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1.
Biol Bull ; 240(2): 132-143, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33939942

RESUMO

AbstractThe lifestyle of symbiotic species in the genus Synalpheus can vary from pair living to eusocial. A pair-living social system commonly implies the adoption of a monogamous mating system. In this study, we used the symbiotic shrimp Synalpheus brevicarpus in association with the sponge Dysidea sp. to test the hypothesis that heterosexual pairs of symbiotic shrimps can adopt a monogamous mating system when living in association with a morphologically complex host. We collected a total of 40 sponges, which were inhabited by 76 shrimps: 41 males, 33 females, and 2 juveniles. Synalpheus brevicarpus is sexually dimorphic, with males displaying proportionately larger weaponry (snapping claws) and a smaller average body size than females. Sponges were more often inhabited by a pair of heterosexual shrimps than expected by chance. Larger sponges were inhabited by more than one pair of shrimps in which the sex ratio did not differ significantly from 1∶1. Pairs of heterosexual shrimps were recorded, with females carrying embryos in all stages of embryonic development. Our results indicate that S. brevicarpus is a pair-living shrimp with a monogamous social and mating system that may also guard spaces or areas within its sponge host. Our hypothesis of monogamy is supported by the observations on pair living, sex ratio, and sexual dimorphism in body size and weaponry in this species.


Assuntos
Decápodes , Dysidea , Animais , Feminino , Masculino , Reprodução , Caracteres Sexuais , Simbiose
2.
Bioorg Chem ; 111: 104791, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33848723

RESUMO

Dysiscalarones A-E (1-5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated. Of these metabolites, dysiscalarones A-B (1-2), honulactone A (6), and phyllofolactone I (7) showed inhibitory activities with respective IC50 values of 16.4, 18.5, 2.6, and 3.7 µM, which suggested that the γ-methylated α,ß-unsaturated γ-lactone might be the functional group. In addition, all the seven metabolites showed no significant cytotoxicity against lung cancer PC9 cell line at the concentration of 20 µM.


Assuntos
Dysidea/química , Óxido Nítrico/antagonistas & inibidores , Sesterterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Relação Estrutura-Atividade
3.
J Pharm Biomed Anal ; 197: 113962, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33640688

RESUMO

This study aims to investigate the chemical constituents of sponges Dysidea avara (D. avara) and Axinella sinoxea (A. sinoxea), grown up in the Persian Gulf, as well as dehydrodeoxycholic acid (DHCA) content in methanolic extracts of the selected sponges. The chromatography-mass spectrometry (GC-MS) fingerprint of bioactive compounds from methanolic extracts of the selected marine sponge samples was investigated. Based on molecular docking results, among chemical compounds found in marine sponges, DHCA has anti-inflammatory and antipsoriatic properties. They also indicated that DHCA generated stable complexes with 1w81, 3bqm, and 3k8o receptors (psoriasis-related targets) with a binding energy (BE) of -9.26, -10.62, and -7.59 kcal mol-1, respectively. DHCA is isolated from the methanolic extracts of marine sponge samples on chromatographic plates was quantified after derivatization with anisaldehyde reagent by the validated HPTLC method. In-situ HPTLC-DPPH was also calculated to evaluate the free radical-scavenging activity (FRSA) of DHCA. In-silico ADME (Absorption, Distribution, Metabolism, Excretion) predictions revealed that the compound had minimum toxicity and acceptable human intestinal absorption (HIA), as well as low skin permeability. These can potentially be employed as lead compounds to develop a novel antipsoriatic drug.


