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1.
Chemosphere ; 238: 124647, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31466007

RESUMO

Ground water arsenic contamination is a global menace. Since arsenic may affect the immune system, leading to immunesuppression, we investigated the effects of acute arsenic exposure on the thymus and spleen using Swiss albino mice, exposed to 5 ppm, 15 ppm and 300 ppm of sodium arsenite for 7 d. Effects on cytokine balance and cell survivability were subsequently analyzed. Our data showed that arsenic treatment induced debilitating alterations in the tissue architecture of thymus and spleen. A dose-dependent decrease in the ratio of CD4+-CD8+ T-cells was observed along with a pro-inflammatory response and redox imbalance. In addition, pioneering evidences established the ability of arsenic to induce an up regulation of Hsp90, eventually resulting in stabilization of its client protein Beclin-1, an important autophagy-initiating factor. This association initiated the autophagic process, confirmed by co-immunoprecipitation assay, acridine orange staining and Western blot, indicating the effort of cells trying to survive at lower doses. However, increased arsenic assault led to apoptotic cell death in the lymphoid organs, possibly by increased ROS generation. There are several instances of autophagy and apoptosis taking place either simultaneously or sequentially due to oxidative stress. Since arsenic is a potent environmental stress factor, exposure to arsenic led to a dose-dependent increase in both autophagy and apoptosis in the thymus and spleen, and cell death could therefore possibly be induced by autophagy. Therefore, exposure to arsenic leads to serious effects on the immune physiology in mice, which may further have dire consequences on the health of exposed animals.


Assuntos
Arsênico/farmacologia , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Animais , Apoptose/efeitos dos fármacos , Arsenitos/farmacologia , Relação CD4-CD8 , Inflamação/induzido quimicamente , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/farmacologia , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia
2.
Biochim Biophys Acta Gene Regul Mech ; 1862(6): 657-669, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31075539

RESUMO

Variation in Disrupted-in-Schizophrenia 1 (DISC1) increases the risk for neurodegenerative diseases, schizophrenia, and other mental disorders. However, the functions of DISC1 associated with the development of these diseases remain unclear. DISC1 has been reported to inhibit Akt/mTORC1 signaling, a major regulator of translation, and recent studies indicate that DISC1 could exert a direct role in translational regulation. Here, we present evidence of a novel role of DISC1 in the maintenance of protein synthesis during oxidative stress. In order to investigate DISC1 function independently of Akt/mTORC1, we used Tsc2-/- cells, where mTORC1 activation is independent of Akt. DISC1 knockdown enhanced inhibition of protein synthesis in cells treated with sodium arsenite (SA), an oxidative agent used for studying stress granules (SGs) dynamics and translational control. N-acetyl-cysteine inhibited the effect of DISC1, suggesting that DISC1 affects translation in response to oxidative stress. DISC1 decreased SGs number in SA-treated cells, but resided outside SGs and maintained protein synthesis independently of a proper SG nucleation. DISC1-dependent stimulation of translation in SA-treated cells was supported by its interaction with eIF3h, a component of the canonical translation initiation machinery. Consistent with a role in the homeostatic maintenance of translation, DISC1 knockdown or overexpression decreased cell viability after SA exposure. Our data suggest that DISC1 is a relevant component of the cellular response to stress, maintaining certain levels of translation and preserving cell integrity. This novel function of DISC1 might be involved in its association with pathologies affecting tissues frequently exposed to oxidative stress.


Assuntos
Arsenitos/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Grânulos Citoplasmáticos/metabolismo , DNA Helicases/metabolismo , Fator de Iniciação 3 em Eucariotos/metabolismo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Proteínas do Tecido Nervoso/genética , Proteína Oncogênica v-akt , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Transcriptoma , Proteína 2 do Complexo Esclerose Tuberosa/genética
3.
J Plant Physiol ; 238: 72-79, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31146184

