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1.
Bioorg Med Chem ; 107: 117750, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776567

RESUMO

Analgesia and blood sugar control are considered as two main unmet clinical needs for diabetes related neuropathic pain patients. Transient receptor potential vanilloid type-1 (TRPV1) channel is a highly validated target for pain perception, while no TRPV1 antagonists have been approved due to hyperthermia side effects. Herein, two series of new TRPV1 antagonists with flavonoid skeleton were designed by the structure-based drug design (SBDD) strategy. After comprehensive evaluation, compound CX-3 was identified as a promising TRPV1 antagonist. CX-3 exhibited equivalent TRPV1 antagonistic activity with classical TRPV1 antagonist BCTC in vitro, and exerted better analgesic activity in vivo than that of BCTC in the formalin induced inflammatory pain model without hyperthermia risk. Moreover, CX-3 exhibited robust glucose-lowering effects and showed high selectivity over other ion channels. Overall, these findings identified a first-in-class highly selective TRPV1 antagonist CX-3, which is a promising candidate to target the pathogenesis of diabetes related neuropathic pain.


Assuntos
Analgésicos , Hipoglicemiantes , Canais de Cátion TRPV , Animais , Humanos , Masculino , Camundongos , Ratos , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/síntese química , Relação Dose-Resposta a Droga , Descoberta de Drogas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Estrutura Molecular , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo
2.
Environ Res ; 242: 117781, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38036212

RESUMO

In this study, a novel magnetic nanocomposite of Ru@Fe3O4/rGO was successfully synthesized by a simple hydro-thermal method. The Ru@Fe3O4/rGO particles were assembled and immobilized for innovative magnetically assembled electrode (MAE) without any binder, and the electrode was further applied in heterogeneous electro-Fenton (hetero-EF) process for the degradation of diclofenac (DCF). The results showed that rGO could remarkably enhance the conductivity and catalyze the two-electron oxygen reduction, which greatly improved the generation of H2O2. In addition, the mixture valence of Fe and Ru species might provide rich reaction sites and enhance electron transfer by synergy. Thus, the Ru@Fe3O4/rGO MAE exhibited a stable and high electrocatalytic activity in the hetero-EF process for DCF degradation over a wide pH range from 2 to 9 owing to the higher electroactive surface area (EASA) and lower charge/mass-transfer resistance. The DCF degradation efficiency could reach about 100% within 90 min under pH 5 and current 40 mA, and the Ru@Fe3O4/rGO MAE showed high stability and reusability after five cycles. Theoretically, 1O2 and •OH were the main reactive oxygen species (ROS) participating in DCF degradation in the Ru@Fe3O4/rGO MAE hetero-EF process. Furthermore, according to the LC-MS/MS intermediates, the possible DCF degradation pathway was deduced including dechlorination, hydroxylation and ring opening attacked by ROS. Eleven intermediates were detected during DCF degradation in the MAE hetero-EF process, and the ecological risk of DCF degradation in Ru@Fe3O4/rGO MAE hetero-EF process was significantly reduced. This study provides new insights into the magnetically assembled electrode of Ru@Fe3O4/rGO and displays a new practical application prospect of the materials for high-efficient removal and degradation of DCF from wastewater.


Assuntos
Diclofenaco , Poluentes Químicos da Água , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Cromatografia Líquida , Espectrometria de Massas em Tandem , Eletrodos , Oxirredução
3.
Ecotoxicol Environ Saf ; 279: 116481, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38788562

