Ginseng berry concentrate prevents colon cancer via cell cycle, apoptosis regulation, and inflammation-linked Th17 cell differentiation.

The Asian ginseng root (Panax ginseng C.A. Meyer) is a very commonly used herbal medicine worldwide. Ginseng fruit, including the berry (or pulp) and seed, is also valuable for several health conditions including immunostimulation and cancer chemoprevention. In this study, the anticancer and anti-proliferative effects of the extracts of ginseng berry and seed were evaluated. The ginsenosides in the ginseng berry concentrate (GBC) and ginseng seed extract (GSE) were analyzed. We then evaluated their anti-colorectal cancer potentials, including antiproliferation, cell cycle arrest, and apoptotic induction. Further investigation consisted of the berry's adaptive immune responses, such as the actions on the differentiation of T helper cells Treg, Th1, and Th17. The major constituents in GBC were ginsenosides Re and Rd, which can be compared to those in the root. The GBC significantly inhibited colon cancer cell growth, and its anti-proliferative effect involved mechanisms including G2/M cell cycle arrest via upregulation of cyclin A and induction of apoptosis via regulation of apoptotic related gene expressions. GBC also downregulated the expressions of pro-inflammatory cytokine genes. For the adaptive immune responses, GBC did not influence Th1 and Treg cell differentiation but significantly inhibited Th17 cell differentiation and thus regulated the balance of Th17/Treg for adaptive immunity. Although no ginsenoside was detected in the GSE, interestingly, it obviously enhanced colon cancer cell proliferation with the underlined details to be determined. Our results suggested that GBC is a promising dietary supplement for cancer chemoprevention and immunomodulation.

Tea Consumption and Risk of Chronic Obstructive Pulmonary Disease in Middle-Aged and Older Singaporean Adults.

Objective: The anti-oxidant and anti-inflammatory actions of phytochemicals and the smooth muscle relaxant actions of theophylline present in tea may confer pulmonary protection and reduce COPD risk. We investigated tea consumption (black, oolong, or green) association with COPD risks in a population-based cohort study of older adults aged ≥55. Methods: GOLD criteria was used to identify prevalent and incident cases of COPD (FEV1/FVC <0.70) among 4617 participants and 920 participants free of COPD at baseline who were assessed at follow-up 4.5 years later. Results: Prevalent cases of COPD consumed less tea than their non-COPD counterparts. Estimated odds ratio (OR) and 95% confidence intervals (95% CI) of association with prevalent COPD, adjusted for age, sex, ethnicity, housing type, smoking, alcohol, physical activity and BMI declined across tea consumption levels (p-trend=0.048), and was lowest for ≥3 cups/day (OR=0.77, 95% CI=0.61-0.96). The cumulated incidence of COPD declined across tea consumption categories (p-trend=0.012) and the lowest OR of association (OR=0.35, 95% CI=0.17-0.69) with consuming ≥3 cups/day after co-variate adjustment. Conclusion: Different kinds of tea showed similar non-significant trends of associations but appeared to be strongest for green tea. Tea consumption in this Asian population was associated with lowered COPD prevalence and incidence.

Complementary and alternative asthma treatments and their association with asthma control: a population-based study.

OBJECTIVES: Many patients with asthma spend time and resources consuming complementary and alternative medicines (CAMs). This study explores whether CAM utilisation is associated with asthma control and the intake of asthma controller medications. DESIGN: Population-based, prospective cross-sectional study. SETTING: General population residing in two census areas in the province of British Columbia, Canada. Recruitment was based on random-digit dialling of both landlines and cell phones. PARTICIPANTS: 486 patients with self-reported physician diagnosis of asthma (mean age 52 years; 67.3% woman). PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed CAM use over the previous 12 months, level of asthma control as defined by the Global Initiative for Asthma and the self-reported intake of controller medications. Multivariate logistic regression was performed to study the relationship between any usage of CAMs (outcome), asthma control and controller medication usage, adjusted for potential confounders. RESULTS: A total of 179 (36.8%) of the sample reported CAM usage in the past 12 months. Breathing exercises (17.7%), herbal medicines (10.1%) and vitamins (9.7%) were the most popular CAMs reported. After adjustment, female sex (OR 1.66; 95% CI 1.09 to 2.52) and uncontrolled asthma (vs controlled asthma, OR 2.25, 95% CI 1.30 to 3.89) were associated with a higher likelihood of using any CAMs in the past 12 months. Controller medication use was not associated with CAM usage in general and in the subgroups defined by asthma control. CONCLUSIONS: Clinicians and policy makers need to be aware of the high prevalence of CAM use in patients with asthma and its association with lack of asthma control.

