colorimetric sensor to detect Cu2+.

BACKGROUND AND PURPOSE: Beta adrenergic overstimulation may increase the vascular damage and stroke. However, the underlying mechanisms of beta adrenergic overstimulation in cerebrovascular dysfunctions are not well known. We investigated the possible cerebrovascular dysfunction response to isoproterenol induced beta-adrenergic overstimulation (ISO) in rabbit cerebral arteries (CAs). METHODS: ISO was induced in six weeks aged male New Zealand white rabbit (0.8-1.0 kg) by 7-days isoproterenol injection (300 μg/kg/day). We investigated the alteration of protein expression in ISO treated CAs using 2DE proteomics and western blot analysis. Systemic properties of 2DE proteomics result were analyzed using bioinformatics software. ROS generation and following DNA damage were assessed to evaluate deteriorative effect of ISO on CAs. Intracellular Ca(2+) level change and vascular contractile response to vasoactive drug, angiotensin II (Ang II), were assessed to evaluate functional alteration of ISO treated CAs. Ang II-induced ROS generation was assessed to evaluated involvement of ROS generation in CA contractility. RESULTS: Proteomic analysis revealed remarkably decreased expression of cytoskeleton organizing proteins (e.g. actin related protein 1A and 2, α-actin, capping protein Z beta, and vimentin) and anti-oxidative stress proteins (e.g. heat shock protein 9A and stress-induced-phosphoprotein 1) in ISO-CAs. As a cause of dysregulation of actin-cytoskeleton organization, we found decreased level of RhoA and ROCK1, which are major regulators of actin-cytoskeleton organization. As functional consequences of proteomic alteration, we found the decreased transient Ca(2+) efflux and constriction response to angiotensin II and high K(+) in ISO-CAs. ISO also increased basal ROS generation and induced oxidative damage in CA; however, it decreased the Ang II-induced ROS generation rate. These results indicate that ISO disrupted actin cytoskeleton proteome network through down-regulation of RhoA/ROCK1 proteins and increased oxidative damage, which consequently led to contractile dysfunction in CA.

Background: Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression. Methods: OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia. Results: TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia. Conclusion: Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO. [ABSTRACT FROM AUTHOR]

Background. Suicide is a pressing global health concern, and identifying its risk factors is crucial for prevention. Body weight variability (BWV) has been increasingly recognized as a potential factor impacting physical and mental health outcomes. We aimed to explore the relationship between BWV and the risk of suicide mortality using a nationally representative database. Methods. This population-based cohort study used data from the Korean National Health Insurance Database and included a total of 1,983,701 subjects. BWV was assessed using at least three health examination datasets and validated variability indices (variability independent of the mean (VIM), average successive variability, and coefficient of variation), and patients were divided into BWV quartiles (Q1–Q4). The primary endpoint was suicide-related death. Results. During a median of 11.3 years of follow-up, 5,883 suicide deaths occurred. A higher baseline body weight was associated with a lower risk of suicide. However, greater BWV (VIM) was associated with a significantly greater risk of suicide (adjusted hazard ratio [95% confidence interval], 1.35 [1.26–1.45] in the Q4 group), even after adjusting for baseline body mass index (BMI). Similar results were observed regardless of obesity or BMI category. Consistent findings were observed when using different variability indices. Subgroup analyses according to sex, age, diabetes, and depression also supported these findings. Conclusion. Our study highlights the importance of considering BWV as a potential risk factor for suicide. [ABSTRACT FROM AUTHOR]

Background: This study investigates the association between thyroid function and frailty in the old patients using representative data. Methods: The study was conducted using data from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. The study population included 2,416 participants aged 50 years and older with available thyroid function test data. Frailty assessment was performed using the Fried frailty phenotype. The prevalence of frailty was analyzed across different thyroid diseases and thyroid function parameters. Results: The significant association between thyroid dysfunction and frailty was observed in overt hyperthyroidism and subclinical hyperthyroidism. After adjusting for various factors, the association between thyroid dysfunction and frailty remained significant. On the other hand, overt hypothyroidism did not show a significant association with frailty in the adjusted analysis. For individuals with overt hyperthyroidism and subclinical hyperthyroidism, higher levels of free thyroxine (FT4) were significantly associated with an increased risk of frailty (aOR >999; 95% CI, >999 to 999). Among individuals with overt hypothyroidism, lower level of FT4 levels and high thyrotropin (TSH) levels showed a significant association with frailty risk (FT4: aOR, <0.01; TSH: aOR, 999). In participants with subclinical hypothyroidism, there were no significant associations between parameters for thyroid and frailty risk. Conclusion: These findings suggest that thyroid dysfunction, particularly overt hyperthyroidism and subclinical hyperthyroidism, may be associated with an increased risk of frailty in the old patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the associations of body composition and the risk of fracture in postmenopausal women, stratified based on bone mineral density. Methods: A population-based cohort study using the database of the National Screening Program for Transitional Ages with women aged 66 years was performed. Bone mineral density was categorized as normal, osteopenia, and osteoporosis. The following body mass index (BMI) categories for general obesity were used: underweight (<18.5), normal (18.5-22.9), overweight (23-24.9), obese (25-29.9), and severely obese (≥30 kg/m²). Waist circumference (WC) used for central obesity assessment was categorized into 5 groups. Newly diagnosed fracture during the follow-up period defined based on ICD-10 codes was the primary outcome. Results: During 7.7 ± 1.4 years of follow-up, 41 672 (17.9%) participants experienced any fracture, 20 326 (8.7%) experienced vertebral fractures (VFs), and 2883 (1.2%) experienced hip fractures (HFs). The adjusted hazard ratios (aHRs) for any fracture showed a progressive increase with higher BMI and WC categories in individual with osteopenia and osteoporosis. Regarding VF, aHR was highest in severely obese individuals with osteoporosis (aHR [95% CI], 3.45 [2.99-3.97]) and in individuals with WC ≥ 95 cm with osteoporosis (4.79 [4.09-5.60]). The aHR [95% CI] for HF was highest in the underweight group with osteopenia (1.94 [1.16-3.27]) and osteoporosis (2.96 [2.15-4.10]). In central obesity individuals with WC ≥ 95 cm, aHR [95% CI] for HF was 2.80 [1.91-4.91]. Conclusions: General obesity and central obesity are not protective against any fracture, VF and HF in postmenopausal women with osteopenia or osteoporosis. [ABSTRACT FROM AUTHOR]