SCGB1C1 Plays a Critical Role in Suppression of Allergic Airway Inflammation through the Induction of Regulatory T Cell Expansion.

The nanosized vesicles secreted from various cell types into the surrounding extracellular space are called extracellular vesicles (EVs). Although mesenchymal stem cell-derived EVs are known to have immunomodulatory effects in asthmatic mice, the role of identified pulmonary genes in the suppression of allergic airway inflammation remains to be elucidated. Moreover, the major genes responsible for immune regulation in allergic airway diseases have not been well documented. This study aims to evaluate the immunomodulatory effects of secretoglobin family 1C member 1 (SCGB1C1) on asthmatic mouse models. C57BL/6 mice were sensitized to ovalbumin (OVA) using intraperitoneal injection and were intranasally challenged with OVA. To evaluate the effect of SCGB1C1 on allergic airway inflammation, 5 µg/50 µL of SCGB1C1 was administrated intranasally before an OVA challenge. We evaluated airway hyperresponsiveness (AHR), total inflammatory cells, eosinophils in the bronchoalveolar lavage fluid (BALF), lung histology, serum immunoglobulin (Ig), the cytokine profiles of BALF and lung-draining lymph nodes (LLN), and the T cell populations in LLNs. The intranasal administration of SCGB1C1 significantly inhibited AHR, the presence of eosinophils in BALF, eosinophilic inflammation, goblet cell hyperplasia in the lung, and serum total and allergen-specific IgE. SCGB1C1 treatment significantly decreased the expression of interleukin (IL)-5 in the BALF and IL-4 in the LLN, but significantly increased the expression of IL-10 and transforming growth factor (TGF)-ß in the BALF. Furthermore, SCGB1C1 treatment notably increased the populations of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in asthmatic mice. The intranasal administration of SCGB1C1 provides a significant reduction in allergic airway inflammation and improvement of lung function through the induction of Treg expansion. Therefore, SCGB1C1 may be the major regulator responsible for suppressing allergic airway inflammation.

Efficacy and Safety of IDegAsp in a Real-World Korean Population with Type 2 Diabetes Mellitus.

Background: This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp. Methods: This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106). Results: In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. -0.51%, P<0.001; 5.21 mg/dL vs. -23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods. Conclusion: In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Dyslipidemia Fact Sheet in South Korea, 2022.

Objective: This study aimed to investigate the prevalence and status of dyslipidemia management among South Korean adults, as performed by the Korean Society of Lipid and Atherosclerosis under the name Dyslipidemia Fact Sheet 2022. Methods: We analyzed the lipid profiles, age-standardized and crude prevalence, management status of hypercholesterolemia and dyslipidemia, and health behaviors among Korean adults aged ≥20 years, using the Korea National Health and Nutrition Examination Survey data between 2007 and 2020. Results: In South Korea, the crude prevalence of hypercholesterolemia (total cholesterol ≥240 mg/dL or use of a lipid-lowering drug) in 2020 was 24%, and the age-standardized prevalence of hypercholesterolemia more than doubled from 2007 to 2020. The crude treatment rate was 55.2%, and the control rate was 47.7%. The crude prevalence of dyslipidemia (more than one out of three conditions [low-density lipoprotein-cholesterol ≥160 or the use of a lipid-lowering drug, triglycerides ≥200, or high-density lipoprotein-cholesterol (men and women) <40 mg/dL]) was 40.2% between 2016 and 2020. However, it increased to 48.2% when the definition of hypo-high-density lipoprotein-cholesterolemia in women changed from <40 to <50 mg/dL. Conclusion: Although the prevalence of hypercholesterolemia and dyslipidemia has steadily increased in South Korea, the treatment rate remains low. Therefore, continuous efforts are needed to manage dyslipidemia through cooperation between the national healthcare system, patients, and healthcare providers.

Public Awareness of Dyslipidemia Among the Korean Population: A Survey Study.

