Compound K modulates fatty acid-induced lipid droplet formation and expression of proteins involved in lipid metabolism in hepatocytes.

BACKGROUND & AIMS: A key factor in the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) is hepatic steatosis. Incubation of human hepatic cells with free fatty acids (FFAs) causes accumulation of neutral lipids in lipid droplets (LDs) and serves as a model for hepatic steatosis. Ginsenosides, active constituents of ginsengs, have demonstrated beneficial effects in various pharmacological areas, including diabetes, however their effect on lipid accumulation in hepatocytes remains unclear. Here, we examine the effect of compound K (ComK), an active metabolite of ginsenosides, on the regulation of LD formation and on the expression of proteins involved in lipid homeostasis in hepatocytes. METHODS: HuH7 cells were pretreated with ComK, followed by lipid loading with FFA. LDs were visualized using Oil Red O staining and immunohistochemistry for the LD-related protein PLIN2. Triglyceride levels were determined in isolated LDs. The expression of proteins involved in lipid homeostasis was examined by Western blotting. RESULTS: Treatment with ComK significantly decreased LD formation in FFA-loaded HuH7 cells and increased phosphorylation levels of AMPK, and its substrate ACC. ComK also increased protein expression of peroxisome proliferator-activated receptor-α (PPAR-α) and acyl-CoA oxidase (ACOX1) together with elevated activity of a PPAR-α response element reporter construct. These effects were inhibited by the PPAR-α antagonist MK886. CONCLUSIONS: ComK reduced LD formation and TG accumulation in FFA-loaded hepatocytes, in part by up-regulating AMPK activity and PPAR-α related pathways. These results suggest that ComK may have efficacy for the treatment of hepatic steatosis and associated diseases.

The effect of pH on crystal characteristics and IR absorbance of copper sulfide nanoparticles.

Copper sulfide, CuS, was synthesized by an aqueous sonochemical method and it was investigated the effect of pH on crystal characteristics of CuS and IR absorbance. The formed CuS has main peaks as 27.68 degrees, 29.28 degrees, 31.79 degrees, 32.85 degrees, 47.94 degrees, 52.72 degrees and 59.3 degrees with the hexagonal structure. Average diameter of CuS was about 18 nm and molar ratio of Cu:S was as 1:1. The CuS prepared at pH 11 presents the highest visible light transmittance of 82.6% and that at pH 4 presents the highest IR rejected of 93.8%. The formation of CuS was affected by pH and led to new absorption band in the IR region. The CuS nanoparticles from this study could be used as thermal insulating materials for car- and house-window films with a high IR-cut.

An aqueous extract of Salacia oblonga root, a herb-derived peroxisome proliferator-activated receptor-alpha activator, by oral gavage over 28 days induces gender-dependent hepatic hypertrophy in rats.

Activation of peroxisome proliferator-activated receptor (PPAR)-alpha by natural and synthetic chemicals induces hepatic hypertrophy. An aqueous extract of Salacia oblonga root (SOW) is an Ayurvedic medicine with anti-diabetic and anti-obesity properties. In the present study, it was found that SOW (100, 300 and 900mg/kg, once daily by oral gavage over a 28 day period) elicited dose-related increases in liver weight (LW) by 1.6%, 13.4% and 42.5%, respectively, and in the ratio of LW to body weight by 8.8%, 16.7% and 40.2%, respectively, in male rats. These effects were less pronounced in females. SOW selectively increased liver mass in male rats but Sudan red staining was not different, which indicates that hepatic lipid accumulation was similar in both genders. However, SOW even at the highest dosage did not influence serum ALT and AST activities in male or female rats. Moreover, SOW was found to activate PPAR-alpha in human hepatoma-derived HepG2 cells, as evidenced by the upregulation of PPAR-alpha and acyl-CoA oxidase mRNA expression. Thus, SOW-dependent PPAR-alpha activation may precede the development of the gender difference in hepatic hypertrophy; this process may be influenced by sex hormone status.

The outcome of percutaneous stent implantation in congenital heart disease: experience of a single institute.