RESUMO

Manganese (Mn) overexposure has been associated with the development of neurological damage reminiscent of Parkinson's disease, while the underlying mechanisms have yet to be fully characterized. This study aimed to investigate the mechanisms leading to injury in dopaminergic neurons induced by Mn and identify novel treatment approaches. In the in vivo and in vitro models, ICR mice and dopaminergic neuron-like PC12 cells were exposed to Mn, respectively. We treated them with anti-ferroptotic agents ferrostatin-1 (Fer-1), deferoxamine (DFO), HIF-1α activator dimethyloxalylglycine (DMOG) and inhibitor LW6. We also used p53-siRNA to verify the mechanism underlying Mn-induced neurotoxicity. Fe and Mn concentrations increased in ICR mice brains overexposed to Mn. Additionally, Mn-exposed mice exhibited movement impairment and encephalic pathological changes, with decreased HIF-1α, SLC7A11, and GPX4 proteins and increased p53 protein levels. Fer-1 exhibited protective effects against Mn-induced both behavioral and biochemical changes. Consistently, in vitro, Mn exposure caused ferroptosis-related changes and decreased HIF-1α levels, all ameliorated by Fer-1. Upregulation of HIF-1α by DMOG alleviated the Mn-associated ferroptosis, while LW6 exacerbated Mn-induced neurotoxicity through downregulating HIF-1α. p53 knock-down also rescued Mn-induced ferroptosis without altering HIF-1α protein expression. Mn overexposure resulted in ferroptosis in dopaminergic neurons, mediated through the HIF-1α/p53/SLC7A11 pathway.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Encéfalo , Ferroptose , Subunidade alfa do Fator 1 Induzível por Hipóxia , Manganês , Camundongos Endogâmicos ICR , Proteína Supressora de Tumor p53 , Animais , Ferroptose/efeitos dos fármacos , Células PC12 , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Manganês/toxicidade , Encéfalo/efeitos dos fármacos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Ratos , Masculino , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Cicloexilaminas/farmacologia , Fenilenodiaminas/toxicidade , Fenilenodiaminas/farmacologia , Desferroxamina/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Aminoácidos Dicarboxílicos
4.
J Environ Sci (China) ; 141: 63-89, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38408835

RESUMO

Covalent organic frameworks (COFs) are a new kind of crystalline porous materials composed of organic molecules connected by covalent bonds, processes the characteristics of low density, large specific surface area, adjustable pore size and structure, and easy to functionalize, which have been widely used in the field of membrane separation technology. Recently, there are more and more researches focusing on the preparation methods, separation application, and mechanism of COF membranes, which need to be further summarized and compared. In this review, we primarily summarized several conventional preparation methods, such as two-phase interfacial polymerization, in-situ growth on substrate, unidirectional diffusion method, layer-by-layer assembly method, mixed matrix membranes, and so on. The advantages and disadvantages of each method are briefly summarized. The application potential of COF membrane in liquid separation are introduced from four aspects: dyeing wastewater treatment, heavy metal removal, seawater desalination and oil-water separation. Then, the mechanisms including pore structure, hydrophilic/hydrophobic, electrostatic repulsion/attraction and Donnan effect are introduced. For the efficient removal of different kind of pollutions, researchers can select different ligands to construct membranes with specific pore size, hydrophily, salt or organic rejection ability and functional group. The ideas for the design and preparation of COF membranes are introduced. Finally, the future direction and challenges of the next generation of COF membranes in the field of separation are prospected.


Assuntos
Estruturas Metalorgânicas , Separação de Fases , Cloreto de Sódio , Difusão , Poluição Ambiental
5.
J Proteome Res ; 22(8): 2577-2592, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37403919

RESUMO

Metabolic dysfunction is associated with nonalcoholic steatohepatitis (NASH) development. However, omics studies investigating metabolic changes in NASH patients are limited. In this study, metabolomics and lipidomics in plasma, as well as proteomics in the liver, were performed to characterize the metabolic profiles of NASH patients. Moreover, the accumulation of bile acids (BAs) in NASH patients prompted us to investigate the protective effect of cholestyramine on NASH. The liver expression of essential proteins involved in FA transport and lipid droplets was significantly elevated in patients with NASH. Furthermore, we observed a distinct lipidomic remodeling in patients with NASH. We also report a novel finding suggesting an increase in the expression of critical proteins responsible for glycolysis and the level of glycolytic output (pyruvic acid) in patients with NASH. Furthermore, the accumulation of branched chain amino acids, aromatic amino acids, purines, and BAs was observed in NASH patients. Similarly, a dramatic metabolic disorder was also observed in a NASH mouse model. Cholestyramine not only significantly alleviated liver steatosis and fibrosis but also reversed NASH-induced accumulation of BAs and steroid hormones. In conclusion, NASH patients were characterized by perturbations in FA uptake, lipid droplet formation, glycolysis, and accumulation of BAs and other metabolites.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Lipidômica , Resina de Colestiramina/metabolismo , Proteômica , Fígado/metabolismo , Metabolômica
6.
Anal Chem ; 95(50): 18635-18643, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38064655