RESUMO

Sodium arsenite (NaAsO2) was especially used as a dormant spray to control grapevine trunk diseases (GTDs) in European vineyards until 2003 when it was banned. It was an efficient product but it was banned due to high risk for human health and the environment. Now, as one of the consequences with climatic changes, GTDs threaten the sustainability of vineyards since no similar and efficacious sprays are presently available to reduce the impact of GTDs. Research efforts were devoted to identify other active ingredients and biological control agents but they remained limited in term of efficacy. New solutions might follow from a better understanding of the modes of action of sodium arsenite which are currently lacking, specially its impact on grapevine physiology. For this study, grafted plants cv. Tempranillo were sprayed by sodium arsenite at the end of the winter. During the vegetative period, the impact on plant physiology was studied by measurement of the photosynthetic activity, the vine growth and development, and some defense responses. Our results showed that arsenic was translocated throughout the vine with an increasing gradient from the leaves to the root system, that photosynthesis was firstly reduced and then stimulated, and that plant tolerance responses were induced especially antioxidant system. The activation of grapevine defense responses by sodium arsenite could be a complementary action to fight fungal pathogens in addition to the fungicide effect.


Assuntos
Arsenitos/farmacologia , Compostos de Sódio/farmacologia , Vitis/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Caules de Planta/efeitos dos fármacos , Caules de Planta/metabolismo , Reação em Cadeia da Polimerase , Vitis/crescimento & desenvolvimento , Vitis/fisiologia
4.
Biochim Biophys Acta Mol Cell Res ; 1866(10): 1676-1686, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31029697

RESUMO

The three canonical members of the family of homeodomain-interacting protein (HIP) kinases fulfill overlapping and distinct roles in cellular stress response pathways. Here we systematically compared all three endogenous HIPKs for their intracellular distribution and mutual interactions. The endogenous HIPKs are contained in high molecular weight complexes of ~700 kDa but do not directly interact physically. Under basal conditions, HIPK1 was mostly cytoplasmic, while HIPK3 was found in the nucleus and HIPK2 occurred in both compartments. Inhibition of nuclear export by leptomycin B resulted in the nuclear accumulation of mainly HIPK1 and HIPK2, indicating constitutive dynamic nucleocytoplasmic shuttling. The carcinogenic chemical stressor sodium arsenite caused the induction of HIPK2-dependent cell death and also resulted in a rapid and complete nuclear translocation of HIPK2, showing that the intracellular distribution of this kinase can undergo dynamic regulation.


Assuntos
Transporte Ativo do Núcleo Celular/fisiologia , Proteínas de Transporte/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Arsenitos/farmacologia , Proteínas de Transporte/genética , Morte Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Ácidos Graxos Insaturados , Células HCT116 , Células HEK293 , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fosforilação , Transporte Proteico , Proteínas Serina-Treonina Quinases/genética , Compostos de Sódio/farmacologia
5.
Biomol NMR Assign ; 13(1): 249-254, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30868366

RESUMO

Human linker histone H1 plays a seminal role in eukaryotic DNA packaging. H1 has a tripartite structure consisting of a central, conserved globular domain, which adopts a winged-helix fold, flanked by two variable N- and C-terminal domains. Here we present the backbone resonance assignments of the N-terminal domain and globular domain of human linker histone H1x in the presence and absence of the secondary structure stabilizer sodium perchlorate. Analysis of chemical shift changes between the two conditions is consistent with induction of transient secondary structural elements in the N-terminal domain of H1x in high ionic strength, which suggests that the N-terminal domain adopts significant alpha-helical conformations in the presence of DNA.


Assuntos
Histonas/química , Ressonância Magnética Nuclear Biomolecular , Percloratos/farmacologia , Compostos de Sódio/farmacologia , Humanos , Domínios Proteicos , Estrutura Secundária de Proteína
6.
Exp Parasitol ; 200: 55-60, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30790573

RESUMO

This study aimed to observe the effects of sodium arsenite (NaAsO2) on apoptosis of Echinococcus granulosus protoscoleces induced by albendazole (ABZ), and to explore the potential mechanism of NaAsO2. According to the following final concentrations, the experimental groups were divided into 10 µM NaAsO2, 20 µM NaAsO2, 80 µM ABZ, 10 µM NaAsO2+80 µM ABZ, and 20 µM NaAsO2+80 µM ABZ. Viability was detected with 0.1% eosin staining. The ultrastructural alterations were visualized by scanning electron microscopy. Caspase-3 activity was assessed with colorimetric assay. Meanwhile, ELISA or WST were applied to detect the activities of antioxidases in NaAsO2 treatment groups. The maximum protoscolicidal effect was seen with the combination 20 µM NaAsO2+80 µM ABZ. The ultrastructural damage detected after NaAsO2+ABZ incubation were greater than those caused by ABZ alone and its primary damage site was the tegument of the parasite. The caspase-3 activity was clearly higher in protoscoleces treated with the combination of NaAsO2+ABZ than when drugs were used separately. The activities of NQO-1, HO-1, GST, and SOD were significantly lower in protoscoleces incubated with NaAsO2 than the untreated controls (P < 0.05). According to our results, ABZ could induce protoscoleces apoptosis, and NaAsO2 could significantly augment sensitivity of protoscoleces to ABZ.


