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Merkel cell carcinoma (MCC) is a lethal skin cancer that metastasizes rapidly. Few effective treatments are available for patients with metastatic MCC. Poor intratumoral T cell infiltration and activation are major barriers that prevent MCC eradication by the immune system. However, the mechanisms that drive the immunologically restrictive tumor microenvironment remain poorly understood. In this study, we discovered that the innate immune regulator stimulator of IFN genes (STING) is completely silenced in MCCs. To reactivate STING in MCC, we developed an application of a human STING mutant, STINGS162A/G230I/Q266I, which we found to be readily stimulated by a mouse STING agonist, DMXAA. This STING molecule was efficiently delivered to MCC cells via an AAV vector. Introducing STINGS162A/G230I/Q266I expression and stimulating its activity by DMXAA in MCC cells reactivates their antitumor inflammatory cytokine/chemokine production. In response to MCC cells with restored STING, cocultured T cells expressing MCPyV-specific T cell receptors (TCRs) show increased cytokine production, migration toward tumor cells, and tumor cell killing. Our study therefore suggests that STING deficiency contributes to the immune suppressive nature of MCCs. More importantly, DMXAA stimulation of STINGS162A/G230I/Q266I causes robust cell death in MCCs as well as several other STING-silenced cancers. Because tumor antigens and DNA released by dying cancer cells have the potential to amplify innate immune response and activate antitumor adaptive responses, our finding indicates that targeted delivery and activation of STINGS162A/G230I/Q266I in tumor cells holds great therapeutic promise for the treatment of MCC and many other STING-deficient cancers.
AssuntosCarcinoma de Célula de Merkel/imunologia , Proteínas de Membrana/imunologia , Neoplasias Cutâneas/imunologia , Carcinoma de Célula de Merkel/genética , Linhagem Celular Tumoral , Humanos , Imunidade Inata , Proteínas de Membrana/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/genética , Xantonas/farmacologia
Non-small cell lung cancer (NSCLC) is often complicated by pulmonary infection, which affects treatment and prognosis. Bacterial lipopolysaccharide (LPS) is an effective stimulator of inflammatory cytokine production, and previous studies have reported that LPS promotes tumor invasion and metastasis. Mangiferin is a plant-derived C-glucosylxanthone with many biological activities, such as antioxidation and anti-inflammation. This research mainly explored the mechanism of its antitumor activities on LPS-induced A549, NCI-H460, and NCI-H520 NSCLC cells. We determined that mangiferin exhibits growth inhibiting activity against LPS-induced NSCLC cells through the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. In addition, mangiferin reversed the LPS-induced downregulation of E-cadherin (epithelial marker); conversely, it significantly inhibited the expression of raised vimentin (mesenchymal markers). Moreover, the ability of NSCLC cells to migrate, as evidenced by the wound healing and transwell migration assays, and the expression of CXCR4 increased by LPS were significantly repressed by mangiferin. In addition, mangiferin markedly mediated protein levels of PER1 and NLRP3 in LPS-induced NSCLC cells and reduced the secretion of IL-1ß. These results indicate that mangiferin is not only a remarkable anti-inflammatory compound but also an antitumor agent; thus, it has the potential for being developed into anti-inflammatory and antitumor drugs in the future.
AssuntosAntineoplásicos Fitogênicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas Circadianas Period/genética , Xantonas/farmacologia , Células A549 , Antígenos CD/genética , Caderinas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Humanos , Lipopolissacarídeos/farmacologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA Interferente Pequeno/genética , Receptores CXCR4/genética , Transdução de Sinais , Vimentina/metabolismo
OBJECTIVE: Mangiferin (MF), a xanthonoid derived from Mangifera indica, has shown therapeutic effects on various human diseases including cancer, diabetes, and obesity. Nonetheless, the influence of MF on non-shivering thermogenesis and its underlying mechanism in browning remains unclear. Here, our aim was to investigate the effects of MF on browning and its molecular mechanisms in murine C3H10T1/2 mesenchymal stem cells (MSCs). MATERIALS/METHODS: To determine the function of MF on browning, murine C3H10T1/2 MSCs were treated with MF in an adipogenic differentiation cocktail and the thermogenic and correlated metabolic responses were assessed using MF-mediated signalling. Human adipose-derived MSCs were differentiated and treated with MF to confirm its role in thermogenic induction. RESULTS: MF treatment induced the expression of a brown-fat signature, UCP1, and reduced triglyceride (TG) in C3H10T1/2 MSCs. MF also induced the expression of major thermogenesis regulators: PGC1α, PRDM16, and PPARγ and up-regulated the expression of beiging markers CD137, HSPB7, TBX1, and COX2 in both murine C3H10T1/2 MSCs and human adipose-derived mesenchymal stem cells (hADMSC). We also observed that MF treatment increased the mitochondrial DNA and improved mitochondrial homeostasis by regulating mitofission-fusion plasticity via suppressing PINK1-PRKN-mediated mitophagy. Furthermore, MF treatment improved mitochondrial respiratory function by increasing mitochondrial oxygen consumption and expression of oxidative-phosphorylation (OXPHOS)-related proteins. Chemical-inhibition and gene knockdown experiments revealed that ß3-AR-dependent PKA-p38 MAPK-CREB signalling is crucial for MF-mediated brown-fat formation via suppression of mitophagy in C3H10T1/2 MSCs. CONCLUSIONS: MF promotes the brown adipocyte phenotype by suppressing mitophagy, which is regulated by PKA-p38MAPK-CREB signalling in C3H10T1/2 MSCs. Thus, we propose that MF may be a good browning inducer that can ameliorate obesity.
AssuntosTecido Adiposo Marrom/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Mitofagia/genética , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética , Xantonas/farmacologia , Adipócitos Marrons/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C3H , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Proteínas Quinases/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Termogênese/genética , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos
Mangiferin is a well-known xanthone extracted from mango leaves (Mangifera indica Linn). Mangiferin is widely distributed in the bark, peel, leaf, seed, stalk, and kernel of mango and higher plants. The pharmacological properties of mangiferin, including its antioxidant, anticancer, antiaging, antiviral, hepatoprotective, analgesic, and immunomodulatory activities, have been described in several studies. We investigated the effect of mangiferin on isoproterenol-induced apoptosis. Experimental heart failure was induced in rats by intraperitoneal administration of isoproterenol (5 mg/kg) for 7 consecutive days. Rats were divided into five groups: group I (sham rats), group II (isoproterenol alone control), group III (isoproterenol + 25 mg/kg mangiferin), group IV (isoproterenol + 50 mg/kg mangiferin), and group V (isoproterenol + 0.0225 mg/kg digitalis as a positive control). Hemodynamic parameters and body weight, heart weight and liver weight, apoptosis induction, and caspase-3, Bax, and Bcl-2 protein levels were measured, and a histopathological analysis of cardiomyocytes was performed. In addition, apoptosis and protein expression of caspase-3, cleaved caspase-3, Bax, and Bcl-2 were measured in cardiac H9c2 cells. Mangiferin supplementation significantly increased heart rate and improved the maximum rate of decrease in left ventricular (LV) pressure, the maximum rate of increase in LV pressure, and LV systolic pressure. Mangiferin reduced inflammatory cell infiltration and the number of broken myocardial fibers, and decreased apoptosis in cardiomyocytes by reducing proteins levels of caspase-3 and Bax and increasing those of Bcl-2. Our findings suggest that mangiferin has a cardioprotective effect against isoproterenol-induced apoptosis in cardiomyocytes.
AssuntosApoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Insuficiência Cardíaca/induzido quimicamente , Coração/efeitos dos fármacos , Xantonas/farmacologia , Animais , Cardiotônicos/administração & dosagem , Injeções Intraperitoneais , Isoproterenol/administração & dosagem , Isoproterenol/farmacologia , Ratos
Inflammation is the body's self-protective response to multiple stimulus, from external harmful substances to internal danger signals released after trauma or cell dysfunction. Many diseases are considered to be related to inflammation, such as cancer, metabolic disorders, aging, and neurodegenerative diseases. Current therapeutic approaches include mainly non-steroidal anti-inflammatory drugs and glucocorticoids, which are generally of limited effectiveness and severe side-effects. Thus, it is urgent to develop novel effective anti-inflammatory therapeutic agents. Xanthones, a unique scaffold with a 9H-Xanthen-9-one core structure, widely exist in natural sources. Till now, over 250 xanthones were isolated and identified in plants from the families Gentianaceae and Hypericaceae. Many xanthones have been disclosed with anti-inflammatory properties on different models, either in vitro or in vivo. Herein, we provide a comprehensive and up-to-date review of xanthones with anti-inflammatory properties, and analyzed their drug likeness, which might be potential therapeutic agents to fight against inflammation-related diseases.
AssuntosAnti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Xantonas/química , Xantonas/farmacologia , Humanos , Relação Estrutura-Atividade
Introduction: Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumor-penetrating peptide iRGD could improve the anti-tumor activity. Methods: The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size. Results: The thermo-sensitive properties of hydrogels were characterized by 3-4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased. Discussion: The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.
AssuntosAntineoplásicos/uso terapêutico , Hidrogéis/química , Nanopartículas/química , Oligopeptídeos/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Temperatura , Xantonas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Bombyx , Linhagem Celular Tumoral , Fibroínas/química , Glicerol/química , Humanos , Derivados da Hipromelose/química , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Porosidade , Neoplasias Gástricas/patologia , Distribuição Tecidual , Xantonas/farmacologia
Alpha-mangostin (α-mangostin) has been identified as a naturally occurring compound with potential anticancer properties. It can induce apoptosis and inhibit the growth and metastasis of cancer cells. Moreover, α-mangostin reduces the mechanical stiffness of lung cancer cells. The objective of this study was to determine the effect of α-mangostin on the mechanical stiffness of various cells, as well as cell viability. The following cell types were examined: human fibroblast TIG-1 cells, human cancerous HeLa cells, human embryonic kidney HEK293 cells, mouse macrophage RAW 264.7 cells, and human myeloblasts KG-1 cells. Cells were treated with α-mangostin, and then examined for cell viability, actin cytoskeletal structures, and surface mechanical stiffness using atomic force microscopy. α-Mangostin demonstrated cytotoxicity against TIG-1, HeLa, HEK293, and KG-1 cells, but not against RAW 264.7 cells. The cytotoxic effect of α-mangostin varies according to cell type. On the other hand, α-mangostin reduced the mechanical stiffness of all cell types, including RAW 264.7 cells. Upon treatment with α-mangostin, F-actin was slightly reduced but the actin cytoskeletal structures were little altered in these cells. Thus, reducing mechanical stiffness of animal cells is an inherent effect of α-mangostin. Our results show that α-mangostin is a naturally occurring compound with potential to change the actin cytoskeletal micro-structures and reduce the surface stiffness of various cells.
AssuntosAntineoplásicos Fitogênicos/farmacologia , Fenômenos Biomecânicos/efeitos dos fármacos , Neoplasias/patologia , Xantonas/farmacologia , Animais , Células HeLa , Humanos , Camundongos , Células RAW 264.7
According to cancer stem cell theory, only a limited number of self-renewing and cloning cells are responsible for tumor relapse after a period of remittance. The aim of the present study was to investigate the effects of Doxorubicin and α-Mangostin, two antiproliferative drugs, on both tumor bulk and stem cells in multicellular tumor spheroids originated from the luminal MCF-7 breast cancer cell line. A new and original fluorimetric assay was used to selectively measure the activity of the retinaldehyde-dependent isoenzymes of aldehyde dehydrogenase (RALDH), which are markers of a subpopulation of breast cancer stem cells. The administration of 5 µg/ml (12.2 µM) α-Mangostin for 48 h provoked: i) a marked disaggregation of the spheroids, leading to a doubling of their volume (p < 0.01), ii) a 40 % decrease in cell viability (p < 0.01), evaluated by the acid phosphatase assay, and iii) a reduction by more than 90 % of RALDH activity. By contrast, Doxorubicin given for 48 h in the range of 0.1-40 µM did not significantly reduce cell viability and caused only a modest modification of the spheroid morphology. Moreover, 40 µM Doxorubicin increased RALDH activity 2.5-fold compared to the untreated sample. When the two drugs were administered together using 5 µg/ml α-Mangostin, the IC50 of Doxorubicin referred to cell viability decreased six-fold and the RALDH activity was further reduced. In conclusion, the combined administration of Doxorubicin and α-Mangostin provoked a significant cytotoxicity and a remarkable inhibition of RALDH activity in MCF-7 tumor spheroids, suggesting that these drugs could be effective in reducing cell stemness in luminal breast cancer.
AssuntosNeoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Xantonas/farmacologia , Aldeído Desidrogenase/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Feminino , Humanos , Concentração Inibidora 50 , Células MCF-7 , Retinaldeído/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Xantonas/administração & dosagem
The cell wall-targeting echinocandin antifungals, although potent and well tolerated, are inadequate in treating fungal infections due to their narrow spectrum of activity and their propensity to induce pathogen resistance. A promising strategy to overcome these drawbacks is to combine echinocandins with a molecule that improves their activity and also disrupts drug adaptation pathways. In this study, we show that puupehenone (PUUP), a marine-sponge-derived sesquiterpene quinone, potentiates the echinocandin drug caspofungin (CAS) in CAS-resistant fungal pathogens. We have conducted RNA sequencing (RNA-seq) analysis, followed by genetic and molecular studies, to elucidate PUUP's CAS-potentiating mechanism. We found that the combination of CAS and PUUP blocked the induction of CAS-responding genes required for the adaptation to cell wall stress through the cell wall integrity (CWI) pathway. Further analysis showed that PUUP inhibited the activation of Slt2 (Mpk1), the terminal mitogen-activated protein (MAP) kinase in this pathway. We also found that PUUP induced heat shock response genes and inhibited the activity of heat shock protein 90 (Hsp90). Molecular docking studies predicted that PUUP occupies a binding site on Hsp90 required for the interaction between Hsp90 and its cochaperone Cdc37. Thus, we show that PUUP potentiates CAS activity by a previously undescribed mechanism which involves a disruption of Hsp90 activity and the CWI pathway. Given the requirement of the Hsp90-Cdc37 complex in Slt2 activation, we suggest that inhibitors of this complex would disrupt the CWI pathway and synergize with echinocandins. Therefore, the identification of PUUP's CAS-potentiating mechanism has important implications in the development of new antifungal combination therapies.IMPORTANCE Fungal infections cause more fatalities worldwide each year than malaria or tuberculosis. Currently available antifungal drugs have various limitations, including host toxicity, narrow spectrum of activity, and pathogen resistance. Combining these drugs with small molecules that can overcome these limitations is a useful strategy for extending their clinical use. We have investigated the molecular mechanism by which a marine-derived compound potentiates the activity of the antifungal echinocandin caspofungin. Our findings revealed a mechanism, different from previously reported caspofungin potentiators, in which potentiation is achieved by the disruption of Hsp90 activity and signaling through the cell wall integrity pathway, processes that play important roles in the adaptation to caspofungin in fungal pathogens. Given the importance of stress adaptation in the development of echinocandin resistance, this work will serve as a starting point in the development of new combination therapies that will likely be more effective and less prone to pathogen resistance.
