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1.
Acta Pharmacol Sin ; 40(11): 1373-1385, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31444476

RESUMEN

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a "bystander effect" of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.


Asunto(s)
ADN/uso terapéutico , Técnicas de Transferencia de Gen , Neoplasias/terapia , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Animales , Antineoplásicos/uso terapéutico , Apoptosis/fisiología , Línea Celular Tumoral , Dendrímeros/química , Sinergismo Farmacológico , Terapia Genética/métodos , Humanos , Liposomas/química , Neoplasias/tratamiento farmacológico , Péptidos Cíclicos/química
2.
Yi Chuan ; 41(6): 469-485, 2019 Jun 20.
Artículo en Zh | MEDLINE | ID: mdl-31257196

RESUMEN

The field of circular non-coding RNAs have been gradually attracted wide attention with the developments of high-throughput sequencing. In this review, we systematically summarize three driving models for circRNAs biogenesis: intron-pairing-driven, RNA binding protein-driven and lariat-driven. In addition, we also briefly introduce the current research methods of circRNAs, which include high-throughput library construction methods, identification through bioinformatics and common experimental verification. Here, we also systematically summarize the functions of circRNAs, including microRNA (miRNA) or protein sponges, regulating the alternative splicing (AS) and expression of host genes, and extensive translation. Finally, we provide a systematic characterization and the latest research progress of circRNAs, which provide a new perspective for further studies of circRNAs in plants.


Asunto(s)
Empalme Alternativo , ARN/genética , Intrones , MicroARNs , Modelos Genéticos , Plantas/genética , ARN Circular , Proteínas de Unión al ARN
3.
Acta Pharmacol Sin ; 38(6): 885-896, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28479604

RESUMEN

Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes). The Man-liposomes had a mean diameter of 158.8 nm and zeta potential of -15.8 mV. In the HCT8/ADR cells that overexpress the mannose receptors, the Man-liposomes altered the intracellular distribution of Dox, resulting in a high accumulation of Dox in the nuclei and thus displaying the highest cytotoxicity (IC50=0.073 µg/mL) among all the groups. In a subcutaneous HCT8/ADR tumor xenograft model, administration of the Man-liposomes resulted in a tumor inhibition rate of 88.59%, compared to that of 47.46% or 70.54%, respectively, for the treatment with free Dox or free Dox+DHA. The mechanisms underlying the anti-MDR effect of the Man-liposomes involved preferential nuclear accumulation of the therapeutic agents, enhanced cancer cell apoptosis, downregulation of Bcl-xl, and the induction of autophagy.


Asunto(s)
Antineoplásicos/farmacología , Artemisininas/farmacología , Neoplasias del Colon/tratamiento farmacológico , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Artemisininas/administración & dosificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/patología , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Liposomas/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Relación Estructura-Actividad
5.
Acta Pharmacol Sin ; 37(8): 1110-20, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27292613

RESUMEN

AIM: Drug efflux-associated multidrug resistance (MDR) is a main obstacle to effective cancer chemotherapy. Large molecule drugs are not the substrates of P-glycoprotein, and can circumvent drug efflux and be retained inside cells. In this article we report a polymer-drug conjugate nanoparticulate system that can overcome MDR based on size-related exclusion effect. METHODS: Doxorubicin was coupled with the triblock polymeric material cell-penetrating TAT-PEG-poly(aspartic acid). The amphiphilic macromolecules (termed TAT-PEG-Asp8-Dox) could self-assemble into nanoparticles (NPs) in water. The antitumor activity was evaluated in drug-resistant human colon cancer HCT8/ADR cells in vitro and in nude mice bearing HCT8/ADR tumor. RESULTS: The self-assembling TAT-PEG-Asp8-Dox NPs were approximately 150 nm with a narrow particle size distribution, which not only increased the cellular uptake efficiency, but also bypassed P-glycoprotein-mediated drug efflux and improved the intracellular drug retention, thus yielding an enhanced efficacy for killing drug-resistant HCT8/ADR colon cancer cells in vitro. Importantly, the TAT-PEG-Asp8-Dox NPs enhanced the intranuclear disposition of drugs for grater inhibition of DNA/RNA biosynthesis. In nude mice bearing xenografted HCT8/ADR colon cancers, intravenous or peritumoral injection of TAT-PEG-Asp8-Dox NPs for 22 d effectively inhibited tumor growth. CONCLUSION: TAT-PEG-Asp8-Dox NPs can increase cellular drug uptake and intranuclear drug delivery and retain effective drug accumulation inside the cells, thus exhibiting enhanced anticancer activity toward the drug-resistant human colon cancer HCT8/ADR cells.


