Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Molecules ; 27(19)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36235070

RESUMO

Keratinocytes form the physical barrier of the skin and play an important role in the inflammatory process. Amauroderma rugosum is an edible mushroom; however, its pharmacological properties have seldom been studied. Although the anti-inflammatory effect of the organic solvent extract of Amauroderma rugosum has been previously reported, it is not known whether the aqueous extract has a similar effect. In addition, the effect of Amauorderma rugosum extract on skin has never been explored. Therefore, the objectives of the present study were to evaluate the anti-inflammatory effects of the aqueous extract of Amauroderma rugosum on HaCaT keratinocytes, to explore its mechanisms of action, and to study the possible active ingredients involved. The results showed that the aqueous extract of Amauroderm rugosum at a concentration of 1.5 mg/mL was non-toxic to HaCaT cells and inhibited the release of cytokine interleukin-1ß, and chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-stimulated HaCaT cells. Amauroderma rugosum extract reduced the intracellular levels of reactive oxygen species. In addition, Amauroderma rugosum extract reduced the total protein expression of nuclear factor-kappa B (NF-κB) and B-cells inhibitor alpha in HaCaT keratinocytes and inhibited the phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in TNF-α- and INF-γ-stimulated HaCaT keratinocytes. Chemical analysis revealed that the aqueous extract of Amauroderma rugosum contains polysaccharides, triterpenes, and phenolic compounds. Anti-inflammatory compounds, such as gallic acid, guanosine, and uridine, were also present. The anti-inflammatory effect of Amauroderma rugosum could be mimicked by a combination of gallic acid, guanosine, and uridine. In conclusion, our study suggests that the aqueous extract of Amauroderma rugosum exerts anti-inflammatory effects on keratinocytes through its antioxidant and inhibitory effects on MEK/ERK-, Akt/mTOR-, and NF-κB-dependent signaling pathways.


Assuntos
Triterpenos , Fator de Necrose Tumoral alfa , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Quimiocina CCL2/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ácido Gálico/farmacologia , Guanosina/metabolismo , Interferon gama/metabolismo , Interferon gama/farmacologia , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Queratinócitos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Polyporaceae , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Solventes/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Uridina/farmacologia
2.
Mol Biol Rep ; 49(11): 11201-11208, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36107375

RESUMO

BACKGROUND: Nucleoside transporters are crucial in regulating the functions of adenosine. This study investigated the contribution of equilibrative nucleoside transporter (ENT) type 4 to adenosine transport in cardiomyocytes under simulated ischemic conditions and whether the inhibition of ENT4 could protect cardiomyocytes against ischemia-reperfusion injury. METHODS: AC16 human cardiomyocytes were used to create a model to simulate ischemia/reperfusion injury. ENT4 activity was inhibited by decynium-22 or specific siRNA against ENT4. The protein expressions of nucleoside transporters were measured by western blot analysis. The transport activity was studied by [3?H]adenosine uptake. The cell injury was studied by biochemical assays. RESULTS: The [3?H]adenosine uptake in AC16 cells was predominantly mediated by ENTs. ENT1 to ENT4 were present in AC16 cells and their protein expression levels were comparable in normal and ischemic conditions. Decynium-22 or siRNA against ENT4 did not affect the adenosine uptake in AC16 cells under normal conditions but could inhibit the adenosine uptake in AC16 cells by 28% under ischemic conditions. In addition, the cell viability and lactate dehydrogenase release of AC16 cells under ischemia conditions could be reduced by decynium-22 or siRNA against ENT4. CONCLUSION: The cell culture model has suggested that ENT4 may play a role in adenosine transport in cardiomyocytes under ischemic conditions. Inhibition or downregulation of ENT4 may be a potential approach for cardioprotection but this notion should be further validated using animal model.