Assuntos
Dysidea , Poríferos , Animais , Ácido Desoxicólico/análogos & derivados , Humanos , Oceano Índico , Simulação de Acoplamento Molecular
4.
Mar Drugs ; 18(12)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33265937

RESUMO

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder with heterotopic ossification (HO) in soft tissues. The abnormal activation of bone morphogenetic protein (BMP) signaling by a mutant activin receptor-like kinase-2 (ALK2) leads to the development of HO in FOP patients, and, thus, BMP signaling inhibitors are promising therapeutic applications for FOP. In the present study, we screened extracts of 188 Indonesian marine invertebrates for small molecular inhibitors of BMP-induced alkaline phosphatase (ALP) activity, a marker of osteoblastic differentiation in a C2C12 cell line stably expressing ALK2(R206H) (C2C12(R206H) cells), and identified five marine sponges with potent ALP inhibitory activities. The activity-guided purification of an EtOH extract of marine sponge Dysidea sp. (No. 256) resulted in the isolation of dysidenin (1), herbasterol (2), and stellettasterol (3) as active components. Compounds 1-3 inhibited ALP activity in C2C12(R206H) cells with IC50 values of 2.3, 4.3, and 4.2 µM, respectively, without any cytotoxicity, even at 18.4-21.4 µM. The direct effects of BMP signaling examined using the Id1WT4F-luciferase reporter assay showed that compounds 1-3 did not decrease the reporter activity, suggesting that they inhibit the downstream of the Smad transcriptional step in BMP signaling.


Assuntos
Fosfatase Alcalina/antagonistas & inibidores , Diferenciação Celular/efeitos dos fármacos , Dysidea/metabolismo , Inibidores Enzimáticos/farmacologia , Mioblastos Esqueléticos/efeitos dos fármacos , Miosite Ossificante/tratamento farmacológico , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Esteróis/farmacologia , Tiazóis/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Proteína Morfogenética Óssea 4/toxicidade , Linhagem Celular , Inibidores Enzimáticos/isolamento & purificação , Indonésia , Camundongos , Estrutura Molecular , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/patologia , Miosite Ossificante/metabolismo , Miosite Ossificante/patologia , Osteoblastos/metabolismo , Osteoblastos/patologia , Esteróis/isolamento & purificação , Relação Estrutura-Atividade , Tiazóis/isolamento & purificação
5.
PLoS One ; 15(11): e0241582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33253155

RESUMO

Since Marine sponge Dysidea avara is regarded as a source of anti-inflammatory compounds, we decided to evaluate its potential anti-psoriatic activity in a psoriasis Imiquimod-induced in the mouse model. Psoriatic mice were treated with three different methanolic extracts of Dysidea avara compared with betamethasone-treated mice in in- vivo studies. Clinical skin severity was assessed with the psoriasis area index (PASI), whilst ELISA detected the expression of TNF-α, IL-17A, and IL-22. Dysidea avara activity was studied by employing GC-MS (to distinguish compounds), HPTLC (for skin permeation and accumulation), and SEA DOCK to predict single compound potential anti-inflammatory activity. After 7 days of treatment, mice treated with Dysidea avara displayed a dose-dependent, statistically significant improvement compared to controls (p< 0.001). In line with the clinical results, ELISA revealed a statistically significant decrease in IL-22, IL-17A, and TNF-α after treatment; the same SEA DOCK analysis suggests a possible anti-psoriatic activity of the extracts.


Assuntos
Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Dysidea , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Imiquimode/toxicidade , Interleucina-17/análise , Interleucina-17/metabolismo , Interleucinas/análise , Interleucinas/metabolismo , Camundongos , Psoríase/induzido quimicamente , Psoríase/diagnóstico , Psoríase/imunologia , Índice de Gravidade de Doença , Pele/imunologia , Pele/metabolismo , Pele/patologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
6.
Zootaxa ; 4780(3): zootaxa.4780.3.5, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33056514

RESUMO

Differentiation of species within the genus Dysidea Johnston, 1842 (Order Dictyoceratida Minchin, 1900, Family Dysideidae Gray, 1867) is extremely difficult as they lack spicules which are strongly diagnostic in other Demospongiae, and their primary and secondary fibres and the mesh that they form, may be irregular in shape and thickness, thus difficult to measure for comparisons. Here we review species of Dysidea known from the New Zealand Exclusive Economic Zone (EEZ), validating five species: Dysidea cristagalli Bergquist, 1961a, from the Hauraki Gulf; D. hirciniformis (Carter, 1885a) sensu Dendy (1924), from North Cape; D. navicularis Lendenfeld, 1888, from Port Lyttleton on the east coast of the South Island; D. ramsayi (Lendenfeld, 1888) from the Chatham Islands; D. spiculivora Dendy, 1924, from Cape Maria Van Diemen and the Three Kings Islands to the north of New Zealand. Dysidea fragilis (Montagu, 1818) sensu Bergquist (1961b), from Mernoo Bank on Chatham Rise, is now considered to be invalid, and D. elegans (Nardo, 1847) sensu Brøndsted (1927), from the Coromandel Peninsula, is considered unrecognisable. Several partially characterised species have also been cited in the literature. Two new species from Tauranga Harbour, on the northeast coast of the North Island, Dysidea tuapokere sp. nov. and D. teawanui sp. nov., are described. These descriptions are based on fresh material and in situ photography, facilitating clear, informative descriptions, that will enable ease of identification of these species in the future.


