Association between Consumption of Iodine-Rich Foods and Thyroid Cancer Prevalence: Findings from a Large Population-Based Study.

The influence of iodine-rich foods on thyroid cancer (TC) risk remains inadequately understood. Therefore, we aimed to comprehensively investigate the relationship between three iodine-rich food groups and TC prevalence using extensive data from a large Korean population. We assessed the dietary intake of 169,057 participants in the Korean Genome and Epidemiology Study (2004-2013) using a food frequency questionnaire. The top-three iodine-rich food groups (including egg, seaweed, and dairy) were selected based on Korean dietary reference intakes and categorized by weekly consumption frequency. We conducted multiple logistic regression models to examine the relationship between food consumption and TC prevalence. After adjusting for confounding factors, higher seaweed consumption (>5 times/week) was significantly associated with lower TC prevalence (odds ratio [OR], 95% confidence interval [CI] = 0.42, 0.32-0.56, p-value < 0.001). In contrast, compared with moderate dairy consumption (3-4 times/week), lower dairy product intake (<1 time/week) was associated with higher TC prevalence (OR, 95% CI = 1.32, 1.05-1.67, p-value = 0.017). Our findings suggest that sufficient seaweed consumption may offer protection against TC, and incorporating dairy products into the diet may lower TC incidence in the Korean population. The most significant limitations of our study are the absence of 24 h urine samples for iodine status assessment and the lack of clinical data on the diagnosis of thyroid cancer.

Difference in association of carbohydrate intake with all-cause mortality between middle-aged and older Korean adults with and without diabetes mellitus: A prospective study.

BACKGROUND & AIMS: The relationship between diet and health, particularly the role of carbohydrates, has been extensively studied. However, carbohydrate intake based on individual health conditions remains unclear. Here, we aimed to investigate whether the association between carbohydrate intake and all-cause mortality varied between individuals with and without diabetes mellitus (DM). METHODS: This prospective cohort study used data from the Korean Genome and Epidemiology Study (KoGES). Overall, 143,050 participants were included, with 10.1% having DM. Dietary intake was assessed using a semiquantitative food frequency questionnaire. Cox proportional hazards regression models were used to assess the association between carbohydrate intake and mortality after adjusting for confounders. RESULTS: The study showed that 5436 deaths occurred during the median follow-up period of 10.1 years. A significant interaction between carbohydrate intake and DM was observed in the study population (interaction p = 0.061). Higher carbohydrate intake proportion was associated with an increased risk of all-cause mortality among individuals with DM (adjusted hazard ratio [HR], p-value = 1.10 [1.01-1.20], p = 0.032). Conversely, no association was observed between the proportion of carbohydrate intake and all-cause mortality in participants without DM. Additionally, both total sugar and added sugar intakes were associated with an increased risk of all-cause mortality in participants with DM (adjusted HR, p-value = 1.02 [1.01-1.04], p < 0.001 and 1.18 [1.13-1.24], p < 0.001). CONCLUSIONS: High carbohydrate (%) and added sugar intake were associated with an increased mortality risk in individuals with DM. Reducing carbohydrate intake and opting for healthy carbohydrates to mitigate mortality risk may be beneficial for individuals with DM, particularly when compared with the general population.

Assessing the Feasibility and Efficacy of Pre-Sleep Dim Light Therapy for Adults with Insomnia: A Pilot Study.

