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1.
Brief Bioinform ; 24(6)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37756591

RESUMEN

In the process of drug discovery, one of the key problems is how to improve the biological activity and ADMET properties starting from a specific structure, which is also called structural optimization. Based on a starting scaffold, the use of deep generative model to generate molecules with desired drug-like properties will provide a powerful tool to accelerate the structural optimization process. However, the existing generative models remain challenging in extracting molecular features efficiently in 3D space to generate drug-like 3D molecules. Moreover, most of the existing ADMET prediction models made predictions of different properties through a single model, which can result in reduced prediction accuracy on some datasets. To effectively generate molecules from a specific scaffold and provide basis for the structural optimization, the 3D-SMGE (3-Dimensional Scaffold-based Molecular Generation and Evaluation) work consisting of molecular generation and prediction of ADMET properties is presented. For the molecular generation, we proposed 3D-SMG, a novel deep generative model for the end-to-end design of 3D molecules. In the 3D-SMG model, we designed the cross-aggregated continuous-filter convolution (ca-cfconv), which is used to achieve efficient and low-cost 3D spatial feature extraction while ensuring the invariance of atomic space rotation. 3D-SMG was proved to generate valid, unique and novel molecules with high drug-likeness. Besides, the proposed data-adaptive multi-model ADMET prediction method outperformed or maintained the best evaluation metrics on 24 out of 27 ADMET benchmark datasets. 3D-SMGE is anticipated to emerge as a powerful tool for hit-to-lead structural optimizations and accelerate the drug discovery process.

2.
Stem Cells ; 42(2): 116-127, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-37952104

RESUMEN

Human dental pulp stem cells (hDPSCs) play a vital role in the regeneration of the pulp-dentin complex after pulp disease. While the regeneration efficiency relies on the odontoblastic differentiation capacity of hDPSCs, this is difficult to regulate within the pulp cavity. Although nicotinamide riboside (NR) has been found to promote tissue regeneration, its specific role in pulp-dentin complex regeneration is not fully understood. Here, we aimed to explore the role of NR in the odontoblastic differentiation of hDPSCs and its underlying molecular mechanism. It was found that NR enhanced the viability and retarded senescence in hDPSCs with higher NAD+/NADH levels. In contrast to the sustained action of NR, the multi-directional differentiation of hDPSCs was enhanced after NR pre-treatment. Moreover, in an ectopic pulp regeneration assay in nude mice, transplantation of hDPSCs pretreated with NR promoted the formation of a dentin-like structure surrounded by cells positively expressing DMP-1 and DSPP. RNA-Seq demonstrated inhibition of the HIF-1 signaling pathway in hDPSCs pretreated with NR. The number of HIF-1α-positive cells was significantly decreased in hDPSCs pretreated by NR in vivo. Similarly, NR significantly downregulated the expression of HIF-1α in vitro. The findings suggested that NR could potentially regulate hDPSC odontoblastic differentiation and promote the development of innovative strategies for dental pulp repair.


Asunto(s)
Pulpa Dental , Niacinamida , Odontoblastos , Compuestos de Piridinio , Animales , Humanos , Ratones , Diferenciación Celular , Células Cultivadas , Ratones Desnudos , Niacinamida/análogos & derivados , Regeneración , Transducción de Señal , Células Madre/metabolismo
3.
J Formos Med Assoc ; 123 Suppl 2: S104-S113, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37173227

RESUMEN

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.


Asunto(s)
Hiperaldosteronismo , Hipertensión , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Hidrocortisona , Captopril
4.
Eur J Dent Educ ; 28(2): 621-630, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38234068

