The Development of a Permanent Implantable Spacer with the Function of Size Adjustability for Customized Treatment of Regurgitant Heart Valve Disease.

The Pivot Mandu is an innovative device featuring a leak-tight adjustable 3D balloon spacer, incorporating inner mesh support, an outer e-PTFE layer, and a compliant balloon in the middle layer with a specialized detachable system. To assess its feasibility, proof of concept was rigorously evaluated through bench testing and survival porcine animal experiments. The results demonstrated successful remote inflation of the balloon system, with the balloon spacer exhibiting sustained patent and functional integrity over an extended observation period of up to 6 months. A noteworthy feature of the newly designed 3D balloon spacer is its capability for easy size adjustment during procedures, enhancing its adaptability and practicality in clinical settings. This three-layered 3D balloon spacer, with its established long-term patency, exhibits highly encouraging outcomes that hold promise in overcoming the current limitations of spacer devices for heart valve diseases. Given the compelling results from preclinical investigations, the translation of the Pivot Mandu into human trials is strongly warranted.

The Effectiveness of a Mobile Phone-Based Physical Activity Program for Treating Depression, Stress, Psychological Well-Being, and Quality of Life Among Adults: Quantitative Study.

BACKGROUND: Depression is a substantial global health problem, affecting >300 million people and resulting in 12.7% of all deaths. Depression causes various physical and cognitive problems, leading to a 5-year to 10-year decrease in life expectancy compared with the general population. Physical activity is known to be an effective, evidence-based treatment for depression. However, people generally have difficulties with participating in physical activity owing to limitations in time and accessibility. OBJECTIVE: To address this issue, this study aimed to contribute to the development of alternative and innovative intervention methods for depression and stress management in adults. More specifically, we attempted to investigate the effectiveness of a mobile phone-based physical activity program on depression, perceived stress, psychological well-being, and quality of life among adults in South Korea. METHODS: Participants were recruited and randomly assigned to the mobile phone intervention or waitlist group. Self-report questionnaires were used to assess variables before and after treatment. The treatment group used the program around 3 times per week at home for 4 weeks, with each session lasting about 30 minutes. To evaluate the program's impact, a 2 (condition) × 2 (time) repeated-measures ANOVA was conducted, considering pretreatment and posttreatment measures along with group as independent variables. For a more detailed analysis, paired-samples 2-tailed t tests were used to compare pretreatment and posttreatment measurements within each group. Independent-samples 2-tailed t tests were conducted to assess intergroup differences in pretreatment measurements. RESULTS: The study included a total of 68 adults aged between 18 and 65 years, who were recruited both through web-based and offline methods. Of these 68 individuals, 41 (60%) were randomly assigned to the treatment group and 27 (40%) to the waitlist group. The attrition rate was 10.2% after 4 weeks. The findings indicated that there is a significant main effect of time (F1,60=15.63; P=.003; ηp2=0.21) in participants' depression scores, indicating that there were changes in depression level across time. No significant changes were observed in perceived stress (P=.25), psychological well-being (P=.35), or quality of life (P=.07). Furthermore, depression scores significantly decreased in the treatment group (from 7.08 to 4.64; P=.03; Cohen d=0.50) but not in the waitlist group (from 6.72 to 5.08; P=.20; Cohen d=0.36). Perceived stress score of the treatment group also significantly decreased (from 2.95 to 2.72; P=.04; Cohen d=0.46) but not in the waitlist group (from 2.82 to 2.74; P=.55; Cohen d=0.15). CONCLUSIONS: This study provided experimental evidence that mobile phone-based physical activity program affects depression significantly. By exploring the potential of mobile phone-based physical activity programs as a treatment option, this study sought to improve accessibility and encourage participation in physical activity, ultimately promoting better mental health outcomes for individuals with depression and stress.

Oral anticoagulants and concurrent rifampin administration in tuberculosis patients with non-valvular atrial fibrillation.