RESUMO

Cr(III) is a common oxidation state of chromium, and its presence in the environment can occur naturally or as a result of human activities, such as industrial processes, mining, and waste disposal. This article explores the application of machine learning algorithms for the intelligent decision recognition and quantification of Cr(III) in chromium speciation. Three different machine learning models, namely, the Decision Tree (DT) model, the PCA-SVM (Principal Component Analysis-Support Vector Machine) model, and the LDA (Linear Discriminant Analysis) model, were employed and evaluated for accurate and efficient classification of chromium concentrations based on their fluorescence responses. Furthermore, stepwise multiple linear regression analysis was utilized to achieve a more precise quantification of trivalent chromium concentrations through fluorescence visualization. The results demonstrate the potential of machine learning algorithms in accurately detecting and quantifying Cr(III) in chromium speciation with implications for environmental and industrial applications in chromium detection and quantification. The findings from this research pave the way for further exploration and implementation of these models in real-world scenarios, offering valuable insights into various environmental and industrial contexts.

7.
Bioorg Med Chem ; 82: 117237, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36906965

RESUMO

Tumor hypoxia-activated proteolysis targeting chimeras (ha-PROTACs) 9 and 10 were designed and synthesized by incorporating the hypoxia-activated leaving group (1-methyl-2-nitro-1H-imidazol-5-yl)methyl or 4­nitrobenzyl into the structure of the cereblon (CRBN) E3 ligand of an epidermal growth factor receptor 19 deletions (EGFRDel19-based PROTAC 8. The in vitro protein degradation assay demonstrated that 9 and 10 could effectively and selectively degrade EGFRDel19 in tumor hypoxia. Meanwhile, these two compounds showed higher potency in inhibiting cell viability and migration, as well as in promoting cells apoptosis in tumor hypoxia. Moreover, nitroreductase reductive activation assay indicated that prodrugs 9 and 10 could successfully release the active compound 8. This study confirmed the feasibility to develop ha-PROTACs to enhance the selectivity of PROTACs by caging CRBN E3 ligase ligand.


Assuntos
Quimera de Direcionamento de Proteólise , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/metabolismo , Ligantes , Hipóxia Tumoral , Proteólise
8.
Anal Bioanal Chem ; 414(8): 2651-2660, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35165778

RESUMO

In this work, green-emitting carbon quantum dots were successfully prepared through a facile one-step solid-state reaction method. The obtained green-emitting carbon dots (G-CDs) showed good fluorescence stability in NaCl aqueous solution and different pH values. Moreover, the G-CDs showed high sensitivity and selectivity for detecting hypochlorite by both fluorometry and colorimetry. Under the optimized condition, a highly sensitive detection of hypochlorite was established in the range of 0.2-100 µM and 10-150 µM for fluorescent and colorimetric methods, respectively. The corresponding limits of detection (LOD) were 0.0781 µM and 1.82 µM, respectively. Therefore, the G-CDs were successfully applied to determinate hypochlorite in actual water samples. In addition, a paper-based sensor loading with the G-CDs was also developed for rapid visual detection of hypochlorite. The results suggested that the G-CDs could be a promising candidate to detect hypochlorite.