Assuntos
Miócitos Cardíacos , Traumatismo por Reperfusão , Animais , Humanos , Miócitos Cardíacos/metabolismo , Adenosina/metabolismo , Nucleosídeos/metabolismo , RNA Interferente Pequeno/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia
3.
Front Pharmacol ; 13: 928817, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928282

RESUMO

Angiogenesis, the formation of new capillaries from pre-existing vascular networks, plays an important role in many physiological and pathological processes. The use of pro-angiogenic agents has been proposed as an attractive approach for promoting wound healing and treating vascular insufficiency-related problems, such as ischemic heart disease and stroke, which are the leading causes of death worldwide. Traditional herbal medicine has a long history; however, there is still a need for more in-depth studies and evidence-based confirmation from controlled and validated trials. Many in vitro and in vivo studies have reported that herbal medicines and their bioactive ingredients exert pro-angiogenic activity. The most frequently studied pro-angiogenic phytochemicals include ginsenosides from Panax notoginseng, astragalosides and calycosin from Radix Astragali, salvianolic acid B from Salvia miltiorrhiza, paeoniflorin from Radix Paeoniae, ilexsaponin A1 from Ilex pubescens, ferulic acid from Angelica sinensis, and puerarin from Radix puerariae. This review summarizes the progress in research on these phytochemicals, particularly those related to pro-angiogenic mechanisms and applications in ischemic diseases, tissue repair, and wound healing. In addition, an outline of their limitations and challenges during drug development is presented.

4.
Oxid Med Cell Longev ; 2022: 9266178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693699

RESUMO

Clinical outcomes for doxorubicin (Dox) are limited by its cardiotoxicity but a combination of Dox and agents with cardioprotective activities is an effective strategy to improve its therapeutic outcome. Natural products provide abundant resources to search for novel cardioprotective agents. Ganoderma lucidum (GL) is the most well-known edible mushroom within the Ganodermataceae family. It is commonly used in traditional Chinese medicine or as a healthcare product. Amauroderma rugosum (AR) is another genus of mushroom from the Ganodermataceae family, but its pharmacological activity and medicinal value have rarely been reported. In the present study, the cardioprotective effects of the AR water extract against Dox-induced cardiotoxicity were studied in vitro and in vivo. Results showed that both the AR and GL extracts could potentiate the anticancer effect of Dox. The AR extract significantly decreased the oxidative stress, mitochondrial dysfunction, and apoptosis seen in Dox-treated H9c2 rat cardiomyocytes. However, knockdown of Nrf2 by siRNA abolished the protective effects of AR in these cells. In addition, Dox upregulated the expression of proapoptotic proteins and downregulated the Akt/mTOR and Nrf2/HO-1 signaling pathways, and these effects could be reversed by the AR extract. Consistently, the AR extract significantly prolonged survival time, reversed weight loss, and reduced cardiac dysfunction in Dox-treated mice. In addition, oxidative stress and apoptosis were suppressed, while Nrf2 and HO-1 expressions were elevated in the heart tissues of Dox-treated mice after treatment with the AR extract. However, the GL extract had less cardioprotective effect against Dox in both the cell and animal models. In conclusion, the AR water extract demonstrated a remarkable cardioprotective effect against Dox-induced cardiotoxicity. One of the possible mechanisms for this effect was the upregulation of the mTOR/Akt and Nrf2/HO-1-dependent pathways, which may reduce oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis. These findings suggested that AR may be beneficial for the heart, especially in patients receiving Dox-based chemotherapy.


Assuntos
Cardiotoxicidade , Fator 2 Relacionado a NF-E2 , Animais , Apoptose , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/genética , Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Polyporaceae , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Água/farmacologia
5.
Front Pharmacol ; 13: 837555, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35264969

