Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Arch Microbiol ; 205(6): 243, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37209212

RESUMO

Recent improvements in 3D printing technology have increased the usage of 3D printed materials in several areas. An exciting and emerging area of applying these next-generation manufacturing strategies is the development of devices for biomedical applications. The main aim of this work was to investigate the effect of tannic acid, gallic acid, and epicatechin gallate on the physicochemical characteristics of acrylonitrile butadiene-styrene (ABS) and Nylon 3D printing materials using the contact angle method. The adhesion of Staphylococcus aureus on untreated and treated materials was evaluated by scanning electron microscopy (SEM) analysis and the images were treated by MATLAB software. The results of the contact angle measurements showed a significant change in the physicochemical properties of both surfaces, indicated an increase in the electron donor character of 3D printing materials following treatment. Thus, the ABS surfaces treated with tannic acid, gallic acid, and epicatechin gallate have become more electron donating. Furthermore, our results proved the ability of S. aureus to adhere on all materials with a percentage of 77.86% for ABS and 91.62% for nylon. The SEM has shown that all actives molecules were sufficient to obtain better inhibition of bacterial adhesion, which tannic acid has shown a total inhibition of S. aureus on ABS. From these results, our treatment presents a high potential for utilization as an active coating to prevent bacterial attachment and the eventual biofilm development in medical field.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Nylons/farmacologia , Impressão Tridimensional , Estireno/química , Estireno/farmacologia , Taninos/farmacologia , Ácido Gálico/farmacologia
2.
Drug Des Devel Ther ; 15: 1299-1313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790541

RESUMO

BACKGROUND: Organocatalytic asymmetric Michael addition is a strong approach for C-C bond formation. The objective of the study is to design molecules by exploiting the efficiency of Michael Adducts. We proceeded with the synthesis of Michael adducts by tailoring the substitution pattern on maleimide and trans-ß-nitro styrene as Michael acceptors. The synthesized compounds were evaluated for dual cyclooxygenases (COX) and lipoxygenase (LOX) inhibition. METHODS: The compounds (4, 9-11) were synthesized through Michael additions. The cyclooxygenases (COX-1 and 2) and lipoxygenase (5-LOX) assays were used for in vitro evaluations of compounds. After the acute toxicity studies, the in vivo analgesic potential was determined with acetic acid induced writhing, tail immersion, and formalin tests. Furthermore, the possible roles of adrenergic and dopaminergic receptors were also studied. Extensive computational studies were performed to get a better understanding regarding the binding of this compound with protein target. RESULTS: Four Michael adducts (4, 9-11) were synthesized. Compound 4 was obtained in enantio- and diastereopure form. The stereopure compound 4 showed encouraging COX-1 and-2 inhibitions with IC50 values of 128 and 65 µM with SI of 1.94. Benzyl derivative 11 showed excellent COX-2 inhibition with the IC50 value of 5.79 µM and SI value 7.96. Compounds 4 and 11 showed good results in in vivo models of analgesia like acetic acid test, tail immersion, and formalin tests. Our compounds were not active in dopaminergic and adrenergic pathways and so were acting centrally. Through extensive computational studies, we computed binding energies, and pharmacokinetic predictions. CONCLUSION: Our findings conclude that our synthesized Michael products (pyrrolidinedione 4 and nitroalkane 11) can be potent centrally acting analgesics. Our in silico predictions suggested that the compounds have excellent pharmacokinetic properties. It is concluded here that dual inhibition of COX/LOX pathways provides a convincing step towards the discovery of safe lead analgesic molecules.