Assuntos
Albendazol/farmacologia , Anticestoides/farmacologia , Arsenitos/farmacologia , Echinococcus granulosus/efeitos dos fármacos , Compostos de Sódio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Colorimetria , Sinergismo Farmacológico , Equinococose Hepática/tratamento farmacológico , Equinococose Hepática/parasitologia , Echinococcus granulosus/enzimologia , Echinococcus granulosus/ultraestrutura , Microscopia Eletrônica de Varredura , Ovinos
7.
Environ Toxicol ; 34(1): 83-91, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30291770

RESUMO

For the first time, juvenile toxicity of inorganic arsenic (As) was investigated in male rats, focusing on reproductive effects. As is a metalloid naturally occurring in the environment, being the inorganic forms the most toxics. Contaminated drinking water and agricultural products are the main prospectors of intoxication for general population. In the present study, Wistar male rats (21 days old) were distributed into three groups (n = 10/group): control (received vehicle-filtered drinking water), As1 (received AsNaO2 at 0.01 mg L-1 ) and As2 (received AsNaO2 at 10 mg L-1 ). The animals were euthanized on PND 53. Testicular damages increased in As1 and As2 compared to control (ie, presence of vacuolization, acidophilic cells, and epithelium degeneration). Testicular interstitium of As1 and As2 presented fluid's increase and intense inflammatory infiltration. In the epididymis there was reduction of sperm amount in the lumen, besides epithelium areas presenting cribriform aspect in As1 and As2, exfoliation of cells in the light (in As1) and vacuoles (in As2). In epididymis interstitium, inflammatory infiltrates were observed in initial segment of As1 and As2. AsNaO2 changed immunolabeling pattern for androgen receptor in epididymis of As2, although serum testosterone levels was statistically comparable to control. Mass spectrometry revealed higher As concentrations in testis and epididymis of As2 compared to As1 and Control. These results indicate compromise of spermatogenesis and epididymal histophysiology in AsNaO2 -treated animals, possibly impairing sperm quality and fertility in long-term, even at low levels of exposure. Investigations about the reversibility of reproductive damages are necessary to better understand the mechanisms of As reproductive toxicity.


Assuntos
Arsenitos/toxicidade , Epididimo/efeitos dos fármacos , Epididimo/patologia , Maturidade Sexual/efeitos dos fármacos , Compostos de Sódio/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Intoxicação por Arsênico/patologia , Intoxicação por Arsênico/fisiopatologia , Arsenitos/farmacologia , Fertilidade/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Compostos de Sódio/farmacologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testes de Toxicidade , Poluentes Químicos da Água/toxicidade
8.
Probiotics Antimicrob Proteins ; 11(1): 30-42, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-28994024

RESUMO

Managing arsenic intoxication with conventional metal chelators is a global challenge. The present study demonstrated the therapeutic role of probiotics against arsenic-induced oxidative stress and female reproductive dysfunction. Sodium arsenite-treated (1.0 mg/100 g body weight) Wistar female rats were followed up by a post-treatment of commercially available probiotic mixture in powder form (0.25 mg/100 g body weight) orally. Rats that experienced arsenic ingestion showed a significant lessening in the activities of uterine superoxide dismutase (SOD), catalase activities, and the level of non-protein soluble thiol (NPSH) with a concomitant increase in malondialdehyde (MDA) and conjugated dienes (CD). Exposure to arsenic significantly lowered the levels of vitamin B12 and estradiol. Exposure to arsenic highly expressed the inflammatory marker and transcription factor NF-κB. Arsenic-mediated instability of these above parameters was controlled by the probiotics with a rebuilding of better function of anti-oxidant components. Besides its function in regulating endogenous anti-oxidant system, probiotics were able to augment the protection against mutagenic uterine DNA-breakage, necrosis, and ovarian-uterine tissue damages in arsenicated rats.


