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2.
J Cell Physiol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31912899

RESUMO

Endothelial cells (ECs) respond to flow stress via a variety of mechanisms, leading to various intracellular responses that can modulate the vessel wall and lead to diseases if the flow is disturbed. Mechano-microRNAs (miRNAs) are a subset of miRNAs in the ECs that are flow responsive. Mechano-miRNAs were shown to be related to atherosclerosis pathophysiology, and a number of them were identified as pathologic. Here, we exposed human carotid ECs to different wall shear stresses (WSS), high and low, and evaluated the response of miRNAs by microarray and quantitative polymerase chain reaction analysis. We discovered five new mechano-miRNAs that were not reported in that context previously to the best of our knowledge. Moreover, functional pathway analysis revealed that under low WSS conditions, several pathways regulating apoptosis are affected. In addition, KLF2 and KLF4, known atheroprotective genes, were downregulated under low WSS and upregulated under high WSS. KLF2 and VCAM1, both angiogenic, were upregulated under high WSS. NOS3, which is vascular protective, was also upregulated with higher WSS. On the contrary, ICAM-1 and E-selectin, both atherogenic and proinflammatory, were upregulated with high WSS. Collectively, the epigenetic landscape with the gene expression analysis reveals that low WSS is associated with a proapoptotic state, while high WSS is associated with a proliferative and proinflammatory state.

3.
J Membr Biol ; 253(1): 43-55, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820013

RESUMO

Lysophosphatidylcholine (LPC) is a major atherogenic lipid that stimulates an increase in mitochondrial reactive oxygen species (mtROS) and the release of cytokines under inflammasome activation. However, the potential receptors of LPC in macrophages are poorly understood. Members of the transient receptor potential (TRP) channel superfamily, which is crucially involved in transducing environmental irritant stimuli into nociceptor activity, are potential receptors of LPC. In this study, we investigated whether LPC can induce the activation of transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily. The functional expression of TRPA1 was first detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and calcium imaging in human acute monocytic leukemia cell line (THP-1)-derived macrophages. The mechanism by which LPC induces the activation of macrophages through TRPA1 was verified by cytoplasmic and mitochondrial calcium imaging, mtROS detection, a JC-1 assay, enzyme-linked immunosorbent assay, the CCK-8 assay and the lactate dehydrogenase (LDH) cytotoxic assay. LPC induced the activation of THP-1-derived macrophages via calcium influx, and this activation was suppressed by potent and selective inhibitors of TRPA1. These results indicated that TRPA1 can mediate mtROS generation, mitochondrial membrane depolarization, the secretion of IL-1ß and cytotoxicity through cellular and mitochondrial Ca2+ influx in LPC-treated THP-1-derived macrophages. Therefore, the inhibition of TRPA1 may protect THP-1-derived macrophages against LPC-induced injury.

4.
Technol Health Care ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31796716

RESUMO

BACKGROUND: Blood vessels are constantly exposed to flow-induced stresses, and endothelial cells (ECs) respond to these stresses in various ways. OBJECTIVE: In order to facilitate endothelialization after endovascular implantation, cell behaviors around a metallic wire using a flow circulation system are observed. METHODS: A parallel flow chamber was designed to reproduce constant shear stresses (SSs) on cell surfaces and to examine the effects of a straight bare metal wire on cell monolayers. Cells were then exposed to flow for 24 h under SS conditions of 1, 2, and 3 Pa. Subsequently, cell distributions were observed on the plate of the flow chamber and on the surface of the bare metal wire. Flow fields inside the flow chamber were analyzed using computational fluid dynamics under each SS condition. RESULTS: After 24 h, ECs on the bottom plate were concentrated toward the area of flow reattachment. The matching of higher cell density and CFD result suggests that flow-induced stimuli have an influence on EC distributions. CONCLUSION: Typical cell concentration occurs on dish plate along the vortexes, which produces large changes in SSs on cell layer.

