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3.
Artigo em Inglês | MEDLINE | ID: mdl-38047907

RESUMO

Cation incorporation emerges as a promising approach for improving the performance of the kesterite Cu2ZnSn(S,Se)4 (CZTSSe) device. Herein, we report indium (In) doping using the chemical bath deposition (CBD) technique to enhance the optoelectronic properties of CZTSSe thin-film solar cells (TFSCs). To incorporate a small amount of the In element into the CZTSSe absorber thin films, an ultrathin (<10 nm) layer of In2S3 is deposited on soft-annealed precursor (Zn-Sn-Cu) thin films prior to the sulfo-selenization process. The successful doping of In improved crystal growth and promoted the formation of larger grains. Furthermore, the CZTSSe TFSCs fabricated with In doping exhibited improved device performance. In particular, the In-CZTSSe-2-based device showed an improved power conversion efficiency (PCE) of 9.53%, open-circuit voltage (Voc) of 486 mV, and fill factor (FF) of 61% compared to the undoped device. Moreover, the small amount of In incorporated into the CZTSSe absorber demonstrated reduced nonradiative recombination, improved carrier separation, and enhanced carrier transport properties. This study suggests a simple and effective way to incorporate In to achieve high efficiency and low Voc loss.

4.
Sci Rep ; 13(1): 11583, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37463950

RESUMO

In grafted apple, rootstock-derived signals influence scion cold tolerance by initiating physiological changes to survive over the winter. To understand the underlying molecular interactions between scion and rootstock responsive to cold, we developed transcriptomics and metabolomics data in the stems of two scion/rootstock combinations, 'Gala'/'G202' (cold resistant rootstock) and 'Gala'/'M9' (cold susceptible rootstock). Outer layers of scion and rootstock stem, including vascular tissues, were collected from the field-grown grafted apple during the winter. The clustering of differentially expressed genes (DEGs) and gene ontology enrichment indicated distinct expression dynamics in the two graft combinations, which supports the dependency of scion cold tolerance on the rootstock genotypes. We identified 544 potentially mobile mRNAs of DEGs showing highly-correlated seasonal dynamics between scion and rootstock. The mobility of a subset of 544 mRNAs was validated by translocated genome-wide variants and the measurements of selected RNA mobility in tobacco and Arabidopsis. We detected orthologous genes of potentially mobile mRNAs in Arabidopsis thaliana, which belong to cold regulatory networks with RNA mobility. Together, our study provides a comprehensive insight into gene interactions and signal exchange between scion and rootstock responsive to cold. This will serve for future research to enhance cold tolerance of grafted tree crops.


Assuntos
Malus , Malus/genética , Malus/metabolismo , RNA/metabolismo , Perfilação da Expressão Gênica , Metabolômica , Genótipo
5.
Eur Heart J Cardiovasc Pharmacother ; 9(5): 421-426, 2023 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-37291702

RESUMO

AIMS: Atrial fibrillation (AF) is linked to an increased risk of dementia, even in stroke-free patients. The impact of statin therapy on dementia risk is unclear in AF patients receiving oral anticoagulant (OAC) (vitamin K antagonist and direct-acting OAC). We sought to investigate the impact of statin therapy on dementia risk in AF patients receiving OAC. METHODS AND RESULTS: Using the Korean National Health Insurance Service database, 91 018 non-valvular AF (NVAF) patients from January 2013 to December 2017 were included in the analysis. Of the total, 17 700 patients (19.4%) were in the statin therapy group, and 73 318 patients (80.6%) were in the non-statin therapy group. The primary endpoint was the occurrence of dementia. The median duration of follow-up was 2.1 years. Statin therapy was associated with a significantly lower dementia risk than non-statin therapy for CHA2DS2-VASc scores ≥2 (hazard ratio = 0.77, 95% confidence interval 0.64-0.90, P = 0.026) in NVAF patients receiving OAC. The statin therapy group had a significantly lower dementia risk in a dose-dependent relationship compared with the non-statin therapy group (P for trend <0.001). CONCLUSION: In NVAF patients who received OAC, statin therapy lowered the dementia risk compared with no statin therapy. Furthermore, statin therapy is associated with a dose-dependent reduction in dementia risk.