RESUMO

Equilibrative nucleoside transporters (ENTs) play a vital role in nucleotide synthesis, regulation of adenosine function and chemotherapy. Current inhibitors of ENTs are mostly ENT1-selective. Our previous study has demonstrated that 4-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-6-imino-N-(naphthalen-2-yl)-1,3,5-triazin-2-amine (FPMINT) is a novel inhibitor of ENTs, which is more selective to ENT2 than to ENT1. The present study aimed to screen a series of FPMINT analogues and study their structure-activity relationship. Nucleoside transporter-deficient cells transfected with cloned human ENT1 and ENT2 were used as in vitro models. The results of the [3H]uridine uptake study showed that the replacement of the naphthalene moiety with the benzene moiety could abolish the inhibitory effects on ENT1 and ENT2. The addition of chloride to the meta position of this benzene moiety could restore only the inhibitory effect on ENT1 but had no effect on ENT2. However, the addition of the methyl group to the meta position or the ethyl or oxymethyl group to the para position of this benzene moiety could regain the inhibitory activity on both ENT1 and ENT2. The presence of a halogen substitute, regardless of the position, in the fluorophenyl moiety next to the piperazine ring was essential for the inhibitory effects on ENT1 and ENT2. Among the analogues tested, compound 3c was the most potent inhibitor. Compound 3c reduced V max of [3H]uridine uptake in ENT1 and ENT2 without affecting K m. The inhibitory effect of compound 3c could not be washed out. Compound 3c did not affect cell viability, protein expression and internalization of ENT1 and ENT2. Therefore, similar to FPMINT, compound 3c was an irreversible and non-competitive inhibitor. Molecular docking analysis also showed that the binding site of compound 3c in ENT1 may be different from that of other conventional inhibitors. It is expected that structural modification may further improve its potency and selectivity and lead to the development of useful pharmacological agents.

6.
Nat Commun ; 13(1): 1055, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35217665

RESUMO

Plasticity is ubiquitous and plays a critical role in material deformation and damage; it inherently involves the atomistic length scale and picosecond time scale. A fundamental understanding of the elastic-plastic deformation transition, in particular, incipient plasticity, has been a grand challenge in high-pressure and high-strain-rate environments, impeded largely by experimental limitations on spatial and temporal resolution. Here, we report femtosecond MeV electron diffraction measurements visualizing the three-dimensional (3D) response of single-crystal aluminum to the ultrafast laser-induced compression. We capture lattice transitioning from a purely elastic to a plastically relaxed state within 5 ps, after reaching an elastic limit of ~25 GPa. Our results allow the direct determination of dislocation nucleation and transport that constitute the underlying defect kinetics of incipient plasticity. Large-scale molecular dynamics simulations show good agreement with the experiment and provide an atomic-level description of the dislocation-mediated plasticity.

7.
Phytomedicine ; 94: 153824, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34763314

RESUMO

BACKGROUND: The anti-cancer activity of andrographolide (Andro) has been extensively demonstrated in recent years. It is supposed that modifying the chemical structure of Andro can improve its efficacy and reduce its toxicity. PURPOSE: In this study, the anti-cancer effect of a 14ß-(2'-chlorophenoxy) derivative of andrographolide known as AGS-30 was investigated, and its underlying mechanisms were also explored. STUDY DESIGN/METHODS: Different cancer cells were used to evaluate and compare the in vitro anti-cancer effects of Andro and AGS-30. Human colon cancer cells HT-29 and HCT-116 were used to study the underlying anti-cancer mechanisms of AGS-30. HT-29 cells xenografted in nude mouse model was used to compare the in vivo anti-tumour efficacies of Andro and AGS-30. RESULT: In vitro studies showed that AGS-30 possessed an anti-cancer effect by inhibiting the viability, colony formation and migration of cancer cells. It significantly induced the generation of reactive oxygen species (ROS), caused the loss of mitochondrial membrane potential and triggered the apoptosis in colon cancer cells. These effects of AGS-30 were more potent than those of Andro. In addition, the expression levels of proteins associated with apoptosis, including phospho-JNK1/2 as well as cleaved caspase 9, caspase 3, and poly(ADP ribose) polymerase, were elevated in AGS-30-treated colon cancer cells. Moreover, these elevated levels of the proteins were inhibited by the antioxidant N-acetylcysteine and the JNK inhibitor SP600125, suggesting the involvement of ROS/JNK-dependent mechanisms in AGS-30-induced apoptosis. The in vitro anti-cancer effect could be reproduced in an HT-29 colon cancer cell xenografted nude mouse model. CONCLUSION: The anti-cancer effect of AGS-30 is stronger than that of Andro. AGS-30 induces apoptosis of colon cancer cells through ROS/JNK-dependent pathway. Our findings may provide insights for the future development of derivatives of Andro as novel chemotherapeutic agents.


