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1.
J Nanobiotechnology ; 22(1): 160, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589911

RESUMO

Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC1-co-DMA1) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC1-co-DMA1) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC1-co-DMA1) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.


Assuntos
Antioxidantes , Lubrificantes , Animais , Coelhos , Antioxidantes/farmacologia , Materiais Biocompatíveis , Anti-Inflamatórios , Soluções Oftálmicas , Catecóis , Inflamação
2.
Biosens Bioelectron ; 246: 115861, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38029711

RESUMO

Following the discovery of graphene, there has been a surge in exploring other two-dimensional (2D) nanocrystals, including MoS2. Over the past few decades, MoS2-based nanocrystals have shown great potential applications in biosensing, owing to their excellent physico-chemical properties. Unlike graphene, MoS2 shows layer-dependent finite band gaps (∼1.8 eV for a single layer and ∼1.2 for bulk) and relatively strong interaction with the electromagnetic spectrum. The tunability of the size, shape, and intrinsic properties, such as high optical absorption, electron mobility, mechanical strength and large surface area, of MoS2 nanocrystals, make them excellent alternative probe materials for preparing optical, photothermal, and electrical bio/immunosensors. In this review, we will provide insights into the rapid evolutions in bio/immunosensing applications based on MoS2 and its nanohybrids. We emphasized the various synthesis, characterization, and functionalization routes of 2D MoS2 nanosheets/nanoflakes. Finally, we discussed various fabrication techniques and the critical parameters, including the limit of detection (LOD), linear detection range, and sensitivity of the biosensors. In addition, the role of MoS2 in enhancing the performance of biosensors, the limitations associated with current biosensing technologies, future challenges, and clinical implications are addressed. The advantages/disadvantages of each biosensor technique are also summarized. Collectively, we believe that this review will encourage resolute researchers to follow up further with the state-of-the-art MoS2-based biosensing technology.


Assuntos
Técnicas Biossensoriais , Grafite , Nanoestruturas , Nanoestruturas/química , Técnicas Biossensoriais/métodos , Molibdênio/química , Grafite/química , Dissulfetos/química , Imunoensaio
3.
ACS Nano ; 17(24): 25118-25135, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38051575

RESUMO

Dry eye (DE) disease, which is primarily linked to aqueous deficiency, is an escalating health issue worldwide, mainly due to the widespread use of electronic devices. The major obstacles in DE pharmacotherapy include insufficient therapeutic efficacy and low ocular bioavailability. This study presents the development of a ceria-based nanosystem to carry gabapentin (GBT), aiming to offer comprehensive relief from DE symptoms. We prepared multifunctional nanoceria capped with thiolated gelatin followed by cross-linking with glutaraldehyde, yielding a nanocarrier with desirable biocompatibility and antioxidant, anti-inflammatory, antiangiogenic, antiapoptotic, and neuronal protective activities. Specifically, the highly abundant thiol groups on gelatin increased the cellular uptake of the nanocarrier by 2.3-fold and its mucin-binding efficiency by 10-fold, thereby extending ocular retention and amplifying therapeutic activity. Moderate cross-linking of the thiolated gelatin not only enhanced the ocular bioavailability of the nanoceria but also provided slow, degradation-controlled release of GBT to promote the lacrimal stimulation to restore the tear film. In a rabbit model of DE, topical administration of our GBT/nanoceria nanoformulation resulted in comprehensive alleviation of symptoms, including repairing corneal epithelial damage, preserving corneal nerve density, and stimulating tear secretion, demonstrating superior performance in comparison to the free drug. These results underscore the safety and potential of this innovative nanoformulation for DE pharmacotherapy.


