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1.
Nanoscale ; 11(11): 4767-4780, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30816394

RESUMO

Nano-MoS2 has been extensively investigated in materials science and biomedicine. However, the effects of different methods of exposure on their translocation, biosafety, and biotransformation-related degradability remain unclear. In this study, we combined the advantages of synchrotron radiation (SR) X-ray absorption near-edge structure (XANES) and high-resolution single-cell SR transmission X-ray microscopy (SR-TXM) with traditional analytical techniques to investigate translocation, precise degraded species/ratio, and correlation between the degradation and toxicity levels of polyvinylpyrrolidone-modified 2H-phase MoS2 nanosheets (MoS2-PVP NSs). These NSs demonstrated different biodegradability levels in biomicroenvironments with H2O2, catalase, and human myeloperoxidase (hMPO) (H2O2 < catalase < hMPO). The effects of NSs and their biodegraded byproducts on cell viability and 3D translocation at the single-cell level were also assessed. Toxicity and translocation in mice via intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration routes guided by fluorescence (FL) imaging were investigated within the tested dosage. After i.g. administration, NSs accumulated in the gastrointestinal organs and were excreted from feces within 48 h. After i.v. injection, NSs showed noticeable clearance due to their decreased accumulation in the liver and spleen within 30 days when compared with that in the i.p. group, which exhibited slight accumulation in the spleen. This work paves the way for understanding the biological behaviors of nano-MoS2 using SR techniques that provide more opportunities for future applications.


Assuntos
Dissulfetos/farmacocinética , Dissulfetos/toxicidade , Molibdênio/farmacocinética , Molibdênio/toxicidade , Nanoestruturas/toxicidade , Povidona/farmacocinética , Povidona/toxicidade , Animais , Biotransformação , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/administração & dosagem , Dissulfetos/química , Vias de Administração de Medicamentos , Masculino , Camundongos Endogâmicos BALB C , Molibdênio/administração & dosagem , Molibdênio/química , Nanomedicina , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Povidona/administração & dosagem , Povidona/química , Distribuição Tecidual
2.
Mikrochim Acta ; 186(2): 58, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30617543

RESUMO

The authors describe a fluorometric strategy for the determination of dopamine (DA). It is based on the use of aptamer-functionalized MoS2 quantum dots (QDs) and MoS2 nanosheets (NSs). The QDs and NSs were extensively characterized with regard to their physical and chemical properties using methods such as TEM, XRD, FT-IR, EDX and molecular spectroscopies. The aptamer against dopamine was labeled with QDs acting as the energy donor in an energy transfer system, while the NSs serve as the energy acceptor. Under the optimal conditions, the fluorescence (FL) intensity (best measured at excitation/emission peaks of 315/412 nm) increases with increasing DA concentration in the range from 0.1 nM to 1000 nM, with a lower detection limit of 45 pM. The method was successfully applied to the determination of DA in complex matrices. In our perception, the method has a wide scope in that it may be extended to other biomolecules for which respective aptamer are available. The QDs show excellent optical properties, good stability, low cytotoxicity, and may also be applied to fluorometric imaging of live cells. Graphical abstract A "turn-on" fluorometric aptasensor for the determination of dopamine (DA) was established based on aptamer-functionalized molybdenum disulfide quantum dots (MoS2 QDs) and MoS2 nanosheets. This assay exhibits high selectivity and sensitivity with a detection limit as low as 45 pM.


Assuntos
Aptâmeros de Nucleotídeos/química , DNA/química , Dissulfetos/química , Dopamina/análise , Transferência Ressonante de Energia de Fluorescência/métodos , Molibdênio/química , Pontos Quânticos/química , Sequência de Bases , Técnicas Biossensoriais/métodos , Dissulfetos/toxicidade , Células HeLa , Humanos , Limite de Detecção , Molibdênio/toxicidade , Pontos Quânticos/toxicidade
3.
Ecotoxicol Environ Saf ; 169: 778-785, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30597776