Background: Insomnia is increasingly recognized for its marked impact on public health and is often associated with various adverse health outcomes, including cardiovascular diseases and mental health disorders. The aim of this study was to investigate the efficacy of pre-sleep dim light therapy (LT) as a non-pharmacological intervention for insomnia in adults, assessing its influence on sleep parameters and circadian rhythms. Methods: A randomized, open-label, two-arm clinical trial was conducted over two weeks with 40 participants aged 20-60 years, all of whom had sleep disorders (CRIS, KCT0008501). They were allocated into control and LT groups. The LT group received exposure to warm-colored light, minimizing the blue spectrum, before bedtime. The study combined subjective evaluation via validated, sleep-related questionnaires, objective sleep assessments via actigraphy, and molecular analyses of circadian clock gene expression in peripheral blood mononuclear cells. Baseline characteristics between the two groups were compared using an independent t-test for continuous variables and the chi-squared test for categorical variables. Within-group differences were assessed using the paired t-test. Changes between groups were analyzed using linear regression, adjusting for each baseline value and body mass index. The patterns of changes in sleep parameters were calculated using a linear mixed model. Results: The LT group exhibited significant improvements in sleep quality (difference in difference [95% CI]; -2.00 [-3.58, -0.43], and sleep efficiency (LT: 84.98 vs. control: 82.11, p = 0.032), and an advanced Dim Light Melatonin Onset compared to the control group (approximately 30 min). Molecular analysis indicated a significant reduction in CRY1 gene expression after LT, suggesting an influence on circadian signals for sleep regulation. Conclusions: This study provides evidence for the efficacy of LT in improving sleep quality and circadian rhythm alignment in adults with insomnia. Despite limitations, such as a small sample size and short study duration, the results underscore the potential of LT as a viable non-pharmacological approach for insomnia. Future research should expand on these results with larger and more diverse cohorts followed over a longer period to validate and further elucidate the value of LT in sleep medicine. Trial registration: The trial was registered with the Clinical Research Information Service (KCT0008501).

Association between dairy-rich dietary pattern and metabolic dysfunction-associated steatotic liver disease: Findings from the Korean Genome and Epidemiology Study.

BACKGROUNDS: Dietary components and the development of metabolic dysfunction-associated liver disease (MASLD) are closely linked, but large-scale studies on dietary patterns and MASLD are scarce, most previous studies having focused on individual nutrients or foods rather than overall dietary patterns. Therefore, we aimed to investigate the association between dietary patterns and MASLD in Koreans. METHODS: A total of 6,052 participants from the Korean Genome and Epidemiology Study. Dietary intake was assessed using a validated Korean semiquantitative food frequency questionnaire comprising 106 food items. Principal component analysis was used to determine the major dietary patterns. Cox proportional hazard regression analysis was performed to assess the association between the incidence of MASLD and dietary patterns. RESULTS: Four major dietary patterns, namely carnivore, plant-based, dairy-rich, and starch-rich diet patterns, were identified. The carnivore, plant-based, and starch-rich diet patterns showed no significant association with incident MASLD, while the dairy-rich diet pattern was associated with a lower risk of MASLD, also showing significantly lower cumulative incidence of MASLD in the higher adherence to dairy-rich diet pattern. CONCLUSION: The dairy-rich diet pattern was significantly associated with a lower risk of MASLD in Koreans. Appropriate dietary guidance based on dietary patterns is crucial for preventing MASLD.

Secular trends in dietary energy, carbohydrate, fat, and protein intake among Korean adults, 2010-2020 KHANES.

OBJECTIVES: The composition and balance of macronutrient intake play key roles in promoting a longer lifespan. In this study, we aimed to investigate the secular trends in carbohydrate, fat, and protein intakes in South Koreans from 2010 to 2020. METHODS: We examined the dietary nutritional intake of South Koreans using data from the Korean National Health and Nutrition Examination Survey. A total of 60,190 adults aged ≥19 y who completed the 24-h dietary recall interviews in a single day on all survey periods were included in this study. The outcomes included changes in macronutrient intake according to subgroups, such as age; sex; and the presence of diabetes, dyslipidemia, stroke, or heart disease, as well as energy intake from macronutrients. RESULTS: The study population showed a significant decrease in total energy intake from 2010 to 2020, with a corresponding decrease in the percentage of energy intake from carbohydrates (p-values for trend < 0.001). Conversely, the proportions of energy intake from proteins and fats increased during the same period (p < 0.001). Subgroup analyses revealed variations in macronutrient intake trends according to age, sex, obesity status, and underlying diseases. The analysis of trends in energy intake from various fat subtypes, total sugar, and fiber revealed a decrease in the energy intake percentage of total sugar from 2016 to 2020 and an increase in the energy intake percentage of all fat subtypes and fiber from 2013 to 2020. CONCLUSIONS: In the past 10 y, the dietary patterns in Korea have shifted toward the consumption of high-fat and high-protein diets with reduced carbohydrate intake.

Comprehensive assessment of the combined impact of dyslipidemia and inflammation on chronic kidney disease development: A prospective cohort study.

