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1.
Nanomaterials (Basel) ; 12(19)2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36234465

RESUMO

Zinc oxide (ZnO) nanoparticles (NPs) are used as a food additive Zn supplement due to the role of Zn in biological functions. They are directly added to complex processed foods or Zn-fortified functional foods. Hence, the interactions between ZnO NPs and nutritional or functional components can occur. In this study, the effects of ZnO NP interactions with two polyphenols (quercetin and rutin) on cytotoxicity, antioxidant activity, ex vivo intestinal absorption, and solubility were evaluated. Moreover, the characterization on the interactions was carried out by analyzing crystallinity, surface chemical bonding, chemical composition, and surface chemistry. The results demonstrate that the interactions caused higher cytotoxicity, ex vivo intestinal transport, and solubility of ZnO NPs than pristine ZnO NPs but did not affect antioxidant activity nor intestinal absorption of the polyphenols. The interaction effects were more evident by ZnO NPs interacted with quercetin than with rutin. The crystallinity of ZnO NPs was not influenced, but the degree of exposure of the chemical bondings, elemental compositions, and chemical group intensities on the surface of ZnO NPs, quercetin, or rutin were quenched or decreased to some extent by the interactions, especially by ZnO NPs interacted with quercetin. It is, therefore, concluded that the interactions affect chemical characteristics and surface chemical sates of ZnO NPs, quercetin, or rutin, which can cause high cytotoxicity, intestinal absorption, and solubility of ZnO NPs. Further study is required to elucidate the mechanism of action of the interactions.

2.
Int J Mol Sci ; 23(7)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35409381

RESUMO

(1) Background: Synthetic amorphous silica (SAS) is widely used as a food additive and contains nano-sized particles. SAS can be produced by fumed and precipitated methods, which may possess different physiochemical properties, toxicokinetics, and oral toxicity. (2) Methods: The toxicokinetics of fumed SAS and precipitated SAS were evaluated following a single-dose oral administration in rats. The tissue distribution and fate of both SAS particles were assessed after repeated oral administration in rats for 28 d, followed by recovery period for 90 d. Their 28-d repeated oral toxicity was also evaluated. (3) Results: Precipitated SAS showed higher oral absorption than fumed SAS, but the oral absorption of both SAS particles was low (<4%), even at 2000 mg/kg. Our tissue-distribution study revealed that both SAS particles, at a high dose (2000 mg/kg), were accumulated in the liver after repeated administration for 28 d, but the increased concentrations returned to normal levels at 29 d, the first day of the recovery period. A higher distribution level of precipitated SAS than fumed SAS and decomposed particle fates of both SAS particles were found in the liver at 28 d. No significant toxicological findings were observed after 28-d oral administration, suggesting their low oral toxicity. (4) Conclusions: Different manufacturing methods of SAS can, therefore, affect its oral toxicokinetics and tissue distribution, but not oral toxicity.


Assuntos
Aditivos Alimentares , Dióxido de Silício , Animais , Aditivos Alimentares/química , Tamanho da Partícula , Ratos , Dióxido de Silício/química , Distribuição Tecidual , Toxicocinética
3.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210022

RESUMO

Food additive amorphous silicon dioxide (SiO2) particles are manufactured by two different methods-precipitated and fumed procedures-which can induce different physicochemical properties and biological fates. In this study, precipitated and fumed SiO2 particles were characterized in terms of constituent particle size, hydrodynamic diameter, zeta potential, surface area, and solubility. Their fates in intestinal cells, intestinal barriers, and tissues after oral administration in rats were determined by optimizing Triton X-114-based cloud point extraction (CPE). The results demonstrate that the constituent particle sizes of precipitated and fumed SiO2 particles were similar, but their aggregate states differed from biofluid types, which also affect dissolution properties. Significantly higher cellular uptake, intestinal transport amount, and tissue accumulation of precipitated SiO2 than of fumed SiO2 was found. The intracellular fates of both types of particles in intestinal cells were primarily particle forms, but slowly decomposed into ions during intestinal transport and after distribution in the liver, and completely dissolved in the bloodstream and kidneys. These findings will provide crucial information for understanding and predicting the potential toxicity of food additive SiO2 after oral intake.


Assuntos
Intestinos/química , Dióxido de Silício/administração & dosagem , Dióxido de Silício/síntese química , Administração Oral , Animais , Análise Química do Sangue , Células CACO-2 , Linhagem Celular Tumoral , Precipitação Química , Feminino , Humanos , Intestinos/citologia , Rim/química , Fígado/química , Nanopartículas , Octoxinol/química , Tamanho da Partícula , Ratos , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Solubilidade
4.
J Clin Lab Anal ; 30(6): 1061-1070, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27132877

RESUMO

BACKGROUND: Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). METHODS: We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. RESULTS: Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). CONCLUSION: This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.


