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1.
Int J Mol Sci ; 22(21)2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34769467

RESUMO

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.

2.
Small ; 17(42): e2103705, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34558171

RESUMO

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.

3.
Nature ; 597(7877): 503-510, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34552257

RESUMO

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.

4.
Soft Robot ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34388039

RESUMO

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.

5.
Sensors (Basel) ; 20(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050244

RESUMO

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.


Assuntos
Eletrocardiografia , Gelatina , Hidrogéis , Condutividade Elétrica , Eletrodos , Humanos
6.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899792

RESUMO

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.


Assuntos
Anoctamina-1/antagonistas & inibidores , Mallotus (Planta)/metabolismo , Extratos Vegetais/farmacologia , Animais , Anoctamina-1/metabolismo , Anoctamina-1/fisiologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Canais de Cloreto/metabolismo , Humanos , Neoplasias Bucais/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/fisiologia , Células PC-3 , Ratos
7.
J Org Chem ; 85(16): 10994-11005, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32674567

RESUMO

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).


Assuntos
Indolizinas , Benzoquinonas , Humanos , Estrutura Molecular , Quinonas/farmacologia
8.
Biosens Bioelectron ; 163: 112281, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32568694

RESUMO

Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome recognized as the leading cause of maternal and fetal morbidity and mortality worldwide. Painful blood-collection procedures or low accuracy of non-invasive approaches require faster, patient-friendly, and more sensitive diagnostic technologies. Here we report a painless, highly sensitive detection platform using nanoporous microneedles (nMNs) that enables rapid capture of biomarkers present at sub-nanogram levels. The highly porous nanostructures on the nMN surface were prepared by anodization of aluminum MN and then functionalized by immobilization of capture antibodies to detect target biomarkers based on an immunoassay method. The immuno-functionalized nMN array demonstrated rapid capture of an estrogen (E2) biomarker for PE following a 1-min incubation and exhibited a concentration-dependent change in fluorescence intensity over the E2 range of 0.5 ng mL-1 to 1000 ng mL-1 after treatment with fluorescence-detection antibodies. Remarkably, the nMN patch selectively detected sub-nanogram-levels of E2 in subcutaneous interstitial fluid from rats with increased diagnostic accuracy as compared with commercial immunoassay kits. This bio-functionalized nMN platform showed improved biosensing capability for multiple PE-related biomarkers, including hormones and proteins. Furthermore, this painless method demonstrated efficacy as a point-of-need diagnostic platform using portable smartphone-based fluorescence microscope to obtain fluorescence images of biomarker-captured nMN arrays.


Assuntos
Técnicas Biossensoriais , Pré-Eclâmpsia , Animais , Biomarcadores , Feminino , Humanos , Imunoensaio , Pré-Eclâmpsia/diagnóstico , Gravidez , Ratos , Smartphone
9.
Pharmaceutics ; 12(2)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32012667

RESUMO

Glutathione is a natural anti-aging substance that prevents the oxidation of protein thiols from reactive oxygen species. In the pharmaceutical industry, reduced glutathione (GSH) has been widely used for skin whitening due to its ability to inhibit tyrosinase. However, its poor permeability and foul odor limit its use in skin applications. Herein, we report a GSH-loaded dissolving microneedle (MN) patch prepared with hyaluronic acid (HA) that enables enhanced permeation across the skin and reduces the foul odor of GSH. HA was selected to prepare odorless GSH solutions and used for MN fabrications as a carrier of GSH. GSH-loaded MN (GSH-MN) arrays prepared from MN-forming solution containing up to 10% GSH showed good pattern uniformity and appropriate mechanical properties for insertion into the skin. The GSH-MNs with a loading capacity of 17.4% dissolve within 10 min following insertion into porcine skin and release the loaded GSH without being oxidized. This new approach combines functional biopolymers to reduce the characteristic GSH odor and advanced transdermal delivery based on MN technology to enhance skin permeation without pain. We believe this technique could expand the application of GSH in many cosmeceutical fields.

10.
Lasers Surg Med ; 52(7): 647-652, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820466

RESUMO

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.

11.
ACS Nano ; 13(10): 10972-10979, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31124670

RESUMO

Sensors that reproduce the complex characteristics of cutaneous receptors in the skin have important potential in the context of artificial systems for controlled interactions with the physical environment. Multimodal responses with high sensitivity and wide dynamic range are essential for many such applications. This report introduces a simple, three-dimensional type of microelectromechanical sensor that incorporates monocrystalline silicon nanomembranes as piezoresistive elements in a configuration that enables separate, simultaneous measurements of multiple mechanical stimuli, such as normal force, shear force, and bending, along with temperature. The technology provides high sensitivity measurements with millisecond response times, as supported by quantitative simulations. The fabrication and assembly processes allow scalable production of interconnected arrays of such devices with capabilities in spatiotemporal mapping. Integration with wireless data recording and transmission electronics allows operation with standard consumer devices.