BACKGROUND: Evidence and guidelines for Non-vitamin K antagonist oral anticoagulants (NOACs) use when prescribing concurrent rifampin for tuberculosis treatment in patients with non-valvular atrial fibrillation (NVAF) are limited. METHODS: Using the Korean National Health Insurance Service database from January 2009 to December 2018, we performed a population-based retrospective cohort study to assess the net adverse clinical events (NACE), a composite of ischemic stroke or systemic embolism and major bleeding, of NOACs compared with warfarin among NVAF patients taking concurrent rifampin administration for tuberculosis treatment. After a propensity matching score (PSM) analysis, Cox proportional hazards regression was performed in matched cohorts to investigate the clinical outcomes. RESULTS: Of the 735 consecutive patients selected, 465 (63.3%) received warfarin and 270 (36.7%) received NOACs. Among 254 pairs of patients after PSM, the crude incidence rate of NACE was 25.6 in NOAC group and 32.8 per 100 person-years in warfarin group. There was no significant difference between NOAC and warfarin use in NACE (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.48-1.14; P = 0.172). Major bleeding was the main driver of NACE, and NOAC use was associated with a statistically significantly lower risk of major bleeding than that with warfarin use (HR, 0.63; 95% CI, 0.40-1.00; P = 0.0499). CONCLUSIONS: In our population-based study, there was no statically significant difference in the occurrence of NACE between NOAC and warfarin use. NOAC use may be associated with a lower risk of major bleeding than that with warfarin use.

Combined MRI and PSA Strategy Improves Biopsy Decisions Compared with PSA Only: Longitudinal Observations of a Cohort of Patients with a PSA Level Less Than 20 ng/mL.

RATIONALE AND OBJECTIVES: To assess the diagnostic performances of prostate specific antigen (PSA) and PSA with prostate magnetic resonance imaging (MRI) to predict prostate cancer in patients with PSA ≤ 20 ng/mL. MATERIALS AND METHODS: Patients suspected of prostate cancer with a PSA test and prebiopsy MRI were included (n = 881). Prostate biopsy results or follow-up clinical data for 2 years were used to determine the presence of prostate cancer. The diagnostic performance of PSA, MRI, and PSA with MRI (referred to as the protocol) was evaluated. The positive predictive value (PPV) and negative predictive value (NPV) of the MRI were calculated in subgroups of patients with specific ranges of PSA level. RESULTS: Prostate cancer and CSC were diagnosed in 220 and 162 patients, respectively. Adding MRI to PSA could greatly improve specificity and PPV (0.833 and 0.567) for detecting CSC, compared to PSA ≥ 4 ng/mL alone (0.248 and 0.0219). Even though the sensitivity of the protocol (0.679) was lower than PSA (0.938), the NPV of the protocol was comparable to PSA (0.929 vs. 0.924). The protocol consistently showed the superior PPV and NVP to PSA only in not only patients within the gray zone of PSA, but also in patients with higher PSA. CONCLUSION: In conclusion, this longitudinal observational study confirmed that adding prebiopsy MRI to PSA was consistently beneficial in patients with PSA ≤ 20 ng/mL for avoiding unnecessary biopsy despite decrease in the sensitivity.

Safety and efficacy of immediate heparin reversal with protamine after complex percutaneous coronary intervention.

BACKGROUND: Compared to simple percutaneous coronary intervention (PCI), complex PCI is associated with higher bleeding and thrombotic risk. No previous study has evaluated the use of protamine after PCI with contemporary technologies. This study aimed to evaluate the safety and efficacy of manual compression with and without protamine after transfemoral complex PCI. METHODS: We retrospectively analyzed 160 patients (protamine group, n = 92; non-protamine group, n = 68) who underwent complex PCI via the femoral artery. The primary outcome was a composite of in-hospital death, myocardial infarction, stent thrombosis, stroke/systemic embolism, bleeding requiring blood transfusion, and vascular access complications. RESULTS: The primary outcome was significantly lower in the protamine group than in the non-protamine group (4.3% vs. 17.6%; p = 0.006). This was driven mainly by the lower incidences of hematoma in the protamine group (3.3% vs. 13.2%, p = 0.020). Furthermore, the protamine group had a significantly shorter hospital stay than the non-protamine group (4.8 ± 3.7 days vs. 8.4 ± 8.3 days, p = 0.001). While > 90% of the patients had acute coronary syndrome, there were no incidences of myocardial infarction or stent thrombosis in either group. CONCLUSIONS: Among patients who underwent complex PCI via transfemoral access, immediate protamine administration was associated with a significantly lower rate of vascular access complications, especially hematoma, and shorter hospital stay than no protamine administration.

