Use of conditional reprogramming cell, patient derived xenograft and organoid for drug screening for individualized prostate cancer therapy: Current and future perspectives (Review).

Prostate cancer mortality is ranked second among all cancer mortalities in men worldwide. There is a great need for a method of efficient drug screening for precision therapy, especially for patients with existing drug­resistant prostate cancer. Based on the concept of bacterial cell culture and drug sensitivity testing, the traditional approach of cancer drug screening is inadequate. The current and more innovative use of cancer cell culture and in vivo tumor models in drug screening for potential individualization of anti­cancer therapy is reviewed and discussed in the present review. An ideal screening model would have the ability to identify drug activity for the targeted cells resembling what would have occurred in the in vivo environment. Based on this principle, three available cell culture/tumor screening models for prostate cancer are reviewed and considered. The culture conditions, advantages and disadvantages for each model together with ideas to best utilize these models are discussed. The first screening model uses conditional reprogramed cells derived from patient cancer cells. Although these cells are convenient to grow and use, they are likely to have different markers and characteristics from original tumor cells and thus not likely to be informative. The second model employs patient derived xenograft (PDX) which resembles an in vivo approach, but its main disadvantages are that it cannot be easily genetically modified and it is not suitable for high­throughput drug screening. Finally, high­throughput screening is more feasible with tumor organoids grown from patient cancer cells. The last system still needs a large number of tumor cells. It lacks in situ blood vessels, immune cells and the extracellular matrix. Based on these current models, future establishment of an organoid data bank would allow the selection of a specific organoid resembling that of an individual's prostate cancer and used for screening of suitable anticancer drugs. This can be further confirmed using the PDX model. Thus, this combined organoid­PDX approach is expected to be able to provide the drug sensitivity testing approach for individualization of prostate cancer therapy in the near future.

Antimicrobial Activities of Sesquiterpene-Rich Essential Oils of Two Medicinal Plants, Lannea egregia and Emilia sonchifolia, from Nigeria.

Lannea egregia (Anacardiaceae) and Emilia sonchifolia (Asteraceae) are plants used in traditional medicine in southwestern Nigeria. The essential oils from the leaves of L. egregia and E. sonchifolia were obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. Both essential oils were dominated by sesquiterpenoids. The major components in L. egregia leaf essential oil were α-panasinsen (34.90%), (E)-caryophyllene (12.25%), α-copaene (11.39%), and selina-4,11-diene (9.29%), while E. sonchifolia essential oil was rich in γ-himachalene (25.16%), (E)-caryophyllene (15.72%), and γ-gurjunene (8.58%). The essential oils were screened for antimicrobial activity against a panel of bacteria and fungi and displayed minimum inhibitory concentrations ranging from 156 µg/mL to 625 µg/mL. Based on these results, either L. egregia or E. sonchifolia essential oil may be recommended for exploration as complementary antibacterial or antifungal agents.

Follow that botanical: Challenges and recommendations for assessing absorption, distribution, metabolism and excretion of botanical dietary supplements.

Botanical dietary supplements are complex mixtures containing one or more botanical ingredient(s), each containing numerous constituents potentially responsible for its purported biological activity. Absorption, distribution, metabolism, and excretion (ADME) data are critical to understand the safety of botanical dietary supplements, including their potential for pharmacokinetic botanical-drug or botanical-botanical interactions. However, ADME data for botanical dietary supplements are rarely available and frequently inadequate to characterize their fate in vivo. Based on an assessment of the current status of botanical dietary supplements ADME research, the following key areas are identified that require robust data for human safety assessment: 1) phytochemical characterization including contaminant analysis and botanical authentication; 2) in vitro and/or in vivo data for identifying potential botanical-botanical or botanical-drug interactions and active/marker constituents; 3) robust ADME study design to include systemic exposure data on active/marker constituents using traditional or novel analytical chemistry and statistical approaches such as poly-pharmacokinetics; and 4) investigation of human relevance. A case study with Ginkgo biloba extract is used to highlight the challenges and proposed approaches in using ADME data for human safety assessment of botanical dietary supplements.