Asunto(s)
Antineoplásicos/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/farmacocinética , Portadores de Fármacos/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Nanopartículas/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Péptidos de Penetración Celular/química , ADN/biosíntesis , Doxorrubicina/administración & dosificación , Portadores de Fármacos/farmacocinética , Humanos , Ratones , Ratones Desnudos , Nanopartículas/química , Tamaño de la Partícula , Péptidos/química , Polietilenglicoles/química , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Heliyon ; 10(3): e24746, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38318012

RESUMEN

Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.

7.
Bioconjug Chem ; 23(1): 125-34, 2012 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-22148643

RESUMEN

Cellular uptake and nuclear localization are two major barriers in gene delivery. In order to evaluate whether additional nuclear localization signals (NLSs) can improve gene transfection efficiency, we introduced different kinds of NLSs to TAT-based gene delivery systems to form three kinds of complexes, including TAT-PV/DNA, TAT/DNA/PV, and TAT/DNA/HMGB1. The DNA binding ability of different vectors was evaluated by agarose gel electrophoresis. The in vitro transfections mediated by different complexes under different conditions were carried out. The cells treated by different complexes were observed by confocal microscopy. The MTT assay showed that all complexes did not exhibit apparent cytotoxicity in both HeLa and Cos7 cell lines even at high N/P ratios. The luciferase reporter gene expression mediated by TAT-PV/DNA complexes exhibited about 200-fold enhancement as compared with TAT/DNA complexes. Confocal study showed that, except TAT/DNA/PV, all other complexes exhibited enhanced nuclear accumulation and cellular uptake in both HeLa and Cos7 cell lines. These results indicated that the introduction of nuclear localization signals could enhance the transfection efficacy of TAT-based peptides, implying that the TAT peptide-based vectors demonstrated here have promising potential in gene delivery.


Asunto(s)
Núcleo Celular/metabolismo , Productos del Gen tat/genética , Señales de Localización Nuclear/metabolismo , Transducción de Señal/genética , Transfección/métodos , Transporte Activo de Núcleo Celular , Animales , Células COS , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Chlorocebus aethiops , ADN/genética , Productos del Gen tat/química , Productos del Gen tat/farmacología , Proteína HMGB1/genética , Células HeLa , Humanos , Relación Estructura-Actividad
8.
Chemistry ; 18(8): 2297-304, 2012 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-22250041

RESUMEN

Two thermo- and pH-sensitive polypeptide-based copolymers, poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide)-b-poly(L-lysine) (P(NIPAAm-co-HMAAm)-b-PLL, P1) and poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide)-b-poly(glutamic acid) (P(NIPAAm-co-HMAAm)-b-PGA, P2), have been designed and synthesized by the ring-opening anionic polymerization of N-carboxyanhydrides (NCA) with amino-terminated P(NIPAAm-co-HMAAm). It was found that the block copolymers exhibit good biocompatibility and low toxicity. As a result of electrostatic interactions between the positively charged PLL and negatively charged PGA, P1 and P2 formed polyion complex (PIC) micelles consisting of polyelectrolyte complex cores and P(NIPAAm-co-HMAAm) shells in aqueous solution. The thermo- and pH-sensitivity of the PIC micelles were studied by UV/Vis spectrophotometry, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Moreover, fluorescent PIC micelles were achieved by introducing two fluorescent molecules with different colors. Photographs and confocal laser scanning microscopy (CLSM) showed that the fluorescence-labeled PIC micelles exhibit thermo- and pH-dependent fluorescence, which may find wide applications in bioimaging in complicated microenvironments.