RESUMEN

INTRODUCTION: To summarize the development of Innovative Undergraduate Dental Talents Training Project (IUDTTP) and investigate the training effect of this extracurricular dental basic research education activity from 2015 to 2020 to obtain educational implications. MATERIALS AND METHODS: The Guanghua School of Stomatology established the IUDTTP in 2015. The authors recorded the development process and analysed the participation situation, training effect, academic performance and overall satisfaction during 2015-2020 through documental analysis, questionnaire and quiz. The t-test, chi-square test and ANOVA were used to test the difference. RESULTS: The educational goal, education module and assessment system of IUDTTP evolved and developed every year. A total of 336 students and 79 mentors attended the IUDTTP from 2015 to 2020, with the participation rate increasing from 45.1% to 73.5%. The participants exhibited favourable basic research abilities, manifesting as the increase of funded projects and published papers and satisfying quiz scores. Almost all students (94.94%) admitted their satisfaction with the IUDTTP. Moreover, the attended students surpassed the non-participants in terms of GPA, the number of acquired scholarships and outstanding graduates (p < .05). Likewise, the enrolment rate of postgraduate participants was significantly higher than non-participants. CONCLUSIONS: To date, the training effect indicated that the IUDTTP has fulfilled the education aim. It brought positive effects on promoting research interest, cultivating research capacities and enhancing academic performance. The potential deficiencies of extracurricular educational activities, including inflexibility in schedule and insufficiency in systematisms, may be remedied by more systematic educational settings in the future.


Asunto(s)
Educación en Odontología , Estudiantes , Humanos , Estudios Retrospectivos , Motivación
5.
Eur J Dent Educ ; 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38148502

RESUMEN

INTRODUCTION: Virtual reality (VR) and haptic simulation technology have been increasingly implemented in dental training. Since the first haptic VR dental simulator (Simodont) was introduced 10 years ago, it has been applied in more than 40 universities in mainland China. This scoping review aimed to review literature, showcasing the teaching reform of dental virtual simulation in mainland China to global dental education peers. METHODS: This scoping review was conducted using the PRISMA extension for scoping review guidelines. Seven electronic databases were searched, and two reviewers independently performed the selection and characterization of the studies. RESULTS: The final scoping review included 12 studies. Four studies focused on the G. V. Black class II cavity, three on manual dexterity skills training, two on full metal crown preparation, one on pulpal access and coronal cavity preparation, one on flipped classroom teaching, and one on 'doctor-patient communication' skills. DISCUSSION: The most critical scenarios, self-assessment, working posture, curriculum setting, training and cost are analysed and discussed. CONCLUSION: Haptic simulation technology is a valuable complementary tool to the phantom head in dental education. The combined utilization of these two training devices has been superior to either in isolation. However, there is a lack of research on the sequencing of the two systems, as well as the appropriate distribution of curriculum between them. It is necessary for educators to organize or engage in experience sharing, collaboration and knowledge dissemination. These actions are essential for promoting effective teaching within dental educational institutions.

6.
Exp Cell Res ; 400(2): 112495, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33524362

RESUMEN

Pulpitis refers to inflammation of the inner pulp by invading microbes, and tissue repair occurs due to odontogenic differentiation of human dental pulp cells (hDPCs) with multidifferentiation potential. Long noncoding RNAs (lncRNAs) can modulate numerous pathological and biological processes; however, the role of lncRNAs in the inflammation and regeneration of the dentin-pulp complex in pulpitis is unclear. Here, we performed high-throughput sequencing to identify differentially expressed lncRNAs between human normal and inflamed pulp and concluded that lncMEG3 (lncRNA maternally expressed gene 3, MEG3) was significantly upregulated in both inflamed pulp and LPS-treated hDPCs. MEG3 expression in the pulp tissue was detected using the RNAscope® technique. RNA pulldown assays identified the MEG3-interacting proteins and the potential mechanisms. With MEG3 knockdown, we investigated the role of MEG3 in the secretion of inflammatory cytokines in LPS-treated hDPCs and odontogenic differentiation of hDPCs. MEG3 downregulation inhibited the secretion of TNF-α, IL-1ß and IL-6 in LPS-treated hDPCs, and the p38/MAPK signaling pathway may be related to this effect. MEG3 knockdown promoted odontogenic differentiation of hDPCs by regulating the Wnt/ß-catenin signaling pathway. Our study suggested that MEG3 has a negative effect on inflammation and regeneration of the dentin-pulp complex in pulpitis.