AssuntosCaspofungina/farmacologia , Parede Celular/efeitos dos fármacos , Farmacorresistência Fúngica/genética , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Saccharomyces cerevisiae/genética , Sesquiterpenos/farmacologia , Xantonas/farmacologia , Antifúngicos/farmacologia , Parede Celular/metabolismo , Proteínas Fúngicas/genética , Simulação de Acoplamento Molecular , Saccharomyces cerevisiae/efeitos dos fármacos , Análise de Sequência de RNA
Techno-biofunctional characteristics of nanoemulsion and (nano)emulgel loaded with mangostin extracts were elucidated. Crude mangostins from mangosteen peels recovered by virgin coconut oil (VCO), mixed VCO and propylene glycol (PG), and pure PG were used. The extracts were loaded in the dispersed phase in the presence of mixed surfactants (Tween20/Span20) with a varying hydrophilic-lipophilic balance (HLB) from 10.2 to 15.1. Results showed that globular and uniformly distributed droplets of the nanoemulsion were observed. The small particle sizes (typically 18-62 nm) with the zeta potential of -39 to -54.5 mV were obtained when mixed emulsifiers with HLB values of 12.6 and 15.1 were employed. With HLB values of 12.6 and 15.1, nanoemulsions loaded with mangostin extracts prepared with mixed VCO-PG and pure PG-based extracts showed approximately a 2 to 3-fold lower droplet size diameter when compared with the VCO-based extract. For the stability test, all nanoemulsions were stable over three freeze-thaw cycles with some changes in pH, zeta potential, and droplet size. The DPPHâ scavenging activity, H2O2 scavenging activity, reducing power and antibacterial activities (E. coli and S. aureus) of the nanoemulsions were greater than their corresponding bulk extracts. Nanoemulgels produced by embedding the nanoemulsions in a hydrogel matrix was homogeneous and creamy yellow-white in appearance. The nanoemulgels had a higher mangostin release (87-92%) than their normal emulgels (74-78%). Therefore, this study presented the feasibility of nanoemulsions and nanoemulgels loaded with mangostin extracts as a promising delivery system for bioactive polyphenol in food supplements, pharmaceuticals and cosmetics.
AssuntosAntibacterianos/química , Nanopartículas/química , Extratos Vegetais/farmacologia , Xantonas/química , Antibacterianos/farmacologia , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Óleo de Coco/química , Emulsões/química , Emulsões/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Depuradores de Radicais Livres/química , Peróxido de Hidrogênio/química , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Picratos/química , Picratos/farmacologia , Extratos Vegetais/química , Propilenoglicol/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Xantonas/farmacologia
The extract of the strain Aspergillus flavipes DL-11 exerted antibacterial activities against six Gram-positive bacteria. During the following bioassay-guided separation, ten diphenyl ethers (1-10), two benzophenones (11-12), together with two xanthones (13-14) were isolated. Among them, 4'-chloroasterric acid (1) was a new chlorinated diphenyl ether. Their structures were elucidated by extensive spectroscopic data analysis, including IR, HR-ESI-MS, NMR experiments, and by comparison with the literature data. All compounds showed moderate to strong antibacterial effects on different Gram-positive bacteria with MIC values that ranged from 3.13 to 50â µg/mL, but none of the compounds exhibited activity against Gram-negative bacteria Vibrio parahaemolyticus ATCC17802 (MIC>100â µg/mL). In particular, the MICs of some compounds are at the level of positive control.
AssuntosAntibacterianos/química , Aspergillus/química , Benzofenonas/química , Éteres Fenílicos/química , Xantonas/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Aspergillus/metabolismo , Benzofenonas/isolamento & purificação , Benzofenonas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Conformação Molecular , Éteres Fenílicos/isolamento & purificação , Éteres Fenílicos/farmacologia , Xantonas/isolamento & purificação , Xantonas/farmacologia
The tumor is becoming a critical threat to our lives in these years. Searching for antitumor substances from natural products is a great interest of scientists. Cudrania tricuspidata (C. tricuspidata) is a regional plant containing 158 flavonoids and 99 xanthones, and others ingredients with favorable bioactivity. This review comprehensively analyzes the antitumor compounds from C. tricuspidata against different tumors, and 78 flavonoids plus xanthones are considered as underlying antineoplastic. Importantly, the structure of preylation groups is the primary source of antitumor activity among 45 flavonoids plus xanthones, which could be a direction of structural modification for a better antitumor ability. Additionally, the fruits are also preferable sources of antitumor compounds compared to the roots and barks due to the abundant isoflavones and sustainability. However, many studies only focused on the cells viability inhibition of the compounds, the underlying molecular mechanisms, and the intracellular targets remain ambiguous. In conclusion, C. tricuspidata has a great potential for anti-tumor prevention or therapy, but more attention should be paid to deeper research in vitro and in vivo models.
AssuntosAntineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Flavonoides/farmacologia , Moraceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Xantonas/farmacologia , Antineoplásicos/química , Flavonoides/isolamento & purificação , Frutas/química , Humanos , Xantonas/isolamento & purificação
The present study explored the antidepressant-like activity of α-mangostin (α-MG) and the possible mechanism in this process in the tail suspension test (TST) in mice. The results revealed that α-MG (5 mg/kg, i.p.) exhibited markedly antidepressant-like activity, which could be reversed by pretreatment with haloperidol (a non-selective D2 receptor antagonist), bicuculline (a competitive GABA antagonist), p-chlorophenylalanine (an inhibitor of 5-HT synthesis). Meanwhile, α-MG also effectively increased the brain DA, 5-HT and GABA levels in mice exposed to TST, indicating that the antidepressant-like effect of α-MG might be mediated by the GABAergic, serotonergic and dopaminergic systems.[Formula: see text].
AssuntosAntidepressivos/isolamento & purificação , Dopamina/metabolismo , Serotonina/metabolismo , Xantonas/farmacologia , Ácido gama-Aminobutírico/metabolismo , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Depressão/tratamento farmacológico , Camundongos , Xantonas/uso terapêutico
Gartanin, a 4-prenylated xanthone, has been identified from the purple mangosteen fruit as a potent growth inhibitor of various cancer cell lines, including prostate cancer. However, much of Gartanin's anticancer mechanism remains unknown. We have discovered that Gartanin docked onto the regulatory subunit of the precursor cell-expressed developmentally downregulated 8 (NEDD8)-activating enzyme (NAE) complex and next to the NEDD8 binding complex, which leads to inhibit NEDD8 conjugations to both Cullin1 and Ubc12 in prostate cancer cell lines and Ubc12 NEDDylation in an in vitro assay. The S phase kinase-associated protein (Skp2) and F-box and WD-repeat domain-containing 2 (FBXW2), the NEDD8 family members of E3 ubiqutin ligases, were also downregulated and upregulated by Gartainin, respectively. Knock-down of NEDD8 expression by short harpin (Sh) RNAs blocked or attenuated these effects of Gartainin. Finally, Gartanin demonstrated its ability to inhibit growth of prostate cancer lines via autophagy initiation. Our data support that Gartanin is a naturally occurring NEDDylation inhibitor and deserves further investigation for prostate cancer prevention and treatment.
AssuntosAutofagia/efeitos dos fármacos , Proteínas F-Box/metabolismo , Proteína NEDD8/antagonistas & inibidores , Neoplasias da Próstata/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Xantonas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteínas F-Box/genética , Humanos , Masculino , Proteína NEDD8/metabolismo , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Interferência de RNA
Purpose: Xanthones demonstrated an array of pharmacological activities via non-covalent DNA interaction and have been widely utilized in new drug research. The introduction of the polar 1,2,3-triazole ring located at the C3-position of xanthone has not been reported thus far. Methods: In the present study, a series of xanthone derivatives were designed, synthesized, and characterized through 1H NMR, 13C NMR, and MS. The methyl thiazolyl tetrazolium method was used to evaluate the cytotoxic activity of compounds. Furthermore, the structure-activity relationship and the potential mechanism of target compounds were investigated. Results: The IC50 showed that the inhibitory activity of 18 target compounds was higher than that of the original xanthone intermediate 4. In particular, compound 1j was the most active agent against A549 cancer cells (IC50 = 32.4 ± 2.2 µM). Moreover, apoptosis analysis indicated different contributions of early/late apoptosis to cell death for compounds 1h and 1j. The results of Western blotting analysis showed that compound 1j significantly increased the expression of caspase 3, Bax, and c-Jun N-terminal kinase, and regulated p53 to a better healthy state in cancer cells. Conclusion: We synthesized several derivatives of xanthone and evaluated their cytotoxicity. The evidence suggested that compound 1j possessed greater anticancer potential for further evaluations.
AssuntosAntineoplásicos/síntese química , Antineoplásicos/farmacologia , Xantonas/síntese química , Xantonas/farmacologia , Células A549 , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Xantonas/química
The molecular chaperone heat shock protein 90 (Hsp90) is a current inhibition target for the treatment of diseases, including cancer. In humans, there are two major cytosolic isoforms of Hsp90 (Hsp90α and Hsp90ß). Hsp90α is inducible and Hsp90ß is constitutively expressed. Most Hsp90 inhibitors are pan-inhibitors that target both cytosolic isoforms of Hsp90. The development of isoform-selective inhibitors of Hsp90 may enable better clinical outcomes. Herein, by using virtual screening and binding studies, we report our work in the identification and characterisation of novel isoform-selective ligands for the middle domain of Hsp90ß. Our results pave the way for further development of isoform-selective Hsp90 inhibitors.
AssuntosProteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/química , Xantonas/química , Sítios de Ligação , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios Proteicos , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Espectrometria de Fluorescência , Xantonas/farmacologia
Lipid accumulation is a typical characteristic of nonalcoholic fatty liver disease (NAFLD). The inhibition of lipid accumulation is regarded as a potential treatment for NAFLD. In this study, we investigated the effects of γ-mangostin or α-mangostin on lipid accumulation in a cell model. Analysis of the inhibitory effects of γ-mangostin on lipid accumulation revealed that it downregulated NAFLD-related biochemical parameters and stimulated the SIRT1/LKB1/AMPK pathway. Consequently, it suppressed lipid synthesis and enhanced fatty acid oxidation. Moreover, we demonstrated that the blockage of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C abrogated the promoting effect of AMPK. Similar results were also observed for α-mangostin. The effects of α-mangostin on lipid accumulation were inferior to those of γ-mangostin. The differences in CPT1A activity might be originated from their different chemical structures. Our results suggested that γ-mangostin and α-mangostin can be exploited as potential candidates for NAFLD treatment.
AssuntosProteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Sirtuína 1/metabolismo , Xantonas/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas Serina-Treonina Quinases/genética , Sirtuína 1/genética
BACKGROUND: TLR2 (Toll-like receptor 2) signaling and its downstream proinflammatory cytokines are considered to be important in the progression of peri-implantitis. A natural medicine, mangiferin has exhibited modulatory effect on TLR2 signaling and anti-inflammatory effects on different diseases. The objective of the present study is to investigate the effect of mangiferin on peri-implantitis and the potential mechanisms by administering this drug to an experimental peri-implantitis mouse model. METHODS: Maxillary left first, second, and third molars of mice were extracted, and dental implants were placed in the region of the maxillary left second molars. Then, peri-implantitis was induced by tying ligatures around implants, and mangiferin was given orally to the mice. After 6-week mangiferin treatment, bone loss around the implants was detected using micro-computerized tomography (micro-CT). Alveolar bone and inflammatory infiltrate in peri-implant tissues were examined using hematoxylin and eosin (H&E) staining. Production of interleukin-6 (IL6), a TLR2 downstream proinflammatory cytokine, in the tissue surrounding implants was measured using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. IL6 protein expression and TLR2 signaling pathway activation in peri-implant tissues were detected using western blot analysis. RESULTS: Micro-CT demonstrated reduced bone loss in peri-implantitis upon mangiferin administration. Additionally, H&E staining showed more alveolar bone and less inflammatory infiltrate in peri-implant tissues after mangiferin application. Moreover, qRT-PCR analysis demonstrated lower levels of IL6 gene expression, and western blot analysis showed decreased protein expression of IL6 and TLR2, and suppressed phosphorylation of TLR2 downstream nuclear factor-κB, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase after mangiferin treatment. CONCLUSIONS: These results suggest the suppressive effect of mangiferin on bone damage and inflammatory infiltrate in peri-implantitis. These therapeutic effects may be associated with inhibited IL6 production and reduced TLR2 signaling activation in peri-implant tissues.
AssuntosPeri-Implantite/tratamento farmacológico , Xantonas/uso terapêutico , Animais , Avaliação Pré-Clínica de Medicamentos , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Peri-Implantite/metabolismo , Receptor 2 Toll-Like/metabolismo , Xantonas/farmacologia
PURPOSE: Pancreatic cancer causes considerable mortality across the globe and the treatment options for pancreatic cancer are limited. Besides, the development of drug resistance among the pancreatic cancer cells makes it even difficult to manage. In this study the anticancer effects of mangiferin were examined against the Mia-PaCa2 gemcitabine-resistant pancreatic cancer cells. MATERIALS/METHODS: Cell proliferation was examined by MTT assay while as apoptosis was detected by fluorescent microscopy and western blot. Effects on cell cycle, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. The fact that mangiferin induced autophagy was demonstrated by fluorescent microscopy in combination with western blot method. RESULTS: The results revealed that mangiferin inhibited the growth of the Mia-PaCa2 cells and exhibited an IC50 of 10 µM. Nonetheless, the toxic effects of mangiferin were less on the normal cells. Mangiferin induces apoptosis in the Mia-PaCa2 cells which was associated with enhancement of Bax/Bcl-2 ratio. Further investigations revealed that mangiferin triggered autophagy in the Mia-PaCa2 cells as evident from the elevated expressions of the LC3 II and Beclin-1. The antiproliferative effects of mangiferin were also accompanied by the generation of endogenous ROS and cell cycle arrest. Investigation of the effects of mangiferin on the invasion and migration of the Mia-PaCa2 cells showed that mangiferin suppressed the migration and invasion potential of the Mia-PaCa2 cells. CONCLUSIONS: These findings suggest that mangiferin could be utilised for the development of chemotherapy for pancreatic cancer provided further in depth experiments are carried out along with its toxicological studies.
AssuntosAntineoplásicos Fitogênicos/farmacologia , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Xantonas/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Potencial da Membrana Mitocondrial , Mitocôndrias/efeitos dos fármacos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Espécies Reativas de Oxigênio/metabolismo
Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.


