Impact of low-density lipoprotein cholesterol on progression of aortic valve sclerosis and stenosis.

Background: Little research has been assessed atherosclerotic risk factors at various stages of calcific aortic valve disease. This study sought to determine risk factors of patients with aortic valve sclerosis (AVS) and mild to moderate aortic stenosis (AS). Methods: The study included 1,007 patients diagnosed with AVS or mild to moderate AS according to echocardiographic criteria. Patients were identified as a rapid progression group if the annualized difference in peak aortic jet velocity (Vmax) between two echocardiographic examinations was >0.08 m/s/yr in AVS and >0.3 m/s/yr in AS, respectively. We used multivariable logistic regression analyses to assess the factors associated with rapid disease progression or progression to severe AS. Results: Among 526 AVS patients, higher LDL-C level (odds ratio [OR] 1.22/per 25 mg/dl higher LDL-C, 95% confidence interval [CI] 1.05-1.43) was significantly associated with rapid disease progression. Compared to patients with LDL-C level <70 mg/dl, the adjusted OR for rapid progression were 1.32, 2.15, and 2.98 for those with LDL-C level of 70-95 mg/dl, 95-120 mg/dl, and ≥120 mg/dl, respectively. Among 481 mild to moderate AS patients, the baseline Vmax (OR 1.79/per 0.5 m/s higher Vmax, 95% CI 1.18-2.70) was associated with rapid progression. Compared to patients with Vmax 2.0-2.5 m/s, the adjusted OR for rapid progression were 2.47, 2.78, and 3.49 for those with Vmax of 2.5-3.0 m/s, 3.0-3.5 m/s, and 3.5-4.0 m/s, respectively. LDL-C and baseline Vmax values were independently associated with progression to severe AS. Conclusion: Atherosclerotic risk factors such as LDL-C were significantly associated with the rapid progression in AVS and baseline Vmax was important in the stage of mild to moderate AS.

Trends in treatment patterns and survival outcomes in pancreatic cancer: A nationwide population-based study in Korea.

BACKGROUND: The treatment of pancreatic cancer has evolved; however, real-world data on treatment trends remain scarce. This study investigated treatment patterns for pancreatic cancer and patient survival using a nationwide population-based study in Korea. METHODS: Using the National Health Insurance database, data from 78,920 patients diagnosed with pancreatic cancer in Korea between 2006 and 2019 were extracted. Treatment patterns and survival by age group and year of diagnosis were examined. RESULTS: Primary treatment was delivered as follows: 16,562 patients (21.0%) underwent surgery, 20,998 patients (26.6%) received chemotherapy, 1332 patients (1.7%) received chemoradiotherapy, and 40,040 patients (50.7%) received supportive care only. The proportion of patients undergoing surgery or chemotherapy increased gradually in all age groups over time. The commonly used anti-cancer drugs have changed from gemcitabine±erlotinib to gemcitabine+nab-paclitaxel and FOLFIRINOX. Survival improved mainly in patients who underwent surgery or chemotherapy. Median overall survival for all patients improved from 5.5 months in 2006-2008 to 9.8 months in 2018-2019, with greater improvement observed in younger age groups: 8.8-18.8 months, age ≤59 years, 6.8-14.6 months, age 60-69 years, 4.2-8.3 months, age 70-79 years and 2.4-3.4 months, age ≥80 years (all p < 0.0001). CONCLUSIONS: An increase in the rates of surgery and chemotherapy for pancreatic cancer was observed. Survival rates for pancreatic cancer have generally improved over the past decade and are greater in patients undergoing surgery or chemotherapy and in younger age groups.

How can progression be predicted in patients with mild to moderate aortic valve stenosis?

