Sunlight Exposure and Phototherapy: Perspectives for Healthy Aging in an Era of COVID-19.

Most humans depend on sunlight exposure to satisfy their requirements for vitamin D3. However, the destruction of the ozone layer in the past few decades has increased the risk of skin aging and wrinkling caused by excessive exposure to ultraviolet (UV) radiation, which may also promote the risk of skin cancer development. The promotion of public health recommendations to avoid sunlight exposure would reduce the risk of skin cancer, but it would also enhance the risk of vitamin D3 insufficiency/deficiency, which may cause disease development and progression. In addition, the ongoing global COVID-19 pandemic may further reduce sunlight exposure due to stay-at-home policies, resulting in difficulty in active and healthy aging. In this review article, we performed a literature search in PubMed and provided an overview of basic and clinical data regarding the impact of sunlight exposure and vitamin D3 on public health. We also discuss the potential mechanisms and clinical value of phototherapy with a full-spectrum light (notably blue, red, and near-infrared light) as an alternative to sunlight exposure, which may contribute to combating COVID-19 and promoting active and healthy aging in current aged/superaged societies.

Moscatilin Inhibits Metastatic Behavior of Human Hepatocellular Carcinoma Cells: A Crucial Role of uPA Suppression via Akt/NF-κB-Dependent Pathway.

Hepatocellular carcinoma (HCC) frequently shows early invasion into blood vessels as well as intrahepatic metastasis. Innovations of novel small-molecule agents to block HCC invasion and subsequent metastasis are urgently needed. Moscatilin is a bibenzyl derivative extracted from the stems of a traditional Chinese medicine, orchid Dendrobium loddigesii. Although moscatilin has been reported to suppress tumor angiogenesis and growth, the anti-metastatic property of moscatilin has not been elucidated. The present results revealed that moscatilin inhibited metastatic behavior of HCC cells without cytotoxic fashion in highly invasive human HCC cell lines. Furthermore, moscatilin significantly suppressed the activity of urokinase plasminogen activator (uPA), but not matrix metalloproteinase (MMP)-2 and MMP-9. Interestingly, moscatilin-suppressed uPA activity was through down-regulation the protein level of uPA, and did not impair the uPA receptor and uPA inhibitory molecule (PAI-1) expressions. Meanwhile, the mRNA expression of uPA was inhibited via moscatilin in a concentration-dependent manner. In addition, the expression of phosphorylated Akt, rather than ERK1/2, was inhibited by moscatilin treatment. The expression of phosphor-IκBα, and -p65, as well as κB-luciferase activity were also repressed after moscatilin treatment. Transfection of constitutively active Akt (Myr-Akt) obviously restored the moscatilin-inhibited the activation of NF-κB and uPA, and cancer invasion in HCC cells. Taken together, these results suggest that moscatilin impedes HCC invasion and uPA expression through the Akt/NF-κB signaling pathway. Moscatilin might serve as a potential anti-metastatic agent against the disease progression of human HCC.

Characterization Of Secondary Metabolites From The Rhizome Of Cynara Scolymus And Their Antioxidant Properties.

The aerial portions of Cynara scolymus commonly have been eaten as vegetables or functional foods by the people lived in Mediterranean region. In preliminary antioxidant screening, the rhizome portions (CSR) of this species showed better potential than leaves ones. However, neither phytochemical nor pharmacology studies of CSR have been reported to date. The purpose of this research was to identify the active components from CSR through bioassay-guided fractionation. The antioxidant properties of secondary metabolites 1-9 were evaluated in this investigation. Compounds 4-6, 8, and 9 showed antioxidant activities based on DPPH free radical scavenging activity with IC50 values of 22.91-147.21 µM. Besides, compound 8 significantly and dose-dependently reduced H2O2-induced ROS levels in keratinocyte HaCaT cells without cytotoxicity toward HaCaT. Overall, our studies demonstrated the rhizome of C. scolymus could be used as a new natural antioxidant like the edible aerial portions and phenolic compounds are the active components.

Risk of major autoimmune diseases in female breast cancer patients: A nationwide, population-based cohort study.

