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1.
Analyst ; 147(21): 4793-4803, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36189885

RESUMO

To date, several smart stents have been proposed to continuously detect biological cues, which is essential for tracking patients' critical vital signs and therapy. However, the proposed smart stent fabrication techniques rely on conventional laser micro-cutting or 3D printing technologies. The sensors are then integrated into the stent structure using an adhesive, conductive epoxy, or laser micro-welding process. The sensor packaging method using additional fabrication processes can cause electrical noise, and there is a possibility of sensor detachment from the sent structure after implantation, which may pose a significant risk to patients. Herein, we are demonstrating for the first time a single-step fabrication method to develop a smart stent with an integrated sensor for detecting in-stent restenosis and assessing the functional dynamics of the heart. The smart stent is fabricated using a microelectromechanical system (MEMS)-based micromachining technology. The proposed smart stent can detect biological cues without additional power and wirelessly transmit the signal to the network analyzer. The cytocompatibility of the smart stent is confirmed through a cytotoxicity test by monitoring the cell growth, proliferation, and viability of the cultured cardiomyocytes. The capacitance of the smart stent exhibits an excellent linear relationship with the applied pressure. The exceptional sensitivity of the pressure sensor enabled the proposed smart stent to detect biological cues during in vivo analysis. The preliminary findings confirmed the proposed smart stent's higher level of structural integrity, durability and repeatability. Finally, the practical feasibility of the smart stent is demonstrated by monitoring diastole and systole at various beat rates using a phantom. The results of the phantom study showed a similar pattern to the human model, indicating the potential use of the proposed multifunctional smart stent for real-time applications.


Assuntos
Reestenose Coronária , Sistemas Microeletromecânicos , Humanos , Reestenose Coronária/etiologia , Stents
2.
Proc Natl Acad Sci U S A ; 116(25): 12516-12523, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31164420

RESUMO

BACE1 is the rate-limiting enzyme for amyloid-ß peptides (Aß) generation, a key event in the pathogenesis of Alzheimer's disease (AD). By an unknown mechanism, levels of BACE1 and a BACE1 mRNA-stabilizing antisense RNA (BACE1-AS) are elevated in the brains of AD patients, implicating that dysregulation of BACE1 expression plays an important role in AD pathogenesis. We found that nuclear factor erythroid-derived 2-related factor 2 (NRF2/NFE2L2) represses the expression of BACE1 and BACE1-AS through binding to antioxidant response elements (AREs) in their promoters of mouse and human. NRF2-mediated inhibition of BACE1 and BACE1-AS expression is independent of redox regulation. NRF2 activation decreases production of BACE1 and BACE1-AS transcripts and Aß production and ameliorates cognitive deficits in animal models of AD. Depletion of NRF2 increases BACE1 and BACE1-AS expression and Aß production and worsens cognitive deficits. Our findings suggest that activation of NRF2 can prevent a key early pathogenic process in AD.


Assuntos
Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Transtornos Cognitivos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/genética , Transtornos Cognitivos/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Isotiocianatos/farmacologia , Camundongos , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/biossíntese , Regiões Promotoras Genéticas , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Sulfóxidos , Transcrição Gênica
3.
J Korean Med Sci ; 37(42): e306, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36325610

RESUMO

A 43-year-old man presented with cardiac arrest 2 days after the second coronavirus disease 2019 (COVID-19) vaccination with an mRNA vaccine. Electrocardiograms showed ventricular fibrillation and type 1 Brugada pattern ST segment elevation. The patient reported having no symptoms, including febrile sensation. There were no known underlying cardiac diseases to explain such electrocardiographic abnormalities. ST segment elevation completely disappeared in two weeks. Although there were no genetic mutations or personal or family history typical of Brugada syndrome, flecainide administration induced type 1 Brugada pattern ST segment elevation. This case suggests that COVID-19 vaccination may induce cardiac ion channel dysfunction and cause life threatening ventricular arrhythmias in specific patients with Brugada syndrome.


