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1.
Small ; 20(13): e2302589, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37967327

RESUMO

The nucleation stage plays a decisive role in determining nanocrystal morphology and properties; hence, the ability to regulate nucleation is critical for achieving high-level control. Herein, glass microfluidic chips with S-shaped mixing units are designed for the synthesis of Au@Pt core/shell materials. The use of hydrodynamics to tune the nucleation kinetics is explored by varying the number of mixing units. Dendritic Au@Pt core/shell nanomaterials are controllably synthesized and a formation mechanism is proposed. As-synthesized Au@Pt exhibited excellent ethanol oxidation activity under alkaline conditions (8.4 times that of commercial Pt/C). This approach is also successfully applied to the synthesize of Au@Pd core/shell nanomaterials, thus demonstrating its generality.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38083008

RESUMO

Stress urinary incontinence is the involuntary leakage of urine during increased abdominal pressure, such as coughing, sneezing, laughing, or exercising. It can have a significant negative impact on a person's quality of life and can result in decreased physical activity and social isolation. The presented closure mechanism for a mechatronic intraurethral artificial urinary sphincter is designed to be inserted minimally invasive into the urethra. The device consists of a solid shell, which serves as a housing for the electronics and is designed to enable fixation in the urethra. During micturition, the urine flows through the system, where it is guided through an elastic silicone-tube that, on the one hand, enables closure by a squeezing mechanism and, on the other hand, prevents biofilm growth by oscillation at a frequency of 22.5 Hz. The squeezing mechanism consists of a pinch valve system actuated by a piezo motor. The system has been tested under urodynamic conditions and the results show that it is able to close the urethra effectively to restore continence. The device is able to withstand sudden loads and shows good performance in terms of biofilm prevention during first experiments with artificial urine. The results show that the mechatronic intraurethral artificial urinary sphincter has the potential to be an effective and minimally invasive alternative to current treatment options for stress urinary incontinence.Clinical Relevance- This novel concept of a mechatronic intraurethral artificial urinary sphincter presents a promising alternative treatment option for patients suffering from stress urinary incontinence. As it is designed to be inserted minimally invasive, it reduces the impact and complications associated with current treatment options. The future development and testing of the device could lead to a safe and effective option for clinicians to offer their patients with stress urinary incontinence, which can improve their quality of life, and decrease costs for society and healthcare systems.


Assuntos
Incontinência Urinária por Estresse , Esfíncter Urinário Artificial , Humanos , Incontinência Urinária por Estresse/cirurgia , Qualidade de Vida , Uretra/cirurgia , Micção
3.
Mikrochim Acta ; 190(7): 277, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37380931

RESUMO

Nitric oxide (NO), as a vital signaling molecule related to different physiological and pathological processes in living systems, is closely associated with cancer and cardiovascular disease. However, the detection of NO in real-time remains a difficulty. Here, PtBi alloy nanoparticles (NPs) were synthesized, dealloyed, and then fabricated to NP-based electrodes for the electrochemical detection of NO. Transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and nitrogen physical adsorption/desorption show that dealloyed PtBi alloy nanoparticles (dPtBi NPs) have a porous nanostructure. Electrochemical impedance spectroscopy and cyclic voltammetry results exhibit that the dPtBi NP electrode possesses unique electrocatalytic features such as low charge transfer resistance and large electrochemically active surface area, which lead to its excellent NO electrochemical sensing performance. Owing to the higher density of catalytical active sites formed PtBi bimetallic interface, the dPtBi NP electrode displays superior electrocatalytic activity toward the oxidation of NO with a peak potential at 0.74 V vs. SCE. The dPtBi NP electrode shows a wide dynamic range (0.09-31.5 µM) and a low detection limit of 1 nM (3σ/k) as well as high sensitivity (130 and 36.5 µA µM-1 cm-2). Moreover, the developed dPtBi NP-based electrochemical sensor also exhibited good reproducibility (RSD 5.7%) and repeatability (RSD 3.4%). The electrochemical sensor was successfully used for the sensitive detection of NO produced by live cells. This study indicates a highly effective approach for regulating the composition and nanostructures of metal alloy nanomaterials, which might provide new technical insights for developing high-performance NO-sensitive systems, and have important implications in enabling real-time detection of NO produced by live cells.


