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1.
Nature ; 597(7877): 503-510, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34552257

RESUMEN

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.


Asunto(s)
Biomimética , Equipos y Suministros Eléctricos , Miniaturización/instrumentación , Semillas , Viento , Tecnología Inalámbrica/instrumentación , Colorimetría , Monitoreo del Ambiente/instrumentación , Monitoreo del Ambiente/métodos , Fenómenos Mecánicos , Microfluídica , Vigilancia de la Población/métodos , Rotación
2.
Bioorg Chem ; 150: 107496, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38850590

RESUMEN

Protease-activated receptor 2 (PAR2) has garnered attention as a potential therapeutic target in breast cancer. PAR2 is implicated in the activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) via G protein and beta-arrestin pathways, contributing to the proliferation and metastasis of breast cancer cells. Despite the recognized role of PAR2 in breast cancer progression, clinically effective PAR2 antagonists remain elusive. To address this unmet clinical need, we synthesized and evaluated a series of novel compounds that target the orthosteric site of PAR2. Using in silico docking simulations, we identified compound 9a, an optimized derivative of compound 1a ((S)-N-(1-(benzylamino)-1-oxo-3-phenylpropan-2-yl)benzamide), which exhibited enhanced PAR2 antagonistic activity. Subsequent molecular dynamics simulations comparing 9a with the partial agonist 9d revealed that variations in ligand-induced conformational changes and interactions dictated whether the compound acted as an antagonist or agonist of PAR2. The results of this study suggest that further development of 9a could contribute to the advancement of PAR2 antagonists as potential therapeutic agents for breast cancer.

3.
Environ Res ; 256: 119202, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38782343

RESUMEN

A rational design of heterojunctions with high-quality contacts is essential for efficiently separating photogenerated charge carries and boosting the solar-driven harvesting capability. Herein, we fabricated a novel heterojunction of SnO2 quantum dots-anchored CdS-CdCO3 with g-C3N4 nanosheets as a superior photocatalyst. SnO2 quantum dots (SQDs) with positively charged surfaces were tightly anchored on the negatively charged surface of CdS nanosheets (NSs). The resulting CdS@SnO2 was finally decorated with g-C3N4 NSs, and a new crystalline phase of CdS-CdCO3 was formed during the hydrothermal decoration process, g-C3N4 decorated CdS-CdCO3@SnO2 (CdS-CdCO3@SnO2@g-C3N4). The as-synthesized photocatalysts were evaluated for the degradation of methyl orange dye under solar light conditions. The CdS-CdCO3@SnO2@g-C3N4 exhibited 7.7-fold and 2.3-fold enhancements in photocatalytic activities in comparison to those of the bare CdS and CdS@SnO2 NSs, respectively. The optimal performance of CdS-CdCO3@SnO2@g-C3N4 is primarily attributed to the cascade-type conduction band alignments between 2D/0D/2D heterojunctions, which can harvest maximum solar light and effectively separate photoexcited charge carriers. This work provides a new inspiration for the rational design of 2D/0D/2D heterojunction photocatalyst for green energy generation and environmental remediation applications.


Asunto(s)
Compuestos de Cadmio , Nanocompuestos , Puntos Cuánticos , Compuestos de Estaño , Puntos Cuánticos/química , Compuestos de Cadmio/química , Compuestos de Estaño/química , Nanocompuestos/química , Catálisis , Sulfuros/química , Luz Solar , Procesos Fotoquímicos , Grafito/química , Compuestos Azo/química , Nitrilos/química , Compuestos de Nitrógeno/química
4.
Int J Mol Sci ; 25(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38892219

RESUMEN

Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 µM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 µM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.


