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1.
Nano Lett ; 24(19): 5855-5861, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690800

RESUMO

Quantum dots (QDs) have garnered a significant amount of attention as promising memristive materials owing to their size-dependent tunable bandgap, structural stability, and high level of applicability for neuromorphic computing. Despite these advantageous properties, the development of QD-based memristors has been hindered by challenges in understanding and adjusting the resistive switching (RS) behavior of QDs. Herein, we propose three types of InP/ZnSe/ZnS QD-based memristors to elucidate the RS mechanism, employing a thin poly(methyl methacrylate) layer. This approach not only allows us to identify which carriers (electron or hole) are trapped within the QD layer but also successfully demonstrates QD-based synaptic devices. Furthermore, to utilize the QD memristor as a synapse, long-term potentiation/depression (LTP/LTD) characteristics are measured, resulting in a low nonlinearity of LTP/LTD at 0.1/1. On the basis of the LTP/LTD characteristics, single-layer perceptron simulations were performed using the Extended Modified National Institute of Standards and Technology, verifying a maximum recognition rate of 91.46%.

2.
Biochem Biophys Res Commun ; 710: 149898, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38598903

RESUMO

Type II toxin-antitoxin (TA) systems are ubiquitously distributed genetic elements in prokaryotes and are crucial for cell maintenance and survival under environmental stresses. The antitoxin is a modular protein consisting of the disordered C-terminal region that physically contacts and neutralizes the cognate toxin and the well-folded N-terminal DNA binding domain responsible for autorepression of TA transcription. However, how the two functional domains communicate is largely unknown. Herein, we determined the crystal structure of the N-terminal domain of the type II antitoxin MazE-mt10 from Mycobacterium tuberculosis, revealing a homodimer of the ribbon-helix-helix (RHH) fold with distinct DNA binding specificity. NMR studies demonstrated that full-length MazE-mt10 forms the helical and coiled states in equilibrium within the C-terminal region, and that helical propensity is allosterically enhanced by the N-terminal binding to the cognate operator DNA. This coil-to-helix transition may promote toxin binding/neutralization of MazE-mt10 and further stabilize the TA-DNA transcription repressor. This is supported by many crystal structures of type II TA complexes in which antitoxins form an α-helical structure at the TA interface. The hidden helical state of free MazE-mt10 in solution, favored by DNA binding, adds a new dimension to the regulatory mechanism of type II TA systems. Furthermore, complementary approaches using X-ray crystallography and NMR allow us to study the allosteric interdomain interplay of many other full-length antitoxins of type II TA systems.


Assuntos
Antitoxinas , Mycobacterium tuberculosis , Mycobacterium tuberculosis/metabolismo , Antitoxinas/química , Modelos Moleculares , Fatores de Transcrição/metabolismo , DNA/metabolismo , Proteínas de Bactérias/metabolismo
3.
World J Microbiol Biotechnol ; 40(8): 245, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884883

RESUMO

The addition of plant-growth-promoting bacteria (PGPB) to heavy-metal-contaminated soils can significantly improve plant growth and productivity. This study isolated heavy-metal-tolerant bacteria with growth-promoting traits and investigated their inoculation effects on the germination rates and growth of millet (Panicum miliaceum) and mustard (Brassica juncea) in Cd- and Zn-contaminated soil. Leifsonia sp. ZP3, which is resistant to Cd (0.5 mM) and Zn (1 mM), was isolated from forest soil. The ZP3 strain exhibited plant-growth-promoting activity, including indole-3-acetic acid production, phosphate solubilization, catalase activity, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging. In soil contaminated with low concentrations of Cd (0.232 ± 0.006 mM) and Zn (6.376 ± 0.256 mM), ZP3 inoculation significantly increased the germination rates of millet and mustard 8.35- and 31.60-fold, respectively, compared to the non-inoculated control group, while the shoot and root lengths of millet increased 1.77- and 4.44-fold (p < 0.05). The chlorophyll content and seedling vigor index were also 4.40 and 18.78 times higher in the ZP3-treated group than in the control group (p < 0.05). The shoot length of mustard increased 1.89-fold, and the seedling vigor index improved 53.11-fold with the addition of ZP3 to the contaminated soil (p < 0.05). In soil contaminated with high concentrations of Cd and Zn (0.327 ± 0.016 and 8.448 ± 0.250 mM, respectively), ZP3 inoculation led to a 1.98-fold increase in the shoot length and a 2.07-fold improvement in the seedling vigor index compared to the control (p < 0.05). The heavy-metal-tolerant bacterium ZP3 isolated in this study thus represents a promising microbial resource for improving the efficiency of phytoremediation in Cd- and Zn-contaminated soil.


