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1.
Free Radic Biol Med ; 204: 226-242, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37146698

RESUMO

Influenza A virus can induce nasal inflammation by stimulating the death of nasal mucosa epithelium, however, the mechanism is not clear. In this study, to study the causes and mechanisms of nasal mucosa epithelial cell death caused by Influenza A virus H1N1, we isolated and cultured human nasal epithelial progenitor cells (hNEPCs) and exposed them to H1N1 virus after leading differentiation. Then we performed high-resolution untargeted metabolomics and RNAseq analysis of human nasal epithelial cells (hNECs) infected with H1N1 virus. Surprisingly, H1N1 virus infection caused the differential expression of a large number of ferroptosis related genes and metabolites in hNECs. Furthermore, we have observed a significant reduction in Nrf2/KEAP1 expression, GCLC expression, and abnormal glutaminolysis. By constructing overexpression vector of GCLC and the shRNAs of GCLC and Keap1, we determined the role of NRF2-KEAP1-GCLC signaling pathway in H1N1 virus-induced ferroptosis. In addition, A glutaminase antagonist, JHU-083, also demonstrated that glutaminolysis can regulate the NRF2-KEAP1-GCLC signal pathway and ferroptosis. According to this study, H1N1 virus can induce the ferroptosis of hNECs via the NRF2-KEAP1-GCLC signal pathway and glutaminolysis, leading to nasal mucosal epithelial inflammation. This discovery is expected to provide an attractive therapeutic target for viral-induced nasal inflammation.


Assuntos
Doenças Transmissíveis , Ferroptose , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Humanos , Doenças Transmissíveis/metabolismo , Células Epiteliais/metabolismo , Glutamato-Cisteína Ligase/genética , Inflamação/metabolismo , Vírus da Influenza A/metabolismo , Vírus da Influenza A Subtipo H1N1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Mucosa Nasal/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo
2.
Apoptosis ; 28(3-4): 432-446, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36484960

RESUMO

Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a common risk factor for pulmonary arterial hypertension (PAH). As a hypoxia-induced transcription factor, differentially expressed in chondrocytes (DEC1) negatively regulates the transcription of peroxisome proliferative activated receptor-γ (PPARγ), a recognized protective factor of PAH. However, whether and how DEC1 is associated with PAH pathogenesis remains unclear. In the present study, we found that DEC1 was increased in lungs and pulmonary arterial smooth muscle cells (PASMCs) of rat models of OSA-associated PAH. Oxidative indicators and inflammatory cytokines were also elevated in the blood of the rats. Similarly, hypoxia-treated PASMCs displayed enhanced DEC1 expression and reduced PPARγ expression in vitro. Functionally, DEC1 overexpression exacerbated reactive oxygen species (ROS) production and the expression of pro-inflammatory cytokines (such as TNFα, IL-1ß, IL-6, and MCP-1) in PASMCs. Conversely, shRNA knockdown of Dec1 increased PPARγ expression but attenuated hypoxia-induced oxidative stress and inflammatory responses in PASMCs. Additionally, DEC1 overexpression promoted PASMC proliferation, which was drastically attenuated by a PPARγ agonist rosiglitazone. Collectively, these results suggest that hypoxia-induced DEC1 inhibits PPARγ, and that this is a predominant mechanism underpinning oxidative stress and inflammatory responses in PASMCs during PAH. DEC1 could be used as a potential target to treat PAH.


Assuntos
Hipertensão Arterial Pulmonar , Apneia Obstrutiva do Sono , Ratos , Animais , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/patologia , PPAR gama/genética , PPAR gama/metabolismo , Ratos Sprague-Dawley , Apoptose , Artéria Pulmonar/metabolismo , Estresse Oxidativo , Hipóxia/complicações , Hipóxia/genética , Hipóxia/metabolismo , Inflamação/metabolismo , Citocinas/genética , Citocinas/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/metabolismo , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo
3.
Front Physiol ; 13: 932596, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105285