9.
Ecotoxicol Environ Saf ; 248: 114321, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36427370

RESUMO

Elevated levels of arsenic may be present in groundwater, and long-term exposure to arsenic increases hepatic fibrosis. T helper 2 (Th2) cells are involved in the fibrotic cascade, and cell metabolism is a regulatory factor participating in CD4+ T cell differentiation and function. However, the mechanism for Th2 cell regulation of arsenite-induced hepatic fibrosis is not fully understood. In present study, for arsenite-fed mice, activated hepatic stellate cells may be involved in the infiltration of CD4+ T cells, accompanied by up-regulation of GATA3, a transcription factor, and IL-13, the major Th2 cytokine. Exposed to arsenite, Jurkat cells had increased aerobic glycolysis to promote the cell cycle and cell proliferation. Further, this process elevated levels of marker molecules, including those of the Th2 paradigm characterized by GATA3, IL-4, and IL-13. LX-2 cells were activated when treated with culture medium from Jurkat cells exposed to arsenite. miR-21 may be a therapeutic target for arsenite-induced hepatic fibrosis. In vitro, miR-21 knock-down caused inhibition of the PTEN/PI3K/AKT pathway induced by arsenite. It also reversed the elevated glycolysis and the accelerated cell cycle and cell proliferation. Indeed, this alteration led to diminished expression of GATA3, IL-4, and IL-13 in T cells differentiated under Th2 conditions, which inhibits activation of LX-2 cells. Consistent with the results in vitro, miR-21 knock-out in mice reversed hepatic fibrosis and attenuated the levels of GATA3 and IL-13 induced by arsenite. These findings indicate that miR-21 regulates the glycolysis of CD4+ T cells through the PTEN/PI3K/AKT pathway to accelerate the cell cycle, thereby facilitating CD4+ T cell polarization toward Th2 and releasing the fibrogenic factor IL-13, which participates in arsenite-associated hepatic fibrosis. Inhibition of Th2 polarization of CD4+T cells or miR-21 could be a therapeutic strategy to combat hepatic fibrosis caused by exposure to arsenic.


Assuntos
Arsênio , Arsenitos , MicroRNAs , Camundongos , Animais , Arsenitos/toxicidade , Interleucina-13 , Interleucina-4 , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Cirrose Hepática/induzido quimicamente , Fenótipo , Células Th2 , MicroRNAs/genética
10.
Ecotoxicol Environ Saf ; 247: 114173, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326553

RESUMO

The occupational and environmental health safety of rare earths has attracted considerable attention. In China, the rare earth neodymium oxide (Nd2O3) is extensively refined and utilized. However, the mechanisms of Nd2O3-induced lung injury are elusive. In the present study, we found that exposure of mice to Nd2O3 caused an inflammatory reaction and fibrosis in lung tissues, which was in relation to the Nd2O3-induced higher levels of the lncRNA H19 (H19), tumor necrosis factor receptor 1 (TNFRSF1A), p-p65, and p-IKKß and lower levels of miR-29a-3p. Further, in mouse monocyte macrophage leukemia cells (RAW264.7), Nd2O3 induced an inflammatory reaction, increases of H19 and TNFRSF1A levels, decreases of miR-29a-3p levels, and activation of the nuclear factor (NF)-κB signaling pathway. Further, we established that miR-29a-3p regulates TNFRSF1A expression. Up-regulation of miR-29a-3p and down-regulation of H19 blocked the Nd2O3-induced secretion of TNF-α, MIP-1α, and IL-6; the increases of TNFRSF1A levels; and activation of the NF-κB signaling pathway in RAW264.7 cells. Further, in Nd2O3-treated RAW26.4 cells, H19 inhibited the expression of miR-29a-3p, which targets TNFRSF1A, and activated the NF-κB signaling pathway to enhance the expression of TNF-α, MIP-1α, and IL-6. Moreover, for mice, up-regulation of miR-29a-3p reversed lung tissue inflammation, pulmonary fibrosis, and activation of the NF-κB signaling pathway induced by Nd2O3. In sum, the present investigation shows that H19 via miR-29a-3p is involved in lung inflammation and pulmonary fibrosis induced by Nd2O3, which is a mechanism for the Nd2O3-induced lung inflammatory response and pulmonary fibrosis. This information is useful for development of a biomarker of Nd2O3-induced lung injury.