Assuntos
Neoplasias do Colo , Diterpenos , Animais , Apoptose , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Diterpenos/farmacologia , Humanos , Camundongos , Espécies Reativas de Oxigênio
8.
Phys Rev Lett ; 127(22): 227401, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34889631

RESUMO

Engineering novel states of matter with light is at the forefront of materials research. An intensely studied direction is to realize broken-symmetry phases that are "hidden" under equilibrium conditions but can be unleashed by an ultrashort laser pulse. Despite a plethora of experimental discoveries, the nature of these orders and how they transiently appear remain unclear. To this end, we investigate a nonequilibrium charge density wave (CDW) in rare-earth tritellurides, which is suppressed in equilibrium but emerges after photoexcitation. Using a pump-pump-probe protocol implemented in ultrafast electron diffraction, we demonstrate that the light-induced CDW consists solely of order parameter fluctuations, which bear striking similarities to critical fluctuations in equilibrium despite differences in the length scale. By calculating the dynamics of CDW fluctuations in a nonperturbative model, we further show that the strength of the light-induced order is governed by the amplitude of equilibrium fluctuations. These findings highlight photoinduced fluctuations as an important ingredient for the emergence of transient orders out of equilibrium. Our results further suggest that materials with strong fluctuations in equilibrium are promising platforms to host hidden orders after laser excitation.

9.
Eur J Pharmacol ; 905: 174190, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015322

RESUMO

Narirutin is one of the most common flavanones found in citrus fruits. The vascular effects of its analogues naringenin and naringin have been reported but its effects on the cardiovascular system are largely unknown. In this study, relaxation effect of narirutin and its mechanisms of action were investigated by measuring isometric tension in rat mesenteric arteries. Patch-clamping was also used to study the effect of narirutin on potassium channels in vascular smooth muscle cells. Moreover, its effects on phosphorylation of endothelial nitric oxide synthase, cAMP level and phosphodiesterase activity in rat mesenteric arteries were studied by Western blot and biochemical assays. The results showed that pre-incubation of rat mesenteric arteries with narirutin had no influence on acetylcholine-induced endothelial-dependent relaxation. However, narirutin caused a direct concentration-dependent relaxation in rat mesenteric arteries. This relaxation effect was comparable to that of narirutin's structural analogue naringenin. Narirutin-induced relaxation was reduced by the removal of endothelium, NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor), and 4-aminopyridine (a voltage-gated potassium channel blocker). In addition, narirutin increased the phosphorylation of endothelial nitric oxide synthase and increased the voltage-dependent potassium current in mesenteric arterial smooth muscle cells. These effects were abolished by protein kinase A inhibitor. Furthermore, narirutin could increase cAMP level and inhibit phosphodiesterase activity in rat mesenteric arteries. In conclusion, narirutin has vasorelaxing effect and the mechanism involves the inhibition of phosphodiesterase, which increases intracellular cAMP, thereby stimulating the endothelial nitric oxide synthase and activating the voltage-gated potassium channels in vascular smooth muscle cells.


Assuntos
Dissacarídeos/farmacologia , Flavanonas/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/agonistas , Vasodilatadores/farmacologia , Animais , AMP Cíclico/metabolismo , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Ratos Sprague-Dawley
10.
Opt Express ; 29(6): 9624-9634, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820386

RESUMO

We demonstrate a highly efficient method for the generation of a high-field terahertz (THz) pulse train via optical rectification (OR) in congruent lithium niobate (LN) crystals driven by temporally shaped laser pulses. A narrowband THz pulse has been successfully achieved with sub-percent level conversion efficiency and multi MV/cm peak field at 0.26 THz. For the single-cycle THz generation, we achieved a THz pulse with 373-µJ energy in a LN crystal excited by a 100-mJ laser pulse at room temperature. The conversion efficiency is further improved to 0.77 % pumped by a 20-mJ laser pulse with a smaller pump beam size (6 mm in horizontal and 15 mm in vertical). This method holds great potential for generating mJ-level narrow-band THz pulse trains, which may have a major impact in mJ-scale applications like terahertz-based accelerators and light sources.

