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1.
Sensors (Basel) ; 22(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35270942

RESUMO

Compression therapy is widely used as the gold standard for management of chronic venous insufficiency and venous leg ulcers, and the amount of pressure applied during the compression therapy is crucial in supporting healing. A fibre optic pressure sensor using Fibre Bragg Gratings (FBGs) is developed in this paper to measure sub-bandage pressure whilst removing cross-sensitivity due to strain in the fibre and temperature. The interface pressure is measured by an FBG encapsulated in a polymer and housed in a textile to minimise discomfort for the patient. The repeatability of a manual fabrication process is investigated by fabricating and calibrating ten sensors. A customized calibration setup consisting of a programmable translation stage and a weighing scale gives sensitivities in the range 0.4-1.5 pm/mmHg (2.6-11.3 pm/kPa). An alternative calibration method using a rigid plastic cylinder and a blood pressure cuff is also demonstrated. Investigations are performed with the sensor under a compression bandage on a phantom leg to test the response of the sensor to changing pressures in static situations. Measurements are taken on a human subject to demonstrate changes in interface pressure under a compression bandage during motion to mimic a clinical application. These results are compared to the current gold standard medical sensor using a Bland-Altman analysis, with a median bias ranging from -4.6 to -20.4 mmHg, upper limit of agreement (LOA) from -13.5 to 2.7 mmHg and lower LOA from -32.4 to -7.7 mmHg. The sensor has the potential to be used as a training tool for nurses and can be left in situ to monitor bandage pressure during compression therapy.


Assuntos
Bandagens Compressivas , Úlcera Varicosa , Calibragem , Humanos , Temperatura , Úlcera Varicosa/terapia , Cicatrização
2.
Biochem Cell Biol ; 99(2): 214-222, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32813978

RESUMO

In our study, we explored the effect of astragaloside IV (AgIV) on carboplatin chemotherapy in prostate cancer cell lines in vitro and in vivo. Cell viability assay, colony formation assay, flow cytometry, Western blot, immunohistochemistry, immunofluorescence, and tumor xenograft growth assay were conducted. We found that AgIV significantly decreased the half-maximal inhibitory concentration of carboplatin in prostate cancer cell lines LNCap and PC-3. Moreover, AgIV enhanced the effect of carboplatin in suppressing colony formation and inducing cell apoptosis. A low-dose carboplatin treatment upregulated N-cadherin and Vimentin expression and downregulated E-cadherin expression, but this effect was abolished by combining with AgIV. Carboplatin treatment increased the levels of p-AKT and p-p65 and decreased p-IκBα, but AgIV treatment suppressed this. In addition, AgIV synergized with carboplatin to suppress tumor xenograft growth of PC-3 cells, and decreased pAKT and p-p65 levels in vivo. Our results suggested that AgIV enhanced carboplatin sensitivity in prostate cancer cell lines by suppressing AKT/NF-κB signaling, thus suppressed epithelial-mesenchymal transition induced by carboplatin. Our findings provided a new mechanism for AgIV in overcoming drug resistance of platinum-based chemotherapy and suggested a potential combination therapy of AgIV and carboplatin in prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Carboplatina/farmacologia , NF-kappa B/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos , Camundongos Nus , NF-kappa B/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Tumorais Cultivadas
3.
Sensors (Basel) ; 21(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374272

RESUMO

Daily fetal movement counting based on maternal perception is widely deployed to monitor fetal wellbeing. However, the counting performed by the mother is prone to errors for various reasons. There are limited devices on the market that can provide reliable and automatic counting. This paper presents a prototype of a novel fetal movement monitoring device based on fibre Bragg grating sensors. Deformation of the skin caused by a fetal movement can lead to a change of the strain and stress on the optical fibre sensors, therefore can induce distortions to the breathing pattern of the mother. In the study data was gathered by the sensors through strain measurement and was post-processed using independent component analysis (ICA) and high-pass filtering to show the instances of the fetal movements. Information gathered during user trials with the prototype suggests that the system detects significantly higher numbers of fetus movements than that observed based on the mother's perception. Among the various techniques available for fetal movement monitoring, fibre optic sensing provides many advantages including multiplex capability, flexibility and minimal size, making the concept an attractive solution for reliable monitoring of antenatal fetal movements.