PURPOSE: The efficacy of percutaneous stent implantation for congenital heart disease (CHD) in Korea, where stent availability is limited, has not been determined. This study evaluated the acute and midterm results of stent implantation in different CHD subgroups. METHODS: Stents were implanted in 75 patients with 81 lesions: (1) pulmonary artery stenosis (PAS) group, 56 lesions in 51 patients; (2) coarctation of the aorta (CoA) group, 5 lesions in 5 patients; (3) Fontan group, 13 lesions in 12 patients; (4) ductal stent group, 3 lesions in 3 patients; and (5) other CHD group, 4 lesions in 4 patients. Mean follow-up duration was 2.1 years (0.1-4 years). Medical records were reviewed retrospectively. RESULTS: The minimum lumen diameter (MLD) in PAS and CoA increased from 5.0±1.9 mm and 8.4±1.6 mm to 10.1±3.6 mm and 12.3±2.5 mm, respectively (P<0.01). In the PAS group, pressure gradient decreased from 25.7±15.6 mmHg to 10.4±10.1 mmHg, and right ventricular to aortic pressure ratio from 0.56±0.21 to 0.46±0.19. In the CoA group, the pressure gradient decreased from 50±33 mmHg to 17±8 mmHg. In the ductal stent group, the MLD of the ductus increased from 2.3 mm to 4.3 mm and arterial oxygen saturation from 40%-70% to 90%. No deaths were associated with stent implantation. Stent migration occurred in 3 patients, but repositioning was successful in all. Stent redilation was performed successfully in 26 cases after 29±12 months. CONCLUSION: Percutaneous stent implantation was safe and effective, with acceptable short and mid-term outcomes in Korean CHD patients.

Short-Term Change of Exercise Capacity in Patients with Pulmonary Valve Replacement after Tetralogy of Fallot Repair.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the effect of pulmonary valve replacement (PVR) on exercise capacity and determine cardiopulmonary exercise (CPEX) parameters associated with improvement in right ventricle (RV) function. SUBJECTS AND METHODS: We retrospectively analyzed CPEX and magnetic resonance imaging parameters in a total of 245 patients who underwent PVR from January 1998 to October 2015. In addition, we analyzed the characteristics of the patients who showed improved exercise capacity after PVR. RESULTS: Twenty-eight patients met the inclusion criteria for the study. CPEX parameters after PVR showed no significant changes in all patients. However, baseline predicted peak oxygen uptake (VO2peak) (%) value was significantly lower in patients with significant improvement in exercise capacity after PVR, as compared to patients who showed decreased exercise capacity after PVR (60.83±10.28 vs. 75.81±13.83) (p=0.003). In addition, patients with improved exercise capacity showed a positive correlation between the change of right ventricular ejection fraction (RVEF) (%) and the change of anaerobic threshold (r=0.733, p=0.007); whereas, patients with decreased exercise capacity showed a negative correlation between the change of RVEF (%) and the change of predicted VO2peak (%) (r=-0.575, p=0.020). CONCLUSION: The importance of predicted VO2peak (%) in evaluating exercise capacity differentiated from other CPEX variables. The change of anaerobic threshold and predicted VO2peak (%) might be a useful predictor of the change in RV function after PVR.

Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

Alcohol consumption is the principal factor in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As one of the oldest forms of liver injury known to humans, ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid metabolism and induction of hepatocyte apoptosis, by which chronic alcohol consumption triggers serious complex progression of ALD is well established, there is no universally accepted therapy to prevent or reverse. In this article, we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies. This review is focused on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, available pharmacological drugs and new agents that are under development, liver transplantation, application of complementary medicines, and their combination. The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature. We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD. Through a system review, this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.

Effect of ferric ion added on photodegradation of alachlor in the presence of TiO2 and UV radiation.

The effect of in situ photodeposited ferric ion onto TiO2 surface on the degradation of alachlor was investigated in the presence of the UV radiation. The photodegradation rate of alachlor could be described as an apparent first order. The rate constant (K(a)) of alachlor increased from 0.021 to 0.060 h(-1) as the number of coating times increased from 1- to 5-times in the absence of ferric ion, where the corresponding thicknesses of the TiO2 film were 67 and 174 nm. The rate constant (K(a)) increased from 0.030 to 0.060 h(-1) as pH value decreasd from pH 9 to 5 in the presence of only TiO2 immobilised with 5-times of coating. The rate constant increased slightly from 0.031 to 0.050 h(-1) as the concentration of ferric ion increased from 0.75 to 7.5 mg Fe3+ l(-1) in the absence of TiO2. However, those increased from 0.051 to 0.110 h(-1) in the presence of both TiO2 and ferric ion. In situ photodeposition of ferric ion onto the TiO2 surface enhanced the rate constant of photodegradation of alachlor by about 80% with an adding 7.5 mgFe3+ l(-1). During the alachlor photodegradation, three kinds of non-toxic organic compounds derived from alachlor were detected in 1 h.