Objective: We aimed to assess the level of public awareness regarding dyslipidemia and its management among the Korean population. Methods: We conducted a web- or mobile-based survey study targeting the general population, using various recruitment methods, between July 25, 2022 and August 26, 2022. The questionnaire consisted of 12 questions designed to collect demographic information and evaluate participants' awareness and knowledge about dyslipidemia. Results: In total, 2,882 participants who completed the survey were included in the analysis. Among the participants, a substantial majority (89.1%) were familiar with the concepts of "good cholesterol" and "bad cholesterol," while a comparatively lower percentage (just 46.7%) were acquainted with the term "dyslipidemia." Noticeable variations in understanding were observed when examining specific aspects of dyslipidemia management, including diet, exercise, and pharmacotherapy. Conclusion: The results of this survey underscore the significance of enhancing public awareness about dyslipidemia within the context of health literacy, demonstrating the necessity for a more comprehensive approach that includes education and policymaking to effectively manage dyslipidemia.

Dyslipidemia Fact Sheet in South Korea, 2022.

BACKGRUOUND: This study aimed to investigate the prevalence and status of dyslipidemia management among South Korean adults, as performed by the Korean Society of Lipid and Atherosclerosis under the name Dyslipidemia Fact Sheet 2022. METHODS: We analyzed the lipid profiles, age-standardized and crude prevalence, management status of hypercholesterolemia and dyslipidemia, and health behaviors among Korean adults aged ≥20 years, using the Korea National Health and Nutrition Examination Survey data between 2007 and 2020. RESULTS: In South Korea, the crude prevalence of hypercholesterolemia (total cholesterol ≥240 mg/dL or use of a lipid-lowering drug) in 2020 was 24%, and the age-standardized prevalence of hypercholesterolemia more than doubled from 2007 to 2020. The crude treatment rate was 55.2%, and the control rate was 47.7%. The crude prevalence of dyslipidemia-more than one out of three conditions (low-density lipoprotein cholesterol ≥160 or the use of a lipid-lowering drug, triglycerides ≥200, or high-density lipoprotein cholesterol [HDL-C] [men and women] <40 mg/dL)-was 40.2% between 2016 and 2020. However, it increased to 48.2% when the definition of hypo-HDL-cholesterolemia in women changed from <40 to <50 mg/dL. CONCLUSION: Although the prevalence of hypercholesterolemia and dyslipidemia has steadily increased in South Korea, the treatment rate remains low. Therefore, continuous efforts are needed to manage dyslipidemia through cooperation between the national healthcare system, patients, and healthcare providers.

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors.

Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs. BMNCs cultured under the defined conditions synergistically expressed multiple genes, including those for PDX1, NKX6.1, MAFA, NEUROG3, GLUT2, and insulin, related to pancreatic beta cell development and function. They produced insulin/C-peptide and PDX1, as assessed using immunofluorescence and flow cytometry. The induced cells secreted insulin in a glucose-responsive manner, similar to normal pancreatic beta cells. Grafting BMNC-derived IPCs under kidney capsules of mice with streptozotocin (STZ)-induced diabetes alleviated hyperglycemia by lowering blood glucose levels, enhancing glucose tolerance, and improving glucose-stimulated insulin secretion. Insulin- and PDX1-expressing cells were observed in the IPC-bearing graft sections of nephrectomized mice. Therefore, this study provides a simple protocol for BMNC differentiation, which can be a novel approach for cell-based therapy in diabetes mellitus.

Free-Living Amoeba Vermamoeba vermiformis Induces Allergic Airway Inflammation.

The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/ E2). We axenically cultured KFA5 and KFA21. We applied approximately 1 × 106 to mice's nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4+ interleukin 4+ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.

Bioorthogonal Catalysis for Treatment of Solid Tumors Using Thermostable, Self-Assembling, Single Enzyme Nanoparticles and Natural Product Conversion with Indole-3-acetic Acid.

Bioorthogonal catalysis (BC) generates chemical reactions not present in normal physiology for the purpose of disease treatment. Because BC catalytically produces the desired therapy only at the site of disease, it holds the promise of site-specific treatment with little or no systemic exposure or side effects. Transition metals are typically used as catalytic centers in BC; however, solubility and substrate specificity typically necessitate a coordinating enzyme and/or stabilizing superstructure for in vivo application. We report the use of self-assembling, porous exoshells (tESs) to encapsulate and deliver an iron-containing reaction center for the treatment of breast cancer. The catalytic center is paired with indole-3-acetic acid (IAA), a natural product found in edible plants, which undergoes oxidative decarboxylation, via reduction of iron(III) to iron(II), to produce free radicals and bioactive metabolites. The tES encapsulation is critical for endocytic uptake of BC reaction centers and, when followed by administration of IAA, results in apoptosis of MDA-MB-231 triple negative cancer cells and complete regression of in vivo orthotopic xenograft tumors (p < 0.001, n = 8 per group). When Renilla luciferase (rLuc) is substituted for horseradish peroxidase (HRP), whole animal luminometry can be used to monitor in vivo activity.