Assuntos
Nanopartículas , Óxido Nítrico , Reprodutibilidade dos Testes , Espalhamento a Baixo Ângulo , Difração de Raios X , Ligas
4.
Chem Commun (Camb) ; 59(44): 6730-6733, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37191241

RESUMO

Noble metal nanoporous materials hold great potential in the field of catalysis, owing to their high open structures and numerous low coordination surface sites. However, the formation of porous nanoparticles is restricted by particle size. Herein, we utilized a Pt1Bi2 intermetallic nanocatalyst to develop a dealloying approach for preparing nanoparticles with a bi-continuous porous and core-shell structure and proposed a mechanism for the formation of pores. The particle size used to form the porous structure can be <10 nm, which enhances the nanocatalyst's performance for the oxygen reduction reaction (ORR). This study provides a new understanding of the formation of porous materials via a dealloying approach.

5.
Bioengineered ; 13(3): 5827-5842, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35200111

RESUMO

Circular RNAs (circRNAs) are associated with the progression of gastric cancer (GC). This study investigates the regulation of the circular RNA, hsa_circ_0119412 in GC and its effects on GC cells. The expression of hsa_circ_0119412, microRNA (miR)-1298-5p, and zinc finger BED-type containing 3 (ZBED3) were measured by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK-8) assay, flow cytometry, transwell, and animal assays were performed to identify the roles of hsa_circ_0119412, miR-1298-5p, and ZBED3 in the viability, apoptosis, invasion, and growth of GC cells. The relationship between hsa_circ_0119412, miR-1298-5p, and ZBED3 was confirmed by luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. Our data revealed that hsa_circ_0119412 and ZBED3 expression was upregulated in GC, while miR-1298-5p expression was downregulated. Both the knockdown of hsa_circ_0119412/ZBED3 and miR-1298-5p overexpression inhibited GC cell growth and invasion, and enhanced cell apoptosis, while miR-1298-5p interference or ZBED3 overexpression showed the opposite trend. Mechanistically, hsa_circ_0119412 sponges miR-1298-5p, which regulates ZBED3 expression. Silencing hsa_circ_0119412 inhibits the progression of GC, at least in part, by targeting the miR-1298-5p/ZBED3 axis.


Assuntos
Proteínas de Ligação a DNA , MicroRNAs , RNA Circular , Neoplasias Gástricas , Fatores de Transcrição , Animais , Carcinogênese/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/genética , RNA Circular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
6.
J Healthc Eng ; 2021: 3843830, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956570

RESUMO

This study aimed to investigate the protective effect and molecular mechanism of spironolactone in isoproterenol-induced cardiomyocyte hypertrophy. In this study, primary cardiomyocytes were extracted from the heart of neonatal rats. After stable culture, they were processed with isoproterenol alone or isoproterenol (10 µM) combined with different doses (low dose of 10 µM and high dose of 50 µM), and the cellular activity was determined by MTT experiment. The volume of cells was measured with an inverted microscope and CIAS-1000 cell image analysis system. The mRNA expression levels of ANP and BNP in cells were explored by RT-qPCR. The levels of ANP and BNP proteins and NFATc3 phosphorylation in the nucleus were detected by western blot. The extracellular Ca2+ concentration and CaN activity were measured by colorimetry with the kit. Isoproterenol significantly enlarged the volume of cardiomyocytes (p < 0.001), upregulated mRNA and expression levels of ANP and BNP proteins (p < 0.001), increased extracellular Ca2+ concentration and CaN activity (p < 0.001), and upregulated NFATc3 phosphorylation in the nucleus (p < 0.001). The volume of cells treated with isoproterenol combined with different doses of spironolactone significantly decreased compared with those treated with isoproterenol alone (p < 0.001). mRNA and expression levels of ANP and BNP proteins downregulated significantly (p < 0.001). The extracellular Ca2+ (p < 0.01) concentration and CaN activity (p < 0.001) decreased significantly, and NFATc3 phosphorylation in the nucleus downregulated significantly (p < 0.001). There was no significant difference in cell volume (p=0.999), ANP and BNP mRNA (p=0.695), expression levels of proteins, CaN activity (0.154), and NFATc3 phosphorylation in the nucleus between the cells treated with isoproterenol combined with high-dose spironolactone and those in the control group. In conclusion, spironolactone can reverse isoproterenol-induced cardiomyocyte hypertrophy by inhibiting the Ca2+/CaN/NFATc3 pathway.