RESUMO

Metal pyrithiones (MePTs) are frequently used antifouling biocides in marine coatings. Their main degradation product, 2,2'-dithiobis-pyridine ((PS)2), has been widely detected in seawater and may pose potential ecological risks. In the present study, sexually mature guppies (Poecilia reticulata) were exposed to (PS)2 at concentrations of 0, 20, 200, and 2000 ng/L for 28 days to investigate its reproductive toxicity. The results showed that (PS)2 significantly reduced testosterone (T) levels, spermatogenic cyst number and sperm motility, impeded spermatogenic cell differentiation in male guppies and delayed embryo development in females. These results indicated that (PS)2 could cause reproductive toxicity in guppies. We also examined mRNA expression of indices involved in the hypothalamic-pituitary-gonadal axis and reproductive behaviors. We found that 200 and 2000 ng/L (PS)2 decreased T synthesis by downregulating 17ßHSD and CYP17 mRNA levels, and upregulating the mRNA level of CYP19a1a, which converted T to 17ß-estradiol. (PS)2 also upregulated GnRH1, FSHß, LHß, and LHR mRNA levels, a positive feedback regulation due to the decrease of T levels in male guppies. Furthermore, (PS)2 significantly decreased CYP19a1b mRNA levels in all three exposure groups and thus reduced the display frequency of male guppies. This study was the first to report that (PS)2 could induce reproductive toxicity, which would provide a basis for future assessment of its ecological risk.


Assuntos
2,2'-Dipiridil/análogos & derivados , Desinfetantes/toxicidade , Dissulfetos/toxicidade , Poecilia/fisiologia , Reprodução/efeitos dos fármacos , 2,2'-Dipiridil/toxicidade , Animais , Diferenciação Celular , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Diferenciação Sexual , Maturidade Sexual/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/metabolismo , Testes de Toxicidade
4.
ACS Appl Mater Interfaces ; 11(5): 4858-4866, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30628779

RESUMO

Molybdenum disulfide (MoS2) nanosheets have received considerable interest due to their superior physicochemical performances to graphene nanosheets. As the lateral size and layer thickness decrease, the formed MoS2 quantum dots (QDs) show more promise as photocatalysts, endowing them with potential antimicrobial properties under environmental conditions. However, studies on the antibacterial photodynamic therapy of MoS2 QDs have rarely been reported. Here, we show that MoS2 QDs more effectively promote the creation and separation of electron-hole pair than MoS2 nanosheets, resulting in the formation of multiple reactive oxygen species (ROS) under simulated solar light irradiation. As a result, photoexcited MoS2 QDs show remarkably enhanced antibacterial activity, and the ROS-mediated oxidative stress plays a dominant role in the antibacterial mechanism. The in vivo experiments showed that MoS2 QDs are efficacious in wound healing under simulated solar light irradiation and exert protective effects on normal tissues, suggesting good biocompatibility properties. Our findings provide a full description of the photochemical behavior of MoS2 QDs and the resulting antibacterial activity, which might advance the development of MoS2-based nanomaterials as photodynamic antibacterial agents under environmental conditions.


Assuntos
Antibacterianos , Dissulfetos , Molibdênio , Pontos Quânticos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/química , Dissulfetos/farmacologia , Dissulfetos/toxicidade , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Molibdênio/química , Molibdênio/farmacologia , Molibdênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Processos Fotoquímicos , Pontos Quânticos/química , Pontos Quânticos/efeitos da radiação , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio , Infecção dos Ferimentos
5.
Chem Commun (Camb) ; 54(68): 9462-9465, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30083687

RESUMO

The synergistic effect of two anticancer drugs can significantly overcome the multidrug resistance of tumor cells and improve the drug bioavailability. Herein, two different anticancer drugs, camptothecin and chlorambucil, are successfully connected together by a disulfide linkage to get a novel drug-drug conjugated prodrug (G). Using water-soluble pillar[6]arene (WP6) as a host molecule, a supramolecular host-guest complex WP6⊃G is formed, which can further self-assemble into supramolecular vesicles in aqueous solution. In the specific microenvironment of cancer cells, the disulfide linkage is destroyed and the two anticancer drugs can be released efficiently to achieve a better synergistic effect than a single anticancer drug. Notably, these prodrug nanocarriers can not only effectively kill the cancer cells but also obviously reduce the undesirable side effects on normal cells.