Assuntos
Síndrome de Brugada , COVID-19 , Masculino , Humanos , Adulto , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/etiologia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/etiologia , Vacinas contra COVID-19/efeitos adversos , Eletrocardiografia/efeitos adversos , Vacinação/efeitos adversos , Vacinas de mRNA
4.
J Korean Med Sci ; 37(42): e305, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36325609

RESUMO

BACKGROUND: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. METHODS: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. RESULTS: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. CONCLUSIONS: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.


Assuntos
Serviços Médicos de Emergência , AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Idoso , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/complicações , Hospitalização , República da Coreia , Governo
5.
Analyst ; 146(23): 7160-7167, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34698735

RESUMO

In this study, we developed a multi-layered functional cantilever for real-time force measurement of cardiomyocytes in cell culture media. The functional cantilever with a full-bridge circuit configuration was composed of one polydimethylsiloxane (PDMS) and two polyimide (PI) layers, forming two resistive sensors on each upper side of the two PI layers. The PI layers were chemically bonded using an oxygen plasma treatment, with a thin composite layer consisting of Cr/SiO2/PDMS. These greatly improved the force sensitivity and the long-term reliability of the integrated strain sensor operating in liquids. The nanogrooved PDMS top layer bonded on the upper PI layer was employed to further improve the growth of cardiomyocytes on the functional cantilever. The difference in resistance changes and response characteristics was confirmed by evaluating the characteristics of the multi-layered polymer cantilevers with half-bridge and full-bridge circuit configurations. We also employed the cantilever devices to measure the contraction force of cardiomyocytes for 16 days and side effects in real time in human-induced pluripotent stem cells treated with the cardiovascular drug verapamil. The sensor-integrated cantilever devices are expected to be utilized as a novel biomedical sensor for evaluating the mechanobiology of cardiomyocytes, as well as in drug screening tests.


Assuntos
Polímeros , Dióxido de Silício , Humanos , Fenômenos Mecânicos , Contração Miocárdica , Reprodutibilidade dos Testes
6.
Pacing Clin Electrophysiol ; 44(6): 1133-1136, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33619753

RESUMO

We report a case of cardiac intramural arteriovenous malformations (AVMs) misdiagnosed as hypertrophic cardiomyopathy and presented as life-threatening ventricular arrhythmia storm that was successfully controlled by cardiac sympathetic denervation. A 46-year-old male patient with an implantable cardioverter-defibrillator was admitted for recurrent ventricular tachycardia requiring repeated shock refractory to antiarrhythmic drugs. Although the patient was previously diagnosed with hypertrophic cardiomyopathy, multimodality imaging studies showed large left ventricular intramural AVMs, potentially representing arrhythmogenic substrates. Life-threatening ventricular arrhythmia storm, which could not be controlled by radiofrequency catheter ablation and therapeutic hypothermia. However, cardiac sympathetic denervation surgery successfully controlled the ventricular arrhythmia storm.


Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Imagem Multimodal , Simpatectomia , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/cirurgia , Antiarrítmicos/uso terapêutico , Cardiomiopatia Hipertrófica/diagnóstico , Diagnóstico Diferencial , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade
7.
Cardiovasc Ultrasound ; 19(1): 5, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407517

RESUMO

BACKGROUND: It is unclear whether increased left ventricular (LV) thickness is associated with worse clinical outcomes in severe aortic stenosis (AS). The aim of this study was to determine the effect of increased LV wall thickness (LVWT) on major clinical outcomes in patients with severe AS. METHODS AND RESULTS: This study included 290 severe AS patients (mean age 69.4 ± 11.0 years; 136 females) between January 2008 and December 2018. For outcome assessment, the endpoint was defined as death from all causes, cardiovascular death, and the aortic valve replacement (AVR) surgery rate. During follow-up (48.7 ± 39.0 months), 157 patients had AVR, 43 patients died, and 28 patients died from cardiovascular causes. Patients with increased LVWT underwent AVR surgery much more than those without LVWT (60.0% vs. 39.0%, p < 0.001). Furthermore, in patients with increased LVWT, the all-cause and cardiovascular death rates were significantly lower in the AVR group than in the non-AVR group (8.8% vs. 27.3%, p < 0.001, 4.8%, vs. 21.0%, p < 0.001). Multivariate analysis revealed that increased LVWT, age, dyspnea, and AVR surgery were significantly correlated with cardiovascular death. CONCLUSIONS: In patients with severe AS, increased LVWT was associated with a higher AVR surgery rate and an increased rate of cardiovascular death independent of other well-known prognostic variates. Thus, these findings suggest that increased LVWT might be used as a potential prognostic factor in severe AS patients.