Assuntos
Analgésicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Edema/tratamento farmacológico , Inibidores de Lipoxigenase/farmacologia , Maleimidas/farmacologia , Estireno/farmacologia , Ácido Acético , Analgésicos/síntese química , Analgésicos/química , Animais , Araquidonato 5-Lipoxigenase/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/química , Masculino , Maleimidas/síntese química , Maleimidas/química , Camundongos , Camundongos Endogâmicos BALB C , Prostaglandina-Endoperóxido Sintases/metabolismo , Estireno/síntese química , Estireno/química
3.
J Ind Microbiol Biotechnol ; 48(1-2)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33640981

RESUMO

The global transcriptional response of Escherichia coli to styrene and potential influence of exposure source was determined by performing RNA sequencing (RNA-seq) analysis on both styrene-producing and styrene-exposed cells. In both cases, styrene exposure appears to cause both cell envelope and DNA damage, to which cells respond by down-regulating key genes/pathways involved in DNA replication, protein production, and cell wall biogenesis. Among the most significantly up-regulated genes were those involved with phage shock protein response (e.g. pspABCDE/G), general stress regulators (e.g. marA, rpoH), and membrane-altering genes (notably, bhsA, ompR, ldtC), whereas efflux transporters were, surprisingly, unaffected. Subsequent studies with styrene addition demonstrate how strains lacking ompR [involved in controlling outer membrane (OM) composition/osmoregulation] or any of tolQ, tolA, or tolR (involved in OM constriction) each displayed over 40% reduced growth relative to wild-type. Conversely, despite reducing basal fitness, overexpression of plsX (involved in phospholipid biosynthesis) led to 70% greater growth when styrene exposed. These collective differences point to the likely importance of OM properties in controlling native styrene tolerance. Overall, the collective behaviours suggest that, regardless of source, prolonged exposure to inhibitory styrene levels causes cells to shift from'growth mode' to 'survival mode', redistributing cellular resources to fuel native tolerance mechanisms.


Assuntos
Escherichia coli/efeitos dos fármacos , Estireno/farmacologia , Transcrição Gênica , Tolerância a Medicamentos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , RNA Bacteriano/genética
4.
Chemosphere ; 247: 125800, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31927182

RESUMO

Long-term operational stability of biotrickling filters (BTFs) degrading volatile organic compounds (VOCs) is dependent on both physicochemical as well as biological properties. Effects of increasingly stressful levels of air pollutants on the microbial structure of biofilms within BTFs are not well understood, especially for VOCs such as styrene. To investigate the relationship between biofilm biodiversity and operational stability, the temporal dynamics of a biofilm from a biotrickling filter subjected to stepwise increasing levels of air polluted with styrene was investigated using 16S rDNA pyrosequencing and PCR-denaturing gradient gel electrophoresis (PCR-DGGE). As styrene contaminant loads were increased, microbial community composition was distinctly altered and diversity was initially reduced in early stages but gradually stabilized and increased diversity in later stages, suggesting a recovery and acclimatization period within the microbial community during incremental exposure of the pollutant. Although temporary reductions in known styrene-degrading bacterial genera (Pseudomonas and Rhodococcus) occurred under increased styrene loads, stable BTF performance was maintained due to functional redundancy. New candidate genera for styrene degradation (Azoarcus, Dokdonella) were identified in conditions of high styrene loads, and may have supported the observed stable BTF performance throughout the experiment. Styrene inlet load was found to be important modulator of community composition and may have been partly responsible for the observed temporary reductions of Pseudomonas. Notable differences between dominant genera detected via pyrosequencing compared to species detected by PCR-DGGE suggests that simultaneous implementation of both techniques is valuable for fully characterizing dynamic microbial communities.


Assuntos
Bactérias/isolamento & purificação , Biodegradação Ambiental , Biodiversidade , Biofilmes/efeitos dos fármacos , Filtração/instrumentação , Estireno/farmacologia , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/metabolismo , Poluentes Atmosféricos/farmacologia , Bactérias/metabolismo , Reatores Biológicos/microbiologia , Eletroforese em Gel de Gradiente Desnaturante/métodos , Eletroforese em Gel de Gradiente Desnaturante/normas , Filtração/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sequenciamento de Nucleotídeos em Larga Escala/normas , Microbiota/efeitos dos fármacos , Estireno/metabolismo , Compostos Orgânicos Voláteis/metabolismo
5.
Environ Int ; 133(Pt B): 105199, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31675573