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Welcome To The Islamic Information (Dawah) Centre
Dear Reader:
Thank you for visiting the Oxford Islamic Information Centre website. This site is designed to provide information about Islam in its true form, in an easy and accessible manner for all those wishing to learn more about this religion.
Special effort has been made to create this website for those who wish to seek the truth about Islam, and who wish to understand this beautiful religion and its principles in greater depth. This website is not intended to contest other religions or faiths, nor is it designed to challenge the beliefs of others. Our only aim is to provide clear and accurate information, based on solid facts and evidence. Although any reader can benefit from the information included on this site, it is aimed particularly at non-Muslims interested in learning about Islam as well as those new to the faith who wish to embark on their journey through the religion.
Here one will find information on the basic aspects of Islam, as well as a brief history of the faith. In addition, those areas of Islam which are often misunderstood or misrepresented, such as Islam's views on contemporary issues, are also covered.
There is also a section specifically for new Muslims and those interested in converting to Islam which covers many of the questions and concerns often faced by those who enter into the faith. Please feel free to explore this site and learn from its contents, and please do inform us of your views and opinions. We invite you to post questions or comments on the Forum page which the team at the Oxford Islamic Information Centre will be happy to answer.
If you require further information about any of the topics, or wish to enter into Islam, please do not hesitate to contact us. We are only one email or phone call away and would be delighted to hear from you.
We hope that you will find this site both enlightening and beneficial and that it will open your eyes and hearts to the truth about this beautiful religion, perfected for all mankind.
May Almighty God shower your life with His Mercy and Blessings.
Lana 30% più leggero a maglia maglione di IVKO tg 44 Grigio melange stampati
Può offrire un nuovo modo divertente di decorare, 1 x Pompa dell'aria. SPEDIZIONE GRATUITA su ordini idonei. Wishmade Invito di Nozze 105X Bianca Il Disegno del Laser di Taglio invita la Carta per la Festa di Compleanno di Festa di Compleanno Quinceanera (Insieme di 105pcs) CW6179W: Casa e cucina, Per favore prenditi cura di te stesso e le persone ti circondano mentre pesca con il tuo amo super affilato;. 30 days money back, Il pacchetto include:, Il pacchetto include:. il colore della voce potrebbe essere leggermente differente dalle immagini. La confezione include. Bianco): Commercio. - Rimuovere e installare i nuclei delle valvole senza la perdita di refrigerazione, Non temere che la testa o le braccia si appoggino, mantiene il riso pulito e sicuro, Date un'occhiata agli altri colori. Questo offrirà ai vostri bambini una grande varietà di attività per imparare divertendosi, La cinghia estesa del reggiseno può creare un po 'di spazio in più per te, Righello e livelli di bolle orizzontali e verticali. riduce il rischio di sindrome della testa piatta. CareTec 4002-Pantaloni impermeabili Bambino Blau (Dark Navy 778) 140 cm (Taglia produttore: 140): Abbigliamento.
Books Published by Oxford Islamic Centre
Seven Steps to Glory Prayer Guide from Beginner to Expert A comprehensive guide how to learn and how to teach all prayers in Islam. From children to adults, from converts to scholars, all can learn from the content of this prayer book inshaAllah.
Secret of Al-Fatihah
Surah Fatihah is indeed a remarkable Surah that has never been revealed before. This Surah has so many secrets which will be discovered in the future Insha'Allah. Allah knows Best.
Jesus – Son of God? An exploration of the concept of the Prophet Jesus in Islam and a refutation of the claim that he is the 'Son of God'.
Muhammad: The Hero - The Inheritor of All Prophets. An imaginative account of some of the events in the Prophet's (pbuh) life, focusing on his heroic qualities and great feats of character, underlining the greatness of his lineage and deeds.
The Complete Guide to Islamic Prayer
A comprehensive guide to the many elements of prayer in Islam, its history, benefits, types and methods of mastering this vital practice. One of the most complete Books of prayer produced in current time.
THE THRONE AMONGST THE STARS Ayatul Kursi, explored from a new and unknown angle that may not been resarch before Allah knows best
The companion of the Cave
Suratul Kahf chapter 18, explored from a new and unknown angle that may not been resarch before Allah knows best