Prediction of incident atherosclerotic cardiovascular disease with polygenic risk of metabolic disease: Analysis of 3 prospective cohort studies in Korea.

BACKGROUND AND AIMS: Studies have demonstrated that the risk of atherosclerotic cardiovascular disease (ASCVD) can be assessed by polygenic risk score (PRS) using common genetic variants. Because metabolic syndrome is a well-known, robust risk factor of ASCVD, we established PRS of metabolic disease and analyzed whether this PRS could predict incident ASCVD. METHODS: We constructed PRSs for eight quantifiable metabolic phenotypes-systolic/diastolic blood pressure, body mass index (BMI), four blood lipid components, and fasting blood glucose-by genome-wide association studies of two prospective Korean cohorts (n = 37,285). We conducted a grid search of combinations of metabolic PRSs to identify the most optimal weighted score for incident ASCVD (PRSMetS-ASCVD). The utility of PRSMetS-ASCVD was validated in an independent prospective cohort (n = 4333). RESULTS: The individuals in the highest PRS quintile demonstrated a 1.4-2.0-fold increased risk of incident hypertension, obesity, hyperlipidemia, and diabetes. Using the PRSMetS-ASCVD, we identified 6.7% of the population as a high risk group demonstrating a 3.3-fold (95% confidence interval 1.7-6.1, p < 0.001) higher risk for incident ASCVD. The model combining the PRSMetS-ASCVD demonstrated a better performance for predicting ASCVD than that consisting of only conventional risk factors, such as age, sex, BMI, smoking, hypertension, diabetes and hyperlipidemia. The population with high PRSMetS-ASCVD minimally overlapped with that of high Framingham risk score, thus suggesting the additive independent benefits beyond the Framingham risk score, especially in younger individuals. CONCLUSIONS: The polygenic risk of metabolic disease independently predicts those at an increased risk of ASCVD, identifying those at a genetically high risk of incident ASCVD.

Association of Longitudinal Trajectories of Insulin Resistance With Adverse Renal Outcomes.

OBJECTIVE: To analyze the relationship between time-serial changes in insulin resistance and renal outcomes. RESEARCH DESIGN AND METHODS: A prospective cohort of subjects from the general population without chronic kidney disease (CKD) underwent a biennial checkup for 12 years (n = 5,347). The 12-year duration was divided into a 6-year exposure period, where distinct HOMA for insulin resistance (HOMA-IR) trajectories were identified using latent variable mixture modeling, followed by a 6-year event accrual period, from which the renal outcome data were analyzed. The primary end point was adverse renal outcomes, defined as a composite of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in two or more consecutive checkups or albumin ≥1+ on urine strip. RESULTS: Two distinct groups of HOMA-IR trajectories were identified during the exposure period: stable (n = 4,770) and increasing (n = 577). During the event accrual period, 449 patients (8.4%) developed adverse renal outcomes, and the risk was higher in the increasing HOMA-IR trajectory group than in the stable group (hazard ratio 2.06, 95% CI 1.62-2.60, P < 0.001). The results were similar after adjustment for baseline clinical characteristics, comorbidities, anthropometric and laboratory findings, eGFR, and HOMA-IR. The clinical significance of increasing HOMA-IR trajectory was similar in three or four HOMA-IR trajectories. The increasing tendency of HOMA-IR was persistently associated with a higher incidence of adverse renal outcomes, irrespective of the prevalence of diabetes. CONCLUSIONS: An increasing tendency of insulin resistance was associated with a higher risk of adverse renal outcomes. Time-serial tracking of insulin resistance may help identify patients at high risk for CKD.

The Plasma Atherogenic Index is an Independent Predictor of Arterial Stiffness in Healthy Koreans.