Assuntos
Estenose da Valva Aórtica/diagnóstico , Valva Aórtica/diagnóstico por imagem , Ecocardiografia/métodos , Implante de Prótese de Valva Cardíaca , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular Esquerda/fisiologia , Idoso , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Progressão da Doença , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
8.
Langmuir ; 36(32): 9424-9435, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32659098

RESUMO

Capillary suspensions are ternary solid-liquid-liquid systems produced via the addition of a small amount of secondary fluid to the bulk fluid that contained the dispersed solid particles. The secondary fluid could exert strong capillary forces between the particles and dramatically change the rheological properties of the suspension. So far, research has focused on capillary suspensions that consist of additive-free fluids, whereas capillary suspensions with additives, particularly those of large molecular weight that are highly relevant for industrial purposes, have been relatively less studied. In this study, we performed a systematic analysis of the properties of capillary suspensions that consist of paraffin oil (bulk phase), water (secondary phase), and α-Al2O3 microparticles (particle phase), in which the aqueous secondary phase contained an important eco-friendly polymeric binder, sodium alginate (SA). It was determined that the yield stress of the suspension increased significantly with the increase in the SA content in the aqueous secondary phase, which was attributed to the synergistic effect of the capillary force and hydrogen bonding force that may be related to the increase in the number of capillary bridges. The amounts of SA used to induce a significant change in the yield stress in this study were very small (<0.02% of the total sample volume). The addition of Ca2+ ions to the SA-containing secondary phase further increased the yield stress with possible gelation of the SA chains-in the presence of excess Ca2+ ions, however, the yield stress decreased because of the microscopic phase separation that occurred in the aqueous secondary phase. The microstructures of the sintered porous materials that were produced by using capillary suspensions as precursors were qualitatively well correlated to the rheological behavior of the precursor suspensions, suggesting a new method for the subtle control of the microstructures of porous materials using the addition of minute amounts of polymeric additives.

9.
Cardiovasc Ultrasound ; 17(1): 2, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755201

RESUMO

BACKGROUND: Aortic dilatation is a major risk factor for aortic dissection. The aim of the present study was to assess the relationship between left ventricular (LV) geometry and maximal ascending aorta (MAA). METHODS: We reviewed data from patients who were diagnosed with acute type A aortic dissection and who underwent surgical management from December 2002 to March 2016 at Dong-A University Hospital. Among 151 patients with non-Marfan aortic dissection in the study, 50 who had echocardiography preoperatively were investigated and MAA diameter was analyzed by LV geometric patterns. RESULTS: Patients' mean age was 59.6 ± 13.5 years and 38.0% were male. The mean MAA diameter was 52.9 ± 8.5 mm. MAA diameter was significantly correlated with LV mass index (r = 0.62, P < 0.001). On analysis by LV geometry, MAA diameter showed a significant difference between the 4 groups (P = 0.02), and the eccentric and concentric hypertrophy groups showed significantly larger MAA diameter than the other two groups. CONCLUSION: MAA diameter was associated with LV mass index and was significantly different between LV geometry types. In this study, not only concentric hypertrophy but also eccentric LV hypertrophy was related to larger MAA in type A aortic dissection patients.


Assuntos
Aorta/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Dissecção Aórtica/diagnóstico , Ecocardiografia Doppler/métodos , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Dissecção Aórtica/etiologia , Dissecção Aórtica/fisiopatologia , Aneurisma da Aorta Torácica/fisiopatologia , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
10.
Echocardiography ; 36(6): 1035-1040, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31148208