11.
Oxid Med Cell Longev ; 2021: 6683270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628381

RESUMO

Amauroderma rugosum (AR) is a dietary mushroom in the Ganodermataceae family whose pharmacological activity and medicinal value have rarely been reported. In this study, the antioxidant capacity and neuroprotective effects of AR were investigated. The aqueous extract of AR was confirmed to contain phenolic compounds, polysaccharides, and triterpenes. The results of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and total antioxidant capacity assays revealed that AR extract scavenged reactive oxygen species. Moreover, AR extract decreased the cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis of PC12 cells induced by 6-hydroxydopamine (6-OHDA). In addition, 6-OHDA upregulated the expressions of proapoptotic proteins and downregulated the Akt (protein kinase B)/mTOR- (mammalian target of rapamycin-) and MEK (mitogen-activated protein kinase kinase)/ERK- (extracellular signal-regulated kinases-) dependent signaling pathways. These effects of 6-OHDA were abolished or partially reversed by AR extract. Furthermore, the neuroprotective effects of AR in 6-OHDA-treated PC12 cells were significantly abolished by Akt and MEK inhibitor. Thus, AR extract possesses neuroprotective effects, probably through its antioxidant and antiapoptotic effects. These findings suggest the potential application of AR in the prevention or treatment of oxidative stress-related neurodegenerative diseases such as Parkinson's disease.


Assuntos
Antioxidantes/farmacologia , Apoptose , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/toxicidade , Polyporaceae/química , Animais , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Oxidopamina , Células PC12 , Picratos/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo
12.
Phytomedicine ; 81: 153408, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33234363

RESUMO

BACKGROUND: Therapeutic regimens of breast cancer treatment are increasingly inclined to adopt combination strategy based on the broad spectrum antitumor effect of doxorubicin (Dox). Currently, combination therapy comprises of conventional anti-cancer drugs and angiogenesis inhibitors have been corroborated as an effective approach in cancer treatment. PURPOSE: We explored the ability of a natural anti-angiogenic compound glycyrrhetinic acid (GA), derived from an edible-medicinal herb licorice, to enhance the breast cancer suppression effect of Dox. STUDY DESIGN: The drug ratio of GA and Dox with synergistic anticancer effect against MCF-7 cells was optimized by combination index (CI) value in vitro, followed by evaluation of the improved anticancer effects and reduced side-effects of this combination in vitro and in vivo. METHODS: Cell viability was measured by MTT assay. Analyses of mitochondrial membrane potential and cell apoptosis on MCF-7 cells were performed by JC-1 dye and Annexin V-FITC/PI assays. The cellular accumulation of Dox when combined with GA was evaluated. Levels of apoptosis-related proteins in MCF-7 cells were measured by Western blot analysis. Synergistic anti-angiogenic effects on HUVECs were evaluated. A breast cancer mouse model was established to investigate the anti-tumor effects in vivo. RESULTS: Based on the optimization by CI value, Dox and GA at 1:20 molar ratio was chosen as the optimal combination drug ratio that exhibited synergistic effect against MCF-7 breast cancer cells. In addition, the combination of GA and Dox exhibited significantly enhanced cytotoxicity, apoptosis, and loss of mitochondrial membrane potential via the upregulation of a mitochondrial-dependent apoptosis pathway against MCF-7 cells. Interestingly, the addition of GA increased the intracellular accumulation of Dox in MCF-7 cells. Moreover, VEGF-induced HUVECs proliferation, migration, and tube formation were strongly inhibited by Dox when used with GA via the significant down-regulation of VEGFR2-mediated pathway, indicating that the combination of Dox and GA could exhibit ideal synergistic anti-angiogenesis effect. Expectedly, the enhanced anti-tumor efficacy of Dox and reduced Dox-induced cardiotoxicity when used in combination with GA were evident in a mouse breast tumor model. CONCLUSIONS: These findings support that the combination of Dox with GA is a novel and promising therapeutic strategy for the treatment of breast cancer.


