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The lower hybrid drift wave (LHDW) has been a candidate for anomalous resistivity and electron heating inside the electron diffusion region of magnetic reconnection. In a laboratory reconnection layer with a finite guide field, quasielectrostatic LHDW (ES-LHDW) propagating along the direction nearly perpendicular to the local magnetic field is excited in the electron diffusion region. ES-LHDW generates large density fluctuations (δn_{e}, about 25% of the mean density) that are correlated with fluctuations in the out-of-plane electric field (δE_{Y}, about twice larger than the mean reconnection electric field). With a small phase difference (â¼30°) between two fluctuating quantities, the anomalous resistivity associated with the observed ES-LHDW is twice larger than the classical resistivity and accounts for 20% of the mean reconnection electric field. After we verify the linear relationship between δn_{e} and δE_{Y}, anomalous electron heating by LHDW is estimated by a quasilinear analysis. The estimated electron heating is about 2.6±0.3 MW/m^{3}, which exceeds the classical Ohmic heating of about 2.0±0.2 MW/m^{3}. This LHDW-driven heating is consistent with the observed trend of higher electron temperatures when the wave amplitude is larger. Presented results provide the first direct estimate of anomalous resistivity and electron heating power by LHDW, which demonstrates the importance of wave-particle interactions in magnetic reconnection.
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Directional wicking and spreading of liquids can be achieved by regular micro-patterns of specifically designed topographic features that break the reflection symmetry of the underlying pattern. The present study aims to understand the formation and stability of wetting films during the evaporation of volatile liquid drops on surfaces with a micro-pattern of triangular posts arranged in a rectangular lattice. Depending on the density and aspect ratio of the posts, we observe either spherical-cap shaped drops with a mobile three-phase contact line or the formation of circular or angular drops with a pinned three-phase contact line. Drops of the latter class eventually evolve into a liquid film extending to the initial footprint of the drop and a shrinking cap-shaped drop sitting on the film. The drop evolution is controlled by the density and aspect ratio of the posts, while no influence of the orientation of the triangular posts on the contact line mobility becomes evident. Our experiments corroborate previous results of systematic numerical energy minimization, predicting that conditions for a spontaneous retraction of a wicking liquid film depend weakly on the orientation of the film edge relative to the micro-pattern.
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Using molecular dynamics, the evolution of a metastable solution for "methane + water" was studied for concentrations of 3.36, 6.5, 9.45, 12.2, and 14.8 mol% methane at 270 K and 1 bar during 100 ns. We have found the intriguing behavior of the system containing over 10,000 water molecules: the formation of hydrate-like structures is observed at 6.5 and 9.45 mol% concentrations throughout the entire solution volume. This formation of "blobs" and the following amorphous hydrate were studied. The creation of a metastable methane solution through supersaturation is the key to triggering the collective process of hydrate formation under low pressure. Even the first stage (0-1 ns), before the first fluctuating cavities appear, is a collective process of H-bond network reorganization. The formation of fluctuation cavities appears before steady hydrate growth begins and is associated with a preceding uniform increase in the water molecule's tetrahedrality. Later, the constantly presented hydrate cavities become the foundation for a few independent hydrate nucleation centers, this evolution is consistent with the labile cluster and local structure hypotheses. This new mechanism of hydrogen-bond network reorganization depends on the entropy of the cavity arrangement of the guest molecules in the hydrate lattice and leads to hydrate growth.
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The intrinsic temporal nature of magnetic reconnection at the magnetopause has been an active area of research. Both temporally steady and intermittent reconnection have been reported. We examine the steadiness of reconnection using space-ground conjunctions under quasi-steady solar wind driving. The spacecraft suggests that reconnection is first inactive, and then activates. The radar further suggests that after activation, reconnection proceeds continuously but unsteadily. The reconnection electric field shows variations at frequencies below 10 mHz with peaks at 3 and 5 mHz. The variation amplitudes are â¼10-30 mV/m in the ionosphere, and 0.3-0.8 mV/m at the equatorial magnetopause. Such amplitudes represent 30%-60% of the peak reconnection electric field. The unsteadiness of reconnection can be plausibly explained by the fluctuating magnetic field in the turbulent magnetosheath. A comparison with a previous global hybrid simulation suggests that it is the foreshock waves that drive the magnetosheath fluctuations, and hence modulate the reconnection.