RESUMO

BACKGROUND: It is unclear whether asymmetry itself plays a role in developing eccentric aortic regurgitation (AR) in patients with tricuspid aortic valve (TAV). The aim of this study was to determine whether an asymmetric aortic valve structure may have association with the development of eccentric AR in patients with TAV. METHODS: Of the 164 410 patients who underwent echocardiography between January 2006 and January 2018 at Dong-A University Hospital, 306 (mean age 69.9 ± 12.6 years; 62% men) eccentric AR were identified. After excluding patients with bicuspid and prolapsed AV, 104 patients who had eccentric AR with TAV were enrolled for the study. Comprehensive echocardiographic AV cusp measurements were compared to those of 104 age- and gender-matched control patients with central AR. RESULTS: In the eccentric and central AR groups, 66 (63.5%) and 48 patients (46.2%) had asymmetric AV, respectively. Mean cusp height was significantly larger in the eccentric AR group than in the central AR group (1.8 ± 0.3 cm vs 1.7 ± 0.2 cm, P = 0002). Furthermore, the mean cusp area and average asymmetry index of the cusp area were also significantly larger in the eccentric AR group than in the central AR group (2.6 ± 0.8 cm2 vs 2.3 ± 0.6 cm2 , P = 0.001, and 7.1 ± 4.5% vs 4.9 ± 2.5%, P < 0.001, respectively). CONCLUSION: AV asymmetry indices of eccentric AR were significantly larger than those of patients with central AR. These data suggest that the presence of asymmetric AV might have association with the development of eccentric AR in patients with TAV.


Assuntos
Insuficiência da Valva Aórtica/diagnóstico por imagem , Valva Aórtica/anormalidades , Ecocardiografia/métodos , Valva Tricúspide/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino
12.
Echocardiography ; 35(11): 1782-1787, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30225938

RESUMO

AIMS: The early diastolic mitral annular velocity (e') and mitral E/e' criteria for clinically evaluating diastolic dysfunction in patients with atrial fibrillation (AF) are almost the same as in patients with sinus rhythm. In this study, we aimed to investigate whether e' is useful to assess diastolic function in AF patients. METHODS: Thirty patients who underwent successful electric cardioversion (EC) due to persistent AF and who maintained sinus rhythm for 1 month after EC were enrolled in this study. Transthoracic echocardiography was performed on all patients before and 1 month after EC. Standard diastolic parameters, the global longitudinal strain (GLS), and left ventricular (LV) twist were measured. RESULTS: Conventional Doppler parameters measured before EC were not significantly different from 1 month after EC. However, the lateral and septal e' were significantly decreased 1 month after EC (from 12.8 ± 2.5 to 9.8 ± 2.3 cm/s and from 9.5 ± 1.9 to 7.1 ± 1.5 cm/s, respectively, P < 0.001). Likewise, the lateral and septal E/e' were also significantly increased 1 month after EC (P < 0.001). The GLS was significantly improved from -15.9 ± 2.2% to -19.4 ± 2.4% after EC (P < 0.001), as was the LV twist (from 5.8 ± 1.7° to 9.1 ± 2.4°, P < 0.001). CONCLUSION: We demonstrated that e' was significantly higher in AF compared with during sinus rhythm in the same patients. Thus, in AF patients, diastolic dysfunction should be suspected even when e' values are normal.


Assuntos
Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Ecocardiografia Transesofagiana/métodos , Cardioversão Elétrica/métodos , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Hepatology ; 64(1): 209-23, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26710118

RESUMO

UNLABELLED: Liver fibrosis is a common outcome of chronic liver disease that leads to liver cirrhosis and hepatocellular carcinoma. No US Food and Drug Administration-approved targeted antifibrotic therapy exists. Activated hepatic stellate cells (aHSCs) are the major cell types responsible for liver fibrosis; therefore, eradication of aHSCs, while preserving quiescent HSCs and other normal cells, is a logical strategy to stop and/or reverse liver fibrogenesis/fibrosis. However, there are no effective approaches to specifically deplete aHSCs during fibrosis without systemic toxicity. aHSCs are associated with elevated expression of death receptors and become sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. Treatment with recombinant TRAIL could be a potential strategy to ameliorate liver fibrosis; however, the therapeutic application of recombinant TRAIL is halted due to its very short half-life. To overcome this problem, we previously generated PEGylated TRAIL (TRAILPEG ) that has a much longer half-life in rodents than native-type TRAIL. In this study, we demonstrate that intravenous TRAILPEG has a markedly extended half-life over native-type TRAIL in nonhuman primates and has no toxicity in primary human hepatocytes. Intravenous injection of TRAILPEG directly induces apoptosis of aHSCs in vivo and ameliorates carbon tetrachloride-induced fibrosis/cirrhosis in rats by simultaneously down-regulating multiple key fibrotic markers that are associated with aHSCs. CONCLUSION: TRAIL-based therapies could serve as new therapeutics for liver fibrosis/cirrhosis and possibly other fibrotic diseases. (Hepatology 2016;64:209-223).


Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono , Avaliação Pré-Clínica de Medicamentos , Hepatócitos/efeitos dos fármacos , Humanos , Injeções Intravenosas , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Ratos Sprague-Dawley , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Regulação para Cima
14.
Nanotechnology ; 28(22): 225201, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28488590

RESUMO

A synaptic transistor emulating the biological synaptic motion is demonstrated using the memcapacitance characteristics in a Pt/HfOx/n-indium-gallium-zinc-oxide (IGZO) memcapacitor. First, the metal-oxide-semiconductor (MOS) capacitor with Pt/HfOx/n-IGZO structure exhibits analog, polarity-dependent, and reversible memcapacitance in capacitance-voltage (C-V), capacitance-time (C-t), and voltage-pulse measurements. When a positive voltage is applied repeatedly to the Pt electrode, the accumulation capacitance increases gradually and sequentially. The depletion capacitance also increases consequently. The capacitances are restored by repeatedly applying a negative voltage, confirming the reversible memcapacitance. The analog and reversible memcapacitance emulates the potentiation and depression synaptic motions. The synaptic thin-film transistor (TFT) with this memcapacitor also shows the synaptic motion with gradually increasing drain current by repeatedly applying the positive gate and drain voltages and reversibly decreasing one by applying the negative voltages, representing synaptic weight modulation. The reversible and analog conductance change in the transistor at both the voltage sweep and pulse operations is obtained through the memcapacitance and threshold voltage shift at the same time. These results demonstrate the synaptic transistor operations with a MOS memcapacitor gate stack consisting of Pt/HfOx/n-IGZO.

15.
Nanotechnology ; 28(28): 285203, 2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28643696

RESUMO

Artificial synaptic potentiation and depression characteristics were demonstrated with Pt/CeO2/Pt devices exhibiting polarity-dependent analog memristive switching. The strong and sequential resistance change with its maximum to minimum ratio >105, imperatively essential for stable operation, as repeating voltage application, emulated the potentiation and depression motion of a synapse with variable synaptic weight. The synaptic weight change could be controlled by the amplitude, width, and number of repeated voltage pulses. The voltage polarity-dependent and asymmetric current-voltage characteristics and consequential resistance change are thought to be due to local inhomogeneity of electrical and physical states of CeO2 such as charging at interface states, valence changes of Ce cations, and so on. These results revealed that the CeO2 layer could be a promising material for analog memristive switching elements with strong resistance change, as an artificial synapse in neuromorphic systems.

16.
Ann Neurol ; 77(3): 504-16, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25558977

RESUMO

OBJECTIVE: Stroke is a leading cause of mortality and disability. The peptidyl-prolyl cis/trans isomerase Pin1 regulates factors involved in cell growth. Recent evidence has shown that Pin1 plays a major role in apoptosis. However, the role of Pin1 in ischemic stroke remains to be investigated. METHODS: We used Pin1 overexpression and knockdown to manipulate Pin1 expression and explore the effects of Pin1 in cell death on ischemic stress in vitro and in a mouse stroke model. We also used Pin 1 inhibitor, γ-secretase inhibitor, Notch1 intracellular domain (NICD1)-deleted mutant cells, and Pin1 mutant cells to investigate the underlying mechanisms of Pin1-NICD1-mediated cell death. RESULTS: Our findings indicate that Pin1 facilitates NICD1 stability and its proapoptotic function following ischemic stroke. Thus, overexpression of Pin1 increased NICD1 levels and enhanced its potentiation of neuronal death in simulated ischemia. By contrast, depletion or knockout of Pin1 reduced the NICD1 level, which in turn desensitized neurons to ischemic conditions. Pin1 interacted with NICD1 and increased its stability by inhibiting FBW7-induced polyubiquitination. We also demonstrate that Pin1 and NICD1 levels increase following stroke. Pin1 heterozygous (+/-) and knockout (-/-) mice, and also wild-type mice treated with an inhibitor of Pin1, each showed reduced brain damage and improved functional outcomes in a model of focal ischemic stroke. INTERPRETATION: These results suggest that Pin1 contributes to the pathogenesis of ischemic stroke by promoting Notch signaling, and that inhibition of Pin1 is a novel approach for treating ischemic stroke.