Assuntos
Calcineurina , Cálcio/metabolismo , Miócitos Cardíacos , Fatores de Transcrição NFATC/metabolismo , Espironolactona , Animais , Calcineurina/metabolismo , Hipertrofia , Ratos , Espironolactona/farmacologia
7.
Chemosphere ; 281: 130835, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33992848

RESUMO

The increase in global population size over the past 100 decades has doubled the requirements for energy resources. To mitigate the limited fossil fuel available, new clean energy sources being environmental sustainable for replacement of traditional energy sources are explored to supplement the current scarcity. Biomass containing lignin and cellulose is the main raw material to replace fossil energy given its abundance and lower emission of greenhouse gases and NOx when transformed into energy. Bacteria, fungi and algae decompose lignocellulose leading to generation of hydrogen, methane, bioethanol and biodiesel being the clean energy used for heating, power generation and the automobile industry. Microbial Fuel Cell (MFC) uses microorganisms to decompose biomass in wastewater to generate electricity and remove heavy metals in wastewater. Biomass contains cellulose, hemicellulose, lignin and other biomacromolecules which need hydrolyzation for conversion into small molecules by corresponding enzymes in order to be utilized by microorganisms. This paper discusses microbial decomposition of biomass into clean energy and the five major ways of clean energy production, and its economic benefits for future renewable energy security.


Assuntos
Fontes de Energia Bioelétrica , Lignina , Biocombustíveis , Biomassa , Celulose , Fontes Geradoras de Energia , Metano
8.
Sci Total Environ ; 742: 140681, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167298

RESUMO

The deforestation and burning of the Amazon and other rainforests is having a cascade of effects on global climate, biodiversity, human health and local and regional socioeconomics. This challenging situation demands a sustainable exploitation of the region's resources in accordance with the United Nations (UNs) Sustainable Development Goals (SDGs) in order to meet Good Environmental Status and reduce poverty. The management of forests sustainability spans across at least eight of the 17 UN SDGs mainly to combat desertification, halt biodiversity loss, and reverse land degradation. Significant changes are needed if we are to sustain the world's rainforests and thereby the global climate and biodiversity. These measures and mitigations are of global responsibility requiring both developed and developing nations such as the United States, EU, and China to change their policies and stand regarding their high demand for meat and hardwood. When possible, non-profit tree-planting internet browsers should be implemented by governments and institutions. So far, there is a lack of active use of the UN SDGs and the countries must therefore need to fully adopt the UN SDGs in order to help the situation. One way to enforce this could be through imposing economic penalties to governments and national institutions that do not adhere to for example publishing open access of data and other important information relevant for the mission of the UN SDGs.

9.
ACS Omega ; 5(40): 26237-26244, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33073150

RESUMO

Aqueous polyurethane dispersion (PUD) has attracted increasing attention in a wide range of industrial applications because of their versatile properties as well as ecofriendly nature. In this study, the aqueous PUD used in warp-knitted vamp printing was characterized by Fourier transform infrared spectra, dynamic light scattering, and laser Doppler electrophoresis. The mean diameter and zeta potential are 206.6 nm and -18.3 mV, respectively. The rheological behavior of aqueous PUD as a function of shear rate, temperature, and solid content was investigated experimentally. Besides, a new correlation model was proposed based on the Carreau equation and Arrhenius relation. The resulting model has high accuracy in viscosity estimation under complex conditions according to the prediction interval of 95%. Furthermore, the reasonable ranges of parameters were proposed theoretically for successful printing.

10.
Environ Res ; 191: 110046, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32841638

RESUMO

Locusts differ from ordinary grasshoppers in their ability to swarm over long distances and are among the oldest migratory pests. The ecology and biology of locusts make them among the most devastating pests worldwide and hence the calls for actions to prevent the next outbreaks. The most destructive of all locust species is the desert locust (Schistocerca gregaria). Here, we review the current locust epidemic 2020 outbreak and its causes and prevention including the green technologies that may provide a reference for future directions of locust control and food security. Massive locust outbreaks threaten the terrestrial environments and crop production in around 100 countries of which Ethiopia, Somalia and Kenya are the most affected. Six large locust outbreaks are reported for the period from 1912 to 1989 all being closely related to long-term droughts and warm winters coupled with occurrence of high precipitation in spring and summer. The outbreaks in East Africa, India and Pakistan are the most pronounced with locusts migrating more than 150 km/day during which the locusts consume food equivalent to their own body weight on a daily basis. The plague heavily affects the agricultural sectors, which is the foundation of national economies and social stability. Global warming is likely the main cause of locust plague outbreak in recent decades driving egg spawning of up to 2-400,000 eggs per square meter. Biological control techniques such as microorganisms, insects and birds help to reduce the outbreaks while reducing ecosystem and agricultural impacts. In addition, green technologies such as light and sound stimulation seem to work, however, these are challenging and need further technological development incorporating remote sensing and modelling before they are applicable on large-scales. According to the Food and Agriculture Organization (FAO) of the United Nations, the 2020 locust outbreak is the worst in 70 years probably triggered by climate change, hurricanes and heavy rain and has affected a total of 70,000 ha in Somalia and Ethiopia. There is a need for shifting towards soybean, rape, and watermelon which seems to help to prevent locust outbreaks and obtain food security. Furthermore, locusts have a very high protein content and is an excellent protein source for meat production and as an alternative human protein source, which should be used to mitigate food security. In addition, forestation of arable land improves local climate conditions towards less precipitation and lower temperatures while simultaneously attracting a larger number of birds thereby increasing the locust predation rates.