AIMS: The pressure increase per time unit (dP/dt) in aortic stenosis (AS) jet velocity is assumed to have inter-individual variability in the progressive AS stage. We sought to examine the association of aortic valve (AoV) Doppler-derived dP/dt in patients with mild to moderate AS with risk of progression to severe disease. METHODS AND RESULTS: A total of 481 patients diagnosed with mild or moderate AS [peak aortic jet velocity (Vmax) between 2 and 4 m/s] according to echocardiographic criteria were included. AoV Doppler-derived dP/dt was determined by measuring the time needed for the pressure to increase at a velocity of the AoV jet from 1 m/s to 2 m/s. During a median follow-up period of 2.7 years, 12 of 404 (3%) patients progressed from mild to severe AS and 31 of 77 (40%) patients progressed from moderate to severe AS. AoV Doppler-derived dP/dt had a good ability to predict risk of progression to severe AS (area under the curve = 0.868) and the cut-off value was 600 mmHg/s. In multivariable logistic regression, initial AoV calcium score (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.18-2.73; P = 0.006) and AoV Doppler-derived dP/dt (aOR, 1.52/100 mmHg/s higher dP/dt; 95% CI, 1.10-2.05; P = 0.012) were associated with progression to severe AS. CONCLUSION: AoV Doppler-derived dP/dt above 600 mmHg/s was associated with risk of AS progression to the severe stage in patients with mild to moderate AS. This may be useful in individualized surveillance strategies for AS progression.

Suspicious findings observed retrospectively on CT imaging performed before the diagnosis of pancreatic cancer.

Background: Few studies have focused on computed tomography findings before a pancreatic cancer diagnosis. We aimed to investigate the prediagnostic computed tomography findings of patients who had undergone computed tomography within the prediagnostic period of their pancreatic cancer diagnosis. Methods: Between January 2008 and December 2019, 27 patients who underwent contrast-enhanced abdominal or chest computed tomography including the pancreas within 1 year of a pancreatic cancer diagnosis were enrolled in this retrospective study. The prediagnostic computed tomography imaging findings were divided into pancreatic parenchyma and pancreatic duct findings. Results: All patients underwent computed tomography for reasons unrelated to pancreatic cancer. The pancreatic parenchyma and ducts showed normal findings in seven patients and abnormal findings in 20 patients. Hypoattenuating mass-like lesions were detected in nine patients with a median size of 1.2 cm. Six patients had focal pancreatic duct dilatations, and two patients had distal parenchymal atrophy. In three patients, two of these findings were found simultaneously. Taken together, 14 (51.9%) of 27 patients had findings suggestive of pancreatic cancer in prediagnostic computed tomography. Conclusions: In contrast-enhanced computed tomography performed for other purposes, attention should be paid to the presence of a hypoattenuating mass, focal pancreatic duct dilatation, or distal parenchymal atrophy of the pancreas. These features may be clues for an early diagnosis of pancreatic cancer.

Risk of pancreatic cancer after acute pancreatitis: A population-based matched cohort study.

BACKGROUND: We investigated the short- and long-term risks of pancreatic cancer after the diagnosis of acute pancreatitis. METHODS: This population-based matched-cohort study used data from the Korean National Health Insurance Service database. Patients with acute pancreatitis (n = 25,488) were matched with the control group (n = 127,440) based on age, sex, body mass index, smoking status, and diabetes. We estimated the hazard ratios for developing pancreatic cancer in both groups using Cox regression analysis. RESULTS: During a median follow-up of 5.4 years, pancreatic cancer developed in 479 patients (1.9%) in the acute pancreatitis group and 317 patients (0.2%) in the control group. Compared with the control group, the risk of pancreatic cancer in the acute pancreatitis group was very high within the first 2 years, which gradually decreased over time. The hazard ratio for the risk of developing pancreatitis was 8.46 (95% confidence interval, 5.57-12.84) at 1-2 years, and then decreased to 3.62 (95% confidence interval, 2.26-4.91) at 2-4 years. However, even after 8-10 years, the hazard ratio was still statistically significantly increased to 2.80 (95% confidence interval, 1.42-5.53). After 10 years, there was no significant difference in the risk of pancreatic cancer between the two groups. CONCLUSIONS: The risk of pancreatic cancer increases rapidly after acute pancreatitis diagnosis, gradually declines after 2 years, and remains elevated for up to 10 years. Further studies are needed to determine the long-term effects of acute pancreatitis on the risk of pancreatic cancer.