Bioavailability of wilforlide A in mice and its concentration determination using an HPLC-APCI-MS/MS method.

Wilforlide A (WA), an active compound in Tripterygium wilfordii Hook F (TW) which is a traditional Chinese medicine for treatment of autoimmune diseases, is a quality control marker for TW product. At present, the bioavailability/pharmacokinetics of WA is not known. Such information is not only essential to evaluate the relevance of WA as a quality control maker, but also important for future clinical efficacy studies. Therefore, a high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometric method (HPLC-APCI-MS/MS) was developed and applied to a bioavailability/pharmacokinetic study of WA. WA and celastrol (the internal standard, IS) were extracted by a liquid-liquid extraction method using methyl tert-butyl ether. Multiple reaction monitoring (MRM) scanning in positive ionization mode was used to monitor the transition of m/z 455.1 to 191.3 for WA and 451.3 to 201.2 for IS. This method was validated and applied to a pharmacokinetic study of WA in mice following intravenous administration (IV, 1.2 mg/kg), intraperitoneal injection (IP, 6 mg/kg) and oral administration (PO, 30 mg/kg). The lower limit of quantification (LLOQ) for WA was 10 ng/ml. The intra- and inter-day precision was found to be within 15.4% while the accuracy within 94.1-115.7% for all the quality control and LLOQ samples. The samples were stable under all the usual storage and experimental conditions. The terminal elimination half-lives were 14.7, 9.1 and 22.7 min following IV, IP and PO dosing, while the absolute bioavailability for IP and PO WA were 9.39% and 0.58% respectively. These results indicated that the HPLC-APCI-MS/MS assay was suitable for the pharmacokinetic study of WA. WA was found poorly absorbed when given orally and therefore it may not be a relevant marker for the oral TW products in the market.

Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease?

PURPOSE OF REVIEW: Omega-3 fatty acids are increasingly used for the protection of cardiovascular disease. The main but not the sole mechanism of action is the reduction of triglyceride levels. In this review, we summarize the effect of omega-3 supplements on all-cause and cardiovascular mortality, myocardial infarction, and stroke from the relevant randomized controlled trials. RECENT FINDINGS: Twenty-one randomized controlled trials assessed omega-3 supplementation on mortality and cardiovascular-related outcomes. From these studies, as well as from the relevant meta-analyses, we found that omega-3 supplements do not exert a consistent benefit for cardiovascular protection. There is uncertainty of a clear profit from omega-3 supplementation in cardiovascular disease.

Effect of rosuvastatin or its combination with omega-3 fatty acids on circulating CD34(+) progenitor cells and on endothelial colony formation in patients with mixed dyslipidaemia.

BACKGROUND AND AIMS: Hypercholesterolaemia is associated with a reduced number of circulating progenitor cells, a defect that is restored by statin therapy. We studied the effect of rosuvastatin monotherapy or its combination with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on progenitor cell number and function in patients with mixed dyslipidaemia. METHODS: Fifty patients with mixed dyslipidaemia and fifty-five normolipidaemic, apparently healthy, age- and sex-matched volunteers participated in the study. Patients were randomized to receive a daily dose of either 40 mg rosuvastatin (R group, n = 26) or 10 mg rosuvastatin plus 2 g of ω-3 PUFAs (R + O group, n = 24). The number of circulating CD34(+) and CD34(+)/KDR(+) progenitor cells as well as the number of colony-forming units-endothelial cells (CFU-ECs) at 10 days of culture were assessed at baseline and 3 months post-treatment. RESULTS: The number of CD34(+) and CD34(+)/KDR(+) cells per 10,000 leukocytes as well as the number of CFU-ECs were significantly lower in both patient groups compared with healthy volunteers (all p = 0.03). A 3-month treatment with either R or R + O significantly increased circulating CD34(+) and CD34(+)/KDR(+) cells as well as the number of CFU-ECs compared with baseline (all p = 0.03). Importantly, the increase in the above parameters was inversely correlated with therapy-induced reduction in lipid parameters in both patient groups. CONCLUSIONS: Patients with mixed dyslipidaemia exhibit low numbers of circulating CD34(+) and CD34(+)/KDR(+) cells as well as CFU-ECs in culture, a defect restored by 3-month treatment with either high-rosuvastatin dose or a combination of low-rosuvastatin dose with ω-3 PUFAs. The pathophysiological meaning of our results regarding the increased cardiovascular risk in these patients remains to be established.

Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats.

Piperine (PIP), the major alkaloid component from Piper longum L. and Piper nigrum L., could enhance the bioavailabilities of other drugs including rosuvastatin, peurarin and docetaxel (DOX) via inhibition of CYP3A and P-glycoprotein activity. Nevertheless, the effect of such drug combination usage on the in vivo exposure of PIP has not been investigated due to lack of assay for the simultaneous determination of PIP and other drugs such as DOX. Besides, the reported pharmacokinetics of PIP varied a lot without appropriate bioavailability determined from the same dose. In the current study, an LC/MS/MS method has been developed to simultaneously determine the plasma concentrations of PIP and DOX and further applied to investigate the pharmacokinetics properties of PIP after oral and intravenous administrations as well as the pharmacokinetics interactions between PIP and DOX after their co-administration. A simple protein precipitation method was employed for plasma sample treatment by adding a mixture of methanol and acetonitrile (1:1, v/v) with glibenclamide as internal standard (IS). The LC/MS/MS system consisted of Agilent 6430 series LC pumps and auto-sampler. The chromatographic separation was carried out in 15min on a Waters C18 column (150×3.9mm i.d., 4µm) with a mobile phase containing 0.2% formic acid and acetonitrile (1:1, v/v) at a flow rate of 0.4ml/min. The detection was performed using the positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode with precursor-to-product ion transitions at m/z 286.1→201.1 for PIP, m/z 830.3→548.9 for DOX and m/z 494.2→369.0 for IS. The method demonstrated good linearity for both PIP and DOX over the concentration range of 2.5-1280ng/ml with LLOD at 2.5ng/ml. The intra-day and inter-day precisions were less than 13.34% and relative error (R.E.) representing accuracy was in the range of -11.38 to 3.15%. The recoveries of PIP, DOX and IS were above 75% and there was no matrix effect. PIP and DOX exhibited good stabilities under various conditions. PIP was administrated via intravenous bolus at 3.5mg/kg and via oral administration at 35mg/kg and 3.5mg/kg, while DOX was intravenously administrated at 7mg/kg to Sprague-Daley rats. The plasma concentrations of PIP and DOX were determined using the above developed and validated method. At the dose of 3.5mg/kg, the bioavailability of PIP was calculated to be 25.36%. Its AUC0→t was unproportionally increased with doses, indicating a potential non-linear pharmacokinetics profile of PIP. It was found that the AUC0→t and C0 of DOX and t1/2 of PIP were significantly increased after their combination use, suggesting potential enhanced bioavailability of not only DOX but also PIP, which may lead to the overall enhanced pharmacological effects.

Thiazide-associated hyponatremia in the elderly: what the clinician needs to know.

Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malignancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antidepressants. Sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clinicians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clinical and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides (extracellular volume depletion-related or SIADH-like). Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.

Plasma VEGF and IL-8 Levels in Patients with Mixed Dyslipidaemia. Effect of Rosuvastatin Monotherapy or its Combination at a Lower Dose with Omega-3 Fatty Acids: A Pilot Study.