4.
Cell Mol Neurobiol ; 38(2): 507-515, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28488007

RESUMO

This study aimed to investigate the effects of rat anti-mouse interleukin (IL)-6 receptor antibody (MR16-1) on the recovery of cognitive function in stroke mice. Adult male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO). Mice were randomly assigned into three groups: sham group, model group, and MR16-1 group. After the treatment of MR16-1, spatial learning and memory performance of mice were evaluated by the Morris water maze (MWM) and Y-maze tests. Then, brain slices were obtained and infarct volume and neuronal apoptosis were assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining and Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, respectively. Protein expression levels of apoptosis-associated proteins and multiple inflammatory cytokines were determined by Western blot analysis. Real-time quantitative PCR (RT-PCR) was used to examine the mRNA levels of various inflammatory cytokines in brain slices and cerebrospinal fluid (CSF). The results showed that MR16-1 improved performances of stroke mice in MWM and Y-maze tests. Moreover, MR16-1 ameliorated MCAO-induced infarct, neuronal apoptosis, and inflammatory response. Furthermore, MR16-1 promoted the expression of Bcl-2 and inhibited the expression of Bax in stroke mice, which revealed the inhibitory effect of MR16-1 on neuronal apoptosis. IL-6 levels in brain and CSF were both decreased by MR16-1 treatment in stroke mice. MR16-1 ameliorated cognitive dysfunction and apoptosis in stroke mice, involving the inhibition of inflammatory response and pro-apoptotic Bax, and the up-regulation of anti-apoptotic Bcl-2. The data supported that MR16-1 might be a potential therapeutic drug for the treatment of stroke.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Cognição/fisiologia , Receptores de Interleucina-6/antagonistas & inibidores , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Anticorpos Monoclonais/farmacologia , Cognição/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Distribuição Aleatória , Ratos , Receptores de Interleucina-6/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/metabolismo
5.
Med Sci Monit ; 24: 6165-6177, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30181529

RESUMO

BACKGROUND Epilepsy is a complex neurologic disorder with abnormal electrical impulses in the brain. A crucial role of purinergic signalling in the proper working of the nervous system has been reported but much less is known about the modulation of P2X3 purinergic receptors in epilepsy. This study investigated the effect of NF110, a potent P2X3 receptor antagonist, in the rat epilepsy model of pentylenetetrazole (PTZ)-induced kindling. MATERIAL AND METHODS The mean kindling score, motor activity, locomotion, emotional tension, anxiety, discrimination ability, learning, memory, serum neuron-specific enolase (sNSE), hippocampal IL-1ß and TNF-α, thiobarbituric acid-reactive substance (TBARS), catalase (CAT) and reduced glutathione (GSH), and mitochondrial complex I, II, and IV levels of PTZ-kindling animals were assessed. RESULTS The PTZ-kindling animals have shown impaired motor activity, locomotion, discrimination ability, learning, and memory, along with increased emotional tension, anxiety, neuronal damage (increased sNSE), hippocampal pro-inflammatory mediators (increased IL-1ß and TNF-α), oxidative stress (increased TBARS, decreased GSH and CAT), and mitochondrial dysfunction. The administration of NF110 in 3 different doses has significantly and dose-dependently corrected PTZ-kindling-induced impaired behavior, learning, memory, locomotion, motor activity, discrimination ability, neuronal damage, hippocampal inflammation, oxidative stress, and mitochondrial dysfunction. These beneficial effects of NF110 in PTZ-kindling animals were significantly abolished by the administration of the P2X agonist α, ß methylene-ATP. CONCLUSIONS P2X3 receptors play a very important role in kindling epilepsy and further research should be done to design P2X3 modulators for their possible therapeutic benefits in epileptic disorders.