Development of a Conceptual Model of Occupational Stress for Athletic Directors in Sport Contexts.

Previous studies have reported that occupational stress is a determinant risk factor for both chronic diseases and job performance among organizational leaders. Every occupation has its own culture and occupational climate influencing organizations within the industries. Thus, due to the idiosyncratic features inherent in sports, athletic directors may experience different occupational stressors. To date, there has been no comprehensive review of the occupational stress in athletic director contexts. Thus, based on the literature on both occupational stress and sport leadership, this study proposes a conceptual framework of occupational stress in sport leadership. The model identifies the five higher-order themes of occupational stressors and their associations with the first-level outcomes of individuals and the second-level outcomes of organizations. It also includes the two higher-order moderators of personal and organizational factors. It is hoped that this initiative can invoke interest in this topic to provide health-enhancing environments for athletic directors and quality sport services to society.

A Novel Device for Tricuspid Regurgitation Reduction Featuring 3-Dimensional Leaflet and Atraumatic Anchor: Pivot-TR System.

A new device called the Pivot-TR system was designed to treat tricuspid regurgitation with a novel spacer crossing the valve vertically. Its unique atraumatic anchoring system composed of both the elephant long nose and the inferior vena cava spiral anchor, in addition to the relatively easy implantation mechanism, enabled easy retrieval of the system later on. The system showed promising feasibility and safety results in this swine-based animal experiment, which should encourage human translation study.

Evaluation of micro-RNA in extracellular vesicles from blood of patients with prostate cancer.

Extracellular vesicles (EVs) contain various types of molecules including micro-RNAs, so isolating EVs can be an effective way to analyze and diagnose diseases. A lot of micro-RNAs have been known in relation to prostate cancer (PCa), and we evaluate miR-21, miR-141, and miR-221 in EVs and compare them with prostate-specific antigen (PSA). EVs were isolated from plasma of 38 patients with prostate cancer and 8 patients with benign prostatic hyperplasia (BPH), using a method that showed the highest recovery of RNA. Isolation of EVs concentrated micro-RNAs, reducing the cycle threshold (Ct) value of RT-qPCR amplification of micro-RNA such as miR-16 by 5.12 and miR-191 by 4.65, compared to the values before EV isolation. Normalization of target micro-RNAs was done using miR-191. For miR-221, the mean expression level of patients with localized PCa was significantly higher than that of the control group, having 33.45 times higher expression than the control group (p < 0.01). Area under curve (AUC) between BPH and PCa for miR-221 was 0.98 (p < 0.0001), which was better than AUC for prostate-specific antigen (PSA) level in serum for the same patients. The levels of miR-21 and miR-141 in EVs did not show significant changes in patients with PCa compared to the control group in this study. This study suggests isolating EVs can be a helpful approach in analyzing micro-RNAs with regard to disease.

Septal Reduction Using Transvenous Intramyocardial Cerclage Radiofrequency Ablation: Preclinical Feasibility.

Debulking of left ventricular septal mass is typically accomplished using surgical myectomy, which is morbid, or using transcoronary alcohol septal ablation, which can result in geographic miss and occasional catastrophic nontarget coronary injury. The authors developed and tested operational parameters in vitro and vivo for a device to accomplish transvenous intraseptal radiofrequency ablation to reduce ventricular septal mass using a technique derived from mitral cerclage, which the authors call cerclage ablation. Cerclage ablation appeared feasible in vitro and safe and effective in vivo. Cerclage ablation is an attractive new approach to debulk the interventricular septum in obstructive hypertrophic cardiomyopathy. These data support clinical investigation.