BACKGROUND: Breast cancer is one of the most common malignancies among women. However, there remains no consensus in current literature on the incidence of autoimmune diseases among breast cancer patients. The purpose of this study was to evaluate the risks of major autoimmune diseases (MAD) including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and dermatomyositis (DMtis)/polymyositis (PM) in female breast cancer patients. METHODS: Using the Taiwanese National Health Insurance Research Database (NHIRD) records from 2003 to 2013, we identified newly-diagnosed female breast cancer patients and randomly selected females without breast cancer in the period 2007 to 2013 into a control group. We matched the two cohorts using a 1:4 ratio based on age, and the year of index date for comparison of the risk of major autoimmune diseases. We estimated and compared the relative risks of autoimmune diseases in female breast cancer patients and females without breast cancer. RESULTS: A total of 54,311 females with breast cancer and 217,244 matched females without breast cancer were included in this study. For SLE, the incidence rates were 2.3 (breast cancer group) vs. 10.0 (control group) per 100,000 women years; for RA rates were 19.3 (breast cancer group) vs. 42.7 (control group) per 100,000 women years; and for SS rates were 20.5 (breast cancer group) vs. 38.2 (control group) per 100,000 women years. After adjusting for potential confounders, the hazard ratios (95% confidence intervals) for female breast cancer patients vs. control group were 0.04 (0.01-0.24) for SLE; 0.03 (0.02-0.04) for RA; and 0.21 (0.09-0.48) for SS. CONCLUSION: Female breast cancer patients had lower risks of SLE, RA and SS when compared to female individuals without breast cancer. However, there was no significant difference in the risk of developing DMtis/PM between both groups.

Induction of Autophagic Death of Human Hepatocellular Carcinoma Cells by Armillaridin from Armillaria mellea.

The honey mushroom, Armillaria mellea, is known to have medicinal qualities and has been used in recent years as a health food and dietary supplement worldwide. In Asia, it is commonly consumed as an herbal medicine, being a key component of the Chinese preparation "Tien-ma". Here, we examined the antitumor effects of armillaridin, a bioactive compound isolated from A. mellea, on human hepatocellular carcinoma (HCC) cells. Armillaridin inhibited the growth of human Huh7, HepG2, and HA22T HCC cells, and its cytotoxicity was confirmed by observations of its induction of mitochondrial transmembrane potential collapse. However, armillaridin treatment did not result in large numbers of cells with fragmented chromosomal DNA, suggesting that apoptosis was not responsible for these effects. We therefore tested for signs of autophagic cell death following armillaridin administration. Armillaridin induced LC3 aggregation in green fluorescent protein-LC3-overexpressing cells. Moreover, flow cytometry and immunoblotting revealed that it increased the number of acridine orange-positive cells and upregulated autophagy-related proteins, respectively. Furthermore, armillaridin cytotoxicity was suppressed by the autophagy inhibitor 3-methyladenine. In summary, our results indicated that armillaridin induces HCC cell death by autophagy, and demonstrated the potential of armillaridin as an antihepatoma agent.

Bioavailability of the diterpenoid 14-deoxy-11,12-didehydroandrographolide in rats and up-regulation of hepatic drug-metabolizing enzyme and drug transporter expression.