Assuntos
Epilepsia/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Animais , Benzenossulfonatos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Excitação Neurológica , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pentilenotetrazol , Compostos de Fenilureia/farmacologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , Ratos , Ratos Sprague-Dawley
6.
Small ; 13(33)2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28692762

RESUMO

A new approach for fluorescence imaging in optically turbid media centered on the use of nanoscale ultrasound-switchable FRET-based liposome contrast agents is reported. Liposomes containing lipophilic carbocyanine dyes as FRET pairs with emission wavelengths located in the near-infrared window are prepared. The efficacy of FRET and self-quenching for liposomes with a range of fluorophore concentrations is first calculated from measurement of the liposome emission spectra. Exposure of the liposomes to ultrasound results in changes in the detected fluorescent signal, the nature of which depends on the fluorophores used, detection wavelength, and the fluorophore concentration. Line scanning of a tube containing the contrast agents with 1 mm inner diameter buried at a depth of 1 cm in a heavily scattering tissue phantom demonstrates an improvement in image spatial resolution by a factor of 6.3 as compared with images obtained in the absence of ultrasound. Improvements are also seen in image contrast with the highest obtained being 9% for a liposome system containing FRET pairs. Overall the results obtained provide evidence of the potential the nanoscale ultrasound-switchable FRET-based liposomes studied here have for in vivo fluorescence imaging.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Raios Infravermelhos , Lipossomos/química , Nanopartículas/química , Nefelometria e Turbidimetria , Imagem Óptica , Ultrassom , Corantes Fluorescentes/química , Imagens de Fantasmas , Espectrometria de Fluorescência
7.
J Food Sci Technol ; 52(3): 1724-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25745247

RESUMO

S-allyl-L-cysteine (SAC) is a bioactive compound in garlic (Allium sativum). A novel process including soaking and homogeneous reaction was applied for the effective production of SAC with endogenous γ-glutamyltranspeptidase (γ-GTP, EC 2.3.2.2) in garlic. The effects of temperature and CaCl2 concentration on γ-GTP activity in soaking, and the relationship of SAC production with γ-GTP activity in homogeneous reaction were investigated, using fresh garlic as raw material. The experimental results showed that the γ-GTP in fresh garlic was activated by soaking. The yield rate and the final content of SAC increased linearly with increasing initial γ-GTP activity in the homogeneous reaction at 37 °C. The final SAC content reached 606.3 µg/g (i.e. 32 times higher than that in fresh garlic) after soaking for 72 h in a 10-mM CaCl2 solution at 10 °C, and the homogeneous reaction for 8 h at 37 °C. SAC was produced effectively through the homogeneous reaction with activated endogenous γ-GTP in garlic.

8.
BMC Complement Altern Med ; 14: 127, 2014 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-24708627

RESUMO

BACKGROUND: Angiopoietin (Ang) is one of the major effectors of angiogenesis, playing a critical role in neurovascular remodeling after stroke. Acupuncture has been widely used for treating stroke in China for a long time. Recently, we have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on the expression of Ang-1 and Ang-2 in the brain after ICH. METHODS: ICH was induced by stereotactic injection of collagenase type VII into the right globus pallidus. Adult male Sprague-Dawley rats were randomized into the following four groups: sham-operation (SHAM), stroke-no electroacupuncture (SNE), stroke-EA at the Zusanli acupoint (SEZ), and stroke-EA at a nonacupoint (SEN). EA was applied to the bilateral Zusanli (ST36) acupoint in the SEZ group and a nonacupoint in the SEN group. The expression of Ang-1 and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Some Ang-1 and Ang-2 immunoreactive microvessels with a dilated outline were detected in the perihematomal tissues after ICH, and the vessels extended into the clot from the surrounding area since day 7. The expression of Ang-1 increased notably as long as 2 weeks after ICH, while Ang-2 immunoreactivity declined at about 7 days following a striking upregulation at 3 days. EA at the Zusanli (ST36) acupoint upregulated the expression of Ang-1 and Ang-2 at both the protein and mRNA levels. However, EA at a nonacupoint had little effect on the expression of Ang-1 and Ang-2. CONCLUSIONS: Our data suggest that EA at the Zusanli (ST36) acupoint exerts neuroprotective effects on hemorrhagic stroke by upregulation of Ang-1 and Ang-2.