Assuntos
Síndromes do Olho Seco , Animais , Coelhos , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/diagnóstico , Gabapentina/uso terapêutico , Gelatina , Lágrimas
4.
Nat Phys ; 19(11): 1605-1610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970535

RESUMO

When a system close to a continuous phase transition is subjected to perturbations, it takes an exceptionally long time to return to equilibrium. This critical slowing down is observed universally in the dynamics of bosonic excitations, such as order-parameter collective modes, but it is not generally expected to occur for fermionic excitations. Here using terahertz time-domain spectroscopy, we find evidence for fermionic critical slowing down in YbRh2Si2 close to a quantum phase transition between an antiferromagnetic phase and a heavy Fermi liquid. In the latter phase, the relevant quasiparticles are a quantum superposition of itinerant and localized electronic states with a strongly enhanced effective mass. As the temperature is lowered on the heavy-Fermi-liquid side of the transition, the heavy-fermion spectral weight builds up until the Kondo temperature TK ≈ 25 K, then decays towards the quantum phase transition and is, thereafter, followed by a logarithmic rise of the quasiparticle excitation rate below 10 K. A two-band heavy-Fermi-liquid theory shows that this is indicative of the fermionic critical slowing down associated with heavy-fermion breakdown near the quantum phase transition. The critical exponent of this breakdown could be used to classify this system among a wider family of fermionic quantum phase transitions that is yet to be fully explored.

5.
Adv Sci (Weinh) ; 10(26): e2302174, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37430140

RESUMO

Development of topical bioactive formulations capable of overcoming the low bioavailability of conventional eye drops is critically important for efficient management of ocular chemical burns. Herein, a nanomedicine strategy is presented to harness the surface roughness-controlled ceria nanocages (SRCNs) and poly(l-histidine) surface coatings for triggering multiple bioactive roles of intrinsically therapeutic nanocarriers and promoting transport across corneal epithelial barriers as well as achieving on-demand release of dual drugs [acetylcholine chloride (ACh) and SB431542] at the lesion site. Specifically, the high surface roughness helps improve cellular uptake and therapeutic activity of SRCNs while exerting a negligible impact on good ocular biocompatibility of the nanomaterials. Moreover, the high poly(l-histidine) coating amount can endow the SRCNs with an ≈24-fold enhancement in corneal penetration and an effective smart release of ACh and SB431542 in response to endogenous pH changes caused by tissue injury/inflammation. In a rat model of alkali burn, topical single-dose nanoformulation can efficaciously reduce corneal wound areas (19-fold improvement as compared to a marketed eye drops), attenuate ≈93% abnormal blood vessels, and restore corneal transparency to almost normal at 4 days post-administration, suggesting great promise for designing multifunctional metallic nanotherapeutics for ocular pharmacology and tissue regenerative medicine.


Assuntos
Benzamidas , Traumatismos Oculares , Ratos , Animais , Soluções Oftálmicas
6.
PLoS One ; 18(2): e0281199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36757921

RESUMO

BACKGROUND: Travel, especially international travel, has become one of the most popular leisure activities in the world. The risk of accidents and travel-related illnesses, including infectious and non-communicable diseases, should not be neglected. To provide a more comprehensive pre-travel consultation to international travelers, this study aimed to investigate the knowledge, attitude, and practice of travelers about travel health insurance. METHODS: This was a cross-sectional study. Anonymous structured questionnaires were distributed to 1000 visitors to the Taiwan International Travel Fair in May 2019. RESULTS: The top three important travel health insurances were accidental death and disablement insurance (92%), accidental medical reimbursement (90.4%), and 24-hour emergency assistance (89%). In addition to education level, travel-associated illness, and special activities during travel, a significant association was observed between the willingness to buy various travel health insurances and the willingness of pre-travel consultation. CONCLUSIONS: Most travelers would buy travel health insurance; however, disproportional respondents understood the content of travel health insurance. Most travelers considered travel clinics to be the most reliable information source regarding travel health insurance. Therefore, travel medicine specialists are encouraged to offer more information about travel health insurance during pre-travel consultation.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Viagem , Humanos , Estudos Transversais , Doença Relacionada a Viagens , Seguro Saúde , Inquéritos e Questionários
7.
ACS Nano ; 17(1): 168-183, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36524981