Photodegradation of DDT with the photodeposited ferric ion on the TiO2 film.

The photodegradation capability of DDT has been enhanced by Fe/TiO2 film in a photoreactor with UV radiation. The optimal thickness of TiO2 for the DDT photodegradation was 2.94 microm with a 3-time coating, where the first-order rate constant was 0.077 min(-1). The optimal Fe3+(ferric ion) photodeposition amount was estimated as 3.7 x 10(-4) mg mm(-2) corresponding with 0.73 mg Fe3+ (mg TiO2)(-1). Photoremoval rate of DDT increased with an increasing pH value, while the pH value of solution decreased to acidic region during the DDT photodegradation. The photodegradation efficiency was 85% in 20 min with only TiO2 film and increased from 85% up to 96% by the photodeposition of 0.73 mg Fe3+ (mg TiO2)(-1) on TiO2 film as a sensitizer since the band gap energy of Fe2O3 (2.2 eV) is lower than that of TiO2 (3.0 eV).

Study on the effect of temperature and pressure on nickel-electroplating characteristics in supercritical CO2.

In this work, it was investigated the effect of solubility in supercritical CO2 on the nickel-electroplating characteristics. The plating characteristics could be controlled by electric resistance and dispersion in emulsion as well. CO2 concentration had better be controlled at lower concentration than 50 CO2 wt% to decrease electric resistance since supercritical CO2 is non-polar material. Non-ionic surfactant with EO/PO block copolymer was more efficient than any other surfactant and the dispersion at 0.2 surfactant wt% was better than at any surfactant concentration and over-added surfactant concentration over 0.2 wt% brought to the decrease of dispersion properties. Electric resistance was constant at 20Omega in ranging from pH 2.2 to pH 3.5 and increased slowly to 50Omega at pH 4 and rapidly to 400Omega at pH 5. Characteristics of nickel film has a close relation with solubility in supercritical CO2 and solubility is dependent on pressure and temperature. Solubility at 16 MPa was higher than that any other at pressure and at constant pressure of 16 MPa, solubility in supercritical CO2 increased with an increasing temperature from 31 to 45 degrees C and decreased over 45 degrees C.

Suppressor of cytokine signaling (SOCS) genes are silenced by DNA hypermethylation and histone deacetylation and regulate response to radiotherapy in cervical cancer cells.

Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.

Tetracyclic triterpenoids in herbal medicines and their activities in diabetes and its complications.

Tetracyclic triterpenoids, including the dammarane, cucurbitane, cycloartane, lanostane and protostane groups, is a class of triterpenoids widely distributed in various medicinal plants, particularly those commonly used for the treatment of diabetes and its complications, such as Panax ginseng, Panax quinquefolium, Panax notoginseng, Gynostemma pentaphyllum, Astragalus membranaceus, Momordica charantia, and Ganoderma lucidum. This review highlights recent findings on the chemistry and bioactivities of tetracyclic triterpenoids from these plants and other popular herbal medicines.

Simultaneous expression of allogenic class II MHC and B7.1 (CD80) molecules in A20 B-lymphoma cell line enhances tumor immunogenicity.

We expressed the allogenic class II MHC antigen and B7.1 (CD80) co-stimulatory molecule in A20 beta-lymphoma cells in order to test their efficacy as immuno-stimulating adjuvant agents in inducing tumor-specific immunity. The transduction of the allogenic I-Ab alpha and beta chain genes into A20 cell resulted in a surface expression of the allogenic class II MHC molecules. The expression of the allogenic class II MHC antigen (I-Ab) in A20 cells enhanced the proliferation of T cells in a mixed lymphocyte tumor culture and in vitro cytotoxic T lymphocyte (CTL) generation against parental cells. The B7.1 gene, which is known to be a potent co-stimulatory molecule, was also transduced and expressed in A20 cells, either alone or in combination with I-Ab. The B7.1 transduction alone leads to a similar in vitro immune enhancing effect as I-Ab. When both the I-Ab and B7.1 genes were transduced, the in vitro immunostimulating capacity was further enhanced. Finally, we also tested the A20 cells that were transduced with I-Ab and/or B7.1 for their efficacy as preventive tumor vaccines in vivo. The results indicate that the A20 cells that express both the I-Ab and B7.1 have more potent vaccinating potential, compared to the cells that express only one of the molecules.