Assuntos
Angiopoietina-1/genética , Angiopoietina-2/genética , Lesões Encefálicas/terapia , Eletroacupuntura , Pontos de Acupuntura , Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Animais , Encéfalo/metabolismo , Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , China , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
9.
Nanomaterials (Basel) ; 13(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36770378

RESUMO

Absorption-dominated electromagnetic interference (EMI) shielding is attained by improving impedance matching and conductivity through structural design. Polyvinylidene fluoride (PVDF)-Ti3C2Tx MXene-single-walled carbon nanotubes (SWCNTs) composites with layered heterogeneous conductive fillers and segregated structures were prepared through electrostatic flocculation and hot pressing of the PVDF composite microsphere-coated MXene and SWCNTs in a layer-by-layer fashion. Results suggest that the heterogeneous fillers improve impedance matching and layered coating, and hot compression allows the MXene and SWCNTs to form a continuous conducting network at the PVDF interface, thereby conferring excellent conductivity to the composite. The PVDF-MXene-SWCNTs composite showed a conductivity of 2.75 S cm-1 at 2.5% MXene and 1% SWCNTs. The EMI shielding efficiency (SE) and contribution from absorption loss to the total EMI SE of PVDF-MXene-SWCNTs were 46.1 dB and 85.7%, respectively. Furthermore, the PVDF-MXene-SWCNTs composite exhibited excellent dielectric losses and impedance matching. Therefore, the layered heteroconductive fillers in a segregated structure optimize impedance matching, provide excellent conductivity, and improve absorption-dominated electromagnetic shielding.

10.
Nanoscale Adv ; 5(14): 3549-3574, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37441247

RESUMO

Electromagnetic interference (EMI) is a pervasive and harmful phenomenon in modern society that affects the functionality and reliability of electronic devices and poses a threat to human health. To address this issue, EMI-shielding materials with high absorption performance have attracted considerable attention. Among various candidates, two-dimensional MXenes are promising materials for EMI shielding due to their high conductivity and tunable surface chemistry. Moreover, by incorporating magnetic and conductive fillers into MXene/polymer composites, the EMI shielding performance can be further improved through structural design and impedance matching. Herein, we provide a comprehensive review of the recent progress in MXene/polymer composites for absorption-dominated EMI shielding applications. We summarize the fabrication methods and EMI shielding mechanisms of different composite structures, such as homogeneous, multilayer, segregated, porous, and hybrid structures. We also analyze the advantages and disadvantages of these structures in terms of EMI shielding effectiveness and the absorption ratio. Furthermore, we discuss the roles of magnetic and conductive fillers in modulating the electrical properties and EMI shielding performance of the composites. We also introduce the methods for evaluating the EMI shielding performance of the materials and emphasize the electromagnetic parameters and challenges. Finally, we provide insights and suggestions for the future development of MXene/polymer composites for EMI shielding applications.