Assuntos
Lesão Pulmonar , MicroRNAs , Pneumonia , Fibrose Pulmonar , RNA Longo não Codificante , Animais , Camundongos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , RNA Longo não Codificante/genética , NF-kappa B , Quimiocina CCL3 , Fator de Necrose Tumoral alfa , Interleucina-6 , Inflamação/induzido quimicamente , Inflamação/genética , MicroRNAs/genética
11.
Mikrochim Acta ; 189(1): 44, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978598

RESUMO

A portable and simple method was developed for on-site selective determination of As(III) based on the SERS signal of As(III)-O vibration. The method relies on the synergistic effect of nanoparticles aggregation and analyte adsorption. Experimental results demonstrated that phosphate replaced the ligands of HH@Ag NPs, which in turn facilitated the adsorption of As(III) on the surface of HH@Ag NPs. The phosphate was introduced as an agglomerating agent to improve the detection ability of the method for As(III). The method shows good selectivity and linear relationship between 5 × 10-8 and 0.8 × 10-6 M, with the detection limit of 1.8 × 10-9 M. The method was applied to actual water samples and successfully detected As(III), indicating that the method could have application potential in actual detection scenarios.


Assuntos
Arsênio/análise , Nanopartículas Metálicas/química , Fosfatos/química , Prata/química , Análise Espectral Raman
12.
Mikrochim Acta ; 189(11): 415, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36217040

RESUMO

An enhanced ratiometric fluorescence sensor was built for on-site visual detection of doxycycline (DOX) through the interaction with bovine serum albumin on the surface of red emissive copper nanoclusters. Upon the addition of weakly fluorescent DOX, the red fluorescence from copper nanoclusters gradually decreased through the inner-filter effect (IFE), while a green fluorescence appears and significantly increases, forming an interesting fluorescent isosbestic point, which was assigned to DOX due to sensitization effect of bovine serum albumin. On the basis of this ratiometric fluorescence, the system possessed good limit of detection (LOD) of 45 nM and excellent selectivity for DOX over other tetracyclines. Based on these findings, a paper-based sensor has been fabricated for distinct visual detection of trace DOX and combined with smartphone color recognizer for quantitative detection of DOX (LOD = 83 nM). This method shows broad application prospects in environmental monitoring and food safety.


Assuntos
Cobre , Nanopartículas Metálicas , Antibacterianos , Doxiciclina , Soroalbumina Bovina , Espectrometria de Fluorescência/métodos , Tetraciclinas
13.
J Environ Sci (China) ; 118: 1-13, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35305757

RESUMO

Fine particles associated with haze pollution threaten the health of over 400 million people in China. Owing to excellent non-destructive fingerprint recognition characteristics, Raman and surface-enhanced Raman scattering (SERS) are often used to analyze the composition of fine particles to determine their physical and chemical properties as well as reaction mechanisms. However, there is no comprehensive Raman spectral library of fine particles. Furthermore, various studies that used SERS for fine-particle composition analysis showed that the uniqueness of the SERS substrates and different excitation wavelengths can produce a different spectrum for the same fine-particle component. To overcome this limitation, we conducted SERS experiments with a portable Raman spectrometer using two common SERS substrates (silver (Ag) foil and gold nanoparticles (Au NPs)) and a 785 nm laser. Herein, we introduced three main particle component types (sulfate-nitrate-ammonium (SNA), organic material, and soot) with a total of 39 chemical substances. We scanned the solid Raman, liquid Raman, and SERS spectra of these substances and constructed a fine-particle reference library containing 105 spectra. Spectral results indicated that for soot and SNA, the differences in characteristic peaks mainly originated from the solid-liquid phase transition; Ag foil had little effect on this difference, while the Au NPs caused a significant red shift in the peak positions of polycyclic aromatic hydrocarbons. Moreover, with various characteristic peak positions in the three types of spectra, we could quickly and correctly distinguish substances. We hope that this spectral library will aid in the future identification of fine particles.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Ouro/química , Humanos , Nanopartículas Metálicas/química , Tamanho da Partícula , Prata/química , Análise Espectral Raman/métodos
14.
Epidemiol Infect ; 149: e158, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33888165