Assuntos
Dysidea , Poríferos , Animais , Baías , Nova Zelândia
7.
J Nat Prod ; 83(5): 1577-1584, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32243140

RESUMO

A GNPS molecular networking approach mapped a library of 960 southern Australian marine sponges and prioritized Dysidea sp. (CMB-01171) for chemical investigation. Although the published natural products literature on Australian Dysidea sponges extends back over half a century and suffers from the perception of being near exhausted, fractionation of Dysidea sp. (CMB-01171) led to the discovery of a family of 10 new biosynthetically and chemically related sesquiterpenes. Detailed spectroscopic analysis guided structure elucidation identified dysidealactams A-F (1-6), dysidealactones A and B (7 and 8), and two solvolysis artifacts, 9 and 10. The dysidealactams A-D (1-4) incorporate a rare glycinyl-lactam functionality, while dysidealactam E (5) is particularly noteworthy in incorporating an unprecedented glycinyl-imide moiety. In addition to expanding knowledge of Dysidea natural products, this study demonstrates the value of applying GNPS molecular networking to map chemical diversity and prioritize the selection of marine sponge extracts for more detailed chemical analysis.


Assuntos
Produtos Biológicos/farmacologia , Dysidea/química , Lactamas/química , Sesquiterpenos/farmacologia , Animais , Austrália , Produtos Biológicos/química , Imidas/química , Lactonas/química , Estrutura Molecular , Poríferos/química , Sesquiterpenos/química
8.
Asian Pac J Cancer Prev ; 21(4): 997-1003, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32334461

RESUMO

BACKGROUND: Marine sponge is a rich natural resource of many pharmacological compounds and various bioactive anticancer agents are derived from marine organisms like sponges. METHODS: studying the anticancer activity and Drug ability of marine sponge Dysidea avara using Cell lines oral epithelial cancer cell (KB/C152) and T-lymphocytic leukemia cell line (Jurkat/ E6-1). Marine sponge was collected from Persian Gulf. Several analytical techniques have been used to obtain and recognize stigmasterol, including column chromatography, thin layer chromatography, and gas chromatography-mass spectrometry. The PASS Prediction Activity was used to investigate the apoptosis-inducing effect of stigmasterol. The cytotoxic activity of stigmasterol was examined using yellow tetrazolium salt XTT (sodium 2, 3,-bis (2methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium) assay. The stigmasterol were docked within the protein tyrosine kinase (PTKs) (PDB code: 1t46) and epidermal growth factor receptor (EGFRK) (PDB code: 1M17). Also, the pharmacological characteristics of stigmasterol were predicted using PerADME, SwissADME, and Molinspi ration tools. Apoptosis-inducing effect of stigmasterol indicate the stigmasterol in terms of the possibility of apoptosis in cells. RESULTS: The apoptosis inducement results of known stigmasterol were determined by PASS on-line prediction. The compound exhibit potent cytotoxic properties against KB/C152 cell compared to Jurkat/ E6-1 cell. The stigmasterol showed the cytotoxicity effects on KB/C152 and HUT78 with IC50 ranges of 81.18 and 103.03 µg/ml, respectively. Molecular docking showed that, stigmasterol bound stably to the active sites of the protein tyrosine kinase (PTKs) (PDB code: 1t46) and epidermal growth factor receptor (EGFRK) (PDB code: 1M17). CONCLUSION: The compound showed desirable pharmacokinetic properties (ADME). This provided direct evidence of how a prospective anti-cancer agent can be stigmasterol. The preclinical studies paved the way for a potential new compound of anti-cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Dysidea/química , Leucemia de Células T/patologia , Neoplasias Bucais/patologia , Neoplasias Epiteliais e Glandulares/patologia , Esteróis/farmacologia , Estigmasterol/farmacologia , Animais , Antineoplásicos/química , Sobrevivência Celular , Humanos , Leucemia de Células T/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Esteróis/química , Estigmasterol/química , Células Tumorais Cultivadas
9.
Mar Drugs ; 18(2)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075136