RESUMO

The development of therapeutics for effective treatments of retinal diseases is significantly constrained by various biological barriers. We herein report a nanomedicine strategy to develop nanotherapeutics featured with not only high retinal permeability but also sustained bioactive delivery. Specifically, the nanotherapeutics are rationally designed via aminolysis of resveratrol-encapsulated polycaprolactone nanoparticles (R@PCL NPs), followed by the formation of amide linkages with carboxyl-terminated transacting activator of transcription cell penetrating peptide (T) and metformin (M). The R@PCL-T/M NP nanotherapeutics are demonstrated in vitro to possess persistent drug release profiles, good ocular biocompatibility, and potent bioactive activities for targeting prevailing risk factors associated with retinal diseases. In vivo studies indicate that single-dose intravitreal administration of the R@PCL-T/M NPs can effectively improve retinal permeability (∼15-fold increase), prevent loss of endogenous antioxidants, and suppress the growth of abnormal vessels in the retina with macular degeneration for 56 days. This high treatment efficacy can be ascribed to the enhanced retinal permeability of the nanotherapeutics in conjunction with the sustained pharmacological activity of the dual drugs (R and M) in the retinal pigment epithelial region. These findings show a great promise for the development of pharmacological nanoformulations capable of targeting the retina and thereby treating complex posterior segment diseases with improved efficacies.


Assuntos
Degeneração Macular , Nanopartículas , Doenças Retinianas , Humanos , Resveratrol/farmacologia , Retina , Sistemas de Liberação de Medicamentos
8.
Travel Med Infect Dis ; 49: 102397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35792255

RESUMO

BACKGROUND: Although globalization promotes economic development, cross-border infectious disease transmission is still a serious threat to health. Taiwan is geographically close to Southeast and South Asia, but the needs and expectations of Taiwanese travelers with regard to travel medicine are still largely unknown. This study aimed to clarify the pretravel preparations, needs, willingness to seek pretravel consultation, and factors associated with willingness, in order to provide valuable information for improvement of healthcare service. METHODS: Data were collected with anonymous structured questionnaires distributed to 477 visitors who tried to get travel health information from New Southbound Health Center between June and November 2019. A multivariate stepwise logistic regression analysis was applied to identify factors associated with the visitors' willingness to seek pretravel consultation. RESULTS: A total of 304 questionnaires (64%) were collected. Eighty-three percent of the respondents were willing to seek pretravel consultation. A higher level of education (odds ratio 3.6 [95% CI 1.58-8.22]), having a plan to obtain travel medical insurance (2.5 [1.18-5.28]), concern with gastrointestinal diseases (2.0 [1.04-3.94]), concern with mosquito-borne diseases (2.0 [2.07-3.95]), and concern with noncommunicable diseases (2.2 [1.02-4.96]) were independent factors associated with willingness to seek pretravel consultation.: CONCLUSIONS: We found that most of the travelers were willing to seek pretravel consultation. Our study highlighted the need to enhance awareness about travel-related illness among these travelers. Strategies should be tailored according to these findings to help prevent epidemics and improve healthcare service in the future.


Assuntos
Doença Relacionada a Viagens , Viagem , Humanos , Internacionalidade , Encaminhamento e Consulta , Inquéritos e Questionários
9.
J Clin Med ; 10(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34640449

RESUMO

BACKGROUND: The performance of chest radiography-based age and sex prediction has not been well validated. We used a deep learning model to predict the age and sex of healthy adults based on chest radiographs (CXRs). METHODS: In this retrospective study, 66,643 CXRs of 47,060 healthy adults were used for model training and testing. In total, 47,060 individuals (mean age ± standard deviation, 38.7 ± 11.9 years; 22,144 males) were included. By using chronological ages as references, mean absolute error (MAE), root mean square error (RMSE), and Pearson's correlation coefficient were used to assess the model performance. Summarized class activation maps were used to highlight the activated anatomical regions. The area under the curve (AUC) was used to examine the validity for sex prediction. RESULTS: When model predictions were compared with the chronological ages, the MAE was 2.1 years, RMSE was 2.8 years, and Pearson's correlation coefficient was 0.97 (p < 0.001). Cervical, thoracic spines, first ribs, aortic arch, heart, rib cage, and soft tissue of thorax and flank seemed to be the most crucial activated regions in the age prediction model. The sex prediction model demonstrated an AUC of >0.99. CONCLUSION: Deep learning can accurately estimate age and sex based on CXRs.