RESUMO

Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for metabolic syndrome (MetS). Recent studies have indicated that circadian clock genes were dysregulated in OSA. In addition, it is clear that the impairment of circadian clocks drives the progression of MetS. Therefore, we hypothesized that circadian rhythm disruption links OSA with MetS. Methods: A total of 118 participants, who underwent polysomnography (PSG) and were diagnosed as healthy snorers (control, n = 29) or OSA (n = 89) patients based on the apnea-hypopnea index (AHI), were enrolled in the present study. General information, anthropometric data, blood biochemical indicators, clock gene expressions, and levels of oxidative and inflammatory indicators were collected, determined, and compared in all the participants. Results: We found that Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and Differentiated embryo chondrocyte 1 (Dec1) were upregulated, while Period 1 (Per1) was reduced in OSA patients. In addition, these changing trends were closely associated with the hypoxia indicator of AHI and have a significant impact on the presence of MetS components, such as hyperglycemia (Dec1 and Per1, p < 0.05 and 0.001, respectively), hypertension (Bmal1 and Dec1, p < 0.001 and 0.01, respectively), hyperlipidemia (Dec1, p < 0.01), and obesity (Dec1, p < 0.05). Notably, expressions of Dec1 correlated with IR and predicted the presence of MetS in OSA patients. Finally, we also observed that Dec1 expression was interrelated with levels of both oxidative indicators and inflammatory biomarkers (IL-6) in OSA. Conclusion: This study concluded that circadian clock disruptions, especially Dec1, link OSA with MetS in an oxidative and inflammatory-related manner. Circadian clock Dec1 can be used as a specific biomarker (p < 0.001) and therapeutic target in OSA combined with Mets patients.

4.
Int J Pediatr Otorhinolaryngol ; 159: 111194, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35709564

RESUMO

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep disorder causing cognitive impairments. AIMS: We use the auditory verbal learning test (AVLT), clock drawing test (CDT), Wechsler intelligence scale for children (WISC) and Montreal cognitive assessment (MoCA) to evaluate the memory and spatial impairments of OSHAS in 6-12 years old children patients with different severity. MATERIAL AND METHODS: A total of 137 children of snoring were enrolled following the inclusion criteria of this study. According to the apnea-hypopnea indices (AHI), they were divided into three groups. The AVLT, CDT, WISC and MoCA tests were executed by physicians. The self-rating depression scale (SDS) test was performed for depression screening. RESULTS: Compared with the children in the primary snoring group, the other two groups had higher body mass index (BMI), longer periods of snoring and older age. The AHI, oxygen desaturation index (ODI) and 90% oxygen saturation (TS90%) showed increasing trends whereas the lowest blood oxygen saturation (LSaO2) showed a decreasing trend. Besides, compared with the primary snoring group, the two groups had lower immediate recall scores in AVLT. CONCLUSION: AVLT had clinical values for evaluation of impaired memory function in OSAHS children, suggesting a correlation between cognitive impairments and nocturnal hypoxia.


Assuntos
Apneia Obstrutiva do Sono , Ronco , Criança , Humanos , Hipóxia , Testes Neuropsicológicos , Polissonografia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Ronco/diagnóstico
5.
Nat Commun ; 13(1): 1189, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246542

RESUMO

Improving the catalytic efficiency of platinum for the hydrogen evolution reaction is valuable for water splitting technologies. Hydrogen spillover has emerged as a new strategy in designing binary-component Pt/support electrocatalysts. However, such binary catalysts often suffer from a long reaction pathway, undesirable interfacial barrier, and complicated synthetic processes. Here we report a single-phase complex oxide La2Sr2PtO7+δ as a high-performance hydrogen evolution electrocatalyst in acidic media utilizing an atomic-scale hydrogen spillover effect between multifunctional catalytic sites. With insights from comprehensive experiments and theoretical calculations, the overall hydrogen evolution pathway proceeds along three steps: fast proton adsorption on O site, facile hydrogen migration from O site to Pt site via thermoneutral La-Pt bridge site serving as the mediator, and favorable H2 desorption on Pt site. Benefiting from this catalytic process, the resulting La2Sr2PtO7+δ exhibits a low overpotential of 13 mV at 10 mA cm-2, a small Tafel slope of 22 mV dec-1, an enhanced intrinsic activity, and a greater durability than commercial Pt black catalyst.