OBJECTIVES: Hypercholesterolaemia is associated with increased plasma levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). We studied the effect of rosuvastatin monotherapy or its combination at a lower dose with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in the VEGF and IL-8 plasma levels in patients with mixed dyslipidaemia. METHODS: Fifty patients with mixed dyslipidaemia were recruited. Fifty-five normolipidaemic, apparently healthy, ageand sex- matched subjects acted as controls. Patients were randomized to 40 mg/day rosuvastatin (R group, n=26) or 10 mg/day rosuvastatin plus 2 g/day of ω-3 PUFAs (R+O group, n=24). The levels of VEGF and IL-8 in plasma, were assessed at baseline and 3 months post-treatment. RESULTS: At baseline, both plasma VEGF and IL-8 levels were significantly higher in the R and R+O groups compared with controls (p<0.04, p<0.03 and p<0.02, p<0.03, respectively). Post-treatment levels of VEGF were decreased in the R group while a significant increase was observed in the R+O group, compared with baseline levels (p<0.02 and p<0.03, respectively). Post-treatment IL-8 levels were decreased in both R and R+O groups (p<0.03 and p<0.04, respectively). CONCLUSIONS: We show for the first time that either rosuvastatin monotherapy or its combination at a lower dose with ω-3 PUFAs reduces IL-8 levels in mixed dyslipidaemic patients. High-dose rosuvastatin monotherapy reduces VEGF values, whereas a significant increase is observed in patients receiving lower dose rosuvastatin with ω-3 PUFAs. The clinical significance of the above findings regarding cardiovascular risk remains to be established.

Molecular signatures in the prevention of radiation damage by the synergistic effect of N-acetyl cysteine and qingre liyan decoction, a traditional chinese medicine, using a 3-dimensional cell culture model of oral mucositis.

Qingre Liyan decoction (QYD), a Traditional Chinese medicine, and N-acetyl cysteine (NAC) have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD) at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D) cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours after the irradiation, the tissues were evaluated by hematoxylin and eosin (H and E) and a TUNEL assay to assess histopathology and apoptosis, respectively. Total RNA was extracted and used for microarray gene expression profiling. The tissue-cultures treated with NAC-QYD preserved their integrity and showed no apoptosis. Microarray results revealed that the NAC-QYD caused the upregulation of genes encoding metallothioneins, HMOX1, and other components of the Nrf2 pathway, which protects against oxidative stress. DNA repair genes (XCP, GADD45G, RAD9, and XRCC1), protective genes (EGFR and PPARD), and genes of the NFκB pathway were upregulated. Finally, tissue-cultures treated prophylactically with NAC-QYD showed significant downregulation of apoptosis, cytokines and chemokines genes, and constrained damage-associated molecular patterns (DAMPs). NAC-QYD treatment involves the protective effect of Nrf2, NFκB, and DNA repair factors.

The volatile constituents of Parquetina nigrescens from southwestern Nigeria.

The leaf essential oil of Parquetina nigrescens collected from Badary, Nigeria, was obtained by hydrodistillation and analyzed by gas chromatography - mass spectrometry. The essential oil had a simple composition with only five identified components. The oil was dominated by citral (35.0% neral and 53.7% geranial). The high concentration of citral in the essential oil likely contributes to the ethnomedicinal utility and bioactivities associated with this medicinal plant.

NMR-based lipidomic analysis of blood lipoproteins differentiates the progression of coronary heart disease.

Abnormal lipid composition and metabolism of plasma lipoproteins play a crucial role in the pathogenesis of coronary heart disease (CHD). A (1)H NMR-based lipidomic approach was used to investigate the correlation of coronary artery stenosis with the atherogenic (non-HDL) and atheroprotective (HDL) lipid profiles in 99 patients with CHD of various stages of disease and compared with 60 patients with normal coronary arteries (NCA), all documented in coronary angiography. The pattern recognition models created from lipid profiles predicted the presence of CHD with a sensitivity of 87% and a specificity of 88% in the HDL model and with 90% and 89% in the non-HDL model, respectively. Patients with mild, moderate, and severe coronary artery stenosis were progressively differentiated from those with NCA in the non-HDL model with a statistically significant separation of severe stage from both mild and moderate. In the HDL model, the progressive differentiation of the disease stages was statistically significant only between patients with mild and severe coronary artery stenosis. The lipid constituents of lipoproteins that mainly characterized the initial stages and then the progression of the disease were the high levels of saturated fatty acids in lipids in both HDL and non-HDL particles, the low levels of HDL-phosphatidylcholine, HDL-sphingomyelin, and omega-3 fatty acids and linoleic acid in lipids in non-HDL particles. The conventional lipid marker, total cholesterol, found in low levels in HDL and in high levels in non-HDL, also contributed to the onset of the disease but with a much lower coefficient of significance. (1)H NMR-based lipidomic analysis of atherogenic and atheroprotective lipoproteins could contribute to the early evaluation of the onset of coronary artery disease and possibly to the establishment of an appropriate therapeutic option.

