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1.
Nature ; 613(7944): 460-462, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36653563

RESUMO

Most structural and evolutionary properties of galaxies strongly rely on the stellar initial mass function (IMF), namely the distribution of the stellar mass formed in each episode of star formation1-4. The IMF shapes the stellar population in all stellar systems, and so has become one of the most fundamental concepts of modern astronomy. Both constant and variable IMFs across different environments have been claimed despite a large number of theoretical5-7 and observational efforts8-15. However, the measurement of the IMF in Galactic stellar populations has been limited by the relatively small number of photometrically observed stars, leading to high uncertainties12-16. Here we report a star-counting result based on approximately 93,000 spectroscopically observed M-dwarf stars, an order of magnitude more than previous studies, in the 100-300 parsec solar neighbourhood. We find unambiguous evidence of a variable IMF that depends on both metallicity and stellar age. Specifically, the stellar population formed at early times contains fewer low-mass stars compared with the canonical IMF, independent of stellar metallicities. In more recent times, however, the proportion of low-mass stars increases with stellar metallicity. The variable abundance of low-mass stars in our Milky Way establishes a powerful benchmark for models of star formation and can heavily affect results in Galactic chemical-enrichment modelling, mass estimation of galaxies and planet-formation efficiency.

2.
Environ Res ; 243: 117862, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38065382

RESUMO

To gain a comprehensive understanding of the seasonal variation in the structure of phytoplankton communities in the Southern Yellow Sea (SYS), two research expeditions were conducted from 12 to 24 in April 2019, and from 12 to 22 in October of 2019. During the spring season, the phytoplankton community within the SYS was primarily comprised of diatoms and dinoflagellates, while in autumn, diatoms and cyanobacteria dominated. Thalassiosira rotula and Paralia sulcata were the dominant species in both seasons. In spring, P. sulcata displayed no obvious correlation with any environmental parameter, while in autumn, it exhibited negative correlations with environmental factors. According to the cluster and multidimensional scaling analyses, the phytoplankton community was stratified into three distinct ecological provinces in the SYS: the Western Yellow Sea, the Yellow Sea basin, and the southern coastal region. The phytoplankton community composition was predominantly affected by seasonal fluctuations in temperature and nutrient levels. Notably, the Yellow Sea basin exhibited the lowest phytoplankton abundance, largely because of the impact of the Yellow Sea Cold Water Mass. Furthermore, the presence of cyanobacteria, particularly prevalent in the Yellow Sea basin, may have been facilitated by transport mechanisms associated with the Kuroshio current. Aggregated boosted tree (ABT) and Generalized Additive models (GAM) suggested that temperature, DIN, salinity, and DIP were significant parameters of phytoplankton abundance in SYS. Additionally, the N:P nutrient ratio was a key parameter in governing the structure of phytoplankton communities during both seasons.


Assuntos
Cianobactérias , Diatomáceas , Dinoflagellida , Fitoplâncton , Água do Mar , Estações do Ano , Monitoramento Ambiental/métodos , China
3.
Ann Clin Microbiol Antimicrob ; 22(1): 94, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904155

RESUMO

OBJECTIVES: Antimicrobial susceptibility tests (ASTs) are pivotal tools for detecting and combating infections caused by multidrug-resistant rapidly growing mycobacteria (RGM) but are time-consuming and labor-intensive. DESIGN: We used a Mycobacterium abscessus-based RGM model to develop a rapid (24-h) AST from the beginning of the strain culture, the Clinical Antimicrobials Susceptibility Test Ramanometry for RGM (CAST-R-RGM). The ASTs obtained for 21 clarithromycin (CLA)-treated and 18 linezolid (LZD)-treated RGM isolates. RESULTS: CAST-R-RGM employs D2O-probed Raman microspectroscopy to monitor RGM metabolic activity, while also revealing bacterial antimicrobial drug resistance mechanisms. The results of clarithromycin (CLA)-treated and linezolid (LZD)-treated RGM isolates exhibited 90% and 83% categorical agreement, respectively, with conventional AST results of the same isolates. Furthermore, comparisons of time- and concentration-dependent Raman results between CLA- and LZD-treated RGM strains revealed distinct metabolic profiles after 48-h and 72-h drug treatments, despite similar profiles obtained for both drugs after 24-h treatments. CONCLUSIONS: Ultimately, the rapid, accurate, and low-cost CAST-R-RGM assay offers advantages over conventional culture-based ASTs that warrant its use as a tool for improving patient treatment outcomes and revealing bacterial drug resistance mechanisms.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Mycobacterium , Humanos , Claritromicina/farmacologia , Linezolida/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas
4.
Clin Chem ; 68(8): 1064-1074, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35714147

