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1.
Pestic Biochem Physiol ; 158: 25-31, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378357

RESUMO

Sodium pheophorbide a (SPA) is a natural photosensitizer. To explore its antifungal activity and mechanism, we studied its inhibitory effects on spore germination and mycelial growth of Pestalotiopsis neglecta. We used sorbitol, 2-thiobarbituric acid (TBA) and electron microscopy to determine its effects on cell wall integrity, cell membrane lipid peroxidation and mycelial morphology. Finally, the effects of SPA on enzyme activity in mycelia were determined. The results showed that SPA effectively inhibited spore germination and mycelial growth of P. neglecta under light conditions (4000 lx, 24 h). Scanning electron microscopy (SEM) revealed that SPA treatment resulted in a roughened, twisted and knotted mycelial surface and abnormal mycelial growth. SPA influenced cell wall integrity, and the content of MDA, a cell membrane lipid peroxidation product was significantly increased (P < 0.05). SPA also significantly inhibited SOD, POD and PG activity, but enhanced PPO activity (P < 0.05). In conclusion, SPA may have potential to become a biological pesticide.


Assuntos
Antifúngicos/farmacologia , Clorofila/análogos & derivados , Micélio/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Clorofila/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Micélio/ultraestrutura
2.
Int J Nanomedicine ; 14: 5527-5540, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413561

RESUMO

Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) grafted folate (FA-PEG-b-PAsp) to obtain the block polymer folate polyethylene glycol-b-poly(asparaginyl-chidamide) (FA-PEG-b-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide-a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-b-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.


Assuntos
Aminopiridinas/química , Benzamidas/química , Ácido Fólico/uso terapêutico , Micelas , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/análogos & derivados , Clorofila/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Ácido Fólico/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/metabolismo
3.
Sci Total Environ ; 695: 133867, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31421346

RESUMO

Calcareous spring fens are among the rarest and most endangered wetland types worldwide. The majority of these ecosystems can be found at high latitudes, where they are affected by above average rates of climate change. Particularly winter temperatures are increasing, which results in decreased snow cover. As snow provides an insulating layer that protects ecosystems from subzero temperatures, its decrease is likely to induce stress to plants. To investigate the sensitivity of the bryophyte community - key to the functioning of calcareous spring fens - to changing climatic conditions, we studied the annual variation in ecophysiology of two dominant bryophytes: Campylium stellatum and Scorpidium scorpioides. Further, a snow removal experiment was used to simulate the effect of changing winter conditions. In both species, we observed lowest efficiency of photosystem II (Fv/Fm) in spring, indicating physiological stress, and highest chlorophyll-a, -b and carotenoid concentrations in autumn. Snow removal exacerbated physiological stress in bryophytes. Consequently Fv/Fm, pigment concentrations and chlorophyll to carotenoids ratios declined, while chlorophyll-a to -b ratios increased. Moreover, these effects of winter climate change cascaded to the growing season. C. stellatum, a low hummock inhabitor, suffered more from snow removal (annual mean decline in Fv/Fm 7.7% and 30.0% in chlorophyll-a) than S. scorpioides, a hollow species (declines 5.4% and 14.5%, respectively). Taken together, our results indicate that spring fen bryophytes are negatively impacted by winter climate change, as a result of longer frost periods and increased numbers of freeze-thaw cycles in combination with higher light intensity and dehydration.


Assuntos
Briófitas/fisiologia , Mudança Climática , Estresse Fisiológico/fisiologia , Clorofila/análogos & derivados , Ecossistema , Congelamento , Plantas , Estações do Ano , Neve , Temperatura Ambiente
4.
Environ Sci Pollut Res Int ; 26(26): 26636-26645, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31292867