Discriminative Role of Invasive Left Heart Catheterization in Patients Suspected of Heart Failure With Preserved Ejection Fraction.

Background Recently, diastolic stress testing and invasive hemodynamic measurements have been emphasized for diagnosis of heart failure with preserved ejection fraction (HFpEF) because when determined using noninvasive parameters it can fall into a nondiagnostic intermediate range. The current study evaluated the discriminative and prognostic roles of invasive measured left ventricular end-diastolic pressure in the population with suspected HFpEF, particularly for patients with intermediate Heart Failure Association Pre-test Assessment, Echocardiography & Natriuretic Peptide, Functional Testing, Final Etiology (HFA-PEFF) score. Methods and Results A total of 404 patients with symptoms or signs of HF and preserved left ventricular systolic function were enrolled. All subjects underwent left heart catheterization with left ventricular end-diastolic pressure measurement for confirmation of HFpEF (≥16 mm Hg). The primary outcome was all-cause death or readmission due to HF within 10 years. Among the study population, 324 patients (80.2%) were diagnosed as invasively confirmed HFpEF, and 80 patients (19.8%) were as noncardiac dyspnea. The patients with HFpEF showed a significantly higher HFA-PEFF score than the patients with noncardiac dyspnea (3.8±1.8 versus 2.6±1.5, P<0.001). The discriminative ability of the HFA-PEFF score for diagnosing HFpEF was modest (area under the curve, 0.70 [95% CI, 0.64-0.75], P<0.001). The HFA-PEFF score was associated with a significantly higher 10-year risk of death or HF readmission (per-1 increase, hazard ratio [HR], 1.603 [95% CI, 1.376-1.868], P<0.001). Among the 226 patients with an intermediate HFA-PEFF score (2-4), those with invasively confirmed HFpEF had a significantly higher risk of death or HF readmission within 10 years than the patients with noncardiac dyspnea (24.0% versus 6.9%, HR, 3.327 [95% CI, 1.109-16.280], P=0.030). Conclusions The HFA-PEFF score is a moderately useful tool for predicting future adverse events in suspected HFpEF, and invasively measured left ventricular end-diastolic pressure can provide additional information to discriminate patient prognosis, particularly in those with intermediate HFA-PEFF scores. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04505449.

Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients With Preserved Ejection Fraction.

BACKGROUND: The left atrium (LA) plays an important role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: This study sought to assess the prognostic potential of LA stiffness index in patients who have HFpEF. METHODS: This study retrospectively screened patients with elevated left ventricular end-diastolic pressure (≥16 mm Hg) and preserved ejection fraction (≥50%) between January 1, 2004, and December 31, 2019. All patients underwent left heart catheterization to measure left ventricular end-diastolic pressure. Among these, 307 patients who had suitable image quality for left peak atrial longitudinal strain (PALS) measurement were analyzed. The study population was classified into low LA stiffness (n = 178, early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e']/PALS ≤0.26) and high LA stiffness (n = 129, E/e'/PALS >0.26) according to the best LA stiffness index (E/e'/PALS) cutoff value. The primary outcome was a composite of mortality or hospitalization caused by heart failure during follow-up. RESULTS: LA stiffness index showed good correlations with E/e' (r = 0.737; P < 0.001), LA volume index (r = 0.529; P < 0.001), right ventricular systolic pressure (r = 0.404; P < 0.001), and log N-terminal pro-B-type natriuretic peptide (r = 0.540; P < 0.001). LA stiffness index demonstrated better predictive performance than echocardiographic diastolic parameters did (P < 0.001). Patients with low LA stiffness had better clinical outcomes than those with high LA stiffness during a median follow-up of 6 years did (P < 0.001). In multivariable analysis, LA stiffness index was independently associated with increased risk of the composite endpoint of death or heart failure hospitalization (HR: 1.59 [95% CI: 1.01-2.51]; P = 0.044). CONCLUSIONS: Increased LA stiffness was associated with increased risk for all-cause mortality and hospitalization caused by heart failure in patients who have HFpEF, and its prognostic role was more pronounced than that of indexes of left ventricular filling pressure.