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Based on global hybrid simulation results, we predict that foreshock turbulence can reach the magnetopause and lead to reconnection as well as Earth-sized indents. Both the interplanetary magnetic field (IMF) and solar wind are constant in our simulation, and hence, all dynamics are generated by foreshock instabilities. The IMF in the simulation is mostly Sun-Earth aligned with a weak northward and zero dawn-dusk component, such that subsolar magnetopause reconnection is not expected without foreshock turbulence modifying the magnetosheath fields. We show a reconnection example to illustrate that the turbulence can create large magnetic shear angles across the magnetopause to induce local bursty reconnection. Magnetopause reconnection and indents developed from the impact of foreshock turbulence can potentially contribute to dayside loss of planetary plasmas.
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Understanding the dynamic behavior of hydrogel formation induced by a temperature ramp is essential for the design of gel-based injectable formulation as drug-delivery vehicles. In this study, the dynamic behavior of the hydrogel formation of Pluronic F108 aqueous solutions within different heating rates was explored in both macroscopic and microscopic views. It was discovered that when the heating rate is increased, the gelation temperature window (hard gel region) shrinks and the mechanical strength of the hydrogel decreases. A given system at different heating rates would lead to different crystalline structural evolutions. The time-resolved small-angle X-ray scattering (SAXS) experiments at a heating rate of 10 °C/min disclose that the crystalline structure of micelle packing in the hydrogel exhibits a series of transitions: hexagonal close-packed (HCP) to face-centered cubic (FCC) and body-centered cubic (BCC) structures coexisting and then to the BCC structure along with the increasing temperature. For the system at equilibrium, the BCC structure exclusively dominates the system. Furthermore, the addition of a hydrophobic model drug (ibuprofen) to the F108 aqueous solution promotes hard gel formation at even lower temperatures and concentrations of F108. The SAXS results for the system with ibuprofen at a heating rate of 10 °C/min demonstrate a mixture of FCC and BCC structures coexisting over the whole gelation window compared to the BCC structure that exclusively dominates the system at equilibrium. The addition of ibuprofen would alter the structural evolution to change the delivery path of the encapsulated drug, which is significantly related to the performance of drug release.
Assuntos
Hidrogéis , Ibuprofeno , Espalhamento a Baixo Ângulo , Temperatura , Difração de Raios XRESUMO
Wicking of wetting liquids into micropatterns of posts with homogeneous triangular cross section is studied in experiments and by numerical energy minimizations. To test for directional wicking, we fabricated regular arrays of posts with various combinations of line fractions and aspect ratios using standard photolithography processes. In agreement with numerical energy minimizations of the liquid film morphology, we find spontaneous wicking in the experiments only for line fractions and aspect ratios where the homogeneous liquid film represents the state of lowest interfacial free energy and where no local energy minimum could be detected in our numerical energy minimizations. The numerical results further demonstrate that the stability of a certain morphology of the terminal meniscus controls the direction of wicking relative to the orientation of the triangular posts. The observed selectivity of spontaneous wicking with respect to the meniscus orientation can be exploited to build a microfluidic rectifier for partially wetting liquids.
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The nucleation of methane (CH4), tetrahydrofuran (THF), and CH4 + THF hydrates are investigated by microsecond MD simulations. These three systems exhibit distinct structural developments in the aqueous phase quantified by the formation of cage structures of hydrogen bonded water molecules. The development of a cluster of cages in the CH4 system is limited by the scarce CH4 molecules in the solution, while in the THF system it is limited by the short lifetime of cages. In the CH4 + THF mixed guest system, a small cluster of caged CH4 molecules can be rapidly stabilized by abundant neighboring cages of THF molecules. Therefore, the induction time of the CH4 + THF mixed guest system is found to be significantly shorter than that of the pure CH4 and pure THF systems. Furthermore, the structure of cages found in the initially formed cage clusters are often different from the typical 5(12)6(n) (n = 0, 2, 3, 4) cages observed in clathrate hydrate systems. The cluster of cages may grow or transform into structure I or II clathrate hydrate in the later stages.