Asunto(s)
Diferenciación Celular , Pulpa Dental/citología , Inflamación/patología , Lipopolisacáridos/efectos adversos , Odontogénesis , Pulpitis/patología , ARN Largo no Codificante/genética , Adolescente , Adulto , Apoptosis , Biomarcadores/metabolismo , Proliferación Celular , Células Cultivadas , Citocinas/metabolismo , Pulpa Dental/metabolismo , Regulación de la Expresión Génica , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Pulpitis/genética , Pulpitis/metabolismo , Adulto Joven
7.
Bioorg Chem ; 109: 104701, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33601137

RESUMEN

Four series of double-ring conjugated enones were designed, synthesized and studied for the inhibition of synovial cell activity through the modification of Dysodensiol K core structure, double-ring, double-bond and double-carbonyl groups. For in vitro synovial cell assay of rats, compound 151 and 168 exhibited good inhibitory activities, with IC50 values of 2.71 ± 0.18 and 2.68 ± 0.16 µM respectively. At the same time, the LDH release and LD50 test results revealed that the target compounds were low cytotoxicity and acute toxicity. For in vivo CIA model test through the oral administration, compounds 151 and 168 were exhibited similar effect to positive control group methotrexate.


Asunto(s)
Annonaceae/química , Antirreumáticos/síntesis química , Antirreumáticos/farmacología , Diseño de Fármacos , Animales , Antirreumáticos/efectos adversos , Antirreumáticos/química , L-Lactato Deshidrogenasa/metabolismo , Modelos Moleculares , Estructura Molecular , Ratas , Relación Estructura-Actividad , Membrana Sinovial/citología
8.
Int J Clin Pract ; 75(10): e14491, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34115914

RESUMEN

AIMS: Diabetes mellitus is a major cause of death worldwide, including Taiwan. The mortality data of the subsets of patients who suffered from microvascular or macrovascular complications is limited. The aim of this study was to investigate the causes of in-hospital death of patients with type 2 diabetes, especially the patients with microvascular, macrovascular and both micro-macrovascular complications. METHODS: A total of 12 159 patients with type 2 diabetes were identified from the Taiwan National Health Insurance Research Database (NHIRD) to analyse the causes of death. Type 2 diabetic subjects with microvascular, macrovascular and both micro-macrovascular complications were further classified and compared to patients without microvascular and macrovascular complications in the logistic regression analysis of the risk of death. RESULTS: Pneumonia increased risk of in-hospital death in patients with microvascular, macrovascular and both micro-macrovascular complications, with adjusted odds ratios (AORs) of 2.13 (95% confidence interval [CI] 1.09-4.18), 3.26 (1.71-6.24) and 3.96 (2.17-7.22), respectively. Septicaemia increased risk of in-hospital death in patients with macrovascular (AOR 2.57 [1.31-5.04]) and both micro-macrovascular complications (AOR 4.69 [2.58-8.50]). CONCLUSION: Pneumonia increased risk of in-hospital death among the type 2 diabetic patients with microvascular, macrovascular and both micro-macrovascular complications. Therefore, efforts aim at preventing pneumonia or decreasing its severity may increase survival.


Asunto(s)
Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Diabetes Mellitus Tipo 2/complicaciones , Mortalidad Hospitalaria , Humanos , Factores de Riesgo , Taiwán/epidemiología
9.
Chem Biodivers ; 18(12): e2100687, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34726832

RESUMEN

Toxoplasmosis post serious threaten to human health, leading to severely eye and brain disease, especially for immunocompromised patients and pregnant women. The multiple side effects and long dosing period of current main treatment regiments calls for high effective and low toxicity anti-toxoplasmosis drugs. Herein, we report our efforts to synthesize a series of 2-(piperazin-1-yl)quinazolin-4(3H)-one derivatives and investigate their activity against Toxoplasma gondii tachyzoites in vitro based on cell phenotype screening. Among the 26 compounds, 8w and 8x with diaryl ether moiety at the side chain of piperazine exhibited good efficacy to inhibit T. gondii, with IC50 values of 4 µM and 3 µM, respectively. Structure-activity relationship (SAR) studies implies that hydrophobic aryl at the side chain would be preferred for improvement of activity. Molecular docking study reveals these two compounds appeared high affinity to TgCDPK1 by interaction with the hydrophobic pocket of ATP-binding cleft.