Asunto(s)
Anoctamina-1 , Antineoplásicos , Apoptosis , Movimiento Celular , Proliferación Celular , Hemina , Proteínas de Neoplasias , Neoplasias de la Próstata , Humanos , Anoctamina-1/metabolismo , Anoctamina-1/antagonistas & inhibidores , Masculino , Hemina/farmacología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Proliferación Celular/efectos de los fármacos , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Línea Celular Tumoral , Células PC-3
5.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-36674697

RESUMEN

Anoctamin1 (ANO1), a calcium-activated chloride channel, is involved in the proliferation, migration, and invasion of various cancer cells including head and neck squamous cell carcinoma, lung cancer, and prostate cancer. Inhibition of ANO1 activity or downregulation of ANO1 expression in these cancer cells is known to exhibit anticancer effects. Resveratrol, a natural polyphenol abundant in wines, grapes, berries, soybeans, and peanuts, shows a wide variety of biological effects including anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated the effects of two stereoisomers of resveratrol on ANO1 activity and found that cis- and trans-resveratrol inhibited ANO1 activity with different potencies. Cis- and trans-resveratrol inhibited ANO1 channel activity with IC50 values of 10.6 and 102 µM, respectively, and had no significant effect on intracellular calcium signaling at 10 and 100 µM, respectively. In addition, cis-resveratrol downregulated mRNA and protein expression levels of ANO1 more potently than trans-resveratrol in PC-3 prostate cancer cells. Cis- and trans-resveratrol significantly reduced cell proliferation and cell migration in an ANO1-dependent manner, and both resveratrol isomers strongly increased caspase-3 activity, PARP cleavage, and apoptotic sub-G1 phase ratio in PC-3 cells. These results revealed that cis-resveratrol is a potent inhibitor of ANO1 and exhibits ANO1-dependent anticancer activity against human metastatic prostate cancer PC-3 cells.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias de la Próstata , Masculino , Humanos , Resveratrol/farmacología , Células PC-3 , Anoctamina-1/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Proteínas de Neoplasias/metabolismo
6.
Bioorg Chem ; 126: 105877, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35636126

RESUMEN

A highly efficient domino [4 + 2] annulation process was employed to construct a novel indolizine chemical scaffold. Biological investigation led us to identify 6w as a potent anticancer agent. 6w significantly inhibited cell viability in BxPC3 pancreatic cancer, MCF7 breast cancer, and PC3 prostate cancer cell lines with IC50 values of 0.47 ± 0.04, 1.82 ± 0.08 and 2.68 ± 0.08 µM, respectively. Remarkably, 6w showed a weak effect on cell viability of nontumorigenic human keratinocyte cell line HaCaT compared to the above three types of cancer cells. 6w most potently inhibited cell viability of BxPC3 cells, and 6w also potently reduced cell migration and induced apoptosis in BxPC3 cells through activation of caspase-3 and cleavage of PARP in a dose-dependent manner. These results suggest that 6w can be used for the development of potential anticancer drugs for the treatment of pancreatic cancer.


Asunto(s)
Antineoplásicos , Indolizinas , Neoplasias Pancreáticas , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Línea Celular Tumoral , Humanos , Indolizinas/farmacología , Masculino , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas
7.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36430803

RESUMEN

Chloroquine (CQ) is an antimalaria drug that has been widely used for decades. However, CQ-induced pruritus remains one of the major obstacles in CQ treatment for uncomplicated malaria. Recent studies have revealed that MrgprX1 plays an essential role in CQ-induced itch. To date, a few MrgprX1 antagonists have been discovered, but they are clinically unavailable or lack selectivity. Here, a cell-based high-throughput screening was performed to identify novel antagonists of MrgprX1, and the screening of 2543 compounds revealed two novel MrgprX1 inhibitors, berbamine and closantel. Notably, berbamine potently inhibited CQ-mediated MrgprX1 activation (IC50 = 1.6 µM) but did not alter the activity of other pruritogenic GPCRs. In addition, berbamine suppressed the CQ-mediated phosphorylation of ERK1/2. Interestingly, CQ-induced pruritus was significantly reduced by berbamine in a dose-dependent manner, but berbamine had no effect on histamine-induced, protease-activated receptors 2-activating peptide-induced, and deoxycholic acid-induced itch in mice. These results suggest that berbamine is a novel, potent, and selective antagonist of MrgprX1 and may be a potential drug candidate for the development of therapeutic agents to treat CQ-induced pruritus.