5.
Stem Cell Res ; 40: 101571, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31520889

RESUMO

Autism spectrum disorder (ASD) is a neurological disorder with complex etiologies. In this study, urine cells were collected from a 16-year-old male with ASD and reprogrammed with the human SKOM transcription factors. The patient has a heterozygous C > T mutation of FCGR1B gene that was confirmed by sequencing analysis. The pluripotency was verified by gene expression and capacity of differentiation towards the three germ layers. This kind of iPSC will be valuable for further understanding the pathogenesis of ASD and help to develop drugs for treating ASD.

6.
Stem Cell Res ; 40: 101555, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31491691

RESUMO

The induced pluripotent stem cell (iPSC) line XHCSUi001-A generated from urine cells of a female spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) patient by using the integration-free methods. The induced XHCSUi001-A retained the disease-causing ATXN3 mutation, expressed pluripotency markers, exhibited a normal karyotype and retained the ability to differentiate into the three germ layers in-vitro and in-vivo. This newly induced iPSC line could be a potential tool for researching the disease-specific mechanisms and drug screening of SCA3/MJD.

7.
Cell Physiol Biochem ; 52(6): 1325-1338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31050281

RESUMO

BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory cardiovascular disease. Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors. Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages. In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages. METHODS: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-γ. Intracellular ROS production was assessed by 2'-7'-dichloroflorescein diacetate and flow cytometry. Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot. RESULTS: Model M1 peritoneal macrophages were established after 24 h induction. Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group. Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-α markedly decreased after PDT. The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine. Furthermore, ROS generated by UCNPs- Ce6 mediated PDT activated autophagy. The expression of autophagy related-protein and inflammatory cytokines iNOS, IL-12, and TNF-α were inhibited by the ROS inhibitor N-acetyl cysteine. CONCLUSION: ROS generated by UCNPs-Ce6-mediated PDT activated autophagy and inhibited the expression of pro-inflammatory factors of M1 peritoneal macrophage via the PI3K/AKT/mTOR signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Nanopartículas Metálicas/química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteína Beclina-1/metabolismo , Interleucina-12/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fotoquimioterapia , Porfirinas/química , Porfirinas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
J Am Chem Soc ; 141(23): 9134-9139, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31131600

RESUMO

The flexible organic amine cations on the interfaces of two-dimensional (2D) hybrid organic-inorganic perovskite nanosheets could form relaxed structures, which would lead to exotic optoelectronic properties but are hard to understand. Here, the unusual interfacial relaxation of nanosheets exfoliated from an orthorhombic 2D lead halide perovskite, [(C6H5CH2NH3)2]PbCl4, is interrogated via ultrafast second-harmonic generation (SHG) spectroscopy. The in-plane SHG intensity anisotropy of these nanosheets is found to decrease with reducing layer thickness. Combined first-principles calculations and Monte Carlo simulations reveal that the induced second-order polarization arises primarily from the (C6H5CH2NH3)+ cations; and these organic amine cations form significantly reorganized conformations with decreasing nanosheet thickness due to weakened van der Waals interactions. Because the orientations of organic components at the interface determine their electric properties and specifically the dipolar susceptibility, the resulting structure leads to striking changes in the SHG properties.

9.
Cell Death Dis ; 10(3): 202, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30814492

RESUMO

The authors wish to point out that in Figure 1f, the picture of DAPI in the ATG5 siRNA group is incorrect. During the process of image synthesis, the authors mixed the pictures of DAPI in the control group and ATG5 siRNA group, leading to the duplicate between them of DAPI. Furthermore, the AMPK blot and the AKT blot in Figure 2a were inadvertently duplicated with the third ß-actin in Figure 2a and AKT in Figure 4e, respectively. The authors would like to apologize for any inconvenience this may have caused.