BACKGROUND: 14-Deoxy-11,12-didehydroandrographolide (deAND) is the second most abundant diterpenoid in Andrographis paniculata (Burm. f.) Nees, a traditional medicine used in Asia. To date, the biological activity of deAND has not been clearly investigated. PURPOSE: In this study, we intended to examine the modulatory effect of deAND on hepatic drug metabolism as well as its bioavailability. STUDY DESIGN: deAND prepared from A. paniculata was orally given to Sprague-Dawley rats and changes in plasma deNAD were determined by HPLC-MS. Modulation of deAND on drug-metabolizing enzyme and drug transporter expression as well as the possible mechanism involved was examined in primary rat hepatocytes. RESULTS: After a single oral administration of 50 mg/kg deAND to rats, the maximum plasma concentration (Cmax), time to reach the Cmax, area under the curve (AUC0-24h), mean retention time, and half-life (t1/2) of deAND were 2.65 ± 0.68 µg/ml, 0.29 ± 0.15 h, 6.30 ± 1.66 µg/ml•h, 5.55 ± 2.52 h, and 3.56 ± 1.05 h, respectively. The oral bioavailability was 3.42%. In primary rat hepatocytes treated with up to 10 µM deAND, a dose-dependent increase was noted in the expression of cytochrome P450 (CYP) 1A1/2, CYP2C6, and CYP3A1/2; UDP-glucuronosyltransferase (UGT) 1A1, NAD(P)H:quinone oxidoreductase (NQO1), π form of GSH S-transferase (GSTP), multidrug resistance-associated protein 2, p-glycoprotein, and organic anion transporter protein 2B1. Immunoblotting assay and EMSA revealed that deAND increases the nuclear translocation and DNA binding activity of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and nuclear factor erythroid-derived 2-related factor 2 (Nrf2). Knockdown of AhR and Nrf2 expression abolished deAND induction of CYP isozymes and UGT1A1, NQO1, and GSTP expression, respectively. CONCLUSION: These results indicate that deAND quickly passes through enterocytes in rats and effectively up-regulates hepatic drug-metabolizing enzyme and drug transporter expression in an AhR-, PXR-, and Nrf2-dependent manner.

Effects of the hybrid of neuromuscular electrical stimulation and noxious thermal stimulation on upper extremity motor recovery in patients with stroke: a randomized controlled trial.

BACKGROUND: Neuromuscular electrical stimulation (NMES) and noxious thermal stimulation (NTS) have been developed and incorporated in stroke rehabilitation. OBJECTIVE: This study aimed to compare the effects of NMES, NTS, and the hybrid of NMES and NTS ("Hybrid") on motor recovery of upper extremity (UE) for patients with stroke. METHODS: We conducted a prospective, single-blind randomized controlled trial with concealed allocation. Forty-three patients with chronic stroke (onset >6 months) were randomly assigned to three groups (NMES, NTS, and "Hybrid"). In addition to conventional rehabilitation, participants received 30 min of NMES or 30 min of NTS or 15 min of NTS followed by 15 min of NMES. The treatment period was 8 weeks, 3 days/week, 30 min/time. The UE subscale of Fugl-Meyer assessment (UE-FMA, the primary outcome), Motricity index, modified Ashworth scale, and Barthel index were administered by a blinded assessor at baseline, posttreatment, and one-month follow-up. RESULTS: Most of the participants had mild-to-moderate disability in activity of daily living. No significant differences in the outcome measures at posttreatment and one-month follow-up were found among the NMES group (n = 13), NTS group (n = 13), and the hybrid of NMES and NTS group (n = 17). However, significant score changes in UE-FMA (p < 0.025) from baseline to posttreatment and one-month follow-up were found for the "Hybrid" group. CONCLUSIONS: This study reveals that the hybrid of NMES and NTS therapy appears to be beneficial to UE recovery after stroke but is not superior to NMES or NTS alone.

The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer's Disease-Related Pathologies in APP/PS1 Transgenic Mice.

Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid ß production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid ß and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid ß production and is worth to be further developed for AD therapeutic use.

Overexpression of Insig-2 inhibits atypical antipsychotic-induced adipogenic differentiation and lipid biosynthesis in adipose-derived stem cells.

Atypical antipsychotics (AAPs) are considered to possess superior efficacy for treating both the positive and negative symptoms of schizophrenia; however, AAP use often causes excessive weight gain and metabolic abnormalities. Recently, several reports have demonstrated that AAPs activate sterol regulatory element-binding protein (SREBP). SREBP, SREBP cleavage-activating protein (SCAP) and insulin-induced gene (Insig) regulate downstream cholesterol and fatty acid biosynthesis. In this study, we explored the effects of clozapine, olanzapine and risperidone on SREBP signaling and downstream lipid biosynthesis genes in the early events of adipogenic differentiation in adipose-derived stem cells (ASCs). After the induction of adipogenic differentiation for 2 days, all AAPs, notably clozapine treatment for 3 and 7 days, enhanced the expression of SREBP-1 and its downstream lipid biosynthesis genes without dexamethasone and insulin supplementation. Simultaneously, protein level of SREBP-1 was significantly enhanced via inhibition of Insig-2 expression. By contrast, SREBP-1 activation was suppressed when Insig-2 expression was upregulated by transfection with Insig-2 plasmid DNA. In summary, our results indicate that AAP treatment, notably clozapine treatment, induces early-stage lipid biosynthesis in ASCs. Such abnormal lipogenesis can be reversed when Insig-2 expression was increased, suggesting that Insig/SCAP/SREBP signaling may be a therapeutic target for AAP-induced weight gain and metabolic abnormalities.