Assuntos
Biodegradação Ambiental , Cádmio , Germinação , Mostardeira , Panicum , Microbiologia do Solo , Poluentes do Solo , Zinco , Mostardeira/microbiologia , Mostardeira/crescimento & desenvolvimento , Poluentes do Solo/metabolismo , Cádmio/metabolismo , Zinco/metabolismo , Panicum/microbiologia , Panicum/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Metais Pesados/metabolismo , Solo/química , Ácidos Indolacéticos/metabolismo
4.
Angew Chem Int Ed Engl ; 63(13): e202316942, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38305637

RESUMO

Self-assemblies (i.e., nanoclusters) of the RAS GTPase on the membrane act as scaffolds that activate downstream RAF kinases and drive MAPK signaling for cell proliferation and tumorigenesis. However, the mechanistic details of nanoclustering remain largely unknown. Here, size-tunable nanodisc platforms and paramagnetic relaxation enhancement (PRE) analyses revealed the structural basis of the cooperative assembly processes of fully processed KRAS, mutated in a quarter of human cancers. The cooperativity is modulated by the mutation and nucleotide states of KRAS and the lipid composition of the membrane. Notably, the oncogenic mutants assemble in nonsequential pathways with two mutually cooperative 'α/α' and 'α/ß' interfaces, while α/α dimerization of wild-type KRAS promotes the secondary α/ß interaction sequentially. Mutation-based interface engineering was used to selectively trap the oligomeric intermediates of KRAS and probe their favorable interface interactions. Transiently exposed interfaces were available for the assembly. Real-time NMR demonstrated that higher-order oligomers retain higher numbers of active GTP-bound protomers in KRAS GTPase cycling. These data provide a deeper understanding of the nanocluster-enhanced signaling in response to the environment. Furthermore, our methodology is applicable to assemblies of many other membrane GTPases and lipid nanoparticle-based formulations of stable protein oligomers with enhanced cooperativity.


Assuntos
Proteínas Proto-Oncogênicas p21(ras) , Transdução de Sinais , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas ras/química , Quinases raf/metabolismo , Dimerização
5.
J Med Virol ; 95(12): e29309, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38100632

RESUMO

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Animais , Camundongos , Papillomavirus Humano , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/prevenção & controle , RNA Mensageiro/genética , Proteínas E7 de Papillomavirus/genética , Camundongos Endogâmicos C57BL , Vacinação/métodos , Imunização , Neoplasias do Colo do Útero/prevenção & controle
6.
BMC Infect Dis ; 23(1): 887, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114902

RESUMO

BACKGROUND: Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. METHODS: We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. RESULT: During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens. CONCLUSION: The incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.


Assuntos
Bacteriemia , Infecções Comunitárias Adquiridas , Neoplasias Hematológicas , Pneumonia , Sepse , Choque Séptico , Humanos , Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Escherichia coli , Neoplasias Hematológicas/complicações , Pneumonia/epidemiologia , Pneumonia/complicações , Estudos Retrospectivos , Fatores de Risco , Sepse/complicações , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto
7.
J Sch Nurs ; 39(2): 181-188, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35466764

RESUMO

With the prolongation of non-ordinary situations such as school closures due to the coronavirus disease 2019 (COVID-19) pandemic, high school students have experienced irregular sleep-wake cycles and elevated academic stress resulting from reduced academic achievement and widened gaps in academic performance. This cross-sectional study aimed to investigate the associations among chronotype, social jetlag, lifelong learning competency, and academic stress in high school students during the COVID-19 pandemic. Data were collected through an online survey from May-June 2021. The mean social jetlag was found to be 2 h and 9 min, and multiple regression analysis revealed that social jetlag and lifelong competency affected academic stress. Thus, measures to minimize social jetlag and improve lifelong learning competencies should be implemented to reduce academic stress among high school students. School nurses should identify students with severe social jetlag and provide guidance and interventions to promote sleep hygiene and regular lifestyles.