Asunto(s)
Péptidos/química , Ácido Poliglutámico/análogos & derivados , Polilisina/análogos & derivados , Agua/química , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Micelas , Estructura Molecular , Ácido Poliglutámico/síntesis química , Ácido Poliglutámico/química , Polilisina/síntesis química , Polilisina/química , Polimerizacion , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(3): 669-72, 2012 Mar.
Artículo en Zh | MEDLINE | ID: mdl-22582629

RESUMEN

The present research studied the thermal stability of oxalic acid under high temperature and pressure and its in-situ transformation by Raman spectroscopy using a hydrothermal diamond anvil cell. Raman spectra allow the detection of ionic and covalent atomic aggregates through the acquisition of vibrational spectra that are characteristic of their structures and molecular bond types. The result showed that there was no change in characteristic vibrational Raman peaks of oxalic acid in the low-temperature stage. With the increase in temperature and pressure, the characteristic vibrational Raman peaks of oxalic acid became weaker and the peaks disappeared at a certain high temperature, and decarboxylation happened. Oxalic acid decomposes to produce CO2 and H2, according to the reaction: C2 H2O4-2CO2 + H2. It was found that the decarboxylation was highly related with pressure and that the decarboxylation would be hindered at high pressure. Decarboxylation of oxalic acid under high temperature and pressure showed a linear relationship between temperature and pressure. The data fitting generated the formula: P(MPa) = 12. 839T(K)-5 953.7, R2 = 0.99. The molar volume change of decarboxylation of oxalic acid can be described by deltaV(cm(-3) x mol(-1)) = 16.69-0.002P (MPa) + 0.005 2T(K), R = 0.99.

10.
Psychol Res Behav Manag ; 15: 1271-1282, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35614879

RESUMEN

Background: Psychological distress is reported to be associated with academic burnout in students while the mediation and moderation effect of resilience and personality are less explored. Purpose: The current study was designed to estimate the mediating effect of resilience and the moderation effect of personality between psychological distress and academic burnout. Participants and methods: A total of 613 students were enrolled from two medical universities between December 2020 and January 2021. They were administered with Academic Burnout Scale, 10-item Kessler Psychological Distress Scale (K10), Connor-Davidson Resilience Scale (CD-RISC-10) and NEO Five-Factor Inventory (NEO-FFI). Latent profile analysis and moderated mediation analysis were performed. Results: Three personalities were identified and named as resilient (13.4%), over-controlled (50.2%) and under-controlled (36.4%). Resilience significantly mediated the relationship between psychological distress and academic burnout while personality significantly moderated the relationship between psychological distress and resilience. Conclusion: Resilience and personality may be two important mediators between psychological distress and academic burnout. More attentions should be paid to students with under-controlled personality and resilience-enhancing interventions could be developed to prevent or alleviate academic burnout in future research.

11.
Psychol Res Behav Manag ; 15: 597-606, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35300205

RESUMEN

Background: Psychological resilience is important to mental health and professional development in newly graduated nursing students (NGNSs). However, the association between psychological resilience and mental health in NGNSs is less explored. Purpose: The current study was designed to determine mental health profiles measured by the Kessler 10 scale (K10) and evaluate the non-linear association between psychological resilience and mental health in NGNSs. Methods: A total of 472 NGNSs from the Be Resilient to Nursing Career program were assessed using the K10 and ten-item Connor-Davidson Resilience Scale (CD-RISC 10). Latent profile analysis and generalized additive model analysis were performed. Results: A four-class model based on the K10 was identified: lowest (28.0%), lower-middle (36.4%), upper-middle (26.1%), and highest (9.5%) subgroups. Academic degree and psychological resilience were significant indicators of mental health profiles. Psychological resilience was negatively and nonlinearly correlated with mental health when the CD-RISC 10 score was >17. Conclusion: There exists heterogeneity in NGNSs' mental health. The negative and nonlinear association between psychological resilience and mental health can only be confirmed in NGNSs with moderate and high resilience levels.

12.
Front Psychol ; 13: 779986, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35310284

RESUMEN

This study was designed to estimate the associations between self-efficacy and professional identity. A total of 1,051 freshmen nursing students (FNSs) from the Be Resilient to Nursing Career (BRNC) program were recruited from four universities between September and November 2020. A latent profile and moderated meditation analysis were performed. Four profiles of self-efficacy were identified and named as Lowest (15.6%), Med-low (45.0%), Med-high (32.7%), and Highest (6.7%). The mediating role of resilience and the moderating effect of role models were also identified. Therefore, self-efficacy, resilience, and role models may be three important factors to professional identity in FNSs and these relationships should be further validated in longitudinal or interventional studies.