11.
Mol Genet Genomic Med ; 8(10): e1410, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32735081

RESUMO

BACKGROUND: Tuberous sclerosis complex (TSC), belongs to autosomal dominant genetic disorder, which affects multiple organ systems in the body, including the skin, brain, lungs, kidneys, liver, and eyes. Mutations in TSC1 or TSC2 was proved to be associated with these conditions. METHODS: Gene-panel Sequence of NGS was used to detect the mutation in a Chinese family. The research further investigates whether aberrant splicing and nonsense-mediated mRNA degradation (NMD) could serve as a mechanism cause by TSC1 mutation. MINI-Gene assay apply by pcMINI-TSC1wt/mut plasmids delivered in HeLa and 293T cell lines. Recombinant plasmids expressing wild-type and mutant-type EGFP-TSC1 were constructed and transiently transfected into human embryonic kidney cells 293T by lipofectamine. Real-time PCR and Western Blot were performed to analyze the expression of mRNAs and proteins of EGFP-TSC1 and NMD factor UPF1. RESULTS: The gene test verified a novel heterozygous TSC1 frameshift mutation (TSC1 c.1550_1551del) in the proband and her mother. From MINI-Gene assay, the agarose gel showed that both the mutant and wild-type mRNA possess two main bands, indicating two splicing modes, named band A and B, respectively. The mutation c.1550_1551del has not produced new splicing site, but there is a selective splicing in varying degree significantly after mutation. On the contrary, function validation assay showed that cells transfected with the mutant TSC1 plasmids expressed significantly lower TSC1 in mRNAs and proteins levels, compared with the wild-type TSC1 plasmid transfection. A translation inhibitor cycloheximide and small interfering RNA of UPF1 (siRNA-UPF1) increased mRNA or protein expression of TSC1 significantly in cells transfected with the mutant plasmids. CONCLUSION: Our study demonstrated that the novel TSC1 frameshift mutation (TSC1 c.1550_1551del) trigger aberrant splicing and NMD simultaneously, causing decrease of hamartin, then, leading to tuberous sclerosis complex formation.


Assuntos
Degradação do RNAm Mediada por Códon sem Sentido , Splicing de RNA , Proteína 1 do Complexo Esclerose Tuberosa/genética , Esclerose Tuberosa/genética , Adulto , Feminino , Mutação da Fase de Leitura , Células HEK293 , Células HeLa , Humanos , Linhagem , RNA Helicases/genética , RNA Helicases/metabolismo , Transativadores/genética , Transativadores/metabolismo , Esclerose Tuberosa/patologia , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo
12.
Sleep Med ; 72: 1-4, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32502844

RESUMO

OBJECTIVE: To evaluate sleep disturbances of Chinese frontline medical workers (FMW) under the outbreak of coronavirus disease 2019 (COVID-19), and make a comparison with non-FMW. METHODS: The medical workers from multiple hospitals in Hubei Province, China, volunteered to participate in this cross-sectional study. An online questionnaire, including Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS) and Visual Analogue Scale (VAS), was used to evaluate sleep disturbances and mental status. Sleep disturbances were defined as PSQI>6 points or/and AIS>6 points. We compared the scores of PSQI, AIS, anxiety and depression VAS, as well as prevalence of sleep disturbances between FMW and non-FMW. RESULTS: A total of 1306 subjects (801 FMW and 505 non-FMW) were enrolled. Compared to non-FMW, FMW had significantly higher scores of PSQI (9.3 ± 3.8 vs 7.5 ± 3.7; P < 0.001; Cohen's d = 0.47), AIS (6.9 ± 4.3 vs 5.3 ± 3.8; P < 0.001; Cohen's d = 0.38), anxiety (4.9 ± 2.7 vs 4.3 ± 2.6; P < 0.001; Cohen's d = 0.22) and depression (4.1 ± 2.5 vs 3.6 ± 2.4; P = 0.001; Cohen's d = 0.21), as well as higher prevalence of sleep disturbances according to PSQI > 6 points (78.4% vs 61.0%; relative risk [RR] = 1.29; P < 0.001) and AIS > 6 points (51.7% vs 35.6%; RR = 1.45; P < 0.001). CONCLUSION: FMW have higher prevalence of sleep disturbances and worse sleep quality than non-FMW. Further interventions should be administrated for FMW, aiming to maintain their healthy condition and guarantee their professional performance in the battle against COVID-19.


