Effects of Ganodermanondiol, a New Melanogenesis Inhibitor from the Medicinal Mushroom Ganoderma lucidum. PUMID/DOI：DOI: 10.3390/ijms17111798 Int J Mol Sci. 2016 Oct 27;17(11). pii: E1798. Ganoderma lucidum, a species of the Basidiomycetes class, has been attracting international attention owing to its wide variety of biological activities and great potential as an ingredient in skin care cosmetics including "skin-whitening" products. However, there is little information available on its inhibitory effect against tyrosinase activity. Therefore, the objectives of this study were to investigate the chemical composition of G. lucidum and its inhibitory effects on melanogenesis. We isolated the active compound from G. lucidum using ethanol extraction and ethyl acetate fractionation. In addition, we assayed its inhibitory effects on tyrosinase activity and melanin biosynthesis in B16F10 melanoma cells. In this study, we identified a bioactive compound, ganodermanondiol, which inhibits the activity and expression of cellular tyrosinase and the expression of tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF), thereby decreasing melanin production. Furthermore, ganodermanondiol also affected the mitogen-activated protein kinase (MAPK) cascade and cyclic adenosine monophosphate (cAMP)-dependent signaling pathway, which are involved in the melanogenesis of B16F10 melanoma cells. The finding that ganodermanondiol from G. lucidum exerts an inhibitory effect on tyrosinase will contribute to the use of this mushroom in the preparation of skin care products in the future. Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2-mediated antioxidant enzymes. PUMID/DOI：DOI: 10.1016/j.fct.2012.12.016 Food Chem Toxicol. 2013 Mar;53:317-24. Ganodermanondiol, a biologically active compound, was isolated from the Lingzhi mushroom (Ganoderma lucidum). The present study examined the protective effects of ganodermanondiol against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity. Ganodermanondiol protected human liver-derived HepG2 cells through nuclear factor-E2-related factor 2 (Nrf2) pathway-dependent heme oxygenase-1 expressions. Moreover, ganodermanondiol increased cellular glutathione levels and the expression of the glutamine-cysteine ligase gene in a dose-dependent manner. Furthermore, ganodermanondiol exposure enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its upstream kinase activators, LKB1 and Ca(2+)/calmodulin-dependent protein kinase-II (CaMKII). This study indicates that ganodermanondiol exhibits potent cytoprotective effects on t-BHP-induced hepatotoxicity in human liver-derived HepG2 cells, presumably through Nrf2-mediated antioxidant enzymes and AMPK. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. PUMID/DOI：9810695 Chem Pharm Bull (Tokyo). 1998 Oct;46(10):1607-12. Two new lanostane-type triterpenes, lucidumol A and ganoderic acid beta, were isolated from the spores of Ganoderma (G.) lucidum, together with a new natural one and seven that were known. The structures of the new triterpenes were determined as (24S)-24,25-dihydroxylanost-8-ene-3,7-dione and 3 beta,7 beta-dihydroxy-11,15-dioxolanosta-8,24(E)-dien-26-oic acid, respectively, by chemical and spectroscopic means. The quantitative analyses of 5 fruiting bodies, antlered form and spores of G. lucidum were performed by high performance liquid chromatography and demonstrated that ganoderic alcohol and acid contents were quite high in the spore. Of the compound isolated, ganoderic acid beta, (24S)-lanosta-7,9(11)-diene-3 beta,24,25-triol (called lucidumol B), ganodermanondiol, ganodermanontriol and ganolucidic acid A showed significant anti-human immunodeficiency virus (anti-HIV)-1 protease activity with IC50 values of 20-90 microM. Triterpenoids from Ganoderma lucidum inhibit the activation of EBV antigens as telomerase inhibitors. PUMID/DOI：DOI: 10.3892/etm.2017.4883 Exp Ther Med. 2017 Oct;14(4):3273-3278. Nasopharyngeal carcinoma (NPC) is a malignant disease that threatens the health of humans. To find effective agents for the inhibition of Epstein-Barr virus (EBV) infection, which is associated with NPC, a phytochemical investigation of Ganoderma lucidum was carried out in the present study. Five triterpenoids were identified, including ganoderic acid A (compound 1), ganoderic acid B (compound 2), ganoderol B (compound 3), ganodermanontriol (compound 4), and ganodermanondiol (compound 5), on the basis of spectroscopic analysis. An inhibition of EBV antigens activation assay was implemented to elucidate the triterpenoids from G. lucidum and potentially prevent NPC. All the triterpenoids showed significant inhibitory effects on both EBV EA and CA activation at 16 nmol. At 3.2 nmol, all the compounds moderately inhibited the activation of the two antigens. The activity of telomerase was inhibited by these triterpenoids at 10 μM. Molecular docking demonstrated that compound 1 was able to inhibit telomerase as a ligand. In addition, the physicochemical properties of these compounds were calculated to elucidate their drug-like properties. These results provided evidence for the application of these triterpenoids and whole G. lucidum in the treatment of NPC.
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Comparing self-rating health responses across individuals and cultures is misleading due to different reporting behaviors. Anchoring vignettes is a technique that allows identifying and adjusting self-rating responses for reporting heterogeneity (RH).