Assuntos
Arsenitos/farmacologia , L-Lactato Desidrogenase/sangue , NF-kappa B/fisiologia , Probióticos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sódio/farmacologia , Útero/metabolismo , Vitamina B 12/sangue , Animais , Dano ao DNA , Estradiol/sangue , Feminino , Peroxidação de Lipídeos , Ratos , Superóxido Dismutase/metabolismo
9.
Cell Death Dis ; 9(11): 1129, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30425239

RESUMO

We show that 3-morpholinosydnonimine (SIN-1)-induced nitric oxide (NO) triggers the formation of SGs. Whereas the composition of NO-induced SGs is initially similar to sodium arsenite (SA)-induced type I (cytoprotective) SGs, the progressive loss of eIF3 over time converts them into pro-death (type II) SGs. NO-induced SG assembly requires the phosphorylation of eIF2α, but the transition to type II SGs is temporally linked to the mTOR-regulated displacement of eIF4F complexes from the m7 guanine cap. Whereas SA does not affect mitochondrial morphology or function, NO alters mitochondrial integrity and function, resulting in increased ROS production, decreased cytoplasmic ATP, and plasma membrane permeabilization, all of which are supported by type II SG assembly. Thus, cellular energy balance is linked to the composition and function of NO-induced SGs in ways that determine whether cells live or die.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Apoptose/efeitos dos fármacos , Grânulos Citoplasmáticos/efeitos dos fármacos , Fibroblastos/metabolismo , Óxido Nítrico/metabolismo , Trifosfato de Adenosina/biossíntese , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Arsenitos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Grânulos Citoplasmáticos/metabolismo , Grânulos Citoplasmáticos/ultraestrutura , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 3 em Eucariotos/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Fator de Iniciação 4F em Eucariotos/genética , Fator de Iniciação 4F em Eucariotos/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Molsidomina/análogos & derivados , Molsidomina/metabolismo , Molsidomina/farmacologia , Doadores de Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Biossíntese de Proteínas , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sódio/farmacologia , Estresse Fisiológico , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
10.
Int J Food Microbiol ; 284: 40-47, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29990638

RESUMO

Concerns have been on the rise regarding the use of chlorine-based sanitizers for fresh produce sanitation due to the production of toxic disinfection by-products (DBPs). This study was undertaken to evaluate the efficacy of activated persulfate in inactivating Escherichia coli O157:H7 and Listeria monocytogenes in pure culture. The objectives were to study the effect of persulfate to activator ratios and determine the major contributing radical in pathogen inactivation. A five-strain cocktail of each pathogen was treated with sodium persulfate activated by ferrous sulfate or sodium hydroxide for 60 s or 120 s. Non-selective agars supplemented with sodium pyruvate were used for pathogen enumeration. The steady-state concentrations of free radicals were quantified using HPLC-DAD. Radical scavengers (tert-butanol, isopropanol, and benzoquinone) were used to determine the major contributing radical in pathogen inactivation. The results showed more than 7 log CFU/mL reductions can be achieved in 120 s for both pathogens at appropriate activation conditions. For ferrous activation, the persulfate to ferrous ratio played an important role in the overall inactivation efficacy. The maximum pathogen reduction (7.77 log CFU/mL for E. coli O157:H7 and 7.25 log CFU/mL for L. monocytogenes) was achieved at persulfate to ferrous molar ratio of 1:0.33 when the initial persulfate concentration was set at 40 mmol/L. Further increase or decrease of ferrous ratio always leads to lower pathogen reductions. For alkaline activation, the inactivation efficacy increased with more initial sodium hydroxide. The maximum reduction was achieved at 40 mmol/L persulfate with 30 mmol/L sodium hydroxide for E. coli O157:H7 (6.21 log CFU/mL reduction) and at 500 mmol/L persulfate with 350 mmol/L sodium hydroxide for L. monocytogenes (8.64 log CFU/mL reduction). Also, persulfate activated by sodium hydroxide always achieved significantly (P < 0.05) higher microbial reductions than sodium hydroxide or persulfate alone. L. monocytogenes was generally more resistant against the activated persulfate treatment compared with E. coli O157:H7, which might be due to the different cell envelop structures between Gram-positive and Gram-negative bacteria. Hydroxyl radical was demonstrated to be the major radical to inactivate both pathogens in ferrous activation while superoxide radical was demonstrated to be the major radical to inactivate both pathogens in alkaline activation.