Assuntos
Antineoplásicos/farmacologia , Camptotecina/farmacologia , Clorambucila/farmacologia , Portadores de Fármacos/química , Compostos de Amônio Quaternário/química , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Camptotecina/síntese química , Camptotecina/metabolismo , Camptotecina/toxicidade , Clorambucila/síntese química , Clorambucila/metabolismo , Clorambucila/toxicidade , Dissulfetos/síntese química , Dissulfetos/metabolismo , Dissulfetos/farmacologia , Dissulfetos/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Glutationa/metabolismo , Humanos , Células MCF-7 , Tamanho da Partícula , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Pró-Fármacos/toxicidade , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/toxicidade , Solubilidade , Água/química
6.
Chem Commun (Camb) ; 54(49): 6368-6371, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29869650

RESUMO

Gene silencing using small interfering RNA (siRNA) is a promising strategy for the treatment of multiple diseases. However, the low in vivo stability of siRNA, its poor pharmacokinetics and inability to penetrate inside cells limit its employment in the clinic. Here, we present a novel redox-sensitive micellar nanopreparation based on a triple conjugate of polyethylene glycol, polyethyleneimine and phosphatidylethanolamine, PEG-SS-PEI-PE (PSSPD). This non-toxic system efficiently condenses siRNA and specifically downregulates target green fluorescent protein (GFP) only under reducing conditions via intracellular siRNA release after de-shielding of PEG due to increased glutathione (GSH) levels characteristic of cancer cells.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , RNA Interferente Pequeno/química , Animais , Linhagem Celular , Dissulfetos/síntese química , Dissulfetos/química , Dissulfetos/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Glutationa/química , Camundongos , Micelas , Nanopartículas/toxicidade , Oxirredução , Tamanho da Partícula , Fosfatidiletanolaminas/síntese química , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/toxicidade , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Polietilenoimina/síntese química , Polietilenoimina/química , Polietilenoimina/toxicidade
7.
Environ Sci Technol ; 51(18): 10834-10842, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28841301

RESUMO

Sheetlike molybdenum disulfide (MoS2) and boron nitride (BN) nanomaterials have attracted attention in the past few years due to their unique material properties. However, information on adverse effects and their underlying mechanisms for sheetlike MoS2 and BN nanomaterials is rare. In this study, cytotoxicities of sheetlike MoS2 and BN nanomaterials on human hepatoma HepG2 cells were systematically investigated at different toxic end points. Results showed that MoS2 and BN nanomaterials decreased cell viability at 30 µg/mL and induced adverse effects on intracellular ROS generation (≥2 µg/mL), mitochondrial depolarization (≥4 µg/mL), and membrane integrity (≥8 µg/mL for MoS2 and ≥2 µg/mL for BN). Furthermore, this study first found that low exposure concentrations (0.2-2 µg/mL) of MoS2 and BN nanomaterials could increase plasma membrane fluidity and inhibit transmembrane ATP binding cassette (ABC) efflux transporter activity, which make both nanomaterials act as a chemosensitizer (increasing arsenic toxicity). Damage to plasma membrane and release of soluble Mo or B species might be two reasons that both nanomaterials inhibit efflux pump activities. This study provides a systematic understanding of the cytotoxicity of sheetlike MoS2 and BN nanomaterials at different exposure levels, which is important for their safe use.


Assuntos
Compostos de Boro/toxicidade , Dissulfetos/toxicidade , Molibdênio/toxicidade , Nanoestruturas/toxicidade , Transportadores de Cassetes de Ligação de ATP/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Células Hep G2 , Humanos
8.
Nanotoxicology ; 11(6): 781-793, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28714804