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The aim of the present study was to identify the effect of canavanine on the imidazoline receptor because canavanine is a guanidinium derivative that has a similar structure to imidazoline receptor ligands. Transfected Chinese hamster ovary-K1 cells expressing imidazoline receptors (nischarin (NISCH)-CHO-K1 cells) were used to elucidate the direct effects of canavanine on imidazoline receptors. In addition, the imidazoline I3 receptor has been implicated in stimulation of insulin secretion from pancreatic ß-cells. Wistar rats were used to investigate the effects of canavanine (0.1, 1 and 2.5 mg/kg, i.v.) on insulin secretion. In addition the a specific I3 receptor antagonist KU14R (4 or 8 mg/kg, i.v.) was used to block I3 receptors. Canavanine decreased blood glucose by increasing plasma insulin in rats. In addition, canavanine increased calcium influx into NISCH-CHO-K1 cells in a manner similar to agmatine, the endogenous ligand of imidazoline receptors. Moreover, KU12R dose-dependently attenuated canavanine-induced insulin secretion in HIT-T15 pancreatic ß-cells and in the plasma of rats. The data suggest that canavanine is an agonist of I3 receptors both in vivo and in vitro. Thus, canavanine would be a useful tool in imidazoline receptor research.
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Canavanina/farmacologia , Receptores de Imidazolinas/metabolismo , Insulina/metabolismo , Animais , Glicemia/metabolismo , Células CHO , Cálcio/metabolismo , Cricetinae , Cricetulus , Secreção de Insulina , Masculino , Ratos , Ratos WistarRESUMO
Canavanine is a guanidinium derivative that contains the basic structure of the ligand(s) of imidazoline receptor (I-R). Canavanine has been reported to activate the imidazoline I-3 receptor (I-3R) both in vivo and in vitro. Additionally, the activation of the imidazoline I-2B receptor (I-2BR) by guanidinium derivatives may increase glucose uptake. Therefore, the effect of canavanine on the I-2BR was investigated in the present study. Glucose uptake into cultured C2 C12 cells was determined using the radio-ligated tracer 2-[(14) C]-deoxy-glucose. The changes in 5' AMP-activated protein kinase (AMPK) expression were also identified using Western blotting analysis. The canavanine-induced glucose uptake was inhibited in a dose-dependent manner by BU224 (0.01-1 µmol/L), which is a specific I-2BR antagonist, in the C2 C12 cells. Additionally, the canavanine-stimulated AMPK phosphorylation and glucose transporter (GLUT4) expression were also sensitive to BU224 inhibition in the C2 C12 cells. Moreover, both canavanine-stimulated glucose uptake and AMPK phosphorylation were attenuated by high concentrations of amiloride (1-2 µmol/L), which is another established I-2BR inhibitor, in a dose-dependent manner in C2 C12 cells. Additionally, compound C abolished the canavanine-induced glucose uptake and AMPK phosphorylation at a concentration (0.1 µmol/L) sufficient to inhibit AMPK. In conclusion, these data demonstrated that canavanine has an ability to activate I-2BR through the AMPK pathway to increase glucose uptake, which indicates I-2BR as a new target for diabetic therapy.
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Canavanina/farmacologia , Glucose/metabolismo , Receptores de Imidazolinas/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Camundongos , Fosforilação/efeitos dos fármacosRESUMO
The effects of a density asymmetry across the current sheet on anti-parallel magnetic reconnection are studied systematically in a laboratory plasma. Despite a significant density ratio of up to 10, the in-plane magnetic field profile is not significantly changed. On the other hand, the out-of-plane Hall magnetic field profile is considerably modified; it is almost bipolar in structure with the density asymmetry, as compared to quadrupolar in structure with the symmetric configuration. Moreover, the ion stagnation point is shifted to the low-density side, and the electrostatic potential profile also becomes asymmetric with a deeper potential well on the low-density side. Nonclassical bulk electron heating together with electromagnetic fluctuations in the lower hybrid frequency range is observed near the low-density-side separatrix. The dependence of the ion outflow and reconnection electric field on the density asymmetry is measured and compared with theoretical expectations. The measured ion outflow speeds are about 40% of the theoretical values.