RESUMO

This study utilized effect-directed analysis (EDA) combined with full-scan screening analysis (FSA) to identify aryl hydrocarbon receptor (AhR)-active compounds in sediments of inland creeks flowing into Lake Sihwa, South Korea. The specific objectives were to (i) investigate the major AhR-active fractions of organic extracts of sediments by using H4IIE-luc in vitro bioassay (4 h and 72 h exposures), (ii) quantify known AhR agonists, such as polycyclic aromatic hydrocarbons (PAHs) and styrene oligomers (SOs), (iii) identify unknown AhR agonists by use of gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOFMS), and (iv) determine contributions of AhR agonists to total potencies measured by use of the bioassay. FSA was conducted on fractions F2.6 and F2.7 (aromatics with log Kow 5-7) in extracts of sediment from Siheung Creek (industrial area). Those fractions exhibited significant AhR-mediated potency as well as relatively great concentrations of PAHs and SOs. FSA detected 461 and 449 compounds in F2.6 and F2.7, respectively. Of these, five tentative candidates of AhR agonist were selected based on NIST library matching, aromatic structures and numbers of rings, and available standards. Benz[b]anthracene, 11H-benzo[a]fluorene, and 4,5-methanochrysene exhibited significant AhR-mediated potency in the H4IIE-luc bioassay, and relative potencies of these compounds were determined. Potency balance analysis demonstrated that these three newly identified AhR agonists explained 1.1% to 67% of total induced AhR-mediated potencies of samples, which were particularly great for industrial sediments. Follow-up studies on sources and ecotoxicological effects of these compounds in coastal environments would be required.


Assuntos
Sedimentos Geológicos/análise , Receptores de Hidrocarboneto Arílico/agonistas , Poluentes Químicos da Água/farmacologia , Animais , Bioensaio/métodos , Linhagem Celular Tumoral , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas , Lagos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Ratos , República da Coreia , Estireno/análise , Estireno/farmacologia , Poluentes Químicos da Água/análise
6.
J Eval Clin Pract ; 25(6): 955-961, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31290239

RESUMO

This paper analyses the methods of the International Agency for Research on Cancer (IARC) for evaluating the carcinogenicity of various agents. I identify two fundamental evidential principles that underpin these methods, which I call Evidential Proximity and Independence. I then show, by considering the 2018 evaluation of the carcinogenicity of styrene and styrene-7,8-oxide, that these principles have been implemented in a way that can lead to inconsistency. I suggest a way to resolve this problem: admit a general exception to Independence and treat the implementation of Evidential Proximity more flexibly where this exception applies. I show that this suggestion is compatible with the general principles laid down in the 2019 version of IARC's methods guide, its Preamble to the Monographs.


Assuntos
Pesquisa Biomédica , Carcinogênese , Compostos de Epóxi/farmacologia , Neoplasias , Saúde Pública , Estireno/farmacologia , Pesquisa Biomédica/ética , Pesquisa Biomédica/métodos , Pesquisa Biomédica/normas , Carcinógenos/farmacologia , Causalidade , Humanos , Agências Internacionais/ética , Agências Internacionais/normas , Conhecimento , Filosofia Médica , Saúde Pública/ética , Saúde Pública/normas
7.
J Chem Ecol ; 45(5-6): 474-489, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31053976

RESUMO

Bark beetles kill apparently vigorous conifers during epidemics by means of pheromone-mediated aggregation. During non-endemic conditions the beetles are limited to use trees with poor defense, like wind-thrown. To find olfactory cues that help beetles to distinguish between trees with strong or weak defense, we collected volatiles from the bark surface of healthy felled or standing Picea abies trees. Furthermore, living trees were treated with methyl jasmonate in order to induce defense responses. Volatiles were analyzed by combined gas chromatography and electroantennographic detection (GC-EAD) on Ips typographus antennae. Compounds eliciting antennal responses were characterized by single sensillum recording for identification of specific olfactory sensory neurons (OSN). Release of monoterpene hydrocarbons decreased, while oxygenated compounds increased, from spring to early summer in felled trees. In both beetle sexes particular strong EAD activity was elicited by trace amounts of terpene alcohols and ketones. 4-Thujanol gave a very strong response and the absolute configuration of the tested natural product was assigned to be (+)-trans-(1R,4S,5S)-thujanol by stereoselective synthesis and enantioselective gas chromatography. One type of OSN responded to all ketones and five other OSN were characterized by the type of compounds that elicited responses. Three new OSN classes were found. Of the eight EAD-active compounds found in methyl jasmonate-treated bark, the known anti-attractant 1,8-cineole was the one most strongly induced. Our data support the hypothesis that highly active oxygenated host volatiles could serve as positive or negative cues for host selection in I. typographus and in other bark beetles.