RESUMO

Single-layer molybdenum disulfide (SLMoS2) is a novel kind of 2D nanosheet that has attracted great attention regarding its use in biosensors, drug delivery, tissue engineering, and therapy. However, our results demonstrated that SLMoS2 accelerated proliferation and promoted myogenic differentiation and epithelial-mesenchymal transition (EMT) in human embryonic lung fibroblasts (HELFs). The abnormal proliferation and differentiation of HELFs contribute to idiopathic pulmonary fibrosis. Specifically, SLMoS2 significantly stimulated the expression of myofibroblast- and mesenchymal-associated genes and proteins. The Akt-mTOR-p70S6K signaling pathway plays a critical role in the acceleration of proliferation and promotion of myogenic differentiation and EMT in HELFs induced by SLMoS2. After cell uptake, SLMoS2 was primarily located in the cytoplasm and the perinuclear region and activated Akt-dependent signaling due to the generation of reactive oxygen species (ROS). Moreover, bovine serum albumin (BSA) binding markedly inhibited the cellular uptake of SLMoS2 and the production of intracellular ROS due to an increased thickness and reduced adhesion of HELFs. BSA binding also mitigated the SLMoS2-activated phosphorylation of Akt-dependent signaling pathways. This study is the first to illustrate the induction of cellular proliferation and differentiation by SLMoS2 and the related mediation by proteins through Akt-mTOR-p70S6K signaling pathway.


Assuntos
Proliferação de Células/efeitos dos fármacos , Dissulfetos/toxicidade , Molibdênio/toxicidade , Nanoestruturas/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Fosforilação
9.
J Colloid Interface Sci ; 496: 261-266, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28235720

RESUMO

Sandwich-like molybdenum sulfide/mesoporous organosilica nanosheets (denoted as MoS2@MOS) have been prepared for the first time via direct growth of ethane-bridged mesostructured organosilica on MoS2 nanosheets by using cetyltrimethylammonium bromide (CTAB) as structure directing agent. The obtained MoS2@MOS nanosheets possess well-defined sandwich-like structure, high surface area (∼920cm2/g), uniform pore size (∼4.2nm), large pore volume (∼1.41cm3g-1). In vitro cytotoxicity assessments demonstrate that the MoS2@MOS nanosheets have excellent biocompatibility. Owing to the encapsulation of the MoS2, the obtained MoS2@MOS nanosheets have photo-thermal conversion capability and photo-thermally controlled drug release property. These properties make the MoS2@MOS nanosheets promising for biomedical applications.


Assuntos
Dissulfetos/química , Molibdênio/química , Nanoestruturas/química , Compostos de Organossilício/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Cetrimônio , Compostos de Cetrimônio/química , Dissulfetos/toxicidade , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Temperatura Alta , Humanos , Lasers , Células MCF-7 , Molibdênio/toxicidade , Nanoestruturas/efeitos da radiação , Nanoestruturas/toxicidade , Compostos de Organossilício/toxicidade , Tamanho da Partícula , Porosidade , Propriedades de Superfície
10.
Cell Biol Toxicol ; 33(1): 41-56, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27581547

RESUMO

p21-activated kinase 1 (Pak1)-a key node protein kinase regulating various cellular process including angiogenesis-has been recognised to be a therapeutic target for multitude of diseases, and hence, various small molecule inhibitors targeting its activity have been tested. However, the direct toxic and anti-angiogenic effects of these pharmacologic agents have not been examined. In this study, we evaluate the translational efficacy of Pak1 inhibitor IPA-3 using zebrafish toxicity model system to stratify its anti-angiogenic potential and off-target effects to streamline the compound for further therapeutic usage. The morphometric analysis has shown explicit delay in hatching, tail bending, pericardial sac oedema and abnormal angiogenesis. We provide novel evidence that Pak1 inhibitor could act as anti-angiogenic agents by impeding the development of sub-intestinal vessel (SIV) and intersegmental vessels (ISVs) by suppressing the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), neurophilin 1 (NRP1) and its downstream genes matrix metalloproteinase (MMP)-2 and MMP-9. Knockdown studies using 2-O-methylated oligoribonucleotides targeting Pak1 also revealed similar phenotypes with inhibition of angiogenesis accompanied with deregulation of major angiogenic factor and cardiac-specific genes. Taken together, our findings indicate that Pak1 signalling facilitates enhanced angiogenesis and also advocated the design and use of small molecule inhibitors of Pak1 as potent anti-angiogenic agents and suggest their utility in combinatorial therapeutic approaches targeting anomalous angiogenesis.