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The evaporation process of a sessile drop of water on soft patterned polydimethylsiloxane (PDMS) substrates is investigated in this study. Different softness of a regular pillar-like patterned PDMS substrate can be achieved by controlling the mixing ratio of a PDMS's prepolymer base and a curing agent at 10 : 1, 20 : 1 and 30 : 1. The receding contact angle is smaller for softer pillar-like patterned substrates. Consequently, the evaporation rate is faster on softer pillar-like substrates. A sessile drop on the regular pillar-like PDMS substrates, prepared at the mixing ratio of a base to a curing agent of 10 : 1 and 20 : 1, is observed to start evaporating in the constant contact radius (CCR) mode then switching to the constant contact angle (CCA) mode via stepwise jumping of the contact line, and finally shifting to the mixed mode sequentially. During the evaporation, a wetting transition from the Cassie to the Wenzel state occurs earlier for the softer substrate because softer pillars relatively cannot stand the increasingly high Laplace pressure. For the softest regular pillar-like PDMS substrate prepared at the mixing ratio of the base to the curing agent of 30 : 1 (abbreviated by PDMS-30 : 1 substrate), the pillars collapse irreversibly after the sessile drop exhibits the wetting transition into the Wenzel state. Furthermore, it is interesting to find out that the initial stage of evaporation of a sessile drop on the PDMS-30 : 1 substrate in the Cassie state is in the CCR mode followed by the CCA mode with stepwise retreatment of the contact line. Further evaporation would induce the wetting transition from the Cassie to the Wenzel state (due to the collapse of pillars) and resume the CCR mode followed by the CCA mode again sequentially.
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Rose petals exhibit superhydrophobicity with strong adhesion to pin water drops, known as the 'petal effect.' It is generally believed that the petal effect is attributed to dual-scale roughness, that is, the surface possesses both a nanostructure and a microstructure (Feng et al 2008 Langmuir 24 4114). In this study, we demonstrate that the dual-scale roughness is not a necessary condition for a surface of the petal effect. A surface of single-scale roughness, either at the nanoscale or the microscale alone, within a certain roughness region may also exhibit the petal effect. The surface roughness plays the essential role on the wetting behavior and governs the contact angle in the Wenzel or Cassie state, as well as the contact angle hysteresis. A water drop on the surface of the petal effect under the condition of the advancing and receding contact angle would fall into, respectively, the Cassie and Wenzel state, which leads to a contact angle hysteresis large enough to pin the water drop. On both single and dual textured hydrophobic surfaces, a sequence of wetting transitions: Wenzel state â petal state (sticky superhydrophobic state) â lotus state (slippery superhydrophobic state) is consistently observed by simply increasing the surface roughness.
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The enthalpy, entropy, and free energy of water are important physical quantities for understanding many interesting phenomena in biological systems. However, conventional approaches require different treatments to incorporate quantum and diffusive effects of water in different states of matter. In this work, we demonstrate the use of the two-phase thermodynamic (2PT) model as a unified approach to obtain the properties of water over the whole phase region of water from short (â¼20 ps) classical molecular dynamics trajectories. The 2PT model provides an effective way to separate the diffusive modes (gas-like component) from the harmonic vibrational modes (solid-like component) in the vibrational density of states (DoS). Therefore, both diffusive and quantum effect can be properly accounted for water by applying suitable statistical mechanical weighting functions to the DoS components. We applied the 2PT model to systematically examine the enthalpy, entropy, and their temperature dependence of five commonly used rigid water models. The 2PT results are found to be consistent with those obtained from more sophisticated calculations. While the thermodynamic properties determined from different water models are largely similar, the phase boundary determined from the equality of free energy is very sensitive to the small inaccuracy in the values of enthalpy and absolute entropy. The enthalpy, entropy, and diffusivity of water are strongly interrelated, which challenge further improvement of rigid water model via parameter fitting. Our results show that the 2PT is an efficient method for studying the properties of water under various chemical and biological environments.