RESUMO

One of the most common anthropogenic impacts on river ecosystems is the effluent discharge from wastewater treatment plants. The effects of this contamination on stream biota may be intensified in Mediterranean climate regions, which comprise a drought period that leads to flow reduction, and ultimately to stagnant pools. To assess individual and combined effects of flow stagnation and sewage contamination, biofilm and gastropod grazers were used in a 5-week experiment with artificial channels to test two flow velocity treatments (stagnant flow/basal flow) and two levels of organic contamination using artificial sewage (no sewage input/sewage input). Stressors' effects were determined on biofilm total biomass and chlorophyll (Chl) content, on oxygen consumption and growth rate of the grazers (Theodoxus fluviatilis), and on the interaction grazer-biofilm given by grazer's feeding activity (i.e., biofilm consumption rate). The single effect of sewage induced an increase in biofilm biomass and Chl-a content, simultaneously increasing both grazers' oxygen consumption and their feeding activity. Diatoms showed a higher sensitivity to flow stagnation, resulting in a lower content of Chl-c. Combined stressors interacted antagonistically for biofilm total biomass, Chl-b contents, and grazers's feeding rate. The effect of sewage increasing biofilm biomass and grazing activity was reduced by the presence of flow stagnation (antagonist factor). Our findings suggest that sewage contamination has a direct effect on the functional response of primary producers and an indirect effect on primary consumers, and this effect is influenced by water flow stagnation.


Assuntos
Biofilmes/crescimento & desenvolvimento , Biota , Conservação dos Recursos Hídricos , Rodófitas/fisiologia , Esgotos/química , Poluentes da Água/toxicidade , Abastecimento de Água , Biomassa , Clorofila/análogos & derivados , Clorofila/análise , Diatomáceas , Ecossistema , Rios , Instalações de Eliminação de Resíduos
5.
Ecotoxicol Environ Saf ; 182: 109426, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31301595

RESUMO

Quagga (Dreissena rostriformis bugensis) and zebra (D. polymorpha) mussels are broadcast spawners that produce planktonic, free swimming veligers, a life history strategy dissimilar to native North American freshwater bivalves. Dreissenid veligers require highly nutritious food to grow and survive, and thus may be susceptible to increased mortality rates during harsh environmental conditions like cyanobacteria blooms. However, the impact of cyanobacteria and one of the toxins they can produce (microcystin) has not been evaluated in dreissenid veligers. Therefore, we exposed dreissenid veligers to eleven distinct cultures (isolates) of cyanobacteria representing Anabaena, Aphanizomenon, Dolichospermum, Microcystis, and Planktothrix species and the cyanotoxin microcystin to determine the lethality of cyanobacteria on dreissenid veligers. Six-day laboratory bioassays were performed in microplates using dreissenid veligers collected from the Detroit River, Michigan, USA. Veligers were exposed to increasing concentrations of cyanobacteria and microcystin using the green algae Chlorella minutissima as a control. Based on dose response curves formulated from a Probit model, the LC50 values for cyanobacteria used in this study range between 15.06 and 135.06 µg/L chlorophyll-a, with the LC50 for microcystin-LR at 13.03 µg/L. Because LC50 values were within ranges observed in natural waterbodies, it is possible that dreissenid recruitment may be suppressed when veliger abundances overlap with seasonal cyanobacteria blooms. Thus, the toxicity of cyanobacteria to dreissenid veligers may be useful to include in models forecasting dreissenid mussel abundance and spread.


Assuntos
Cianobactérias/fisiologia , Dreissena/fisiologia , Proliferação Nociva de Algas , Animais , Bivalves , Chlorella , Clorofila/análogos & derivados , Água Doce , Microcistinas , Microcystis , Plâncton , Rios
6.
Ecotoxicol Environ Saf ; 182: 109368, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31254857

RESUMO

Groundwater is habitually used for watering purposes in rural areas where the rainfall is not enough to adequately cover the crop requirements. However, groundwater sources could be naturally contaminated with trace micropollutants like As and associated elements (B, V and F) adversely affecting the plant health. In this work, non-destructive methodologies based on reflectance and chlorophyll emission processes were applied to assess the presence of micropollutants in watering by using a widespread crop (soybean plant). One of the most substantial results is that the co-occurrence of As, V, B and F in the watering solution clearly produced a synergistic effect in the plants. In fact, both reflectance and fluorescence techniques were proved in this work to be effective in detecting non-destructively stress by multielement treatment. Particularly, for reflectance measurements the most sensitive parameters were the derivative peak area between 480 and 560 nm and the chlorophyll content. Furthermore, it was demonstrated that it is possible to successfully use a portable hyperspectral spectroradiometer instead of a conventional spectrophotometer as the determinations performed with both instruments were positively correlated. Concerning fluorescence, variable emission of chlorophyll-a was more sensitive to stress than steady-state emission. The parameter Fv/F0 was a valuable indicator of stress but the quantum yields of PSII and NPQ stood out as the most sensitive indices with variations of around 60 and 100% respectively.