10.
Plant Pathol J ; 37(1): 57-71, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33551697

RESUMO

Rice sheath blight (ShB), caused by Rhizoctonia solani Kühn AG1-IA, is one of the destructive rice diseases worldwide. The aims of this study were to develop biocontrol strategies focusing on field sanitation and foliar application with a biocontrol agent for ShB management. Streptomyces padanus PMS-702 showed a great antagonistic activity against R. solani. Fungichromin produced by S. padanus PMS-702, at 3.07 mg/l inhibited 50% mycelial growth, caused leakage of cytoplasm, and inhibited the formation of infection structures of R. solani. Fungichromin could reach to 802 mg/l when S. padanus PMS-702 was cultured in MACC broth for 6 days. Addition of 0.5% S. padanus PMS-702 broth into soil decreased the survival rate of the pathogen compared to the control. Soil amended with 0.5% S. padanus broth and 0.5% tea seed pomace resulted in the death of R. solani mycelia in the infested rice straws, and the germination of sclerotia was inhibited 21 days after treatment. Greenhouse trials revealed that S. padanus cultured in soybean meal-glucose (SMGC-2) medium after mixing with different surfactants could enhance its efficacy for inhibiting the pathogen. Of six surfactants tested, the addition of 2% tea saponin was the most effective in suppressing the pathogen. S. padanus broth after being fermented in SMGC-2, mixed with 2% tea saponin, diluted 100 fold, and sprayed onto rice plants significantly reduced ShB disease severity. Thus, S. padanus PMS-702 is an effective biocontrol agent. The efficacy of S. padanus PMS-702 for disease control could be improved through formulation.

11.
Database (Oxford) ; 20182018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30376045

RESUMO

OBJECTIVE: A major challenge in precision medicine is the development of patient-specific genetic biomarkers or drug targets. The firsthand information of the genes associated with the pathologic pathways of interest is buried in the ocean of biomedical literature. Gene ontology concept recognition (GOCR) is a biomedical natural language processing task used to extract and normalize the mentions of gene ontology (GO), the controlled vocabulary for gene functions across many species, from biomedical text. The previous GOCR systems, using either rule-based or machine-learning methods, treated GO concepts as separate terms and did not have an efficient way of sharing the common synonyms among the concepts. MATERIALS AND METHODS: We used the CRAFT corpus in this study. Targeting the compositional structure of the GO, we introduced named concept, the basic conceptual unit which has a conserved name and is used in other complex concepts. Using the named concepts, we separated the GOCR task into dictionary-matching and machine-learning steps. By harvesting the surface names used in the training data, we wildly boosted the synonyms of GO concepts via the connection of the named concepts and then enhanced the capability to recognize more GO concepts in the text. The source code is available athttps://github.com/jeroyang/ncgocr. RESULTS: Named concept gene ontology concept recognizer (NCGOCR) achieved 0.804 precision and 0.715 recall by correct recognition of the non-standard mentions of the GO concepts. DISCUSSION: The lack of consensus on GO naming causes diversity in the GO mentions in biomedical manuscripts. The high performance is owed to the stability of the composing GO concepts and the lack of variance in the spelling of named concepts. CONCLUSION: NCGOCR reduced the arduous work of GO annotation and amended the process of searching for the biomarkers or drug targets, leading to improved biomarker development and greater success in precision medicine.


Assuntos
Algoritmos , Pesquisa Biomédica , Ontologia Genética , Publicações , Semântica , Aprendizado de Máquina , Reprodutibilidade dos Testes
12.
Materials (Basel) ; 11(2)2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29425135

RESUMO

Electrochemical-metallization-type resistive random access memories (ReRAMs) show promising performance as next-generation nonvolatile memory. In this paper, the Cu chemical displacement technique (CDT) is used to form the bottom electrode of ReRAM devices. Compared with conventional deposition methods, the Cu-CDT method has numerous advantages for ReRAM fabrication, including low cost, low temperature fabrication, and the provision of unconsolidated Cu film and large surface roughness. Moreover, the Cu-CDT method is a favorable candidate for overcoming the Cu etching problem and is thus suitable for fabricating ReRAM devices. Using this technique, the surface morphology of a thin Cu film can be easily controlled. The obtained results show that the electric fields during the Forming and SET operations decreased, and the on-state current increased in the RESET operation, as the Cu-CDT displacement time was increased. The Cu-CDT samples exhibited a low operation field, large memory window (>106), and excellent endurance switching cycle characteristics. Moreover, this paper proposes a model to explain the electrical characteristics of ReRAM, which are dependent on the surface morphology.