Assuntos
COVID-19 , Sono , Humanos , Ritmo Circadiano , Estudos Transversais , Pandemias , Estudantes , Síndrome do Jet Lag , Inquéritos e Questionários
8.
Am J Respir Cell Mol Biol ; 66(4): 415-427, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35073245

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by fibroproliferative matrix molecule accumulation, collagen deposition, and apoptosis. Activated leukocyte cell-adhesion molecule (ALCAM; CD166) is a cell-adhesion molecule that has been implicated in adhesive and migratory attribution, including leukocyte homing and trafficking and cancer metastasis. We investigated the role of ALCAM on pulmonary fibrosis development in murine models. Thus, a bleomycin-induced pulmonary fibrosis model was established with wild-type and ALCAM-/- mice. Pulmonary fibrosis was also induced in transforming growth factor-ß1 (TGF-ß1)-transgenic mice that conditionally overexpress TGF-ß1 upon doxycycline administration. In both models, observed reduced ALCAM levels in lung tissue and BAL fluid in pulmonary fibrosis-induced wild-type mice compared with control mice. We also observed reduced ALCAM expression in the lung tissue of patients with pulmonary fibrosis compared with normal lung tissue. ALCAM-/- mice showed an exacerbated lung fibrosis response compared with wild-type mice, and this was accompanied by increased cell death. Further investigation for identification of the signaling pathway revealed that PI3K and ERK signaling pathways are involved in bleomycin-induced fibrosis. Collectively, these results highlight that ALCAM plays a protective role in the pathogenesis of pulmonary fibrosis that inhibits epithelial cell apoptosis through the PI3K-Akt signaling pathway. Our findings demonstrate the potential of ALCAM as a therapeutic target for IPF and may aid the development of new strategies for the management and treatment of patients with IPF.


Assuntos
Molécula de Adesão de Leucócito Ativado , Antígenos CD/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas Fetais/metabolismo , Fibrose Pulmonar Idiopática , Molécula de Adesão de Leucócito Ativado/metabolismo , Animais , Bleomicina , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Leucócitos/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
9.
J Korean Med Sci ; 37(3): e21, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35040296

RESUMO

BACKGROUND: In 2017, we established an airway call (AC) team composed of anesthesiologists to improve emergency airway management outside the operating room. In this retrospective analysis of prospectively collected data from the airway registry, we describe the characteristics of patients attended to and practices by the AC team during the first 4 years of implementation. METHODS: All AC team activations in which an airway intervention was performed by the AC team between June 2017 and May 2021 were analyzed. RESULTS: In all, 359 events were analyzed. Activation was more common outside of working hours (62.1%) and from the intensive care unit (85.0%); 36.2% of AC activations were due to known or anticipated difficult airway, most commonly because of acquired airway anomalies (n = 49), followed by airway edema or bleeding (n = 32) and very young age (≤ 1 years; n = 30). In 71.3% of the cases, successful intubation was performed by the AC team at the first attempt. However, three or more attempts were performed in 33 cases. The most common device used for successful intubation was the videolaryngoscope (59.7%). Tracheal intubation by the AC team failed in nine patients, who then required surgical airway insertion by otolaryngologists. However, there were no airway-related deaths. CONCLUSIONS: When coupled with appropriate assistance from an otolaryngologist AC system, an AC team composed of anesthesiologists could be an efficient way to provide safe airway management outside the operating room. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006643.


Assuntos
Manuseio das Vias Aéreas/normas , Equipe de Respostas Rápidas de Hospitais/normas , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Manuseio das Vias Aéreas/métodos , Manuseio das Vias Aéreas/estatística & dados numéricos , Anestesiologistas/estatística & dados numéricos , Criança , Feminino , Equipe de Respostas Rápidas de Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Sistema de Registros/estatística & dados numéricos , República da Coreia/epidemiologia , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos
10.
Sensors (Basel) ; 21(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066273

RESUMO

A mandibular advancement device (MAD) is a commonly used treatment modality for patients with mild-to-moderate obstructive sleep apnea. Although MADs have excellent therapeutic efficacy, dental side effects were observed with long-term use of MADs. The aim of this study was to analyze the force distribution on the entire dentition according to the materials and design of the MADs. Three types of MADs were applied: model 1 (single layer of polyethylene terephthalate glycol (PETG)), model 2 (double layer of PETG + thermoplastic polyurethane (TPU)), and model 3 (core-reinforced multilayer). In the maxilla, regardless of the model, the incisors showed the lowest force distribution. In most tooth positions, the force distribution was lower in models 2 and 3 than in model 1. In the mandible, the mandibular second molar showed a significantly lower force in all models. The mandibular incisors, canines, and molars showed the highest force values in model 1 and the lowest values in model 3. Depending on the material and design of the device, the biomechanical effect on the dentition varies, and the core-reinforced multilayered MAD can reduce the force delivered to the dentition more effectively than the conventional single- or double-layer devices.