13.
Bioconjug Chem ; 22(8): 1567-75, 2011 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-21688833

RESUMEN

The nonviral vector with iodine-nuclear localization sequence (namely, NLS-I) targeting breast cancer cells was fabricated. Ternary complexes were formed via charge interactions among NLS-I peptides, PEI 1800, and DNA, and we investigated their cellular internalization, nuclear accumulation as well as transfection efficiency. All the experiments were assessed by employing MCF-7 cells that express sodium/iodide symporter and HeLa cells that lack the expression of the symporter. In MCF-7 cells, cell internalization and nuclear accumulation of NLS-I was markedly increased compared to that in NLS. In addition, compared to that of the PEI1800/DNA complex, PEI1800/DNA/NLS-I complexes exhibited much enhanced luciferase reporter gene expression by up to 130-fold. By contrast, in HeLa cells, the evident improvements of cellular internalization, nuclear accumulation, and transfection efficiency by NLS-I were not observed. This study demonstrates an alternative method to construct a nonviral delivery system for targeted gene transfer into breast cancer cells.


Asunto(s)
Transporte Activo de Núcleo Celular , Neoplasias de la Mama/tratamiento farmacológico , Terapia Genética/métodos , Yodo/metabolismo , Señales de Localización Nuclear/farmacocinética , Transfección/métodos , Neoplasias de la Mama/patología , Línea Celular Tumoral , ADN/farmacocinética , ADN/uso terapéutico , Femenino , Humanos , Yodo/farmacocinética , Yodo/uso terapéutico , Señales de Localización Nuclear/metabolismo , Señales de Localización Nuclear/uso terapéutico , Polietileneimina/farmacocinética , Polietileneimina/uso terapéutico , Simportadores/metabolismo
14.
J Prosthet Dent ; 105(5): 338-46, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21530760

RESUMEN

STATEMENT OF PROBLEM: Resilient (nonrigid) and non-resilient (rigid) attachments are used in extension base partial removable dental prostheses for retention. However, the biomechanical effects of these 2 types of retainers on the terminal abutment and supporting tissues, which may influence clinical treatment planning, have not been compared. PURPOSE: The purpose of this study was to compare the mechanical effects of 2 types of extracoronal attachments (rigid and nonrigid) in distal extension removable partial prostheses on the alveolar ridge and abutment tooth periodontal ligament. MATERIAL AND METHODS: A finite element model of a human left mandible edentulous arch distal to the second premolar was fabricated. The second premolar was the terminal abutment for an attachment-retained denture. Two types of attachments (rigid and nonrigid) were modeled in the study. For the nonrigid attachment, there was movement between the patrix and matrix component of the attachment, but there was no movement between the 2 component parts for the rigid attachment. Six levels of loading (100, 150, 200, 250, 300, and 350 N) were applied from 3 directions (axial, buccolingual, and mesiodistal) on the central fossa of the first and second molars. Denture motion and stress distributions of denture supporting tissues were observed. Maximum equivalent stress values (SEQV) were recorded for 6 regions (cervical bone, cervical and apical periodontal ligaments, mesial and distal ridges, and mucosa). The data were divided into 2 groups according to the attachment type. Paired t tests were used to compare the values of the 2 groups. Factorial ANOVA was used to test the difference between the loading directions (α=.05). Multiple linear regression was used to analyze the interactions among the factors of region, direction, and level (α=.05). RESULTS: Stress distributions in the rigid and nonrigid attachment models were similar but the magnitudes were different. For all 3 loading directions, significantly different stresses in the alveolar ridge and periodontal tissue of the terminal abutment were found between the rigid and nonrigid groups (P<.05). There were significant differences among the 3 loading directions (P<.05). In the nonrigid group, the stress ratio of the mesial to the distal area was higher than that of the rigid group from axial and mesiodistal loading (P<.05). Linear interactions were found between the direction and level and region and level combinations (P<.05). Movement between the patrix and matrix components increased as loading increased. The most obvious movement of attachment occurred when loading was in the buccolingual direction. CONCLUSIONS: Stress on the terminal abutment can be reduced by the use of an extracoronal resilient attachment that allocates more loads onto the distal edentulous ridge. The level of loading influenced the extent of reduction. A resilient attachment with a universal hinge had the most movement when loading was in the buccolingual direction. Interactions were found between direction and level, as well as region and level combinations (P<.05).