Bench to bed evidences for pharmacokinetic and pharmacodynamic interactions involving oseltamivir and chinese medicine.

Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although C max, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P < 0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P < 0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe.

Recommendations for severe hypertriglyceridemia treatment, are there new strategies?

This review considers drug combinations and newer treatment strategies for patients with severe hypertriglyceridemia. Hypertriglyceridemia is associated with an atherogenic metabolic profile and in most studies with increased cardiovascular disease risk. Patients with severe hypertriglyceridemia also have increased incidence of pancreatitis. All types of severe hypertriglyceridemia are associated with a reduction in lipoprotein lipase activity. Patients with severe hypertriglyceridemia and abdominal pain or pancreatitis should be hospitalized and treated with hypolipidemic drugs and, if needed, with insulin/dextrose infusion or therapeutic apheresis. Fibrates are the first-line treatment in patients with severe hypertriglyceridemia. Omega-3 fatty acids and niacin are very useful drugs for patients with hypertriglyceridemia. Statins in high doses exhibit a significant hypotriglyceridemic activity. Drugs that interfere with chylomicron production such as orlistat are also useful for hypertriglyceridemic patients. In most patients with severe hypertriglyceridemia drug combinations are needed to maintain an acceptable triglyceride concentration. Gene therapy is under development for patients with known genetic abnormalities of triglyceride metabolism. Clinicians should be vigilant for the recognition and prompt treatment of patients with severe hypertriglyceridemia aimed to avoid the serious complication of pancreatitis and to reduce their cardiovascular risk.

Evaluation of the inhibition of carbohydrate hydrolyzing enzymes, the antioxidant activity, and the polyphenolic content of Citrus limetta peel extract.

Type 2 diabetes mellitus is one of the most frequent causes of death in Mexico, characterized by chronic hyperglycemia. One alternative strategy for this metabolic abnormality is inhibiting the enzymes responsible for the metabolism of carbohydrates. We evaluated whether the aqueous Citrus limetta peel extract could inhibit the metabolism of carbohydrates. We found that this extract inhibited primarily the enzyme α-amylase by 49.6% at a concentration of 20 mg/mL and to a lesser extent the enzyme α-glucosidase with an inhibition of 28.2% at the same concentration. This inhibition is likely due to the high polyphenol content in the Citrus limetta peel (19.1 mg GAE/g). Antioxidant activity of the Citrus limetta peel demonstrated dose-dependent antioxidant activity, varying from 6.5% at 1.125 mg/mL to 42.5% at 20 mg/mL. The study of these polyphenolic compounds having both antihyperglycemic and antioxidant activities may provide a new approach to the management of type 2 diabetes mellitus.

Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application.

INTRODUCTION: Nutraceutical is a food, or part of a food, used for the prevention and/or treatment of diseases. A number of nutraceuticals serve as candidates for development of prostate cancer chemopreventive agents because of promising epidemiological, preclinical and pilot clinical findings. Their mechanisms of action may involve an ability to target multiple molecular pathways in carcinogenesis without eliciting toxic side effects. AREAS COVERED: This review provides an overview of several nutraceuticals, including green tea polyphenol, omega-3 fatty acids, vitamin D, lycopene, genistein, quercetin, resveratrol and sulforaphane, for the clinical relevance to chemoprevention of prostate cancer. Their mechanisms of action on regulating key processes of carcinogenesis are also discussed. For each of these agents, a brief summary of completed or currently ongoing clinical trials related to the chemopreventive efficacy on prostate cancer is given. EXPERT OPINION: Even though a few clinical trials have been conducted, review of these results indicate that further studies are required to confirm the clinical efficacy and safety, and to provide a guidance on how to use nutraceuticals for optimal effect. Future cancer prevention clinical trials for the nutraceuticals should recruit men with an increased risk of prostate cancer.