Assuntos
Técnicas Biossensoriais , Fenômenos Físicos , Pele/metabolismo , Tato/fisiologia , Eletrônica , Fenômenos Mecânicos , Pele/química , Temperatura , Tato/genética
12.
Nat Biomed Eng ; 3(1): 37-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932064

RESUMO

Pressures in the intracranial, intraocular and intravascular spaces are clinically useful for the diagnosis and management of traumatic brain injury, glaucoma and hypertension, respectively. Conventional devices for measuring these pressures require surgical extraction after a relevant operational time frame. Bioresorbable sensors, by contrast, eliminate this requirement, thereby minimizing the risk of infection, decreasing the costs of care and reducing distress and pain for the patient. However, the operational lifetimes of bioresorbable pressure sensors available at present fall short of many clinical needs. Here, we present materials, device structures and fabrication procedures for bioresorbable pressure sensors with lifetimes exceeding those of previous reports by at least tenfold. We demonstrate measurement accuracies that compare favourably to those of the most sophisticated clinical standards for non-resorbable devices by monitoring intracranial pressures in rats for 25 days. Assessments of the biodistribution of the constituent materials, complete blood counts, blood chemistry and magnetic resonance imaging compatibility confirm the biodegradability and clinical utility of the device. Our findings establish routes for the design and fabrication of bioresorbable pressure monitors that meet requirements for clinical use.


Assuntos
Implantes Absorvíveis , Doença Crônica , Pressão Intracraniana , Monitorização Fisiológica/instrumentação , Dióxido de Silício/química , Temperatura , Cicatrização , Animais , Feminino , Cinética , Imageamento por Ressonância Magnética , Masculino , Camundongos , Ratos Endogâmicos Lew , Distribuição Tecidual
13.
Science ; 363(6430)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819934

RESUMO

Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) require multiple wires connected to rigid sensors with strongly adherent interfaces to the skin. We introduce a pair of ultrathin, soft, skin-like electronic devices whose coordinated, wireless operation reproduces the functionality of these traditional technologies but bypasses their intrinsic limitations. The enabling advances in engineering science include designs that support wireless, battery-free operation; real-time, in-sensor data analytics; time-synchronized, continuous data streaming; soft mechanics and gentle adhesive interfaces to the skin; and compatibility with visual inspection and with medical imaging techniques used in the NICU. Preliminary studies on neonates admitted to operating NICUs demonstrate performance comparable to the most advanced clinical-standard monitoring systems.


Assuntos
Eletrônica/instrumentação , Terapia Intensiva Neonatal , Monitorização Fisiológica/instrumentação , Tecnologia sem Fio/instrumentação , Diagnóstico por Imagem , Desenho de Equipamento , Humanos , Recém-Nascido , Dispositivos Lab-On-A-Chip , Pele , Sinais Vitais
14.
ACS Nano ; 12(5): 4164-4171, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29641889

RESUMO

Recently developed approaches in deterministic assembly allow for controlled, geometric transformation of two-dimensional structures into complex, engineered three-dimensional layouts. Attractive features include applicability to wide ranging layout designs and dimensions along with the capacity to integrate planar thin film materials and device layouts. The work reported here establishes further capabilities for directly embedding high-performance electronic devices into the resultant 3D constructs based on silicon nanomembranes (Si NMs) as the active materials in custom devices or microscale components released from commercial wafer sources. Systematic experimental studies and theoretical analysis illustrate the key ideas through varied 3D architectures, from interconnected bridges and coils to extended chiral structures, each of which embed n-channel Si NM MOSFETs (nMOS), Si NM diodes, and p-channel silicon MOSFETs (pMOS). Examples in stretchable/deformable systems highlight additional features of these platforms. These strategies are immediately applicable to other wide-ranging classes of materials and device technologies that can be rendered in two-dimensional layouts, from systems for energy storage, to photovoltaics, optoelectronics, and others.


Assuntos
Eletrônica/instrumentação , Nanoestruturas/química , Silício/química , Análise de Elementos Finitos , Iluminação , Fenômenos Mecânicos , Metais/química , Óxidos/química , Dióxido de Silício
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