Assuntos
Fibrilação Atrial , Demência , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Inibidores do Fator Xa , Demência/diagnóstico , Demência/epidemiologia , Demência/prevenção & controle
6.
Front Cardiovasc Med ; 10: 1021277, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36815018

RESUMO

Background: The relationship between elevated serum uric acid (SUA) levels and cardiovascular outcomes after stent implantation remains uncertain. This study sought to evaluate the impact of SUA on 12-month cardiovascular outcomes after stent implantation. Methods: We performed a retrospective study of patients who successfully underwent stent implantation and enrolled 3,222 patients with coronary artery disease (CAD) from a single center. SUA levels were measured before stent implantation. The patients were divided into six groups (<4, 4-4.9, 5-5.9, 6-6.9, 7-7.9 and ≥ 8 mg/dL) at SUA intervals of 1.0 mg/dL. The incidence of cardiovascular outcomes in the six groups was monitored for 1 year after stent implantation and the hazard ratios were estimated. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular outcomes were estimated using a Cox proportional hazard regression analysis. The primary endpoint was all-cause death. The secondary endpoint was a composite of all-cause death, myocardial infarction, target vessel revascularization, stent thrombosis and stroke. The follow-up duration was 12 months. Results: Over the 12-month follow-up period, there were 101 all-cause deaths and 218 MACCE. After adjustment for several parameters, the group with SUA levels of more than or equal to 8 mg/dL had significantly higher hazard ratios in the incidence of all-cause death or MACCE. The group with <4.0 mg/dL had significantly higher hazard ratios in all-cause death only in male patients. In contrast, there were no significant differences observed for cardiovascular outcomes in female patients. Conclusions: Our study identified a U-shaped association between SUA levels and cardiovascular outcomes during 12-month follow-up for males, but not for females. Further studies are warranted to clarify the sex differences between SUA levels and clinical outcomes.

7.
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
8.
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
9.
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
10.
ACS Appl Mater Interfaces ; 14(18): 20866-20874, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35499459

RESUMO

Copper (Cu) is present not only in the electrode for inverted-structure halide perovskite solar cells (PSCs) but also in transport layers such as copper iodide (CuI), copper thiocyanate (CuSCN), and copper phthalocyanine (CuPc) alternatives to spiro-OMeTAD due to their improved thermal stability. While Cu or Cu-incorporated materials have been effectively utilized in halide perovskites, there is a lack of thorough investigation on the direct reaction between Cu and a perovskite under thermal stress. In this study, we investigated the thermal reaction between Cu and a perovskite as well as the degradation mechanism by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Kelvin probe force microscopy (KPFM). The results show that high temperatures of 100 °C induce Cu to be incorporated into the perovskite lattice by forming "Cu-rich yet organic A-site-poor" perovskites, (CuxA1-x)PbX3, near the grain boundaries, which result in device performance degradation.

11.
J Cardiovasc Dev Dis ; 9(5)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35621871

RESUMO

(1) Background: Limited data exist on the safety and efficacy of epicardial left ventricular (LV) lead placement using video-assisted thoracoscopic surgery (VATS) for cardiac resynchronization therapy (CRT). (2) Methods: Acute and post-discharge outcomes of CRT were compared between patients with epicardial LV leads (Epicardial-LV group, n = 13) and those with endocardial LV leads (Endocardial-LV group, n = 243). (3) Results: Epicardial LV leads were implanted via VATS alone (n = 8) or along with mini-thoracotomy (n = 5), for failed endocardial implantation (n = 11) or recurrent lead dislodgement (n = 2). All epicardial procedures under general anesthesia with one-lung ventilation were successfully completed in 1.0 ± 0.4 h without phrenic nerve stimulation. LV pacing thresholds in the epicardial-LV (1.5 ± 1.0 V) and endocardial-LV (1.3 ± 0.8 V) were comparable (p = 0.651). All patients were discharged alive post-VATS 8.8 ± 3.9 days. During the follow-up (34.3 ± 28.6 months), all patients with epicardial LV leads stayed alive except for one cardiac death post-CRT 14 months and one heart transplantation post-CRT 30 months. All epicardial LV leads maintained stable performance without dislodgement/significant changes in pacing threshold/impedance. LV lead dislodgement occurred only in endocardial-LV (7/243, 2.9%). Efficacy in both groups was comparable in terms of QRS narrowing, increase in LV ejection fraction, and survival free of cardiac death, or heart-failure-related hospitalization. (4) Conclusions: Epicardial LV lead placement using VATS can be a safe and effective alternative to endocardial implantation, with comparable acute and post-discharge outcomes achieved by both approaches.