Assuntos
Inibidores da Angiogênese/farmacologia , Dissulfetos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Naftóis/toxicidade , Testes de Toxicidade , Peixe-Zebra/embriologia , Quinases Ativadas por p21/antagonistas & inibidores , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/embriologia , Dissulfetos/química , Embrião não Mamífero/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Modelos Animais , Naftóis/química , Neovascularização Fisiológica/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Quinases Ativadas por p21/metabolismo
11.
J Agromedicine ; 21(4): 373-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27409156

RESUMO

Dimethyl disulfide (DMDS) is a new soil fumigant that is considered a replacement for methyl bromide. In 2014, the Florida Department of Health (FDOH) received several complaints of illness following a strong DMDS odor in Hillsborough County. Public health investigation of DMDS-related illness was conducted to assess illness and identify areas to target for prevention activities. This investigation included surveillance, interviews, review of medical records, review of supporting documentation, and determination of pesticide-related illness and injury case status. FDOH interviewed 66 people complaining of illness related to DMDS. Thirty-two were classified as possible and 11 as suspicious cases of DMDS-related illness. Among cases, the mean age was 48 years (range: 3-71 years). The majority were non-Hispanic (n = 43, 100%), white (n = 40, 93%), and female (n = 23, 53.5%). The most common signs and symptoms reported by exposed people included eye pain, throat irritation, nausea, dizziness, headache, and fatigue. There were 88% of cases classified as having low severity of illness and 12% classified as having moderate severity. The average distance from an application site among individuals who reported being exposed at or near their home was 0.74 miles for those classified as cases (n = 36) and 2.84 miles for those not classified as cases (n = 21, P < .05). This is the first known comprehensive report of DMDS-related illness in humans. Even though illnesses associated with DMDS in this investigation were generally of low severity, it is important to identify better ways to prevent off-target movement of DMDS and to improve notification to communities when nearby DMDS applications are planned.


Assuntos
Dissulfetos/toxicidade , Exposição Ambiental/efeitos adversos , Fumigação/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Florida , Humanos , Masculino , Pessoa de Meia-Idade , Odorantes , Adulto Jovem
12.
Free Radic Biol Med ; 96: 45-56, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27085841

RESUMO

The regulatory mechanisms of yeast Sir2, the founding member of the sirtuin family involved in oxidative stress and aging, are unknown. Redox signaling controls many cellular functions, especially under stress situations, with dithiol glutaredoxins (Grxs) playing an important role. However, monothiol Grxs are not considered to have major oxidoreductase activity. The present study investigated the redox regulation of yeast Sir2, together with the role and physiological impact of monothiol Grx3/4 as Sir2 thiol-reductases upon stress. S-glutathionylation of Sir2 upon disulfide stress was demonstrated both in vitro and in vivo, and decreased Sir2 deacetylase activity. Physiological levels of nuclear Grx3/4 can reverse the observed post-translational modification. Grx3/4 interacted with Sir2 and reduced it after stress, thereby restoring telomeric silencing activity. Using site-directed mutagenesis, key cysteine residues at the catalytic domain of Sir2 were identified as a target of S-glutathionylation. Mutation of these residues resulted in cells with increased resistance to disulfide stress. We provide new mechanistic insights into Grx3/4 regulation of Sir2 by S-deglutathionylation to increase cell resistance to stress. This finding offers news perspectives on monothiol Grxs in redox signaling, describing Sir2 as a physiological substrate regulated by S-glutathionylation. These results might have a relevant role in understanding aging and age-related diseases.


Assuntos
Glutarredoxinas/genética , Glutationa/metabolismo , Estresse Oxidativo/genética , Oxirredutases/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/genética , Sirtuína 2/genética , Envelhecimento/genética , Envelhecimento/patologia , Sequência de Aminoácidos , Cisteína/genética , Dissulfetos/toxicidade , Glutarredoxinas/metabolismo , Glutationa/genética , Mutagênese Sítio-Dirigida , Oxirredução , Oxirredutases/metabolismo , Processamento de Proteína Pós-Traducional/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/metabolismo , Sirtuína 2/metabolismo , Estresse Fisiológico/genética
13.
Ecotoxicology ; 25(2): 291-301, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26661591