Prognostic implications of coronary artery disease and stress tests in patients with elevated left ventricular filling pressure and preserved ejection fraction.

Background: The prognostic role of myocardial ischemia in patients with heart failure with preserved ejection fraction (HFpEF) has not been fully elucidated. Therefore, we investigated the change in echocardiographic parameters and clinical outcomes based on the presence of epicardial coronary artery disease (CAD) and positive stress tests in HFpEF patients. Methods: Symptomatic patients with left ventricular end diastolic pressure ≥15 mmHg who underwent coronary angiography were analyzed between January 2000 and August 2019 after exclusion of patients with acute coronary syndrome. Results: A total of 555 HFpEF patients were invasively confirmed, 285 (51%) had angiographically-proven CAD. HFpEF patients with CAD displayed greater deterioration in left ventricular ejection fraction (p = 0.002) over time but this was not observed in those without CAD (p = 0.99) on follow-up echocardiography; however, the mitral annulus early diastolic velocity (e') was significantly decreased in both groups (p < 0.001 and p = 0.003, respectively). Among 274 patients that received stress tests, those with positive stress tests showed a decline in e' (p 0.001), but this was not found in subjects with negative stress tests (p = 0.44). There was no significant difference in all-cause mortality between patients with CAD and without CAD (p = 0.26) with a median follow-up of 10.6 years. Conclusion: In HFpEF patients, CAD was associated with greater deterioration in the left ventricular systolic function but not with mortality during the follow-up. In addition, myocardial ischemia with a positive stress test may contribute to greater deterioration of diastolic dysfunction.

Association of longitudinal left atrial strain with mortality after tricuspid valve surgery.

AIMS: Tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR) is becoming more common, but the associated mortality remains high. Therefore, we evaluated the clinical and echocardiographic parameters associated with all-cause mortality in patients with severe functional TR who underwent TV surgery. METHODS AND RESULTS: A total of 286 patients with severe functional TR who underwent TV replacement or repair was analysed between January 2006 and December 2017. We assessed changes in conventional echocardiographic parameters and strain, such as peak atrial longitudinal strain (PALS). During a median follow-up period of 5.3 years, 71 (24.8%) patients died due to any cause. When comparing groups with and without all-cause deaths, there were no significant differences in terms of sex, co-morbidities, medication use, and surgery type. However, patients who died were older and more likely to have refractory atrial fibrillation (AF). With multivariate Cox modelling, age >65 years (adjusted hazard ratio [HR], 2.81, 95% confidence interval [CI], 1.59-4.96; P < 0.001), refractory AF (adjusted HR, 2.84, 95% CI, 1.36-5.94; P = 0.006), lower albumin level (adjusted HR, 0.50, 95% CI, 0.31-0.82), and reduced PALS (adjusted HR, 1.87, 95% CI, 1.06-3.33; P = 0.032) were significant determinants of all-cause mortality. PALS decline was associated with refractory AF (adjusted HR, 5.74, 95% CI, 2.81-11.7; P < 0.001) and the absence of a Maze procedure (adjusted HR, 2.95, 95% CI, 1.51-5.78; P = 0.002). CONCLUSIONS: A reduction in PALS was significantly associated with all-cause mortality in our cohort of patients with severe functional TR who underwent TV surgery. This phenomenon is related to refractory AF and more aggressive intervention for AF is necessary concomitant with TV surgery.