BACKGROUND: There remains a limited comprehensive understanding of how dyslipidemia and chronic inflammation collectively contribute to the development of chronic kidney disease (CKD). OBJECTIVE: We aimed to identify clusters of individuals with five variables, including lipid profiles and C-reactive protein (CRP) levels, and to assess whether the clusters were associated with incident CKD risk. METHODS: We used the Korean Genome and Epidemiology Study-Ansan and Ansung data. K-means clustering analysis was performed to identify distinct clusters based on total cholesterol, triglyceride, non-high-density lipoprotein (HDL)-C, HDL-C, and CRP levels. Cox proportional hazards models were used to examine the association between incident CKD risk and the different clusters. RESULTS: During the mean 10-year follow-up period, CKD developed in 1,645 participants (690 men and 955 women) among a total of 8,053 participants with a mean age of 51.8 years. Four distinct clusters were identified: C1, low cholesterol group (LC); C2, high-density lipoprotein cholesterol group (HC); C3, insulin resistance and inflammation group (IIC); and C4, dyslipidemia and inflammation group (DIC). Cluster 4 had a significantly higher risk of incident CKD compared to clusters 2 (hazard ratio (HR) 1.455 [95% confidence interval (CI) 1.234-1.715]; p < 0.001) and cluster 1 (HR 1.264 [95% CI 1.067-1.498]; p = 0.007) after adjusting for confounders. Cluster 3 had a significantly higher risk of incident CKD compared to clusters 2 and 1. CONCLUSION: Clusters 4 and 3 had higher risk of incident CKD compared to clusters 2 and 1. The combination of dyslipidemia with inflammation or insulin resistance with inflammation appears to be pivotal in the development of incident CKD.

How to walk to reduce footstep noise in multi-story residential buildings.

Loud footsteps from upstairs cause disturbance to downstairs neighbours in multi-story residential buildings. In this experiment, we examined how participants walk when asked to walk quietly and evaluated the efficiency of their quiet walking patterns. Changes in vertical impact loading rates during the early stance phase, walking speed, and lower limb muscle activity when asked to walk quietly were evaluated from twenty-six young participants. Study data show that participants who struck the ground with the rearfoot reduced the impact loading rate by 44.6% with 29.3% slower walking speed than normal walking. Those who struck with the fore- or mid-foot reduced the impact loading by 69.2% with a 23.4% decrease in speed. Quiet walking with the non-rearfoot strike pattern reduced the impact loading by 48.7%, even when asked to walk as fast as normal walking. The results support the non-rearfoot strike pattern as an efficient walking strategy for lowering footstep impact.Practitioner summary: Data of this study show that voluntary gait alteration, such as adopting a non-rearfoot strike pattern, can reduce footstep impact. The study results propose that implementing such changes could be beneficial in addressing floor noise issues of multi-story residential buildings.Abbreviations: RFS: Rearfoot strike; NRFS: non-rearfoot strike; COP: Center of pressure; NW: Normal walking; QWs: Quiet walking at a preferred slower speed; QWn: Quiet walking at the speed of normal walking; EMG: Electromyography; BW: Body weight; iNEMG: integrated normalized EMG.

Dietary Habits of Newly Diagnosed Patients with Breast Cancer in Korea.

Background: In patients with breast cancer, a healthy diet can help reduce breast cancer-specific recurrence, mortality, and comorbid chronic disease rates. There have been few studies on dietary habits immediately after breast cancer diagnosis, especially those involving the Asian population. Therefore, this study aimed to compare the nutritional habits of newly diagnosed patients with breast cancer and the general population without cancer in Korea using propensity score (PS) matching. Methods: We conducted a case-controlled study of 157 patients with breast cancer and 2,363 cancer-free control participants from the Korea National Health and Nutrition Examination Survey. The PS values for the predicted probability of patients with breast cancer and the general population were estimated using logistic regression analysis, including age and body mass index. The dietary patterns were assessed using a 24-hour recall of 1 day and the Food Frequency Questionnaire. Results: PS matching showed that patients with breast cancer consumed fewer calories and carbohydrates; however, they consumed more protein and fat compared to the general population. Compared to the general population, patients with breast cancer consumed more healthy foods such as fish, seaweed, vegetables, fruit, mixed-grain rice, and nuts; however, they also consumed more soup, stew, and red meat. Conclusion: Newly diagnosed patients with breast cancer have some healthy dietary habits compared to the general population. However, there is considerable room for improvement in their diet quality. Our results support the need to develop tailored dietary recommendations for patients with breast cancer during the diagnostic and posttreatment periods to improve their diet quality.

