[Show abstract][Hide abstract] ABSTRACT: Background:
Descurainia sophia seeds have a variety of pharmacological functions and been widely used in traditional folk medicine. However, their effects on human drug metabolizing enzyme (DME) activities have not been elucidated. The present study investigated the inhibitory effects of an ethanol extract of D. sophia seeds (EEDS) on human Phase I/II (DMEs) and P-glycoprotein (p-gp) in vitro.
The enzyme activities of human Phase I (cytochrome P450s, CYPs), Phase II (uridine diphosphate glucuronosyltransferases, UGTs) DMEs, and the drug transporter P-gp were determined in the presence of various concentrations of EEDS using commercially available luminogenic assay systems. The mode of enzyme inhibition and the inhibitory constant (Ki) value of EEDS were graphically determined with Lineweaver-Burk double reciprocal plots and secondary plots, respectively.
The enzyme activity assays showed that EEDS moderately inhibited the CYP1A2, CYP2C9, and CYP2C19 isoforms with half maximal inhibitory concentrations (IC50) of 47.3, 25.8, and 38.7 μg/mL, respectively. Graphical analyses with Lineweaver-Burk double reciprocal plots and secondary plots indicated that EEDS competitively inhibited CYP2C9 with a Ki value of 19.8 μg/mL; however, it inhibited CYP2C9 and CYP2C19 in a mixed mode with Ki values of 5.2, and 11.9 μg/mL, respectively. Other Phase I (CYP2C8, CYP2D6, and CYP3A4) and Phase II (UGT1A1 and UGT2B7) enzymes as well as P-gp were weakly or negligibly affected by EEDS with concentrations up to 500 μg/mL.
EEDS is a selective inhibitor of CYP1A2, CYP2C9, and CYP2C19 with moderate enzymatic inhibition. Clinically, full consideration should be given to a potential toxic adverse effect from a herb-drug interaction when drugs that are particularly susceptible to CYP1A2, CYP2C9, or CYP2C19-mediated metabolism are taken together with EEDS. Characterization of metabolic profiles of specific herbal drugs could help consumers and medical specialists to use them safely as a complementary and alternative medicine.
Preview · Article · Dec 2015 · BMC Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3S,4S)-3-angeloyl-4-tigloylkhellactone (1) along with 12 pyranocoumarins (2-13), two furanocoumarins (14, 15), and a polyacetylene (16) were isolated from the roots of Peucedanum praeruptorum using chromatographic separation methods. The structures of the compounds were determined using spectroscopic analysis with nuclear magnetic resonance (NMR) and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). The multidrug-resistance (MDR) reversal and anti-inflammatory effects of all the isolated compounds were evaluated in human sarcoma MES-SA/Dx5 and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among the 16 tested compounds, two (2 and 16) downregulated nitric oxide (NO) production and five (1, 7, 8, 11, and 13) inhibited the efflux of drugs by MDR protein, indicating the reversal of MDR. Therefore, these compounds may be potential candidates for the development of effective agents against MDR forms of cancer.
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis is the process of new vessel formation from pre-existing blood vasculature and is critical for continuous tumor growth. We previously reported that an ethanolic extract of Gleditsia sinensis thorns (EEGS) and its active constituent, cytochalasin H, have anti-angiogenic activity in vitro and in vivo via suppression of endothelial cell functions. In the present study, EEGS and cytochalasin H were observed to efficiently inhibit tumor growth in an in ovo xenograft model without significant toxicity. We repeatedly observed the anti-tumor and anti-metastatic effects of EEGS in representative animal models. These results suggest that EEGS and its active constituent, cytochalasin H, are potential candidates for the development of anti-angiogenic cancer drugs.