RESUMO

BACKGROUND: The battle against Helicobacter pylori (H. pylori) infections demands fast, reliable, and sensitive methods for pathogen identification (ID), antimicrobial susceptibility tests (ASTs) based on metabolic response, and genome-wide mutation profiling that reveals resistance mechanisms. METHODS: Here we introduce Clinical Antimicrobial Susceptibility Test Ramanometry for H. pylori (CAST-R-HP), and its validation with clinical samples. This method performs rapid ID, metabolism inhibition-based AST, and high-quality whole-genome sequencing for cells of targeted resistance phenotype, all at precisely 1-cell resolution and directly from biopsy samples. RESULTS: In CAST-R-HP, automated acquisition and machine learning of single-cell Raman spectra (SCRS) enable distinguishing individual H. pylori cells directly from a biopsy sample, with 98.5 ± 0.27% accuracy in ID. Moreover, by adding a 48- to72-h D2O feeding and drug exposure step prior to SCRS acquisition, CAST-R-HP reports AST for levofloxacin and clarithromycin with 100% accuracy, based on metabolic inhibition level. Furthermore, CAST-R-HP supports rapid sorting, low-bias DNA amplification, and full genome sequencing of single H. pylori cells with the SCRS defined, targeted drug-susceptibility phenotype, via Raman-activated gravity-driven cell encapsulation and sequencing. The genome-wide mutation map (maximum 99.70% coverage), at precisely 1-cell resolution, not only elucidates the drug-susceptibility phenotypes but also unveils their underlying molecular mechanisms. CONCLUSION: The culture independency, shorter turnaround time, high resolution, and comprehensive information output suggest that CAST-R-HP is a powerful tool for diagnosing and treating H. pylori infections.


Assuntos
Anti-Infecciosos , Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Biópsia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Humanos , Testes de Sensibilidade Microbiana
5.
Mar Drugs ; 20(6)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35736194

RESUMO

In this study, the anti-inflammatory activity of sulfated polysaccharides isolated from the green seaweed Codium fragile (CFCE-PS) was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results demonstrated that CFCE-PS significantly increased the viability of LPS-induced RAW 264.7 cells in a concentration-dependent manner. CFCE-PS remarkably and concentration-dependently reduced the levels of inflammatory molecules including prostaglandin E2, nitric oxide (NO), interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 in LPS-stimulated RAW 264.7 cells. In addition, in vivo test results indicated that CFCE-PS effectively reduced reactive oxygen species, cell death, and NO levels in LPS-stimulated zebrafish. Thus, these results indicate that CFCE-PS possesses in vitro and in vivo anti-inflammatory activities and suggest it is a potential ingredient in the functional food and pharmaceutical industries.


Assuntos
Clorófitas , Lipopolissacarídeos , Animais , Anti-Inflamatórios/farmacologia , Clorófitas/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Polissacarídeos/farmacologia , Células RAW 264.7 , Sulfatos/farmacologia , Peixe-Zebra/metabolismo
6.
Mar Drugs ; 20(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36135746