Assuntos
Predisposição Genética para Doença/genética , Janus Quinase 2/genética , Policitemia Vera/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/genética , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Policitemia Vera/epidemiologia , República da Coreia/epidemiologia , Estatísticas não Paramétricas , Trombocitemia Essencial/epidemiologia , Adulto Jovem
5.
Genome Announc ; 3(4)2015 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-26205864

RESUMO

Pseudomonas putida strain SJ3, which possesses caprolactam-degrading ability, was isolated from dyeing industry wastewater in Daegu, Republic of Korea. Here, we describe the draft genome sequence and annotation of the strain. The 5,596,765-bp-long genome contains 4,293 protein-coding genes and 68 RNA genes with 61.70% G+C content.

6.
Biochem Biophys Res Commun ; 456(1): 110-5, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-25446107

RESUMO

RNA leukemia viruses induce T-cell lymphoblastic lymphomas or myeloid leukemias. Infection of cells with Moloney murine leukemia virus (M-MuLV) up-regulates the expression of a number of cellular genes, including those involved in T-lymphocyte activation. Previously, we demonstrated that this up-regulation occurs via the trans-activation activity of the M-MuLV long terminal repeat (LTR) sequences which produce an LTR-encoded transcript. Sequence analysis of the LTR revealed a potential transcription unit for RNA polymerase III (Pol III) within the U3 region that is actively occupied by Pol II factors. Here, we provide the direct evidence of involvement of Pol III in the trans-activation process and demonstrate the precise localization of the intragenic control elements for accurate and active Pol III transcription. Deletions of a copy of the directed repeats and further immediate upstream sequences significantly abrogated the generation of LTR-encoded transcript and abolished the trans-activational activity, whereas the deletion of a copy of directed repeats alone proportionally reduced the transcript size, but still retained moderately high trans-activational activity. In electrophoretic mobility shift assay, the fraction containing a multiple transcription factor TFIIIC complex strongly bound to the LTR-U3 probe containing the essential control elements. The specificity of the DNA-TFIIIC interaction was confirmed by conducting competition assays with DNA fragments containing a genuine Pol III-transcribed gene, VA1, and by vaccinia virus infection which stimulates the expression of Pol III factors. However, a deletion mutant lacking an essential control element bound to the TFIIIC complex poorly, consequently resulting in weak Pol III transcription as assessed by an IRES-GFP reporter system. This correlation strongly supports the possibility that the generation of LTR-encoded transcript is directed by Pol III. Therefore, this finding suggests the involvement of Pol III transcription in the retrovirus-induced activation of cellular genes, potentially contributing to leukemogenesis.


Assuntos
RNA Polimerase III/metabolismo , Retroviridae/genética , Sequências Repetidas Terminais , Células 3T3 , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Citometria de Fluxo , Deleção de Genes , Regulação da Expressão Gênica , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Células Jurkat , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Leucemia Murina de Moloney , Mutação , Plasmídeos/metabolismo , Transcrição Gênica , Ativação Transcricional , Fator de Necrose Tumoral alfa/metabolismo
7.
Genome Announc ; 1(5)2013 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-24029767

RESUMO

Photorhabdus temperata strain M1021 is an entomopathogenic bacterium belonging to the family Enterobacteriaceae and is symbiotically associated with nematodes. The draft genome sequence of P. temperata strain M1021 consists of 5,598,253 bp with a G+C content of 43.7%, and it has 6,120 protein-coding genes.

8.
Biochimie ; 91(1): 102-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18534198

RESUMO

The cell proliferation of p53-deficient Jurkat T cells is controlled after prolonged exposure to human lactoferrin (Lf). However, the molecular mechanism by which Lf influences these cellular responses remains unclear. In this study, we demonstrate that Lf-induced apoptosis in Jurkat T cells occurs in a dose- and time-dependent manner via the regulation of c-Jun N-terminal kinase (JNK) activity. Jurkat cells exposed to Lf for 1 day, especially at concentrations in excess of 500 microg/ml, showed typical apoptosis, as indicated by decreased cell viability and increased Annexin V binding. Our results also showed that Lf induced the activation of caspase 9 and caspase 3 activation, as demonstrated by our detection of cleaved caspases and PARP. Lf-induced apoptosis did not influence Bcl-2 expression via an ERK1/2 phosphorylation pathway, but was rather associated with the level of Bcl-2 phosphorylation. The treatment of cells with the specific JNK inhibitor SP600125, but not the p38 MAPK inhibitor SB203580, revealed that the JNK-Bcl-2 signaling cascade is required for Lf-induced apoptosis. When JNK activation was abolished by SP600125, no Bcl-2 phosphorylation was detected, and the Lf-treated Jurkat cells did not undergo cell death. These findings indicate that Lf functions as a biological mediator of apoptosis in the human leukemia Jurkat T-cell line, via the JNK-associated Bcl-2 signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Células Jurkat/metabolismo , Lactoferrina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/fisiologia , Western Blotting , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Humanos , Células Jurkat/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Biochem Biophys Res Commun ; 376(1): 180-5, 2008 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-18765232

RESUMO

Reduction/oxidation disorder is one of the most common ailments in HIV-infected patients, and such patients are frequently left exposed to chronic oxidative stress after the generation of reactive oxygen species (ROS). Although a variety of clinical trials to inhibit HIV infection have been conducted by focusing on oxidative stress, their precise targets and reaction mechanism have remained unclear. In this study, we demonstrate that H2O2 treatment strongly induced HIV long terminal repeat (LTR)-driven luciferase expression in Jurkat T lymphocytes via NF-kappaB activation. Treatment with the SN50 peptide or the mutation of NF-kappaB binding site on LTR resulted in impaired LTR activity in response to ROS. H2O2 induced both IkappaB degradation and covalent modification of p65. CBP/p300-induced hyperacetylation as well as phosphorylation of p65 was implicated in ROS-mediated LTR activation. The results of our study showed that ROS-induced HIV LTR activation involves immediate early NF-kappaB activation at the post-translational level.