Asunto(s)
Bencilisoquinolinas , Cloroquina , Ratones , Animales , Cloroquina/efectos adversos , Prurito/inducido químicamente , Prurito/tratamiento farmacológico , Histamina , Ubiquitina-Proteína Ligasas
8.
Int J Mol Sci ; 23(18)2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36142527

RESUMEN

Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal domain. Once activated, PAR2 is rapidly desensitized and internalized by phosphorylation and ß-arrestin recruitment. Due to its irreversible activation mechanism, some agonists that rapidly desensitized PAR2 have been misconceived as antagonists, and this has impeded a better understanding of the pathophysiological role of PAR2. In the present study, we found that GB83, initially identified as a PAR2 antagonist, is a bona fide agonist of PAR2 that induces unique cellular signaling, distinct from trypsin and PAR2-activating peptide (AP). Activation of PAR2 by GB83 markedly elicited an increase in intracellular calcium levels and phosphorylation of MAPKs, but in a delayed and sustained manner compared to the rapid and transient signals induced by trypsin and PAR2-AP. Interestingly, unlike PAR2-AP, GB83 and trypsin induced sustained receptor endocytosis and PAR2 colocalization with ß-arrestin. Moreover, the recovery of the localization and function of PAR2 was significantly delayed after stimulation by GB83, which may be the reason why GB83 is recognized as an antagonist of PAR2. Our results revealed that GB83 is a bona fide agonist of PAR2 that uniquely modulates PAR2-mediated cellular signaling and is a useful pharmacological tool for studying the pathophysiological role of PAR2.


Asunto(s)
Calcio , Receptor PAR-2 , Calcio/metabolismo , Péptidos , Receptor PAR-2/metabolismo , Tripsina , beta-Arrestinas
9.
Small ; 17(42): e2103705, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34558171

RESUMEN

To identify high-efficiency metal-nitrogen-doped (M-N-C) electrocatalysts for the electrochemical CO2 -to-CO reduction reaction (CO2 RR), a method that uses density functional theory calculation is presented to evaluate their selectivity, activity, and structural stability. Twenty-three M-N4 -C catalysts are evaluated, and three of them (M = Fe, Co, or Ni) are identified as promising candidates. They are synthesized and tested as proof-of-concept catalysts for CO2 -to-CO conversion. Different key descriptors, including the maximum reaction energy, differences of the *H and *CO binding energy (ΔG*H -ΔG*CO ), and *CO desorption energy (ΔG*CO→CO( g ) ), are used to clarify the reaction mechanism. These computational descriptors effectively predict the experimental observations in the entire range of electrochemical potential. The findings provide a guideline for rational design of heterogeneous CO2 RR electrocatalysts.

10.
Int J Mol Sci ; 22(21)2021 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-34769467

RESUMEN

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including oral squamous cell carcinoma (OSCC). OSCC is a highly aggressive cancer and the most common oral malignancy. ANO1 has been proposed as a potential candidate for targeted anticancer therapy. In this study, we performed a cell-based screening to identify novel regulators leading to the downregulation of ANO1, and discovered cinobufagin, which downregulated ANO1 expression in oral squamous cell carcinoma CAL-27 cells. ANO1 protein levels were significantly reduced by cinobufagin in a dose-dependent manner with an IC50 value of ~26 nM. Unlike previous ANO1 inhibitors, short-term (≤10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells. Notably, cinobufagin inhibited cell proliferation of CAL-27 cells expressing high levels of ANO1 more potently than that of ANO1 knockout CAL-27 cells. In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells. These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.


Asunto(s)
Anoctamina-1/genética , Bufanólidos/farmacología , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Proteínas de Neoplasias/genética , Animales , Anoctamina-1/metabolismo , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Ensayos de Selección de Medicamentos Antitumorales , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Ratones Endogámicos C57BL , Neoplasias de la Boca/genética , Proteínas de Neoplasias/metabolismo , Células Tumorales Cultivadas
11.
J Org Chem ; 85(16): 10994-11005, 2020 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-32674567

RESUMEN

A highly efficient synthetic route to new quinone-indolizine hybrids was accomplished from quinones and N-substituted pyrrole-2-carboxaldehydes via a domino Michael addition-aldol condensation-aromatization sequence through which the central pyridine ring was constructed in atom-economical and environment-friendly manner. Post modification of the resulting products was also demonstrated, enabling further expansion of this heterocyclic chemical space. Biological evaluation of the quinone-indolizine hybrids revealed potent anticancer effects in human prostate adenocarcinoma cells (PC-3) and oral adenosquamous carcinoma cells (CAL-27).