Assuntos
Agricultura , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Clorofila/análogos & derivados , Fluorescência , Folhas de Planta , Soja , Água
7.
Inorg Chem ; 58(11): 7295-7302, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31091081

RESUMO

Cerium oxide (CeO x) with a reversible surface Ce3+/Ce4+ redox pair has played an important role in catalytic reactions, whereas catalase mimetics of CeO x have attracted little attention in the field of biotherapy. Herein, a smart photosensitizer-cerium oxide nanoprobe was developed to represent a promising paradigm in high-performance photodynamic therapy. The photosensitizer was linked to CeO x nanoparticles through a substrate peptide (EGPLGVRGK) of matrix metalloproteinase-2 (MMP-2). The smart nanoprobe could be converted from the "silent state" before arriving at the cancer cells to the "activated state" within the cells to turn on the fluorescence and 1O2 generation when the peptide linker (EGPLGVRGK) was cut by the cancer biomarker MMP-2. Moreover, CeO x played the role of an excellent catalase-like compound to decompose endogenous hydrogen peroxide to relieve tumor hypoxia. Via the conventional application of CeO x, our study showed innovatively how a smart nanoprobe could relieve tumor hypoxia and achieve a therapeutic effect for highly selective and efficient personalized treatment.


Assuntos
Cério/química , Cério/metabolismo , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Sequência de Aminoácidos , Transporte Biológico , Clorofila/análogos & derivados , Clorofila/química , Clorofila/farmacologia , Células Hep G2 , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Modelos Moleculares , Conformação Molecular , Peptídeos/química , Fármacos Fotossensibilizantes/farmacologia
8.
Environ Monit Assess ; 191(6): 318, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31044287

RESUMO

The representativeness of aquatic ecosystem monitoring and the precision of the assessment results are of high importance when implementing the EU's Water Framework Directive that aims to secure a good status of waterbodies in Europe. However, adapting monitoring designs to answer the objectives and allocating the sampling resources effectively are seldom practiced. Here, we present a practical solution how the sampling effort could be re-allocated without decreasing the precision and confidence of status class assignment. For demonstrating this, we used a large data set of 272 intensively monitored Finnish lake, coastal, and river waterbodies utilizing an existing framework for quantifying the uncertainties in the status class estimation. We estimated the temporal and spatial variance components, as well as the effect of sampling allocation to the precision and confidence of chlorophyll-a and total phosphorus. Our results suggest that almost 70% of the lake and coastal waterbodies, and 27% of the river waterbodies, were classified without sufficient confidence in these variables. On the other hand, many of the waterbodies produced unnecessary precise metric means. Thus, reallocation of sampling effort is needed. Our results show that, even though the studied variables are among the most monitored status metrics, the unexplained variation is still high. Combining multiple data sets and using fixed covariates would improve the modeling performance. Our study highlights that ongoing monitoring programs should be evaluated more systematically, and the information from the statistical uncertainty analysis should be brought concretely to the decision-making process.


Assuntos
Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Poluição Química da Água/estatística & dados numéricos , Clorofila/análogos & derivados , Clorofila/análise , Ecossistema , Monitoramento Ambiental/estatística & dados numéricos , Europa (Continente) , Finlândia , Lagos , Fósforo/análise , Rios , Qualidade da Água
9.
Biochim Biophys Acta Bioenerg ; 1860(6): 452-460, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30986391