NEUROPROTECTIVE EFFECT OF TERMINALIA CHEBULA EXTRACTS AND ELLAGIC ACID IN PC12 CELLS.

BACKGROUND: Alzheimer's disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aß25-35)-induced cell toxicity in an undifferentiated pheochromocytoma (PC12) cell line. MATERIALS AND METHODS: The T. chebula extracts were prepared using the methanol, water, and 95% ethanol. Specifically, the ellagic acid was obtained in our laboratory. Assays including cell toxicity and changes in intracellular reactive oxygen species (ROS) and calcium level were evaluated to examine the neuroprotective effects and mechanisms of the T. chebula extracts and ellagic acid. RESULTS: The methanolic and water extracts of T. chebula and ellagic acid exhibited the strongest neuroprotective activity against Aß25-35-induced PC12 cell damages at 0.5-5.0 µg/ml. The ellagic acid also exhibited partial neuroprotective activity against H2O2-induced PC12 cell damages at 0.5-5.0 µg/ml. The methanolic and water extracts of T. chebula and ellagic acid protected PC12 cells from Aß25-35-mediated cell damages and enhanced cell viability thorough two key mechanisms by: (1) inhibiting ROS production and (2) reducing calcium ion influx. CONCLUSION: The T. chebula represents a promising plant-source as medicine in the application for the treatment of AD. Further investigation focusing on the active component of T. chebula extracts e.g., ellagic acid is crucial to verify the neuroprotective efficacy and mechanisms in vivo.

Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma.

Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine "Tianma". Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alamarBlue(®) assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In conclusion, our study indicates the potential of armillarikin as an effective agent for hepatoma or leukemia therapies.

New Furanone and Sesquiterpene from the Pericarp of Calocedrus formosana.

One new γ-lactone, namely calolactone (1), together with one new drimane-type sesquiterpene, namely caloterpene (2), were isolated from the pericarp of Calocedrus formosana Florin. Their structures were elucidated by spectroscopic and mass spectrometric analysis.

Calophyllolide content in Calophyllum inophyllum at different stages of maturity and its osteogenic activity.

Calophyllum inophyllum is a coastal plant rich in natural substances. Its ingredients have been used for the development of an anti-human immunodeficiency virus (HIV) drug. In this study, we collected C. inophyllum fruit, and the ethanol extract of the fruit was chromatographically separated using silica gel and Sephadex LH-20 columns to obtain the major compound, calophyllolide. The fruits were harvested from September to December in 2011; a quantitative analysis of the calophyllolide content was conducted using HPLC to explore the differences between the different parts of the fruit during the growing season. The results showed that in fruits of C. inophyllum, calophyllolide exists only in the nuts, and dried nuts contain approximately 2 mg·g-1 of calophyllolide. The calophyllolide levels in the nuts decreased during maturity. In addition, calophyllolide dose-dependently enhanced alkaline phosphatase (ALP) activity in murine osteoblastic MC3T3-E1 cells, without significant cytotoxicity. The expression of osteoblastic genes, ALP and osteocalcin (OCN), were increased by calophyllolide. Calophyllolide induced osteoblasts differentiation also evidenced by increasing mineralization and ALP staining.

Armillaridin, a Honey Medicinal Mushroom, Armillaria mellea (Higher Basidiomycetes) Component, Inhibits Differentiation and Activation of Human Macrophages.