Asunto(s)
Indolizinas , Benzoquinonas , Humanos , Estructura Molecular , Quinonas/farmacología
12.
Lasers Surg Med ; 52(7): 647-652, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31820466

RESUMEN

BACKGROUND AND OBJECTIVE: Various clinical and animal studies have applied low-level laser therapy (LLLT) to treat oral ulcers. However, most previous studies applied lasers with small pinpoint irradiation, which required multiple laser irradiations to cover the complete extent of the ulcer. The objective of this study was to evaluate the effect of LLLT using a 635 nm diode laser via a transoral device to cover the whole lesion on oral ulcers in an animal model. STUDY DESIGN/MATERIALS AND METHODS: An animal model of oral ulcers was developed with a 6 mm skin punch in the right buccal mucosa of Wistar rats (males, body weight 200-250 g). Three days after the mucosal injury, LLLT (spot size 2 cm2 ) was conducted once a day for 5 days. Twenty-eight rats were randomly assigned into four groups according to energy density (control group, 5, 20, 75 J/cm2 ). The size of the ulcers was measured and histologic analysis were performed ten days after the initial mucosal injury. RESULTS: The mean size of the oral ulcers was significantly smaller in rats treated with an energy density of 20 J/cm2 than that of any other group (control group or energy densities of 5 or 75 J/cm2 ). The irradiation of oral ulcers with an energy density of 20 J/cm2 accelerated the oral mucosa wound healing process and decreased inflammation and granulation tissue, resulting in good reepithelization. However, the histologic outcomes of rats irradiated with energy densities of 5 or 75 J/cm2 were comparable with those of the control group. CONCLUSION: LLLT using a 635 nm diode laser for oral ulcers with a transoral cylindrical device for wide light distribution may accelerate the wound healing process. LLLT with large-surface irradiation may be a substitute for previous LLLT for oral mucosal lesions conducted in a punctuate manner. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.


Asunto(s)
Terapia por Luz de Baja Intensidad , Úlceras Bucales , Animales , Láseres de Semiconductores/uso terapéutico , Masculino , Úlceras Bucales/etiología , Úlceras Bucales/radioterapia , Ratas , Ratas Wistar , Roedores
13.
Sensors (Basel) ; 20(20)2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33050244

RESUMEN

Patch-type hydrogel electrodes have received increasing attention in biomedical applications due to their high biocompatibility and conformal adherence. However, their poor mechanical properties and non-uniform electrical performance in a large area of the hydrogel electrode should be improved for use in wearable devices for biosignal monitoring. Here, we developed self-adherent, biocompatible hydrogel electrodes composed of biodegradable gelatin and conductive polymers for electrocardiography (ECG) measurement. After incorporating conductive poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) into gelatin hydrogels crosslinked by natural crosslinkers (genipin), the mechanical properties and electrical conductivity of the hydrogel electrodes were improved and additionally optimized by adjusting the amounts of crosslinker and PEDOT:PSS, respectively. Furthermore, the effect of dimethyl sulfoxide, as a dopant, on the conductivity of hydrogels was investigated. The gelatin-based, conductive hydrogel patch displayed self-adherence to human skin with an adhesive strength of 0.85 N and achieved conformal contact with less skin irritation compared to conventional electrodes with a chemical adhesive layer. Eyelet-type hydrogel electrodes, which were compatible with conventional ECG measurement instruments, exhibited a comparable performance in 12-lead human ECG measurement with commercial ECG clinical electrodes (3M Red Dot). These self-adherent, biocompatible, gelatin-based hydrogel electrodes could be used for monitoring various biosignals, such as in electromyography and electroencephalography.


Asunto(s)
Electrocardiografía , Gelatina , Hidrogeles , Conductividad Eléctrica , Electrodos , Humanos
14.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899792

RESUMEN

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3-6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 µM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.