Effectiveness of the triglyceride-glucose index and triglyceride-glucose-related indices in predicting cardiovascular disease in middle-aged and older adults: A prospective cohort study.

BACKGROUNDS: Cardiovascular disease (CVD) risk assessment is a crucial component of public health. We aimed to determine the predictive value of the triglyceride-glucose (TyG) index and TyG-related indices for new-onset CVD. METHODS: This prospective study included 7,808 participants aged 40-69 years from the Ansung-Ansan cohort database. Our analysis was stratified by diabetes status. The hazard ratio (HR) with a 95% confidence interval (CI) for incident CVD was computed using multiple Cox proportional-hazards regression models. To evaluate the predictive performance of these indices for new-onset CVD, we calculated the Harrell's C-index (95% CI). RESULTS: In this study, a total of 6,890 participants did not have diabetes at baseline, while 918 participants had diabetes. In participants without diabetes, compared to the lowest tertile, fully adjusted HR and 95% CI for new-onset CVD in the highest tertile were as follows: TyG (HR 1.42, 95% CI 1.06-1.90), TyG-body mass index (BMI) (HR 1.92, 95% CI 1.19-3.10), TyG-waist circumference (WC) (HR 2.37, 95% CI 1.61-3.49), and TyG-waist-to-height ratio (WHtR) (HR 2.20, 95% CI 1.47-3.28). However, no significant associations were observed between TyG, modified TyG indices, and new-onset CVD in participants with diabetes. Notably, the C-indice of TyG-WC and TyG-WHtR were significantly higher than those of TyG and TyG-BMI in participants without diabetes. CONCLUSIONS: TyG-BMI, TyG-WC, and TyG-WHtR were associated with an increased risk of new-onset CVD in participants without diabetes. Furthermore, TyG-WC and TyG-WHtR showed better predictive performances for new-onset CVD than TyG and TyG-BMI in participants without diabetes.

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation.

BACKGROUND: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. METHODS: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. RESULTS: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. CONCLUSION: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

Saponins Derived from the Korean Endemic Plant Heloniopsis koreana Inhibit Diffuse-type Gastric Cancer Cells.

Diffuse-type gastric cancer (GC) is a type of stomach cancer that occurs in small clusters of cells that are widely spread. It does not typically manifest with symptoms until the advanced stages and often goes undetected in routine imaging tests. In addition, there is no specific targeted therapy for diffuse-type GC and it has a high mortality risk. Hence, it is worthwhile to discover molecules against this cancer. In this study, the extract of Heloniopsis koreana, which is endemic to Korea, exhibited cytotoxicity against two diffuse-type GC cell lines, MKN1 and SNU668. This led to the isolation of 10 compounds, including a new cinnamic acid glycoside. Of the compounds, saponin Th (4) and SNF 11 (5) showed potent activities with IC50 values of 3.66 and 3.85 µM, respectively, in MKN1 cells, and 1.8 and 1.98 µM, respectively, in SNU668 cells. These compounds prevented cancer cell division, invasion, and colony formation in both cell lines. In addition, these compounds induced cancer cell death through conventional cell death pathways, showing an increase in ADP-ribose polymerase, caspase 3, and BAX and a decrease in BCL2.

Comparison of METS-IR and HOMA-IR for predicting new-onset CKD in middle-aged and older adults.