[Show abstract][Hide abstract] ABSTRACT: We undertook this study to estimate an accurate incidence and spread patterns of occult PTC in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study are 82 consecutive patients who underwent total thyroidectomy under a preoperative diagnosis of solitary PTC. All thyroidectomy specimens were serially sectioned in 2-mm thickness and whole-thyroid mapping was carried out for additional foci of occult PTC. The frequencies of occult lesions detected in the whole and contralateral lobe were determined, and clinicopathologic factors associated with multifocality were assessed. Whole-thyroid mapping revealed 66 occult PTC lesions missed by pre-operative ultrasound in 37 (45.1%) of 82 patients. The great majority (92.5%) of the occult PTC was smaller than 3 mm in size and 25 patients (30.5%) had contralateral lesions. We found that male sex was an independent predictor of multifocality (OR 3.00, 95% CI 1.11-8.14), adjusting for preoperative findings. Analysis with pathologic parameters showed that male sex (OR 5.03, 95% CI 1.68-15.08) and extrathyroidal extensions (OR 3.03, 95% CI 1.03-8.95) were associated with multifocal PTC. However, none of the clinicopathologic factors evaluated predicted contralateral PTC. Our study demonstrates the diagnostic limitations of ultrasound for the detection of multifocal PTC, and the need to consider the possibility of occult lesions in the management of solitary PTC, especially in male patients.
No preview · Article · Jun 2015 · Endocrine Related Cancer
[Show abstract][Hide abstract] ABSTRACT: Thyroid cancer is the most common malignancy in Korea; in 2012, about 44,000 new cases (19.6% of all malignancies) were registered and the estimated age-standardized incidence rate of thyroid cancer was 73.6 per 100,000 (17.3 and 88.6 per 100,000 in men and women, respectively). Despite the steep increase in its incidence, the age-standardized mortality rate of thyroid cancer has remained stable and 10-year relative survival rate is 99.2%. Increased detection using high-resolution ultrasonography may have contributed to the increased incidence of thyroid cancer if not all. However, the effectiveness of thyroid cancer screening using ultrasonography has not been fully evaluated as to whether screening and early diagnosis could decrease the morbidity or mortality of thyroid cancer. A multidisciplinary expert committee for developing a guideline for thyroid cancer screening was organized and established a recommendation for thyroid cancer screening using ultrasonography in Korea based on scientific evidence for the first time. In conclusion, the current evidence is insufficient to assess the balance of benefits and harms of the thyroid cancer screening by ultrasonography and the recommendation is that thyroid ultrasonography is not routinely recommended for healthy subjects.
Full-text · Article · Apr 2015 · Journal of the Korean Medical Association
[Show abstract][Hide abstract] ABSTRACT: Purpose: Anthocyanins from purple sweet potato (PSP) have been investigated in vitro and in animals and found to have a protective effect against oxidative hepatic damage. In this study, we investigated that aqueous extract of PSP can ameliorate the dysfunction of lipid metabolism in mice fed a high fat/cholesterol diet. Methods: Forty C57BL/6J mice were randomly divided into 5 groups (n = 8) and fed one of the following diets for 8 weeks; normal fat (NF) diet; high fat/ cholesterol (HFC) diet; HFC with 1.25% PSP (HFPL) diet; HFC with 2.5% PSP (HFPM) diet; HFC with 5% PSP (HFPH) diet. Results: Non-alcoholic fatty liver was manifested in the HFC group by showing increased levels in plasma alanine aminotransferase (ALT) activity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), increased level of TC and presence of many large lipid droplets in the liver, and increased fat cell size in the HFC group compared with the NF group. However, administration of HFC induced a significant decrease in food intake, resulting in decrease in fat mass. Coadministration of PSP did not lead to reversal of body weight changes, ALT activity, and lipid levels in plasma and the liver, but suppressed excess enlargement of the fat cell size through increasing carnitine palmitoyltransferase-1 (CPT-1) gene expression in the liver. Accordingly, the number of fat droplets in the liver was reduced in PSP administered groups. Conclusion: Taken together, these results suggest that PSP may have a protective effect on the dysfunction of lipid metabolism. Conduct of further studies on the coordinated regulation of PSP for lipid metabolic homeostasis at the liveradipose tissue axis is needed.
