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OBJECTIVE: Our research aimed to investigate the therapeutic effects of Tubastatin-A, a glucocorticoid receptor (GR) mitochondrial translocation inhibitor, and mitoquinone (MitoQ), an antioxidant, on attenuating dexamethasone (DEX)-induced macrophage apoptosis. METHODS: We treated RAW264.7 macrophages with different combinations of DEX and either Tubastatin-A or MitoQ. Parameters such as mitochondrial GR translocation, mitochondrial reactive oxygen species levels, mitochondrial membrane potential, mitochondrial permeability transition pore opening, cytochrome C efflux to the cytosol, and apoptosis were subsequently evaluated in the different treatment groups via qRT-PCR, western blotting, and immunofluorescence assays. RESULTS: DEX intervention increased the translocation of GRs into the mitochondria, while reducing the expression of the mitochondrial gene MT-CO1 and the activity of mitochondrial respiratory chain complex IV in macrophages. In addition, DEX administration increased mtROS levels, mitochondrial permeability transition pore opening, and mitochondrial cytochrome C release in macrophages, which promoted their apoptosis. We found that Tubastatin-A inhibited mitochondrial GR translocation and reversed the DEX-induced increase in GR levels within the mitochondria. Furthermore, Tubastatin-A mitigated various mitochondrial changes induced by DEX, including reducing the efflux of mitochondrial cytochrome C and inhibiting macrophage apoptosis. Similarly, MitoQ exerted its effects on macrophage apoptosis by reducing mtROS levels through the mitochondrial pathway. CONCLUSIONS: The DEX-mediated translocation of GR into mitochondria disrupts the mitochondrial function of macrophages, which induces their apoptosis. By inhibiting mitochondrial translocation of GR and reducing mtROS levels, Tubastatin-A and MitoQ can effectively attenuate macrophage apoptosis, which has clinical implications for reducing the notable side effects associated with glucocorticoid use.
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Apoptose , Dexametasona , Glucocorticoides , Macrófagos , Mitocôndrias , Receptores de Glucocorticoides , Receptores de Glucocorticoides/metabolismo , Animais , Camundongos , Apoptose/efeitos dos fármacos , Células RAW 264.7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/farmacologia , Ubiquinona/análogos & derivados , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Compostos OrganofosforadosRESUMO
Microglia are resident macrophages within the central nervous system, serving as the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage to brain tissue, but the specific mechanism remains unclear. This study was divided into two parts: a glucocorticoid receptor (GR) mitochondrial translocation intervention experiment and a mitochondrial oxidative stress inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results showed that DEX increased the translocation of GRs to mitochondria, and this effect was accompanied by decreases in the expression of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine triphosphate (ATP) was decreased. An elevation in the level of mitochondrial oxidative stress and the opening of the mitochondrial permeability transition pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly suppressed the mitochondrial translocation of GRs, improved the expression of mitochondrial genes, promoted the restoration of mitochondrial function, and inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study substantiates that the increase in the mitochondrial translocation of GRs mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which indicates that the regulation of mitochondrial pathways by GCs is pathogenic to microglia.
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Glucocorticoides , Piroptose , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Microglia/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Estresse Oxidativo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
The traditional semiconductor photocatalysts for solving the related environmental aggravation are often challenged by the recombination of photogenerated carriers. Designing an S-scheme heterojunction photocatalyst is one of the keys to tackling its practical application problems. This paper reports an S-scheme AgVO3/Ag2S heterojunction photocatalyst constructed via a straightforward hydrothermal approach that exhibits outstanding photocatalytic degradation performances to the organic dye Rhodamine B (RhB) and antibiotic Tetracycline hydrochloride (TC-HCl) driven by visible light. The results show that AgVO3/Ag2S heterojunction with a molar ratio of 6:1 (V6S) possesses the highest photocatalytic performances, 99% of RhB can be almost degraded by 0.1 g/L V6S within 25 min light illumination, and about 72% of TC-HCl can be photodegraded with the act of 0.3 g/L V6S under 120 min light irradiation. Meanwhile, the AgVO3/Ag2S system exhibits superior stability and maintains high photocatalytic activity after 5 repeated tests. Moreover, the EPR measurement and radical capture test identify that superoxide radicals and hydroxyl radicals mainly contribute to the photodegradation process. The present work demonstrates that constructing an S-scheme heterojunction can effectively inhibit the recombination of carriers, providing insights into the fabrication of applied photocatalysts for practical wastewater purification treatment.