RESUMO

(P700+ - P700) Fourier transform visible and infrared difference spectra (DS) have been obtained using photosystem I (PSI) complexes isolated from cells of Fischerella thermalis PCC 7521 grown under white light (WL) or far-red light (FRL). PSI from cells grown under FRL (FRL-PSI) contain ~8 chlorophyll f (Chl f) molecules (Shen et al., Photosynth. Res. Jan. 2019). Both the visible and infrared DS indicate that neither the PA or PB pigments of P700 are Chl f molecules, but do support the conclusion that at least one of the A-1 cofactors is a Chl f molecule. The FTIR DS indicate that the hydrogen bond to the 131-keto CO group of the PA pigment of P700 is weakened in FRL-PSI, as might be expected given that the proteins that bind the P700 pigments are substantially different in FRL-PSI (Gan et al., Science 345, 1312-1317, 2014). The FTIR DS obtained using FRL-PSI display a band at 1664 cm-1 that is assigned (based on density functional theory calculations) to the 21-formyl CO group of Chl f, that upshifts 5 cm-1 upon P700+ formation. This is much less than expected for a cation-induced upshift, indicating that the Chl f molecule is not one of the pigments of P700. In WL-PSI the A-1 cofactor is a Chl a molecule with 131-keto and 133-methylester CO mode vibrations at 1696 and 1750 cm-1, respectively. In FRL-PSI the A-1 cofactor is a Chl f molecule with 131-keto and 133-methylester CO mode vibrations at 1702 and 1754 cm-1, respectively.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/efeitos da radiação , Clorofila/análogos & derivados , Cianobactérias/química , Luz , Complexo de Proteína do Fotossistema I/química , Proteínas de Bactérias/metabolismo , Clorofila/química , Clorofila/metabolismo , Cianobactérias/metabolismo , Ligações de Hidrogênio , Modelos Moleculares , Estrutura Molecular , Fotossíntese , Complexo de Proteína do Fotossistema I/metabolismo , Espectrofotometria
10.
Mar Drugs ; 17(4)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999602

RESUMO

Marine organisms, particularly cyanobacteria, are important resources for the production of bioactive secondary metabolites for the treatment of human diseases. In this study, a bioassay-guided approach was used to discover metabolites with lipid-reducing activity. Two chlorophyll derivatives were successfully isolated, the previously described 132-hydroxy-pheophytin a (1) and the new compound 132-hydroxy-pheofarnesin a (2). The structure elucidation of the new compound 2 was established based on one- and two-dimensional (1D and 2D) NMR spectroscopy and mass spectrometry. Compounds 1 and 2 showed significant neutral lipid-reducing activity in the zebrafish Nile red fat metabolism assay after 48 h of exposure with a half maximal effective concentration (EC50) of 8.9 ± 0.4 µM for 1 and 15.5 ± 1.3 µM for 2. Both compounds additionally reduced neutral lipid accumulation in 3T3-L1 multicellular spheroids of murine preadipocytes. Molecular profiling of mRNA expression of some target genes was evaluated for the higher potent compound 1, which indicated altered peroxisome proliferator activated receptor gamma (PPARγ) mRNA expression. Lipolysis was not affected. Different food materials (Spirulina, Chlorella, spinach, and cabbage) were evaluated for the presence of 1, and the cyanobacterium Spirulina, with GRAS (generally regarded as safe) status for human consumption, contained high amounts of 1. In summary, known and novel chlorophyll derivatives were discovered from marine cyanobacteria with relevant lipid-reducing activities, which in the future may be developed into nutraceuticals.


Assuntos
Clorofila/análogos & derivados , Clorofila/farmacologia , Cianobactérias/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Brassica/química , Proteínas de Transporte/metabolismo , Linhagem Celular , Chlorella/química , Clorofila/química , Clorofila/isolamento & purificação , Ácido Graxo Sintase Tipo I/metabolismo , Lipólise , Camundongos , PPAR gama/metabolismo , Sirtuína 1/metabolismo , Spinacia oleracea/química , Spirulina/química , Peixe-Zebra
11.
Molecules ; 24(7)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987301

RESUMO

We present ground and excited state frequency calculations of the recently discovered extremely red-shifted chlorophyll f. We discuss the experimentally available vibrational mode assignments of chlorophyll f and chlorophyll a which are characterised by particularly large downshifts of 13¹-keto mode in the excited state. The accuracy of excited state frequencies and their displacements are evaluated by the construction of Franck-Condon (FC) and Herzberg-Teller (HT) progressions at the CAM-B3LYP/6-31G(d) level. Results show that while CAM-B3LYP results are improved relative to B3LYP calculations, the displacements and downshifts of high-frequency modes are underestimated still, and that the progressions calculated for low temperature are dominated by low-frequency modes rather than fingerprint modes that are Resonant Raman active.