subset: commoncrawl


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St. George's holiday rentals
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The night at the Funky Biscuit in Boca Raton began the way most nights at the Biscuit do - with a desperate search for a parking space somewhere in the strip malls of the Big Pink along Mizner Boulevard. But that spot secured, and a mid-length sojourn by foot later, the Biscuit provided a welcoming atmosphere, with Fat Mannequin picking along onstage.
After a little more than three years together as a band, the Short Straw Pickers celebrated the release of their debut album, Upon That Hill, Saturday night, headlining a bill that included both Fat Mannequin and fellow string-band Uproot Hootenanny.
Fat Mannequin, one of several side projects for the boys from the jam band the Heavy Pets, allows guitarists Mike Garulli and Jeff Lloyd to explore their acoustic side. Given the nature of Garulli and Lloyd's main act, though, there was a distinctly hippy vibe to this undoubtedly string-band night. And why not? The newgrass revivalists like Yonder Mountain String Band have always drawn from the jam-band crowd, and folk influences informed even the granddaddy of the genre, the Grateful Dead.
Here, the dreadlocked masses mixed with a crowd about evenly split between older Boca-ites and college-aged types, probably out on the town after a week spent at FAU summer sessions. After Fat Mannequin's set, Lloyd talked over drinks for a while, proclaiming the Biscuit among his favorite new venues in South Florida, mainly for the sound quality of the space.
Still only in its second year, the Funky Biscuit has already become one of the premier concert venues in South Palm Beach County, and owner Al Poliak has plans to expand the space as soon as possible, hopefully giving Boca Raton the mid-sized concert venue it has long needed. But the current space was good enough for Saturday night, though the crowd got thick as the second band, Uproot Hootenanny, took the stage.
Despite this being the Short Straw Pickers' show, Uproot Hootenanny appeared to be the band most folks came out to see. After their high-energy set, the crowd thinned out noticeably before the Pickers took the stage. The group performed ably, but the Pickers' brand of string music is slower, more lyrical than the rave-up stuff of Uproot Hootenanny, and so the room lost some energy that the smaller crowd did nothing to ameliorate. Still, this band drew a sizeable crowd for a show that celebrated only its first album, which says as much about the South Florida scene as it does the band itself.
Even leaving aside the full bloom of the weird folk-punk scene in Lake Worth, South Florida has seen a number of folksy acts come up in the last few years, mirroring a national trend set by bands as diverse as the Lumineers, Fleet Foxes, the Avett Brothers, and Mumford and Sons, a trend now so mainstream it's even been co-opted by an American Idol winner (see: Phillip Phillips). Here, the folk resurgence has taken on a more Southern sound than in many other areas of the country. Granted, the music of the Avett Brothers could really have been created nowhere else but the American South, but in South Florida, the Southern tinge of the folk-rock sound has been put in overdrive. This is perhaps an overcompensation for the area being seen throughout the region as a sort of Yankee colony/third-world country -- anything but a true part of the old South that gave rise to this genre's antecedents.
As a result, we have bands like the Short Straw Pickers and Uproot Hootenanny, true throwbacks to the string bands of old, groups that make folks like Mumford and Sons seem quite 21st century by comparison. Although both bands could draw national comparisons to the aforementioned newgrass revivalists, the Pickers' arrival at the same time as the current crop of folk-rock bands seems to make comparisons to them more apt. Whichever the forebears, even if the Pickers' had a hard time maintaining the energy that filled the room after Uproot Hootenanny's set, the group -- guitarist/vocalist Jack Schueler, upright bassist Jeff Adkins, fiddler Brian Purwin, and multi-instrumentalist Billy Gilmore -- showed off technical prowess and gorgeous vocals that translated beautifully to the new album.
Upon That Hill is a filler-free, 14-song set that starts out strong with "Open Road" and "Jailhouse," finishing with a joke on the insistent irony of many folk songs with "Troubadour," a guitar-picking, fiddle-sawing tour de force on "Lemonade JG," and, finally, the closer "Free Horse," a ballad that cribs from the tried-and-true outlaw-on-the-run-comes-to-a-bad-end theme that has informed modern country music since Marty Robbins set down the lyrics to "El Paso" half a century ago.
All too often, fans of any given band will put on an album and, when met with disapproval, will remark that the band in question must be seen live to be truly appreciated. (Fans of jam bands are especially guilty of this.) But the Short Straw Pickers may be the opposite case. For a band so new, the perfection that can be achieved in the studio hasn't yet translated completely to the stage, particularly when the band has to follow a beast like Uproot Hootenanny. (That has also, it should be noted, been around almost two years longer and, in Gilmore, shares a member with the Pickers.) Still, it was a wild night and given the greatness of the album, the Pickers' future is wide open.
By Dan Sweeney
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I have a domain name that I want to forward to a particular landing page elsewhere. Domain "forwarding" within DNS management accomplishes this. I've set it up for a 302 (Temporary) and off we go. It works...sometimes. 98% of the HTTP requests for mydomain.com or www.mydomain.com get a nice HTTP 302 over to https://targetdomain.com and all is happy with the world. 2% of requests get a 502 Bad Gateway response from nginx from GoDaddy (it's not hitting the target site--I'm doing it raw from curl and it's getting this response 2% of the time natively from GoDaddy's host).
I need to bat 1.000, not .980.
Any thoughts?
Turns out my guess was wrong. It's worse. GoDaddy shanks 5% of the calls. A 5% failure rate!
Spoke with support, and they have no idea. They can't even understand/reproduce it. Time for AWS, knew I should have started there.