Assuntos
Desinfecção/métodos , Escherichia coli O157/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Compostos de Sódio/farmacologia , Sulfatos/farmacologia , Contagem de Colônia Microbiana , Escherichia coli O157/metabolismo , Compostos Ferrosos/química , Microbiologia de Alimentos , Radicais Livres/análise , Listeria monocytogenes/metabolismo , Hidróxido de Sódio/química
11.
J Environ Qual ; 47(4): 786-794, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30025063

RESUMO

Stored liquid dairy manure is a hotspot for methane (CH) emission, thus effective mitigation strategies are required. We assessed sodium persulfate (NaSO), potassium permanganate (KMnO), and sodium hypochlorite (NaOCl) for impacts on the abundance of microbial communities and CH production in liquid dairy manure. Liquid dairy manure treated with different rates (1, 3, 6, and 9 g or mL L slurry) of these chemicals or their combinations were incubated under anoxic conditions at 22.5 ± 1.3°C for 120 d. Untreated and sodium 2-bromoethanesulfonate (BES)-treated manures were included as negative and positive controls, respectively, whereas sulfuric acid (HSO)-treated manure was used as a reference. Quantitative real-time polymerase chain reaction was used to quantify the abundances of bacteria and methanogens on Days 0, 60, and 120. Headspace CH/CO ratios were used as a proxy to determine CH production. Unlike bacterial abundance, methanogen abundance and CH/CO ratios varied with treatments. Addition of 1 to 9 g L slurry of NaSO and KMnO reduced methanogen abundance (up to ∼28%) and peak CH/CO ratios (up to 92-fold). Except at the lowest rate, chemical combinations also reduced the abundance of methanogens (up to ∼17%) and CH/CO ratios (up to ninefold), although no impacts were observed when 3% NaOCl was used alone. With slurry acidification, the ratios reduced up to twofold, whereas methanogen abundance was unaffected. Results suggest that NaSO and KMnO may offer alternative options to reduce CH emission from stored liquid dairy manure, but this warrants further assessment at larger scales for environmental impacts and characteristics of the treated manure.


Assuntos
Metano/metabolismo , Permanganato de Potássio/farmacologia , Compostos de Sódio/farmacologia , Sulfatos/farmacologia , Bactérias/metabolismo , Indústria de Laticínios , Esterco
12.
J Biol Chem ; 293(32): 12525-12534, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-29945972

RESUMO

Adaptations and responses to stress conditions are fundamental processes that all cells must accomplish to maintain or restore cellular homeostasis. Cells have a plethora of response pathways to mitigate the effect of different environmental stressors. The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. Therefore, understanding their regulation under different stress conditions is of great interest. Here, using a range of human and murine cells, we show that TFEB and TFE3 are activated upon induction of acute oxidative stress by sodium arsenite via an mTOR complex 1 (mTORC1)-independent process. We found that the mechanism of arsenite-stimulated TFEB and TFE3 activation instead involves protein phosphatase 2A (PP2A)-mediated dephosphorylation at Ser-211 and Ser-321, respectively. Depletion of either the catalytic (PPP2CA+B) or regulatory (PPP2R2A/B55α) subunits of PP2A, as well as PP2A inactivation with the specific inhibitor okadaic acid, abolished TFEB and TFE3 activation in response to sodium arsenite. Conversely, PP2A activation by ceramide or the sphingosine-like compound FTY720 was sufficient to induce TFE3 nuclear translocation. MS analysis revealed that PP2A dephosphorylates TFEB at several residues, including Ser-109, Ser-114, Ser-122, and Ser-211, thus facilitating TFEB activation. Overall, this work identifies a critical mechanism that activates TFEB and TFE3 without turning off mTORC1 activity. We propose that this mechanism may enable some cell types such as immune or cancer cells that require simultaneous TFEB/TFE3 and mTORC1 signaling to survive and achieve robust cell growth in stressful environments.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Estresse Oxidativo , Proteína Fosfatase 2/farmacologia , Animais , Arsenitos/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Células Cultivadas , Humanos , Camundongos , Fosforilação , Transdução de Sinais , Compostos de Sódio/farmacologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-29624480