Assuntos
Clorofila A/química , Clorofila/análogos & derivados , Modelos Químicos , Algoritmos , Clorofila/química , Modelos Moleculares , Análise Espectral
12.
Biosci Biotechnol Biochem ; 83(7): 1181-1192, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31032736

RESUMO

Interaction between foods and drugs is an important consideration in pharmaceutical therapy. Therefore, here, we examined the suppressive effects of the extracts from seven edible herbs on the induction of CYP3A4 gene expression in rifampicin-treated HepG2 cells. We evaluated the structure and suppressive activity of the most effective active compound isolated from dried peppermint (Mentha piperita L.). The structure of the compound was identified as that of pheophorbide a based on spectroscopic data. It suppressed the induction of CYP3A4 mRNA expression by rifampicin in a dose-dependent manner. Quantitative high-performance liquid chromatography showed that 2 g of dry leaves 0.43 mg in one cup of peppermint tea. These findings demonstrate that pheophorbide a suppresses the induction of CYP3A4 mRNA expression in rifampicin-treated HepG2 cells. Pheophorbide is known to cause photosensitivity. However, the effective dose of pheophorbide a that had a suppressive effect was very low, indicating a high safety margin. Abbreviations: DAD: diode array detector; DMEM: Dulbecco's modified Eagle's medium; ELISA: enzyme-linked immunosorbent assay; HPLC: high-performance liquid chromatography; PCR: polymerase chain reaction; PXR: pregnane X receptor; CAR: constitutive androstane receptor; AHR: aryl hydrocarbon receptor; TLC: thin-layer chromatography.


Assuntos
Antibióticos Antituberculose/farmacologia , Clorofila/análogos & derivados , Citocromo P-450 CYP3A/genética , Mentha piperita/química , Extratos Vegetais/farmacologia , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/biossíntese , Rifampina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Clorofila/farmacologia , Cromatografia Líquida de Alta Pressão , Células Hep G2 , Humanos , Estrutura Molecular , Extratos Vegetais/química , Espectroscopia de Prótons por Ressonância Magnética , Relação Estrutura-Atividade
13.
Photochem Photobiol Sci ; 18(6): 1479-1494, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30964476

RESUMO

Chlorophylls are fundamental macrocyclic cofactors in photosynthetic reaction centers and light-harvesting complexes. Their biological function is well understood on the basis of protein structural data and a significant body of information indicates that the conformation of tetrapyrroles plays a large role in controlling their biological activity. While there is no small molecule crystal structure of chlorophyll, the normal-coordinate structural decomposition (NSD) method is a very useful analytical tool for conformational analysis of chlorophylls, using tetrapyrroles that mimic their structure. NSD allows for an analysis of the individual macrocyclic distortion modes and their contributions to the overall conformation. Herein, we present our own validation of the NSD program and use it to carry out a conformational analysis of chlorophyll-related compounds. Metal insertions, peripheral substituents, and solvents in the unit cell give rise to different NSD profiles in chlorophyll derivatives. These range from planar and non-planar conformations upon metal insertions, to polar peripheral substituents, and fused rings in chlorins. Substituent effects are clearly evidenced in highly ß-substituted chlorins and while bacteriochlorins and isobacteriochlorins experience similar effects to the chlorins, they are also subject to solvent effects, causing the macrocycle to be non-planar. Overall, we report a first conformational analysis of all 'chlorophyll'-related small molecule crystal structures at an atomic level.


Assuntos
Clorofila/análogos & derivados , Clorofila/química , Fotossíntese , Complexo de Proteínas do Centro de Reação Fotossintética/química , Porfirinas/química , Conformação Molecular , Pigmentação
14.
Molecules ; 24(4)2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30823562

