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Compounds from Lingzhi has been demonstrated the ability for inhibiting tyrosinase (a key enzyme in melanogenesis) activity. In this study, we investigated the anti-melanogenic activity from the submerged mycelial culture of Ganoderma weberianum and elucidated the skin lightening mechanism by B16-F10 murine melanoma cells. From the cellular context, several fractionated mycelium samples exhibited anti-melanogenic activity by reducing more than 40% extracellular melanin content of B16-F10 melanoma cells. In particular, the fractionated chloroform extract (CF-F3) inhibited both secreted and intracellular melanin with the lowest dosage (25 ppm). Further analysis demonstrated that CF-F3 inhibited cellular tyrosinase activity without altering its protein expression. Taken together, our study has demonstrated that the chemical extracts from submerged mycelial culture of G. weberianum have the potential to serve as an alternative anti-melanogenic agent.

Poverty, family stability, and social policies influence the ability of adolescents to attend school. Likewise, being enrolled in school may shape an adolescent’s risk for HIV and pregnancy. We identified trends in school enrollment, factors predicting school enrollment (antecedents), and health risks associated with staying in or leaving school (consequences). Data from the Rakai Community Cohort Study (RCCS) were examined for adolescents 15–19 years (n = 21,735 person-rounds) from 1994 to 2013. Trends, antecedents, and consequences were assessed using logistic and linear regression with robust variance estimation. Qualitative data were used to explore school leaving among HIV+ and HIV− youths (15–24 years). School enrollment and socioeconomic status (SES) rose steadily from 1994 to 2013 among adolescents; orphanhood declined after availability of antiretroviral therapy. Antecedent factors associated with school enrollment included age, SES, orphanhood, marriage, family size, and the percent of family members

Numerous breast cancer patients who achieve an initial response to HER-targeted therapy rapidly develop resistance within one year, leading to treatment failure. Observations from clinical samples indicate that such resistance correlates with an increase in Src, EGFR, and PI3K/Akt activities and a decrease in PTEN activity. Furthermore, Akt survival signaling activation is also found in tumors treated by toxic chemotherapeutic agents. Because cotreatment with a PI3K inhibitor is a promising strategy to delay acquired resistance by preventing secondary gene activation, we therefore investigated the effects of a newly identified compound, (-)-Liriopein B (LB), on PI3K/Akt signaling activity in breast cancer cells. Our results showed that nontoxic doses of LB are able to inhibit AKT activation in both luminal-like MCF-7 and basal-like MDA-MB-231 breast cancer cells. Low doses of LB also inhibited cell migration, invasion, and cancer-stem cell sphere formation. Suppression of EGF-induced EGFR and ERK1/2 activation by LB might contribute in part to retardation of cancer progression. Furthermore, LB increases sensitivity of MDA-MB-231 cells to gefitinib in vitro, suggesting that EGFR may not be the only target of LB. Finally, a small scale in vitro kinase assay screen demonstrated that LB has a potent inhibitory effect on multiple kinases, including PI3K, Src, EGFR, Tie2, lck, lyn, RTK5, FGFR1, Abl, and Flt. In conclusion, this study demonstrates for the first time that the compound LB improves tumor therapeutic efficacy and suggests LB as a promising candidate for studying new leads in the development of kinase inhibitors.

A modified HPLC method for resveratrol determination for rapid screening of phenotypes of seedling population was developed for the Taiwan native Polygonum cuspidatum. The resveratrol concentration was 3.89 ± 1.03 mg.g−1 of the rhizome dry weight. In in vitro culturing of 11 acclimatized lines of genotype-dependent plants, which were replanted in the original location, only three genotypes showed a distant resemblance to regenerated lines and native plants. The genotype 051111 line in in vitro plants showed high resveratrol expression grown under acclimatized conditions and original locations. Resveratrol and its glucoside-piceid revealed mutual transformation depending on the growth climates.

Importance Polycyclic aromatic hydrocarbons are widespread urban air pollutants from combustion of fossil fuel and other organic material shown previously to be neurotoxic. Objective In a prospective cohort study, we evaluated the relationship between Attention Deficit Hyperactivity Disorder behavior problems and prenatal polycyclic aromatic hydrocarbon exposure, adjusting for postnatal exposure. Materials and Methods Children of nonsmoking African-American and Dominican women in New York City were followed from in utero to 9 years. Prenatal polycyclic aromatic hydrocarbon exposure was estimated by levels of polycyclic aromatic hydrocarbon- DNA adducts in maternal and cord blood collected at delivery. Postnatal exposure was estimated by the concentration of urinary polycyclic aromatic hydrocarbon metabolites at ages 3 or 5. Attention Deficit Hyperactivity Disorder behavior problems were assessed using the Child Behavior Checklist and the Conners Parent Rating Scale- Revised. Results High prenatal adduct exposure, measured by elevated maternal adducts was significantly associated with all Conners Parent Rating Scale-Revised subscales when the raw scores were analyzed continuously (N = 233). After dichotomizing at the threshold for moderately to markedly atypical symptoms, high maternal adducts were significantly associated with the Conners Parent Rating Scale-Revised DSM-IV Inattentive (OR = 5.06, 95% CI [1.43, 17.93]) and DSM-IV Total (OR = 3.37, 95% CI [1.10, 10.34]) subscales. High maternal adducts were positivity associated with the DSM-oriented Attention Deficit/Hyperactivity Problems scale on the Child Behavior Checklist, albeit not significant. In the smaller sample with cord adducts, the associations between outcomes and high cord adduct exposure were not statistically significant (N = 162). Conclusion The results suggest that exposure to polycyclic aromatic hydrocarbons encountered in New York City air may play a role in childhood Attention Deficit Hyperactivity Disorder behavior problems.