BACKGROUND: Chronic kidney disease (CKD) has emerged as a mounting public health issue worldwide; therefore, prompt identification and prevention are imperative in mitigating CKD-associated complications and mortality rate. We aimed to compare the predictive powers of the homeostatic model assessment for insulin resistance (HOMA-IR) and the metabolic score for insulin resistance (METS-IR) for CKD incidence in middle-aged and older adults. METHODS: This study used longitudinal prospective cohort data from the Korean Genome and Epidemiology Study. A total of 10,030 participants, aged 40-69 years, residing in the Ansung or Ansan regions of the Republic of Korea, were recruited between 2001 and 2002 through a two-stage cluster sampling method. We compared the predictive powers of METS-IR and HOMA-IR for CKD prevalence and incidence, respectively. CKD prevalence was measured by the area under the receiver operating characteristic (ROC) curve (AUC), and the indices' predictive performance for CKD incidence were assessed using Harrell's concordance index and time-dependent ROC curve analysis. RESULTS: A total of 9261 adults aged 40-69 years at baseline and 8243 adults without CKD were included in this study. The AUCs and 95% confidence intervals (CIs) of HOMA-IR and METS-IR for CKD prevalence at baseline were 0.577 (0.537-0.618) and 0.599 (0.560-0.637), respectively, with no significant difference (p = 0.337). The Heagerty's integrated AUC for METS-IR in predicting CKD incidence was 0.772 (95% CI 0.750-0.799), which was significantly higher than that of HOMA-IR (0.767 [95% CI 0.742-0.791], p = 0.015). CONCLUSION: METS-IR surpassed HOMA-IR in predicting CKD incidence and was as effective as HOMA-IR in predicting CKD prevalence. This implies that METS-IR could be a valuable indicator for early detection and prevention of CKD among Korean adults.

Clinical outcome of graft removal versus preservation in abdominal aortic graft infection: a systematic review and meta-analysis.

Purpose: The purpose of this study was to compare the clinical outcomes of abdominal aortic graft infection (AGI) treated with removal of the graft vs. graft preservation. Methods: The electronic databases PubMed, Embase, and Cochrane Library for studies that reported on AGI were searched. Observational studies and case series of at least 10 cases that reporting on the prevalence, microbiology, and outcomes of AGI were included. Results: Our search identified 23 studies that met our inclusion criteria, reporting on a total of 873 patients who underwent open surgical repair (OSR) or endovascular aneurysm repair (EVAR). Of these patients, 833 received graft removal, and 40 received graft preservation. The prevalence of AGI was reported to be 1.0% (95% confidence interval [CI], 0.5%-1.8%) after OSR and 0.4% (95% CI, 0%-1.1%) after EVAR. The pooled estimates of 1-year, 2-year, and 5-year mortality were 28.7% (95% CI, 19.4%-38.8%), 36.6% (95% CI, 24.6%-49.5%), and 51.8% (95% CI, 38.4%-65.1%) in the graft removal group and 16.1% (95% CI, 4.1%-32.2%), 18.5% (95% CI, 5.7%-35.1%), and 50.0% (95% CI, 31.6%-68.4%) in the graft preservation group. The 30-day mortality rate's risk ratio (RR) for graft removal vs. preservation was 0.98 (95% CI, 0.40-2.38), while the 1-year mortality rate's RR was 3.44 (95% CI, 1.60-7.42). Conclusion: The 30-day mortality rate of AGI treatment was found to be high, whether using graft removal or preservation. In selected patients, implementing antibiotics with graft preservation as an initial management may be helpful in reducing the mortality rate.

Association between experience of insulin resistance and long-term cardiovascular disease risk: findings from the Korean Genome and Epidemiology Study (KOGES).

PURPOSE: Although the correlation between insulin resistance (IR) and cardiovascular disease (CVD) risk is well-established, the impact of changes in IR status over time has received little attention. This study aimed to investigate the effect of IR on CVD risk in a large prospective cohort of middle-aged Korean adults. METHODS: We assessed 3597 participants from the Korean Genome and Epidemiology Study (KoGES). Participants were categorized as having IR if their HOMA-IR was ≥2.5 at least once during the exposure period. Multivariate Cox proportional hazards regression analysis was performed to assess hazard ratios (HRs) with 95% CIs for incident CVD after adjusting for confounders. RESULTS: Among a total of 3597 participants, 2259 did not have IR and 1138 had IR. The cumulative incidence rate of CVD in the IR group was significantly higher than that in the non-IR group (log-rank test, p = 0.015). Compared to the non-IR group, the HR and 95% CI for incident CVD in the IR group was 1.40 (1.07-1.83) in the unadjusted model. The presence of IR during the exposure period was significantly associated with a higher risk of incident CVD after adjusting for age, sex, body mass index, diabetes, hypertension, dyslipidemia, C-reactive protein, physical activity, alcohol intake, and smoking status (HR = 1.37; 95% CI: 1.01-1.84). CONCLUSION: Individuals who have experienced IR have a consistently higher likelihood of developing CVD than those who have never had IR. More intensive efforts should be made to prevent IR in middle-aged and older adults.