Incidence and clinical impact of early recurrence of atrial tachyarrhythmia after surgical ablation for atrial fibrillation.

BACKGROUND: Atrial tachyarrhythmias (ATAs) are common within the 3-month blanking period after catheter ablation of atrial fibrillation (AF). However, little evidence is available regarding the current guidelines on the blanking period after surgical AF ablation. We investigate the incidence and significance of early recurrence of atrial tachyarrhythmia (ERAT) and evaluate the optimal blanking period after surgical AF ablation. METHODS: Data from 259 patients who underwent surgical AF ablation from 2009 to 2016 were collected. ERAT was defined as documented ATA episodes lasting for 30 s. A multivariate Cox proportional hazard model was constructed to evaluate the role of ERAT as a predictor of late recurrences (LR) for AF. RESULTS: In total, 127 patients (49.0%) experienced their last episodes of ERAT during the first (n = 65), second (n = 14), or third (n = 48) month of the 3-month blanking period (p < .001). One year freedom from ATAs was 97.8% in patients without ERAT compared with 95.4%, 64.3%, and 8.3% in patients with ERAT in the first, second, and third months after the index procedure, respectively (p < .001). Hazard ratios of LR according to the timing of the last episode of ERAT first, second, and third months after the procedure were 2.84, 16.70, and 119.75, respectively. CONCLUSIONS: The ERAT occurred in 49.0% of patients within the first 3 months after surgical ablation. The occurrence of ERAT within 3 months after surgical AF ablation was a significant independent predictor of LR. Hence, the currently accepted 3-month blanking period may be considered for redefining in patients with AF surgical ablation.

Incidence of Cardiovascular Events and Safety Profile of Prasugrel in Korean Patients With Acute Coronary Syndrome.

BACKGROUND: Dual antiplatelet therapy is commonly used for patients with acute coronary syndrome (ACS). This study aimed to evaluate the safety and efficacy of aspirin and prasugrel at standard dosages in Korean patients using clinical outcome data.Methods and Results:For this prospective multicenter phase IV post-marketing surveillance (PMS) study, ACS patients from 29 July 2012 to 28 July 2016 were recruited. Patients received aspirin at a dose of 75-150 mg daily and a standard dose of prasugrel. Bleeding events were recorded and summarized to evaluate safety. Data on adverse events (AEs) and composite events such as cardiovascular (CV) death, myocardial infarction (MI), and stroke were recorded and summarized to assess efficacy. Of the 3,283 patients recruited, data from 3,110 and 3,044 patients were included in the safety and efficacy analyses, respectively (median treatment duration, 172 days). The most frequently reported AE was ecchymosis (2.8%). The number of patients with major bleeding was 29/3,110 (0.93%). The discontinuation rate for any reason was 12.6%. The number of cases that ended in CV death, MI, stroke, stent thrombosis, or unplanned coronary revascularization was 26/3,044 (0.85%). CONCLUSIONS: The present results are similar to those observed in clinical trials where administration of low-dose aspirin plus prasugrel was associated with a low rate of major bleeding and CV events.

Effect of membrane insertion for tricuspid regurgitation using immersed-boundary lattice Boltzmann method.

BACKGROUND: Tricuspid regurgitation is treated by valve repair or replacement. However, these methods have limitations, and alternative treatment methods are therefore required. OBJECTIVES: In this study, a new method of tricuspid valve treatment using artificial membrane insertion is analyzed. We performed tricuspid valve simulations using an artificial membrane inserted into the right ventricle (RV) or right atrium (RA). METHODS: We use the lattice Boltzmann method with the immersed boundary condition to model the structural motion of the valve leaflet. The effect of membrane insertion is analyzed in terms of the stress, force, and impulse on the valve leaflet, along with the velocity, pressure, jet volume, and Reynolds stress in the flow field. RESULTS: While the use of either membrane (RA or RV) leads to improved valve closure relative to the use of no membrane, the RV membrane is more effective than the RA membrane in achieving improved valve closure. In addition, a larger membrane area with a shorter distance between the leaflet and membrane increases membrane efficacy. CONCLUSION: Our results suggest that membrane insertion can form an effective new method for the treatment of tricuspid regurgitation.