10.
Cytotechnology ; 71(2): 489-496, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30707337

RESUMO

Recently, our group has contrasted an endothelial cell-smooth muscle cell (EC-SMC) co-culture model with 3D-cultured SMCs and found that SMCs could respond to high shear stress (SS), which has not been explored before. SMCs were not directly exposed to the flow but were under an EC monolayer; therefore, it is necessary to explore the influence of EC on SMC behaviors under high SS for understanding the mechanism of SMC response to various magnitudes of SS. In the present study, TGF-ß1 expression in ECs in an EC-SMC co-culture model was suppressed by an siRNA transfection method. Next, phenotypic changes were observed and MMP-2 and -9 productions were measured in SMCs in the co-culture model after 72-h flow exposure to different SS levels. We confirmed that TGF-ß1 expression in ECs could influence SMC phenotypic change under SS conditions and that TGF-ß1 expression in ECs could also change MMP-2 production but not MMP-9 production in SMCs under SS conditions in the co-culture model. These results could be useful for understanding the mechanisms of SMC response to SS, particularly for understanding signal transduction emanating from ECs.

11.
Environ Sci Eur ; 30(1): 45, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30574433

RESUMO

Background: Identifying typical odor-causing compounds is essential for odor problem control in drinking water. In this study, aiming at a major water source reservoir in hot and humid areas in southern China, which encountered seasonable odor problems in recent years, an integrated approach including comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC-TOFMS), flavor profile analysis (FPA) and quantitative real-time polymerase chain reaction (qPCR) was adopted to investigate the odor occurrence. Results: The results indicated that earthy-musty odor is blamed to the seasonable odor problems, and it is consistent with the complaints results from consumers. Fifty-four typical odor compounds were investigated in the reservoir and twelve were detected, of which, 2-methylisoborneol (2-MIB) was significantly increased during the odor event. Pseudanabaena sp. is the dominant species in the reservoir, which can be further represented by the number of mic gene with qPCR method (R 2 = 0.746, P < 0.001). Oxygen consumption (CODMn) and dissolved organic carbon (DOC) have great influence on growth of Pseudanabaena sp., and the release of 2-MIB from the Pseudanabaena sp. cells is affected by temperature and light. Conclusion: Our findings demonstrated that 2-MIB is the odor-caused substance in the reservoir and Pseudanabaena sp. is the main 2-MIB producer, which was confirmed as a benthic filamentous algae. Due to CODMn and DOC have great influence on Pseudanabaena sp. growth, further measures to reduce the CODMn and DOC input should be performed. We also demonstrated that the 2-MIB release is affected by temperature and light. The risk of sudden increase of 2-MIB will be reduced by raising the depth of water in the reservoir. Our study will improve the understanding of T&O problems in this city, as well as in other hot and humid area.

12.
Cell Physiol Biochem ; 48(4): 1616-1627, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30071509

RESUMO

BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory cardiovascular disease. Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors. Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages. In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages. METHODS: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-γ. Intracellular ROS production was assessed by 2'-7'-dichloroforescein diacetate and flow cytometry. Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot. RESULTS: Model M1 peritoneal macrophages were established after 24 h induction. Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group. Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-α markedly decreased after PDT. The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine. Furthermore, ROS generated by UCNPs-Ce6 mediated PDT activated autophagy. The expression of autophagy related-protein and inflammatory cytokines iNOS, IL-12, and TNF-α were inhibited by the ROS inhibitor N-acetyl cysteine. CONCLUSIONS: ROS generated by UCNPs-Ce6-mediated PDT activated autophagy and inhibited the expression of pro-inflammatory factors of M1 peritoneal macrophage via the PI3K/AKT/mTOR signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Interleucina-12/metabolismo , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Nanopartículas de Magnetita/química , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fotoquimioterapia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de IgG/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Neuroscience ; 384: 188-202, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29782904