RESUMO

Limited data are available on the effects of molybdenum (Mo) on avian wildlife, which impairs evaluation of ecological exposure and risk. While Mo is an essential trace nutrient in birds, little is known of its toxicity to birds exposed to molybdenum disulfide (MoS2), the predominant form found in molybdenite ore. The chemical form and bioavailability of Mo is important in determining its toxicity. Avian toxicity tests typically involve a soluble form of Mo, such as sodium molybdate dihydrate (SMD, Na2MoO4·2H2O); however MoS2 is generally insoluble, with low bioaccessibility under most environmental conditions. The current study monitored survival and general health (body weight and food consumption) of 9-day old northern bobwhite exposed to soluble Mo (SMD) and ore-related Mo (MoS2) in their diet for 30 days. Toxicity and bioavailability (e.g. tissue distribution) of the two Mo forms were compared. Histopathology evaluations and serum, kidney, liver, and bone tissue sample analyses were conducted. Copper, a nutrient integrally associated with Mo toxicity, was also measured in the diet and tissue. No treatment-related mortality occurred and no treatment-related lesions were recorded for either Mo form. Tissue analyses detected increased Mo concentrations in serum, kidney, liver, and bone tissues following exposure to SMD, with decreasing concentrations following a post-exposure period. For the soluble form, a No-Observed-Adverse-Effect Concentration (NOAEC) of 1200 mg Mo as SMD/kg feed (134 mg SMD/kg body weight/day) was identified based on body weight and food consumption. No adverse effects were observed in birds exposed to MoS2 at the maximum dose of 5000 mg MoS2/kg feed (545 mg MoS2/kg body weight/day). These results show that effects associated with MoS2, the more environmentally prevalent and less bioavailable Mo form, are much less than those observed for SMD. These data should support more realistic representations of exposure and risks to avian receptors from environmental Mo.


Assuntos
Colinus/metabolismo , Dissulfetos/toxicidade , Molibdênio/toxicidade , Poluentes do Solo/toxicidade , Animais , Colinus/crescimento & desenvolvimento , Comportamento Alimentar/efeitos dos fármacos , Feminino , Longevidade/efeitos dos fármacos , Masculino , Ganho de Peso/efeitos dos fármacos
14.
Sci Rep ; 5: 17422, 2015 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-26632249

RESUMO

Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.


Assuntos
Dissulfetos/química , Molibdênio/química , Nanoestruturas/química , Fototerapia/métodos , Animais , Adesão Celular/efeitos dos fármacos , Adesão Celular/efeitos da radiação , Linhagem Celular Tumoral , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/efeitos da radiação , Dissulfetos/toxicidade , Feminino , Hemólise/efeitos dos fármacos , Humanos , Hipertermia Induzida/métodos , Lasers , Lisossomos/efeitos dos fármacos , Lisossomos/efeitos da radiação , Teste de Materiais , Camundongos Endogâmicos BALB C , Molibdênio/toxicidade , Nanotecnologia/métodos , Polietilenoglicóis , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Small ; 11(38): 5079-87, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26237579

RESUMO

2D molybdenum disulfide (MoS2 ) has distinct optical and electronic properties compared to aggregated MoS2 , enabling wide use of these materials for electronic and biomedical applications. However, the hazard potential of MoS2 has not been studied extensively. Here, a comprehensive analysis of the pulmonary hazard potential of three aqueous suspended forms of MoS2 -aggregated MoS2 (Agg-MoS2 ), MoS2 exfoliated by lithiation (Lit-MoS2 ), and MoS2 dispersed by Pluronic F87 (PF87-MoS2 )-is presented. No cytotoxicity is detected in THP-1 and BEAS-2B cell lines. However, Agg-MoS2 induces strong proinflammatory and profibrogenic responses in vitro. In contrast, Lit- and PF87-MoS2 have little or no effect. In an acute toxicity study in mice, Agg-MoS2 induces acute lung inflammation, while Lit-MoS2 and PF87-MoS2 have little or no effect. In a subchronic study, there is no evidence of pulmonary fibrosis in response to all forms of MoS2 . These data suggest that exfoliation attenuates the toxicity of Agg-MoS2 , which is an important consideration toward the safety evaluation and use of nanoscale MoS2 materials for industrial and biological applications.