Introduction to The neurosciences and music IV: learning and memory.

The conference entitled "The Neurosciences and Music-IV: Learning and Memory'' was held at the University of Edinburgh from June 9-12, 2011, jointly hosted by the Mariani Foundation and the Institute for Music in Human and Social Development, and involving nearly 500 international delegates. Two opening workshops, three large and vibrant poster sessions, and nine invited symposia introduced a diverse range of recent research findings and discussed current research directions. Here, the proceedings are introduced by the workshop and symposia leaders on topics including working with children, rhythm perception, language processing, cultural learning, memory, musical imagery, neural plasticity, stroke rehabilitation, autism, and amusia. The rich diversity of the interdisciplinary research presented suggests that the future of music neuroscience looks both exciting and promising, and that important implications for music rehabilitation and therapy are being discovered.

Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis.

We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC(50) values of 32.02 microM and 1.39 microM, respectively. SCH or GOM at concentrations up to 100 microM did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GOM could affect cellular drug metabolism in addition to drug uptake.

Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene.

Novel chemotherapeutic agents derived from active phytochemicals could be used as adjuvants and improve the anti-carcinogenicity of standard drug treatments. However, their precise mechanisms of action are sometimes unclear. In this study, the anti-carcinogenic effect of the herbal diterpenoid pseudolaric acid B (PAB) on the growth and apoptosis of colon cancer cells was investigated, and to compare that with the more toxic compound triptolide. PAB induced growth inhibition and apoptosis in HT-29 cells, which were associated with cell cycle arrest at the G(2)/M phase, modulation of cyclin expression and downregulation of the protooncogene c-myc. In addition, PAB also inhibited bcl-x(L) expression, induced cleavage of procaspase-3 and its substrate poly(ADP-ribose) polymerase (PARP), which together caused DNA fragmentation and nuclear chromatin condensation. Concomitantly, the modulation of the growth-related and apoptotic factors by PAB was accompanied by the increased protein and gene expression of the nonsteroidal anti-inflammatory drug-activated gene (NAG-1), which occurred along with cyclooxygenase-2 inhibition. The effects of PAB on PARP cleavage and NAG-1 overexpression were not reversible upon removal of the drug from the culture medium. Similar cytotoxic and pro-apoptotic effects were also attained by treating the HT-29 cells with another diterpenoid triptolide, but its actions on cell cycle progression and on the upstream transcriptional regulation of NAG-1 both took place in a less coherent manner. These findings exemplify the potential of herbal terpenoids, particularly PAB, in modulating colon cancer carcinogenesis through known molecular targets and precise mechanism of action.

Isolation of a trypsin inhibitor with deletion of N-terminal pentapeptide from the seeds of Momordica cochinchinensis, the Chinese drug mubiezhi.

A trypsin inhibitor, MCCTI-1, with a molecular weight of 3479 Da as determined by mass spectrometry, was isolated from Momordica cochinchinensis seeds with a procedure involving extraction with 5% acetic acid, ammonium sulfate precipitation, ion exchange chromatography on CM-Sepharose and reverse-phase high performance liquid chromatography. The sequence of its first 13 N-terminal amino acid residues was ILKKCRRDSDCPG which was about 85% identical with the sequence of trypsin inhibitor MCTI-1 from Momordica charantia Linn. When compared with the sequences of most other squash family trypsin inhibitors, the sequence of MCCTI-1 was characterized by the deletion of a pentapeptide from the N-terminus. Trypsin inhibitors also existed in seeds of some hitherto uninvestigated Cucurbitaceae species.