The plasma atherogenic index (AIP) has been suggested as a useful independent predictor of cardiovascular diseases (CVDs) in high CV risk patients. We investigated the association between AIP and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) in healthy adults. A total of 3468 healthy subjects without any metabolic or CV diseases were enrolled. Anthropometric and CV risk factors were measured. The AIP was defined as the base 10 logarithm of the ratio of the concentration of triglycerides to high-density lipoprotein-cholesterol. Subjects were classified into AIP quartiles. There were gradual deteriorations in metabolic parameters and increase in baPWV across the increasing AIP quartiles. In a fully adjusted analysis, compared with Q1 (lowest quartile) group, the odds ratio (95% confidence interval) for increased baPWV was higher in Q2 1.51, Q3 1.64, and Q4 (highest quartile) 2.77 among men, and Q2 1.09, Q3 1.55, and Q4 1.83 among women (all P trend  <0 .05). There was a strong association between AIP and baPWV, and a higher AIP was an independent predictor of increased arterial stiffness in healthy Korean men and women. The AIP may be a simple screening tool for subclinical atherosclerosis.

Cumulative exposure amount of PM2.5 in the ambient air is associated with coronary atherosclerosis - Serial coronary CT angiography study.

BACKGROUND: We investigated the change of coronary atherosclerosis with long-term exposure to fine particulate matter of aerodynamic diameter <2.5 â€‹µm (PM2.5) using coronary computed tomography angiography (CCTA). METHODS: Subjects undergoing serial CCTAs between January 2007 and December 2017 (n â€‹= â€‹3,127) were analyzed. Each individual's cumulative amount of PM2.5 exposure between the two CCTAs was evaluated by Kriging interpolation and zonal analysis, considering the time interval between the two CCTAs. The main outcome was progression of coronary artery calcium (CAC) with additional semiquantitative analysis on the changes in the severity and composition of atherosclerotic plaques. RESULTS: The CAC scores increased by 30.8 Agatston units per-year under a median PM2.5 concentration 24.9 â€‹µg/m3 and tended to increase with the cumulative amount of PM2.5 exposure (r â€‹= â€‹0.321, p â€‹<0.001). The CAC progressed in 1,361 (43.5%) subjects during a median 53 months follow-up. The cumulative amount of PM2.5 exposure was independently associated with CAC progression (adjusted OR 1.09, p â€‹<0.001). By random forest analysis, the relative impact of cumulative amount of PM2.5 exposure on CAC progression was higher than that of traditional cardiovascular risk factors and the average concentration of PM2.5. The extent of coronary atherosclerosis and newly developed calcified plaque on follow-up were also significantly associated with the cumulative amount of PM2.5 exposure. CONCLUSIONS: Cumulative exposure to air pollution is associated with the progression of diffuse coronary calcification, the importance of which may be more significant than other traditional cardiovascular risk factors. Further investigations into the causality between PM2.5 and coronary atherosclerosis are warranted to improve global cardiovascular health.

Association between pancreatic fibrosis and development of pancreoprivic diabetes after pancreaticoduodenectomy.

This study investigated the correlation between pancreatic fibrosis (PF) and development of pancreoprivic diabetes after pancreaticoduodenectomy (PD). Ninety-five patients who underwent PD at Gangnam Severance Hospital between 2014 and 2017 were enrolled. PF grade was evaluated with alpha-smooth muscle actin (SMA) and Masson's trichrome (TRC) staining. New-onset pancreoprivic diabetes and recurrence of disease were evaluated using fasting blood glucose measurement and radiography taken at 3-month intervals. Sixty-one patients did not have preoperative diabetes, however, 40 (65.6%) patients developed pancreoprivic diabetes after PD. High-grade PF was more common in the diabetes group than in the normal group (SMA, 42.5% vs. 28.6%, P = 0.747; TRC, 47.5% vs. 28.6%, P = 0.361). The 1-year cumulative incidence of hyperglycemia/pancreoprivic diabetes was higher with high-grade PF than low-grade PF (SMA, 94.4% vs. 73.0%, P = 0.027; TRC, 89.3% vs. 75.0%, P = 0.074). The SMA-TRC combined high-grade group had a higher proportion of primary pancreatic disease than the combined low-grade group (90.0% vs. 37.5%, P = 0.001). The 5-year disease-free survival of patients with pancreatic cancer was worse with high-grade PF than low-grade PF (SMA, 24.5% vs. 66.3%, P = 0.026; TRC, 23.6% vs. 58.4%, P = 0.047). In conclusion, patients with severe PF are more likely to develop pancreoprivic diabetes after PD and have worse disease-free survival.

Association between BDNF Polymorphism and Depressive Symptoms in Patients Newly Diagnosed with Type 2 Diabetes Mellitus.