Assuntos
Dissulfetos/toxicidade , Pulmão/patologia , Molibdênio/toxicidade , Testes de Toxicidade/métodos , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Dissulfetos/química , Humanos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Molibdênio/química
16.
Nanotechnology ; 26(31): 315102, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26183754

RESUMO

Transition metal dichalgogenides such as MoS2 have recently emerged as hot two-dimensional (2D) materials due to their superior electronic and catalytic properties. Recently, we have reported the usefulness of MoS2 nanosheets toward the electrochemical detection of neurotransmitters and glucose (Narayanan et al 2014 Nanotechnology 25 335702). Furthermore, there are reports available in the literature that demonstrate the usefulness of MoS2 nanosheets for biosensing and energy storage applications (Zhu et al 2013 J. Am. Chem. Soc. 135 5998-6001; Pumera and Loo 2014 Trends Anal. Chem. 61 49-53; Lee et al 2014 Sci. Rep. 4 7352; Stephenson et al 2014 Energy Environ. Sci. 7 209-31). Understanding the cytotoxic effect of any material is very important prior to employing them for any in vivo biological applications such as implantable sensors, chips, or carriers for drug delivery and cell imaging purposes. Herein, we report the cytotoxicity of the MoS2 nanosheets based on the cytotoxic assay results and electrical impedance analysis using rat pheochromocytoma cells (PC12) and rat adrenal medulla endothelial cells (RAMEC). Our results indicated that the MoS2 nanosheets synthesized in our work are safe 2D nanosheets for futuristic biomedical applications.


Assuntos
Materiais Biocompatíveis/toxicidade , Dissulfetos/toxicidade , Molibdênio/toxicidade , Nanoestruturas/toxicidade , Medula Suprarrenal/citologia , Animais , Materiais Biocompatíveis/química , Células Cultivadas , Espectroscopia Dielétrica , Dissulfetos/química , Células Endoteliais/química , Molibdênio/química , Nanoestruturas/química , Células PC12/química , Ratos
17.
Toxicol Ind Health ; 31(12): 1116-27, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23681548

RESUMO

The freshwater carp, Cyprinus carpio, was exposed to 0.5 mg (30% of median lethal concentration (LC50)), 1.0 mg (60% of LC50), and 1.6 mg (LC50) of dithiopyridine herbicide per liter for acute (24 h) and 1/10 of LC50 (0.2 mg/L/day) for sublethal (1, 3, 7, 14, and 21 days) experiments. The herbicide bioaccumulation was significantly affected by the acute exposure levels and the experimental periods and was positively correlated with them. One-way analysis of variance revealed that the acute and sublethal exposure to the herbicide as well as the experimental periods caused significant reduction in the concentrations of catecholamines (dopamine (DA) and norepinephrine (NE)), elevation of acetylcholine (ACh), and was associated with a marked decrease in the activity of acetylcholinesterase (AChE). In comparison with the corresponding controls, most levels of the DA and NE and the activity of AChE were significantly decreased, whereas the concentration of ACh was markedly elevated, during acute and sublethal exposure. In the acute and sublethal experiments, the herbicide accumulated in the brain was inversely proportional to the levels of DA and NE and the activity of AChE but has a direct correlation with the concentration of ACh. In addition, the brain's AChE activity was negatively correlated with ACh content during the acute (r = -0.94) and sublethal (r = -0.78) experiments.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Carpas , Dissulfetos/toxicidade , Herbicidas/toxicidade , Neurônios/efeitos dos fármacos , Piridinas/toxicidade , Análise de Variância , Animais , Aquicultura , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Egito , Doenças dos Peixes/induzido quimicamente , Doenças dos Peixes/metabolismo , Neurônios/metabolismo , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/veterinária , Resíduos de Praguicidas/toxicidade , Distribuição Aleatória , Distribuição Tecidual , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Toxicocinética , Poluentes Químicos da Água/toxicidade
18.
Dermatitis ; 25(4): 191-4, 2014 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25000237