The effect of prolonged walking on leg muscle activity patterns and vulnerability to perturbations.

Understanding the consequences and ecological relevance of muscle fatigue is important to guide the development of strategies to preserve independence. However, few studies have examined walking-related fatigue and the effects on walking instability. Our purpose was to investigate the effects of prolonged walking on leg muscle activity and vulnerability to balance perturbations. Eighteen healthy young adults completed a 30-min walking trial at their preferred walking speed while leg muscle activities were recorded. Before and after the 30-min walk, participants responded to five 5% body weight lateral force perturbations. Time-frequency analysis with wavelet transformation and principal component analyses assessed neuromuscular adaptations of muscles to prolonged walking. Following prolonged walking, we observed a time-dependent increase in EMG intensities at slower frequencies for the soleus and tibialis anterior and a decrease in mean amplitudes for the soleus, lateral gastrocnemius, and semitendinosus. Mean mediolateral CoM displacement following perturbations averaged 21% larger after the 30-min walk. Our results suggest that walking for 30 min at a comfortable speed elicits complex neuromuscular adaptations indicative of local muscle fatigue and an increased vulnerability to walking balance perturbations. These findings could inform fatigue monitoring systems or walking assistive devices aimed at reducing walking-related fatigue and maintaining independent mobility.

Visualizing the chaperone-mediated folding trajectory of the G protein ß5 ß-propeller.

The Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with ß-propeller domains. Here, we determine the structures of human CCT in complex with its accessory co-chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gß5, a component of Regulator of G protein Signaling (RGS) complexes. Cryoelectron microscopy (cryo-EM) and image processing reveal an ensemble of distinct snapshots that represent the folding trajectory of Gß5 from an unfolded molten globule to a fully folded ß-propeller. These structures reveal the mechanism by which CCT directs Gß5 folding through initiating specific intermolecular contacts that facilitate the sequential folding of individual ß sheets until the propeller closes into its native structure. This work directly visualizes chaperone-mediated protein folding and establishes that CCT orchestrates folding by stabilizing intermediates through interactions with surface residues that permit the hydrophobic core to coalesce into its folded state.

Identification of novel pathogenic roles of BLZF1/ATF6 in tumorigenesis of gastrointestinal stromal tumor showing Golgi-localized mutant KIT.

Gastrointestinal stromal tumors (GISTs) frequently show KIT mutations, accompanied by overexpression and aberrant localization of mutant KIT (MT-KIT). As previously established by multiple studies, including ours, we confirmed that MT-KIT initiates downstream signaling in the Golgi complex. Basic leucine zipper nuclear factor 1 (BLZF1) was identified as a novel MT-KIT-binding partner that tethers MT-KIT to the Golgi complex. Sustained activation of activated transcription factor 6 (ATF6), which belongs to the unfolded protein response (UPR) family, alleviates endoplasmic reticulum (ER) stress by upregulating chaperone expression, including heat shock protein 90 (HSP90), which assists in MT-KIT folding. BLZF1 knockdown and ATF6 inhibition suppressed both imatinib-sensitive and -resistant GIST in vitro. ATF6 inhibitors further showed potent antitumor effects in GIST xenografts, and the effect was enhanced with ER stress-inducing drugs. ATF6 activation was frequently observed in 67% of patients with GIST (n = 42), and was significantly associated with poorer relapse-free survival (P = 0.033). Overall, GIST bypasses ER quality control (QC) and ER stress-mediated cell death via UPR activation and uses the QC-free Golgi to initiate signaling.

Oxidative balance score inversely associated with the prevalence and incidence of metabolic syndrome: analysis of two studies of the Korean population.