Armillaridin (AM) is an aromatic ester compound isolated from honey medicinal mushroom, Armillaria mellea, which has anti-cancer potential. This study was designed to examine the effects of AM on differentiation and activation macrophages, the major ontogeny of innate immunity. Macrophages were derived from CD14+ monocytes which were sorted from human peripheral blood mononuclear cells. Cell viability was assessed by trypan blue exclusion test. Cells were stained with Liu's dye for observation of morphology. Expression of surface antigens was examined by flow cytometric analysis. Phagocytosis and generation of reactive oxygen species (ROS), as functional assays, were evaluated by counting engulfed yeasts and DCFH-DA reaction. The viability of macrophages was not significantly reduced by AM. AM at nontoxic concentrations markedly increased cytoplasmic vacuoles. The expression of surface CD14, CD16, CD36, and HLA-DR was suppressed. The phagocytosis function, but not ROS production, of macrophages was inhibited by AM. Armillaridin could inhibit the differentiation and activation of human macrophages. It may have potential to be developed as a biological response modifier for inflammatory diseases.

A New Bithiophene from the Root of Echinops grijsii.

A new bithiophene, 5-(4-hydroxy-3-methoxy-1-butyny)-2,2'-bithiophene (1), and sixteen known thiophenes: 2-(3,4-dihydroxybut-1-ynyl)-5-(penta-1,3-diynyl)thiophene (2), α-terthienyl (3), 5-(3,4-dihydroxybut-1-ynyl)-2,2'-bithiophene (4), 5-acetyl-2,2'-bithiophene (5), 5-formyl-2,2'-bithiophene (6), methyl 2,2'-bithiophene-5-carboxylate (7), 5-(but-3-en-1-ynyl)-2,2'-bithiophene (8), 5-(4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (9), cardopatine (10), isocardopatine (11), 5-(3-hydroxy-4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (12), 5-(3-hydroxymethyl-3-isovaleroyloxyprop-1-ynyl)-2,2'-bithiophene (13), 5-(4-hydroxy-1-butynyl)-2,2'-bithiophene (14), 5-(4-acetoxy-1-butynl)-2,2'-bithiophene (15), 2,2'-bithiophene-5-carboxylic acid (16) and 2-(4-hydroxybut-1-ynyl)-5-(penta-1,3-diynyl)thiophene (17) were isolated from the roots of Echinops grjisii Hance. Among them, compounds 6, 7 and 16 were isolated from a natural source for the first time. Compounds 2, 4 and 14 exhibited significant anti-inflammatory activity against nitrite of LPS-stimulated production in the RAW 264.7 cell line.

Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.

PURPOSE: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. METHODS AND MATERIALS: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. RESULTS: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). CONCLUSIONS: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

Moscatilin induces apoptosis and mitotic catastrophe in human esophageal cancer cells.

Moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii, has been shown to possess anticancer activity. We examined the effect of moscatilin on human esophageal cancer cells, including squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cells and its possible mechanisms. Moscatilin suppressed the growth of both the histological cell lines in a dose- and time-dependent manner. Morphological changes indicative of apoptosis and mitotic catastrophe were observed following moscatilin treatment. The population of cells in the sub-G1 phase and polyploidy phase significantly increased after treatment. Immunofluorescence revealed multipolar mitosis and subsequent multinucleation in moscatilin-treated cells, indicating the development of mitotic catastrophe. Western blot showed a marked increase in expressions of polo-like kinase 1 and cyclin B1 after exposure to moscatilin. In conclusion, moscatilin inhibits growth and induces apoptosis and mitotic catastrophe in human esophageal SCC- and ADC-derived cell lines, indicating that moscatilin has broad potential against esophageal cancer.

Cudrania cochinchinensis attenuates amyloid ß protein-mediated microglial activation and promotes glia-related clearance of amyloid ß protein.