RESUMO

BACKGROUND: Contact eczema to foods, spices, and food additives can occur in occupational and nonoccupational settings in those who grow, handle, prepare, or cook food. Pizza is one of the most eaten foods in every continent, and pizza making is a common work in many countries. OBJECTIVE: We aimed to evaluate the occurrence and the causes of contact dermatitis in pizza makers in Naples. METHODS: We performed an observational study in 45 pizza makers: all the enrolled subjects had to answer a questionnaire designed to detect personal history of respiratory or cutaneous allergy, atopy; work characteristics and timing were also investigated. Every subject attended the dermatology clinic for a complete skin examination, and when needed, patients were patch tested using the Italian baseline series of haptens integrated with an arbitrary pizza makers series. RESULTS: Our results reported that 13.3% of the enrolled pizza makers (6/45) presented hand eczema, and that 8.9% (4/45) were affected by occupational allergic contact dermatitis. Diallyl disulfide and ammonium persulfate were the responsible substances. CONCLUSIONS: Performing patch tests in pizza makers and food handlers affected by hand contact dermatitis is useful. We propose a specific series of haptens for this wide working category.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Dermatite Ocupacional/diagnóstico , Dermatoses da Mão/diagnóstico , Restaurantes , Adulto , Compostos Alílicos/toxicidade , Sulfato de Amônio/toxicidade , Culinária , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/etiologia , Dissulfetos/toxicidade , Eczema/induzido quimicamente , Eczema/diagnóstico , Alimentos/toxicidade , Dermatoses da Mão/etiologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Inquéritos e Questionários , Adulto Jovem
19.
ACS Nano ; 8(7): 6922-33, 2014 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-24905027

RESUMO

We report here a simple, high-yield yet low-cost approach to design single-layer MoS2 nanosheets with controllable size via an improved oleum treatment exfoliation process. By decorating MoS2 nanosheets with chitosan, these functionalized MoS2 nanosheets have been developed as a chemotherapeutic drug nanocarrier for near-infrared (NIR) photothermal-triggered drug delivery, facilitating the combination of chemotherapy and photothermal therapy into one system for cancer therapy. Loaded doxorubicin could be controllably released upon the photothermal effect induced by 808 nm NIR laser irradiation. In vitro and in vivo tumor ablation studies demonstrate a better synergistic therapeutic effect of the combined treatment, compared with either chemotherapy or photothermal therapy alone. Finally, MoS2 nanosheets can also be used as a promising contrast agent in X-ray computed tomography imaging due to the obvious X-ray absorption ability of Mo. As a result, the high-throughput oleum treatment exfoliation process could be extended for fabricating other 2D nanomaterials, and the NIR-triggered drug release strategy was encouraging for simultaneous imaging-guided cancer theranostic application.


Assuntos
Dissulfetos/química , Portadores de Fármacos/química , Raios Infravermelhos , Molibdênio/química , Nanoestruturas/química , Nanotecnologia , Temperatura Ambiente , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Dissulfetos/toxicidade , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Modelos Moleculares , Conformação Molecular , Molibdênio/toxicidade
20.
J Agric Food Chem ; 62(21): 4864-9, 2014 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-24820184

RESUMO

The combination of dimethyl disulfide (DMDS) and dazomet (DZ) is a potential alternative to methyl bromide (MB) for soil disinfestation. The efficacy of DMDS plus DZ in controlling key soilborne pests was evaluated in a laboratory study and in two commercial cucumber greenhouses. Laboratory studies found that all of the combinations had positive synergistic effects on root-knot nematodes, two key soilborne fungi, and two major weed seeds. Greenhouse trials revealed that the combination of DMDS and DZ (30 + 25 g m(-2)) successfully suppressed Meloidogyne spp. root galling, sharply reduced the colony-forming units of Fusarium spp. and Phytophthora spp. on media, maintained high cucumber yields, and was not significantly different from MB or DMDS alone, but better than DZ alone. All of the chemical treatments provided significantly better results than the nontreated control. The results indicate that the combination of DMDS and DZ is an efficient MB alternative for cucumber production.


Assuntos
Cucumis sativus/crescimento & desenvolvimento , Dissulfetos/toxicidade , Hidrocarbonetos Bromados/toxicidade , Controle de Pragas/métodos , Doenças das Plantas/prevenção & controle , Tiadiazinas/toxicidade , Controle de Plantas Daninhas/métodos , Animais , China , Cucumis sativus/microbiologia , Cucumis sativus/parasitologia , Fungos/efeitos dos fármacos , Nematoides/efeitos dos fármacos , Doenças das Plantas/microbiologia , Doenças das Plantas/parasitologia , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/crescimento & desenvolvimento
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