PURPOSE: Little is known about the relationship between brain-derived neurotrophic factor (BDNF) gene polymorphisms and psychiatric symptoms in diabetes patients. We investigated the effects of BDNF Val/66/Met polymorphism, glucose status, psychological susceptibility, and resilience on anxiety and depression symptoms in patients newly diagnosed with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We examined biochemical factors and BDNF polymorphism in 89 patients who were newly diagnosed with T2DM. Psychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS), and the Connor-Davidson Resilience Scale (CD-RISC) and Impact of Event Scale (IES) were used to assess psychological resilience and susceptibility to psychological distress, respectively. Logistic regression analyses were conducted to investigate factors associated with psychiatric symptoms. RESULTS: We determined that 62 patients (70%) were Met-carriers. No significant differences were found between the Val/Val homozygous and Met-carrier groups regarding age, sex, body mass index, and clinical factors related to glycemic control and lipid profiles. HADS-anxiety and HADS-depression scores and IES factor scores were higher in the Met-carrier than the Val/Val homozygous group. Hemoglobin A1c (HbA1c) level was significantly inversely correlated with the severity of depressive symptoms. Resilience factors showed significant inverse correlations, and IES factors showed positive correlations with depressive symptom severity. In the logistic regression analysis model, depressive symptoms were significantly associated with HbA1c and BDNF polymorphism, whereas only the hyperarousal factor of the IES scale was associated with anxiety. CONCLUSION: Depressive symptoms are associated with the presence of the Met-carriers and lower HbA1c in patients newly diagnosed with T2DM.

Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status.

BACKGROUND: This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. RESULTS: In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. CONCLUSION: The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Hippo/MST blocks breast cancer by downregulating WBP2 oncogene expression via miRNA processor Dicer.

WBP2 transcription coactivator is an emerging oncoprotein and a key node of convergence between EGF and Wnt signaling pathways. Understanding how WBP2 is regulated has important implications for cancer therapy. WBP2 is tightly controlled by post-translational modifications, including phosphorylation and ubiquitination, leading to changes in subcellular localization, protein-protein interactions, and protein turnover. As the function of WBP2 is intricately linked to YAP and TAZ, we hypothesize that WBP2 is negatively regulated by the Hippo tumor suppressor pathway. Indeed, MST is demonstrated to negatively regulate WBP2 expression in a kinase-dependent but LATS-independent manner. This was observed in the majority of the breast cancer cell lines tested. The effect of MST was enhanced by SAV and concomitant with the inhibition of the transcription co-activation, in vitro and in vivo tumorigenesis activities of WBP2, resulting in good prognosis in xenografts. Downregulation of WBP2 by MST involved miRNA but not proteasomal or lysosomal degradation. Our data support the existence of a novel MST-Dicer signaling axis, which in turn regulates both WBP2 CDS- and UTR-targeting miRNAs expression, including miR-23a. MiR-23a targets the 3'UTR of WBP2 mRNA directly. Significant inverse relationships between WBP2 and MST or miR23a expression levels in clinical specimens were observed. In conclusion, WBP2 is a target of the Hippo/MST kinase; MST is identified as yet another rheostat in the regulation of WBP2 and its oncogenic function. The findings have implications in targeted therapeutics and precision medicine for breast cancer.

Association between atherogenic index of plasma and coronary artery calcification progression in Korean adults.

BACKGROUND: Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD). Recently, atherogenic index of plasma (AIP) has been proposed as a novel predictive marker for CVD, and few cross sectional studies have demonstrated a relationship between AIP and coronary artery disease. The present study investigated the association between AIP and the progression of coronary artery calcification (CAC) in Korean adults without CVD. METHODS: A total of 1124 participants who had undergone CAC measurement at least twice by multi-detector computed tomography (CT) at a health check-up center were enrolled. Their anthropometric measurements and various cardiovascular risk factors were assessed. AIP was defined as the base 10 logarithm of the ratio of the concentration of triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C). CAC progression was defined as either incident CAC in a CAC-free population at baseline, or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACS) in subjects with detectable CAC at baseline. RESULTS: CAC progression was observed in 290 subjects (25.8%) during the mean follow-up of 4.2 years. All subjects were stratified into three groups according to AIP. There were significant differences in cardiovascular parameters among groups at baseline. The follow-up CAC and the incidence of CAC progression increased gradually with rising AIP tertiles. In logistic regression analysis, the odds ratio for CAC progression was 2.27 when comparing the highest to the lowest tertile of AIP (95% CI: 1.61-3.19; P for trend < 0.01). However, this association was attenuated after adjustment for multiple risk factors (P for trend = 0.67). CONCLUSIONS: There is a significant correlation between AIP and the progression of CAC in subjects without CVD. Although AIP was not an independent predictor of CAC progression, AIP should be considered when estimating the current as well as future CVD risk, along with other traditional risk factors.