6.
ACS Appl Mater Interfaces ; 13(50): 59993-60001, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34890504

RESUMO

Electrochemical CO2 reduction (ECR) technology is promising to produce value-added chemicals and alleviate the climate deterioration. Interface engineering is demonstrated to improve the ECR performance for metal and oxide composite catalysts. However, the approach to form a substantial interface is still limited. In this work, we report a facile one-pot coprecipitation method to synthetize novel silver and silver-doped ceria (Ag/CeO2) nanocomposites. This catalyst provides a rich 3D interface and high Ce3+ concentration (33.6%), both of which are beneficial for ECR to CO. As a result, Ag/CeO2 exhibits a 99% faradaic efficiency and 10.5 A g-1 mass activity to convert CO2 into CO at an overpotential of 0.83 V. The strong interfacial interaction between Ag and CeO2 may enable the presence of surface Ce3+ and guarantee the improved durability during the electrolysis. We also develop numerical simulation to understand the local pH effect on the ECR performance and propose that the superior ECR performance of Ag/CeO2 is mainly due to the accelerated CO formation rate rather than the suppressed hydrogen evolution reaction.

7.
Front Cell Dev Biol ; 9: 757168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765605

RESUMO

Background: The hypoxia-induced pro-proliferative and anti-apoptotic characteristics of pulmonary arterial endothelial cells (PAECs) play critical roles in pulmonary vascular remodeling and contribute to hypoxic pulmonary arterial hypertension (PAH) pathogenesis. However, the mechanism underlying this hypoxic disease has not been fully elucidated. Methods: Bioinformatics was adopted to screen out the key hypoxia-related genes in PAH. Gain- and loss-function assays were then performed to test the identified hypoxic pathways in vitro. Human PAECs were cultured under hypoxic (3% O2) or normoxic (21% O2) conditions. Hypoxia-induced changes in apoptosis and proliferation were determined by flow cytometry and Ki-67 immunofluorescence staining, respectively. Survival of the hypoxic cells was estimated by cell counting kit-8 assay. Expression alterations of the target hypoxia-related genes, cell cycle regulators, and apoptosis factors were investigated by Western blot. Results: According to the Gene Expression Omnibus dataset (GSE84538), differentiated embryo chondrocyte expressed gene 1-peroxisome proliferative-activated receptor-γ (Dec1-PPARγ) axis was defined as a key hypoxia-related signaling in PAH. A negative correlation was observed between Dec1 and PPARγ expression in patients with hypoxic PAH. In vitro observations revealed an increased proliferation and a decreased apoptosis in PAECs under hypoxia. Furthermore, hypoxic PAECs exhibited remarkable upregulation of Dec1 and downregulation of PPARγ. Dec1 was confirmed to be crucial for the imbalance of proliferation and apoptosis in hypoxic PAECs. Furthermore, the pro-surviving effect of hypoxic Dec1 was mediated through PPARγ inhibition. Conclusion: For the first time, Dec1-PPARγ axis was identified as a key determinant hypoxia-modifying signaling that is necessary for the imbalance between proliferation and apoptosis of PAECs. These novel endothelial signal transduction events may offer new diagnostic and therapeutic options for patients with hypoxic PAH.

8.
Adv Mater ; 33(41): e2103392, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34436805

RESUMO

Corner-sharing oxides usually suffer from structural reconstruction during the bottleneck oxygen-evolution reaction (OER) in water electrolysis. Therefore, introducing dynamically stable active sites in an alternative structure is urgent but challenging. Here, 1D 5H-polytype Ba5 Bi0.25 Co3.75 FeO14- δ oxide with face-sharing motifs is identified as a highly active and stable candidate for alkaline OER. Benefiting from the stable face-sharing motifs with three couples of combined bonds, Ba5 Bi0.25 Co3.75 FeO14- δ can maintain its local structures even under high OER potentials as evidenced by fast operando spectroscopy, contributing to a negligible performance degradation over 110 h. Besides, the higher Co valence and smaller orbital bandgap in Ba5 Bi0.25 Co3.75 FeO14- δ endow it with a much better electron transport ability than its corner-sharing counterpart, leading to a distinctly reduced overpotential of 308 mV at 10 mA cm-2 in 0.1 m KOH. Further mechanism studies show that the short distance between lattice-oxygen sites in face-sharing Ba5 Bi0.25 Co3.75 FeO14- δ can accelerate the deprotonation step (*OOH + OH-  = *OO + H2 O + e- ) via a steric inductive effect to promote lattice-oxygen participation. In this work, not only is a new 1D face-sharing oxide with impressive OER performance discovered, but also a rational design of dynamic stable and active sites for sustainable energy systems is inaugurated.