RESUMO

Seaweeds are potential ingredients in the cosmeceutical industry. Our previous study demonstrates that the phlorotannin-enriched extract of Ecklonia maxima (EME-EA) containing dieckol and eckmaxol possesses strong anti-inflammatory activity and suggests the cosmeceutical potential of EME-EA. In order to evaluate the cosmeceutical potential of EME-EA, the anti-melanogenesis and photoprotective effects of EME-EA were investigated in this study. EME-EA remarkably inhibited mushroom tyrosinase and melanogenesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 cells. In addition, EME-EA significantly suppressed UVB-induced HaCaT cell death that was consistent with inhibition of apoptosis and reduction in scavenging intracellular reactive oxygen species. Furthermore, EME-EA significantly inhibited collagen degradation and matrix metalloproteinases expression in UVB-irradiated HDF cells in a concentration-dependent manner. These results indicate that EME-EA possesses strong anti-melanogenesis and photoprotective activities and suggest EME-EA is an ideal ingredient in the pharmaceutical and cosmeceutical industries.


Assuntos
Cosmecêuticos , Phaeophyceae , Anti-Inflamatórios , Benzofuranos , Colágeno/metabolismo , Metaloproteinases da Matriz , Melaninas , Monofenol Mono-Oxigenase/metabolismo , Phaeophyceae/metabolismo , Espécies Reativas de Oxigênio , alfa-MSH/farmacologia
7.
Mar Drugs ; 19(8)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34436269

RESUMO

Seaweed of Saccharina japonica is the most abundantly cultured brown seaweed in the world, and has been consumed in the food industry due to its nutrition and the unique properties of its polysaccharides. In this study, fucoidan (LJNF3), purified from S. japonica, was found to be a novel sulfated galactofucan, with the monosaccharide of only fucose and galactose in a ratio of 79.22:20.78, and with an 11.36% content of sulfate groups. NMR spectroscopy showed that LJNF3 consists of (1→3)-α-l-fucopyranosyl-4-SO3 residues and (1→6)-ß-d-galactopyranose units. The molecular mechanism of the anti-inflammatory effect in RAW264.7 demonstrated that LJNF3 reduced the production of nitric oxide (NO), and down-regulated the expression of MAPK (including p38, ENK and JNK) and NF-κB (including p65 and IKKα/IKKß) signaling pathways. In a zebrafish experiment assay, LJNF3 showed a significantly protective effect, by reducing the cell death rate, inhibiting NO to 59.43%, and decreasing about 40% of reactive oxygen species. This study indicated that LJNF3, which only consisted of fucose and galactose, had the potential to be developed in the biomedical, food and cosmetic industries.


Assuntos
Anti-Inflamatórios/farmacologia , Organismos Aquáticos/química , Fucose/farmacologia , Galactose/farmacologia , Alga Marinha/química , Animais , Concentração Inibidora 50 , Camundongos , Células RAW 264.7/efeitos dos fármacos , Peixe-Zebra
8.
Mar Drugs ; 19(5)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063550

RESUMO

In the present study, the in vitro and in vivo anti-inflammatory effects of the sulfated polysaccharides isolated from Sargassum fulvellum (SFPS) were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that SFPS improved the viability of LPS-stimulated RAW 264.7 macrophages from 80.02 to 86.80, 90.09, and 94.62% at the concentration of 25, 50, and 100 µg/mL, respectively. Also, SFPS remarkably and concentration-dependently decreased the production levels of inflammatory molecules including nitric oxide (NO), tumor necrosis factor-alpha, prostaglandin E2, interleukin-1 beta, and interleukin-6 in LPS-treated RAW 264.7 macrophages. In addition, SFPS significantly inhibited the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-treated RAW 264.7 macrophages. Furthermore, the in vivo test results indicated that SFPS improved the survival rate of LPS-treated zebrafish from 53.33 to 56.67, 60.00, and 70.00% at the concentration of 25, 50, and 100 µg/mL, respectively. In addition, SFPS effectively reduced cell death, reactive oxygen species, and NO levels in LPS-stimulated zebrafish. Taken together, these results suggested that SFPS possesses strong in vitro and in vivo anti-inflammatory activities, and could be used as an ingredient to develop anti-inflammatory agents in the functional food and pharmaceutical industries.