Assuntos
Avanço Mandibular , Apneia Obstrutiva do Sono , Humanos , Placas Oclusais , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-34304695

RESUMO

Control over particulate matter (PM) emission from grilling is required for improving public health and air quality. The performance of mirror-symmetrical multi-compartment scrubbers with an upflow (U-type) and downflow baffle (D-type) configuration was evaluated for PM emission control from grilling at a flow rate of 30 m3 min-1. The PM removal efficiency of the U-type scrubber was the highest when the water level was 8 cm (95.6%), and the pressure drops recorded at the water levels of 6, 8 and 10 cm were 103, 122 and 153 mmH2O, respectively. Although PM removal efficiency of the D-type scrubber was over 91.0% at the water levels of 8, 10 and 12 cm, the pressure drops were 124, 142 and 185 mmH2O, respectively. A comprehensive evaluation of the water volume, pressure drop and PM removal performance, as well as device size, revealed that the U-type scrubber with a PM removal efficiency of 92% or higher and a pressure drop of 122 mmH2O or lower at the water levels of 6-8 cm was more economical for removing PM from grilling gas than the D-type scrubber.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Material Particulado/análise
12.
J Gastroenterol Hepatol ; 29 Suppl 4: 80-92, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25521739

RESUMO

BACKGROUND AND AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs), the most highly prescribed drugs in the world for the treatment of pain, inflammation, and fever, are associated with gastric mucosal damages including ulcer directly or indirectly. This study was aimed to document the preventive effects of an organosulfur constituent of garlic, S-allyl cysteine (SAC), against NSAIDs-induced gastric damages, as well the elucidation of its pharmacological actions, such as anti-inflammatory, anti-oxidative, and cytoprotective actions. METHODS: Different doses of SAC were administrated intragastrically before the indomethacin administration. After killing, in addition to gross and pathological evaluations of ulcer, the expressions of inflammatory mediators, including cyclooxygenase-2, prostaglandin E2 , IL-1ß, tumor necrosis factor-α, IL-6, and anti-oxidant capacity, were analyzed by Western blot analysis or ELISA, respectively. Transferase deoxytidyl uridine end labeling assay, periodic acid and Schiff staining, F4/80 staining, and CD31 staining were compared among doses of SAC. Detailed documentation of in vitro biological actions of SAC, including NF-κB, histone deacetylator inhibition, phase 2 enzyme, and MAPKs, was performed. RESULTS: SAC was very effective in preventing indomethacin-induced gastric damages in a low dose through significant decreases in macrophage infiltration as well as restorative action. Indomethacin-induced expressions of inflammatory mediators were all significantly attenuated with SAC in accordance with histone deacetylator inhibition. In addition, SAC significantly increased the total anti-oxidant concentration and mucus secretion, and allows for a significant induction of HO-1. However, these preventive effects of SAC were dependent on dosage of SAC; higher dose above 10 µM paradoxically aggravated NSAID-induced inflammation. CONCLUSION: Synthetic SAC can be promising therapeutics agent to provide potent anti-inflammatory, anti-oxidative, and mucosa protective effects against NSAID-induced damages.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Cisteína/análogos & derivados , Mucosa Gástrica/metabolismo , Heme Oxigenase-1/metabolismo , Histona Desacetilases/metabolismo , Indometacina/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios , Antioxidantes , Cisteína/farmacologia , Cisteína/uso terapêutico , Citoproteção/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Mucosa Gástrica/patologia , Técnicas In Vitro , Camundongos Endogâmicos C57BL , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
13.
J Control Release ; 366: 104-113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128883

RESUMO

Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome. Optimized SdPNs displayed better tumor targeting and PPI inhibition properties than the comparable small molecule inhibitor in vivo. Kinetics of PPI inhibition for SdPNs were gradual and controllable in contrast to the rapid inhibition kinetics of the small molecule. Because SdPN is modular, any appropriate peptide inhibitor can be incorporated into the platform without concern for the poor pharmacokinetic properties of the peptide.