RESUMO

Sphingosine-1-phosphate (S1P) is a sphingolipid molecule produced by the action of sphingosine kinases (SphK) on sphingosine. It possesses various intracellular functions through its interactions with intracellular proteins or via its action on five G-protein-coupled cell membrane receptors. Following transient global cerebral ischemia (tGCI), only the CA1 subregion of the hippocampus undergoes apoptosis. In this study, we evaluated S1P levels and S1P-processing enzyme expression in different hippocampal areas following tGCI in rats. We found that S1P was upregulated earlier in CA3 than in CA1. This was associated with upregulation of SphK1 in both regions; however, SphK2 was downregulated quickly in CA3. S1P lyase was also downregulated in CA3, but not in CA1. Spinster 2, the S1P exporter, was upregulated early in both regions, but was quickly downregulated in CA3. Together, these effects explain the variable levels of S1P in the CA1 and CA3 areas and indicate that S1P levels play a role in the preferential resistance of the CA3 subregion to tGCI-induced ischemia. FTY720 did not improve neuronal survival in the CA1 subregion, indicating that these effects were due to intracellular S1P accumulation. In conclusion, the findings suggest that intracellular S1P levels affect neuronal cell fate following tGCI.


Assuntos
Hipocampo/metabolismo , Ataque Isquêmico Transitório/metabolismo , Lisofosfolipídeos/metabolismo , Neurônios/metabolismo , Esfingosina/análogos & derivados , Animais , Apoptose/fisiologia , Regulação para Baixo , Hipocampo/patologia , Ataque Isquêmico Transitório/patologia , Masculino , Células PC12 , Ratos , Ratos Sprague-Dawley , Esfingosina/metabolismo , Regulação para Cima
14.
Nano Lett ; 18(2): 1344-1350, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29370525

RESUMO

Recently, nonlinear hybrid metasurface comes into an attractive new concept in the research of nanophotonics and nanotechnology. It is composed of semiconductors with an intrinsically large nonlinear susceptibility and traditional plasmonic metasurfaces, offering opportunities for efficiently generating and manipulating nonlinear optical responses. A high second-harmonic generation (SHG) conversion efficiency has been demonstrated in the mid-infrared region by using multiquantum-well (MQW)-based plasmonic metasurfaces. However, it has yet to be demonstrated in the visible region. Here, we present a new type of nonlinear hybrid metasurfaces for the visible region, which consists of a single layer of tungsten disulfide (WS2) and a phased gold nanohole array. The results indicate that a large SHG susceptibility of ∼10-1 nm/V at 810 nm is achieved, which is 2-3 orders of magnitude larger than that of typical plasmonic metasurfaces. Nonlinear metalenses with the focal lengths of 30, 50, and 100 µm are demonstrated experimentally, providing a direct evidence for both generating and manipulating SH signals based on the nonlinear hybrid metasurfaces. It shows great potential applications in designing of integrated, ultrathin, compacted, and efficient nonlinear optical devices, such as frequency converters, nonlinear holography, and the generation of nonlinear optical vortex beams.

15.
Cell Death Dis ; 8(6): e2864, 2017 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-28594401

RESUMO

Macrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect. First, we found that PDT notably enhanced the cholesterol efflux and the induction of autophagy in both THP-1 and peritoneal macrophage-derived foam cells. The autophagy inhibitor 3-methyladenine and an ATG5 siRNA significantly attenuated PDT-induced autophagy, which subsequently suppressed the ABCA1-mediated cholesterol efflux. Furthermore, the reactive oxygen species (ROS) produced by PDT were responsible for the induction of autophagy, which could be blocked by the ROS inhibitor N-acetyl cysteine (NAC). NAC also reversed the PDT-induced suppression of p-mTOR and p-Akt. Therefore, our findings demonstrate that PDT promotes cholesterol efflux by inducing autophagy, and the autophagy was mediated in part through the ROS/PI3K/Akt/mTOR signaling pathway in THP-1 and peritoneal macrophage-derived foam cells.