RESUMO

The study aimed to investigate behavioural intentions to receive free and self-paid COVID-19 vaccinations (BICV-F and BICV-SP) among Chinese university students if the vaccine was 80% effective with rare mild side effects, to examine their associations with social media exposures and peer discussions regarding COVID-19 vaccination, and to explore the mediational role of perceived information sufficiency about COVID-19 vaccination. An online anonymous survey (N = 6922) was conducted in November 2020 in five Chinese provinces. Logistic regression and path analysis were adopted. The prevalence of BICV-F and BICV-SP were 78.1% and 57.7%. BICV-F was positively associated with the frequencies of passive social media exposure (adjusted odds ratio (AOR) = 1.32, P < 0.001), active social media interaction (AOR = 1.13, P < 0.001) and peer discussions (AOR = 1.17, P < 0.001). Indirect effects of the three factors on BICV-F via perceived information sufficiency were all significant (P < 0.001). The direct effect of active social media interaction on BICV-F was significantly negative (P < 0.001). Similar associations/mediations were observed for BICV-SP. The COVID-19 vaccination intention of Chinese university students needs improvement. Boosting social media exposures and peer discussions may raise students' perceived information sufficiency and subsequently increase their vaccination intention. Considering the potential negative effect of active social media interaction, caution is needed when using social media to promote COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19 , Comportamentos Relacionados com a Saúde , Intenção , Mídias Sociais/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Adolescente , Adulto , COVID-19/prevenção & controle , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , SARS-CoV-2 , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
15.
Ecotoxicol Environ Saf ; 208: 111609, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396129

RESUMO

With the wide application of neodymium oxide nanoparticles (NPs-Nd2O3) in various fields, their health hazards have aroused public concern in recent years. However, data regarding the cytotoxicity of NPs-Nd2O3 is limited. In this study, we investigated the function and mechanism of long-chain non-coding RNAs (lncRNAs) in NPs-Nd2O3-induced airway inflammation. Treatment with NPs-Nd2O3 induced an inflammatory response in human bronchial epithelial cells (16HBE) by upregulating the expression of interleukin-6 (IL-6) and interleukin-8 (IL-8). The levels of LDH and intracellular ROS in the cells treated by various doses of NPs-Nd2O3 also increased significantly. After treatment with 10 µg/ml NPs-Nd2O3, RNA microarray and real-time quantitative polymerase chain reaction (qRT-PCR) showed a significant upregulation of lncRNA loc105377478. Functional experiments suggested lncRNA loc105377478 enhanced the expression of IL-6, IL-8 and ROS in NPs-Nd2O3-treated 16HBE cells, and it was further demonstrated that lncRNA loc105377478 promoted the activation of NF-κB by negatively regulating ADIPOR1 expression. Moreover, the expression of IL-6 and IL-8 in NPs-Nd2O3-treated 16HBE cells was regulated by lncRNA loc105377478, which was mediated by the NF-κB signaling pathway. In conclusion, lncRNA loc105377478 promotes NF-κB activation by negatively regulating ADIPOR1 expression, thereby upregulating the expression of IL-6 and IL-8 in 16HBE cells treated with NPs-Nd2O3.