Assuntos
Inibidores da Angiogênese/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Ácido Glicirretínico/administração & dosagem , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
ACS Nano ; 14(7): 8449-8458, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32538617

RESUMO

The inspection of Friedel's law in ultrafast electron diffraction (UED) is important to gain a comprehensive understanding of material atomic structure and its dynamic response. Here, monoclinic gallium telluride (GaTe), as a low-symmetry, layered crystal in contrast to many other 2D materials, is investigated by mega-electronvolt UED. Strong out-of-phase oscillations of Bragg peak intensities are observed for Friedel pairs, which does not obey Friedel's law. As evidenced by the preserved mirror symmetry and supported by both kinematic and dynamic scattering simulations, the intensity oscillations are provoked by the lowest-order longitudinal acoustic breathing phonon. Our results provide a generalized understanding of Friedel's law in UED and demonstrate that by designed misalignment of surface normal and primitive lattice vectors, coherent lattice wobbling and effective shear strain can be generated in crystal films by laser pulse excitation, which is otherwise hard to achieve and can be further utilized to dynamically tune and switch material properties.

14.
BioData Min ; 13: 2, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32351618

RESUMO

BACKGROUND AND OBJECTIVE: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. METHODS: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. RESULTS: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. CONCLUSION: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

15.
Science ; 368(6493): 885-889, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32439793

RESUMO

Simultaneous observation of nuclear and electronic motion is crucial for a complete understanding of molecular dynamics in excited electronic states. It is challenging for a single experiment to independently follow both electronic and nuclear dynamics at the same time. Here we show that ultrafast electron diffraction can be used to simultaneously record both electronic and nuclear dynamics in isolated pyridine molecules, naturally disentangling the two components. Electronic state changes (S1→S0 internal conversion) were reflected by a strong transient signal in small-angle inelastic scattering, and nuclear structural changes (ring puckering) were monitored by large-angle elastic diffraction. Supported by ab initio nonadiabatic molecular dynamics and diffraction simulations, our experiment provides a clear view of the interplay between electronic and nuclear dynamics of the photoexcited pyridine molecule.

16.
J Nutr Biochem ; 77: 108268, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31830590

RESUMO

Glycyrrhetinic acid (GA) is a major bioactive compound of licorice. The objective of this study was to investigate the effects of GA on ovarian cancer, particularly those related to angiogenesis and apoptosis, and to elucidate the underlying mechanisms of action. In vitro studies showed that GA significantly inhibited proliferation, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. GA inhibited the phosphorylation of major receptors and enzymes involved in angiogenesis, such as VEGFR2, mTOR, Akt, ERK1/2, MEK1/2, p38 and JNK1/2 in HUVECs. In addition, GA induced apoptosis, loss of mitochondrial membrane potential and cell cycle arrest in G1 phase in A2780 ovarian cancer cells. The proapoptotic effect of GA involved the increased phosphorylation of p38 and JNK1/2; increased cleavage of caspase 3, caspase 9 and PARP; reduced phosphorylation of mTOR, Akt and ERK1/2; and reduced expressions of survivin and cyclin D1. Ex vivo studies showed that GA significantly inhibited microvessel sprouting in rat aortic ring model. In vivo studies showed that GA inhibited the formation of new blood vessels in zebrafish and mouse Matrigel plug. GA also significantly reduced the size of ovarian cancer xenograft tumors in nude mice. Taken together, GA possesses potential antitumor effects, and the underlying mechanisms may involve the inhibition of signaling pathways related to angiogenesis and the activation of apoptotic pathways in cancer cells. Our findings suggest that GA could serve as an effective regimen in the prevention or treatment of cancer.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Glicirretínico/farmacologia , Neovascularização Patológica/prevenção & controle , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/prevenção & controle , Animais , Aorta/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Nus , Invasividade Neoplásica , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
17.
Biochem Pharmacol ; 171: 113694, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706845