Enzymatic bioconversion of ginseng powder increases the content of minor ginsenosides and potentiates immunostimulatory activity.

Background: Ginsenosides are biologically active components of ginseng and have various functions. In this study, we investigated the immunomodulatory activity of a ginseng product generated from ginseng powder (GP) via enzymatic bioconversion. This product, General Bio compound K-10 mg solution (GBCK10S), exhibited increased levels of minor ginsenosides, including ginsenoside-F1, compound K, and compound Y. Methods: The immunomodulatory properties of GBCK10S were confirmed using mice and a human natural killer (NK) cell line. We monitored the expression of molecules involved in immune responses via enzyme-linked immunosorbent assay, flow cytometry, NK cell-targeted cell destruction, quantitative reverse-transcription real-time polymerase chain reaction, and Western blot analyses. Results: Oral administration of GBCK10S significantly increased serum immunoglobulin M levels and primed splenocytes to express pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ. Oral administration of GBCK10S also activated NK cells in mice. Furthermore, GBCK10S treatment stimulated a human NK cell line in vitro, thereby increasing granzyme B gene expression and activating STAT5. Conclusion: GBCK10S may have potent immunostimulatory properties and can activate immune responses mediated by B cells, Th1-type T cells, and NK cells.

Lifestyle, body mass index, diabetes, and the risk of pancreatic cancer in a nationwide population-based cohort study with 7.4 million Korean subjects.

BACKGROUND: Large-scale epidemiological studies on pancreatic cancer in non-Western populations are insufficient. We investigated the risk factors for pancreatic cancer. METHODS: Using the Korean National Health Insurance database, subjects who participated in the health examination program between 2005 and 2006 were identified and followed up until 2017. Adjusted hazard ratios (HRs) for pancreatic cancer risk were estimated using a Cox proportional hazards model. RESULTS: During 11.5 years follow-up, 22,543 of 7,445,947 participants were newly diagnosed with pancreatic cancer. Compared with normal-weight subjects, pancreatic cancer risk was increased in those with severe obesity (BMI ≥ 28 kg/m2) (HR = 1.16; 95% CI, 1.11-1.23). Subjects with diabetes had an increased risk compared with those without diabetes (HR = 1.48; 95% CI, 1.43-1.53). Current smokers had a higher risk than never smokers (HR = 1.43; 95% CI, 1.38-1.48). Current smoking combined with diabetes increased the risk compared with never smokers without diabetes (HR = 2.13; 95% CI, 2.00-2.28). Current smoking combined with BMI ≥ 25 kg/m2 had an increased risk compared with never smokers with BMI < 23 kg/m2 (HR = 1.55; 95% CI, 1.46-1.65). CONCLUSION: Smoking, obesity, and diabetes are significant risk factors for pancreatic cancer in Koreans. Lifestyle modifications for smoking and obesity would be beneficial for pancreatic cancer prevention.

Higher heart rate variability as a predictor of atrial fibrillation in patients with hypertension.

The autonomic nervous system (ANS) plays an important role in the initiation and maintenance of atrial fibrillation (AF). However, the meaning of higher heart rate variability (HRV) in predicting AF remains unclear. Among 2100 patients in the Holter registry, a total of 782 hypertensive patients were included in this study. Baseline HRV was measured by time domain and frequency domain methods using 24-h Holter monitoring. The primary outcome was the development of AF. During an average follow-up of 1.1 years, 44 patients developed AF. Higher HRV parameters including high-frequency (P < 0.001), the square root of the mean squared differences of successive NN intervals (P < 0.001), and the percentage of NN intervals that are more than 50 ms different from the previous interval (P < 0.001) were associated with the occurrence of AF in univariate analysis. Premature atrial contractions burden, lower baseline heart rate, age, hemodialysis, coronary artery disease, and chronic heart failure were also associated with AF. In Cox regression analysis, higher HRV (representing excessive autonomic fluctuation) was an independent risk factor for AF. Excessive autonomic fluctuation represented by higher HRV in patients with hypertension was associated with an increased risk of AF.