RESUMO

Wet scrubbing is regarded as an effective method to remove hydrophobic organic odorants. The focus of wet scrubbing is to choose an appropriate scrubbing liquid. In this study, methyl mercaptan (CH3SH) was selected as a representative hydrophobic organic odorant for treatment by wet scrubbing using several types of scrubbing solution: ethanol (C2H5OH), lead acetate ((CH3COO)2Pb), sodium hypochlorite (NaClO), and sodium hydroxide (NaOH). A comparative analysis of the treatment efficiency, operation cost, and environmental impact was conducted. Results of the technical and economic comparison indicate that the C2H5OH solution is the best choice of scrubbing solution among those tested. These findings serve as a reference for engineering design and operation for the removal of hydrophobic organic odorants.


Assuntos
Desodorantes/análise , Detergentes/análise , Compostos de Sulfidrila/isolamento & purificação , Desodorantes/química , Desodorantes/farmacologia , Detergentes/química , Detergentes/farmacologia , Odorantes/prevenção & controle , Compostos de Sódio/análise , Compostos de Sódio/química , Compostos de Sódio/farmacologia , Hidróxido de Sódio/análise , Hidróxido de Sódio/química , Hidróxido de Sódio/farmacologia , Instalações de Eliminação de Resíduos
14.
Gen Comp Endocrinol ; 263: 62-71, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29656046

RESUMO

Early life-stages of amphibians rely on the innate immune system for defense against pathogens. While thyroid hormones (TH) are critical for metamorphosis and later development of the adaptive immune system, the role of TH in innate immune system development is less clear. An integral part of the innate immune response are pro-inflammatory cytokines - effector molecules that allow communication between components of the immune system. The objective of this study was to characterize the expression of key pro-inflammatory cytokines, tumor necrosis factor-α (TNFα), interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ), throughout amphibian development and determine the impacts of thyroidal modulation on their expression. Xenopus laevis were sampled at various stages of development encompassing early embryogenesis to late prometamorphosis and cytokine expression was measured by real-time PCR. Expression of TNFα and IL-1ß were transient over development, increasing with developmental stage, while IFN-γ remained relatively stable. Functionally athyroid, premetamorphic tadpoles were exposed to thyroxine (0.5 and 2 µg/L) or sodium perchlorate (125 and 500 µg/L) for seven days. Tadpoles demonstrated characteristic responses of advanced development with thyroxine exposure and delayed development (although to a lesser extent) and increased thyroid gland area and follicular cell height with sodium perchlorate exposure. Exposure to thyroxine for two days resulted in decreased expression of IL-1ß in tadpole trunks. Sodium perchlorate had negligible effects on cytokine expression. Overall, these results demonstrate that cytokine transcript levels vary with stage of tadpole development but that their ontogenic regulation is not likely exclusively influenced by thyroid status. Understanding the direct and indirect effects of altered hormone status may provide insight into potential mechanisms of altered immune function during amphibian development.


Assuntos
Citocinas/genética , Citocinas/metabolismo , Metamorfose Biológica , Glândula Tireoide/fisiologia , Xenopus laevis , Animais , Antitireóideos/farmacologia , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento , Metamorfose Biológica/efeitos dos fármacos , Metamorfose Biológica/genética , Metamorfose Biológica/fisiologia , Percloratos/farmacologia , Compostos de Sódio/farmacologia , Hormônios Tireóideos/metabolismo , Tiroxina/metabolismo , Transcriptoma/efeitos dos fármacos , Xenopus laevis/genética , Xenopus laevis/crescimento & desenvolvimento , Xenopus laevis/metabolismo
15.
Colloids Surf B Biointerfaces ; 166: 269-276, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29604569

RESUMO

Functionalization of titanium devices with various bioactive molecules enhances many of their properties as implants, including biocompatibility, which is typically assessed by macrophage activation and inflammation. However, functionalization requires prior introduction of reactive groups, to which bioactive agents can then be grafted. Thus, we investigated the inflammatory properties of titanium pretreated with NaOH, titanium pretreated with NaOH and then with 3-aminopropyl triethoxysilane, and titanium pretreated with dopamine. Inflammation, macrophage polarization, and activation of NF-κB signaling were assessed by real-time PCR and western blotting. The data demonstrate that silanized titanium is the least inflammatory, and promotes macrophage M2 polarization with modest engagement of the NF-κB signaling pathway. Importantly, silanization introduces a reactive amino group, providing more opportunities for further functionalization.