9.
Spine (Phila Pa 1976) ; 46(20): E1083-E1088, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33710113

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVE: To describe the epidemiology and clinical outcomes of pediatric patients with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) in mainland China for the first time. SUMMARY OF BACKGROUND DATA: SCIWORA is a syndrome that often occurs in children mainly due to the unique biomechanics of the pediatric spine. Although there have been numerous retrospective studies on pediatric SCIWORA, and mainland China has more patients with SCI than anywhere else, pediatric patients with SCIWORA in mainland China has not been described in any study. METHODS: Review of all cases with SCIWORA at Beijing Children's Hospital between July 2007 and December 2019. RESULTS: Of the 189 pediatric patients with SCI 140 had SCIWORA (age: 5.65 ±â€Š2.60 years, male-to-female ratio: 2:5). Main causes of injuries were sports (41%, mostly backbend), falls (27%), traffic accidents (10%), and violence (8%). Lesions were located at the thoracic (77%), cervical (10%), multiple (5%), and lumbar (4%) levels. Incubation period was 2 ±â€Š6 hours. Pathological characteristics of SCI were detected in 96% patients by magnetic resonance imaging (MRI). Based on the American Spinal Injury Association impairment scale (AIS), many patients had complete impairment (50% AIS A, 45% AIS B/C/D, 1% AIS E). Particularly, the five patients with normal MRI tended to have mild injury (AIS D) (P < 0.001), but they still showed abnormal reflex. In the one patient who could not be graded at all by AIS, his only functional deficits were abnormal upper and lower limb muscle tones. A total of 59% patients were treated with methylprednisolone, dexamethasone, or both. Out of 76 patients 59 showed neurological improvement before discharge. The only association among age, cause of injury, level of lesion, incubation period, AIS grade, type of corticosteroid therapy, and neurological improvement was between level of lesion and AIS grade (P < 0.001). CONCLUSION: Demographic and clinical differences exist in patients with SCIWORA. MRI and detailed neurological examinations should both be performed for proper diagnosis. There is still a need to develop better treatment strategy for these patients.Level of Evidence: 4.


Assuntos
Traumatismos da Medula Espinal , Acidentes de Trânsito , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Estudos Retrospectivos , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/epidemiologia
10.
Nat Commun ; 12(1): 660, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510153

RESUMO

Electrochemical CO2 reduction (ECR) is highly attractive to curb global warming. The knowledge on the evolution of catalysts and identification of active sites during the reaction is important, but still limited. Here, we report an efficient catalyst (Ag-D) with suitable defect concentration operando formed during ECR within several minutes. Utilizing the powerful fast operando X-ray absorption spectroscopy, the evolving electronic and crystal structures are unraveled under ECR condition. The catalyst exhibits a ~100% faradaic efficiency and negligible performance degradation over a 120-hour test at a moderate overpotential of 0.7 V in an H-cell reactor and a current density of ~180 mA cm-2 at -1.0 V vs. reversible hydrogen electrode in a flow-cell reactor. Density functional theory calculations indicate that the adsorption of intermediate COOH could be enhanced and the free energy of the reaction pathways could be optimized by an appropriate defect concentration, rationalizing the experimental observation.

11.
Front Cell Dev Biol ; 9: 803981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35047513

RESUMO

Paris saponin has shown great therapeutic value in cancer therapy. We used isolated Paris saponin II (PSII), an active component of Paris saponin, and demonstrated its antitumor effect on human head and neck squamous cell carcinoma cell lines. Additionally, we investigated its mechanisms of action in vivo by establishing a xenograft mouse model. The results showed that PSII had presented strong anticancer effects on both hypopharyngeal malignant tumor cell lines (FaDu) and laryngeal carcinoma cell lines (Tu212 and Tu686). In addition, we successfully isolated and cultured the head and neck squamous stem cells and the primary fibroblasts to perform metabonomics studies. The results showed that RPII remarkably decreased energy metabolism, and type III nitric oxide synthase 3 (NOS3) may be a target to block tumor growth. Furthermore, we found that PSII inhibited HNSCC proliferation and metastasis by inhibiting the nitric oxide metabolic pathway. Overall, these results demonstrated that PSII is a potent anticancer agent, and the metabonomics analysis is a valuable tool to investigate and establish the antitumor effects of traditional Chinese medicines.