Preview · Article · Feb 2015 · Journal of Nutrition and Health
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of gastrectomy on diabetes mellitus (DM) and hypertension (HTN) in non-obese gastric cancer patients.
A total of 100000 patients, diagnosed with either type 2 DM or HTN, were randomly selected from the 2004 Korean National Health Insurance System claims. Among them, 360 diabetes and 351 hypertensive patients with gastric cancer who had been regularly treated without chemotherapy from January 2005 to December 2010 were selected. They were divided into three groups according to their treatment methods: total gastrectomy (TG), subtotal gastrectomy (STG) and endoscopic resection (ER).
The drug discontinuation rate of anti-diabetic and anti-hypertensive agents after gastric cancer treatment was 9.7% and 11.1% respectively. DM appeared to be improved more frequently (22.8%) and earlier (mean ± SE 28.6 ± 1.8 mo) in TG group than in the two other groups [improved in 9.5% of ER group (37.4 ± 1.1 mo) and 6.4% of STG group (47.0 ± 0.8 mo)]. The proportion of patients treated with multiple drugs decreased more notably in TG group compared to others (P = 0.001 in DM, and P = 0.035 in HTN). In TG group, adjusted hazard ratio for the improvement of DM was 2.87 (95%CI: 1.15-7.17) in a multi-variate analysis and better control of DM was observed with survival analysis (P < 0.001).
TG was found to decrease the need for anti-diabetic medications which can be reflective of improved glycemic control, to a greater extent than either ER or STG in non-obese diabetic patients.
[Show abstract][Hide abstract] ABSTRACT: Context: With recent technical advances in radiotherapy (RT) planning, simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) has made possible the delivery of high radiation dose to the tumor, minimizing surrounding normal tissues. Objective: To evaluate the clinical effectiveness and safety of postoperative SIB-IMRT in patients with locoregionally advanced papillary thyroid cancer (PTC). Design: This was a propensity score matched case control study. Setting: This study was conducted at tertiary referring center. Patients or other Participants: This study included locoregionally advanced PTC (pT4 or N1b) patients who underwent thyroid cancer surgery and radioactive iodine ablation (RIA) followed by postoperative SIB-IMRT (RT group) under a phase II trial or no postoperative RT (Non-RT group) Intervention: Postoperative SIB-IMRT was the intervention. Main Outcome Measures: locoregional relapse free survival (LRFS) was compared between RT group and Non-RT group. Results: Multivariate analysis showed that several factors, including gender, American Thyroid Association risk category and use of postoperative RT, significantly associated with LRFS in all 201 patients (p<0.05 each). In the 118 propensity score matched patients, there were no significant differences in baseline characteristic between the RT and Non-RT groups, but the LRFS rate was significantly higher in the RT than in the Non-RT group (4 years: 100% vs. 84.6%, p = 0.002). Overall, SIB-IMRT was well tolerated, with no grade ≥3 toxicity, and was completed as planned in all patients. Conclusions: Postoperative SIB-IMRT is feasible and effective in improving locoregional control in patients with locally advanced PTC. Large scale randomized studies are warranted.
No preview · Article · Jan 2015 · Journal of Clinical Endocrinology & Metabolism
[Show abstract][Hide abstract] ABSTRACT: Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors.
We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP).
The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively.
This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP.
Preview · Article · Dec 2014 · Nutrition research and practice
[Show abstract][Hide abstract] ABSTRACT: A remarkable increase in the number of thyroid cancer cases has been reported in recent years; however, the markers to predict high-risk groups have not been fully established.
We conducted a case-control study (257 cases and 257 controls) that was nested in the Cancer Screenee Cohort Study between August 2002 and December 2010; the mean follow-up time for this study was 3.1 +/- 2.2 years. The levels of total triiodothyronine (TT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), anti-thyroperoxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb) were measured using samples with pre-diagnostic status. Logistic regression models were used to examine the association between thyroid function/autoimmunity and thyroid cancer risk.