12.
Korean Circ J ; 52(7): 513-526, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35491480

RESUMO

BACKGROUND AND OBJECTIVES: Atrial tachycardias (ATs) from noncoronary aortic cusp (NCC) uncovered after radiofrequency ablation for atrial fibrillation (AF) are rarely reported. This study was conducted to investigate the prevalence and clinical characteristics of NCC ATs detected during AF ablation and compare their characteristics with de novo NCC ATs without AF. METHODS: Consecutive patients who underwent radiofrequency catheter ablation for AF were reviewed from the multicenter AF ablation registry of 11 tertiary hospitals. The clinical and electrophysiological characteristics of NCC AT newly detected during AF ablation were compared with its comparators (de novo NCC AT ablation cases without AF). RESULTS: Among 10,178 AF cases, including 1,301 redo ablation cases, 8 (0.08%) NCC AT cases were discovered after pulmonary vein isolation (PVI; 0.07% in first ablation and 0.15% in redo ablation cases). All ATs were reproducibly inducible spontaneously or with programmed atrial stimulation without isoproterenol infusion. The P-wave morphological features of tachycardia were variable depending on the case, and most cases exhibited 1:1 atrioventricular conduction. AF recurrence rate after PVI and NCC AT successful ablation was 12.5% (1 of 8). Tachycardia cycle length was shorter than that of 17 de novo ATs from NCC (303 versus 378, p=0.012). No AV block occurred during and after successful AT ablation. CONCLUSIONS: Uncommon NCC ATs (0.08% in AF ablation cases) uncovered after PVI, showing different characteristics compared to de-novo NCC ATs, should be suspected irrespective of P-wave morphologies when AT shows broad propagation from the anterior interatrial septum.

13.
Micromachines (Basel) ; 14(1)2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36677123

RESUMO

Over the years, several bare metal and crack-based strain sensors have been proposed for various fields of science and technology. However, due to their low gauge factor, metal-based strain sensors have limited practical applications. The crack-based strain sensor, on the other hand, demonstrated excellent sensitivity and a high gauge factor. However, the crack-based strain sensor exhibited non-linear behavior at low strains, severely limiting its real-time applications. Generally, the crack-based strain sensors are fabricated by generating cracks by bending a polymer film on which a metal layer has been deposited with a constant curvature. However, the random formation of cracks produces nonlinear behavior in the crack sensors. To overcome the limitations of the current state of the art, we propose a V-groove-based metal strain sensor for human motion monitoring and Morse code generation. The V-groove crack-based strain sensor is fabricated on polyurethane acrylate (PUA) using the modified photolithography technique. During the procedure, a V-groove pattern formed on the surface of the sensor, and a uniform crack formed over the entire surface by concentrating stress along the groove. To improve the sensitivity and selectivity of the sensor, we generated the cracks in a controlled direction. The proposed strain sensor exhibited high sensitivity and excellent fidelity compared to the other reported metal strain sensors. The gauge factor of the proposed V-groove-induced crack sensor is 10-fold higher than the gauge factor of the reported metal strain sensors. In addition, the fabricated V-groove-based strain sensor exhibited rapid response and recovery times. The practical feasibility of the proposed V-groove-induced crack-based strain sensor is demonstrated through human motion monitoring and the generation of Morse code. The proposed V-groove crack sensor can detect multiple motions in a variety of human activities and is anticipated to be utilized in several applications due to its high durability and reproducibility.

15.
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
16.
Brain Sci ; 11(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34573190

RESUMO

Objective: There is limited literature comparing the uniportal full endoscopic posterolateral transforaminal lumbar interbody fusion outside-in approach (ETLIF (O)) with the inside-out approach (ETLIF (I)). Methods: Radiological evaluation was performed on disc height restoration and coronal wedging angle, and operation time (inferior articular process resection time/total operation time) and clinical evaluation were made. Result: 48 cases of inside-out and 38 cases of outside-in cases were included. Compared to inside-out, the outside-in approach had significantly less operative time required to resect inferior articular process: 36.55 ± 10.37, and total operative time: 87.45 ± 20.14 min compared to 49.83 ± 23.97 and 102.56 ± 36.53 min, respectively, for the inside-out approach, p < 0.05. Compared to the preoperative state, both cohorts achieved significant improvement of VAS and ODI at post-operative 1 week, 3 months and at final follow up. Both cohorts achieved statistically significant increased disc height with 5.00 ± 2.87 mm, 5.49 ± 2.33 mm and statistically significant improvement in coronal wedge angle with 1.76 ± 1.63°, 3.24 ± 2.92° in the inside-out and outside-in approaches respectively. Conclusions: Complete removal of inferior articular process is the key part of endoscopic fusion with two methods that can be applied: an inside-out approach or an outside-in approach. Comparing both techniques, the outside-in approach has a shorter operative time required for inferior articular process resection and total length of operation with similar good clinical and radiological outcomes.

