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1.
Acta Pharmacol Sin ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789496

RESUMO

Renal tubular epithelial cell senescence plays a critical role in promoting and accelerating kidney aging and age-related renal fibrosis. Senescent cells not only lose their self-repair ability, but also can transform into senescence-associated secretory phenotype (SASP) to trigger inflammation and fibrogenesis. Recent studies show that mitochondrial dysfunction is critical for renal tubular cell senescence and kidney aging, and calcium overload and abnormal calcium-dependent kinase activities are involved in mitochondrial dysfunction-associated senescence. In this study we investigated the role of mitochondrial calcium overload and mitochondrial calcium uniporter (MCU) in kidney aging. By comparing the kidney of 2- and 24-month-old mice, we found calcium overload in renal tubular cells of aged kidney, accompanied by significantly elevated expression of MCU. In human proximal renal tubular cell line HK-2, pretreatment with MCU agonist spermine (10 µM) significantly increased mitochondrial calcium accumulation, and induced the production of reactive oxygen species (ROS), leading to renal tubular cell senescence and age-related kidney fibrosis. On the contrary, pretreatment with MCU antagonist RU360 (10 µM) or calcium chelator BAPTA-AM (10 µM) diminished D-gal-induced ROS generation, restored mitochondrial homeostasis, retarded cell senescence, and protected against kidney aging in HK-2 cells. In a D-gal-induced accelerated aging mice model, administration of BAPTA (100 µg/kg. i.p.) every other day for 8 weeks significantly alleviated renal tubuarl cell senescence and fibrosis. We conclude that MCU plays a key role in promoting renal tubular cell senescence and kidney aging. Targeting inhibition on MCU provides a new insight into the therapeutic strategy against kidney aging.

2.
J Chromatogr A ; 1614: 460725, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31767260

RESUMO

In this work, a new analytical method based on polydopamine functionalized magnetic graphene (PDA@MG) adsorbent material has been developed to determine three triazole fungicides in water samples. As previous step, a novel polydopamine functionalized PDA@MG adsorbent material has been successfully prepared, which was characterized by fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscope (TEM), and vibrating sample magnetometer (VSM). Based on this novel material, a new magnetic solid phase extraction (MSPE) method coupled with high performance liquid chromatography (HPLC) has been established for the determination of triazole fungicides in water samples. The main factors which could affect the experimental results were optimized. Under the optimal conditions, good linarites has been achieved in the range of 0.2-50 µg L-1, with the correlation coefficients (R2) were between 0.9962 and 0.9996. The limits of detections (LODs) were 0.0048-0.0084 µg L-1, and the relative standard deviations (RSDs) were between 1.7% and 4.8%. In addition, enrichment factors (EFs) were 572-916 times, which showed triazole fungicides residues could be accurately extracted and analyzed in this way. In the final experiment, the established method was applied to the detection of target analyzes in water samples. Satisfied results could be obtained for tebuconazole, propiconazole, and flusilazole. The recoveries of five water samples were between 69.4% and 106.4%, and the RSD were between 1.0% and 6.5%. The development method is more easy, effective, green and environmental-friendly, and has potential for application.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fungicidas Industriais/análise , Grafite/química , Indóis/química , Polímeros/química , Triazóis/análise , Adsorção , Fungicidas Industriais/isolamento & purificação , Limite de Detecção , Fenômenos Magnéticos , Silanos/análise , Extração em Fase Sólida/métodos , Triazóis/isolamento & purificação
3.
Chirality ; 30(3): 293-301, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29314232

RESUMO

Enantiomers of chiral molecules can undergo interconversion leading to markedly different toxicities, which can introduce significant uncertainty when evaluating biological and environmental fates. However, enantiomerization (the reversible conversion of one enantiomer into the other) related to soil microorganism is rarely understood. For better understanding, S-triadimefon and R-triadimefon enantiopure were incubated in different soils with different pH value. Both high-performance liquid chromatography and high-throughput sequencing technology were used to explore target analytes quantitatively and microbial taxa related to the conversion process. Results revealed a significant enantiomerization among the soils. The alkaline soil from Beijing had a faster conversion than neutral soil from Changchun, while acidic soil from Wuhan had no conversion. At the same results, analysis of bacteria community showed higher abundance of Arthrobacter and Halomonas genus in alkaline soil than neutral soil after treatments, but the acidic soil was lower. Moreover, Arthrobacter and Halomonas were responsible for converting S-triadimefon to R-triadimefon and R-triadimefon to S-triadimefon in alkaline and neutral soil, respectively. Thus, these genera may be one of the reasons to explain the enantiomerization in different soils observed in this study. Thus, research at microbial level is necessary for efficient ecological risk assessment of chiral fungicide.

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