Assuntos
Regulação Viral da Expressão Gênica , Repetição Terminal Longa de HIV/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Acetilação , Sítios de Ligação , Genes Reporter , Repetição Terminal Longa de HIV/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacocinética , Proteínas I-kappa B/antagonistas & inibidores , Proteínas I-kappa B/metabolismo , Células Jurkat , Luciferases/genética , Mutação , Peptídeos/farmacologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Biossíntese de Proteínas , Espécies Reativas de Oxigênio/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo , Ativação Transcricional , Fatores de Transcrição de p300-CBP
10.
Cell Microbiol ; 10(3): 583-92, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17877750

RESUMO

The vaccinia virus (VV) replicates robustly and alters the progression of the cell cycle via an unknown mechanism. Herein, we provide evidence for the existence of a unique VV infection-induced cell cycle control mechanism. The regulation is correlated with the inactivation of p53 and Rb, which are associated with the RNA polymerase III transcription factor B (TFIIIB) subunits, TBP and Brf1 respectively. VV infection induced the expression of Mdm2 and its translocation into the nucleus, thereby resulting in a disruption of p53. VV also stimulated the expression of TFIIIB and TFIIIC, and consequently induced tRNA synthesis. On the other hand, the total level of Rb was not significantly influenced, but the level of hypo-phosphorylated Rb was enhanced, partially due to the VV-induced downregulation of cyclin-dependent kinases 4 and 6. However, the hypo-phosphorylated Rb appeared to be largely sequestered into a complex with Brf1, which resulted in the blockage of Rb function to repress E2F1 transactivation, thereby leading to a moderately higher proportion of cells in the S and G(2) phases. Conversely, the enforced expression of exogenous Rb restored the normally observed cell cycle patterns. Overall, these controls may contribute to the efficient replication of the virus in rapidly growing cells.


Assuntos
Ciclo Celular , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Proteína de Ligação a TATA-Box/metabolismo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Vaccinia virus/fisiologia , Linhagem Celular , Núcleo Celular/química , Quinase 4 Dependente de Ciclina/biossíntese , Quinase 6 Dependente de Ciclina/biossíntese , Regulação para Baixo , Fator de Transcrição E2F1/metabolismo , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Polimerase III/metabolismo , RNA de Transferência/biossíntese , Fator de Transcrição TFIIIB/biossíntese , Fatores de Transcrição TFIII/biossíntese , Regulação para Cima
11.
J Immunol ; 179(9): 5686-92, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17947640

RESUMO

The activation of NF-kappaB by neutrophil lactoferrin (Lf) is regulated via the IkappaB kinase (IKK) signaling cascade, resulting in the sequential phosphorylation and degradation of IkappaB. In this study, we observed that Lf protein augmented p65 phosphorylation at the Ser(536), but not the Ser(276) residue, and stimulated the translocation of p65 into the nucleus. Lf was also shown to enhance the association between p65 and CREB-binding protein/p300 in vivo. To elucidate the mechanism by which Lf triggers these signaling pathways, we attempted to delineate the roles of the upstream components of the IKK complex, using their dominant-negative mutants and IKKalpha(-/-) and IKKbeta(-/-) mouse embryonic cells. We demonstrated that both IKKalpha and IKKbeta as well as NF-kappaB-inducing kinase are indispensable for Lf-induced p65 phosphorylation. However, MAPK kinase kinase 1 is not essentially required for this activation. We also observed that Lf-induced p65 phosphorylation was either partially or completely abrogated as the result of treatment with the mutant forms of TNFR-associated factor (TRAF) 2, TRAF5, or TRAF6. Moreover, we demonstrated that Lf directly interacted with TRAF5. Expression of the dominant-negative mutant of TRAF5 or its small interfering RNA almost completely abrogated the Lf-induced p65 phosphorylation. These results suggest that signaling pathways, including TRAFs/NF-kappaB-inducing kinase/IKKs, may be involved in the regulation of Lf-induced p65 activation, thereby resulting in the activation of members of the NF-kappaB family.


Assuntos
Quinase I-kappa B/metabolismo , Lactoferrina/farmacologia , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo , Proteína de Ligação a CREB/metabolismo , Linhagem Celular , Humanos , Fosforilação/efeitos dos fármacos , Ligação Proteica , Subunidades Proteicas/metabolismo , Serina/genética , Serina/metabolismo , Ativação Transcricional/genética
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