Assuntos
Células Epiteliais/efeitos dos fármacos , NF-kappa B/metabolismo , Nanopartículas/química , Nanopartículas/toxicidade , Neodímio/toxicidade , Óxidos/toxicidade , RNA Longo não Codificante/genética , Receptores de Adiponectina/metabolismo , Brônquios/efeitos dos fármacos , Brônquios/imunologia , Brônquios/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Relação Dose-Resposta a Droga , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Humanos , Inflamação , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Neodímio/química , Óxidos/química , Transdução de Sinais , Regulação para Cima
16.
Drug Chem Toxicol ; 44(2): 130-139, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31258002

RESUMO

Diabetes mellitus is a significant global public health issue. The diabetic state not only precipitates chronic disease but also has the potential to change the toxicity of drugs and chemicals. Acrylonitrile (AN) is a potent neurotoxin widely used in industrial products. This study used a streptozotocin (STZ)-induced diabetic rat model to examine the role of cytochrome P450 2E1 (CYP2E1) in acute AN toxicity. The protective effect of phenethyl isothiocyanate (PEITC), a phytochemical inhibitor of CYP2E1, was also investigated. A higher incidence of convulsions and loss of the righting reflex, and decreased rates of survival, as well as elevated CYP2E1 activity, were observed in diabetic rats treated with AN when compared to those in non-diabetic rats, suggesting that diabetes confers susceptibility to the acute toxicity of AN. Pretreatment with PEITC (20-80 mg/kg) followed by AN injection alleviated the acute toxicity of AN in diabetic rats as evidenced by the decreased incidence of convulsions and loss of righting reflex, and increased rates of survival. PEITC pretreatment at 40 and 80 mg/kg decreased hepatic CYP2E1 activity in AN-exposed diabetic rats. PEITC pretreatment (20 mg/kg) increased the glutathione (GSH) content and glutathione S-transferase (GST) activity and further decreased ROS levels in AN-exposed diabetic rats. Collectively, STZ-induced diabetic rats were more sensitive to AN-induced acute toxicity mainly due to CYP2E1 induction, and PEITC pretreatment significantly alleviated the acute toxicity of AN in STZ-induced diabetic rats. PEITC might be considered as a potential effective chemo-preventive agent against AN-induced acute toxicity in individuals with an underlying diabetic condition.


Assuntos
Acrilonitrila/toxicidade , Inibidores do Citocromo P-450 CYP2E1/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Isotiocianatos/farmacologia , Animais , Citocromo P-450 CYP2E1/efeitos dos fármacos , Citocromo P-450 CYP2E1/metabolismo , Inibidores do Citocromo P-450 CYP2E1/administração & dosagem , Relação Dose-Resposta a Droga , Isotiocianatos/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Reflexo de Endireitamento/efeitos dos fármacos , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Estreptozocina , Taxa de Sobrevida
17.
Toxicol Ind Health ; 37(11): 695-704, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34643460

RESUMO

Acrylonitrile (AN) is a known animal carcinogen and suspected human carcinogen. Recently, occupational exposure to AN has considerably increased. Previously, we demonstrated that streptozotocin-induced diabetes potentiates AN-induced acute toxicity in rats and that the induced cytochrome P450 2E1 (CYP2E1) is responsible for this effect. In the present study, we examined whether induction of CYP2E1 is also the underlying mechanism for the potentiation of AN-induced acute toxicity in type 2 diabetes in db/db mice. The effect of phenethyl isothiocyanate (PEITC) in reducing potentiation was also investigated. The mice were randomly divided into the normal control, diabetic control, AN, diabetes + AN, PEITC + AN, and diabetes + PEITC + AN groups. PEITC (40 mg/kg) was orally administered to rats for 3 days, and 1 h after the last PEITC gavage, 45 mg/kg AN was intraperitoneally injected. Time to death was observed. The CYP2E1 level and enzymatic activity, cytochrome c oxidase (CCO) activity, and reactive oxygen species (ROS) levels were measured. The survival rate was decreased in AN-treated db/db mice compared with that in AN-treated wild-type mice. The hepatic CYP2E1 level and enzymatic activity remained unaltered in db/db mice. Phenethyl isothiocyanate alleviated AN-induced acute toxicity in db/db mice as evident in the increased survival rate, restored CCO activity, and decreased ROS level in both the liver and brain. The study results suggested that CYP2E1 may not be responsible for the sensitivity to AN-induced acute toxicity in db/db mice and that PEITC reduced the potentiation of AN-induced acute toxicity in db/db mice.