Assuntos
Besouros/fisiologia , Monoterpenos/química , Estireno/química , Acetatos/farmacologia , Animais , Monoterpenos Bicíclicos , Ciclopentanos/farmacologia , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Monoterpenos/síntese química , Monoterpenos/farmacologia , Oxilipinas/farmacologia , Picea/química , Picea/metabolismo , Casca de Planta/química , Casca de Planta/efeitos dos fármacos , Casca de Planta/metabolismo , Estereoisomerismo , Estireno/farmacologia
8.
Colloids Surf B Biointerfaces ; 172: 532-540, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30216903

RESUMO

Antimicrobial properties of methyl methacrylate - ethyl acrylate and styrene - ethyl acrylate copolymers, both as latexes and after film formation were tested. The polymers were synthesized using a cationic surfactant, cetytrimethylammonium bromide (CTAB) as an emulsifier, in presence of either a cationic or an anionic initiator. The resulting latex particles showed sizes between 50 and 320 nm (larger for the anionic initiator), and ζ-potential between +30 and +70 mV (more positive for the cationic initiator). Dialysis did not change significantly the size distribution and ζ-potential of the latexes, and most of them inhibited growth of Gram-negative (E. coli), Gram-positive (S. aureus, B. subtilis) and yeast (C. albicans). On the other hand, only few compositions were effective against Gram-negative P. aeruginosa. Both completely ("dry") and incompletely ("wet") formed films produced from the respective latexes showed similar, although less pronounced antimicrobial activity pattern. The analysis of streaming potential for the films confirmed that part of the positive surface charge brought by non-covalent binding of CTAB to the polymer chains, is lost during dialysis of the latexes and during rinsing, especially under high-shear flow. From the practical point of view, films with the best mechanical and antimicrobial properties can be achieved using polymers with high proportion of ethyl acrylate, while nature of the co-monomer and initiator do not play crucial roles.


Assuntos
Acrilatos/farmacologia , Anti-Infecciosos/farmacologia , Polímeros/farmacologia , Estireno/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Dureza , Látex/química , Testes de Sensibilidade Microbiana , Peso Molecular , Eletricidade Estática
9.
Eur J Med Chem ; 150: 633-641, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29558734

RESUMO

A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC50 = 0.12-0.35 µM) than the reference drug metronidazole (IC50 = 1.79 µM). The most active compounds were found to be non-toxic (up to 50 µM) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action. Docking studies showed significant binding affinity in the active site of E. histolytica thioredoxin reductase (EhTrR) protein.


Assuntos
Antiprotozoários/farmacologia , Entamoeba histolytica/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Metronidazol/farmacologia , Estireno/farmacologia , Triazóis/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Entamoeba histolytica/enzimologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Metronidazol/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Estireno/química , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/metabolismo , Triazóis/química
10.
Eur J Med Chem ; 146: 621-635, 2018 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-29407986