This article aims to test two crucial assumptions of vignette equivalence (VE) and response consistency (RC) that are required to be met before vignettes can be used to adjust self-rating responses for RH.
We used self-ratings, vignettes, and objective measures covering domains of mobility and cognition from the WHO study on global AGEing and adult health, administered to older adults aged 50 years and above from eight low- and middle-income countries in Africa and Asia. For VE, we specified a hierarchical ordered probit (HOPIT) model to test for equality of perceived vignette locations. For RC, we tested for equality of thresholds that are used to rate vignettes with thresholds derived from objective measures and used to rate their own health function.
There was evidence of RH in self-rating responses for difficulty in mobility and cognition. Assumptions of VE and RC between countries were violated driven by age, sex, and education. However, within a country context, assumption of VE was met in some countries (mainly in Africa, except Tanzania) and violated in others (mainly in Asia, except India).
We conclude that violation of assumptions of RC and VE precluded the use of anchoring vignettes to adjust self-rated responses for RH across countries in Asia and Africa.
reporting heterogeneity, mobility, cognition, self-rating, anchoring vignettes, vignette equivalence, response consistency
Use of anchoring vignettes to evaluate health reporting behavior amongst adults aged 50 years and above in Africa and Asia - testing assumptions
Siddhivinayak Hirve,1,2,* Xavier Gomez-Olive,3 Samuel Oti,4 Cornelius Debpuur,5 Sanjay Juvekar,1 Stephen Tollman,3 Yulia Blomstedt,2 Stig Wall,2,# and Nawi Ng2,#
Combined estrogen-progestogen contraceptives (oral contraceptives or OCs) and progestogen-only contraceptives (POCs) are synthetic steroids that bind to steroid hormone receptors, which are widespread throughout the body. They have a profound effect on cellular physiology. Combined OCs have been classified by the International Agency for Research on Cancer (IARC) as Group 1 carcinogens, but their findings have not been updated recently. In order to update the information and better understand the impact that OCs and POCs have on the risk of development of cancers, a comprehensive literature search was undertaken, focusing on more recently published papers. In agreement with the IARC, the recent literature confirms an increased risk of breast cancer and cervical cancer with the use of OCs. The recent literature also confirms the IARC conclusion that OCs decrease the risk of ovarian and endometrial cancers. However, there is little support from recent studies for the IARC conclusion that OCs decrease the risk of colorectal cancer or increase the risk of liver cancer. For liver cancer, this may be due to the recent studies having been performed in areas where hepatitis is endemic. In one large observational study, POCs also appear to increase the overall risk of developing cancer. OCs and POCs appear to increase the overall risk of cancer when carefully performed studies with the least intrinsic bias are considered.
Breast cancer, Cancer, Cervical cancer, Colorectal cancer, Contraception, Contraceptive, Endometrial cancer, Estrogen, Ovarian cancer, Progestogen
Association of Combined Estrogen-Progestogen and Progestogen-Only Contraceptives with the Development of Cancer
William V. Williams, MD,1,2 Louise A. Mitchell, MTS, MA,3 S. Kathleen Carlson,4 and Kathleen M. Raviele, MD5
There are well-documented associations of glaucoma with high-dose radiation exposure, but only a single study suggesting risk of glaucoma, and less conclusively macular degeneration, associated with moderate-dose exposure. We assessed risk of glaucoma and macular degeneration associated with occupational eye-lens radiation dose, using participants from the US Radiologic Technologists Study, followed from the date of surveys in 1994-1998, 2003-2005 to the earliest of diagnosis of glaucoma or macular degeneration, cancer other than non-melanoma skin cancer, or date of last survey (2012-2014). We excluded those with baseline disease or previous radiotherapy history. Cox proportional hazards models with age as timescale were used. There were 1631 cases of newly self-reported doctor-diagnosed cases of glaucoma and 1331 of macular degeneration among 69,568 and 69,969 eligible subjects, respectively. Estimated mean cumulative eye-lens absorbed dose from occupational radiation exposures was 0.058 Gy. The excess relative risk/Gy for glaucoma was −0.57 (95% CI −1.46, 0.60, p = 0.304) and for macular degeneration was 0.32 (95% CI −0.32, 1.27, p = 0.381), suggesting that there is no appreciable risk for either endpoint associated with low-dose and low dose-rate radiation exposure. Since this is the first examination of glaucoma and macular degeneration associated with low-dose radiation exposure, this result needs to be replicated in other low-dose studies.
Occupational radiation exposure and glaucoma and macular degeneration in the US radiologic technologists
Mark P. Little,corresponding author1 Cari M. Kitahara,1 Elizabeth K. Cahoon,1 Marie-Odile Bernier,1,2 Raquel Velazquez-Kronen,1 Michele M. Doody,1 David Borrego,1 Jeremy S. Miller,3 Bruce H. Alexander,4 Steven L. Simon,1 Dale L. Preston,5 Craig Meyer,4 Martha S. Linet,1 and Nobuyuki Hamada6