Antiobesity Effects of Extract from Spergularia marina Griseb in Adipocytes and High-Fat Diet-Induced Obese Rats.

Obesity has recently risen and become a serious health concern in Korea according to the westernized diet and altered lifestyle. Hence, there is a growing interest in the supplementation of phytochemicals to find a safe and effective functional ingredient to treat obesity. Spergularia marina Griseb (SM) has traditionally been used as a natural herb against chronic diseases in Korea. In this study, we investigated the antiobesity effects of SM in vitro and in vivo. SM ethanol extract (SME) inhibited proliferation and differentiation in murine adipocytes and primary porcine pre-adipocytes in a dose-dependent manner. In the in vivo study, supplementation of SM powder (SMP) remarkably attenuated fat accumulation in HFD-induced obese rats. In addition, SMP supplementation improved lipid profiles in the serum and tissues of high-fat induced obese rats. Collectively, these data indicated that SME exhibited antiobesity effects by modulating adipogenesis and lipolysis. Furthermore, SMP could be developed as an obesity-induced metabolic syndrome treatment.

The herbal extract ALS-L1023 from Melissa officinalis alleviates visceral obesity and insulin resistance in obese female C57BL/6J mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) has traditionally been used as a medicinal herb to treat stress, anxiety, and insomnia. Current reports suggest that not only chronic stress stimulates angiogenesis, but angiogenesis also regulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from Melissa officinalis inhibits angiogenesis, we hypothesized that ALS-L1023 could suppress visceral obesity and insulin resistance in obese female C57BL/6J mice, a mouse model of obese premenopausal women. MATERIALS AND METHODS: The mice were grouped and fed for 16 weeks as follows: 1) low-fat diet (LFD), 2) high-fat diet (HFD), or 3) HFD supplemented with 0.4 or 0.8% ALS-L1023. Variables and determinants of visceral obesity, insulin resistance, and pancreatic dysfunction were then assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: ALS-L1023 decreased weight gain, visceral adipocyte size, and serum lipid levels in HFD-fed obese mice. ALS-L1023 also normalized hyperglycemia and hyperinsulinemia and concomitantly reduced blood glucose levels during oral glucose tolerance tests. The pancreatic islet size and insulin-positive ß-cell area were significantly reduced in ALS-L1023-treated mice compared with untreated obese controls, reaching a level similar to that of LFD-fed lean mice. ALS-L1023 suppressed pancreatic lipid accumulation, infiltration of inflammatory cells, and collagen levels. ALS-L1023 treatment altered the pancreatic expression of genes involved in steatosis, inflammation, and fibrosis. CONCLUSIONS: Our findings indicate that the herbal extract ALS-L1023 from Melissa officinalis not only inhibits visceral obesity, but also attenuates the increased fasting blood glucose, impaired glucose tolerance, and pancreatic dysfunction seen in female obese mice. These results suggest that ALS-L1023 may be effective in the prevention of visceral obesity and insulin resistance in obese premenopausal women.

Left atrial cross-sectional area is a novel measure of atrial shape associated with cardioembolic strokes.

OBJECTIVE: Cardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes. METHODS: A cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA. RESULTS: A total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p<0.001), independent of age, gender, atrial fibrillation, left ventricular ejection fraction and CHA2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119). CONCLUSIONS: LA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

Factors Influencing the Treatment Effect of Superelastic Wire Orthonyxia for Nail Plate Deformity.