17.
J Med Chem ; 64(20): 15091-15110, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583507

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement. The nonreceptor tyrosine kinase c-Abl has shown a potential role in the progression of PD. As such, c-Abl inhibition is a promising candidate for neuroprotection in PD and α-synucleinopathies. Compound 5 is a newly synthesized blood-brain barrier penetrant c-Abl inhibitor with higher efficacy than existing inhibitors. The objective of the current study was to demonstrate the neuroprotective effects of compound 5 on the α-synuclein preformed fibril (α-syn PFF) mouse model of PD. Compound 5 significantly reduced neurotoxicity, activation of c-Abl, and Lewy body pathology caused by α-syn PFF in cortical neurons. Additionally, compound 5 markedly ameliorated the loss of dopaminergic neurons, c-Abl activation, Lewy body pathology, neuroinflammatory responses, and behavioral deficits induced by α-syn PFF injection in vivo. Taken together, these results suggest that compound 5 could be a pharmaceutical agent to prevent the progression of PD and α-synucleinopathies.


Assuntos
Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Fármacos Neuroprotetores/química , Doença de Parkinson/metabolismo , Proteínas Proto-Oncogênicas c-abl/metabolismo , Relação Estrutura-Atividade
18.
J Clin Med ; 10(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207339

RESUMO

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12-7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

19.
Biosens Bioelectron ; 190: 113380, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34111727

RESUMO

Herein, we propose a novel biosensing platform involving an array of 64 hybrid cantilevers and integrated strain sensors to measure the real-time contractility of the drug-treated cardiomyocytes (CMs). The strain sensor is integrated on the polyimide (PI) cantilever. To improve the strain sensor reliability and construct the engineered cardiac tissue, the nanogroove-patterned polydimethylsiloxane (PDMS) encapsulation layer is bonded on the PI cantilever. The preliminary sensing characteristics demonstrate the superior structural integrity, robustness, enhanced sensitivity, and repeatability of the proposed devices. The long-term durability and biocompatibility of the PI/PDMS hybrid cantilever is verified by evaluating the cell viability and contractility. We also validate the proposed biosensing platform for cardiotoxicity measurement by applying it to two specific cardiovascular drugs: quinidine and verapamil. In response to quinidine and verapamil, the engineered CMs exhibited negative inotropic and chronotropic effects. The fabricated cantilever device successfully detected the quinidine-induced adverse effects in CMs such as early after depolarization (EADs) and Torsade de points (TdP) in real-time. The array of hybrid cantilevers with integrated strain sensors has the potential to satisfy the need for innovative analytic platforms owing to its high throughput and simplified data analysis.


Assuntos
Técnicas Biossensoriais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Cardiotoxicidade , Dimetilpolisiloxanos , Humanos , Reprodutibilidade dos Testes
20.
Acta Neuropathol Commun ; 9(1): 78, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902708

RESUMO

Alzheimer's disease (AD) is the most common cause of age-related dementia. Increasing evidence suggests that neuroinflammation mediated by microglia and astrocytes contributes to disease progression and severity in AD and other neurodegenerative disorders. During AD progression, resident microglia undergo proinflammatory activation, resulting in an increased capacity to convert resting astrocytes to reactive astrocytes. Therefore, microglia are a major therapeutic target for AD and blocking microglia-astrocyte activation could limit neurodegeneration in AD. Here we report that NLY01, an engineered exedin-4, glucagon-like peptide-1 receptor (GLP-1R) agonist, selectively blocks ß-amyloid (Aß)-induced activation of microglia through GLP-1R activation and inhibits the formation of reactive astrocytes as well as preserves neurons in AD models. In two transgenic AD mouse models (5xFAD and 3xTg-AD), repeated subcutaneous administration of NLY01 blocked microglia-mediated reactive astrocyte conversion and preserved neuronal viability, resulting in improved spatial learning and memory. Our study indicates that the GLP-1 pathway plays a critical role in microglia-reactive astrocyte associated neuroinflammation in AD and the effects of NLY01 are primarily mediated through a direct action on Aß-induced GLP-1R+ microglia, contributing to the inhibition of astrocyte reactivity. These results show that targeting upregulated GLP-1R in microglia is a viable therapy for AD and other neurodegenerative disorders.


Assuntos
Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Microglia/metabolismo , Neuroproteção/fisiologia , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/toxicidade , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Exenatida/administração & dosagem , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fragmentos de Peptídeos/toxicidade
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