Assuntos
Ansiedade/epidemiologia , Infecções por Coronavirus/epidemiologia , Depressão/epidemiologia , Pessoal de Saúde/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Adulto , Ansiedade/psicologia , Betacoronavirus , COVID-19 , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Depressão/psicologia , Surtos de Doenças , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Pandemias , Prevalência , SARS-CoV-2 , Fatores Sexuais , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , Escala Visual Analógica
13.
J Imaging ; 5(11)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34460506

RESUMO

The spatial resolution and light detected in fluorescence imaging for small animals are limited by light scattering, absorption and autofluorescence. To address this, novel near-infrared fluorescent contrast agents and imaging configurations have been investigated. In this paper, the influence of the light wavelength and imaging configurations (full-field illumination system and scanning system) on fluorescence imaging are compared quantitatively. The surface radiance for both systems is calculated by modifying the simulation tool Near-Infrared Fluorescence and Spectral Tomography. Fluorescent targets are embedded within a scattering medium at different positions. The surface radiance and spatial resolution are obtained for emission wavelengths between 620 nm and 1000 nm. It was found that the spatial resolution of the scanning system is independent of the tissue optical properties, whereas for full-field illumination, the spatial resolution degrades at longer wavelength. The full width at half maximum obtained by the scanning system is 25% lower than that obtained by the full-field illumination system when the targets are located in the middle of the phantom. The results indicate that although imaging at near-infrared wavelength can achieve a higher surface radiance, it may produce worse spatial resolution.

14.
Biomed Pharmacother ; 97: 1501-1513, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29793313

RESUMO

Epilepsy is a common and devastating neurological disorder. Inflammatory processes and apoptosis in brain tissue have been reported in human epilepsy. Scoparone (6,7-dimethoxycoumarin) is an important chemical substance, which has multiple beneficial activities, including antitumor, anti-inflammatory and anti-coagulant properties. In our present study, we attempted to investigate if scoparone could attenuate seizures-induced blood brain barrier breakdown, inflammation and apoptosis. Pilocarpine (Pilo) and methylscopolamine were used to establish acute seizure animal model. Scoparone suppressed the leakage of blood brain barrier, inflammation and apoptosis. In hippocampus and cortex, the expression of inflammation-associated molecules, such as chemokine (CXC motif) ligand 1 (CXCL-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-6, hypoxia-inducible factor 1α (HIF-1α), and monocyte chemoattractant protein-1 (MCP-1), were reduced by scoparone through inactivating toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) pathway. Scoparone reduced apoptotic levels in hippocampus by TUNEL analysis, along with decreased Caspase-3 and PARP cleavage. In addition, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway in Pilo-induced acute seizures was also inactivated by scoparone. In vitro, we confirmed that scoparone inhibited LPS-caused astrocytes activation as proved by the reduced glial fibrillary acidic protein (GFAP) levels, inflammation and apoptosis, which were at least partly dependent on AKT suppression. The results above indicated that scoparone could relieve pilocarpine (Pilo)-induced seizures against neural cell inflammation and apoptosis.


Assuntos
Cumarínicos/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Cumarínicos/farmacologia , Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Pilocarpina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Convulsões/enzimologia , Convulsões/patologia , Receptor 4 Toll-Like/metabolismo
15.
Turk Neurosurg ; 28(2): 241-247, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27943229

RESUMO

AIM: Angiogenesis occurs after intracerebral hemorrhage (ICH). Hypoxia-inducible factor-1? (HIF-1?) is a critical regulator of angiogenesis. However, its role in the central nervous system remains controversial. 2-Methoxyestradiol (2ME2), a natural metabolite of estrogen, is known to inhibit HIF-1?. In the present study, we investigated the effect of 2ME2 in a rat model of ICH-induced angiogenesis. MATERIAL AND METHODS: Sprague-Dawley male rats (n=50) were randomly divided into 5 groups: Sham operated group; ICH; ICH+2ME2; and ICH+Vehicle groups. ICH model was induced by stereotactic injection of collagenase type VII into the right globus pallidus. 2ME2 or vehicle (10% dimethyl sulfoxide) was administered intraperitoneally 10 min after ICH. Angiogenesis and expression of HIF-1? was evaluated by immunohistochemistry, quantitative real time-reverse transcription polymerase chain reaction and western blot, respectively. RESULTS: Proliferating cell nuclear antigen (PCNA)-labeled nuclei were detected in cerebral endothelial cells (ECs) around the hematoma. The labeling peaked at 14 days post-ICH. HIF-1?-immunoreactive microvessels with dilated outline were detected in the perihematomal tissues. The vessels extended into the clot from the surrounding tissues from day 7 onwards. HIF-1? protein levels increased, while no change was observed in HIF-1? mRNA expression after ICH. 2ME2 decreased the PCNA-labeled nuclei in cerebral ECs and down-regulated the expression of HIF-1? protein as well, while it had little effect on the mRNA expression of HIF-1?. CONCLUSION: HIF-1? inhibitor, 2ME2, inhibited post-ICH angiogenesis by suppressing HIF-1? expression, thus exerting detrimental effects in ICH.