RESUMO

Photodynamic therapy (PDT) is an established therapeutic modality for the management of cancers. Conjugation with tumor-specific small molecule ligands (e.g., short peptides or peptidomimetics) could increase the tumor targeting of PDT agents, which is very important for improving the outcome of PDT. However, compared with antibody molecules, small molecule ligands have a much weaker affinity to their receptors, which means that their tumor enrichment is not always ideal. In this work, we synthesized multimeric RGD ligand-coupled conjugates of pyropheophorbide-a (Pyro) to increase the affinity through multivalent and cluster effects to improve the tumor enrichment of the conjugates. Thus, the dimeric and trimeric RGD peptide-coupled Pyro conjugates and the monomeric one for comparison were efficiently synthesized via a convergent strategy. A short polyethylene glycol spacer was introduced between two RGD motifs to increase the distance required for multivalence. A subsequent binding affinity assay verified the improvement of the binding towards integrin αvß3 receptors after the increase in the valence, with an approximately 20-fold improvement in the binding affinity of the trimeric conjugate compared with that of the monomeric conjugate. In vivo experiments performed in tumor-bearing mice also confirmed a significant increase in the distribution of the conjugates in the tumor site via multimerization, in which the trimeric conjugate had the best tumor enrichment compared with the other two conjugates. These results indicated that the multivalence interaction can obviously increase the tumor enrichment of RGD peptide-conjugated Pyro photosensitizers, and the prepared trimeric conjugate can be used as a novel antitumor photodynamic agent with high tumor enrichment.


Assuntos
Antineoplásicos/síntese química , Oligopeptídeos/síntese química , Fármacos Fotossensibilizantes/síntese química , Animais , Linhagem Celular Tumoral , Clorofila/análogos & derivados , Clorofila/química , Desenho de Drogas , Feminino , Humanos , Integrina alfaVbeta3/química , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Fotoquimioterapia , Polietilenoglicóis/química , Ligação Proteica , Multimerização Proteica , Relação Estrutura-Atividade , Distribuição Tecidual
15.
Int J Pharm ; 562: 313-320, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30898641

RESUMO

Photosensitizer-based photodynamic therapy (PDT) has attracted great attention in cancer treatment. However, achieving efficient delivery of photosensitizers is still a great challenge for their clinical applications. The photosensitizer-encapsulating delivery nanosystem usually suffers from poor stability, complex preparation process and low drug loading. Herein, we utilize a surfactant-like chemotherapeutic agent, mitoxantrone (MTX), as a nanocarrier to deliver a photosensitizer pyropheophorbide a (PPa) for antitumor therapy. MTX consists of aromatic rings (hydrophobic part) and two amino-groups and two hydroxyl-groups (hydrophilic part) with planar structure, which could interact with PPa via π-π stacking, hydrophobic interactions, intermolecular hydrogen bonding and electrostatic interactions. This system (PPa@MTX) spontaneously forms near-spherical nanostructures (∼150 nm), has a high loading capacity for PPa (56.5%) and exhibits a pH-responsive drug release manner in vitro. In vivo antitumor efficacy evaluations show that the pegylated PPa@MTX nanosystem has increased accumulation in tumor tissues and enhanced antitumor efficacy in female BALB/c mice bearing murine mammary carcinoma (4T1) tumor cells, compared to free PPa. Employing the surfactant-like drug as nanocarriers, our results show that the "drug-delivering-drug" strategy is a good foundation for the development of novel PDT-based drug delivery system against cancer.


Assuntos
Antineoplásicos , Clorofila/análogos & derivados , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Mitoxantrona , Nanoestruturas , Fármacos Fotossensibilizantes , Tensoativos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Clorofila/administração & dosagem , Clorofila/química , Clorofila/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Feminino , Camundongos Endogâmicos BALB C , Mitoxantrona/administração & dosagem , Mitoxantrona/química , Mitoxantrona/farmacocinética , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Tensoativos/administração & dosagem , Tensoativos/química , Tensoativos/farmacocinética
16.
Environ Pollut ; 248: 429-437, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826605

RESUMO

The application of biochar in remediation and recovery of heavy metals and/or organic contaminants in water and soil is increasing. However, the adverse effect of biochar to aquatic organisms has not received enough attention. In this study, we conducted a study on the biotoxicity of biochar pyrolyzed from pine needle under oxygen-limited conditions. The toxicity of biochar was expressed with the following endpoints: cell growth, chlorophyll-a (Chl-a), reactive oxygen species (ROS), superoxide dismutase (SOD) content of Scenedesmus obliquus (S. obliquus) and the luminescence of Photobacterium phosphoreum (P. phosphoreum). Here, the effect of free radicals (FRs) contained in biochar was stressed. Our results show that the toxicity of biochar is significantly correlated with the concentration of FRs in biochar particles. Meanwhile, we found the FRs-containing biochar could induce the production of acellular ROS (such as ·OH) in water, which would also induce the production of interior cellular ROS in aquatic organisms. Our findings provide a new insight into the mechanism of toxicity aroused by biochar applications and aid in understanding its potential ecological risk.