RESUMO

The present study seeks to describe the design and synthesis of six new Michael adducts of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamate with nitrostyrenes and their in vitro antiproliferative activity against human cervical cancer cell lines [HeLa (HPV 18 positive), CaSki (HPV 16 positive) and ViBo (HPV negative) cervical cancer cell lines]. Virtual screening of the physicochemical properties of all compounds have also been presented. All the compounds exploited significant antiproliferative activity on the three cervical cancer cell lines. Compound 8a was found to be most potent, displaying in vitro antiproliferative activity against HeLa, CaSki and ViBo cervical cancer cell lines superior to Cisplatin and Paclitaxel with IC50 values 0.99 ±â€¯0.007, 2.36 ±â€¯0.016 and 0.73 ±â€¯0.002 µM respectively. In addition, compound 8a did not trigger the necrosis cell death to the test cancer cell lines. Further mechanistic study revealed that compound 8a could inhibit the cancer cell proliferation by inducing apoptosis through caspase-3 activation. Moreover, cell cycle analysis indicated that compound 8a could arrest the cell cycle at the G1 phase for HeLa and CaSki cancer cells. At the predetermined IC50 values on cancer cells, compound 8a did not induce any necrotic (cytotoxic) death to the normal human lymphocytes. In the present design, (1S,4S)-2,5-diazabicyclo[2.2.1]heptane system was found to be superior than the piperazine counterpart 11.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Compostos Aza/farmacologia , Nitrocompostos/farmacologia , Estireno/farmacologia , Tiocarbamatos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos Aza/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Estrutura Molecular , Nitrocompostos/química , Relação Estrutura-Atividade , Estireno/química , Tiocarbamatos/química , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia
11.
Int J Biochem Cell Biol ; 92: 104-114, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28958615

RESUMO

BACKGROUND: Coumarins occurs naturally across plant kingdoms exhibits significant pharmacological properties and pharmacokinetic activity. The conventional, therapeutic agents are often associated with poor stability, absorption and increased side effects. Therefore, identification of a drug that has little or no-side effect on humans is consequential. Here, we investigated the antiproliferative activity of styrene substituted biscoumarin against various human breast cancer cell lines, such as MCF-7, (ER-) MDA-MB-231 and (AR+) MDA-MB-453. Styrene substituted biscoumarin induced cell death by apoptosis in MDA-MB-231 cell line was analyzed. METHODS: Antiproliferative activity of Styrene substituted biscoumarin was performed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Styrene substituted biscoumarin induced apoptosis was assessed by Hoechst staining, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining and flow cytometric analysis. Migratory and proliferating characteristic of breast cancer cell line MDA-MB-231 was also analyzed by wound healing and colony formation assay. Furthermore, mRNA expression of BAX and BCL-2 were quantified using qRT-PCR and protein expression level analyzed by Western blot. RESULTS: The inhibition concentration (IC50) of styrene substituted biscoumarin was assayed against three breast cancer cell lines. The inhibition concentration (IC50) value of styrene substituted biscoumarin toward MDA-MB-231, MDA-MB-453 and MCF-7 cell lines was 5.63, 7.30 and 10.84µg/ml respectively. Styrene substituted biscoumarin induced apoptosis was detected by Hoechst staining, DAPI/PI analysis and flow-cytometric analysis. The migration and proliferative efficiency of MDA-MB-231 cells were completely arrested upon styrene substituted biscoumarin treatment. Also, mRNA gene expression and protein expression of pro-apoptotic (BAX) and anti-apoptotic (BCL-2) genes were analyzed by qRT-PCR and western blot analysis upon styrene substituted biscoumarin treatment to MDA-MB-231 cells. Our results showed that styrene substituted biscoumarin downregulated BCL-2 gene expression and upregulated BAX gene expression to trigger apoptotic process. CONCLUSION: Styrene substituted biscoumarin could induce apoptosis through intrinsic mitochondrial pathway in breast cancer cell lines, particularly in MDA-MB-231. Our data suggest that styrene substituted biscoumarin may act as a potential chemotherapeutic agent against breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cumarínicos/química , Estireno/química , Estireno/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Células MCF-7
12.
Biochim Biophys Acta Biomembr ; 1859(11): 2155-2160, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28847501

RESUMO

Extracting membrane proteins from biological membranes by styrene-maleic acid copolymers (SMAs) in the form of nanodiscs has developed into a powerful tool in membrane research. However, the mode of action of membrane (protein) solubilization in a cellular context is still poorly understood and potential specificity for cellular compartments has not been investigated. Here, we use fluorescence microscopy to visualize the process of SMA solubilization of human cells, exemplified by the immortalized human HeLa cell line. Using fluorescent protein fusion constructs that mark distinct subcellular compartments, we found that SMA solubilizes membranes in a concentration-dependent multi-stage process. While all major intracellular compartments were affected without a strong preference, plasma membrane solubilization was found to be generally slower than the solubilization of organelle membranes. Interestingly, some plasma membrane-localized proteins were more resistant against solubilization than others, which might be explained by their presence in specific membrane domains with differing properties. Our results support the general applicability of SMA for the isolation of membrane proteins from different types of (sub)cellular membranes.