Assuntos
Inflamação/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , NF-kappa B/metabolismo , Titânio/farmacologia , Linhagem Celular , Humanos , Inflamação/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Propilaminas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Silanos/farmacologia , Compostos de Sódio/farmacologia
16.
Toxicol Ind Health ; 34(4): 237-252, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29519201

RESUMO

The aim of this study was to assess whether there are differences between the results of determining oxidative stress markers obtained from different origin cell lines after exposure to chemicals generating free radicals. The studies considered two markers of oxidative stress: the level of thiobarbituric acid reactive substances (TBARS) and superoxide dismutase activity. The evaluation was performed in five cell lines: Chinese hamster ovary (CHO-9) cells, lung adenocarcinoma A549, macrophages RAW264.7, skin carcinoma cells A431, and keratinocytes HaCaT. Three compounds generating free radicals were used as a source of reactive oxygen/nitrogen: 2,2'-azobis-2-methyl-propanimidamide dihydrochloride (AAPH), sodium persulfate (SP), and 3-morpholinosydnonimine hydrochloride (SIN-1). The most appropriate cell line to assess the level of TBARS proved to be the murine macrophage cell line RAW 264.7. Equally, good performance was observed in the lung cancer cell line A549, but only when tested with AAPH and SP. In the case of measuring superoxide dismutase activity, it appeared that the most suitable cell line was also the RAW 264.7 line, although dispersion increased significantly at the highest concentrations of AAPH and SP measurements. When choosing a cell line to determine oxidative stress, the specificity of the stress-inducing compound and the parameter determined should be taken into consideration.


Assuntos
Linhagem Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/biossíntese , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Células A549 , Amidinas/farmacologia , Animais , Células CHO , Cricetulus , Humanos , Queratinócitos , Camundongos , Molsidomina/análogos & derivados , Molsidomina/farmacologia , Células RAW 264.7 , Neoplasias Cutâneas , Compostos de Sódio/farmacologia , Sulfatos/farmacologia
17.
Molecules ; 23(2)2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29389889

RESUMO

Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine Erigeron breviscapus (Vant.) Hand-Mazz., which is widely used in China. Recently, accumulating evidence has highlighted the potential role of scutellarin and its main metabolite scutellarein in the treatment of cancer. To explore novel anticancer agents with high efficiency, a series of new scutellarein derivatives with a long aliphatic chain were synthesized, and the antiproliferative activities against Jurkat, HCT-116 and MDA-MB-231 cancer cell lines were assessed. Among them, compound 6a exhibited the strongest antiproliferative effects on Jurkat (IC50 = 1.80 µM), HCT-116 (IC50 = 11.50 µM) and MDA-MB-231 (IC50 = 53.91 µM). In particular, 6a even showed stronger antiproliferative effects than the positive control NaAsO2 on Jurkat and HCT-116 cell lines. The results showed that a proper long aliphatic chain enhanced the antiproliferative activity of scutellarein.


Assuntos
Antineoplásicos/farmacologia , Apigenina/farmacologia , Erigeron/química , Glucuronatos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apigenina/síntese química , Apigenina/química , Apigenina/isolamento & purificação , Arsenitos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glucuronatos/síntese química , Glucuronatos/isolamento & purificação , Células HCT116 , Humanos , Concentração Inibidora 50 , Células Jurkat , Compostos de Sódio/farmacologia , Relação Estrutura-Atividade
18.
J Cell Biol ; 217(4): 1303-1318, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29463567

RESUMO

Stress granules (SGs) are cytosolic, nonmembranous RNA-protein complexes. In vitro experiments suggested that they are formed by liquid-liquid phase separation; however, their properties in mammalian cells remain unclear. We analyzed the distribution and dynamics of two paradigmatic RNA-binding proteins (RBPs), Ras GTPase-activating protein SH3-domain-binding protein (G3BP1) and insulin-like growth factor II mRNA-binding protein 1 (IMP1), with single-molecule resolution in living neuronal cells. Both RBPs exhibited different exchange kinetics between SGs. Within SGs, single-molecule localization microscopy revealed distributed hotspots of immobilized G3BP1 and IMP1 that reflect the presence of relatively immobile nanometer-sized nanocores. We demonstrate alternating binding in nanocores and anomalous diffusion in the liquid phase with similar characteristics for both RBPs. Reduction of low-complexity regions in G3BP1 resulted in less detectable mobile molecules in the liquid phase without change in binding in nanocores. The data provide direct support for liquid droplet behavior of SGs in living cells and reveal transient binding of RBPs in nanocores. Our study uncovers a surprising disconnect between SG partitioning and internal diffusion and interactions of RBPs.