Assuntos
Hemorragia Cerebral/patologia , Estradiol/análogos & derivados , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Neovascularização Fisiológica/efeitos dos fármacos , 2-Metoxiestradiol , Animais , Estradiol/farmacologia , Imuno-Histoquímica , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
16.
J Neurosurg ; 129(3): 732-739, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29076782

RESUMO

OBJECTIVE Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH. METHODS ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[ N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats' brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively. RESULTS Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH. CONCLUSIONS Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.


Assuntos
Astrócitos/fisiologia , Hemorragia Cerebral/fisiopatologia , Modelos Animais de Doenças , Gliose/fisiopatologia , Receptor Notch1/fisiologia , Transdução de Sinais/fisiologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Hemorragia Cerebral/patologia , Dipeptídeos/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Proteína Jagged-1/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
17.
Exp Ther Med ; 14(3): 2329-2334, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28962163

RESUMO

The aim of the present study was to investigate the roles of microRNA (miR)-138 and interferon-stimulated gene 15 (ISG15) in patients with oral squamous cell carcinoma (OSCC). miR-138 and ISG15 expression in cancer tissues was detected, and the influence on proliferation, migration and invasion of OSCC cell lines was assessed. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the expression of miR-138 and ISG15 in resected cancer tissues and pericancerous tissues harvested from patients with OSCC. The protein level of ISG15 was determined via western blot analysis. The constructed pGCMV/EGFP/miR-138 plasmid was transfected into CAL27 and SCC-15 OSCC cell lines via a liposome method to upregulate miR-138 expression. The transfection efficiency was determined based on miR-138 expression levels, and changes in proliferation, migration and invasion were subsequently compared with those in untransfected cells. The expression of ISG15 mRNA and protein was also detected in OSCC cells. miR-138 was significantly downregulated (P<0.05) in cancer tissues compared with adjacent normal tissues in patients with OSCC, whereas ISG15 mRNA expression levels were significantly higher in pericancerous tissues (P<0.05). ISG15 protein levels were also significantly higher in pericancerous tissues (P<0.05). ISG15 protein and mRNA levels were significantly decreased in the transfected cells compared with the untransfected cells, which indicated that miR-138 overexpression inhibited ISG15 expression. Additionally, the invasion, migration and proliferation abilities of successfully transfected CAL27 and SCC-15 cells were significantly decreased compared with the untransfected cells (P<0.05). The results of the present study suggest that miR-138 functions as a tumor-suppressive miR and serves an important role in OSCC via regulating ISG15 expression. These findings suggest that miR-138 is able to inhibit the proliferation, migration and invasion of OSCC cell lines.