13.
Chin J Physiol ; 61(1): 1-13, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29374954

RESUMO

Telmisartan (Tel) is recognized as a non-peptide blocker of AT1R. Whether this agent has any direct effects on ion currents remains unexplored. In whole-cell current recordings, addition of Tel increased the peak amplitude of voltage-gated Na⁺ (NaV) current (INa) accompanied by the increased time constant of INa inactivation in differentiated NSC-34 motor neuron-like cells. Tel-stimulated INa in these cells is unlinked to either blockade of AT1R or activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). In order to explore how this compound affects the amplitude and kinetics of INa in neurons, a Hodgkin-Huxley-based (HH-based) model designed to mimic effect of Tel on the functional activities of neurons was computationally created in this study. In this framework, the parameter for h inactivation gating variable, which was changed in a stepwise fashion, was implemented to predict changes in membrane potentials (V) as a function of maximal Na⁺ (GNa), K⁺ conductance (GK), or both. As inactivation time course of INa was increased, the bifurcation point of V versus GNa became lower, and the range between subcritical and supercritical values at the bifurcation of V versus GK correspondingly became larger. During a slowing in INa inactivation, the critical boundary between GNa and GK was shifted towards the left. Simulation studies demonstrated that progressive slowing in the inactivation time course of INa resulted in unanticipated increase of neuronal excitability by mimicking the effect of Tel in neuronal cells. Collectively, Tel can directly interact with the NaV channel to increase peak INa as well as to slow INa inactivation. It is thus highly likely that the effects of Tel or its structurally similar drugs could be another intriguing mechanism underlying their pharmacological actions in neurons or neuroendocrine cells occurring in vivo.


Assuntos
Benzimidazóis/farmacologia , Benzoatos/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Animais , Células Cultivadas , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , Telmisartan
14.
Eur J Pharmacol ; 819: 233-241, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29225191

RESUMO

Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic ß-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time-, state- and concentration-dependent manner in these cells and the inhibition was not reversed by diazoxide, nicorandil or chlorotoxin. The value of dissociation constant for CUR-induced suppression of IK(DR) in INS-1 cells was 1.26µM. Despite the inability of CUR to alter the activation rate of IK(DR), it accelerated current inactivation elicited by membrane depolarization. Increasing CUR concentrations shifted the inactivation curve of IK(DR) to hyperpolarized potential and slowed the recovery of IK(DR) inactivation. CUR, DMC, and BDMC all exerted depressant actions on IK(DR) amplitude to a similar magnitude, although DMC and BDMC did not increase current inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated Na+ current. CUR, DMC and BDMC depolarized the resting potential and increased firing frequency of action potentials. The CUR-mediated decrease of IK(DR) and the increase of current inactivation also occurred in ßTC-6 INS-1 cells. Taken these results together, these effects may be one of the possible mechanisms contributing their insulin-releasing effect.


Assuntos
Curcumina/química , Curcumina/farmacologia , Canais de Potássio de Retificação Tardia/metabolismo , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Cinética , Ratos
15.
Cell Physiol Biochem ; 41(5): 2053-2066, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28456794

RESUMO

BACKGROUND: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. METHODS: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH3) cells were evaluated by patch clamp techniques. RESULTS: ART inhibited the amplitude of delayed-rectifier K+ current (IK(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on IK(DR) with an IC50 value of 11.2 µM and enhanced IK(DR) inactivation with a KD value of 14.7 µM. The steady-state inactivation curve of IK(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of IK(DR) in GH3 cells. ART also decreased the peak amplitude of voltage-gated Na+ current (INa) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late INa, was effective at reversing ART-induced prolongation in inactivation time constant of INa. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. CONCLUSION: Under ART exposure, the inhibitory actions on both IK(DR) and INa could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Artemisininas/farmacologia , Canais de Potássio de Retificação Tardia/antagonistas & inibidores , Lactonas/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Animais , Canais de Potássio de Retificação Tardia/metabolismo , Relação Dose-Resposta a Droga , Proteínas de Neoplasias/metabolismo , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Prolactinoma/metabolismo , Prolactinoma/patologia , Ratos
16.
Biochim Biophys Acta ; 1864(1): 42-51, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26542736