Assuntos
Fracionamento Celular/métodos , Maleatos/farmacologia , Polímeros/farmacologia , Estireno/farmacologia , Frações Subcelulares , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Células HeLa , Humanos , Bicamadas Lipídicas , Maleatos/química , Microscopia de Fluorescência , Polímeros/química , Poliestirenos/química , Solubilidade , Estireno/química , Frações Subcelulares/química , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/ultraestrutura
13.
J Ind Microbiol Biotechnol ; 43(5): 595-604, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26803503

RESUMO

Fermentative production of styrene from glucose has been previously demonstrated in Escherichia coli. Here, we demonstrate the production of styrene from the sugars derived from lignocellulosic biomass depolymerized by fast pyrolysis. A previously engineered styrene-producing strain was further engineered for utilization of the anhydrosugar levoglucosan via expression of levoglucosan kinase. The resulting strain produced 240 ± 3 mg L(-1) styrene from pure levoglucosan, similar to the 251 ± 3 mg L(-1) produced from glucose. When provided at a concentration of 5 g L(-1), pyrolytic sugars supported styrene production at titers similar to those from pure sugars, demonstrating the feasibility of producing this important industrial chemical from biomass-derived sugars. However, the toxicity of contaminant compounds in the biomass-derived sugars and styrene itself limit further gains in production. Styrene toxicity is generally believed to be due to membrane damage. Contrary to this prevailing wisdom, our quantitative assessment during challenge with up to 200 mg L(-1) of exogenously provided styrene showed little change in membrane integrity; membrane disruption was observed only during styrene production. Membrane fluidity was also quantified during styrene production, but no changes were observed relative to the non-producing control strain. This observation that styrene production is much more damaging to the membrane integrity than challenge with exogenously supplied styrene provides insight into the mechanism of styrene toxicity and emphasizes the importance of verifying proposed toxicity mechanisms during production instead of relying upon results obtained during exogenous challenge.


Assuntos
Biomassa , Metabolismo dos Carboidratos , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Lignina/metabolismo , Estireno/metabolismo , Estireno/toxicidade , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Escherichia coli/citologia , Escherichia coli/genética , Glucose/análogos & derivados , Glucose/metabolismo , Lignina/química , Fluidez de Membrana/efeitos dos fármacos , Estireno/farmacologia
14.
J Drug Target ; 24(5): 399-407, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26302870

RESUMO

Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 µM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.


Assuntos
Antineoplásicos/farmacologia , Maleatos/farmacologia , Metaloporfirinas/farmacologia , Poliestirenos/farmacologia , Protoporfirinas/farmacologia , Estireno/farmacologia , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Feminino , Células HeLa , Heme Oxigenase-1/metabolismo , Humanos , Masculino , Camundongos , Micelas , Tamanho da Partícula , Permeabilidade , Fotoquimioterapia/métodos , Solubilidade , Neoplasias do Colo do Útero/tratamento farmacológico
15.
Appl Environ Microbiol ; 80(20): 6539-48, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25128338

RESUMO

The application of whole cells as biocatalysts is often limited by the toxicity of organic solvents, which constitute interesting substrates/products or can be used as a second phase for in situ product removal and as tools to control multistep biocatalysis. Solvent-tolerant bacteria, especially Pseudomonas strains, are proposed as promising hosts to overcome such limitations due to their inherent solvent tolerance mechanisms. However, potential industrial applications suffer from tedious, unproductive adaptation processes, phenotypic variability, and instable solvent-tolerant phenotypes. In this study, genes described to be involved in solvent tolerance were identified in Pseudomonas taiwanensis VLB120, and adaptive solvent tolerance was proven by cultivation in the presence of 1% (vol/vol) toluene. Deletion of ttgV, coding for the specific transcriptional repressor of solvent efflux pump TtgGHI gene expression, led to constitutively solvent-tolerant mutants of P. taiwanensis VLB120 and VLB120ΔC. Interestingly, the increased amount of solvent efflux pumps enhanced not only growth in the presence of toluene and styrene but also the biocatalytic performance in terms of stereospecific styrene epoxidation, although proton-driven solvent efflux is expected to compete with the styrene monooxygenase for metabolic energy. Compared to that of the P. taiwanensis VLB120ΔC parent strain, the maximum specific epoxidation activity of P. taiwanensis VLB120ΔCΔttgV doubled to 67 U/g of cells (dry weight). This study shows that solvent tolerance mechanisms, e.g., the solvent efflux pump TtgGHI, not only allow for growth in the presence of organic compounds but can also be used as tools to improve redox biocatalysis involving organic solvents.