Impact of Total Ischemic Time on the Recovery of Regional Wall Motion Abnormality after STEMI in the Modern Reperfusion Era.

BACKGROUND: Total ischemic time (TIT) is an important factor for predicting mortality among patients with ST-segment elevation myocardial infarction (STEMI). However, the correlation between TIT and the extent of wall motion abnormality has not been well studied. Therefore, we investigated changes in the wall motion score index (WMSI) value based on TIT in STEMI patients who underwent primary percutaneous coronary intervention (PCI) and subsequent transthoracic echocardiography. METHODS: STEMI patients who underwent primary PCI and follow-up coronary angiography were analyzed after the exclusion of cases of in-stent restenosis (ISR). WMSI values were calculated by dividing the sum of scores by the number of segments visualized. RESULTS: A total of 189 patients underwent primary PCI for STEMI, and 151 had no ISR with a median follow-up of 12.3 months. TIT was 180 (117-369) minutes in a subset of 151 patients (mean age of 62 years; 76% male). Among patients without ISR, 109 (72%) demonstrated a decrease in the WMSI value during the follow-up period. The WMSI values of patients with TITs of 180 minutes or less were significantly decreased relative to those among patients with TITs of greater than 180 minutes (p=0.020). Among patients with TITs of 180 minutes or less, the TIT was significantly shorter among those with a reduction in the WMSI value than among those with an increase in the WMSI value (106 [81-124] vs. 133 [100-151] minutes; p=0.018). TIT was an independent predictor for a reduction in the WMSI value among these patients (adjusted hazard ratio: 0.976 (0.957-0.995); p=0.016). CONCLUSIONS: In the modern reperfusion era of STEMI, patients with TITs of 180 minutes or less experienced a significant degree of recovery from regional wall motion abnormalities.

Predictor of atrial fibrillation recurrence in patients who underwent a tricuspid valve operation with modified Cox maze procedure.

BACKGROUND: Recurrence of any atrial arrhythmia after surgical ablation is known as a negative predictor of cardiovascular events and total mortality. However, there have been no focused studies for atrial fibrillation (AF) recurrence prediction in patients with significant tricuspid regurgitation (TR), and the risk-benefit estimation of surgical ablation in tricuspid valve (TV) surgery is not fully established. METHOD: We screened 385 patients who underwent a TV operation between 2001 and 2017. After excluding patients who did not undergo a maze operation, 158 patients were enrolled. Enrolled patients were divided by recurrence of AF. We analyzed the difference between the AF recurrence group and no AF recurrence group, and AF recurrence factors in terms of clinical risk factors and echocardiographic risk factors. The hazard ratio (HR) and 95% confidence intervals (CIs) were presented using a Cox proportional hazard model. RESULTS: Among 158 patients, AF recurred in 65 patients within 10 years. For AF prediction, age was most the important clinical factor and right atrium (RA) diameter was the most important echocardiographic parameters. In patients with a larger RA diameter over 49.2 mm, the prevalence of AF recurrence was higher (HR 4.322, 95% CI [2.185-8.549], log rank p value < .001). In clinical outcome, there was no significant difference between the AF recurrence group and the no recurrence group in terms of death, TR recurrence, heart failure, and stroke. However, the risk of permanent pacemaker (PPM) insertion was higher in the AF recurrence group (HR 10.240, 95% CI [1.257-83.480], log rank p value .007) compared to the no recurrence group. CONCLUSION: Age and RA enlargement are key predictors of AF recurrence after TV operation with the CM procedure in patients with significant TR.

Inhibition of melanogenesis by Aster yomena callus pellet extract in melanoma cells and patients with skin pigmentation.

Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena. This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. Excessive melanogenesis was induced in B16F10 melanoma cells using α-melanocyte stimulating hormone (α-MSH). The effects of AYC-P-E treatment on melanin biosynthesis inducers and melanin synthesis inhibition were assessed. Based on the results, a clinical study was conducted in subjects with skin pigmentation. AYC-P-E inhibited melanogenesis in α-MSH-treated B16F10 cells, accompanied by decreased mRNA and protein expression of melanin biosynthesis inducers, including cyclic AMP response element-binding protein (CREB), tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), and TRP-2. This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment.

Ethanol Extract of Orostachys japonicus A. Berger (Crassulaceae) Protects Against Type 2 Diabetes by Reducing Insulin Resistance and Hepatic Inflammation in Mice.

Type 2 diabetes (T2D) is a threaten human health problem, and accompanied by hyperglycemia and disorder of insulin secretion, is a major cause of abnormalities in maintaining blood glucose homeostasis. Also, low-grade inflammation, as well as insulin resistance (IR), is a common feature in patients with T2D. Numerous causes of the outbreak of T2D have been suggested by researchers, who indicate that genetic background and epigenetic predisposition, such as overnutrition and deficient physical activity, hasten the promotion of T2D milieu. Orostachys japonicus A. Berger (O. japonicus) is a herbal and remedial plant whose various activities include hemostatic, antidotal, febrile, and anti-inflammatory. Hence, we designed to evaluate the antidiabetic efficacy of ethanol extracts of O. japonicus (OJE). Six-week-old C57BL/Ksj-db/db (db/db) mice were used. The results showed that mice given various concentrations of OJE (0, 50, 100, and 200 mg/kg per day) for 8 weeks showed significantly reduced hyperglycemia, IR, and liver injury, confirmed by measuring diabetic parameters, serum, and hepatic biochemicals. Furthermore, the treatment of OJE markedly decreased the mRNA levels of proinflammatory cytokines, lipid accumulation, and gluconeogenesis-related genes. Consistently, western blot analysis indicated that mice treated with OJE showed increased levels of phospho-c-Jun N-terminal kinase, phospho-Akt, glucose transporters 2 and 4 (GLUT2 and GLUT4) in T2D mice. Likewise, much the same results were obtained in in vitro experiments. Taken together, OJE had hopeful advantage in sustaining the glucose homeostasis and diminishing IR, and could be a safe alternative remedy for treating T2D.

The Metabolite Profile in Culture Supernatant of Aster yomena Callus and Its Anti-Photoaging Effect in Skin Cells Exposed to UVB.

Aster yomena (A. yomena) extract has anti-inflammatory, antioxidant, anti-asthma, and anti-atopic effects. However, the commercial use of A. yomena extract requires a long processing time with specific processing steps (including heat treatment and ethanol precipitation), and there are various environmental problems. We aimed to build a system to produce A. yomena extract by culturing the callus in a bioreactor that can allow rapid process scale-up to test the effect of extract (AYC-CS-E) isolated from culture supernatant of A. yomena callus on photoaging of human keratinocytes (HaCaT) caused by ultraviolet B (UVB) exposure. Through screening analysis based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), 17 major metabolites were tentatively identified from AYC-CS-E for the first time. The suppression of cell proliferation caused by UVB was effectively alleviated in UVB-irradiated HaCaT cells treated with AYC-CS-E. Treatment with AYC-CS-E strongly induced the formation of type I procollagen and the inhibition of elastase in UVB-irradiated HaCaT cells and significantly reduced the expression of matrix metalloproteinase (MMP)-1. In addition, treatment of UVB-irradiated HaCaT cells with AYC-CS-E effectively improved various factors associated with an inflammatory reaction, skin damage recovery, skin moisture retention, and hyper-keratinization caused by photoaging, such as reactive oxygen species (ROS), pro-inflammatory cytokines, transforming growth factor beta (TGF-ß), MMP-3, MMP-9, filaggrin, hyaluronic acid synthase 2 (HAS-2), keratin 1 (KRT-1), nuclear factor-kappa B (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) at the gene and protein levels. These results suggest that AYC-CS-E can be used as a cosmetic ingredient for various skin diseases caused by photoaging, and the current callus culture system can be used commercially to supply cosmetic ingredients.