RESUMO

Cdc42 regulates pathways related to cell division. Dysregulation of Cdc42 can lead to cancer, cardiovascular diseases and neurodegenerative diseases. GTP induced activation mechanism plays an important role in the activity and biological functions of Cdc42. P-loop, Switch I and Switch II are critical regions modulating the enzymatic activity of Cdc42. We applied amide hydrogen/deuterium exchange coupled with liquid chromatography mass spectrometry (HDXMS) to investigate the dynamic changes of apo-Cdc42 after GDP, GTP and GMP-PCP binding. The natural substrate GTP induced significant decreases of deuteration in P-loop and Switch II, moderate changes of deuteration in Switch I and significant changes of deuteration in the α7 helix, a region far away from the active site. GTP binding induced similar effects on H/D exchange to its non-hydrolysable analog, GMP-PCP. HDXMS results indicate that GTP binding blocked the solvent accessibility in the active site leading to the decrease of H/D exchange rate surrounding the active site, and further triggered a conformational change resulting in the drastic decrease of H/D exchange rate at the remote α7 helix. Comparing the deuteration levels in three activation states of apo-Cdc42, Cdc42-GDP and Cdc42-GMP-PCP, the apo-Cdc42 has the most flexible structure, which can be stabilized by guanine nucleotide binding. The rates of H/D exchange of Cdc42-GDP are between the GMP-PCP-bound and the apo form, but more closely to the GMP-PCP-bound form. Our results show that the activation of Cdc42 is a process of conformational changes involved with P-loop, Switch II and α7 helix for structural stabilization.


Assuntos
Medição da Troca de Deutério/métodos , Nucleotídeos de Guanina/química , Conformação Proteica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Proteína cdc42 de Ligação ao GTP/química , Sequência de Aminoácidos , Nucleotídeos de Guanina/metabolismo , Guanosina Difosfato/química , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/análogos & derivados , Guanosina Trifosfato/química , Guanosina Trifosfato/metabolismo , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Eletricidade Estática , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-25157073

RESUMO

Gene ontology (GO) annotation is a common task among model organism databases (MODs) for capturing gene function data from journal articles. It is a time-consuming and labor-intensive task, and is thus often considered as one of the bottlenecks in literature curation. There is a growing need for semiautomated or fully automated GO curation techniques that will help database curators to rapidly and accurately identify gene function information in full-length articles. Despite multiple attempts in the past, few studies have proven to be useful with regard to assisting real-world GO curation. The shortage of sentence-level training data and opportunities for interaction between text-mining developers and GO curators has limited the advances in algorithm development and corresponding use in practical circumstances. To this end, we organized a text-mining challenge task for literature-based GO annotation in BioCreative IV. More specifically, we developed two subtasks: (i) to automatically locate text passages that contain GO-relevant information (a text retrieval task) and (ii) to automatically identify relevant GO terms for the genes in a given article (a concept-recognition task). With the support from five MODs, we provided teams with >4000 unique text passages that served as the basis for each GO annotation in our task data. Such evidence text information has long been recognized as critical for text-mining algorithm development but was never made available because of the high cost of curation. In total, seven teams participated in the challenge task. From the team results, we conclude that the state of the art in automatically mining GO terms from literature has improved over the past decade while much progress is still needed for computer-assisted GO curation. Future work should focus on addressing remaining technical challenges for improved performance of automatic GO concept recognition and incorporating practical benefits of text-mining tools into real-world GO annotation. DATABASE URL: http://www.biocreative.org/tasks/biocreative-iv/track-4-GO/.