Asunto(s)
Antiprotozoarios/farmacología , Quinazolinonas/farmacología , Toxoplasma/efectos de los fármacos , Antiprotozoarios/síntesis química , Antiprotozoarios/química , Relación Dosis-Respuesta a Droga , Simulación del Acoplamiento Molecular , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Quinazolinonas/síntesis química , Quinazolinonas/química
10.
BMC Med Educ ; 21(1): 403, 2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34315452

RESUMEN

BACKGROUND: The National Dental Undergraduate Clinical Skills Competition known as the Guanghua Cup was held in Guangzhou, China, for three consecutive years from 2017 to 2019 to promote the clinical teaching of undergraduate dental education and to enhance communication among different universities. The present study aimed to introduce the organization, procedures, and consequences of the competition, in addition to analyzing the influences of competition on the reform of undergraduate dental education. METHODS: By analyzing the descriptive statistics of the Guanghua Cup, the competitions' organization, the participating students' performances, and the outcomes of competitions were analyzed. After distributing questionnaires to all participants of the 2nd and 3rd Cups, their attitudes towards the competition and their evaluation of the role of the competitions in promoting undergraduate dental education were analyzed. RESULTS: A total of 24 schools participated in the 3 competition years. The contents of the competitions covered cariology, endodontics, periodontology, prosthodontics, oral and maxillofacial surgery, dental anatomy, and first aid (e.g., operative skills and theoretical knowledge). Compared with those of the 2nd Cup, the mean scores of the operative skills significantly improved in the stations related to periodontology, prosthodontics, and dental anatomy (p < 0.05) in the 3rd Cup. In addition, 338 valid questionnaires were collected, for a response rate of 87.79 %. Overall, the participants spoke highly of the Guanghua Cup. Based on their self-perception and self-evaluation, the majority of interviewees agreed that the competition helped develop collegiality and teamwork among the participating students, improved the students' clinical skills and promoted the improvement of teaching resources (e.g., purchasing and updating equipment, models or experimental materials). CONCLUSIONS: The competition enjoyed the widest coverage since it involved dental schools from all of the different geographical regions of China. Dental students could exhibit their clinical skills in a competitive environment and develop collegiality and teamwork. Future competitions should be optimized through their organization and contents. The education quality of the participating schools affected by such competition should be investigated in a more objective and comparable way.


Asunto(s)
Competencia Clínica , Endodoncia , China , Educación en Odontología , Humanos , Estudiantes , Encuestas y Cuestionarios
11.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34445703

RESUMEN

Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.


Asunto(s)
Pulpa Dental/metabolismo , Pulpa Dental/fisiología , Regeneración Tisular Guiada Periodontal/métodos , Animales , Humanos , Células Madre Mesenquimatosas/metabolismo , Regeneración/fisiología , Estudios Retrospectivos , Tratamiento del Conducto Radicular/métodos , Células Madre/metabolismo , Ingeniería de Tejidos/métodos
12.
Phys Chem Chem Phys ; 22(16): 8808-8816, 2020 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-32285900

RESUMEN

Amorphous CaO-SiO2-Al2O3 (CSA) slags are widely used in the glass, ceramic, cement and metallurgy industries. Temperature, as an external condition, plays an important role in the thermal conductivity of silicates. Herein, the effects of temperature on the thermal conductivity of CSA slags were systematically investigated by using equilibrium molecular dynamics (EMD) simulations. Moreover, the effects of the composition and the structural unit on the thermal conductivity of CSA slags were examined. The results showed that the thermal conductivity of amorphous CSA slags significantly increases with an increase in temperature in the range of 1273 to 1973 K. Furthermore regression analysis based on a machine learning method showed that the temperature is the most crucial factor that affects the thermal conductivity of amorphous CSA slags, and high CaO/Al2O3 and CaO/SiO2 molar ratios can lead to high thermal conductivity.