12.
Small ; 16(51): e2006800, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33251694

RESUMO

Exploring active, stable, and low-cost bifunctional electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is crucial for water splitting technology associated with renewable energy storage in the form of hydrogen fuel. Here, a newly designed antiperovskite-based hybrid composed of a conductive InNNi3 core and amorphous InNi(oxy)hydroxide shell is first reported as promising OER/HER bifunctional electrocatalyst. Prepared by a facile electrochemical oxidation strategy, such unique hybrid (denoted as EO-InNNi3 ) exhibits excellent OER and HER activities in alkaline media, benefiting from the inherent high-efficiency HER catalytic nature of InNNi3 antiperovskite and the promoting role of OER-active InNi(oxy)hydroxide thin film, which is confirmed by theoretical simulations and in situ Raman studies. Moreover, an alkaline electrolyzer integrated EO-InNNi3 as both anode and cathode delivers a low voltage of 1.64 V at 10 mA cm-2 , while maintaining excellent durability. This work demonstrates the application of antiperovskite-based materials in the field of overall water splitting and inspires insights into the development of advanced catalysts for various energy applications.

13.
Nat Commun ; 11(1): 3376, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632311

RESUMO

Ion leaching from pure-phase oxygen-evolving electrocatalysts generally exists, leading to the collapse and loss of catalyst crystalline matrix. Here, different from previous design methodologies of pure-phase perovskites, we introduce soluble BaCl2 and SrCl2 into perovskites through a self-assembly process aimed at simultaneously tuning dual cation/anion leaching effects and optimizing ion match in perovskites to protect the crystalline matrix. As a proof-of-concept, self-assembled hybrid Ba0.35Sr0.65Co0.8Fe0.2O3-δ (BSCF) nanocomposite (with BaCl2 and SrCl2) exhibits the low overpotential of 260 mV at 10 mA cm-2 in 0.1 M KOH. Multiple operando spectroscopic techniques reveal that the pre-leaching of soluble compounds lowers the difference of interfacial ion concentrations and thus endows the host phase in hybrid BSCF with abundant time and space to form stable edge/face-sharing surface structures. These self-optimized crystalline structures show stable lattice oxygen active sites and short reaction pathways between Co-Co/Fe metal active sites to trigger favorable adsorption of OH- species.

14.
ACS Appl Mater Interfaces ; 12(27): 30449-30456, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32558536

RESUMO

Microbial electrosynthesis (MES) is an electricity-driven technology for the microbial reduction of CO2 to organic commodities. However, the limited solubility of CO2 in a solution and the inefficient electron transfer make it impossible for microorganisms to obtain an efficient surface for catalytic interaction, thus resulting in the low efficiency of MES. To address this, we introduce a multifunctional perovskite-based cathode material Pr0.5(Ba0.5Sr0.5)0.5Co0.8Fe0.2O3-δ-carbon felt (Pr0.5BSCF-CF), which provides a simultaneously significant increase in CO2 absorption and hydrogen production. As a result, the volumetric acetate production rate of MES obtained by Pr0.5BSCF-CF is 0.24 ± 0.01 g L-1 day-1, and it achieves a maximum acetate titer of 13.74 ± 0.20 g L-1 within 70 days. An adequate supply of CO2 and H2 also provides a sufficient amount of substrates and energy for the self-replication of the biocatalysts in the MES reactor. This effect not only increases the amount of biocatalysts but also optimizes the functions of the biocatalysts; the above benefits further improve the production efficiency of the MES system. This strategy demonstrates that the development of perovskite-based multifunctional cathodes with a simultaneous supplementation of substrates and electrons is a promising approach toward improving the MES efficiency.