Assuntos
Grânulos Citoplasmáticos/metabolismo , DNA Helicases/metabolismo , Microscopia Confocal , Neurônios/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Imagem Individual de Molécula/métodos , Estresse Fisiológico , Animais , Arsenitos/farmacologia , Grânulos Citoplasmáticos/efeitos dos fármacos , DNA Helicases/genética , Difusão , Humanos , Cinética , Modelos Biológicos , Neurônios/efeitos dos fármacos , Células PC12 , Proteínas de Ligação a Poli-ADP-Ribose/genética , Ligação Proteica , Transporte Proteico , RNA Helicases/genética , Proteínas com Motivo de Reconhecimento de RNA/genética , Proteínas de Ligação a RNA/genética , Ratos , Compostos de Sódio/farmacologia
19.
Biol Trace Elem Res ; 181(2): 234-241, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28512695

RESUMO

To further characterize the mechanisms underlying liver toxicity induced by arsenic, we examined in this study the effect of arsenic on thioredoxin (Trx) and the apoptotic signaling pathways in human liver HHL-5 cells. The cells were treated with 0, 2, 5, and 10 µM of sodium arsenite for 24 h, and the changes of Trx1 and thioredoxin reductase (TrxR1) as well as intracellular ROS and apoptosis were examined. A concentration-dependent increase in mRNA and protein levels of Trx1 and TrxR1 was observed in arsenic-treated cells. Intracellular ROS levels and apoptosis were also significantly increased in a concentration-dependent manner. In line with this, protein levels of Bax and cytochrome C were increased and Bcl-2 was decreased by arsenic treatments. Increases in caspase 3 activity were observed. These results indicate that Trx is involved in arsenic-induced liver cell injury, probably through the apoptotic signaling pathway. However, further studies are needed to elucidate on these findings.


Assuntos
Apoptose/efeitos dos fármacos , Intoxicação por Arsênico/metabolismo , Intoxicação por Arsênico/patologia , Arsenitos/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Compostos de Sódio/farmacologia , Tiorredoxinas/metabolismo , Arsenitos/administração & dosagem , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Fígado/metabolismo , Compostos de Sódio/administração & dosagem , Relação Estrutura-Atividade
20.
Minim Invasive Ther Allied Technol ; 27(2): 90-96, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28604147

RESUMO

PURPOSE: Alkali metal ablation is newly emerging as an effective, economic and minimally invasive ablation therapy. This study is dedicated to demonstrate the high efficiency of NaK alloy ablation on in vivo tumors with different stages in mice. MATERIAL AND METHODS: Panc02 tumor cells were injected into 21 female C57B/L mice, which were divided into three groups. Two experimental groups of mice received the same percutaneous NaK alloy injection for a week apart. The inner temperature response and surface temperature distribution were measured using a thermal couple and an infrared camera. After each ablation experiment, two mice in each group were chosen randomly to make pathological sections. The tumor volumes were measured once every two days. At the end, all tumors were cut off to calculate the tumor inhibition rates. RESULTS: The NaK alloy-induced ablation therapy produced an obvious temperature increase (85 °C) in the ablation region and the high temperature distribution was relatively concentrated. The histopathology sections showed that developing stage tumors received incomplete destruction of the malignant cells compared with early stage tumors. The tumor inhibition rate in the early and developing tumor treatment groups were 88.5% and 67.6%, respectively. CONCLUSIONS: This technology provides a nearly thorough ablation treatment for early stage tumors and also a palliative treatment for developing tumors.


Assuntos
Técnicas de Ablação/métodos , Ligas/administração & dosagem , Hipertermia Induzida/métodos , Metais Alcalinos/administração & dosagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Ligas/farmacologia , Animais , Temperatura Corporal , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Metais Alcalinos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Compostos de Potássio/administração & dosagem , Compostos de Potássio/farmacologia , Compostos de Sódio/administração & dosagem , Compostos de Sódio/farmacologia , Carga Tumoral
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