13.
BMC Med Educ ; 20(1): 474, 2020 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-33243248

RESUMEN

BACKGROUND: English education in professional areas has become more and more important with the increasing internationalization of health profession education in countries around the world. In this study, we aimed to evaluate current Chinese stomatology English education based on Chinese participants' ability to apply stomatology English during an international stomatology skill competition called the 'Guanghua Cup activity'. METHODS: The registration rate of English and Chinese volunteers and the answer rate and accuracy of Chinese and international contestants on the English knowledge quiz were statistically described. A five-point Likert scale questionnaire was delivered to all participants. The data were analyzed using the Spearman test, Kruskal-Wallis rank sum test and Mann-Whitney U test. RESULTS: Among the 194 students, the English and Chinese volunteer registration rate was 7.73 and 30.93%, respectively. The answer rate of Chinese contestants and international contestants in the English quiz was 25 and 75%, with an accuracy rate of 50 and 66.70%, respectively. The questionnaire was graded by Likert five-level classification. There was a positive correlation between the use of English textbooks in classes and the communication with international teachers and students in the competition (Rs = 0.348, p = 0.016). English volunteers had more preparation in English before the competition, more opportunities to communicate with international peers, and greater improvement in English ability than the contestants and Chinese volunteers (p < 0.001). After the competition, all participants paid more attention to stomatology English (p < 0.001). CONCLUSIONS: Chinese stomatology students have difficulty in stomatology English application. The 'Guanghua Cup' helps to improve English proficiency of English volunteers and arouses the interest of stomatology English for all participants. Chinese stomatology school needs to strengthen and reach a consensus in stomatology English education.


Asunto(s)
Medicina Oral , China , Competencia Clínica , Humanos , Estudiantes , Encuestas y Cuestionarios
14.
Int J Mol Sci ; 21(7)2020 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-32252223

RESUMEN

Accumulated evidence suggests that binding kinetic properties-especially dissociation rate constant or drug-target residence time-are crucial factors affecting drug potency. However, quantitative prediction of kinetic properties has always been a challenging task in drug discovery. In this study, the VolSurf method was successfully applied to quantitatively predict the koff values of the small ligands of heat shock protein 90α (HSP90α), adenosine receptor (AR) and p38 mitogen-activated protein kinase (p38 MAPK). The results showed that few VolSurf descriptors can efficiently capture the key ligand surface properties related to dissociation rate; the resulting models demonstrated to be extremely simple, robust and predictive in comparison with available prediction methods. Therefore, it can be concluded that the VolSurf-based prediction method can be widely applied in the ligand-receptor binding kinetics and de novo drug design researches.


Asunto(s)
Biología Computacional , Descubrimiento de Drogas , Ligandos , Modelos Moleculares , Bibliotecas de Moléculas Pequeñas , Programas Informáticos , Biología Computacional/métodos , Diseño de Fármacos , Proteínas HSP90 de Choque Térmico/agonistas , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/química , Cinética , Modelos Teóricos , Unión Proteica , Relación Estructura-Actividad Cuantitativa , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/química
15.
Molecules ; 25(24)2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33353070

RESUMEN

The ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp) is a physiologically essential membrane protein that protects many tissues against xenobiotic molecules, but limits the access of chemotherapeutics into tumor cells, thus contributing to multidrug resistance. The atomic-level mechanism of how substrates and inhibitors differentially affect the ATP hydrolysis by P-gp remains to be elucidated. In this work, atomistic molecular dynamics simulations in an explicit membrane/water environment were performed to explore the effects of substrate and inhibitor binding on the conformational dynamics of P-gp. Distinct differences in conformational changes that mainly occurred in the nucleotide-binding domains (NBDs) were observed from the substrate- and inhibitor-bound simulations. The binding of rhodamine-123 can increase the probability of the formation of an intermediate conformation, in which the NBDs were closer and better aligned, suggesting that substrate binding may prime the transporter for ATP hydrolysis. By contrast, the inhibitor QZ-Leu stabilized NBDs in a much more separated and misaligned conformation, which may result in the deficiency of ATP hydrolysis. The significant differences in conformational modulation of P-gp by substrate and inhibitor binding provided a molecular explanation of how these small molecules exert opposite effects on the ATPase activity. A further structural analysis suggested that the allosteric communication between transmembrane domains (TMDs) and NBDs was primarily mediated by two intracellular coupling helices. Our computational simulations provide not only valuable insights into the transport mechanism of P-gp substrates, but also for the molecular design of P-gp inhibitors.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Simulación de Dinámica Molecular , Péptidos Cíclicos/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/química , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfato/metabolismo , Regulación Alostérica/efectos de los fármacos , Colorantes Fluorescentes/química , Humanos , Hidrólisis , Péptidos Cíclicos/química , Conformación Proteica , Rodamina 123/química
16.
J Chem Inf Model ; 59(1): 159-169, 2019 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-30422654