RESUMO

The chemical analysis of the sponge Dysidea avara afforded the known sesquiterpene quinone avarone, along with its reduced form avarol. To further explore the role of the thiazinoquinone scaffold as an antiplasmodial, antileishmanial and antischistosomal agent, we converted the quinone avarone into the thiazinoquinone derivative thiazoavarone. The semisynthetic compound, as well as the natural metabolites avarone and avarol, were pharmacologically investigated in order to assess their antiparasitic properties against sexual and asexual stages of Plasmodium falciparum, larval and adult developmental stages of Schistosoma mansoni (eggs included), and also against promastigotes and amastigotes of Leishmania infantum and Leishmania tropica. Furthermore, in depth computational studies including density functional theory (DFT) calculations were performed. A toxic semiquinone radical species which can be produced starting both from quinone- and hydroquinone-based compounds could mediate the anti-parasitic effects of the tested compounds.


Assuntos
Cicloexenos/farmacologia , Leishmania/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quinonas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Sesquiterpenos/farmacologia , Tiazinas/farmacologia , Animais , Antiparasitários/farmacologia , Dysidea/química , Leishmania infantum/efeitos dos fármacos , Leishmania tropica/efeitos dos fármacos
10.
J Nat Prod ; 83(2): 516-523, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990554

RESUMO

Granulosane A (1), a new C27 bishomoscalarane sesterterpenoid with a rare 6/6/6/8 tetracyclic skeleton, together with eight additional new C27 bishomoscalarane sesterterpenes (2, 8-14) and five new C26 20,24-bishomo-25-norscalarane sesterterpenes (3-7), were isolated from the marine sponge Dysidea granulosa collected in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculation methods. Compound 4 showed antiproliferative activities against two cancer cell lines.


Assuntos
Antineoplásicos/isolamento & purificação , Dysidea/química , Sesterterpenos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , China , Humanos , Estrutura Molecular , Polissacarídeos/química , Poríferos/química , Sesterterpenos/química , Sesterterpenos/farmacologia
11.
J Liposome Res ; 30(3): 218-226, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146614

RESUMO

The liposomal integration method, in conjunction with electron paramagnetic resonance (EPR) spectroscopy, has been presented for the investigation of antioxidant activity of selected water-insoluble compound towards biologically relevant free radicals. This method was applied to avarol, a sesquiterpenoid hydroquinone isolated from the marine sponge Dysidea avara. The antioxidant activity of water-insoluble avarol towards •OH, O2•- and NO• radicals was attained by its incorporation into the DPPC liposomes bilayer, and towards ascorbyl radicals in the organic solvent. Avarol's activity towards •OH, O2•-, NO• and ascorbyl radicals was 86.2%, 50.9%, 23.6% and 61.8%, respectively, showing its significant radical scavenging potential.


Assuntos
Antioxidantes/farmacologia , Radicais Livres/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Dysidea/química , Lipossomos , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Solubilidade , Água/química
12.
Environ Sci Process Impacts ; 21(10): 1754-1763, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31532404