Bioavailability enhancement of glucosamine hydrochloride by chitosan.

Glucosamine, as a dietary supplement for management of osteoarthritis, has a low and erratic oral bioavailability due to its transport-mediated absorption and presystemic loss in liver and GI tract. The present study described an effective approach to improve glucosamine intestinal absorption and hence its bioavailability using chitosan. Effects of chitosan on intestinal permeability and pharmacokinetics of glucosamine were evaluated in Caco-2 cell monolayer and rats, respectively. In addition, randomized crossover pharmacokinetic studies in beagle dogs were performed to evaluate the oral bioavailabilities of the developed glucosamine oral formulations containing chitosan (QD-Glu solution and QD-Glu tablet) in comparison to its commercial products. Caco-2 permeability studies demonstrated that chitosan could enhance the absorptive transport of glucosamine by 1.9-4.0-fold via the reversible opening of the cell tight junction. After oral administration of glucosamine solutions containing chitosan in rats, it was found that 0.5% (w/v) chitosan exhibited the highest enhancement in Cmax (2.8-fold) and AUC0-∞ (2.5-fold) of glucosamine. Further pharmacokinetic studies in beagle dogs demonstrated that QD-Glu solution and QD-Glu tablet showed much higher relative bioavailabilities of 313% and 186%, when comparing with Wellesse™ solution and Voltaflex™ tablet, respectively. In conclusion, chitosan could serve as a promising oral absorption enhancer for glucosamine.

Utilization of gene expression signature for quality control of traditional Chinese medicine formula Si-Wu-Tang.

The current study utilized a combined pharmacokinetic and genomic approach to demonstrate the feasibility of a new quality control method by using a panel of special differentially expressed genes (DEGs) as unique fingerprint to serve as marker of in vivo bioactivity for a representative traditional Chinese medicine (TCM) formula, Si-Wu-Tang (SWT). The method involves firstly obtaining possible in vivo active components, i.e., the "absorbable" components from the permeate of the Caco-2 monolayer model to simulate oral administration of two specific SWT products (CU-SWT, J-SWT), their component single herbs (Angelicae, Chuanxiong, Paeoniae, and Rehmanniae), and a standard mixture of active compounds (ferulic acid, ligustilide, senkyunolide A). Then, these respective absorbable components were incubated with MCF-7 cells to determine the gene expression profile using microarray processing/analysis as well as real-time PCR. From the available DEGs identified following the incubation, the magnitude of change in DEGs by real-time PCR was found to be consistent with that by microarray. The designated DEGs from the CU-SWT permeate were found to be distinct from other 19 products. Furthermore, the changes in the DEGs resulting from MCF-7 cells treated by eight replicate extracts of CU-SWT on three separate days were consistent. These results demonstrated sufficient specificity and consistency of the DEG panel which could serve as a unique bioactive "fingerprint" for the designated SWT product. The present method for DEG determination may be applied to other TCM products and with further definitive study can potentially provide a unique method for quality control of TCM in the future.

Current evidence and future perspectives of omega-3 polyunsaturated fatty acids for the prevention of cardiovascular disease.

Omega-3 fatty acids have been traditionally used for the prevention of major cardiovascular events in patients with or without a history of cardiovascular disease. Their main mechanism of action is to lower triglyceride levels, but they also exert anti-arrythmic and anti-inflammatory properties, they reduce blood pressure levels and stabilize the atherosclerotic plaques. There is a vast amount of evidence derived from randomized studies that seems to question their benefit for the prevention of major cardiovascular events. Upcoming trials will help to better clarify their use in certain indications.