Assuntos
Depsipeptídeos , Nanoestruturas , Cinética
14.
NPJ Vaccines ; 9(1): 34, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360752

RESUMO

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

15.
Exp Lung Res ; 39(4-5): 173-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23647087

RESUMO

Reactive oxygen species (ROS) are known aggravating factors for airway inflammation in asthma. Glutathione S-transferases (GSTs) detoxify ROS and toxic compounds in environmental exposures. However, little is known about the regulation of GST and expression of GST subtypes in asthma. The aim of this study was to evaluate how GSTs are regulated in asthma. We observed total GST activity and expression of GST subtypes in murine asthma models and GST expressions in induced sputum cells of asthmatics. Total GST activity was increased in BAL fluids of OVA-treated murine asthma model. GSTP and GSTA are highly expressed in peribronchiolar mononuclear inflammatory cells and epithelial cells in OVA-treated mice. GSTM are expressed in epithelial cells in both OVA and PBS-treated groups. GSTP1 mRNA expression was increased in the lung of OVA-treated mice compared with PBS-treated mice. GSTA1, GSTM1, and GSTT1 mRNA expressions were not different between both groups. GSTA1 mRNA expression was increased in induced sputum cells of asthmatics compared with healthy controls. GSTP1, GSTM1, and GSTT1 mRNA expressions were not different between asthmatics and healthy controls. In asthmatics, GSTP1 and GSTA1 mRNA expressions were higher in induced sputum cells of asthmatics with PC20 ≤ 4 mg/ml than those with PC20 > 4 mg/ml. GSTM1 and GSTT1 mRNA expressions were not different between two groups. These findings suggest that GSTs are upregulated in the airways of asthmatics in response to increased oxidative stress. GSTP and GSTA are thought to play an important role in protecting the airways of asthmatics compared with GSTM and GSTT.


Assuntos
Asma/enzimologia , Glutationa S-Transferase pi/metabolismo , Glutationa Transferase/metabolismo , Isoenzimas/metabolismo , Pulmão/enzimologia , Animais , Asma/induzido quimicamente , Asma/genética , Asma/imunologia , Líquido da Lavagem Broncoalveolar/química , Estudos de Casos e Controles , Modelos Animais de Doenças , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Isoenzimas/genética , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina , Estresse Oxidativo , RNA Mensageiro/metabolismo , Escarro/enzimologia , Regulação para Cima
16.
Front Mol Neurosci ; 16: 1111388, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873104

RESUMO

Chd8+/N2373K mice with a human C-terminal-truncating mutation (N2373K) display autistic-like behaviors in juvenile and adult males but not in females. In contrast, Chd8+/S62X mice with a human N-terminal-truncating mutation (S62X) display behavioral deficits in juvenile males (not females) and adult males and females, indicative of age-differential sexually dimorphic behaviors. Excitatory synaptic transmission is suppressed and enhanced in male and female Chd8+/S62X juveniles, respectively, but similarly enhanced in adult male and female mutants. ASD-like transcriptomic changes are stronger in newborn and juvenile (but not adult) Chd8+/S62X males but in newborn and adult (not juvenile) Chd8+/S62X females. These results point to age-differential sexual dimorphisms in Chd8+/S62X mice at synaptic and transcriptomic levels, in addition to the behavioral level.

17.
Environ Sci Pollut Res Int ; 30(6): 16612-16625, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36184709

RESUMO

Rhizoremediation is a promising method based on the synergism between plant and rhizobacteria to remediate soil co-contaminated with heavy metals and total petroleum hydrocarbons (TPHs). A plant growth-promoting (PGP) rhizobacterium with diesel-degrading capacity and heavy metal tolerance was isolated from the rhizosphere of tall fescue (Festuca arundinacea L.), after which the effects of its inoculation on rhizoremediation performance were evaluated in heavy metal- and diesel-contaminated soil planted with tall fescue. The bacterial isolate (Novosphingobium sp. CuT1) was characterized by its indole-3-acetic acid (IAA) production, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, and siderophore productivity as PGP traits. CuT1 was able to grow on 1/10 LB-agar plates containing 5 mM of Cu or 5 mM of Pb. To evaluate the remediation effect of heavy metal- and diesel-contaminated soil by CuT1 inoculation, the experimental conditions were prepared as follows. The soil was artificially contaminated with heavy metals (Cu and Pb) at a final concentration of 500 ppm. The soil was then further contaminated with diesel at final concentrations of 0, 10,000, and 30,000 ppm. Finally, all plots were planted with tall fescue, a representative hyperaccumulating plant. Compared to the rhizoremediation performance of the co-contaminated soil (Cu + Pb + diesel) without inoculation, the bioavailable Cu concentrations in the soil and the tall fescue biomass were significantly increased in CuT1 inoculation. Additionally, the root growth of tall fescue was also promoted in CuT1 inoculation. Correlation analysis showed that Cu bioavailability and bioconcentration factor were positively correlated with CuT1 inoculation. The diesel removal efficiency showed a positive correlation with CuT1 inoculation, although the diesel removal was below 30%. CuT1 inoculation was positively correlated with IAA and dehydrogenase activity in the soil. Moreover, the dry biomass of the tall fescue's roots was highly associated with CuT1 inoculation. Collectively, our findings suggest that Novosphingobium sp. CuT1 can be utilized as an applicable bioresource to enhance rhizoremediation performance in heavy metal- and TPH-contaminated soils.