Assuntos
Apoptose/fisiologia , Isquemia/metabolismo , Neurônios/metabolismo , Peptidilprolil Isomerase/metabolismo , Receptor Notch1/metabolismo , Acidente Vascular Cerebral/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/patologia , Modelos Animais de Doenças , Humanos , Isquemia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptidilprolil Isomerase/antagonistas & inibidores , Peptidilprolil Isomerase/genética , Estabilidade Proteica , Estrutura Terciária de Proteína/fisiologia , Transdução de Sinais/fisiologia , Acidente Vascular Cerebral/tratamento farmacológico
17.
Sensors (Basel) ; 16(6)2016 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-27271619

RESUMO

This paper describes the fabrication and characterization of a wireless pressure sensor for smart stent applications. The micromachined pressure sensor has an area of 3.13 × 3.16 mm² and is fabricated with a photosensitive SU-8 polymer. The wireless pressure sensor comprises a resonant circuit and can be used without the use of an internal power source. The capacitance variations caused by changes in the intravascular pressure shift the resonance frequency of the sensor. This change can be detected using an external antenna, thus enabling the measurement of the pressure changes inside a tube with a simple external circuit. The wireless pressure sensor is capable of measuring pressure from 0 mmHg to 230 mmHg, with a sensitivity of 0.043 MHz/mmHg. The biocompatibility of the pressure sensor was evaluated using cardiac cells isolated from neonatal rat ventricular myocytes. After inserting a metal stent integrated with the pressure sensor into a cardiovascular vessel of an animal, medical systems such as X-ray were employed to consistently monitor the condition of the blood vessel. No abnormality was found in the animal blood vessel for approximately one month. Furthermore, a biodegradable polymer (polycaprolactone) stent was fabricated with a 3D printer. The polymer stent exhibits better sensitivity degradation of the pressure sensor compared to the metal stent.


Assuntos
Técnicas Biossensoriais/instrumentação , Monitorização Fisiológica/instrumentação , Stents , Tecnologia sem Fio/instrumentação , Implantes Absorvíveis , Animais , Desenho de Equipamento , Humanos , Polímeros/química , Ratos , Pressão Venosa/fisiologia
18.
Ann Rheum Dis ; 74(1): 267-74, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24255545

RESUMO

OBJECTIVE: To test the hypothesis that Notch signalling plays a role in the pathogenesis of rheumatoid arthritis (RA) and to determine whether pharmacological inhibition of Notch signalling with γ-secretase inhibitors can ameliorate the RA disease process in an animal model. METHODS: Collagen-induced arthritis was induced in C57BL/6 or Notch antisense transgenic mice by immunisation with chicken type II collagen (CII). C57BL/6 mice were administered with different doses of inhibitors of γ-secretase, an enzyme required for Notch activation, at disease onset or after onset of symptoms. Severity of arthritis was monitored by clinical and histological scores, and in vivo non-invasive near-infrared fluorescence (NIRF) images. Micro-CT was used to confirm joint destruction. The levels of CII antibodies and cytokines in serum were determined by ELISA and bead-based cytokine assay. The expression levels of cytokines were studied by quantitative PCR in rheumatoid synovial fibroblasts. RESULTS: The data show that Notch signalling stimulates synoviocytes and accelerates their production of proinflammatory cytokines and immune responses involving the upregulation of IgG1 and IgG2a. Pharmacological inhibition of γ-secretase and antisense-mediated knockdown of Notch attenuates the severity of inflammatory arthritis, including arthritis indices, paw thickness, tissue damage and neutrophil infiltration, and reduces the levels of active NF-κB, ICAM-1, proinflammatory cytokines and matrix metalloproteinase-3 activity in the mouse model of RA. CONCLUSIONS: These results suggest that Notch is involved in the pathogenesis of RA and that inhibition of Notch signalling is a novel approach for treating RA.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Citocinas/imunologia , Receptores Notch/imunologia , Transdução de Sinais/imunologia , Membrana Sinovial/imunologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Citocinas/efeitos dos fármacos , Dipeptídeos/farmacologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores Notch/antagonistas & inibidores , Receptores Notch/efeitos dos fármacos , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos
19.
Mol Ther ; 22(2): 397-408, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24145554