Assuntos
Anti-Inflamatórios/farmacologia , Polissacarídeos/farmacologia , Sargassum/química , Alga Marinha/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Morte Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Sulfatos/química , Taxa de Sobrevida , Peixe-Zebra
9.
Molecules ; 26(22)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34833989

RESUMO

Skin is the largest organ of humans. Overexposure to ultraviolet (UV) is the primary environmental factor that causes skin damage. The compound, (-)-loliode, isolated from the brown seaweed Sargassum horneri, showed strong antioxidant and anti-inflammatory activities in in vitro and in vivo models. To further explore the potential of (-)-loliode in cosmetics, in the present study, we investigated the photoprotective effect of (-)-loliode in vitro in skin cells and in vivo in zebrafish. The results indicated that (-)-loliode significantly reduced intracellular reactive oxygen species (ROS) level, improved cell viability, and suppressed apoptosis of UVB-irradiated human keratinocytes. In addition, (-)-loliode remarkably attenuated oxidative damage, improved collagen synthesis, and inhibited matrix metalloproteinases expression in UVB-irradiated human dermal fibroblasts. Furthermore, the in vivo test demonstrated that (-)-loliode effectively and dose-dependently suppressed UVB-induced zebrafish damage displayed in decreasing the levels of ROS, nitric oxide, lipid peroxidation, and cell death in UVB-irradiated zebrafish. These results indicate that (-)-loliode possesses strong photoprotective activities and suggest (-)-loliode may an ideal ingredient in the pharmaceutical and cosmeceutical industries.


Assuntos
Apoptose/efeitos dos fármacos , Benzofuranos , Derme/metabolismo , Fibroblastos/metabolismo , Queratinócitos/metabolismo , Sargassum/química , Alga Marinha/química , Protetores Solares , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos da radiação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Linhagem Celular , Humanos , Espécies Reativas de Oxigênio/metabolismo , Protetores Solares/química , Protetores Solares/isolamento & purificação , Protetores Solares/farmacologia , Raios Ultravioleta/efeitos adversos
10.
Mar Drugs ; 18(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33255947

RESUMO

Inflammation is a complicated host-protective response to stimuli and toxic conditions, and is considered as a double-edged sword. A sulfated Saccharinajaponica polysaccharide (LJPS) with a sulfate content of 9.07% showed significant inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells and zebrafish. Its chemical and structural properties were investigated via HPLC, GC, FTIR, and NMR spectroscopy. In vitro experiments demonstrated that LJPS significantly inhibited the generation of nitric oxide (NO) and prostaglandin E2 (PGE2) via the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and suppressed pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1ß production via the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signal pathways in LPS-induced RAW 264.7 cells. Moreover, LJPS showed strong protective effects against LPS-induced inflammatory responses in zebrafish, increasing the survival rate, reducing the heart rate and yolk sac edema size, and inhibiting cell death and the production of intracellular reactive oxygen species (ROS) and NO. Its convenience for large-scale production and significant anti-inflammatory activity indicated the potential application of LJPS in functional foods, cosmetics, and pharmaceutical industries.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Phaeophyceae/metabolismo , Polissacarídeos/farmacologia , Alga Marinha/metabolismo , Animais , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Macrófagos/enzimologia , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Peixe-Zebra/embriologia
11.
Mar Drugs ; 18(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32549256

RESUMO

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry.


Assuntos
Laminaria/química , Polissacarídeos/farmacologia , Protetores Solares/farmacologia , Raios Ultravioleta/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Embrião não Mamífero , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Polissacarídeos/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/isolamento & purificação , Peixe-Zebra
12.
Langmuir ; 35(11): 4094-4100, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791688

RESUMO

We have developed microsized perfluorocarbon (PFC) emulsions with different sizes as artificial oxygen carriers (OCs) via Shirasu porous glass membrane emulsification. Monodispersed PFC emulsions with narrow size distribution were obtained. By changing the membrane pore size, we were able to precisely control the size of emulsions and fabricate emulsions similar in size to human red blood cells. Behaviors of Pluronics with different physiochemical properties (F127, F68, P85, and P103) as surfactants were also investigated, which evidenced that the type and concentration of Pluronics have a major impact on the size of emulsions and the response to different thermal conditions. The F127-stabilized microsized PFC emulsions were stable even during autoclave sterilization. The emulsions were loaded with Ru(ddp)-an oxygen-sensitive probe-on their surfaces to indicate oxygen concentration. Finally, incubations with HeLa cells that show fluorescence in response to hypoxia cultured in 2D and 3D suggested promising potential of our emulsions for OCs.