Functional complementation of yeast vma1 delta cells by a plant subunit A homolog rescues the mutant phenotype and partially restores vacuolar H(+)-ATPase activity.

The ability of a vacuolar H(+)-ATPase (V-ATPase) subunit homolog (subunit A) from plants to rescue the vma mutant phenotype of yeast was investigated as a first step towards investigating the structure and function of plant subunits in molecular detail. Heterologous expression of cotton cDNAs encoding near-identical isoforms of subunit A in mutant vma1 delta yeast cells successfully rescued the mutant vma phenotype, indicating that subunit A of plants and yeast have retained elements essential to V-ATPases during the course of evolution. Although vacuoles become acidified, the plant-yeast hybrid holoenzyme only partially restored V-ATPase activity (approximately 60%) in mutant yeast cells. Domain substitution of divergent N- or C-termini only slightly enhanced V-ATPase activity, whereas swapping both domains acted synergistically, increasing coupled ATP hydrolysis and proton translocation by approximately 22% relative to the native plant subunit. Immunoblot analysis indicated that similar amounts of yeast, plant or plant-yeast chimeric subunits are membrane-bound. These results suggest that subunit A terminal domains contain structural information that impact V-ATPase structure and function.

Removal of polyphenolic compounds from aqueous plant extracts using polyamide minicolumns.

An improved method for the removal of polyphenolic compounds from aqueous extracts of plants is presented. The method removes > 99% polyphenolic compounds from 5 mg of extract. The method is simple, robust and reproducible. We examined the removal of polyphenolics from 5 different aqueous extracts of Chinese medicinal herbs.

Inhibition of glycohydrolase enzymes by aqueous extracts of Chinese medicinal herbs in a microplate format.

A microplate assay, for use with a variety of glycohydrolase enzymes, was developed to aid the screening of Chinese medicinal herb extracts for the presence of potential anti-viral and anti-lymphoma compounds. The microplate assay method described offers greater convenience, speed and reproducibility over existing methods. The enzymes tested were alpha-glucosidase, beta-glucosidase and beta-glucuronidase. The assay can be easily adapted for use with other glycohydrolase enzymes. Of the 12 herb extracts examined four did not inhibit any of the enzymes (< 50% inhibition), one inhibited alpha-glucosidase only (> 50% inhibition), six inhibited beta-glucuronidase only, and one inhibited both alpha-glucosidase and beta-glucuronidase. None of the extracts were capable of inhibiting beta-glucosidase to any significant extent.

A comparison of human immunodeficiency virus type 1 inhibition by partially purified aqueous extracts of Chinese medicinal herbs.

A multiple screening approach to detect compounds inhibitory to various aspects of the human immunodeficiency virus type 1 (HIV-1) life-cycle has been applied to aqueous extracts of 19 herbs traditionally used in Chinese medicine as anti-viral agents. The extracts were tested for their ability to inhibit HIV-1 in a series of in vitro assays. The extracts were tested for inhibition of the interaction between HIV-1 gp120 and immobilized CD4 receptor, inhibition of recombinant HIV-1 reverse transcriptase and for inhibition of three glycohydrolase enzymes that contribute to viral protein glycosylation. Six of the herb extracts (30%) were potent inhibitors of the interaction between HIV-1 gp120 and the CD4 receptor (ID50 5.6 - 79.4 microg/ml), two extracts (10%) contained potent reverse transcriptase inhibitors (ID50 16.9 - 26.0 microg/ml) and 14 extracts (75%) were able to inhibit at least one of the glycohydrolase enzymes.

Oldenlandia diffusa and Scutellaria barbata augment macrophage oxidative burst and inhibit tumor growth.

Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumors. In this study we determined the effects of these phytochemicals on oxidative burst as an indicator of phagocytic function in a murine macrophage cell line J774 using an automated micro-fluorometric assay. A dose-dependent augmentation of oxidative burst was observed with OD as well as SB. The effect of OD and SB on the growth of a murine renal cell carcinoma (Renca) was also determined. Balb/c mice were transplanted subcutaneously with 1 x 10(5) Renca cells and were randomized into groups of 10 to receive oral feeding of OD (4 mg/day), SB (4 mg/day), or saline as control. Oral feeding with either OD or SB significantly inhibited the growth of Renca in mice. The data of this study show that OD and SB are capable of enhancing macrophage function in vitro and inhibiting tumor growth in vivo.

Thermal biofeedback as an effective substitute for sympatholytic medication in moderate hypertension: a failure to replicate.

Thirty-three moderate hypertensives were converted to a 2-drug regimen of metoprolol and diuretic and BPs stabilized at a well-controlled level. They then completed one of three conditions over an 8-week interval: (I) 16 sessions of TBF (hand and foot warming); (II) 16 sessions of frontal EMG-BF; (III) regular home monitoring of BP. Attempts were then made to withdraw the patients from the sympatholytic medication. Those successfully withdrawn were followed up for one year. There were no significant advantages for TBF over the other two conditions in the short term or with long-term follow-up. Only 27% of treated patients (including Condition III failures who were remedicated and treated with TBF) were successfully off of the sympatholytic at a one-year follow-up. The generally poor results on clinical outcome were confirmed by clinic BPs, home BPs by patients, and 24-hour ambulatory BPs.

[Stereological studies on the brain development of fetuses in cretinism endemic region after supplement of iodized salt for 10 years].

Epidemiologic reports indicated that in the cretinism endemic regions the incidence of cretinism decreased obviously after supplement of iodized salt but there still existed many cretinoid cases accompanied with mild impairment of intelligence and retardation of somatic development. This suggests that some factors other than iodine deficiency might also play an important role in the pathogenesis of cretinism. 21 brains of therapeutically aborted fetuses from cretinism endemic region after a supplement of iodized salt for ten years were studied under both light and electron microscopes. Serum T3, T4 and TSH of the fetuses and their mothers were coincidentally assayed. The brain development of fetuses from the endemic region was noticed to be still retarded as compared with those from the non-endemic region, despite that the serum hormones of the fetuses and their mothers in the endemic region showed no more significant difference from those in the non-endemic region. The retardation of the brain development could be evidenced by the increase of cellular density, decrease of the average volume of neurocytes, increase of the volume ratio between nucleus and cytoplasma per neuron, as well as decrease in number and average surface area of the mitochondria, and all of these were obtained in the cerebral cortex, hippocampus and the layer of Purkinje's cells of the cerebellum.

Preparation of cross-section specimens for transmission electron microscopy from alpha-Al2O3/Ni solid state bonded bicrystal interfaces.

The technique which is described combines the advantages of the techniques formerly proposed in the literature in each stage of the preparation of transmission electron microscopy (TEM) specimens including a single metal-ceramic interface. It allows easy handling of the thin foils in spite of their brittleness. Preferential thinning of the softer material in the two-phase foil is prevented, and both sides of the interface are thinned down to comparable thicknesses. The nickel-alumina bicrystal interface observed in TEM is neat and free from any reaction layer. This method is easily adaptable to other metal-ceramic systems.

Transcutaneous bilirubinometer: its use in Chinese term infants and the effect of haematocrit and phototherapy on the TcB index.

The application of the transcutaneous bilirubinometer in screening for neonatal jaundice was evaluated in 259 full-term Chinese infants: 202 who had not received any treatment and 57 who were receiving phototherapy. The transcutaneous bilirubin index correlated well with the serum bilirubin level (SB) of the untreated infants and the coefficient of correlation was slightly higher for TcB readings obtained over the mid-sternal area (r = 0.91; P less than 0.001) than those over the forehead (r = 0.85; P less than 0.001). Transcutaneous bilirubinometry was unreliable in predicting the SB level in infants receiving phototherapy even if the SB readings were obtained over shaded skin. The haematocrit of the infants, though having a statistically significant effect on the TcB index, contributed only minimally to the regression line and correlation coefficient between the TcB index and SB level.