Assuntos
Gafanhotos , Animais , Surtos de Doenças , Ecossistema , Segurança Alimentar , Aquecimento Global , Humanos , Índia , Quênia , Paquistão
11.
J Environ Health Sci Eng ; 17(1): 135-140, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31321041

RESUMO

BACKGROUND: Aniline compounds are widely applied as important chemical raw materials. However, they are so toxic and harmful to humans and environment that they need to be removed by an effective and economic approach, such as enzymatic reaction, which is in line with contemporary green development concepts. METHODS: The effects of major factors, such as temperature, reaction time, concentration of laccase and the initial concentration of substrate on the removal of substrate were investigated by OFAT approach. After simulated wastewater is treated with enzymes, aniline concentration was determined by N-(1-Naphthyl)ethylene-diamine dihydrochloride spectrophotometric method. Concentration of o-phenylenediamine was determined by ferric ammonium alum spectrophotometric method. RESULTS: For the removal of aniline, the optimum conditions were as follows: 50 °C, initial aniline concentration of 80 mg/L and laccase concentration of 1 g/L. In this case, the total removal of aniline reached 97.1% after 8 h, this also involves the volatilization of aniline itself. The optimum conditions of o-phenylenediamine were as follows: 50 °C, initial concentration of 100 mg/L and laccase concentration of 1 g/L. Under the above condition, the o-phenylenediamine could be removed completely after 60 min. CONCLUSION: The results show that the removal of aniline compounds by laccase from white-rot fungi has good effect and potential application prospect.

12.
Environ Sci Pollut Res Int ; 26(4): 3814-3822, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30539399

RESUMO

Chitosan/Co-Fe-layered double hydroxides (CS/LDHs) were prepared by coprecipitation method, which is a kind of composite material with excellent properties. The structure of CS/LDHs was characterized by SEM, FTIR, and XRD, which proved that chitosan (CS) was successfully induced into hydrotalcite and CS/LDHs still possess the structural characteristics of hydrotalcite. The adsorption of 2,4-dichlorophenol (2,4-DCP) was studied with CS/LDHs and LDHs as adsorbent separately. The activity of immobilized laccase (L-CS/LDHs) with CS/LDHs as carrier is significantly better than that of the one (L-LDHs) using LDHs as carrier. Under the optimum conditions (pH = 6, 55 °C, 48 h), L-CS/LDHs exhibited better removal performance for 2,4-DCP (81.53%, 100 mg/L) than LDHs (63.55%); the removal of 2,4-DCP by L-CS/LDHs is excellent, exceeding 97% as its initial concentration below 60 mg/L. It includes the catalytic action of laccase and dechlorination of Fe3+ and Co2+, and the adsorption can be ignored under the optimal conditions. After 5 cycles, it maintained 67% (L-CS/LDHs) and 54% (L-LDHs) of the original removal.


Assuntos
Hidróxido de Alumínio/química , Quitosana/química , Clorofenóis/análise , Cobalto/química , Poluentes Ambientais/análise , Ferro/química , Hidróxido de Magnésio/química , Adsorção , Enzimas Imobilizadas/química , Lacase/química
13.
Onco Targets Ther ; 11: 7603-7612, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464509