Assuntos
Engenharia Genética/métodos , Pseudomonas/genética , Pseudomonas/metabolismo , Estireno/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biocatálise , Farmacorresistência Bacteriana , Compostos de Epóxi/metabolismo , Compostos de Epóxi/farmacologia , Deleção de Genes , Dados de Sequência Molecular , Pseudomonas/efeitos dos fármacos , Solventes/farmacologia , Estireno/farmacologia
16.
Bioengineered ; 5(2): 114-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24637704

RESUMO

Bacterial two-component systems (TCSs) are of vital importance in the translation of rapidly changing environmental conditions into appropriate cellular regulatory responses enabling adaptation, growth, and survival. The diverse range of environmental signals that TCSs can process, coupled with discrete modular domains within TCS proteins, offers considerable potential for the rational design of bio-sensor and/or bio-reporter strains. In this study we functionally characterize the multi-domain StyS sensor kinase associated with sensing of the aromatic pollutant styrene by Pseudomonas putida CA-3. Deletion analysis of discrete domains was performed and the ability of the truncated StyS sensor proteins to activate a cognate reporter system in an E. coli host assessed. The essential histidine kinase and PAS input domains were identified for StyS dependent activation of the reporter system. However, co-expression of an ABC-transporter protein StyE, previously linked to styrene transport in P. putida CA-3, enabled activation of the reporter system with a StyS construct containing a non-essential PAS input domain, suggesting a novel role for intracellular detection and/or activation. Site directed mutagenesis and amino acid deletions were employed to further characterize the PAS sensing domains of both input regions. The potential implications of these findings in the use of multi-domain sensor kinases in rational design strategies and the potential link between transport and intracellular sensing are discussed.


Assuntos
Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas Quinases/química , Proteínas Quinases/metabolismo , Pseudomonas putida/fisiologia , Estireno/química , Estireno/farmacologia , Transportadores de Cassetes de Ligação de ATP/genética , Sítios de Ligação , Ativação Enzimática/efeitos dos fármacos , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Líquido Intracelular/efeitos dos fármacos , Líquido Intracelular/metabolismo , Mutagênese Sítio-Dirigida , Ligação Proteica , Estrutura Terciária de Proteína , Pseudomonas putida/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Relação Estrutura-Atividade
17.
Mater Sci Eng C Mater Biol Appl ; 33(7): 4063-70, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23910315

RESUMO

Copolymer of styrene, and vinylpyrrolidone was prepared by various techniques. Different nanometals and nanometal oxides were added into the copolymer as antimicrobial agents against Sulfate Reducing Bacteria (SRB). The nanocomposite chemical structure was confirmed by using FTIR, (1)H NMR spectroscopy and thermogravimetric analysis (TGA). The biocidal action of these nanocomposites against the SRB was detected using sulfide determination method in Postgate medium B. The data indicated that the nanocomposites had an inhibitory effect on the growth of SRB and reduced the bacterial corrosion rate of mild steel coupons. The prepared nanocomposites have high inhibition efficiency when applied as coatings and show less efficiency when applied as solids or solution into SRB medium. The copolymer and its nanocomposites effectively reduced the total corrosion rate as determined by total weight loss method.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Metais/farmacologia , Nanocompostos/química , Pirrolidinonas/farmacologia , Estireno/farmacologia , Cromatografia em Gel , Corrosão , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Peso Molecular , Nanocompostos/ultraestrutura , Oxirredução/efeitos dos fármacos , Tamanho da Partícula , Pirrolidinonas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Estireno/química , Sulfatos/metabolismo , Propriedades de Superfície , Termogravimetria
18.
Mater Sci Eng C Mater Biol Appl ; 33(3): 1209-13, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23827562