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure has been shown to increase DNA adduct levels and to affect neurodevelopment. Micronutrients may modify the adverse effect of PAH on neurodevelopment. Thus, we examined if micronutrient concentrations modified the association between PAH exposure and neurodevelopmental outcomes.151 children from a birth cohort who had micronutrient concentrations measured in cord blood and completed the Child Behavioral Checklist (CBCL), between the ages of 6 and 9 years, were evaluated. Prenatal airborne PAH exposure was measured by personal air monitoring. The betas and 95% CI for the associations of antioxidant concentrations and PAH exposure with each of the outcomes of CBCL raw score and dichotomized standardized T-score (based on clinical cutpoints) were estimated, respectively, by multivariable poisson and logistic models.Children below the median for alpha-tocopherol and gamma-tocopherol concentrations, compared to those above, were more likely to have thought problems, aggressive behavior and externalizing problems (p0.05). Lower carotenoid concentration was associated with more thought problems (MVβ=0.60, p0.001) and externalizing problems (MVβ=0.13, p0.05) for the same contrast. No statistically significant associations were observed between retinol concentrations and neurodevelopmental symptoms. Overall, no consistent patterns were observed when we examined the interaction between antioxidants (e.g., alpha-tocopherol) and PAH in relation to CBCL symptoms (e.g., internalizing and externalizing problems, p0.05).Lower alpha-tocopherol, gamma-tocopherol and carotenoid levels may adversely affect healthy neurodevelopment, even after accounting for PAH exposure. Future research to confirm these findings are warranted given the importance of identifying modifiable factors for reducing harmful PAH effects.

S-Petasin is the main sesquiterpene ofPetasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1–5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma.S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC50) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis,S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (Ki) of 25.3 and 18.1 μM, respectively. Both IC50andKivalues for PDE3 were significantly greater than those for PDE4.S-Petasin (10–30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (Penh) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition,S-petasin (10–30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG2alevel in serum of these mice. The PDE4Hvalue ofS-petasin was >300 μM; therefore, its PDE4H/PDE4Lvalue was calculated to be >17. In conclusion, the present results forS-petasin at least partially explain whyPetasites formosanusis used as a folk medicine to treat asthma in Taiwan.

In the presence of neostigmine (0.1 μM), S-isopetasin competitively antagonized cumulative acetylcholine-induced contractions in guinea pig trachealis, because the slope [1.18±0.15 (n=6)] of Schild's plot did not significantly differ from unity. The pA2 value of S-isopetasin was calculated to be 4.62±0.05 (n=18). The receptor binding assay for muscarinic receptors of cultured human tracheal smooth muscle cells (HTSMCs) was performed using [ 3 H]-N-methylscopolamine ([ 3 H]-NMS). Saturation binding assays were carried out with [ 3 H]-NMS in the presence (non-specific binding) and absence (total binding) of atropine (1 μM). Analysis of the Scatchard plot (y=0.247–1.306x, r 2 =0.95) revealed that the muscarinic receptor binding sites in cultured HTSMCs constituted a single population (nH=1.00). The equilibrium dissociation constant (Kd) and the maximal receptor density (Bmax) for [ 3 H]-NMS binding were 766 pM and 0.189 pmol/mg of protein, respectively. The −logIC50 values of S-isopetasin, methoctramine, and 1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) for displacing 0.4 nM [ 3 H]-NMS-specific binding were 5.05, 6.25, and 8.56, respectively, which suggests that [ 3 H]-NMS binding is predominantly on muscarinic M3 receptors of cultured HTSMCs. The inhibitory effectsofS-isopetasin onenhanced pause (Penh) value were similar to that ofipratropium bromide, areference drug. The duration of action of S-isopetasin (20 μM), also similar to that of ipratropium bromide (20 μM), was 3 h. In contrast to ipratropium bromide, which non-selectively acts on muscarinic receptors, S-isopetasin preferentially acts on muscarinic M3 receptors. In conclusion, S-isopetasin may be beneficial as a bronchodilator in the treatment of chronic obstructive pulmonary disease and asthma exacerbations. © 2008 Elsevier B.V. All rights reserved.