RESUMO

An integrated in vitro and in silico approach was applied to evaluate the potency of hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and spongiadioxins (OH-PBDDs) isolated from Dysidea sponges on the activity of the recombinant α-d-galactosidase of the GH36 family. It was revealed for the first time that all compounds rapidly and apparently irreversibly inhibited the bacterial α-d-galactosidase. The structure-activity relationship study in the series of OH-PBDEs showed that the presence of an additional hydroxyl group in 5 significantly enhanced the potency (IC50 4.26 µM); the increase of bromination in compounds from 1 to 3 increased their potency (IC50 41.8, 36.0, and 16.0 µM, respectively); the presence of a methoxy group decreased the potency (4, IC50 60.5 µM). Spongiadioxins 6, 7, and 8 (IC50 16.6, 33.1, and 28.6 µM, respectively) exhibited inhibitory action comparable to that of monohydroxylated diphenyl ethers 1-3. Docking analysis revealed that all compounds bind in a pocket close to the catalytic amino acid residues. Molecular docking detected significant compound-enzyme interactions in the binding sites of α-d-galactosidase. Superimposition of the enzyme-substrate and the enzyme-inhibitor complexes showed that their binding sites overlap.


Assuntos
Dioxinas/química , Dysidea/química , Éteres Difenil Halogenados/química , alfa-Galactosidase/química , Animais , Dioxinas/isolamento & purificação , Éteres Difenil Halogenados/isolamento & purificação , Halogenação , Modelos Moleculares , Simulação de Acoplamento Molecular , Domínios Proteicos , alfa-Galactosidase/antagonistas & inibidores
13.
Org Lett ; 21(16): 6190-6193, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31246040

RESUMO

The chemical investigation of the marine sponge Dysidea frondosa discovered a pair of unprecedented bioconjugates that are composed of a meroterpene and an unusual psammaplysin alkaloid. The structures of frondoplysins A (1) and B (2) were characterized by analysis of HRMS and NMR data coupled with single-crystal X-ray diffraction. Frondoplysin A was found to be a potent inhibitor targeting protein-tyrosine phosphatase 1B (PTP1B) with an IC50 value of 0.39 µM.


Assuntos
Alcaloides/química , Dysidea/química , Inibidores Enzimáticos/farmacologia , Alcaloides/farmacologia , Alcaloides/toxicidade , Animais , Animais Geneticamente Modificados , Antioxidantes/química , Antioxidantes/farmacologia , Cristalografia por Raios X , Inibidores Enzimáticos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Peixe-Zebra/genética
14.
In Vitro Cell Dev Biol Anim ; 55(3): 149-158, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30747414

RESUMO

Sponges are rich sources of novel natural products. Production in cell cultures may be an option for supply of these compounds but there are currently no sponge cell lines. Because there is a lack of understanding about the precise conditions and nutritional requirements that are necessary to sustain sponge cells in vitro, there has yet to be a defined, sponge-specific nutrient medium. This study utilized a genetic algorithm approach to optimize the amino acid composition of a commercially available basal cell culture medium in order to increase the metabolic activity of cells of the marine sponge Dysidea etheria. Four generations of the algorithm were carried out in vitro in wet lab conditions and an optimal medium combination was selected for further evaluation. When compared to the basal medium control, there was a twofold increase in metabolic activity. The genetic algorithm approach can be used to optimize other components of culture media to efficiently optimize chosen parameters without the need for detailed knowledge on all possible interactions.


Assuntos
Algoritmos , Técnicas de Cultura de Células/métodos , Meios de Cultura/química , Meios de Cultura/farmacologia , Dysidea/citologia , Aminoácidos/análise , Animais , Dysidea/efeitos dos fármacos
15.
Org Lett ; 21(3): 767-770, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30676034

RESUMO

Three unusual meroterpenoids, septosones A-C (1-3), were isolated from the marine sponge Dysidea septosa. The structures were determined by analysis of spectroscopic data combined with single-crystal X-ray diffraction and ECD calculations. Septosone A (1) features an unprecedented "septosane" carbon skeleton, whereas septosones B (2) and C (3) share a rare spiro[4.5]decane motif. Septosone A showed in vivo anti-inflammatory activity in CuSO4-induced transgenic fluorescent zebrafish likely through inactivation of the NF-κB signaling pathway.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Carbono/química , Dysidea/química , Terpenos/química , Terpenos/farmacologia , Animais , Células HEK293 , Humanos , Modelos Moleculares , Conformação Molecular , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
16.
Sci Rep ; 8(1): 16081, 2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30382170