RESUMEN

Recent research has increasingly suggested that the crucial factors affecting drug potencies are related not only to the thermodynamic properties but also to the kinetic properties. Therefore, in silico prediction of ligand-binding kinetic properties, especially the dissociation rate constant ( koff), has aroused more and more attention. However, there are still a lot of challenges that need to be addressed. In this paper, steered molecular dynamics (SMD) combined with residue-based energy decomposition was employed to predict the dissociation rate constants of 37 HIV-1 protease inhibitors (HIV-1 PIs). For the first time, a predictive model of the dissociation rate constant was established by using the interaction-energy fingerprints sampled along the ligand dissociation pathway. On the basis of the key fingerprints extracted it can be inferred that the dissociation rates of 37 HIV-1 PIs are basically determined in the first half of the dissociation processes and that the H-bond interactions with active-site Asp25 and van der Waals interactions with flap-region Ile47 and Ile50 have important influences on the dissociation processes. In general, the strategy established in this paper can provide an efficient way for the prediction of dissociation rate constants as well as the unbinding mechanism research.


Asunto(s)
Inhibidores de la Proteasa del VIH/química , Simulación de Dinámica Molecular , Dominio Catalítico , Proteasa del VIH/metabolismo , Inhibidores de la Proteasa del VIH/farmacología , Enlace de Hidrógeno , Cinética , Termodinámica
17.
Sensors (Basel) ; 18(12)2018 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-30558327

RESUMEN

Tactility is an essential perception for intelligent equipment to acquire external information. It can improve safety and performance during human-machine interactions. Based on the uniqueness theorem of the electrostatic field, a novel flexible film tactile sensor that can detect contact position and be made into any plane shape is proposed in this paper. The tactile sensor included an indium tin oxide (ITO) film, which was uniformly coated on the polyethylene terephthalate (PET) substrate. A specially designed strong conductive line was arranged along the edge of the flexible ITO film, which has weak conductivity. A bias excitation was applied to both ends of the strong conductive line. Through the control of the shape of the strong conductive line, a uniform electric field can be constructed in the whole weak conductive plane. According to the linear relationship between position and potential in the uniform electric field, the coordinate of the contact position can be determined by obtaining the potential of the contact point in the weak conducting plane. The sensor uses a three-layer structure, including an upper conductive layer, an intermediate isolation layer, and a lower conductive layer. A tactile sensor sample was fabricated. The experiment results showed that the principle of the tactile sensor used for the contact position detection is feasible and has certain precision of position detection. The sensor has good flexibility, and can be made into any plane shape, and has only four wires. It is capable of covering large areas of robot arms, and provides safety solutions for most robots.

18.
Sensors (Basel) ; 19(1)2018 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-30577675

RESUMEN

Electronic skin is an important means through which robots can obtain external information. A novel flexible tactile sensor capable of simultaneously detecting the contact position and force was proposed in this paper. The tactile sensor had a three-layer structure. The upper layer was a specially designed conductive film based on indium-tin oxide polyethylene terephthalate (ITO-PET), which could be used for detecting contact position. The intermediate layer was a piezoresistive film used as the force-sensitive element. The lower layer was made of fully conductive material such as aluminum foil and was used only for signal output. In order to solve the inconsistencies and nonlinearity of the piezoresistive properties for large areas, a Radial Basis Function (RBF) neural network was used. This includes input, hidden, and output layers. The input layer has three nodes representing position coordinates, X, Y, and resistor, R. The output layer has one node representing force, F. A sensor sample was fabricated and experiments of contact position and force detection were performed on the sample. The results showed that the principal function of the tactile sensor was feasible. The sensor sample exhibited good consistency and linearity. The tactile sensor has only five lead wires and can provide the information support necessary for safe human-computer interactions.