RESUMO

Among various proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), tumor necrosis factor (TNF)-α plays a pivotal role in the release of other cytokines and induction of chronic inflammation. Even though siRNA has the therapeutic potential, they have a challenge to be delivered into the target cells because of their poor stability in physiological fluids. Herein, we design a nanocomplex of polymerized siRNA (poly-siRNA) targeting TNF-α with thiolated glycol chitosan (tGC) polymers for the treatment of RA. Poly-siRNA is prepared through self-polymerization of thiol groups at the 5' end of sense and antisense strand of siRNA and encapsulated into tGC polymers, resulting in poly-siRNA-tGC nanoparticles (psi-tGC-NPs) with an average diameter of 370 nm. In the macrophage culture system, psi-tGC-NPs exhibit rapid cellular uptake and excellent in vitro TNF-α gene silencing efficacy. Importantly, psi-tGC-NPs show the high accumulation at the arthritic joint sites in collagen-induced arthritis (CIA) mice. Treatment monitoring data obtained by the matrix metalloproteinase 3-specific nanoprobe and microcomputed tomography show that intravenous injection of psi-tGC-NPs significantly inhibits inflammation and bone erosion in CIA mice, comparable to methotrexate (5 mg/kg). Therefore, the availability of psi-tGC-NP therapy that target specific cytokines may herald new era in the treatment of RA.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Quitosana , Inativação Gênica , Nanopartículas , RNA Interferente Pequeno/genética , Compostos de Sulfidrila , Fator de Necrose Tumoral alfa/genética , Animais , Artrite Experimental , Artrite Reumatoide/patologia , Linhagem Celular , Quitosana/química , Modelos Animais de Doenças , Expressão Gênica , Macrófagos/metabolismo , Masculino , Camundongos , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , Compostos de Sulfidrila/química , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
20.
Tohoku J Exp Med ; 235(2): 135-44, 2015 02.
Artigo em Inglês | MEDLINE | ID: mdl-25746157

RESUMO

Coronary artery disease (CAD) is a primary cause of mortality and morbidity in dialysis patients. However, it is difficult to select the proper point for coronary angiographic procedure, because dialysis patients frequently do not display typical symptoms. Vascular calcification (VC) scores of artery or aorta on plain radiographs are associated with CAD events and may be predictive of CAD in dialysis patients. Therefore, we evaluated whether high or meaningful VC scores on plain radiographs are related with the severity of lesions detected by coronary angiography (CAG) in dialysis patients. We retrospectively enrolled dialysis patients who underwent CAG and checked several plain radiographs within one year before or after CAG. Significant VC is defined as high or meaningful VC scores, such as long abdominal aortic calcification and medial artery calcification on feet. Of all 55 patients, 41 patients (74.5%) exhibited significant VC on plain radiographs and 23 patients (41.8%) underwent stent insertion. Among the 23 patients, longer stents were used in 18 patients with significant VC (34.1 ± 19.5 mm vs. 16.6 ± 15.2 mm, P = 0.029). Patients with significant VC showed higher prevalence rate of severe coronary artery calcification (P = 0.007) and diffuse/tubular stenosis (P = 0.012), detected by CAG, than those without significant VC. Thus, high or meaningful VC scores on plain radiographs were associated with the degree of calcification or stenosis detected by CAG. In conclusion, VC scores on plain radiographs may be predictive of calcification or stenosis of coronary artery before CAG in dialysis patients.


Assuntos
Angiografia Coronária , Diálise Renal , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/patologia , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Constrição Patológica , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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