Asunto(s)
Pilares Dentales , Análisis del Estrés Dental , Diseño de Dentadura , Retención de Dentadura/instrumentación , Dentadura Parcial Removible , Análisis de Varianza , Bases para Dentadura , Ajuste de Precisión de Prótesis , Análisis de Elementos Finitos , Humanos
15.
Org Biomol Chem ; 8(14): 3142-8, 2010 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-20480122

RESUMEN

Two kinds of arginine-rich amphiphilic lipopeptides with hydrophobic aliphatic tails (C(12)GR(8)GDS, LP1 and C(18)GR(8)GDS, LP2) were designed and synthesized as functional gene vectors. With hydrophobic tail modification, these amphiphilic lipopeptides could bind DNA more efficiently and form stable spherical complexes in comparison with the control peptide (AcGR(8)GDS, P1). Moreover, the size and zeta potential results demonstrated the charge density and stability of the vector/DNA complexes could be improved with the increasing length of the aliphatic tails. In vitro transfection experiments showed that LP1 and LP2 could induce much higher gene expression level (luciferase expression) as compared with P1. Due to the incorporation of arginine-glycine-aspartic acid (RGD) sequences which could be specifically recognized by integrins alpha(upsilon)beta(3) and alpha(upsilon)beta(5) over-expressed on cancer cells, these lipopeptides could be specifically recognized by cancer cells, i.e. LP1 and LP2 exhibited relatively higher transfection efficiency in HeLa cell line than that of P2 and P3 without RGD sequence. While the transfection efficiencies of LP2 and P2 were similar in 293T cells. Lipopeptides exhibited very low cell cytotoxicity in both HeLa and 293T cell lines even at high concentration.


Asunto(s)
Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Lipopéptidos/química , Lipopéptidos/metabolismo , Oligopéptidos , Transfección/métodos , Secuencia de Aminoácidos , ADN/química , ADN/metabolismo , Portadores de Fármacos/toxicidad , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Lipopéptidos/toxicidad , Modelos Moleculares , Conformación de Ácido Nucleico , Tamaño de la Partícula
16.
ACS Omega ; 5(3): 1448-1456, 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-32010817

RESUMEN

Effects of deformation texture and grain size on mechanical properties and corrosion behavior of the Mg-3Al-1Zn (AZ31) alloys were systematically investigated. The results revealed that the ultimate tensile strength (UTS) and fracture elongation (FE) significantly increased from 232 to 273 MPa and 12.5 to 26.4%, respectively. According to the immersion and electrochemical measurements, the results indicated that the corrosion resistance of the alloy was improved obviously. Via electron backscattered diffraction (EBSD), corrosion morphology showed that the propagation of local pitting corrosion was suppressed, which is ascribed to grain refinement, higher texture intensity, and lower dislocation density after rolling and subsequent annealing.

17.
Materials (Basel) ; 13(5)2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-32121129

RESUMEN

The high-temperature superplastic deformation behavior of rolled Mg-8Al-2Sn (AT82) and Mg-8Al-1Sn-1Zn (ATZ811) alloys were investigated in this study. During tensile deformation at 573 K, no obvious grain growth occurred in both alloys, because of the high-volume fraction of second phases located at grain boundaries. Meanwhile, texture weakening was observed, suggesting that grain boundary sliding (GBS) is the dominant superplastic deformation mechanism, which agreed well with the strain rate sensitivity (m) and the activation energy (Q) calculations. The microstructural evolution during tensile deformation manifested that there were more and larger cavities in AT82 than ATZ811 during high-temperature tensile deformation. Therefore, superior superplasticity was found in the ATZ811 alloy that presented a tensile elongation of ~510% under a strain rate of 10-3 s-1 at 573 K, in contrast to the relatively inferior elongation of ~380% for the AT82 alloy. Meanwhile, good tensile properties at ambient temperature were also obtained in ATZ811 alloy, showing the ultimate tensile strength (UTS) of ~355 MPa, yield strength (YS) of ~250 MPa and elongation of ~18%. Excellent mechanical performance at both ambient and elevated temperatures can be realized by using economical elements and conventional rolling process, which is desirable for the industrial application of Mg alloy sheets.

18.
Bioorg Med Chem Lett ; 18(18): 4972-7, 2008 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-18762425

RESUMEN

Pharmacophore models of Polo-like kinase-1 (PLK1) inhibitors have been established by using the HipHop and HypoGen algorithms implemented in the Catalyst software package. The best quantitative pharmacophore model, Hypo1, which has the highest correlation coefficient (0.9895), consists of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic feature, and one hydrophobic aliphatic feature. Hypo1 was further validated by test set and cross validation method. Then Hypo1 was used as a 3D query to screen several databases including Specs, NCI, Maybridge, and Chinese Nature Product Database (CNPD). The hit compounds were subsequently subjected to filtering by Lipinski's rule of five and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally, a total of 20 compounds were selected and have been shifted to in vitro and in vivo studies. As far as we know, this is the first report on the pharmacophore modeling even the first publicly reported virtual screening study of PLK1 inhibitors.