Assuntos
Fluorocarbonos/química , Vidro/química , Oxigênio/química , Emulsões/química , Fluorescência , Células HeLa , Humanos , Membranas Artificiais , Tamanho da Partícula , Porosidade , Propriedades de Superfície
13.
Cell Mol Neurobiol ; 37(2): 211-222, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26971524

RESUMO

Progressive accumulation of beta-amyloid (Aß) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer's disease (AD). Hence, inhibition of Aß-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aß-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aß-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aß-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aß were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aß-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aß-induced neurotoxicity.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Curcumina/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Fragmentos de Peptídeos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
14.
Neurochem Res ; 42(4): 997-1005, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27995497

RESUMO

Chemotherapy has always been one of the most effective ways in combating human glioma. However, the high metastatic potential and resistance toward standard chemotherapy severely hindered the chemotherapy outcomes. Hence, searching effective chemotherapy drugs and clarifying its mechanism are of great significance. Salinomycin an antibiotic shows novel anticancer potential against several human tumors, including human glioma, but its mechanism against human glioma cells has not been fully elucidated. In the present study, we demonstrated that salinomycin treatment time- and dose-dependently inhibited U251 and U87 cells growth. Mechanically, salinomycin-induced cell growth inhibition against human glioma was mainly achieved by induction of G1-phase arrest via triggering reactive oxide species (ROS)-mediated DNA damage, as convinced by the activation of histone, p53, p21 and p27. Furthermore, inhibition of ROS accumulation effectively attenuated salinomycin-induced DNA damage and G1 cell cycle arrest, and eventually reversed salinomycin-induced cytotoxicity. Importantly, salinomycin treatment also significantly inhibited the U251 tumor xenograft growth in vivo through triggering DNA damage-mediated cell cycle arrest with involvement of inhibiting cell proliferation and angiogenesis. The results above validated the potential of salinomycin-based chemotherapy against human glioma.


Assuntos
Dano ao DNA/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Glioma/metabolismo , Piranos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dano ao DNA/fisiologia , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G1 do Ciclo Celular/fisiologia , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Piranos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
Bioorg Med Chem ; 25(24): 6647-6652, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29100735

RESUMO

The free fatty acid receptor 4 (FFA4) has emerged as a promising anti-diabetic target due to its function in improvement of insulin secretion and insulin resistance. The FFA4 agonist TUG-891 revealed great potential as a widely used pharmacological tool, but it has been suffered from high plasma clearance probably because the phenylpropanoic acid is vulnerable to ß-oxidation. To identify metabolically stable analog without influence on physiological mechanism of TUG-891, we tried to incorporate deuterium at the α-position of phenylpropionic acid to afford compound 4 (GPU-028). As expected, GPU-028 revealed a longer half-life (T1/2 = 1.66 h), lower clearance (CL = 0.97 L/h/kg) and higher maximum plasma concentration (Cmax = 2035.23 µg/L), resulting in a 4-fold higher exposure than TUG-891. Although GPU-028 exhibited a similar agonistic activity in comparison to TUG-891, the hypoglycemic effect of GPU-028 was better than that of TUG-891 after treatment over four weeks in diet-induced obese mice. These positive results indicated that GPU-028 might be a better pharmacological tool than TUG-891 to explore physiological function of FFA4, especially on the in vivo study.