Assuntos
Carvão Vegetal/toxicidade , Recuperação e Remediação Ambiental/métodos , Radicais Livres/toxicidade , Photobacterium/metabolismo , Espécies Reativas de Oxigênio/toxicidade , Scenedesmus/metabolismo , Organismos Aquáticos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Clorofila/análogos & derivados , Clorofila/análise , Metais Pesados/análise , Solo/química , Superóxido Dismutase/análise
17.
BMC Genomics ; 20(1): 207, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30866821

RESUMO

BACKGROUND: Halomicronema hongdechloris was the first cyanobacterium to be identified that produces chlorophyll (Chl) f. It contains Chl a and uses phycobiliproteins as its major light-harvesting components under white light conditions. However, under far-red light conditions H. hongdechloris produces Chl f and red-shifted phycobiliprotein complexes to absorb and use far-red light. In this study, we report the genomic sequence of H. hongdechloris and use quantitative proteomic approaches to confirm the deduced metabolic pathways as well as metabolic and photosynthetic changes in response to different photo-autotrophic conditions. RESULTS: The whole genome of H. hongdechloris was sequenced using three different technologies and assembled into a single circular scaffold with a genome size of 5,577,845 bp. The assembled genome has 54.6% GC content and encodes 5273 proteins covering 83.5% of the DNA sequence. Using Tandem Mass Tag labelling, the total proteome of H. hongdechloris grown under different light conditions was analyzed. A total of 1816 proteins were identified, with photosynthetic proteins accounting for 24% of the total mass spectral readings, of which 35% are phycobiliproteins. The proteomic data showed that essential cellular metabolic reactions remain unchanged under shifted light conditions. The largest differences in protein content between white and far-red light conditions reflect the changes to photosynthetic complexes, shifting from a standard phycobilisome and Chl a-based light harvesting system under white light, to modified, red-shifted phycobilisomes and Chl f-containing photosystems under far-red light conditions. CONCLUSION: We demonstrate that essential cellular metabolic reactions under different light conditions remain constant, including most of the enzymes in chlorophyll biosynthesis and photosynthetic carbon fixation. The changed light conditions cause significant changes in the make-up of photosynthetic protein complexes to improve photosynthetic light capture and reaction efficiencies. The integration of the global proteome with the genome sequence highlights that cyanobacterial adaptation strategies are focused on optimizing light capture and utilization, with minimal changes in other metabolic pathways. Our quantitative proteomic approach has enabled a deeper understanding of both the stability and the flexibility of cellular metabolic networks of H. hongdechloris in response to changes in its environment.


Assuntos
Proteínas de Bactérias/metabolismo , Cianobactérias/crescimento & desenvolvimento , Proteômica/métodos , Sequenciamento Completo do Genoma/métodos , Adaptação Fisiológica , Proteínas de Bactérias/genética , Ciclo do Carbono , Clorofila/análogos & derivados , Clorofila/metabolismo , Cianobactérias/genética , Cianobactérias/metabolismo , Evolução Molecular , Tamanho do Genoma , Luz , Anotação de Sequência Molecular , Fotossíntese , Ficobiliproteínas/genética , Ficobiliproteínas/metabolismo , Filogenia , Espectrometria de Massas em Tandem
18.
Environ Sci Pollut Res Int ; 26(12): 11940-11950, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825122

RESUMO

Dust storms affect the primary productivity of the ocean by providing necessary micronutrients to the surface layer. One such dust storm during March 2012 led to a substantial reduction in visibility and enhancement in aerosol optical depth (AOD) up to ~ 0.8 (AOD increased from 0.1 to 0.9) over the Arabian Sea. We explored the possible effects and mechanisms through which this particular dust storm could impact the ocean's primary productivity (phytoplankton concentration), using satellite-borne remote sensors and reanalysis model data (2003-2016). The climatological analyses revealed anomalous March 2012 in terms of dust deposition and enhancement in phytoplankton concentration in the month of March during 2003-2016 over this region. The studied dust storm accounts for increase in the daily average surface dust deposition rate from ~ 3 to ~53 mg m-2 day-1, which is followed by a significant enhancement in the chlorophyll-a (Chl_a) concentration (~ 2 to ~9 mg m-3). We show strong association between a dust storm and an event of anomalously high biological production (with a 4-day forward lag) in the Arabian Sea. We suggest that the increase in biological production results from the superposition of two complementary processes (deposition of atmospheric nutrients and deepening of the mixed layer due to dust-induced sea surface temperature cooling) that enhance nutrient availability in the euphotic layer.