Assuntos
Aterosclerose , Autofagia/efeitos dos fármacos , Colesterol/metabolismo , Células Espumosas/metabolismo , Macrófagos Peritoneais/metabolismo , Nanopartículas/química , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Espumosas/patologia , Humanos , Macrófagos Peritoneais/patologia , Camundongos , Células THP-1
16.
Oxid Med Cell Longev ; 2017: 8519169, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28191279

RESUMO

Monocyte-derived macrophages participate in infaust inflammatory responses by secreting various types of proinflammatory factors, resulting in further inflammatory reactions in atherosclerotic plaques. Autophagy plays an important role in inhibiting inflammation; thus, increasing autophagy may be a therapeutic strategy for atherosclerosis. In the present study, hydroxysafflor yellow A-mediated sonodynamic therapy was used to induce autophagy and inhibit inflammation in THP-1 macrophages. Following hydroxysafflor yellow A-mediated sonodynamic therapy, autophagy was induced as shown by the conversion of LC3-II/LC3-I, increased expression of beclin 1, degradation of p62, and the formation of autophagic vacuoles. In addition, inflammatory factors were inhibited. These effects were blocked by Atg5 siRNA, the autophagy inhibitor 3-methyladenine, and the reactive oxygen species scavenger N-acetyl cysteine. Moreover, AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 decreased significantly after HSYA-SDT. These effects were inhibited by the PI3K inhibitor LY294002, the AKT inhibitor triciribine, the mTOR inhibitor rapamycin, mTOR siRNA, and N-acetyl cysteine. Our results demonstrate that HSYA-SDT induces an autophagic response via the PI3K/Akt/mTOR signaling pathway and inhibits inflammation by reactive oxygen species in THP-1 macrophages.


Assuntos
Autofagia/efeitos dos fármacos , Chalcona/análogos & derivados , Macrófagos/efeitos dos fármacos , Quinonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Terapia por Ultrassom/métodos , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Chalcona/farmacologia , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Técnicas de Silenciamento de Genes , Humanos , Microscopia Eletrônica de Transmissão , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo
17.
Opt Express ; 25(2): 1296-1307, 2017 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-28158013

RESUMO

We systematically study the contribution of local-field distribution to second-harmonic generation (SHG) in cross-shaped Ag nanohole arrays, which is usually covered by resonance enhancement effect. By increasing one arm-length of the centrosymmetric cross-shaped Ag nanohole, the local-field distribution varies from centrosymmetric to non-centrosymmetric, while the localized surface plasmon resonance peak is red-shifted to the wavelength of the pumping laser accordingly. Both experimental and stimulated results indicate that the contribution of the asymmetric local-field distribution to SHG is quantitatively separated from a strong resonance enhancement effect. It shows that the pure effective second-order nonlinear susceptibility increases as the asymmetric degree of local-field distribution increases, and the largest effective second-order nonlinear susceptibility is ~2.5 times to that in a centrosymmetric local-field distribution. Our results provide evidence for optimizing the design of nonlinear plasmonic nanoantennas and metasurfaces.

18.
Cell Death Dis ; 8(1): e2558, 2017 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-28102849

RESUMO

Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced. The first two effects were blocked by the reactive oxygen species scavenger, N-acetyl cysteine. BBR-SDT also reduced the phosphorylation of Akt and mTOR, two key molecules in the PI3K/AKT/mTOR signaling pathway, which is responsible for inducing autophagy. Correspondingly, treatment with the autophagy inhibitor, 3-methyladenine, or the PI3K inhibitor, LY294002, abolished the autophagy-induced effects of BBR-SDT. Furthermore, induction of cholesterol efflux by BBR-SDT was reversed by an inhibition of autophagy by 3-methyladenine or by a small interfering RNA targeting Atg5. Taken together, these results demonstrate that BBR-SDT effectively promotes cholesterol efflux by increasing reactive oxygen species generation, and this subsequently induces autophagy via the PI3K/AKT/mTOR signaling pathway in both 'normal' macrophages and lipid-loaded macrophages (foam cells). Thus, BBR-SDT may be a promising atheroprotective therapy to inhibit the progression of atherosclerosis and should be further studied.