Assuntos
Compostos de Bifenilo/farmacologia , Deutério/química , Descoberta de Drogas , Propionatos/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Animais , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/química , Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacocinética , Compostos de Bifenilo/uso terapêutico , Células CHO , Cricetulus , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Obesidade/tratamento farmacológico , Fenilpropionatos/administração & dosagem , Fenilpropionatos/farmacocinética , Fenilpropionatos/uso terapêutico , Propionatos/química , Propionatos/metabolismo , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
16.
Mar Drugs ; 15(2)2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28230766

RESUMO

Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene), which are unique compounds from marine brown algae. In our present study, a procedure for extraction and enrichment of phlorotannins from S. fusiforme with highly antioxidant potentials was established. After comparison of different extraction methods, the optimal extraction conditions were established as follows. The freeze-dried seaweed powder was extracted with 30% ethanol-water solvent with a solid/liquid ratio of 1:5 at temperature of 25 °C for 30 min. After extraction, the phlorotannins were fractioned by different solvents, among which the ethyl acetate fraction exhibited both the highest total phlorotannin content (88.48 ± 0.30 mg PGE/100 mg extract) and the highest antioxidant activities. The extracts obtained from these locations were further purified and characterized using a modified UHPLC-QQQ-MS method. Compounds with 42 different molecular weights were detected and tentatively identified, among which the fuhalol-type phlorotannins were the dominant compounds, followed by phlorethols and fucophlorethols with diverse degree of polymerization. Eckol-type phlorotannins including some newly discovered carmalol derivatives were detected in Sargassum species for the first time. Our study not only described the complex phlorotannins composition in S. fusiforme, but also highlighted the challenges involved in structural elucidation of these compounds.


Assuntos
Produtos Biológicos/química , Phaeophyceae/química , Sargassum/química , Taninos/química , Antioxidantes/química , Peso Molecular , Floroglucinol/química , Polimerização , Polímeros/química , Alga Marinha/química
17.
Cell Mol Neurobiol ; 36(5): 647-55, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26224360

RESUMO

Hypothermia treatment is one of the neuroprotective strategies that improve neurological outcomes effectively after brain damage. Minimally invasive surgery (MIS) has been an important treatment of intracerebral hemorrhage (ICH). Herein, we evaluated the neuroprotective effect and mechanism of MIS joint local cooling lavage (LCL) treatment on ICH via detecting the inflammatory responses, oxidative injury, and neuronal apoptosis around the hematoma cavity in rats. ICH model was established by type IV collagenase caudatum infusion. The rats were treated with MIS 6 h after injection, and then were lavaged by normothermic (37 °C) and hypothermic (33 °C) normal saline in brain separately. The results indicated that MIS joint LCL treatment showed enhanced therapeutic effects against ICH-induced inflammation injury and apoptosis in rats, as convinced by the decline of TUNEL-positive cells, followed by the decrease of IL-1ß and LDH and increase of IL-10 and SOD. This study demonstrated that the strategy of using MIS joint LCL may achieve enhanced neuroprotection against ICH-induced inflammation injury and apoptosis in rats with potential clinic application.


Assuntos
Apoptose/efeitos dos fármacos , Edema Encefálico/cirurgia , Hemorragia Cerebral/complicações , Procedimentos Cirúrgicos Minimamente Invasivos , Animais , Lesões Encefálicas/cirurgia , Hemorragia Cerebral/terapia , Inflamação/cirurgia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neurônios/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Irrigação Terapêutica/métodos
18.
Neurochem Res ; 41(6): 1439-47, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26846141

RESUMO

Selenocysteine (SeC) a natural available selenoamino acid exhibits novel anticancer activities against human cancer cell lines. However, the growth inhibitory effect and mechanism of SeC in human glioma cells remain unclear. The present study reveals that SeC time- and dose-dependently inhibited U251 and U87 human glioma cells growth by induction of S-phase cell cycle arrest, followed by the marked decrease of cyclin A. SeC-induced S-phase arrest was achieved by inducing DNA damage through triggering generation of reactive oxygen species (ROS) and superoxide anion, with concomitant increase of TUNEL-positive cells and induction of p21waf1/Cip1 and p53. SeC treatment also caused the activation of p38MAPK, JNK and ERK, and inactivation of AKT. Four inhibitors of MAPKs and AKT pathways further confirmed their roles in SeC-induced S-phase arrest in human glioma cells. Our findings advance the understanding on the molecular mechanisms of SeC in human glioma management.