Asunto(s)
Proteínas de Ciclo Celular/antagonistas & inhibidores , Diseño de Fármacos , Evaluación Preclínica de Medicamentos/métodos , Compuestos Heterocíclicos/síntesis química , Compuestos Heterocíclicos/farmacología , Modelos Moleculares , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Algoritmos , Compuestos Heterocíclicos/química , Concentración 50 Inhibidora , Estructura Molecular , Relación Estructura-Actividad , Quinasa Tipo Polo 1
19.
Zhen Ci Yan Jiu ; 43(1): 44-8, 2018 Jan 25.
Artículo en Zh | MEDLINE | ID: mdl-29383894

RESUMEN

OBJECTIVE: To assess the safety and efficacy of transcutaneous electrical acupoint stimulation (TEAS) for depression in late pregnancy and impacts on inflammatory cytokines. METHODS: A total of 150 pregnant women with depression in late pregnancy were randomized into a high intensity group (n=52), a low intensity group (n=49) and a control group (n=49). TEAS was applied at bilateral Neiguan (PC 6) and Shenmen (HT 7) for 6 weeks. The intensities of TEAS in the high intensity group, the low intensity group and the control group were 10, 5 and 0 mA, respectively. During the process of TEAS, the blood pressure, pulse, uterine contraction and the fetal heart rate were recorded. Depression was evaluated by 24-item Hamilton depression scale (HAMD) before TEAS and after 2-week, 4-week, 6-week treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1 ß) and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA) before and after 6-week treatment. Delivery outcomes were observed. The correlation was analyzed between HAMD difference value and the diffe-rence values of TNF-α, IL-1 ß and IL-6, respectively. RESULTS: The blood pressure, pulse and fetal heart rate had no statistical significance before and after treatment in the three groups (P>0.05). The HAMD scores at all the time points were lower than that before treatment in the high intensity group (P<0.05), which were lower compared with those in the low intensity group and the control group (P<0.05). The HAMD score in the low intensity group decreased after 6-week treatment compared with that before treatment and was lower than that in the control group (P<0.05). The serum levels of IL-1 ß and IL-6 in the high intensity group decreased compared with those before treatment and were lower compared with those in the low intensity group and the control group after 6-week treatment (P<0.05). There was no significant difference in the deliver outcomes among the three groups (P>0.05). The variation of HAMD score did not have significant correlation with those of TNF-α, IL-1 ß and IL-6 (P>0.05). CONCLUSION: TEAS is safe and effective for depression in late pregnancy and can regulate the serum levels of IL-1 ß and IL-6 without influencing on delivery outcome.


Asunto(s)
Puntos de Acupuntura , Estimulación Eléctrica Transcutánea del Nervio , Citocinas , Depresión , Electroacupuntura , Femenino , Humanos , Interleucina-1beta , Embarazo
20.
Materials (Basel) ; 11(6)2018 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-29861443

RESUMEN

A high extrusion ratio of 166:1 was applied to commercial AZ61 alloy in one step with an extrusion speed of 2.1 m·min-1. The effects of DA (direct aging) treatment on the microstructure and tensile properties of extruded alloy were investigated. The extruded alloy exhibits fine DRXed grains and the average grain size is ~11 µm. After DA treatment at 170 °C, the tensile strength and 0.2% offset yield strength is enhanced from 314 to 336 MPa and from 169 to 191 MPa respectively, sacrificing elongation from 26.5% to 23.3%. The grain size and texture distribution of extruded AZ61 scarcely evolve during the post aging treatment. However, the enhanced strength in peak-aged alloy is mainly caused by the high-density elliptical Mg17Al12 precipitates distributing uniformly along the grain boundaries or within the grains, by precipitation and dispersion hardening. Furthermore, the nano-sized precipitates effectively inhibit grains from coarsening by triggering pinning effects along the grain boundaries at elevated temperature. As a result, the peak-aged alloy exhibits a better superplasticity of 306.5% compared with that of 231.8% of extruded sample. This work provides a practical one-step method for mass-producing Mg alloy sheets with excellent tensile strength and ductility compared with those fabricated by conventional extrusion methods.

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