Assuntos
Aterosclerose/tratamento farmacológico , Autofagia/efeitos dos fármacos , Colesterol/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Autofagia/genética , Berberina/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Colesterol/genética , Cromonas/administração & dosagem , Humanos , Lipídeos/biossíntese , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Morfolinas/administração & dosagem , Proteína Oncogênica v-akt , Fosfatidilinositol 3-Quinases/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Ultrassonografia
19.
Medicine (Baltimore) ; 96(52): e9539, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29384972

RESUMO

The retrospective study aimed at investigating the safety and clinical efficacy of long-term application of tolvaptan in patients >90 years old with hyponatremia. Although tolvaptan has been used to treat hyponatremia, the effect of its long-term use in elderly patients was unknown.Seven patients over 90 with isovolumic or hypervolemic hyponatremia admitted to the PLA Navy General Hospital between October 2011 and October 2013 were enrolled. The patients' serum sodium levels <135 mmol/L persisted for more than 3 months, and oral treatment with tolvaptan lasted for more than 12 months. Tolvaptan dose started from 7.5 mg once daily, with maximum dose no more than 30 mg daily. Clinical and laboratory data of the patients before and after treatment were compared.Serum sodium and chlorine levels increased significantly in the 1st 3 days after treatment (P < .05). All patients' serum sodium levels were above 135 mmol/L 1 month after treatment, and sustained through 1 year after treatment, without extra sodium supplementation. No serious complications were observed.The result indicated a significant improvement in the serum sodium levels and no serious adverse effects after long-term use in very elderly patients.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Benzazepinas/uso terapêutico , Hiponatremia/tratamento farmacológico , Idoso de 80 Anos ou mais , Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Benzazepinas/administração & dosagem , Benzazepinas/efeitos adversos , Peso Corporal , Cloro/sangue , Relação Dose-Resposta a Droga , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , Sódio/sangue , Fatores de Tempo , Tolvaptan
20.
Cell Death Dis ; 7(12): e2527, 2016 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-28005078

RESUMO

Lipid catabolism disorder is the primary cause of atherosclerosis. Transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy to promote lipid degradation. Hypericin-mediated sonodynamic therapy (HY-SDT) has been proved non-invasively inducing THP-1-derived macrophage apoptosis; however, it is unknown whether macrophage autophagy could be triggered by HY-SDT to influence cellular lipid catabolism via regulating TFEB. Here, we report that HY-SDT resulted in the time-dependent THP-1-derived macrophage autophagy activation through AMPK/AKT/mTOR pathway. Besides, TFEB nuclear translocation in macrophage was triggered by HY-SDT to promote autophagy activation and lysosome regeneration which enhanced lipid degradation in response to atherogenic lipid stressors. Moreover, following HY-SDT, the ABCA1 expression level was increased to promote lipid efflux in macrophage, and the expression levels of CD36 and SR-A were decreased to inhibit lipid uptake, both of which were prevented by TFEB knockdown. These results indicated that TFEB nuclear translocation activated by HY-SDT was not only the key regulator of autophagy activation and lysosome regeneration in macrophage to promote lipolysis, but also had a crucial role in reverse cholesterol transporters to decrease lipid uptake and increase lipid efflux. Reactive oxygen species (ROS) were adequately generated in macrophage by HY-SDT. Further, ROS scavenger N-acetyl-l-cysteine abolished HY-SDT-induced TFEB nuclear translocation and autophagy activation, implying that ROS were the primary upstream factors responsible for these effects during HY-SDT. In summary, our data indicate that HY-SDT decreases lipid content in macrophage by promoting ROS-dependent nuclear translocation of TFEB to influence consequent autophagy activation and cholesterol transporters. Thus, HY-SDT may be beneficial for atherosclerosis via TFEB regulation to ameliorate lipid overload in atherosclerotic plaques.


Assuntos
Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Lipídeos/química , Macrófagos/citologia , Macrófagos/metabolismo , Perileno/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Ultrassom , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Adenilato Quinase/metabolismo , Apoptose/efeitos dos fármacos , Antígenos CD36/metabolismo , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoproteção/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/ultraestrutura , Perileno/farmacologia , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Depuradores Classe A/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
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