RESUMO

The innate immune system helps animals to navigate the microbial world. The response to microbes relies on the specific recognition of microbial-associated molecular patterns (MAMPs) by immune receptors. Sponges (phylum Porifera), as early-diverging animals, provide insights into conserved mechanisms for animal-microbe crosstalk. However, experimental data is limited. We adopted an experimental approach followed by RNA-Seq and differential gene expression analysis in order to characterise the sponge immune response. Two Mediterranean species, Aplysina aerophoba and Dysidea avara, were exposed to a "cocktail" of MAMPs (lipopolysaccharide and peptidoglycan) or to sterile artificial seawater (control) and sampled 1 h, 3 h, and 5 h post-treatment for RNA-Seq. The response involved, first and foremost, a higher number of differentially-expressed genes in A. aerophoba than D. avara. Secondly, while both species constitutively express a diverse repertoire of immune receptors, they differed in their expression profiles upon MAMP challenge. The response in D. avara was mediated by increased expression of two NLR genes, whereas the response in A. aerophoba involved SRCR and GPCR genes. From the set of annotated genes we infer that both species activated apoptosis in response to MAMPs while in A. aerophoba phagocytosis was additionally stimulated. Our study assessed for the first time the transcriptomic responses of sponges to MAMPs and revealed conserved and species-specific features of poriferan immunity as well as genes potentially relevant to animal-microbe interactions.


Assuntos
Bactérias/classificação , Biomarcadores/análise , Dysidea/microbiologia , Poríferos/microbiologia , Receptores Imunológicos/genética , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Perfilação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Peptidoglicano/farmacologia , Filogenia
17.
Asian Pac J Cancer Prev ; 19(8): 2149-2154, 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30139218

RESUMO

Background: Acute lymphoblastic leukemia (ALL) is one of the most dominant malignancies among children, characterized by production of immature and dysfunctional blasts which are resistant to cytotoxic chemotherapeutic agents. Therefore, research protocols are currently focusing on discovery of novel anti-cancer agents to enhance survival rates and decrease unwanted side effects. Approximately two-thirds of the planet is covered by oceans with a massive range of marine organisms of interest to scientists in pharmaceutical fields. Methods: Among marine resources, sponges are known to have beneficial effects in the treatment of numerous malignancies. One fraction of crude extracts containing α-Santonin was made from the Persian Gulf marine sponge, Dysidea avara, and investigated for anticancer effects. Results: Treatment of ALL B-lymphocytes with the Dysidea avara extract caused augmentation in ROS generation, decline in mitochondrial membrane potential, mitochondrial swelling, release of cytochrome c from mitochondria and activation of caspase-3 only in mitochondria isolated from B-ALL lymphocytes. Conclusion: In brief, our results suggest that Dysidea avara extracts may selectively induce apoptosis in malignant pediatric lymphocytes.


Assuntos
Antineoplásicos/farmacologia , Linfócitos B/patologia , Dysidea/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Santonina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Proliferação de Células/efeitos dos fármacos , Criança , Citocromos c/metabolismo , Humanos , Oceano Índico , Mitocôndrias/efeitos dos fármacos , Poríferos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Células Tumorais Cultivadas
18.
Appl Microbiol Biotechnol ; 102(18): 7865-7875, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30039331

RESUMO

BC194, a derivative of borrelidin (BN) that features a lower cytotoxicity than that of BN due to an altered starter unit, trans-1,2-cyclobutanedicarboxylic acid (trans-1,2-CBDA), is a potent inhibitor of angiogenesis. However, BC194 production has only been reported to occur via mutasynthesis, which requires tedious, multistep genetic manipulation. In this study, we surveyed several factors contributing to the precursor-directed biosynthesis of BC194 and provided an alternative method for the production of BC194 that is directly applicable to other BN-producing strains. First, the precursor-directed biosynthesis of BC194 by a BN-producing strain, Streptomyces rochei MB037 derived from sponge Dysidea arenaria, was carried out in modified Radix astragali (RA) medium with 5 mM trans-1,2-CBDA. Next, possible inhibitors of BN starter unit trans-1,2-cyclopentanedicarboxylic acid (trans-1,2-CPDA) biosynthesis were investigated. It was found that potassium ferricyanide was a possible inhibitor of 3,4-dihydroxyphenylacetate 2,3-dioxygenase (DHPAO) and capable of suppressing the yield of BN and increasing the BC194 yield by 112.5% (from 5.2 ± 0.76 to 11.9 ± 0.59 mg/L). BC194 yield was further enhanced in the presence of 50 mM trans-1,2-CBDA, reaching 20.2 ± 0.62 mg/L. Furthermore, 3% macroporous adsorbent DA-201 resin was added to the fermentation broth, enabling a further 36.6% increase in BC194 production and reaching 27.59 ± 1.15 mg/L. Moreover, an efficient separation of BC194 with approximately 95% purity was developed by employing high-speed counter-current chromatography (HSCCC), achieving an improved recovery (approximately 93%).