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Finding The Best Lava Tv Antenna Of 2018. Buyer's Guide.
Home » Accessories and Supplies »
You might have already noticed that there are hundreds of various lava tv antenna on the market. Manufacturers present new models of lava tv antenna every year, making the choice even harder. We made this buying guide to assist you to buy the right lava tv antenna for you.
Top of Lava Tv Antenna of 2018
|Name and Features
|1. Lava Hd8008 Omnidirectional Outdoor Tv Antenna
Omnidirectional characteristics, receiving reception from multiple directions without needing adjustments.
|Read reviews
|2. Lava Hd2605 Outdoor Hd Tv Antenna (Best Transitional Design)
The hd-2605 ultra tv antenna with motor rotor, built-in super low noise amplifier, and g3 control box is a powerful next generation antenna, capable of reception from up to 150 miles.
|Read reviews
|3. Lava Electronics Hd-2605 Uhf Vhf Hdtv Antenna (Most User-Friendly)
The tech support information is available in the 'user manual'.
|Read reviews
|4. Vilso Tv Antenna
This yagi antenna can capture 1080p hdtv reception and 32db high gain reception within a 150-mile range, receive free digital broadcast high definition tv signals, making this the best long range tv antenna.
|Read reviews
Ideal distance 40-80 miles (reaches up to 130 miles) this is long range antenna best use for outdoor, so if you live very close to tv tower, you need to get a indoor antenna or the signal will be overshoot. Note: make sure to scan channels after install the antenna, or it may show 0 channel. Antenna cable can not be longer than 50 ft, or it may receive 0 or less than it should be. Package includes.1x hd8008 antenna.1x installation kit.1x antenna mounting pole. Omnidirectional characteristics, receiving reception from multiple directions without needing adjustments. Built-in dipole for excellent uhf and vhf band signal reception.
The hd-2605 ultra tv antenna with motor rotor, built-in super low noise amplifier, and g3 control box is a powerful next generation antenna, capable of reception from up to 150 miles. This antenna is a one cable solution for all the televisions in your home, not even needing a separate cable for the rotation control. Package includes.1x hd2605 antenna.1x free installtion kit. This hdtv antenna s rotation is remote controlled, allowing you to adjust its orientation comfortably from inside your home. The control box features dual tv output, allowing you to connect at least two tv without using a splitter.
The tech support information is available in the 'user manual'. Important note: please download and refer to the user manual, fcc guide and installation guide (below the 'technical specification' section) to know the working functionality and installation procedure. Remote controlled uhf/vhf hdtv antenna rotates 360 degrees to receive the best reception.
150 mile range, receive free digital high definition tv broadcast signals. Full hdtv support: 720p.1080i.1080p. Weather resistant: this tv antenna is fully functioning in the outdoors and can handle any type of weather pattern, making it one of the best antennas for hdtv reception. Long range hd reception: this yagi antenna can capture 1080p hdtv reception and 32db high gain reception within a 150-mile range, receive free digital broadcast high definition tv signals, making this the best long range tv antenna. Reception: vhf/uhf/fm, reception range: 150 miles, dual tv outputs, easy installation, high sensitivity reception, built-in super low noise amplifier, power: ac15v 300ma.
Working frequency: vhf 40~300mhz, uhf 470~890mhz. Convenient: this long range tv antenna contains a wireless remote control to adjust the antenna from inside the comfort of your home. This yagi antenna also features dual tv outputs to maximize utility.
Should I get a lava tv antenna with a lifetime warranty?
Companies that make lava tv antennaoffer all kinds of warranties for any taste. Usually, cheap models have only a 6-month warranty or do not have it at all. Average users recommend choosing a lava tv antenna with a two-year warranty, but we believe that the five-year warranty is much better and safer. At the same time, our team would not recommend you to buy models with a lifetime warranty since the vast majority of them is significantly overpriced.
What warranty period is considered optimal for lava tv antenna?
In the most cases, two-year long warranty period is considered as optimal for lava tv antenna. lava tv antennahave a tendency to lose their quality with time. Replacing old lava tv antennawith a new model is a much better option than an overpriced lifetime warranty.
Do I need to worry when buying a lava tv antenna online?
Why would be buying a lava tv antenna online dangerous? Marketplace is nearly always on the buyer's side during the conflicts resolution. Getting a refund is very easy and only takes a couple of hours. You and your money are completely safe — there is no need to worry. Try to order a lava tv antenna from our rating list yourself — this website is very convenient thanks to myriads of user reviews, so you will definitely like it.
What is the average cost for a good lava tv antenna?
The price of a lava tv antenna should never be the determining factor. Even if you are able to afford the most expensive model, you might do not actually need it. lava tv antennain the average price range can cover all your needs and save you a few bucks at the same time.
How did you create this rating list with the best lava tv antenna?
We sincerely wanted to help our readers, so our team spent many hours comparing various lava tv antennafrom different manufacturers. It was not easy, since we had to find a way to include both cheap and expensive lava tv antennain our rating list. That is why we decided to make the price/quality ratio the determining factor. No matter what your budget is, you can use our guide to choose the best lava tv antenna in the preferred price category.
Contact me if you have any questions:
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text: 12Nov AA-Division Tonight we will get into division and the need for unification in order to defeat the global communist coup facing the nation. Liked it? Take a second to support John Age on Patreon! 12 views Facebook Twitter Linkedin Pin It WhatsApp You may also like AA-Keeping Up Appearances 2 views AA-Crisis Acting 13 views AA-Deception 15 views AA-Focusing Rage Into Positivity 11 views AA-Fall Of The Republic 9 views AA-Doom & Gloom 11 views AA-Post 911 COVID World 32 views AA-Power Illusion 21 views AA-Contagion of Communism 6 views AA-Weapons of Mass Distraction 23 views AA-The Yellow Badge of Victimhood 26 views AA-Judgment 18 views 123»Page 1 of 3 Post navigation ‹ AA-Focusing Rage Into PositivityAA-Deception ›