Photodegradation of bisphenol-A with TiO2 immobilized on the glass tubes including the UV light lamps.

Photodegradation experiments of bisphenol-A (BPA) were performed with TiO(2) particles as a photocatalyst, where particles were immobilized using a titanium sol-solution synthesized by a sol-gel method. The effects of immobilized TiO(2)-film thickness, UV radiation intensity, and pH on the photodegradation of BPA were investigated. Apparent rate constant of the first order increased with increasing TiO(2)-coating time from 1 to 3, however, decreased over 4-coating time. Rate constant (K) increased with increasing the UV light intensity, which was related with the number of inserted UV lamps. Rate constant (K) increased as the pH value shifted from basic to acidic regions. Four kinds of byproducts were derived during the photodegradation of BPA, which were identified as 1.1-ethenylidenebis-benzene, 4-isopropylphenol, 4-tert-butylphenol, and phenol.

Removal of Cu(II) from aqueous solutions by adsorption process with anatase-type titanium dioxide.

The experiment was performed in the reactor with suspended anatase-type titanium dioxide particles. The adsorption amount increased rapidly with an increasing pH value from pH 2 to 5 and remained constant over pH 5. The adsorption amount of Cu(2+) increased with temperature from 15 degrees C to 40 degrees C. The adsorption equilibrium constant (K(ads)) was 0.854 and adsorption isotherm of Cu(2+) adsorption on titanium dioxide was more suitable in Langmuir adsorption isotherm than in Freundlich isotherm. The adsorption rate was rapid with an increasing number of UV lamps of 254 nm.

Removal of paraquat dissolved in a photoreactor with TiO2 immobilized on the glass-tubes of UV lamps.

Experiments were performed to investigate the effects of operating parameters, such as air-inflow rate, UV-light intensity, and film thickness of the photocatalyst, on the photo-decomposition efficiency of paraquat in an immersion-type reactor with TiO2 immobilized by three kinds of methods on the glass tube of UV lamps. As the number of TiO2 coating-time increased from 1 to 4, film thickness on the glass tube by a dip-coating method increased from 355 to 1180 A. The removal efficiency of paraquat using TiO2 prepared by the hydrothermal method was the highest, being 99% in a 12 h operation of 3-type TiO2 immobilized by a sol-gel method and a hydrothermal method, including a commercial product P-25, while that in the absence of TiO2 with only the UV light was the lowest, being 50% in 12 h. The conversion ratios of paraquat at the volumetric flow rates of 5, 10, and 20 mL min(-1) were 46%, 25%, and 17% in 18 h, respectively.

The preparation of TiO2 nanometer photocatalyst film by a hydrothermal method and its sterilization performance for Giardia lamblia.

The photocatalytic property of TiO(2) is utilized to sterilize the Giardia lamblia in an aqueous solution in this study. The TiO(2) colloidal solution used for the film was prepared by the modified hydrothermal method and it was directly coated on a UV-lamp, which was set up using a photoreactor manufactured in our laboratory. The TiO(2) film was very stably attached to the UV-lamp, and it was transparent until 5-time coating. The size of the TiO(2) particle in the film was distributed around 20-30 nm and the film thickness was about 200 nm per 1-time coating. The G. lamblia cell was just partially damaged under UV-irradiation without a TiO(2) photocatalyst, but the dead cell became very small and the dead body finally disappeared with an increase in the intensity of UV-irradiation after 2 h. In addition, under the TiO(2)/UV-irradiation system, the sterilized (dead) rate of G. lamblia was very fast. The sterilizing power increased at lower pH in the initial step, but it rather increased at a higher pH in the final step. And the sterilization of G. lamblia was very sensitive to the temperature, and resulted in an increase in the sterilized rate at higher temperatures. On the basis of these experimental observations, it can be concluded that TiO(2) photocatalyst under UV-irradiation could be adopted as one of the sterilization modalities for the G. lamblia.

Adsorption characteristics of Ni(II) on gamma-type alumina particles and its determination of overall adsorption rate by a differential bed reactor.