RESUMO

BACKGROUND: High-grade serous ovarian cancer (HGSOC) represents most of the ovarian cancers and accounts for 70%-80 % of related deaths. The overall survival of HGSOC has not been remarkably improved in the past decades, due to the tumor dissemination in peritoneal cavity and invasion of adjacent organs. Therefore, identifying molecular biomarkers is invaluable in helping predicting clinical outcomes and developing targeted chemotherapies. Although there have been studies revealing the prognostic significance of protein tyrosine phosphatase L1 (PTPL1) in breast cancer and lung cancer, its involvement and functions in HGSOC remains to be elucidated. METHODS: We retrospectively enrolled a cohort of HGSOC patients after surgical resection. And analyzed the mRNA and protein levels of PTPL1 in tissue samples. RESULTS: We found that PTPL1 presented a lower expression in HGSOC tissues than in adjacent normal ovarian tissues. Besides, the PTPL1 level was negatively correlated with tumor stage, implying its potential role as a tumor suppressor. Univariate and multivariate analyses identified that patients with higher PTPL1 showed a better overall survival compared to those with lower PTPL1 expression. In addition, cellular experiments confirmed the role of PTPL1 in suppressing tumor proliferation and invasion. Furthermore, we demonstrated that PTPL1 negatively regulated phosphorylation of tyrosine 42 on IκBα (IκBα-pY42). To our knowledge, this is the initial finding on PTPL1 targeting IκBα-pY42 site. Finally, our data indicated that PTPL1 suppressed tumor progression by dephosphorylating IκBα-pY42, which stabilized IκBα and attenuated nucleus translocation of NF-κB. CONCLUSION: Our study revealed a tumor-suppressing role of PTPL1 in HGSOC by targeting IκBα.

14.
Oncol Rep ; 40(4): 2287-2297, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106431

RESUMO

Radiation­induced lung injury (RILI) is a major complication of thoracic radiotherapy that starts as exudative inflammation and proceeds to lung fibrosis, and additional studies are required to develop methods to ameliorate RILI. The aim of this study was to explore whether the nicotinic acetylcholine receptor subtype­7 (α7­nAChR) agonist GTS­21 has a protective effect against RILI. C57BL6 mice were irradiated with 12 Gy to induce a mouse model of RILI. Some of the mice received an i.p. injection of 4 mg/kg GTS­21 for three days with or without radiation treatment. Mice were sacrificed at 1, 3, 7, 14 and 21 days and at 3 and 6 months after irradiation. The results showed that GTS­21 treatment significantly relieved RILI by decreasing TNF­α, IL­1ß and IL­6 production in serum via inhibition of NF­κB activation and downregulation of TLR­4 and HMGB1 expression in the lungs. In addition, we found that GTS­21 may regulate the MMP/TIMP balance in RILI. Finally, we found that GTS­21 inhibited NOX­1 and NOX­2 expression, which subsequently reduced ROS levels and Hif­1α expression in RILI. However, GTS­21 showed little effect on lung tissue without radiation exposure. The results above were also validated in RAW264.7 macrophages. Our results showed that activation of the cholinergic anti­inflammatory pathway via the α7­nAChR agonist GTS­21 reduced RILI. The protective effect of GTS­21 against RILI is partly attributed to inhibition of the HMGB1/TLR4/NF­κB pathway and ROS production. Thus, activation of the α7­nAChR pathway may lead to new possibilities in the therapeutic management of RILI.


Assuntos
Compostos de Benzilideno/farmacologia , Fibrose/tratamento farmacológico , Inflamação/tratamento farmacológico , Lesão Pulmonar/tratamento farmacológico , Agonistas Nicotínicos/farmacologia , Piridinas/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Fibrose/metabolismo , Fibrose/patologia , Inflamação/metabolismo , Inflamação/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia
15.
Mol Immunol ; 80: 33-40, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27825048

RESUMO

CpG-oligodeoxynucleotide (CpG-ODN) is not only reported to protect against airway hyper responsiveness but is also known as a potent vaccine adjuvant for anti-tumor therapy. Little is known about the effect of CpG-ODN in mice with radiation-induced lung fibrosis (RILF), a common late stage form of tissue damage that occurs after thorax radiotherapy (RT). Here, we evaluated the immunomodulatory effects of CpG-ODN on the development of RILF. Mice were divided into four groups: (1) RT, single dose of 12Gy to the whole thorax; (2) CpG, only intraperitoneal injection of CpG-ODN for total 5 weeks; (3) RT+CpG, irradiation plus CpG-ODN treatment before and after irradiation for total 5 weeks; and (4) control (CTL): No RT or CpG-ODN treatment. In this study, we found that CpG-ODN treatment attenuated lung fibrosis and collagen deposition by increasing the number of M1 macrophagocytes, levels of Type-2 cytokines and TGF-ß. CpG-ODN administration up-regulated the expression of TLR9 and STAT1 phosphorylation and reversed the expression of Type-2 immune response key transcription factor GATA-3. Activation of the JAK-STAT1 signaling pathway further enhanced M1 macrophage differentiation and Type-1 cytokine production. This study reveals the mitigating effect of early exposure to CpG-ODN on lung injury caused by irradiation in mice. The potential mechanism of action may be related to enhancement of Type-1 immunity. In conclusion, CpG-ODN may be a potential therapeutic target to treat RILF.