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Poluentes Ambientais , Luz , Iluminação , Antibacterianos , CorantesRESUMO
Thermally driven water-based sorption refrigeration is considered a promising strategy to realize near-zero-carbon cooling applications by addressing the urgent global climate challenge caused by conventional chlorofluorocarbon (CFC) refrigerants. However, developing cost-effective and high-performance water-sorption porous materials driven by low-temperature thermal energy is still a significant challenge. Here, we propose a zeolite-like aluminophosphate with SFO topology (EMM-8) for water-sorption-driven refrigeration. The EMM-8 is characterized by 12-membered ring channels with large accessible pore volume and exhibits high water uptake of 0.28 g·g-1 at P/P0 = 0.2, low-temperature regeneration of 65 °C, fast adsorption kinetics, remarkable hydrothermal stability, and scalable fabrication. Importantly, the water-sorption-based chiller with EMM-8 shows the potential of achieving a record coefficient of performance (COP) of 0.85 at an ultralow-driven temperature of 63 °C. The working performance makes EMM-8 a practical alternative to realize high-efficient ultra-low-temperature-driven refrigeration.
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Objectives: This study aims to investigate the expression patterns of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) in different organs and tissues of MRL/lpr mice aged six and 18 weeks. Materials and methods: Six-week-old female MRL/lpr mice (n=10) were considered young lupus model mice, and 18-week-old MRL/lpr mice (n=10) were considered old lupus model mice. Additionally, six-week-old (n=10) and 39-week-old (n=10) female Balb/c mice were used as the young and old controls, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of MT-CO1 in nine organs/tissues were detected via quantitative polymerase chain reaction (qPCR) and Western blot. Malondialdehyde (MDA) levels were determined with thiobarbituric acid colorimetry. The correlation coefficient of MT-CO1 mRNA levels and MDA levels in each organ/tissue at different ages was analyzed by Pearson correlation analysis. Results: The results showed that most non-immune organs/tissues (heart, lung, liver, kidneys, and intestines) showed increased MT-CO1 expression levels in younger MRL/lpr mice (p<0.05) and decreased MT-CO1 expression in older mice (p<0.05). Expression of MT-CO1 in the lymph nodes was low in younger mice but high in older mice. In other immune organs (spleen and thymus), MT-CO1 expression was low in older MRL/lpr mice. Lower mRNA expression and higher MDA levels were observed in the brains of MRL/lpr mice. However, all MRL/lpr mice showed higher MDA levels than Balb/c mice in every organ no matter younger or older MRL/lpr mice. Conclusion: Our study results suggest that lymphoid mitochondrial hyperfunction at organ level may be an important intrinsic pathogenesis in systemic lupus erythematosus activity, which may affect mitochondrial dysfunction in non-immune organs.
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Two kinds of nanoparticles (gold nanoparticles and Au core Pt shell nanoparticles) on silicon surfaces which were silanization were electrostatically self-assembled. The density of nanoparticles was controlled by changing the time of the substrate immersed in colloids. The substrate was characterized by scanning electron microscope (SEM), and the results indicated that Au and Au@Pt particles were dispersed on the substrate with mono/submonolayers. The authors used pyridine (Py) as a probing molecule, and surface enhanced Raman spectroscopy (SERS) effect was investigated on pure Au and Au-Au@Pt mixed nanoparticle surfaces under the excitation line of 632.8 nm. The results revealed that there is a significant shift of the two characteristic peaks of Py, but the enhancement factors of Au dropped off precipitously with the introduction of the Au@Pt nanoparticles. The authors attributed this effect to the introduction of metal d-states from the metal, which would serve effectively to quench the surface plasmon excitation necessary for large (electromagnetic) enhancements in Raman spectroscopy.