Asunto(s)
Anoctamina-1/antagonistas & inhibidores , Mallotus (Planta)/metabolismo , Extractos Vegetales/farmacología , Animales , Anoctamina-1/metabolismo , Anoctamina-1/fisiología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Canales de Cloruro/metabolismo , Humanos , Neoplasias de la Boca/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/fisiología , Células PC-3 , Ratas
15.
Biomimetics (Basel) ; 9(3)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38534857

RESUMEN

The finger workspace is crucial for performing various grasping tasks. Thus, various soft rehabilitation gloves have been developed to assist individuals with paralyzed hands in activities of daily living (ADLs) or rehabilitation training. However, most soft robotic glove designs are insufficient to assist with various hand postures because most of them use an underactuated mechanism for design simplicity. Therefore, this paper presents a methodology for optimizing the design of a high-degree-of-freedom soft robotic glove while not increasing the design complexity. We defined the required functional workspace of the index finger based on ten frequently used grasping postures in ADLs. The design optimization was achieved by simulating the proposed finger-robot model to obtain a comparable workspace to the functional workspace. In particular, the moment arm length for extension was optimized to facilitate the grasping of large objects (precision disk and power sphere), whereas a torque-amplifying routing design was implemented to aid the grasping of small objects (lateral pinch and thumb-two-finger pinch). The effectiveness of the optimized design was validated through testing with a stroke survivor and comparing the assistive workspace. The observed workspace demonstrated that the optimized glove design could assist with nine out of the ten targeted grasping posture functional workspaces. Furthermore, the assessment of the grasping speed and force highlighted the glove's usability for various rehabilitation activities. We also present and discuss a generalized methodology to optimize the design parameters of a soft robotic glove that uses an underactuated mechanism to assist the targeted workspace. Overall, the proposed design optimization methodology serves as a tool for developing advanced hand rehabilitation robots, as it offers insight regarding the importance of routing optimization in terms of the workspace.

16.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38399447

RESUMEN

The epidermal growth factor receptor (EGFR), also known as ErbB1 and HER1, belongs to the receptor tyrosine kinase family. EGFR serves as the primary driver in non-small-cell lung cancer (NSCLC) and is a promising therapeutic target for NSCLC. In this study, we synthesized a novel chemical library based on a benzofuran-indole hybrid scaffold and identified 8aa as a potent and selective EGFR inhibitor. Interestingly, 8aa not only showed selective anticancer effects against NSCLC cell lines, PC9, and A549, but it also showed significant inhibitory effects against the double mutant L858R/T790M EGFR, which frequently occurs in NSCLC. In addition, in PC9 and A549 cells, 8aa potently blocked the EGFR signaling pathway, cell viability, and cell migration. These findings suggest that 8aa, a benzofuran-indole hybrid derivative, is a novel EGFR inhibitor that may be a potential candidate for the treatment of NSCLC patients with EGFR mutations.

17.
IEEE Trans Biomed Eng ; 70(1): 366-377, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35849669

RESUMEN

Functional rehabilitation of the hand is a complex and difficult process involving a large number of degrees of freedom (DOFs). Soft wearable hand-rehabilitation robots have assisted hand movements with a compact structural design, but effective rehabilitation requires an intuitive control scheme that can manage many DOFs and incorporate interaction with an occupational therapist, which has yet to be developed for this type of device. Thus, we present a soft wearable unilateral telerobotic system that enables various grasping tasks and cooperative interaction between the patient and therapist. The presented system consists of a sensor glove that measures the hand postures of the occupational therapist and a soft robotic glove that assists 4-DOF movements of the patient's hand, including adjustments of the interjoint coordination of the finger and 2-DOF movements of the thumb (flexion/extension and opposition/reposition). The soft robotic glove effectuates hand movements based on the measurements from the sensor glove. A telerobotic impedance-control scheme provides intuitive guidance of various hand postures, along with a fingertip-force vector. The feasible workspace and control performance of the system were evaluated on a healthy recruit and a poststroke patient. The presented system allowed the therapist to increase the patient's thumb workspace by 400% in palmar-dorsal direction and to control the fingertip-force direction at -30°âˆ¼10° range by enabling control of interjoint coordination of the proximal-interphalangeal and metacarpophalangeal joints. These features facilitate patients to perform various postures for stable object grasping. The presented rehabilitation system is suitable for noncontact telehealthcare that facilitates patient-therapist interactions.