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Difusão , Modelos Químicos , Termodinâmica , Água/química , Simulação de Dinâmica Molecular , Teoria QuânticaRESUMO
BACKGROUND: Rhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Recently, it has been mentioned that Rhodiola increases plasma ß-endorphin to lower blood pressure. Thus, the present study aims to investigate the antidiabetic action of Rhodiola in relation to opioids in streptozotocin-induced diabetic rats (STZ-diabetic rats). METHODS: In the present study, the plasma glucose was analyzed with glucose oxidase method, and the determination of plasma ß-endorphin was carried out using a commercially available enzyme-linked immunosorbent assay. The adrenalectomy of STZ-diabetic rats was used to evaluate the role of ß-endorphin. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to investigate mRNA and protein expressions. RESULTS: Rhodiola-water extract dose-dependently lowered the plasma glucose in STZ-diabetic rats and this action was reversed by blockade of opioid µ-receptors using cyprodime. An increase of plasma ß-endorphin by rhodiola-water extract was also observed in same manner. The plasma glucose lowering action of rhodiola-water extract was attenuated in bilateral adrenalectomized rats. In addition, continuous administration of rhodiola-water extract for 3 days in STZ-diabetic rats resulted in an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle and a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These effects were also reversed by blockade of opioid µ-receptors. CONCLUSIONS: Taken together, rhodiola-water extract improves hyperglycemia via an increase of ß-endorphin secretion from adrenal gland to activate opioid µ-receptors in STZ-diabetic rats.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Rhodiola/química , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Animais , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Ensaio de Imunoadsorção Enzimática , Transportador de Glucose Tipo 4/metabolismo , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Extratos Vegetais/química , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Opioides mu/antagonistas & inibidores , Água/química , beta-Endorfina/sangue , beta-Endorfina/metabolismoRESUMO
OBJECTIVES: To study the role of tumor necrosis factor-α in bladder dysfunction associated with obesity. METHODS: Male 8-week-old C57BL/6J mice were divided into three groups: (i) control mice; (ii) vehicle-treated high-fat diet-fed mice; and (iii) etanercept-treated high-fat diet-fed mice. High-fat diet feeding lasted for 12 weeks, vehicle or etanercept (0.8 mg/kg/day, a tumor necrosis factor-α antagonist) treatment was given during the last 4 weeks. At the end of the treatment period, serum tumor necrosis factor-α, total cholesterol, triglyceride and blood glucose were measured. Bladder strip contractile responses to 1 µmol/L acetylcholine or 50 mmol/L KCl were studied in an organ bath. Bladder protein kinase Cζ, nuclear factor-κB and intercellular adhesion molecule-1 expressions were analyzed using western blots. RESULTS: Serum levels of tumor necrosis factor-α total cholesterol, triglyceride and glucose were significantly elevated in high-fat diet-fed mice; and the levels were not ameliorated by etanercept treatment. High-fat diet-fed mouse bladder showed reduced contractile responses to acetylcholine and KCl stimulation accompanied by high expression levels of phospho-protein kinase Cζ, nuclear nuclear factor-κB and intercellular adhesion molecule-1. Etanercept restored normal bladder contractile responses, as well as protein kinase Cζ nuclear factor-κB and intercellular adhesion molecule-1 expressions. CONCLUSIONS: A high-fat diet induces bodyweight gain, hyperlipidemia and hyperglycemia in mice. Elevated serum tumor necrosis factor-α level associated with increased protein kinase Cζ phosphorylation, nuclear factor-κB nuclear migration, intercellular adhesion molecule-1 expression and impaired muscle contractility are shown in the high-fat diet-fed mouse bladder. Tumor necrosis factor-α antagonist treatment restores normal bladder contractility, and protein kinase Cζ nuclear factor-κB and intercellular adhesion molecule-1 levels.