Background: Pro-oxidant/antioxidant imbalances leading to chronic inflammation and insulin resistance can contribute to the development of metabolic syndrome (MetS). Oxidative Balance Score (OBS), a comprehensive measure of exposure to pro- and anti-oxidants, represents an individual's total oxidative balance. This study aimed to evaluate the association between OBS and MetS using two large datasets. Methods: We analyzed data from 2,735 adults older than 19 years from the 2021 Korean National Health and Nutritional Examination Survey (KNHANES) and 5,807 adults aged 40-69 years from the Korean Genome and Epidemiology Study (KoGES). In each dataset, OBS was categorized into sex-specific tertiles (T). Results: In KNHANES, the odds ratios and 95% confidence intervals for prevalent MetS in T3, compared to T1, were 0.44 (0.29-0.65) in men and 0.34 (0.23-0.50) in women after adjusting for confounders. In KoGES, the hazard ratios and 95% confidence intervals for incident MetS in T3, compared to T1, were 0.56 (0.48-0.65) in men and 0.63 (0.55-0.73) in women after adjusting for confounders. Conclusion: OBS appears to be inversely related to MetS, which suggests that adopting lifestyle behaviors that decrease oxidative stress could be an important preventive strategy for MetS.

Sex-Specific Comparison Between Triglyceride Glucose Index and Modified Triglyceride Glucose Indices to Predict New-Onset Hypertension in Middle-Aged and Older Adults.

Background Triglyceride and glucose (TyG) index and TyG-related indices combined with obesity-related markers are considered important markers of insulin resistance. We aimed to examine the association between the TyG index and modified TyG indices with new-onset hypertension and their predictive ability stratified by sex. Methods and Results We analyzed data from 5414 Korean Genome and Epidemiology Study participants aged 40 to 69 years. Multiple Cox proportional hazard regression analyses were conducted to estimate the hazard ratio (HR) and 95% CI for new-onset hypertension according to sex-specific tertile groups after confounder adjustments. To evaluate the predictive performance of these indices for new-onset hypertension, we calculated Harrell's C-index (95% CI). Over a 9.5-year follow-up period, 1014 men and 1012 women developed new-onset hypertension. Compared with the lowest tertile (T) group, the adjusted HR and 95% CI for new-onset hypertension in T3 for TyG, TyG-body mass index, TyG-waist circumference, and TyG-waist-to-height ratio were 1.16 (0.95-1.40), 1.11 (0.84-1.48), 1.77 (1.38-2.27), and 1.68 (1.33-2.13) in men and 1.37 (1.13-1.66), 1.55 (1.16-2.06), 1.43 (1.15-1.79), and 1.64 (1.30-2.07) in women, respectively. The C-indices of TyG-waist-to-height ratio for new-onset hypertension were significantly higher than those of TyG and TyG-body mass index in both men and women. Conclusions TyG and TyG-body mass index were significantly associated with new-onset hypertension only in women. TyG-waist circumference and TyG-waist-to-height ratio were significantly associated with new-onset hypertension in both men and women. A sex-specific approach is required when using TyG and modified TyG indices to identify individuals at risk of incident hypertension.

Association between waist circumference trajectories and incident non-alcoholic fatty liver disease.

PURPOSE: Waist circumference (WC) is linked to non-alcoholic fatty liver disease (NAFLD) incidence. However, the impact of longitudinal WC changes on NAFLD remains unclear. We investigated WC trajectories and NAFLD incidence in a large population-based cohort. METHODS: We analyzed data from 2666 participants without NAFLD, who underwent biennial check-ups for 16 years, divided into a 6-year exposure period and a 10-year event accrual period. Participants were classified into increasing and decreasing WC trajectory groups during the median 5.9-year exposure period by group-based trajectory modeling. Multiple Cox proportional hazard regression analysis estimated the hazard ratio (HR) and 95 % confidence interval (CI) for incident NAFLD. RESULTS: During the median 9.7-year event accrual period, 799 participants developed NAFLD. The increasing WC trajectory group had a higher NAFLD risk than the decreasing group, with an HR of 1.20 (95 % CI: 1.02-1.42). After adjusting for confounders, the adjusted-HR was 1.28 (95 % CI: 1.07-1.53). Subgroup analyses revealed significant findings for groups, regardless of abdominal obesity status. CONCLUSION: An increasing WC trend was associated with a higher NAFLD risk, independent of abdominal obesity status. Monitoring WC changes may facilitate early detection of NAFLD risk groups and promote lifestyle modifications to prevent NAFLD onset.