Significance of Soluble CD93 in Type 2 Diabetes as a Biomarker for Diabetic Nephropathy: Integrated Results from Human and Rodent Studies.

Cluster of differentiation 93 (CD93) is a glycoprotein expressed in activated endothelial cells. The extracellular portion of CD93 can be secreted as a soluble form (sCD93) under inflammatory conditions. As diabetic nephropathy (DN) is a well-known inflammatory disease, we hypothesized that sCD93 would be a new biomarker for DN. We prospectively enrolled 97 patients with type 2 diabetes and evaluated the association between serum sCD93 and DN prevalence. The association between CD93 and development of DN was investigated using human umbilical cord endothelial cells (HUVECs) in vitro and diabetic db/db mice in vivo. Subjects with higher sCD93 levels had a lower estimated glomerular filtration rate (eGFR). The sCD93 level was an independent determinant of both the albumin-to-creatinine ratio (ACR) and the eGFR. The risk of prevalent DN was higher in the high sCD93 group (adjusted odds ratio 7.212, 95% confidence interval 1.244-41.796, p = 0.028). In vitro, CD93 was highly expressed in HUVECs and both CD93 expression and secretion were upregulated after lipopolysaccharides (LPS) stimulation. In vivo, peritoneal and urine sCD93 levels and the renal glomerular expression of CD93 were significantly higher in the db/db mice than in the control db/m+ mice. These results suggest the potential of sCD93 as a candidate biomarker associated with DN.

Supplementation with Korean Red Ginseng Improves Current Perception Threshold in Korean Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. METHODS: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. RESULTS: Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. CONCLUSION: Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.

Nonalcoholic fatty liver disease is an early predictor of metabolic diseases in a metabolically healthy population.

AIMS: The relationship between nonalcoholic fatty liver disease and incident metabolic syndrome in metabolically healthy subjects is unknown. We aimed to investigate whether nonalcoholic fatty liver disease is a predictor of future metabolic syndrome in metabolically healthy subjects. MATERIALS AND METHODS: Subjects who underwent health evaluation at least twice between 2009 and 2015 from the National Health Insurance Service-National Sample Cohort in South Korea were included. Patients without obesity who had no metabolic syndrome components were finally analyzed (n = 28,880). The definition of nonalcoholic fatty liver disease was based on both the hepatic steatosis and fatty liver indices. The incidence of metabolic syndrome, prediabetes/type 2 diabetes, hypertension, and dyslipidemia was compared between the subjects with and without nonalcoholic fatty liver disease. RESULTS: The presence of nonalcoholic fatty liver disease was associated with a higher risk of incident metabolic syndrome, prediabetes/type 2 diabetes, hypertension, and dyslipidemia in the entire cohort (metabolic syndrome: adjusted hazard ratio, 2.10; 95% confidence interval, 1.18-3.71; prediabetes/type 2 diabetes: adjusted hazard ratio, 1.42; 95% confidence interval, 1.06-1.90; hypertension: adjusted hazard ratio, 2.36; 95% confidence interval, 1.35-4.12; dyslipidemia: adjusted hazard ratio, 1.49; 95% confidence interval, 1.07-2.06). A similar finding was observed in the age-, sex-, smoking status-, and body mass index-based 1:5 propensity score-matched cohort of 1,092 subjects (metabolic syndrome: adjusted hazard ratio, 3.56; 95% confidence interval, 1.79-7.07; prediabetes/type 2 diabetes: adjusted hazard ratio, 1.97; 95% confidence interval, 1.04-3.73; hypertension: adjusted hazard ratio, 2.57; 95% confidence interval, 1.35-4.88; dyslipidemia: adjusted hazard ratio, 1.61; 95% confidence interval, 1.12-2.32). CONCLUSIONS: Nonalcoholic fatty liver disease is an early predictor of metabolic dysfunction even in metabolically healthy populations.