Assuntos
Pontos de Checagem do Ciclo Celular/fisiologia , Dano ao DNA/fisiologia , Glioma/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Oncogênica v-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Selenocisteína/farmacologia , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Selênio/farmacologia
19.
Cell Biol Toxicol ; 32(4): 333-45, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27184666

RESUMO

Caudatin as one species of C-21 steroidal from Cynanchum bungei decne displays potential anticancer activity. However, the underlying mechanisms remain elusive. In the present study, the growth suppressive effect and mechanism of caudatin on human glioma U251 and U87 cells were evaluated in vitro. The results indicated that caudatin significantly inhibited U251 and U87 cell growth in both a time- and dose-dependent manner. Flow cytometry analysis revealed that caudatin-induced cell growth inhibition was achieved by induction of cell apoptosis, as convinced by the increase of Sub-G1 peak, PARP cleavage and activation of caspase-3, caspase-7 and caspase-9. Caudatin treatment also resulted in mitochondrial dysfunction which correlated with an imbalance of Bcl-2 family members. Further investigation revealed that caudatin triggered U251 cell apoptosis by inducing reactive oxygen species (ROS) generation through disturbing the redox homeostasis. Moreover, pretreatment of caspase inhibitors apparently weakens caudatin-induced cell killing, PARP cleavage and caspase activation and eventually reverses caudatin-mediated apoptosis. Importantly, caudatin significantly inhibited U251 tumour xenografts in vivo through induction of cell apoptosis involving the inhibition of cell proliferation and angiogenesis, which further validate its value in combating human glioma in vivo. Taken together, the results described above all suggest that caudatin inhibited human glioma cell growth by induction of caspase-dependent apoptosis with involvement of mitochondrial dysfunction and ROS generation.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Caspases/metabolismo , Glioma/tratamento farmacológico , Glicosídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Inibidores de Caspase/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glioma/metabolismo , Glioma/patologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
20.
J Ind Microbiol Biotechnol ; 42(10): 1353-62, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26286088

RESUMO

A bacterial strain capable of hydrolyzing sulfate ester bonds of p-nitrophenyl sulfate (pNPS) and agar was isolated from the coast area of Qingdao, China. It was identified as Marinomonas based on its 16S rRNA gene sequence and named as Marinomonas sp. FW-1. An arylsulfatase with a recovery of 13 % and a fold of 12 was purified to a homogeneity using ion exchange and gel filtration chromatographies. The enzyme was composed of a single polypeptide chain with the molecular mass of 33 kDa estimated using SDS-PAGE. The optimal pH and temperature of arylsulfatase were pH 9.0 and 45, respectively. Arylsulfatase was stable over pH 8-11 and at temperature below 55 °C. The K m and V max of this enzyme for the hydrolysis of pNPS were determined to be 13.73 and 270.27 µM/min, respectively. The desulfation ratio against agar from red seaweed Gelidium amansii and Gracilaria lemaneiformis were 86.11 and 89.61 %, respectively. There was no difference between the DNA electrophoresis spectrum on the gel of the arylsulfatase-treated G. amansii agar and that of the commercial agarose. Therefore, this novel alkaline arylsulfatase might have a great potential for application in enzymatic conversion of agar to agarose.


Assuntos
Ágar/química , Ágar/metabolismo , Arilsulfatases/metabolismo , Marinomonas/enzimologia , Alga Marinha/química , Arilsulfatases/química , Arilsulfatases/isolamento & purificação , China , Cromatografia em Gel , Eletroforese em Gel de Poliacrilamida , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Hidrólise , Marinomonas/classificação , Marinomonas/genética , Marinomonas/isolamento & purificação , Peso Molecular , Nitrobenzenos/metabolismo , RNA Ribossômico 16S/genética , Sefarose/química , Sefarose/metabolismo , Temperatura
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