RESUMO

In this study, we report a simple and cost-effective method for self-sterilized complex coatings obtained by Ag@TiO2 particle incorporation into styrene-acrylic latex. The Ag@TiO2 particles were prepared via a coupling agent modification process. The composite latices characterized by transmission electron microscopy (TEM) study were highly homogeneous at the nanometric scale, and the Ag@TiO2 particles were well dispersed and exhibited an intimate contact between both the organic and inorganic components. The Ag@TiO2 nanoparticles significantly enhanced the absorption in the visible region and engendered a good heat-insulating effect of the complex coatings. Moreover, the Ag@TiO2 nanoparticle incorporation into this polymer matrix renders self-sterilized nanocomposite materials upon light excitation, which are tested against Escherichia coli and Staphylococcus aureus. The complex coatings display an impressive performance in the killing of all micro-organisms with a maximum for a Ag@TiO2 loading concentration of 2-5 wt.%. The weathering endurance of the complex coating was also measured.


Assuntos
Acrilatos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Prata/farmacologia , Esterilização , Estireno/farmacologia , Titânio/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Temperatura Alta , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Eletricidade Estática
19.
Macromol Biosci ; 13(6): 676-81, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23606423

RESUMO

Platelets play a fundamental role in thrombus formation and in the pathogenesis of arterial thrombosis. Patterning surfaces for controlled platelet adhesion paves the way for adhesion and activation mechanisms in platelets and detection of platelet functional defects. Here, a new and simple method based on controlled polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) on the surface of styrene-block-(ethylene-co-butylene)-block-styrene (SEBS) is shown. The competition between polymerization and degradation enables platelet adhesion on SEBS to be switched on and off. The adhesive sites of the platelets can be down to single cell level, and the dysfunctional platelets can be quantitatively detected.


Assuntos
Alcenos/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Etilenos/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Estireno/farmacologia , Animais , Plaquetas/ultraestrutura , Microscopia de Força Atômica , Coelhos , Propriedades de Superfície
20.
Bioresour Technol ; 134: 417-22, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23499180

RESUMO

Two immobilized preparations from Thermomyces lanuginosus lipase (TLL) were compared in the synthesis of butyl butyrate. The commercial Lipozyme TL-IM, and TLL immobilized on styrene-divinylbenzene beads (MCI-TLL) were tested in the esterification reaction using n-hexane as solvent. The variables temperature (30-60°C), substrate molar ratio (1:1 to 5:1), added water (0-1%), and biocatalyst content (3-40%) were evaluated in terms of initial reaction rate for each biocatalyst. SDS-PAGE analysis revealed that MCI-TLL had an immobilized enzymatic load twice as high as Lipozyme TL-IM, but with an activity 3-fold higher. MCI-TLL presented high initial reaction rates up to 1.0 M butyric acid, while Lipozyme TL-IM showed a decrease in its activity above 0.5 M. Moreover, MCI-TLL allowed a productivity of 14.5 mmol g(-1) h(-1), while Lipozyme TL-IM 3.2 mmol g(-1) h(-1), both by mass of biocatalyst.


Assuntos
Ascomicetos/enzimologia , Biotecnologia/métodos , Butiratos/metabolismo , Lipase/metabolismo , Microesferas , Estireno/farmacologia , Compostos de Vinila/farmacologia , Ascomicetos/citologia , Ascomicetos/efeitos dos fármacos , Biocatálise/efeitos dos fármacos , Butiratos/farmacologia , Células Imobilizadas/citologia , Células Imobilizadas/efeitos dos fármacos , Células Imobilizadas/enzimologia , Eletroforese em Gel de Poliacrilamida , Esterificação/efeitos dos fármacos , Cinética , Especificidade por Substrato/efeitos dos fármacos , Temperatura , Água/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...