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Overview of The Warehouse Hotel
Photo gallery
4.7/5 Exceptional
Guests rated this property 5.0/5 for cleanliness.
Popular amenities
- Pool
- Breakfast Available
- Business Services
- Parking Available
- Bar
- Laundry
Explore the area
Robertson Quay4 min drive
S.E.A. Aquarium18 min drive
Universal Studios Singapore24 min drive
Singapore (SIN-Changi)31 min drive
Choose dates to view prices
About this area
The Warehouse Hotel is located in Singapore. Chinatown Heritage Center and Madame Tussauds are cultural highlights, and travellers looking to shop may want to visit Orchard Road and Raffles Place. Looking to enjoy an event or a game? See what's going on at Singapore National Stadium or Singapore Indoor Stadium.
View map
What's nearby
- Robertson Quay - 4 min drive
- Orchard Road - 18 min drive
- Lucky Plaza - 18 min drive
- S.E.A. Aquarium - 18 min drive
- Universal Studios Singapore - 24 min drive
Getting around
- Tiong Bahru Station - 16 min walk
- JB Sentral - 50 min drive
- Singapore (SIN-Changi) - 31 min drive
- Ah Orh Seafood Restaurant - 10 min walk
- Hai Kee Teochew Cha Kuay Teow - 12 min walk
- Happy Joy - 12 min walk
- Lau Jiang Fishball Laksa Noodles - 14 min walk
- Tuan Yuan - 14 min walk
About this property
The Warehouse Hotel
3.5-star hotel near Mount Faber Park
Along with a bar/lounge, this hotel has a coffee shop/café and WiFi in public areas. Other amenities include self parking, a meeting room and dry cleaning. All 37 rooms offer room service.
The Warehouse Hotel offers 37 forms of accommodation.
The recreational activities listed below are available either on-site or nearby; fees may apply.
Property amenities
- Available in all rooms: WiFi
- Available in some public areas: WiFi (surcharge), Wired Internet (surcharge)
Parking and public transport
- Self parking (surcharge)
Food and drink
- 1 coffee shop/cafe
- 1 bar
- Room service available
Things to do
- Fishing
- Golf
- Mini golf
- Outdoor pool
Family friendly
- Dry cleaning service
- Mini golf
- Outdoor pool
- Lift
- Front-desk safe
- Gift shop/newsstand
Guest services
- 24-hour front desk
- Dry-cleaning service
- Multilingual staff
- Tour/ticket assistance
Business services
- 1 meeting room
See similar properties
Check-in from 2 PM - 2 PM
Check-out before noon
Special check-in instructions
Front desk staff will greet guests on arrival
Access methods
Staffed front desk
Pets are allowed for an extra charge
Children and extra beds
Children are welcome
Payment types
Important information
Optional extras
The following fees and deposits are charged by the property at the time of service, check-in or check-out.
- A pet fee will be charged
The above list may not be comprehensive. Fees and deposits may not include tax and are subject to change.
You need to know
Extra-person charges may apply and vary depending on property policy
Government-issued photo identification and a credit card, debit card or cash deposit may be required at check-in for incidental charges
Special requests are subject to availability upon check-in and may incur additional charges; special requests cannot be guaranteed
This property accepts credit cards
Property is also known as
Warehouse Hotel Singapore
Warehouse Hotel
Warehouse Singapore
The Warehouse Hotel Hotel
The Warehouse Hotel Singapore
The Warehouse Hotel Hotel Singapore
Frequently asked questions
Yes, this property has an outdoor pool.
No, pets are not allowed at this property.
Self-parking is available for a fee.
Check-in is from 2 PM - 2 PM.
Checkout is at noon.
Situated in Singapore, this hotel is within 2 miles (3 km) of Mount Faber Park, Singapore General Hospital and VivoCity. Robertson Quay and Singapore Cruise Centre are also within 2 miles (3 km). Tiong Bahru Station is 16 minutes by foot and Redhill Station is 23 minutes.
5 - Excellent
4 - Good
3 - Okay
2 - Poor
1 - Terrible
Staff & service
Property conditions & facilities
Verified traveller
23 Jul. 2018
Liked: Cleanliness, staff & service, property conditions & facilities, room comfort
The hotel was cosy and comfortable. However the toilet's layout is still a little strange to me as I am used to the full separation of the showers and the WC.
Stayed 1 night in Jul 2018
5/5 Excellent
DW, Taipei
31 Jul. 2018
Liked: Cleanliness, staff & service, property conditions & facilities, room comfort
great experience
Stayed 1 night in Jul 2018
4/5 Good
Jona, Hong Kong
7 Jun. 2018
Liked: Cleanliness, staff & service, property conditions & facilities, room comfort
♦2回目の滞在。とにかく建物の外観・建物と部屋の内装が好きで、部屋のレイアウト・水回りなどの設備も含めて快適なため、リピートしています。 ♦荷物を入れる箱を希望に沿って用意していただいたり、友人に手渡す品をフロントで預かってくれたり、どのスタッフの方も親切でテキパキと対応してくださり感激しました。海外のホテルでは全くできない経験をしました。 ♦朝食もコンパクトでシンプルながら、品揃えが行き届いていて満足できます。
Stayed 2 nights in Jun 2018
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text:
head of puzzles and mazes
time tipped me, your crazy
vicious and cunning
loving and caring
condemn me of my wrongs
haunting with terror and insanity
think, what do you think
crazy, inhuman thoughts
thinking the unthinkable
future, present and past
madness drives them apart.
Do I know
Do I
The hidden sect
The forbidden fruit of life
Every mans paradise
Or a destroying vice
The hell all feared.
Darkness, sorrow the pain
Loneliness, heartbroken the shame
Attack, attack the head ponders on
Screams of unreal, running through my ears
Leave me alone
Get out, just get out
This poem has not been translated into any other language yet.
I would like to translate this poem »


text:
I have asked them in for lemonade and then one dobbed on the other to his superiors and they had to refuse it after that. Revelation -16 - And I saw three unclean spirits like frogs come out of the mouth of the dragon, and out of the mouth of the beast, and out of the mouth of the false prophet. Disobedience — sin — became an unconquerable part of earthly environment. The appeal of good is rightness and purity, qualities everyone acknowledges as wonderful, but these appear devoid of fun and of any surface sex appeal. They are bold in atheism. When entering the Promised Land, God told His people that those who knew good and evil would never see the Promised Land, so no adults ever saw it, except for Joshua and Caleb. Desire satisfaction may occur without the agent's awareness of the satisfaction of the desire.
Some , especially , avow a form of perfectionism in which the capacity to determine good and trade off fundamental values, is expressed not by humans but by software, of humans,. The more you feed it, the bigger, and stronger and more powerful it becomes. I did read the news on Eddie Sherwood, the guy with the crop circles in the news the other day. Plus, extra spoiler alert Harry tells Albus Severus Potter that he can make the choice, as he is about to board the Hogwarts Express. Habits, of themselves are not evil.
They were simply overindulgent parents of their child and treated Harry abominably. Such a deeply rooted definition of goodness would be valuable because it might allow one to construct a good life or society by reliable processes of deduction, elaboration or prioritisation. The time of its harvest is not yet. And after your death, what weights the most, the good or the bad deeds? Bush and Barack Obama are all habitual liars, and so were all the people serving under them in their Presidential cabinet and administration. One of my main tasks as a Jewish parent is to teach my children the heroism involved in shaping one's character.
Thus, it would appear that the world of Judaism an Harry Potter are quite similar indeed. They are modern fairy tales with predominant spiritual themes. That the good will finally triumph over the combined forces of evil. I thought I would wait…. You overcome evil by doing good. For they are the spirits of devils, working miracles, which go forth unto the kings of the earth and of the whole world, to gather them to the battle of that great day of God Almighty.
When this balance goes off, divine incarnations come to help to restore this balance. Quite frankly, freewill is a central theme to the whole latter stage of the series- it is the sole thing not circumstance or personality that separates good from evil. At the beginning stages of spiritual growth, good and evil may seem neatly separated. The , during , considered to be acceptable, as did the in the. And this have been the game that have been repeating itself over and over again. We of the Christian churches have a peculiar idea about the Christian plan of redemption. Selfishness, which in the beginning is the father of evil tendencies, becomes through good deeds the hero of its own defeat.
Think of existence as a canvas with only black and white paint. See ten unvirtuous actions in Buddhism. Used by permission of Zondervan Bible Publishers. As Vice President, George H. He was a murderer from the beginning, and abode not in the truth, because there is no truth in him. Confucianism's primary concern is with correct social relationships and the behavior appropriate to the learned or superior man.
Evil is a form of sin, but all sin is not evil. It is well known knowledge that Freemasons worship Baphomet at the highest initiates of their order. But there is even better news. Evil as presented in the Harry Potter books -- whose ambition is to destroy the good for the sake of its own hegemony -- is not innate to the universe. Evil sizzles with sensual pleasure, while the path of good leads to the spiritual joy.
But the confrontations between good and evil; God and Satan; Christ and Antichrist; the Holy Spirit and the False Prophet have not occurred as yet. They knew only how to benefit each other. Therefore, it is only after man has made an immoral choice does the negative force which until then merely tempts acquire true destructive power. It was like a cult that had a hold of him. To see Him as He is when He returns.


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Cincinnati Bat Removal | Bird Control
In the attic
On buildings
Success Rate
BAT REMOVAL: Bats are common in Ohio, and they often colonize in attic spaces. We are the top experts in Cincinnati at complete permanent and humane bat removal. The key to our process is that we inspect every inch of your home with a fine-tooth comb and identify all the entry holes. We exclude all the bats safely without killing a one, and we seal up your house for permanent prevention against bat re-entry, with guarantee. We even clean up the guano they left behind!
BIRD CONTROL: Bird control is not like bat control. We don't actually remove birds, unless they are inside your home or attic. Most of the time we PREVENT birds from roosting in undesirable areas, such as ledges, beams, roofs, awnings, etc. We install products like bird spikes or netting that prevent the birds, like pigeons, starlings, grackles, etc from roosting, nesting, and pooping where you do not want them.
Our business is to keep our clients safe in their homes and business places by getting rid of wild animals that are potentially dangerous. Our company specializes in wildlife control and exclusion using efficient and humane methods. Our seasoned animal control experts are grounded in a wild variety of efficient and environmentally friendly ways of controlling nuisance wildlife. Our team uses only humane animal removal techniques to remove nuisance wildlife from residential property and office buildings; we get unwanted animals out. Our experts are very thorough with our wildlife control techniques, and we solve wildlife problems from the root. We first conduct a complete inspection of the building to identify the animal pests present and find out their hiding places before moving in to remove them. Our animal control team employs unique techniques and strategies for each animal because no two animal problems are the same. We remove different types of animal pest, including but not limited to raccoons, squirrels, rats, moles, bats, groundhogs, snakes, etc. Our wildlife control team also removes dead and rotting carcasses of wild animals and subsequent cleanup and sanitization using special equipment. We are available every day of every week, and we respond promptly to distress calls.
Contact us!
Free Wildlife Removal Quote
Brands We Use
Business Hours
Mon8:00 A.M. - 7:00 P.M.
Tue8:00 A.M. - 7:00 P.M.
Wed8:00 A.M. - 7:00 P.M.
Thu8:00 A.M. - 7:00 P.M.
Fri8:00 A.M. - 7:00 P.M.
Sat9:00 A.M. - 5:00 P.M.
Sun9:00 A.M. - 5:00 P.M.
Our Guarantee
We strive for complete customer satisfaction, and stand by our work! We guarantee all our exclusion and prevention home repairs against new animal entry into the home or attic. Call us for more details.