18.
J Neurotrauma ; 34(8): 1658-1665, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-27825285

RESUMO

Reactive astrogliosis has occurred after intracerebral hemorrhage (ICH). Leukemia inhibitory factor (LIF) can act as a modulator for glial gene expression. Signal transducer and activator of transcription 3 (STAT3) is a critical regulator of reactive astrogliosis. The present study tested whether endogenous LIF acted on ICH-induced reactive astrogliosis via the STAT3 signaling pathway. Rats were divided into three experimental groups: 1) Rats received either an ICH or a needle insertion (sham), 2) Rats received 100 ng LIF or an equal volume of phosphate-buffered saline (PBS) by direct infusion into the lateral ventricle (LV) after ICH, and 3) AG490 (0.25 mg/kg) was injected into the LV to block STAT3 signaling. Brains were perfused to identify proliferating cell nuclear antigen (PCNA)+/glial fibrillary acidic protein (GFAP)+nuclei. The expression of GFAP, LIF, LIF receptor (LIFR), glycoprotein 130 (gp130), and phospho-STAT3 (p-STAT3) was evaluated by immunohistochemistry and Western blot, respectively. After ICH, the number of the PCNA+/GFAP+ nuclei and the expression of GFAP, LIF, LIFR, gp130, and p-STAT3 were increased. Moreover, LIF increased the number of PCNA+/GFAP+ nuclei and the expression of GFAP, LIFR, gp130, and p-STAT3. The number of PCNA+/ GFAP+ nuclei and GFAP protein levels were attenuated markedly after inhibition of p-STAT3. Together, these data suggest that LIF contributes to ICH-related reactive astrogliosis via activation of STAT3 signaling.


Assuntos
Hemorragia Cerebral/metabolismo , Gliose/metabolismo , Fator Inibidor de Leucemia/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Tirfostinas/administração & dosagem , Tirfostinas/farmacologia
19.
Brain Res ; 1642: 131-135, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27017961

RESUMO

The present study aimed to investigate the therapeutic effect of curcumin on hypertension and its putative mechanisms in the cerebral microcirculation. The surgical preparation was made to generate a cranial window for observation of the capillary network in the cerebral cortex region. Digital image processing, intravital videomicroscopy, and laser Doppler flow meter were used in this investigation. The number of open capillaries, arterial blood pressure, red cell velocity, microvascular diameter, circulating endothelial cells, relative blood flow and frequency were determined. Control rats showed severe dysfunction in the microcirculation with increased blood pressure. In curcumin treated mice, the blood pressure significantly reduced compared to their respective controls. Curcumin significantly increased blood velocity and LDF flow in hypertensive and normotensive rats. Curcumin significantly altered the circulating endothelial cells and open capillaries number in the male albino rats. Our results suggested that the curcumin exerts its therapeutic effect in male albino rats by regulating vasomotion function, increasing blood perfusion, releasing the peripheral resistance and opening efficiently capillaries. Taking all these data together, it is concluded that the curcumin might be useful in the regulation of the cerebral microcirculatory function and hypertension.


Assuntos
Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/efeitos dos fármacos , Curcumina/administração & dosagem , Microvasos/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Córtex Cerebral/fisiologia , Células Endoteliais/metabolismo , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Masculino , Microvasos/fisiologia , Ratos , Ratos Wistar
20.
PLoS One ; 11(7): e0159742, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27467748

RESUMO

A new imaging contrast agent is reported that provides an increased fluorescent signal upon application of ultrasound (US). Liposomes containing lipids labelled with pyrene were optically excited and the excimer fluorescence emission intensity was detected in the absence and presence of an ultrasound field using an acousto-fluorescence setup. The acousto-fluorescence dynamics of liposomes containing lipids with pyrene labelled on the fatty acid tail group (PyPC) and the head group (PyPE) were compared. An increase in excimer emission intensity following exposure to US was observed for both cases studied. The increased intensity and time constants were found to be different for the PyPC and PyPE systems, and dependent on the applied US pressure and exposure time. The greatest change in fluorescence intensity (130%) and smallest rise time constant (0.33 s) are achieved through the use of PyPC labelled liposomes. The mechanism underlying the observed increase of the excimer emission intensity in PyPC labelled liposomes is proposed to arise from the "wagging" of acyl chains which involves fast response and requires lower US pressure. This is accompanied by increased lipid lateral diffusivity at higher ultrasound pressures, a mechanism that is also active in the PyPE labelled liposomes.


Assuntos
Meios de Contraste , Fluorescência , Lipossomos , Ultrassom , Acústica , Nanopartículas , Espectrometria de Fluorescência
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