Orostachys japonicus ameliorates acetaminophen-induced acute liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (O. japonicus), referred to as Wa-song in Korea is a traditional and herbal medicine. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of ethanol extract of O. japonicus (OJE) on acetaminophen (N-acetyl-p-aminophenol, APAP) overdose-induced hepatotoxicity have not been determined yet. AIM OF THE STUDY: The present study was aimed to investigate the effects of OJE against APAP-induced acute liver injury (ALI) and explore the underlying mechanisms. MATERIALS AND METHODS: Mice were treated orally with OJE (50, 100, or 200 mg/kg) for seven days before APAP (300 mg/kg) injection. After 12 h of APAP treatment, serum and liver tissues were collected. An in vitro system using primary hepatocytes was also applied in this study. RESULTS: Pretreatment with OJE, especially at a dose of 200 mg/kg, reduced APAP overdose-induced ALI in mice, as evidenced by decreased serum alanine/aspartate aminotransferase levels, histopathological damage, and inflammation. Consistently, OJE pretreatment reduced the gene transcription of cytochrome P450 (CYP) 3A11 and CYP1A2 in livers of mice injected with or without APAP, at least in part, via inactivation of nuclear receptor pregnane X receptor (PXR). Furthermore, the role of PXR in mediating the OJE regulation of CYPs was confirmed in primary hepatocytes, which showed that OJE pretreatment inhibited PXR activity and APAP hepatotoxicity enhanced by pregnenolone 16α-carbonitrile, a mouse agonist of PXR. Besides, the antioxidative activity provided by OJE, involving increases in hepatic glutathione (GSH) content and decreases in malondialdehyde levels, has been shown to exert hepatoprotective effects in normal and injured livers. Moreover, APAP-activated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in mice liver were indirectly inhibited by pretreatment with OJE. CONCLUSIONS: Taken together, our findings showed that OJE attenuated APAP-induced ALI by decreasing APAP-metabolizing enzymes via inactivation of PXR and the restoration of hepatic GSH content. Therefore, OJE could be a promising hepatoprotective agent.

Risk for metabolic syndrome in the population with visceral fat area measured by bioelectrical impedance analysis.

BACKGROUND/AIMS: To investigate whether visceral fat area (VFA) measured by bioelectric impedance analysis (BIA) was associated with metabolic syndrome in subjects with and without obesity. METHODS: A total 23,202 participants who underwent medical check-ups were assessed. Participants were stratified by body mass index (BMI) and VFA. We evaluated six different groups for metabolic syndrome: Group 1 (normal weight and low VFA), Group 2 (normal weight and high VFA), Group 3 (overweight and low VFA), Group 4 (overweight and high VFA), Group 5 (obesity and low VFA), and Group 6 (obesity and high VFA). RESULTS: Metabolic syndrome traits and metabolic syndrome were significantly more prevalent in the high-VFA (≥ 100 cm2 ) subgroup in each BMI group. Adjusted logistic regression analyses revealed that the odds ratio for metabolic syndrome compared with Group 1 was the highest in Group 6 (24.53; 95% confidence interval [CI], 21.77 to 27.64). Notably, the odds ratio of Group 2 was higher than that of Group 3 (2.92; 95% CI, 2.30 to 3.69 vs. 2.57; 95% CI, 2.23 to 2.97). CONCLUSION: Our study demonstrates that the combination of BMI assessment and VFA determination by BIA may be a useful method for predicting the risk of metabolic syndrome. The VFA by BIA may be a useful target for interventions to improve metabolic syndrome.