BACKGROUND: Microglial inflammation may significantly contribute to the pathology of Alzheimer's disease. To examine the potential of Cudrania cochinchinensis to ameliorate amyloid ß protein (Aß)-induced microglia activation, BV-2 microglial cell line, and the ramified microglia in the primary glial mixed cultured were employed. RESULTS: Lipopolysaccharide (LPS), Interferon-γ (IFN-γ), fibrillary Aß (fAß), or oligomeric Aß (oAß) were used to activate microglia. LPS and IFN-γ, but not Aßs, activated BV-2 cells to produce nitric oxide through an increase in inducible nitric oxide synthase (iNOS) expression without significant effects on cell viability of microglia. fAß, but not oAß, enhanced the IFN-γ-stimulated nitric oxide production and iNOS expression.The ethanol/water extracts of Cudrania cochinchinensis (CC-EW) and the purified isolated components (i.e. CCA to CCF) effectively reduced the nitric oxide production and iNOS expression stimulated by IFN-γ combined with fAß. On the other hand, oAß effectively activated the ramified microglia in mixed glial culture by observing the morphological alteration of the microglia from ramified to amoeboid. CC-EW and CCB effectively prohibit the Aß-mediated morphological change of microglia. Furthermore, CC-EW and CCB effectively decreased Aß deposition and remained Aß in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aß clearance. Results are expressed as mean ± S.D. and were analyzed by ANOVA with post-hoc multiple comparisons with a Bonferroni test. CONCLUSIONS: The components of Cudrania cochinchinensis including CC-EW and CCB are potential for novel therapeutic intervention for Alzheimer's disease.

Therapeutic and radiosensitizing effects of armillaridin on human esophageal cancer cells.

Background. Armillaridin (AM) is isolated from Armillaria mellea. We examined the anticancer activity and radiosensitizing effect on human esophageal cancer cells. Methods. Human squamous cell carcinoma (CE81T/VGH and TE-2) and adenocarcinoma (BE-3 and SKGT-4) cell lines were cultured. The MTT assay was used for cell viability. The cell cycle was analyzed using propidium iodide staining. Mitochondrial transmembrane potential was measured by DiOC6(3) staining. The colony formation assay was performed for estimation of the radiation surviving fraction. Human CE81T/VGH xenografts were established for evaluation of therapeutic activity in vivo. Results. AM inhibited the viability of four human esophageal cancer cell lines with an estimated concentration of 50% inhibition (IC50) which was 3.4-6.9 µM. AM induced a hypoploid cell population and morphological alterations typical of apoptosis in cells. This apoptosis induction was accompanied by a reduction of mitochondrial transmembrane potential. AM accumulated cell cycle at G2/M phase and enhanced the radiosensitivity in CE81T/VGH cells. In vivo, AM inhibited the growth of CE81T/VGH xenografts without significant impact on body weight and white blood cell counts. Conclusion. Armillaridin could inhibit growth and enhance radiosensitivity of human esophageal cancer cells. There might be potential to integrate AM with radiotherapy for esophageal cancer treatment.

Active Component of Antrodia cinnamomea Mycelia Targeting Head and Neck Cancer Initiating Cells through Exaggerated Autophagic Cell Death.

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer. Previously, we identify head and neck cancer initiating cells (HN-CICs), which are highly tumorigenic and resistant to conventional therapy. Therefore, development of drug candidates that effectively target HN-CICs would benefit future head and neck cancer therapy. In this study, we first successfully screened for an active component, named YMGKI-1, from natural products of Antrodia cinnamomea Mycelia (ACM), which can target the stemness properties of HNSCC. Treatment of YMGKI-1 significantly downregulated the aldehyde dehydrogenase (ALDH) activity, one of the characteristics of CIC in HNSCC cells. Additionally, the tumorigenic properties of HNSCC cells were attenuated by YMGKI-1 treatment in vivo. Further, the stemness properties of HN-CICs, which are responsible for the malignancy of HNSCC, were also diminished by YMGKI-1 treatment. Strikingly, YMGKI-1 also effectively suppressed the cell viability of HN-CICs but not normal stem cells. Finally, YMGKI-1 induces the cell death of HN-CICs by dysregulating the exaggerated autophagic signaling pathways. Together, our results indicate that YMGKI-1 successfully lessens stemness properties and tumorigenicity of HN-CICs. These findings provide a new drug candidate from purified components of ACM as an alternative therapy for head and neck cancer in the future.