Assuntos
Festuca , Metais Pesados , Poluentes do Solo , Biodegradação Ambiental , Chumbo/farmacologia , Raízes de Plantas , Metais Pesados/farmacologia , Solo , Poluentes do Solo/farmacologia , Microbiologia do Solo
18.
Chemosphere ; 337: 139332, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37364638

RESUMO

The long-term remediation performance under the natural conditions is required to establish the appropriate remediation strategy for contaminated soil. The objective of this study was to compare the long-term remediation efficiency of biostimulation and phytoextraction in contaminated soil containing petroleum hydrocarbons (PHs) and heavy metals. Two types of contaminated soil (soil contaminated with diesel only and co-contaminated with diesel and heavy metals) were prepared. For the biostimulation treatments, the soil was amended with compost, whereas maize, a representative phytoremediation plant, was cultivated for the phytoextraction treatments. There was no significant difference in remediation performance of biostimulation and phytoextraction in the diesel-contaminated soil, in which the maximum total petroleum hydrocarbon (TPH) removability was 94-96% (p < 0.05). However, phytoextraction exhibited the higher removability for TPH and heavy metals than biostimulation in the co-contaminated soil. There was no considerable change in the TPH removal in biostimulation (16-25%), while phytoextraction showed a 75% of TPH removal rate in the co-contaminated soil. Additionally, no significant changes were observed in heavy metals concentration of biostimulation, whereas the removability of heavy metals was 33-63% in phytoextraction. Meanwhile, maize, which is a suitable plant for phytoextraction, showed a translocation factor (translocating efficiency from roots to shoots) value of >1. Correlation analysis revealed that soil properties (pH, water content, and organic content) negatively correlated with pollutants removal. Additionally, the soil bacterial communities were changed over the investigated period, and the types of pollutants exerted a significant influence on the bacterial community dynamics. This study performed a pilot-scale comparison of two types of biological remediation technologies under natural environmental conditions and provided information on changes in the bacterial community structures. This study can be useful for establishing appropriate biological remediation methods to restore soil contaminated with PHs and heavy metals.


Assuntos
Poluentes Ambientais , Metais Pesados , Petróleo , Poluentes do Solo , Solo/química , Biodegradação Ambiental , Metais Pesados/análise , Petróleo/análise , Poluentes Ambientais/análise , Poluentes do Solo/análise , Microbiologia do Solo , Hidrocarbonetos/análise
19.
RSC Adv ; 13(47): 33269-33275, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37964900

RESUMO

We propose that the post-deposition oxidation of the IGZO surface is essential for improving the interface quality, with Al2O3 prepared by atomic layer deposition (ALD) employing a common metal precursor trimethylaluminum (TMA). Here, the ALD-Al2O3 process was conducted using H2O as an oxidant at a substrate temperature of 150 °C after IGZO deposition. The depth-resolved X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) data reveal the defect-rich and poor interface of the standard Al2O3/IGZO stack due to the redox reaction between the IGZO surface and TMA. The anion character of the IGZO was modified by introducing fluorine, which is known as a stability enhancer for oxide semiconductors. We highlight that the presence of the fluorine also improves the interface quality with ALD-Al2O3. As a consequence of the fluorine incorporation prior to the ALD-Al2O3 process, the chemical reduction reaction of the IGZO surface was effectively alleviated, resulting in a defect-passivated and sharp interface owing to the strong oxidizing nature of the fluorine.

20.
BMB Rep ; 56(2): 114-119, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36593107

RESUMO

Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis. [BMB Reports 2023; 56(2): 114-119].


Assuntos
Histonas , Cirrose Hepática , Camundongos , Animais , Histonas/metabolismo , Fígado/metabolismo , Modelos Animais de Doenças , Dieta Hiperlipídica
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