Assuntos
Compostos de Cálcio/química , Óxidos/química , Titânio/química , Dióxido de Carbono/química , Catálise , Técnicas Eletroquímicas/métodos , Eletrodos
15.
Environ Sci Pollut Res Int ; 26(3): 2353-2362, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30467747

RESUMO

Selective estrogen receptor modulators such as tamoxifen (TAM) significantly reduce the risks of developing estrogen receptor-positive (ER+) breast cancer. Low concentrations (nanomolar range) of bisphenol A (BPA) shows estrogenic effects and further promotes the proliferation of hormone-dependent breast cancer cells. However, whether or not BPA can influence TAM-treatment resistance in breast cancer has not drawn much attention. In the current study, low concentrations of BPA reduced TAM-induced cytotoxicity of MCF-7 cells, which was proved by the suppression of cell apoptosis, transition of cell cycle from G1 to S phase, and upregulation of cyclin D1 and ERα. Simultaneously, the mRNA levels of estrogen-related receptor γ (ERRγ) and its coactivators, peroxisome proliferation-activated receptor γ coactivator-1α (PGC-1α), and PGC-1ß, were increased. However, the similar effects were not observed in MDA-MB-231 cells. Our results indicated that low concentrations of BPA decreased the sensitivity of TAM in MCF-7 cells rather than in MDA-MB-231 cells. These different actions likely involved the interaction of relative receptors and coactivators. This study provided a possible support that the exposure of BPA in environmental media may potentially induce TAM resistance to breast cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Neoplasias da Mama/tratamento farmacológico , Fenóis/toxicidade , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Tamoxifeno/farmacologia , Compostos Benzidrílicos/administração & dosagem , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Relação Dose-Resposta a Droga , Receptor alfa de Estrogênio/genética , Estrogênios/toxicidade , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Fenóis/administração & dosagem , Fator Trefoil-1/genética
16.
Adv Sci (Weinh) ; 5(9): 1800514, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30250794

RESUMO

Hydrogen production from renewable electricity relies upon the development of an efficient alkaline water electrolysis device and, ultimately, upon the availability of low cost and stable electrocatalysts that can promote oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Normally, different electrocatalysts are applied for HER and OER because of their different reaction intermediates and mechanisms. Here, the synthesis of a heterostructured CoP@a-CoOx plate, which constitutes the embedded crystalline cobalt phosphide (CoP) nanoclusters and amorphous cobalt oxides (CoOx) nanoplates matrix, via a combined solvothermal and low temperature phosphidation route is reported. Due to the presence of synergistic effect between CoP nanoclusters and amorphous CoOx nanoplates in the catalyst, created from the strong nanointerfaces electronic interactions between CoP and CoOx phases in its heterostructure, this composite displays very high OER activity in addition to favorable HER activity that is comparable to the performance of the IrO2 OER benchmark and approached that of the Pt/C HER benchmark. More importantly, an efficient and stable alkaline water electrolysis operation is achieved using CoP@a-CoOx plate as both cathode and anode as evidenced by the obtainment of a relatively low potential of 1.660 V at a 10 mA cm-2 current density and its marginal increase above 1.660 V over 30 h continuous operation.

17.
Toxicology ; 410: 231-246, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153467

RESUMO

Breast cancer is the most diagnosed diseases and the second-leading cause of death in females, among which the estrogen receptor positive (ER+) patients are more common of all cases. In present study, we selected MCF-7 as an in vitro model and investigated the combinatorial anti-proliferative effects of tamoxifen and naringenin on ER+ breast cancer, and then explored the potential mechanisms involved in mitochondrial dysfunction and oxidative stress mediated by several estrogen receptor subtypes. Six assessment endpoints including cell viability, cell migration, cell cycle, cell apoptosis, mRNA, and protein expression were estimated. Tamoxifen and naringenin were shown to inhibit the cell growth of MCF-7 cells at higher concentrations, and co-exposure with them significantly inhibited cell proliferation in an additive manner. Results from a wound healing assay indicated that the combined treatment of tamoxifen and naringenin markedly suppressed cell migration compared with the single exposure by downregulating the expression of MMP-9 and MMP-2. Flow cytometry analysis revealed that the combined treatment of tamoxifen and naringenin blocked cell cycle in G2/M phase through suppressing the transcription of cell cycle regulation proteins. Simultaneously, co-treatment with them also induced cell apoptosis by regulating the expression of mitochondrial apoptotic proteins as well as by simulating the production of reactive oxygen species (ROS). Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) analysis results further demonstrated that the two nuclear estrogen receptors-ERα66 and ERß, as well as the two membrane estrogen receptors-ERα36 and GPR30 were downregulated when cells were exposed to single tamoxifen, whereas naringenin treatment group not only downregulated the expression of ERα66 and GPR30 but also upregulated ERß and ERα36. Interestingly, co-treatment group resulted in significant downregulation of ERα66, ERα36 and GPR30 but upregulation of ERß. Taken together, co-treatment of tamoxifen and naringenin could inhibit cell proliferation more effectively in ER+ breast cancer cells, which was associated with a modulation of the expression levels of several estrogen receptors.