Assuntos
Acrilonitrila/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Animais , Citocromo P-450 CYP2E1/análise , Isotiocianatos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio , Taxa de Sobrevida
18.
Sensors (Basel) ; 21(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34640926

RESUMO

Sulfamethazine (SMZ) as a broad antibiotic is widely used in livestock and poultry. However, the abuse of SMZ in livestock feed can lead to SMZ residues in food and the resistance of bacteria to drugs. Thus, a method for the detection of SMZ in food is urgently needed. In this study, quantum dot (QD) nanobeads (QBs) were synthesized by encapsulating CdSe/ZnS QDs using a microemulsion technique. The prepared QBs as signal probes were applied in lateral flow immunoassay (LFIA) for the detection of SMZ in chicken and milk. Our proposed method had limits of detection of 0.1138-0.0955 ng/mL and corresponding linear ranges of 0.2-12.5, 0.1-15 ng/mL in chicken and milk samples, respectively. The recovery of LFIA for the detection of SMZ was 80.9-109.4% and 84-101.6% in chicken and milk samples, respectively. Overall, the developed QBs-LFIA had high reliability and excellent potential for rapid and sensitive screening of SMZ in food.


Assuntos
Pontos Quânticos , Animais , Galinhas , Imunoensaio , Leite/química , Reprodutibilidade dos Testes , Sulfametazina/análise
19.
J Environ Sci (China) ; 104: 216-224, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33985724

RESUMO

The nondestructive characterization of the mixing state of individual fine particles using the traditional single particle analysis technique remains a challenge. In this study, fine particles were collected during haze events under different pollution levels from September 5 to 11 2017 in Beijing, China. A nondestructive surface-enhanced Raman scattering (SERS) technique was employed to investigate the morphology, chemical composition, and mixing state of the multiple components in the individual fine particles. Optical image and SERS spectral analysis results show that soot existing in the form of opaque material was predominant during clear periods (PM2.5 ≤ 75 µg/m3). During polluted periods (PM2.5 > 75 µg/m3), opaque particles mixed with transparent particles (nitrates and sulfates) were generally observed. Direct classical least squares analysis further identified the relative abundances of the three major components of the single particles: soot (69.18%), nitrates (28.71%), and sulfates (2.11%). A negative correlation was observed between the abundance of soot and the mass concentration of PM2.5. Furthermore, mapping analysis revealed that on hazy days, PM2.5 existed as a core-shell structure with soot surrounded by nitrates and sulfates. This mixing state analysis method for individual PM2.5 particles provides information regarding chemical composition and haze formation mechanisms, and has the potential to facilitate the formulation of haze prevention and control policies.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Pequim , China , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/análise , Estações do Ano , Análise Espectral Raman
20.
J Fluoresc ; 30(3): 463-470, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32140947

RESUMO

Herein, we report an interesting finding about the new application of oxytetracycline (OTC), as a fluorescent probe for the detection of calcium ion (Ca2+), which proved that it can offer an expeditious, highly sensitive, and selective detection method for Ca2+. Upon the addition of Ca2+, the fluorescence of OTC could be significantly enhanced with rapid response and high sensitivity, and achieved a good limit of detection as low as 125 nM in aqueous solution. The complex formed via Ca2+ coordinating to the hydroxyl group of OTC contributes to the fluorescence enhancement, which has been proved by several characterization methods including UV-vis analysis, binding constant determination, and fluorescence titration. The method avoided complexity for EDTA measurement of Ca2+ in running water as proposed previously. Taking advantage of good availability, stability and operability, the OTC was further successfully applied to the detection of Ca2+ in a real environment. Graphical Abstract.


Assuntos
Cálcio/análise , Fluorescência , Corantes Fluorescentes/química , Oxitetraciclina/química , Íons/análise , Espectrometria de Fluorescência
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