19.
J Prosthet Dent ; 120(4): 609-616, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29724549

RESUMEN

STATEMENT OF PROBLEM: The use of composite resin to restore teeth has increased substantially during the last decades. However, secondary caries and the fracture of restorations are the leading reasons for clinical restoration failure. Mechanically strong composite resins with caries-inhibition capabilities are needed. Although antibacterial dimethacrylate quaternary ammonium monomers have been synthesized, composite resin containing dimethacrylate quaternary ammonium monomers and glass fillers has rarely been reported. PURPOSE: The purpose of this in vitro study was to evaluate the possibility of the clinical use of an experimental composite resin containing urethane dimethacrylate quaternary ammonium compound (UDMQA-12) by investigating its antibacterial activity, cytotoxicity, flexural strength, and flexural modulus. MATERIAL AND METHODS: Antibacterial activity against Streptococcus mutans was investigated by means of direct contact test. The antibacterial activity of specimens after water immersion and saliva treatment was also tested. These were compared with a commercially available composite resin, Z250, and a glass ionomer cement, Fuji VII. Effects of the eluent from the experimental composite resin on the metabolic activity of human dental pulp cells were quantified. Disks of 1 mm in thickness and 15 mm in diameter were used in the antibacterial and cytotoxic tests. Flexural strength and flexural modulus were measured with a 3-point bend test with bars of 2×2×25 mm. Three commercially available composite resins (Filtek Z250, G-aenial Anterior, and G-aenial Posterior) were used as controls in the flexural test. RESULTS: Bacterial growth was inhibited on the experimental composite resin. After water immersion or saliva treatment, the experimental composite resin showed significant antibacterial effect compared with the conventional composite resin (P<.05). No significant difference was found in cytotoxicity between the experimental composite resin and the conventional composite resin (P>.05), and a significantly higher cytotoxicity was shown by glass ionomer cement compared with the experimental composite resin and the conventional composite resin (P<.05). The conventional composite resin had the highest flexural strength and flexural modulus (P<.05), followed by the experimental composite resin, then G-ænial Posterior and G-ænial Anterior. CONCLUSIONS: The antibacterial experimental composite resin was biocompatible and had mechanical properties similar to those of some commercially available composite resins. It might, therefore, be useful in preventing the occurrence of secondary caries.


Asunto(s)
Antibacterianos/farmacología , Resinas Compuestas/farmacología , Citotoxinas/farmacología , Compuestos de Amonio Cuaternario/farmacología , Antibacterianos/química , Resinas Compuestas/química , Citotoxinas/química , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Resistencia Flexional , Humanos , Técnicas In Vitro , Metacrilatos/química , Metacrilatos/farmacología , Pruebas de Sensibilidad Microbiana , Poliuretanos/química , Poliuretanos/farmacología , Compuestos de Amonio Cuaternario/química , Streptococcus mutans/efectos de los fármacos
20.
Cell Tissue Res ; 364(2): 309-18, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26646542

RESUMEN

Long noncoding RNAs (lncRNAs) have recently emerged as an important class of regulatory molecules in diverse biological processes, although lncRNA involvement in the odontoblast-like differentiation of human dental pulp cells (hDPCs) is poorly understood. We investigate the expression of lncRNAs in this differentiation and explore their underlying role and the involved mechanism. Integrated comparative lncRNA microarray profiling was used to examine lncRNA expression during this differentiation. The differential expression of lncRNAs was validated by quantitative real-time reverse transcription plus the polymerase chain reaction. Differential lncRNA overexpression was performed with an adenoviral vector and the role and mechanism was then investigated in odontoblast-like differentiation. We identified 139 differentially expressed lncRNAs during this differentiation. Among them, five lncRNAs differentially expressed in microarray analysis were validated. Notably, lncRNA DANCR expression was significantly downregulated during hDPC differentiation to odontoblast-like cells in a time-dependent manner. Moreover, lncRNA DANCR overexpression blocked mineralized nodule formation and the expression of DSPP and DMP-1 in hDPCs after 14 days of odontogenic induction. Importantly, the upregulation of DANCR significantly decreased the expression levels of p-GSK-3ß and ß-catenin expression indicating that lncRNA DANCR can inhibit the activation of the Wnt/ß-catenin signal pathway during the odontoblast-like differentiation of hDPCs. Thus, the modulation of Wnt/ß-catenin signaling by lncRNA DANCR represents a potential therapeutic option for reparative dentin formation and regenerative endodontics.


Asunto(s)
Diferenciación Celular/genética , Pulpa Dental/citología , Odontoblastos/citología , Odontogénesis/genética , ARN Largo no Codificante/genética , Proteínas Wnt/antagonistas & inhibidores , Vía de Señalización Wnt/genética , beta Catenina/antagonistas & inhibidores , Células Cultivadas , Dentina/metabolismo , Glucógeno Sintasa Quinasa 3 beta/biosíntesis , Humanos , beta Catenina/biosíntesis
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