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Contração Muscular , Obesidade/complicações , Fator de Necrose Tumoral alfa/sangue , Doenças da Bexiga Urinária/etiologia , Bexiga Urinária/metabolismo , Animais , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Etanercepte , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Técnicas In Vitro , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Obesidade/sangue , Fosforilação/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Bexiga Urinária/efeitos dos fármacos , Doenças da Bexiga Urinária/sangue , Doenças da Bexiga Urinária/tratamento farmacológicoRESUMO
The dilational modulus (E) of polymer films has been commonly measured using the oscillating ring/bubble/drop methods with an external force, and often without specifying the state of the adsorbed film. This study explores an approach where E was determined from the relaxations of surface tension (ST) and surface area (SA) of natural perturbations, in which ST and SA were monitored using a pendant bubble tensiometer. The E of the adsorbed film of PAA (polyacrylic acid) was evaluated for aqueous solutions at CPAA = 5 × 10-4 g/cm3, [MW = 5, 25, and 250 (kDa)]. The E (=dγ/dlnA) was estimated from the surface dilational rate (dlnA/dt) and the rate of ST change (dγ/dt) of the bubble surface from the natural perturbation caused by minute variations in ambient temperature. The data revealed that (i) a considerable time is required to reach the equilibrium-ST (γeq) and to attain the saturated dilational modulus (Esat) of the adsorbed PAA film, (ii) both γeq and Esat of PAA solutions increase with MW of PAA, (iii) a lower MW solution requires a longer time to reach its γeq and Esat, and (iv) this approach is workable for evaluating the E of adsorbed polymer films.
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BACKGROUND: An impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (K(ATP)) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac K(ATP) channels in diabetic disorders. METHODS: Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on cardiac function and the expression of K(ATP) channels. K(ATP) channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of K(ATP) channels by Western blot and Northern blot analysis. RESULTS: The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of K(ATP) channel. Two subunits of cardiac K(ATP) channel (SUR2A and kir 6.2) were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac K(ATP) in these diabetic rats. CONCLUSIONS: Both mRNA and protein expression of cardiac K(ATP) channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some K(ATP) channel drugs.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Canais KATP/metabolismo , Miócitos Cardíacos/metabolismo , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Glicemia/metabolismo , Pressão Sanguínea , Northern Blotting , Western Blotting , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatologia , Diazóxido/farmacologia , Relação Dose-Resposta a Droga , Regulação para Baixo , Sequestradores de Radicais Livres/farmacologia , Frequência Cardíaca , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Canais KATP/efeitos dos fármacos , Canais KATP/genética , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Florizina/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Droga/metabolismo , Estreptozocina , Receptores de Sulfonilureias , Fatores de Tempo , Regulação para CimaRESUMO
Silymarin is an active constituent contained in the seeds of the milk thistle plant and is widely used as a hepatic protection agent due to its antioxidant-like activity. In the present study we evaluated the potential action of silymarin against cervical cancer and investigated its mechanism of action. Treatment of cervical cancer cells (C-33A) with silymarin resulted in a significant decrease in cell viability. Silymarin induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 3. Silymarin also inhibited the phosphorylation of Akt with an increase in expression of phosphatase and tensin homolog (PTEN). We also observed that silymarin suppressed C-33A cell invasion and wound-healing migration in a concentration-dependent manner. Western-blot analysis showed that silymarin significantly inhibited the expression of matrix metalloproteinase-9 (MMP-9) in C-33A cells. Furthermore, we applied siRNA to lower the PTEN gene, which diminished the anticancer actions of silymarin. Taken together, these results show that silymarin has the potential to suppress the survival, migration and invasion of C-33A cancer cells; thus, it could be developed as a promising agent for the treatment of cervical cancer in the future.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Silimarina/farmacologia , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Genes bcl-2/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , PTEN Fosfo-Hidrolase/efeitos dos fármacos , PTEN Fosfo-Hidrolase/genética , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Neoplasias do Colo do Útero/tratamento farmacológico , Cicatrização/efeitos dos fármacosRESUMO
Recent evidence showed the role of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Cardiac contraction induced by various agents is critical in restoring the activity of peroxisome proliferator-activated receptors δ (PPARδ) in cardiac myopathy. Because dobutamine is an agent widely used to treat heart failure in emergency setting, this study is aimed to investigate the change of PPARδ in response to dobutamine. Neonatal rat cardiomyocytes were used to examine the effects of dobutamine on PPARδ expression levels and cardiac troponin I (cTnI) phosphorylation via Western blotting analysis. We show that treatment with dobutamine increased PPARδ expression and cTnI phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. These increases were blocked by the antagonist of ß1-adrenoceptors. Also, the action of dobutamine was related to the increase of calcium ions and diminished by chelating intracellular calcium. Additionally, dobutamine-induced action was reduced by the inhibition of downstream messengers involved in this calcium-related pathway. Moreover, deletion of PPARδ using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPARδ is increased by dobutamine in cardiac cells.