Asunto(s)
Robótica , Dispositivos Electrónicos Vestibles , Humanos , Mano , Pulgar , Dedos , Fuerza de la Mano
18.
IEEE Int Conf Rehabil Robot ; 2023: 1-6, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37941170

RESUMEN

Brain plasticity plays a significant role in functional recovery after stroke, but the specific benefits of hand rehabilitation robot therapy remain unclear. Evaluating the specific effects of hand rehabilitation robot therapy is crucial in understanding how it impacts brain activity and its relationship to rehabilitation outcomes. This study aimed to investigate the brain activity pattern during hand rehabilitation exercise using functional magnetic resonance imaging (fMRI), and to compare it before and after 3-week hand rehabilitation robot training. To evaluate it, an fMRI experimental environment was constructed to facilitate the same hand posture used in rehabilitation robot therapy. Two stroke survivors participated and the conjunction analysis results from fMRI scans showed that patient 1 exhibited a significant improvement in activation profile after hand rehabilitation robot training, indicative of improved motor function in the bilateral motor cortex. However, activation profile of patient 2 exhibited a slight decrease, potentially due to habituation to the rehabilitation task. Clinical results supported these findings, with patient 1 experiencing a greater increase in FMA score than patient 2. These results suggest that hand rehabilitation robot therapy can induce different brain activity patterns in stroke survivors, which may be linked to patient-specific training outcomes. Further studies with larger sample sizes are necessary to confirm these findings.


Asunto(s)
Corteza Motora , Robótica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Robótica/métodos , Imagen por Resonancia Magnética , Recuperación de la Función/fisiología
19.
Front Psychol ; 13: 958945, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36051216

RESUMEN

Managing learning continuity is critical for successful MOOC learning. Thus, enabling learners to have learning persistence needs to be integrated into the MOOC learning design. Motivation effort is a critical component enabling students to maintain continuous MOOC learning. The expectancy-value theory explains why learners engage in learning: (1) they have a higher perceived ability for learning success, (2) place value on learning, and (3) avoid psychological costs. However, it is unclear how these factors affect MOOC learning persistence and how learners' motivation is formed from this perspective. This experimental study explored how learners' motivational variables affect their learning persistence, focusing on the expectancy-value theory. The results of this study indicated that academic self-efficacy and task value had significant positive effects on learning persistence. The structural relationship of antecedent, process, and outcome variables showed that teaching presence as an antecedent had a significantly positive effect on academic self-efficacy and task value. Among the three factors of the expectancy-value theory, only the task value influenced learning persistence through student engagement as a mediator. Based on the results, suggestions are provided for motivating MOOC environments that support learners' continuous MOOC learning.

20.
Soft Robot ; 9(4): 734-744, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34388039

RESUMEN

The human hand is one of the most complex and compact grippers that has arisen as a product of natural genetic engineering; it is highly versatile, as it handles power and precision tasks. Since proper contact points and force directions are required to ensure versatility and secure a stable grip on an object, there must be a large workspace and controllable tip force directions for the digits. Although they are important, many individuals with neuromuscular diseases experience loss of these features. Thus, we propose a high-degree-of-freedom (DOF) soft robotic glove inspired by the anatomical features of human hands. The mechanism for adjusting the position and force direction of each tip is based on the structure of the extrinsic and intrinsic muscle-tendon units. The large thumb workspace was achieved by assisting opposition/reposition and flexion/extension to enable various grasping postures. A bidirectional actuation control mechanism with a cable-actuated agonist and an elastomer antagonist increased the assisted DOF and maintained compactness. The kinematic and kinetic performances of our device were evaluated by performing tests with eight stroke survivors. The thumb workspace increased by 43%, 207%, and 248% in the distal-proximal, dorsal-palmar, and radial-ulnar directions, respectively. The pinching shear force decreased by 54% and 45% for the nonthumb digits and thumb, respectively. These device-assisted improvements allowed objects to be stably grasped and manipulated in various postures. The novel device can assist individuals with impaired hand function to improve their grasping performance. Clinical Research Information Service (CRIS) Registration Number: KCT0004855.


Asunto(s)
Robótica , Mano , Fuerza de la Mano , Humanos , Pulgar , Extremidad Superior
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