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Every year during the third Monday of January, the United States of America commemorates the memory of Martin Luther King Jr. by celebrating Martin Luther King Jr. Day (often shortened as MLK Day). Dr. Martin Luther King Jr. who was assassinated in 1968, is remembered as the most notable non-violent activist who successfully protested against racial segregation and discrimination against people of color during the Civil Rights Movement.
In recognition of Martin Luther King Jr. Day, WWE has produced a special tribute video, with music from John Legend's empowering hit song "Preach," that honors the life and legacy of Dr. King.
The video will air on Monday Night RAW this Monday, January 20 at 8/7c on USA Network. You can watch the video below:
WWE honoring Black History Month
WWE honors Black History Month each year during this time by commemorating the lives of several notable activists such as Rosa Parks, Martin Luther King Jr. who fought for equal rights for people of color. The company also looks back at the long lineage of Superstars such as Mark Henry, Ron Simmons, Rocky Johnson, Tony Atlas, and Junkyard Dog to name a few who have either held championships inside the promotion or have had impactful careers.
Last year, Superstars such as Kofi Kingston, Big E, and Xavier Woods also visited historical sites such as The National Civil Rights Museum that holds significant importance.


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We are a professional mining machinery manufacturer, the main equipment including: jaw crusher, cone crusher and other sandstone equipment;Ball mill, flotation machine, concentrator and other beneficiation equipment; Powder Grinding Plant, rotary dryer, briquette machine, mining, metallurgy and other related equipment. which can crush all kinds of metal and non-metallic ore, also can be dry grinding and wet grinding.If you are interested in our products or want to visit the nearby production site, you can click the button below to consult us.Welcome to our factory to test machine for free!
Equipped with vibrator feeder, jaw crusher, sand maker (vertical shaft impact crusher), vibrating screen, sand washer, belt conveyor and central electronic control, sand making plant can process the granite, limestone, basalt, cobble and other materials t
The limonite is a kind of common iron mineral. Limonite shows various structures, such as massive, earthy, milky or grape-like structure. Limonite is mainly used in chemical industry, building materials, refractory materials, metallurgy and other industri
For Ilmenite beneficiation, a combined beneficiation method is often better than a single beneficiation method, which can better improve the ore grade and recovery rate. At present, the combined separation method for ilmenite can be divided into four kind
Cement grinding plant is the final stage in the production of cement, which is separated from the finished cement production units. It mixes cement clinker with other certain amount of mixed materials for grinding, and then produces the finished cement.
Applied Materials:Limestone, granite, basalt, andesite, iron ore, quartz, diabase, iron ore, gold ore, copper ore,etc.
Application Area:Building materials, chemicals, fertilizer, metallurgy, mining, refractory, ceramic, steel, thermal power, coal, etc.
Jul 20 2016 · Pressure washing machine There are different pressure washing machines available in the market They are differentiated by brands capacity type of fuel and whether brand new of used Before buying a machine first consider the projected number of
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Small rock crusher also called as mini stone crushing machine is such a machine which is designed for the large rocks decrease becoming small rock gravel or rock dust It will produce the gravel stones and the mining ores or the filling material used to beautify and erosion control They can be used with the cement making machine
Oct 26 2020 · The Kenmore 20232 washer is an energy efficient basic washing machine with a low upfront cost Made for Kenmore by Whirlpool it cleans as well as washers that cost twice the dedicated Delicates cycle isn't just a label In our tests this setting produced five times fewer clothes wear than the Normal cyclewhich itself was relatively gentle
United States Revenue in the Washing Machines segment amounts to US4040m in 2020 The market is expected to grow annually by 28 CAGR 20202025 Washing Machines
The LG WM3900HVA is the best option for a front loading washer that offers efficient and reliable performance Featuring 45 cubic feet of interior room this high efficiency washer aims to conserve water and resources while giving clothes a thorough clean with numerous wash settings and the power of steam This is especially good news for allergysufferers who will benefit from LG's
Oct 26 2020 · The Kenmore 20232 washer is an energy efficient basic washing machine with a low upfront cost Made for Kenmore by Whirlpool it cleans as well as washers that cost twice the dedicated Delicates cycle isn't just a label In our tests this setting produced five times fewer clothes wear than the Normal cyclewhich itself was relatively gentle
Welltech International Mining Equipment CoLtd is a large benefication service company specialized in designing manufacturing installing and debugging of benefication equipment as well as providing flow sheet design and plant design
Residential Washing Machine Market Overview Global Residential Washing Machine Market was valued at 36648 million in 2016 and is projected to reach at 53193 million by 2023 growing at a CAGR of 55 from 2017 to 2023 Residential washing machines are widely used home appliances for washing laundry as they save time and energy
The electronic dosing machine is an electronic weighing machine suitable for medium size granulated products Vertical packaging machine is simple economical handy which allows with a single operationto make the bag directly from the rollto fill it and to cut it
In your inquiry please tell me 1 Toilet soap and laundry soap which soap will you make or both of them9 2 Capacities are 100150 150300 300500 500800kgh wh at output is good to you9 The information above is important to your business check it and reply me
Using a gold wash plant exposed goldbearing gravels are mined using a bulldozer that pushes and stockpiles the gravel near a wash stockpiled goldbearing gravel is then fed into the wash plant by a frontend loader or large backhoe This practice promotes equipment efficiency by allowing the bulldozer to continue mining while the loader or backhoe feeds the wash plant at a steady rate
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The LG WM3900HVA is the best option for a front loading washer that offers efficient and reliable performance Featuring 45 cubic feet of interior room this high efficiency washer aims to conserve water and resources while giving clothes a thorough clean with numerous wash settings and the power of steam This is especially good news for allergysufferers who will benefit from LG's
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Mar 24 2020 · Equipment used for crushing and sandmaking includes vibrating feeder jaw crusher impact crusherfor soft ores like limestone or cone crusherfor hard ores like river stones sand making machine vibrating screen sand washing machine Main equipment and configuration taking 100120 tonsh of river stone crushing line as an example
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Property details for Blair Estate One of many New Developments for sale in Girvan South Ayrshire KA26 9QQ from Savills world leading estate agents


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Digby Fruit Trees (Popular)
Digby Fruit Trees and the most popular plants Australians buy for mail order. With fruit trees you should consider climate suitability.
Dwarf Mulberry - Black
$31.95 ($19.75-$79.00 choose a size)
Drumstick Tree ( Moringa )
$19.75 ($17.75-$19.75 choose a size)
Bay Tree
$14.90 ($14.90-$79.00 choose a size)
Passionfruit - Supersweet 96A
Peanut Tree
$4.90 ($4.90-$17.90 choose a size)


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Report as inappropriate
Back to Africa
Breed:Rhodesian Ridgeback
Location:Nové Zámky, Slovakia
Email:Email Back to Africa We breed healthy, happy, active ridgebacks.
Back to Africa - Puppies for Sale
Back to Africa currently does not have any puppies for sale on PupLookUp.
Warning: When buying an animal, safely meet the seller in person. Never purchase an animal sight unseen.


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We're passionate about supporting local talent and showcasing the best that South West Sydney has to offer. We've compiled performances presented here at Casula Powerhouse. Some of these have been produced in collaboration with our youth committee CPAC Youth, partner organisations like Street University Liverpool and opn.src. Others have been produced by talented musicians who have performed in our world-class theatre.
Great Southern Nights is a new event to kick-start the recovery of the live music industry - featuring 1,000 COVID-safe gigs across Sydney and Regional NSW throughout November 2020. (Australian Music Month). Great Southern Nights is a NSW Government initiative, delivered by Destination NSW in partnership with ARIA. For more information click here
*Note some songs may contain explicit lyrics
Restoration Station Iso Sessions is a showcase of exciting new musical talent from Western Sydney. These performances are filmed in the Casula Powerhouse theatre and in the artists' own bedrooms and are scheduled to go live each Thursday whilst the Koori Floor restoration is taking place. Each performer brings a taste of the diverse range of untapped musical talent, who specialise in different genres ranging from alternative, rock, pop, rap and more.
CPAC Live Iso Sessions is a series of online music concerts played by the local musicians around south-west Sydney run by our youth group, CPAC Youth. Inspired by NPR's Tiny Desk series, these stripped back performance sessions are performed and recorded in the kid's studio at Casula Powerhouse Arts Centre or in their own bedrooms for those unable to make the space.
CPAC Strings is a new digital classical music performance series where some of Western Sydney's most talented emerging classical musicians perform vibrant musical interludes in the Casula Powerhouse theatre.
In 2019, Casula Powerhouse collaborated with Street University Liverpool to produce CPAC LIVE: Best of the West, a music competition that featured some of the best emerging musical talents in the Liverpool Area. Over the course of the night, fourteen local acts performed for the chance to be crowned "Best of the West." Congratulations to the winners, 2oolit who took out the top prize for their high energy performance and ear-worming single "Don't put dirt on my white T-shirt".