BACKGROUND: Orthonyxia is an effective, noninvasive treatment for transverse nail curvature deformity. OBJECTIVE: To discover the factors influencing treatment results of superelastic wire orthonyxia (SEWO). MATERIAL AND METHODS: A retrospective study was conducted using clinical records of patients treated with SEWO. A multiple linear regression model was used to explain the correlation between correction pace (% per week) and the other collected variables (patient age, sex, position of treated toe, wire diameter [WD, mm], wire residence time [WRT, weeks], nail plate thickness [PT, mm], baseline nail curvature index [NCI], number of previous treatments, and the correction pace of previous treatments [CPT, % per week]). A logistic regression model was used to identify risk factors for adverse effects. RESULTS: A total of 475 cases were collected from 197 patients. The correction pace was positively related to baseline NCI, WD, and correction pace in previous treatment. Also, it was negatively related to WRT and nail PT. No clinical factor was correlated with the occurrence of side effects. CONCLUSION: The correction pace of SEWO is affected by the baseline NCI, the diameter of the wire, nail PT, the CPT, and the WRT.

Size-based analysis of extracellular vesicles using sequential transfer of an evaporating droplet.

We report spatial separation of extracellular vesicle (EVs) populations based on particle size by using an approach that exploits Marangoni flow and the coffee-ring effect in microdroplets. Sequential transfer of a drying droplet progressively increases the mean size of EVs in the sample by repeated subsampling of a droplet during coffee-ring formation. This method allows size-based sorting, separation, and eventual retrieval of EVs for RNA and protein analysis. To demonstrate the biomedical relevance of this method, EVs from prostate cancer patients were analyzed; results revealed that the expression of cancer-associated genes and proteins was higher in small EVs than in large EVs. This ability to sort EVs using a combination of coffee ring with Marangoni flow and sequential droplet-transfer allows analysis of subpopulations of EVs, and will facilitate further studies of EVs.

The polyherbal composition Gyeongshingangjeehwan 18 attenuates glucose intolerance and pancreatic steatosis in C57BL/6J mice on a high-fat diet.

Ethnopharmacologic relevance: Gyeongshingangjeehwan 18 (GGEx18) is a polyherbal composition derived from Ephedra sinica Stapf (Ephedraceae), Laminaria japonica Aresch (Laminariaceae), and Rheum palmatum L. (Polygonaceae) that is used as an antiobesity drug in Korean clinics. Its constituents are traditionally known to combat obesity, dyslipidemia, and insulin resistance. OBJECTIVE: This study was undertaken to investigate the effects of GGEx18 on glucose metabolism and pancreatic steatosis in obese C57BL/6 J mice fed a high-fat diet (HFD) and to examine the related cellular and molecular mechanisms. MATERIALS AND METHODS: The mice were grouped and fed for 13 weeks as follows: 1) low-fat diet, 2) HFD, or 3) HFD supplemented with GGEx18 (500 mg/kg/day). Various factors affecting insulin sensitivity and pancreatic function were then assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: GGEx18 treatment of obese mice reduced body weight, total fat, and visceral fat mass. GGEx18 inhibited hyperglycemia and hyperinsulinemia and improved glucose and insulin tolerance. GGEx18 also decreased serum leptin levels and concomitantly increased adiponectin levels. Furthermore, GGEx18-treated mice exhibited reduced pancreatic fat accumulation and normalized insulin-secreting ß-cell area. GGEx18 increased pancreatic expression of genes promoting fatty acid ß-oxidation (i.e., MCAD and VLCAD), whereas expression levels of lipogenesis-related genes (i.e., PPARγ, SREBP-1c, and FAS) declined. DISCUSSION AND CONCLUSION: GGEx18 curtailed impaired glucose metabolism and pancreatic steatosis in our mouse model by regulating pancreatic genes that govern lipid metabolism and improving insulin sensitivity. This composition may benefit patients with impaired glucose tolerance, insulin resistance, and pancreatic dysfunction.

The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia. OBJECTIVE: This study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved. METHODS: C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice. RESULTS: Mice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid ß-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD. DISCUSSION AND CONCLUSION: These results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.