RESUMO

Poor bioavailability and limited efficacy are challenges associated with using andrographolide as a therapeutic agent. We recently synthesized AGS-30, a new andrographolide derivative, in our laboratory. In this study we investigated the potential anti-tumor effect of AGS-30 and the underlying mechanisms, particularly those related to angiogenesis. Results from our in vitro experiments showed that AGS-30 exerted anti-angiogenic effects by inhibiting endothelial cell proliferation, migration, invasion, and tube formation. Phosphorylation and activation of angiogenesis-related signaling molecules (e.g., vascular endothelial growth factor [VEGF] receptor 2, mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2, mechanistic target of rapamycin [mTOR], protein kinase B [Akt], and p38) were markedly reduced by AGS-30. Meanwhile, AGS-30 potently inhibited cell proliferation and phosphorylation of cell survival-related proteins (e.g., Akt, mTOR, and ERK1/2) and decreased the expression of VEGF in HT-29 colon cancer cells. AGS-30 blocked microvessel sprouting in a rat aortic ring model and blood vessel formation in zebrafish embryos and a mouse Matrigel plug model. Additionally, AGS-30 suppressed tumor growth and angiogenesis in HT-29 colon cancer cell xenografts in nude mice. These effects were not observed when same concentration of andrographolide, the parent compound of AGS-30, was used. Thus, AGS-30 exerted a strong antitumor effect by inhibiting tumor cell growth and angiogenesis and is a candidate compound for the treatment of cancer.


Assuntos
Inibidores da Angiogênese/farmacologia , Diterpenos/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Neovascularização Patológica/prevenção & controle , Peixe-Zebra/embriologia , Inibidores da Angiogênese/química , Animais , Animais Geneticamente Modificados , Células Cultivadas , Diterpenos/química , Embrião não Mamífero/irrigação sanguínea , Embrião não Mamífero/embriologia , Células HT29 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Estrutura Molecular , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Peixe-Zebra/genética
18.
Phys Rev Lett ; 123(9): 097601, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31524450

RESUMO

Complex systems, which consist of a large number of interacting constituents, often exhibit universal behavior near a phase transition. A slowdown of certain dynamical observables is one such recurring feature found in a vast array of contexts. This phenomenon, known as critical slowing-down, is well studied mostly in thermodynamic phase transitions. However, it is less understood in highly nonequilibrium settings, where the time it takes to traverse the phase boundary becomes comparable to the timescale of dynamical fluctuations. Using transient optical spectroscopy and femtosecond electron diffraction, we studied a photoinduced transition of a model charge-density-wave (CDW) compound LaTe_{3}. We observed that it takes the longest time to suppress the order parameter at the threshold photoexcitation density, where the CDW transiently vanishes. This finding can be captured by generalizing the time-dependent Landau theory to a system far from equilibrium. The experimental observation and theoretical understanding of dynamical slowing-down may offer insight into other general principles behind nonequilibrium phase transitions in many-body systems.

19.
Nano Lett ; 19(8): 4981-4989, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31260315

RESUMO

The light-induced selective population of short-lived far-from-equilibrium vibration modes is a promising approach for controlling ultrafast and irreversible structural changes in functional nanomaterials. However, this requires a detailed understanding of the dynamics and evolution of these phonon modes and their coupling to the excited-state electronic structure. Here, we combine femtosecond mega-electronvolt electron diffraction experiments on a prototypical layered material, MoTe2, with non-adiabatic quantum molecular dynamics simulations and ab initio electronic structure calculations to show how non-radiative energy relaxation pathways for excited electrons can be tuned by controlling the optical excitation energy. We show how the dominant intravalley and intervalley scattering mechanisms for hot and band-edge electrons leads to markedly different transient phonon populations evident in electron diffraction patterns. This understanding of how tuning optical excitations affect phonon populations and atomic motion is critical for efficiently controlling light-induced structural transitions of optoelectronic devices.

20.
Sci Adv ; 5(5): eaaw0392, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31139748

RESUMO

Materials exposed to extreme radiation environments such as fusion reactors or deep spaces accumulate substantial defect populations that alter their properties and subsequently the melting behavior. The quantitative characterization requires visualization with femtosecond temporal resolution on the atomic-scale length through measurements of the pair correlation function. Here, we demonstrate experimentally that electron diffraction at relativistic energies opens a new approach for studies of melting kinetics. Our measurements in radiation-damaged tungsten show that the tungsten target subjected to 10 displacements per atom of damage undergoes a melting transition below the melting temperature. Two-temperature molecular dynamics simulations reveal the crucial role of defect clusters, particularly nanovoids, in driving the ultrafast melting process observed on the time scale of less than 10 ps. These results provide new atomic-level insights into the ultrafast melting processes of materials in extreme environments.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...