When the markers were categorized by the tertile distributions of the control group, the highest tertile of FT4 (OR = 1.73, 95% CI = 1.11 - 2.69) and the middle tertile of TSH (OR = 1.77, 95% CI = 1.14 - 2.74) were associated with an increased risk of thyroid cancer by multivariate analyses. In addition, an elevated risk for thyroid cancer was found in subjects with TPOAb levels above 30 IU/mL (OR = 8.47, 95% CI = 5.39 - 13.33 for 30-60 IU/mL and OR = 4.48, 95% CI = 2.59 - 7.76 for >=60 IU/mL). Stratified analyses indicated that some of these associations differed by sex, BMI, smoking status, and the duration of follow-up.
This study demonstrated that the levels of biomarkers of thyroid function/autoimmunity, particularly the presence of TPOAb, might be used as diagnostic markers for predicting thyroid cancer risk. Our findings suggest that careful monitoring of thyroid biomarkers may be helpful for identifying Korean populations at high-risk for thyroid cancer.
[Show abstract][Hide abstract] ABSTRACT: Poor electrochemical output of a lithium-ion battery at low temperature is an existing general concern, which restricts their application as energy storage devices. In the current work, low temperature behaviours of coin full cells prepared with specific loading amount, thickness and packing density were investigated. Graphite anode and LiNi0.6Co0.2Mn0.2O2 cathode were prepared with different laminates from low to high loading and thickness. Coin full cell discharge capacity and capacity retention was comparatively investigated both at room temperature (25 °C) and low temperature (−32 °C). The results demonstrated that the cells prepared with low loading and lesser thickness displayed a better low temperature performance in terms of capacity retention. Furthermore, electrochemical impedance spectroscopic analysis determined that at low temperature the electrodes with a lower loading showed a less charge-transfer resistance (Rct) than that of those with a higher loading.
No preview · Article · Nov 2014 · Physica Status Solidi (A) Applications and Materials
[Show abstract][Hide abstract] ABSTRACT: Activation of β-catenin in neurons regulates mitochondrial function and protects against protein misfolding disorders, including Alzheimer's disease and Huntington's disease. Melatonin, a natural secretory product of the pineal gland, exerts neuroprotective effects through the activation of β-catenin. In this study, melatonin increased β-catenin protein expression and activation in human neuroblastoma cell lines SH-SY5Y cells. Melatonin also inhibited PrP (106-126)-induced neurotoxicity and the inhibition attenuated by treatment of β-catenin inhibitor ICG-001. Activation of β-catenin blocked PrP (106-126)-mediated down-regulation of anti-apoptotic protein survivin and Bcl-2. Reduction of mitochondrial membrane potential, translocation of Bax and cytochrome c release which induced by PrP (106-126) treatment were inhibited by β-catenin activation, which contributed to prevented PrP (106-126)-induced neuronal cell death. In conclusion, β-catenin activation by melatonin prevented PrP (106-126)-induced neuronal cell death through regulating anti-apoptotic proteins and mitochondrial pathways. These results also suggest the therapeutic value of wnt/ β-catenin signaling in prion-related disorders as influenced by melatonin.This article is protected by copyright. All rights reserved.
No preview · Article · Sep 2014 · Journal of Pineal Research
[Show abstract][Hide abstract] ABSTRACT: Background
Subclinical thyroid dysfunction might influence a bone health. We evaluated whether subclinical hypothyroidism adversely affects bone health including bone mineral density (BMD), level of vitamin D, and bone turnover status in patients with hip fracture.
We evaluated 471 patients aged 50 years or older, who underwent hip fracture surgeries. BMD, level of vitamin D, bone turnover status, and one-year mortality were compared between subclinical hypothyroidism group and control group.
BMD of femur and the level of 25-hydroxy-vitamin D (25-[OH]D) were similar in the two groups. There were no significant differences in bone turnover markers according to thyroid function. No significant differences were observed between the groups in utilization of intensive care unit (ICU), length of hospital stay, mobility, and one-year mortality.
Subclinical hypothyroidism was not associated with reduced bone health, including BMD, the level of 25-(OH)D, and bone turnover marker.