Assuntos
Poluentes Atmosféricos/análise , Poeira/análise , Monitoramento Ambiental , Fitoplâncton/fisiologia , Aerossóis/análise , Clorofila/análogos & derivados , Clorofila A , Fitoplâncton/crescimento & desenvolvimento , Estações do Ano
19.
Eur J Pharm Sci ; 129: 68-78, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30597205

RESUMO

2-[1-Hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a second-generation photosensitizer, is employed in photodynamic therapy (PDT) for the treatment of various malignant lesions. PDT is a drug-device combined targeted treatment, and the clinical responses depend to a large extent on the photosensitizer distribution in target tissues and light exposure. In the present study, we aimed to give some suggestion for the development of HPPH-PDT from the perspective of photosensitizer biodistribution. For the first time, a PBPK model of HPPH was developed, which adequately described HPPH concentration-time profiles in rats plasma and various tissues. The rat PBPK model was further extrapolated to simulate the HPPH disposition in mouse and human. The simulated HPPH human serum concentrations yield a satisfactory agreement with observations at multiple dosing levels. It turned out that overweight may have a significant influence on HPPH exposure in human. Model simulated concentration-time profiles in human target tissues were also obtained. The appropriate time window to conduct light exposure for the treatment of digestive cancer and skin cancer could be 24-48 h and 48-96 h post-dose, respectively. Model simulations can explain the relevant clinical responses to some extent. The incorporation of the PBPK model into PDT could provide the photosensitizer concentrations not only in blood but also in target tissues, which may accelerate the development of this kind of treatment.


Assuntos
Clorofila/análogos & derivados , Animais , Clorofila/farmacocinética , Feminino , Humanos , Masculino , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Ratos , Ratos Sprague-Dawley , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Distribuição Tecidual/fisiologia
20.
Photosynth Res ; 140(1): 115-127, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30604202

RESUMO

Chlorophylls (Chls) are pigments involved in light capture and light reactions in photosynthesis. Chl a, Chl b, Chl d, and Chl f are characterized by unique absorbance maxima in the blue (Soret) and red (Qy) regions with Chl b, Chl d, and Chl f each possessing a single formyl group at a unique position. Relative to Chl a the Qy absorbance maximum of Chl b is blue-shifted while Chl d and Chl f are red-shifted with the shifts attributable to the relative positions of the formyl substitutions. Reduction of a formyl group of Chl b to form 7-hydroxymethyl Chl a, or oxidation of the vinyl group of Chl a into a formyl group to form Chl d was achieved using sodium borohydride (NaBH4) or ß-mercaptoethanol (BME/O2), respectively. During the consecutive reactions of Chl b and Chl f using a three-step procedure (1. NaBH4, 2. BME/O2, and 3. NaBH4) two new 7-hydroxymethyl Chl a species were prepared possessing the 3-formyl or 3-hydroxymethyl groups and three new 2-hydroxymethyl Chl a species possessing the 3-vinyl, 3-formyl, or 3-hydroxymethyl groups, respectively. Identification of the spectral properties of 2-hydroxymethyl Chl a may be biologically significant for deducing the latter stages of Chl f biosynthesis if the mechanism parallels Chl b biosynthesis. The spectral features and chromatographic properties of these modified Chls are important for identifying potential intermediates in the biosynthesis of Chls such as Chl f and Chl d and for identification of any new Chls in nature.


Assuntos
Clorofila/química , Spinacia oleracea/química , Boroidretos/química , Clorofila/análogos & derivados , Clorofila/isolamento & purificação , Clorofila A/química , Clorofila A/isolamento & purificação , Mercaptoetanol/química , Oxirredução , Fotossíntese , Folhas de Planta/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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