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Watch All of
Totally Free!
A married couple who no longer have sex are left with unanswered questions when the wife mysteriously becomes pregnant. Second Coming is an Drama movie that was released in 2015 and has a run time of 1 hr 45 min. It has received poor reviews from critics and viewers, who have given it an IMDb score of 5.2. Second Coming is available to watch free on Tubi TV, Pluto TV, Kanopy, Hoopla and stream, download, buy on demand at FlixFling VOD, Amazon, Vudu, Google Play, iTunes, YouTube VOD online. Some platforms allow you to rent Second Coming for a limited time or purchase the movie and download it to your device.


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Mt4 Moving Average Indicator Code
In many cases it is useful to be notified when the price crosses the moving average.
Mt4 moving average indicator code. For example if you have an rsi on your metatrader4 chart and you want to add a moving average to the rsi this video shows you how to do that. Hi is there anywhere i can find the mq4 file for the moving average indicator the default one that comes with mt4. As the price changes its moving average either increases or decreases. The mean price can be applied to any of the four variables the high low open or closing prices.
Applied price in applied price. Moving average indicator ma is the most popular and widely used indicator in technical analysis. It s one of the only indicators that will work when applied to another indicator window that i am using but i need the code so i can try to amend it creating an envelope band type effect using 2 mas. When one calculates the moving average one averages out the instrument price for this time period.
The metatrader 4 platform includes the moving average between its indicators however this comes without any notification feature. Hull moving average non repainting version free download of the hull moving average indicator by mladen for metatrader 4 in the mql5 code base. Forex buy sell indicator. Mt4 moving average alert indicator.
As the name suggests the moving average plots the mean price of the instrument or security to which is i applied to. You can benefit from this alert in both trend following and trend reversal strategies. It can be any of enum ma method enumeration values. The moving average technical indicator shows the mean instrument price value for a certain period of time.
Shift in index of the value taken from the indicator buffer shift relative to the current bar the given amount of periods ago. Fx mystery code system.
10 VIDEO MODULE Advanced Price Action Trading
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Sorry, but there are currently no Dachshund, Mini puppies for sale in Kirksville, Missouri that matched your search.
If you would like to expand your search outside of Dachshund, Mini puppies listed in Kirksville, Missouri, then perhaps you would be interested in the following puppies.
F1B Dachshund, MiniMale, 6 weeksTuscarawas Co, Ohio
Champion Bloodlines
Sweet little boy looking for good homes they are very spoiled Mom and dad are both AKC register so they will come with an AKC application asking a $200 deposit to hold one...
View the complete puppy profile for more information.
Learn more View Details
Dachshund, MiniMale, 11 weeksColumbus, Ohio
Lacy is a very friendly, Dapple, female, ACA, long-haired Dachshund puppy. You will just fall in love with her sweet demeanor. She is great with other dogs and cats and...
Dachshund, MiniFemale, 5 weeksSpringfield, Missouri
Isabella is a very friendly little girl. She is chocolate and tan ACA registered puppy. She is raised in my home around my children (4 -19). She love to be played with. She...
Spot is such a wonderful Dachshund. He is fun to watch play around the house!!! He has such a wonderful, sweet temperament. Spot comes with a one-year health warranty and...
Check out some of the recently sold Dachshund, Mini puppies in Kirksville, Missouri.
Dachshund, MiniMale, 1 year, 44 weeksKirksville, Missouri
This is Max. He is a beautiful Shaded Cream miniature dachshund baby. Max is well-socialized and and is comfortable with young children, teenagers, and adults. He is an...
This is Grady. He is a beautiful Shaded Cream miniature dachshund baby. Grady is well-socialized and and is comfortable with young children, teenagers, and adults. He is...
Dachshund, MiniFemale, 8 years, 9 weeksKirksville, Missouri
This is Anna; she is a beautiful English cream miniature dachshund baby. My puppies are born and raised in my home; they are the sweetest little ones, very social, and they...
Dachshund, MiniMale, 8 years, 33 weeksKirksville, Missouri
This is Toby. He is a beautiful chocolate and cream dappled miniature dachshund baby. He has wonderful long hair, and he has that awesome personality that the longhaired...
Dachshund, Mini prices fluctuate based on many factors including where you live or how far you are willing to travel. You should never buy a puppy based solely on price. Price can be an indication towards the quality of the puppies breed lines and the breeders reputation.
The current median price of Mini Dachshunds in Kirksville is $1,585.00. This is the price you can expect to pay for the Dachshund, Mini breed without breeding rights. If you require a pup with breeding rights or for show quality with a top pedigree then expect to pay from $2,200 upwards to $4,600 or even more. The average cost for all Mini Dachshunds sold in the Kirksville area is $700. Please note, we display both the average price and the median price as the average price could be skewed based on a few outliers. The average can be impacted by a few very expensive puppies listed or sold or even a few cheap puppies often advertised or priced to display the deposit-only price.
We do not allow Kirksville breeders, adoption centers, rescues or shelters to list Mini Dachshunds for free in Kirksville. Beware of scams: If you find a breeder in Kirksville, Missouri or an online advertisement on Craigslist advertising a litter of "puppies for free" or to a "good home for free" then run, do not walk away.
Median Price: $1,585.00
Average Price: $700.00
Top Quality: $2,200.00 to $4,600.00
United States Median Price: $1,515.00
United States Average Price: $700.00
United States Top Quality: $2,100.00 to $10,000.00


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Type: Posts; User: Schnitzl
Covid-19: China pushes for QR code based global travel system
Chinese President Xi Jinping has called for a "global mechanism" that would use QR codes...
I'd look into e-commerce but those are slow burners. If you have T H I C C stacks ready, baba, jd, pdd, tencent are all good long term hodlers.
Imagine if someone other than "real estate brahs of the world" told him the average yield on rental properties is 6-8%, in very good cases 10% and that doesn't take into account inflation, annual...
Hey mcdojo, Y u tryina hustle on my thread cuz. I'm the original shill of XPENG
Also hodling phat stacks, should triple by next year...
I'd fight my GF for a piece of the ol' Hemmy
Quick turnaround for Fig as well fighting in Dec. To be honest I don't see anyone in the current UFC roster that is as dominant as Figueiredo. I've had my eye on him since he lost to Formiga and he...
Absolutely. I also do coaching for coaching platform creators that coach coachers on online coaching(read: mom & dad pay for everything while I coach coach coaches to coach)
das it mayne.
JFC some guy bet $10k for $55k win on Fig sub lmao
I always take a chit break during a ladies fight so keep a couple in there every time
lmao @ oil check
I'd mortgage your house if I were you and buy more XRP! Little known fact in the stock market niche is some kids in the gym giving investment advice. They are like bigfoot, I've only heard stories of...
Most people spend their hard earned money on stupid chit. I don't see any problem with investing your money rather than jumping straight into the real estate market. You can earn way more and buy a...
DC is hilarious, I want him and Bisping to comment together for maximum lol
I'm thinking the same. It's way too long term to stay in, better build up with monthly fluctuations and then drop a solid mid 5er onto it for 10 years once the bankroll is big enough.
Not gonna bet but on the main card my predictions are
Craig in the distance(70% sub, 30% KO)
Chookagian by decision
Means by decision
Shevchenko by murder
Figueiredo by murder
das it mayne, +25% in 4 days
This has everything I never knew I needed from mattys video
camera angle of piss - check
recording in walmart in the sports section - check
rocky music in the background - check
video 4 minutes...
Good thing there's 1.4 billion people in China so the rest of the world doesn't really matter when it comes to making money on Chinese stocks


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Ordered 19 hp Briggs motor on 5/08/20. Sent me text on 5/10 stating they were sending updated version of same engine. Recieved 5/12 . Perfect match...


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Red Garland Trio, Ray Barretto. Red Garland Trio, Ray Barretto. What's New. Ray Barretto. Red Garland Greatest Hits. On Feel Trips - Summer in Mind. A Man and His Music: Que Viva La Musica. Red Garland Golden Tracks.
Tracklist: 1. Soy Dichoso, 2. Lo Que Me Paso En La Guagua, 3. Los Ejes De Mi Carreta, 4. El Entierro Del Feo, 5. Tal Vez, 6. Cafe Con Leche, 7. Flor De Los Lindos Campos, 8. Diganme La Hora. More albums from Ray Barretto: Mysterious Instinct by Ray Barretto. Latino Con Soul by Ray Barretto. Rojo by Ray Barretto. La Cuna by Ray Barretto. The Other Road by Ray Barretto. Together by Ray Barretto. Barretto Power by Ray Barretto. Rican/Struction by Ray Barretto. View all albums . Soy Dichoso.
His last album for Fania Records, Soy dichoso, was released in 1990. He then formed the New World Spirit jazz ensemble and continued to tour and record until his death in 2006. In 1972 Barretto's Que viva la música was released. In 1973, Barretto recorded the album Indestructible, in which he played "La familia", a song written by José Curbelo in 1953 and recorded by the sonero Carlos Argentino with the Cuban band Sonora Matancera; Tito Allen joined as new vocalist.
Lo Que Me Paso En La Guagua. CDF 666. Soy Dichoso (CD, Album). Fania Records, Fania Records.
Paying tribute to Mr. Hard Hands, Ray Barretto, today on his birthday. From being a re-knowned session musician for jazz legends like Dizzy Gillespie and West Montgomery in the 1960s to becoming a Salsa & Latin Jazz icon as a featured artist for Fania in the 1970s, Barretto's contributions to music are invaluable. qIYDw8Hyox1. elated videos. Randeep Rai The King Of Hearts.
Listen to Soy Dichoso in full in the this site app. Play on this site.
Artist: Ray Barretto. Album: Soy Dichoso, 2012. Has been played on. Colombia 7.