Assuntos
Oligodesoxirribonucleotídeos/farmacologia , Pneumonite por Radiação/imunologia , Receptor Toll-Like 9/biossíntese , Animais , Modelos Animais de Doenças , Feminino , Janus Quinases/efeitos dos fármacos , Janus Quinases/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Pneumonite por Radiação/patologia , Fator de Transcrição STAT1/efeitos dos fármacos , Fator de Transcrição STAT1/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
16.
J Radiat Res ; 57(2): 133-41, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26703457

RESUMO

Lung fibrosis may be associated with Type-2 polarized inflammation. Herein, we aim to investigate whether radiation can initiate a Type-2 immune response and contribute to the progression of pulmonary fibrosis in tumor-bearing animals. We developed a tumor-bearing mouse model with Lewis lung cancer to receive either radiation therapy alone or radiation combined with Th1 immunomodulator unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotide (CpG-ODN). The Type-2 immune phenotype in tumors and the histological grade of lung fibrosis were evaluated in mice sacrificed three weeks after irradiation. Mouse lung tissues were analyzed for hydroxyproline and the expression of Type-1/Type-2 key transcription factors (T-bet/GATA-3). The concentration of Type-1/Type-2 cytokines in serum was measured by cytometric bead array. Lung fibrosis was observed to be more serious in tumor-bearing mice than in normal mice post-irradiation. The fibrosis score in irradiated tumor-bearing mice on Day 21 was 4.33 ± 0.82, which was higher than that of normal mice (2.00 ± 0.63; P < 0.05). Hydroxyproline and GATA-3 expression were increased in the lung tissues of tumor-bearing mice following irradiation. CpG-ODN attenuated fibrosis by markedly decreasing GATA-3 expression. Serum IL-13 and IL-5 were elevated, whereas INF-γ and IL-12 expression were decreased in irradiated tumor-bearing mice. These changes were reversed after CpG-ODN treatment. Thus, Type-2 immunity in tumors appeared to affect the outcome of radiation damage and might be of interest for future studies on developing approaches in which Type-1-related immunotherapy and radiotherapy are used in combination.


Assuntos
Imunidade , Neoplasias Pulmonares/radioterapia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/imunologia , Lesões por Radiação/complicações , Lesões por Radiação/imunologia , Animais , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Imunidade/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/farmacologia , Fenótipo , Fosforilação/efeitos dos fármacos , Fibrose Pulmonar/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Lesões por Radiação/sangue , Indução de Remissão , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Raios X
17.
Cancer Biol Ther ; 16(8): 1194-204, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26054751

RESUMO

Evidences suggest that tumor microenvironment may play an important role in cancer drug resistance. Sphingosine kinase 2 (SphK2) is proposed to be the key regulator of sphingolipid signaling. This study is aimed to investigate whether the combination of molecular targeting therapy using a specific inhibitor of SphK2 (ABC294640), with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can enhance the apoptosis of non-small cell lung cancer (NSCLC) cells. Our results revealed that NSCLC cells' sensitivity to TRAIL is correlated with the level of SphK2. Compared with TRAIL alone, the combination therapy enhanced the apoptosis induced by TRAIL, and knockdown of SphK2 by siRNA presented a similar effect. Combination therapy with ABC294640 increased the activity of caspase-3/8 and up-regulated the expression of death receptors (DR). Additional investigations revealed that translocation of DR4/5 to the cell membrane surface was promoted by adding ABC294640. However, expression of anti-apoptosis proteins such as Bcl(-)2 and IAPs was not significantly modified by this SphK2 inhibitor. Overall, this work demonstrates that SphK2 may contribute to the apoptosis resistance in NSCLC, thus indicating a new therapeutic target for resistant NSCLC cells.


Assuntos
Adamantano/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Adamantano/administração & dosagem , Adamantano/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular/métodos , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Transporte Proteico/efeitos dos fármacos , Piridinas/administração & dosagem , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem
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