Assuntos
Biologia Computacional/métodos , Mineração de Dados , Ontologia Genética , Anotação de Sequência Molecular/métodos , Algoritmos , Humanos , Reprodutibilidade dos Testes
18.
Langmuir ; 29(51): 16025-33, 2013 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-24320707

RESUMO

A method for controlling the shapes and sizes of Cu nanoparticles during electrodeposition has been developed by tailoring the surface morphologies of TiN-coated electrodes. Larger octahedral Cu NPs grew on a granular TiN film; smaller, irregular Cu NPs formed on a pyramidal TiN film. The surface morphology of the TiN film affected the accumulation of Cu(2+) and hexadecyltrimethylammonium (CTA(+)) ions, leading to the different shapes and sizes of the resulting Cu NPs. The significant steric effect of the CTA(+) ions was confirmed when using the film of pyramidal TiN as the electrode in the CTAB-containing electrolyte; it contributed to the growth of the smaller, irregular Cu NPs. The sensitivity of the smaller, irregular Cu NPs in the detection of glucose was better than that of the larger, octahedral Cu NPs because of the former's greater increase in the Cu(2+)-to-Cu(0) ratio.


Assuntos
Técnicas Biossensoriais/métodos , Cobre/química , Nanopartículas Metálicas/química , Tamanho da Partícula , Titânio/química , Eletrodos , Glucose/análise , Propriedades de Superfície
19.
Neurointervention ; 8(2): 105-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24024075

RESUMO

The purpose of the technical note is to introduce the complex coil assisted coil embolization method in the treatment of intracranial small aneurysm, in order to enhance the safety of the procedure. The first microcatheter was navigated into the aneurysm sac and the ultrasoft coil was used as the embolization coil. If the embolizations coil could not stay within the aneurysm sac smoothly, such as coil herniation into parent artery during the delivery process. The second microcatheter would be navigated to the aneurysm level in the parent artery. Another complex coil was delivered within the parent artery via the second microcatheter to provide the neck bridge effect in order to enhance the stability of embolization coil. Besides, the protection coil will not disturb the parent artery flow. While the embolization coil was put into the aneurysm sac smoothly under the help of complex protective coil, the protective coil was then withdrawn gently. We use the most magnified view, dual-plane approach simultaneously to observe the stability of embolization coil. The embolization coil would be detached without any evidence of coil motion or vibration. The new method could provide the physiological protective method, without leaving any protective device such as stent within the parent artery.

20.
Am J Emerg Med ; 31(5): 775-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23465874

RESUMO

BACKGROUND: The clinical severities of upper gastrointestinal bleeding (UGIB) are of a wide variety, ranging from insignificant bleeds to fatal outcomes. Several scoring systems have been designed to identify UGIB high- and low-risk patients. The aim of our study was to compare the Glasgow-Blatchford score (GBS) with the preendoscopic Rockall score (PRS) and the complete Rockall score (CRS) in their utilities in predicting clinical outcomes in patients with UGIB. METHODS: We designed a prospective study to compare the performance of the GBS, PRS, and CRS in predicting primary and secondary outcomes in UGIB patients. The primary outcome included the need for blood transfusion, endoscopic therapy, or surgical intervention and was labeled as high risk. The secondary outcomes included rebleeding and 30-day mortality. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values for each system were analyzed. A total of 303 consecutive patients admitted with UGIB during a 1-year period were enrolled. RESULTS: For prediction of high-risk group, AUC was obtained for GBS (0.808), PRS (0.604), and CRS (0.767). For prediction of rebleeding, AUC was obtained for GBS (0.674), PRS (0.602), and CRS (0.621). For prediction of mortality, AUC was obtained for GBS (0.513), PRS (0.703), and CRS (0.620). CONCLUSIONS: In detecting high-risk patients with acute UGIB, GBS may be a useful risk stratification tool. However, none of the 3 score systems has good performance in predicting rebleeding and 30-day mortality because of low AUCs.


Assuntos
Doenças do Esôfago/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Índice de Gravidade de Doença , Gastropatias/diagnóstico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Terapia Combinada , Doenças do Esôfago/mortalidade , Doenças do Esôfago/terapia , Feminino , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/terapia , Técnicas Hemostáticas , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recidiva , Medição de Risco , Sensibilidade e Especificidade , Gastropatias/mortalidade , Gastropatias/terapia
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