Assuntos
Dysidea/microbiologia , Microbiologia Industrial/métodos , Streptomyces/isolamento & purificação , Streptomyces/metabolismo , Animais , Distribuição Contracorrente , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/metabolismo , Fermentação , Streptomyces/classificação , Streptomyces/genética
19.
Org Lett ; 20(10): 3092-3095, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29741384

RESUMO

Dysiarenone (1), a dimeric C21 meroterpenoid featuring an unprecedented 2-oxaspiro[bicyclo[3.3.1]nonane-9,1'-cyclopentane] carbon skeleton, was isolated from the marine sponge Dysidea arenaria. The structure of 1 was determined by HRMS and NMR spectroscopic analyses coupled with ECD calculations. Dysiarenone showed inhibitory activities against COX-2 expression and the production of prostaglandin E2 with an IC50 value of 6.4 µM in LPS-stimulated RAW264.7 macrophages.


Assuntos
Dysidea/química , Animais , Ciclo-Oxigenase 2 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Terpenos
20.
Biomed Pharmacother ; 100: 417-425, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29471244

RESUMO

AIMS: To investigate the cytoprotective effects of two sesquiterpene aminoquinones isolated from the marine sponge Dysidea fragilis, Dysidaminone H (DA8) and 3'-methylamino-avarone (DA14), we examined their effects against hydrogen peroxide (H2O2)-induced oxidative injury in human keratinocyte cell line and elucidated the underlying mechanisms. MAIN METHODS: Cell viability was detected using a CCK-8 assay kit. Intracellular reactive oxygen species (ROS) production was measured by fluorescence of 2, 7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA). Messenger RNA and protein expression were measured by real-time quantitative PCR and western blotting analysis. Immunocytochemistry was performed to determine the intracellular location of nuclear factorerythroid 2 p45 related factor 2 (Nrf2). The antioxidant response element (ARE)-luciferase reporter gene assay and RNA interference were used to establish the role of ARE and Nrf2. KEY FINDINGS: DA8 and DA14 (DAs) resisted H2O2induced decline of cell viability by inhibiting the accumulation of ROS. Meanwhile, DAs increased HO-1 expression and ARE activity and induced Nrf2 expression, as well as the accumulation of Nrf2 in the cell nucleus. However, silencing of Nrf2 abolished DAs-induced HO-1 expression and ARE luciferase activation. In addition, DAs induced the phosphorylation of both cyclic AMP-activated protein kinase-α (AMPKα) and extracellular signal-regulated kinase (ERK), while specific inhibitors of AMPKα and ERK abrogated HO1 upregulation and Nrf2 activation. SIGNIFICANCE: DAs provided cytoprotective effects against H2O2-induced cytotoxicity by activation of the Nrf2/ARE/HO-1 pathway via phosphorylation of AMPKα and ERK. The findings suggested that DA8 and DA14 might be the candidate therapeutic agents for skin diseases caused by oxidative injury.


Assuntos
Elementos de Resposta Antioxidante/fisiologia , Dysidea , Heme Oxigenase-1/metabolismo , Queratinócitos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Sesquiterpenos/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoquinolinas/isolamento & purificação , Aminoquinolinas/farmacologia , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Relação Dose-Resposta a Droga , Humanos , Queratinócitos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/isolamento & purificação
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