The adsorption experiment of nickel ion [Ni(II)] on gamma-type alumina by a differential bed reactor in aqueous solutions was investigated to determine the adsorption characteristics and overall adsorption rate. The adsorbed amount increased rapidly with pH from pH 2 to 6 and kept constant over pH 6. The adsorbed amount of Ni(II) increased with temperature from 20 to 50 degrees C. Correlation coefficients (R2) of Langmuir and Freundlich adsorption isotherms were 0.9268 and 0.9489, respectively, and Freundlich isotherm was more suitable for adsorption on gamma-type alumina than Langmuir isotherm. The overall adsorption rate of Ni(II) on gamma-type alumina at pH 6 by a differential bed rector was determined as follows: r = 68.77Ce(1.61) - 17.60qe(0.36). Al(III) ions in solutions were away from the alumina surface during the adsorption of Ni(II) and Al(III) concentration increased with an increasing Ni(II) adsorbed amount on alumina.

Photodegradation of alachlor with the TiO(2) film immobilised on the glass tube in aqueous solution.

Alachlor photodegradation was performed using TiO(2), which was synthesized by a modified sol-gel method. The thickness of a TiO(2) film immobilised by a 5-time dip-coating was 174 nm and the average diameter of TiO(2) particles was about 10-15 nm in SEM images. The crystal structure of a TiO(2) film calcinated at 300 degrees C for 1 h was observed as a typical anatase type. The stability of a TiO(2) film by a modified sol-gel method was 4% better than TiO(2) by a typical sol-gel method. The removal rate of alachlor with both Fe(3+) and UV radiation in the absence of TiO(2) was 0.28 mg/l/h in 10 h and the removal rate of alachlor with Fe(3+)/UV in the presence of TiO(2) was 0.32 g/l/h, which was higher by 14% than that with Fe(3+)/UV system. TOC concentration during the alachlor degradation with both TiO(2) and UV radiation in the absence of added Fe(3+) decreased from 100%, through 81% and 51%, to 44% with time elapses of 4, 8, and 10 h, respectively, while TOC concentration with both added Fe(3+) and UV radiation in the absence of TiO(2) decreased from 100% to 70% in 10 h.

High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell.

Overexpression of high-mobility group box 2 (HMGB2) is recently reported in several malignant cancers and was correlated with poor response to preoperative chemoradiotherapy of colorectal cancer patients. To enhance the chemoradiotherapy efficacy, the biological function of HMGB2 was investigated with respect to radiation response. HMGB2 gene knockdown cells were constructed by infecting shRNA expressing lentivirus and clonogenic assay was performed to count the radiosensitivity. HMGB2 knockdown sensitized HCT-116 and HT-29 colorectal cancer cells to ionizing radiation. This could be due to an increased DNA damage and an inefficient DNA damage repair in HMGB2 knockdown cells. In addition, an exposure to radiation downregulated HMGB2 expression in colorectal cancer cells with an intact TP53 gene. HMGB2 gene expression of TP53-mutant cell was not affected by irradiation. p53-mediated downregulation of HMGB2 was confirmed by direct activation of p53 using Nutlin-3 or by inducing p53 expression using Tet-On system. Luciferase reporter assay showed that HMGB2 promoter activity was inversely correlated with the amount p53 cotransfected. Our study revealed that HMGB2 is necessary to protect colorectal cancer cells from DNA damage and efficient DNA repair and p53-mediated downregulation is a critical mechanism of modulating HMGB2 expression.

Methodologies for investigating natural medicines for the treatment of nonalcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is emerging as a prominent condition in Western countries. In this review we describe the characteristics and current treatments of NAFLD and discuss opportunities for developing new therapeutic management approaches, with a particular emphasis on development of animal studies and in vitro assays for identification of components of natural product medicines. The main manifestation of NAFLD is hepatic lipid accumulation in the form of lipid droplets (LDs), known as hepatic steatosis (fatty liver). Current treatments for NAFLD generally aim to reduce triglyceride (TG) accumulation, often utilizing thiazolidinedines (TZDs) and fibrates, which are known to lower TG levels in hyperlipidemia, diabetes and metabolic syndrome. Both of these compounds act through activation of nuclear receptors of the Peroxisome Proliferator-Activated Receptor (PPAR) family, thereby activating genes involved in triglyceride metabolism. Thus treatment using natural PPAR α and PPAR γ ligands, such as polyunsaturated fatty acids (PUFA), has also been considered. Alternatively, natural medicines for the treatment of NAFLD have a long and successful history of controlling disease without prominent side effects. However, active compounds in natural medicine responsible for lowering hepatic TG levels are yet poorly characterized. This points to the need for medium-high throughput screening assays to identify active components within natural herbs. As outlined in this review, the quantification of the size and number of lipid droplets could provide an opportunity to screen compound libraries derived from natural medicine for their potential to reduce NAFLD.