Assuntos
Antineoplásicos Hormonais/farmacologia , Antagonistas de Estrogênios/farmacologia , Flavanonas/farmacologia , Receptores de Estrogênio/efeitos dos fármacos , Tamoxifeno/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/genética , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismo , Cicatrização/efeitos dos fármacos
18.
Chemistry ; 24(52): 13800-13806, 2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-29981182

RESUMO

Water electrolysis is regarded as a green and highly efficient approach to producing high-purity hydrogen, but commercialization of this technology still requires the development of high-performance and affordable electrocatalysts for the hydrogen evolution reaction (HER). Currently, because of its excellent electrical conductivity and good corrosion resistance in acidic media, cobalt phosphide (CoP) has become a representative non-noble-metal HER catalyst despite its inadequate catalytic activity. Herein, a strategy of multiple catalyst-structure engineering, which simultaneously includes doping, nanostructuring, and in situ nanocarbon coating, was employed to significantly improve the HER performance of CoP. CoP with optimized ruthenium doping and covered by ultrathin graphitic carbon shells shows remarkably high HER catalytic behaviour with a low overpotential of only 73 mV at a current density of 10 mA cm-2 and a small Tafel slope of 46 mV dec-1 , close to that of the Pt/C benchmark, while maintaining excellent durability. Moreover, the ultrathin graphene shell has a significant positive effect on catalytic activity. This work demonstrates the necessity and validity of multifold structural control, which can be widely used to design various materials for different catalytic processes.

19.
Water Res ; 137: 251-261, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29550728

RESUMO

The photochemical conversion and microbial transformation of pollutants mediated by dissolved organic matter (DOM), including 17α-ethinylestradiol (EE2), are often accompanied in natural water. However, there are few studies to explore the connection and mechanism between the two processes. This research aims to investigate the mechanism of DOM after electrochemically modification mediated EE2 combining photodegradation and biodegradation in the environment and it want to explain the natural phenomena of DOM after electrochemical advanced treatment entering the water environment mediated EE2 natural degradation. The results showed that combining photodegradation with biodegradation rates of EE2 mediated by DOM and electrochemically modified DOM (E-DOM) were promoted obviously. The efficiency of EE2 biodegradation was shown to be strongly correlated with electron accepting capacity (EAC) of DOM. Electrochemical modification can increase the EAC of DOM leading to EE2 biodegradation accelerated, and it also can form more triplet-state DOM moieties to promote the EE2 photodegradation in irradiation conditions, due to the increasing of quinone-type structures in DOM. Moreover, cell polymeric secretion (CPS) secreted from the microorganism could be stimulated to an excited state by irradiation, and that also accelerated EE2 degradation. Photolysis combined with biochemical degradation yielded less toxic degradation products. This study shows that the emission of DOM in wastewater after electrochemical treatment could accelerate estrogen degradation and play a positive role on the pollutant transformation in the environment.


Assuntos
Etinilestradiol , Poluentes Químicos da Água , Biodegradação Ambiental , Técnicas Eletroquímicas , Etinilestradiol/química , Etinilestradiol/metabolismo , Etinilestradiol/efeitos da radiação , Fotólise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/efeitos da radiação
20.
Environ Res ; 155: 199-207, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28231547

RESUMO

Xenoestrogens (XEs) mimic or block the synthesis, metabolism and transport of normal endogenous hormones, disturbing normal endocrine function. The available data on the nonmonotonic estrogenic effects of low doses of many XEs are reviewed, covering in vitro, in vivo and epidemiological studies. The observed nonmonotonic patterns of the dose-response curves are discussed, along with possible underlying mechanisms. This review is intended to provide guidance for harm predication and to suggest prevention measures.


Assuntos
Estrogênios/toxicidade , Animais , Relação Dose-Resposta a Droga , Poluentes Ambientais/toxicidade , Humanos , Xenobióticos/toxicidade
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