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1.
J Appl Toxicol ; 44(6): 908-918, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396353

RESUMO

Cadmium (Cd) is one of the most polluting heavy metal in the environment. Cd exposure has been elucidated to cause dysfunction of the glomerular filtration barrier (GFB). However, the underlying mechanism remains unclear. C57BL/6J male mice were administered with 2.28 mg/kg cadmium chloride (CdCl2) dissolved in distilled water by oral gavage for 14 days. The expression of SDC4 in the kidney tissues was detected. Human renal glomerular endothelial cells (HRGECs) were exposed to varying concentrations of CdCl2 for 24 h. The mRNA levels of SDC4, along with matrix metalloproteinase (MMP)-2 and 9, were analyzed by quantitative PCR. Additionally, the protein expression levels of SDC4, MMP-2/9, and both total and phosphorylated forms of Smad2/3 (P-Smad2/3) were detected by western blot. The extravasation rate of fluorescein isothiocyanate-dextran through the Transwell was used to evaluate the permeability of HRGECs. SB431542 was used as an inhibitor of transforming growth factor (TGF)-ß signaling pathway to further investigate the role of TGF-ß. Cd reduced SDC4 expression in both mouse kidney tissues and HRGECs. In addition, Cd exposure increased permeability and upregulated P-Smad2/3 levels in HRGECs. SB431542 treatment inhibited the phosphorylation of Smad2/3, Cd-induced SDC4 downregulation, and hyperpermeability. MMP-2/9 levels increased by Cd exposure was also blocked by SB431542, demonstrating the involvement of TGF-ß/Smad pathway in low-dose Cd-induced SDC4 reduction in HRGECs. Given that SDC4 is an essential component of glycocalyx, protection or repair of endothelial glycocalyx is a potential strategy for preventing or treating kidney diseases associated with environmental Cd exposure.


Assuntos
Células Endoteliais , Glicocálix , Glomérulos Renais , Camundongos Endogâmicos C57BL , Sindecana-4 , Animais , Masculino , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Sindecana-4/metabolismo , Sindecana-4/genética , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Camundongos , Glicocálix/efeitos dos fármacos , Glicocálix/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Cádmio/toxicidade , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
2.
Mediators Inflamm ; 2023: 6685251, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37674786

RESUMO

This review aims at summarizing state-of-the-art knowledge on glycocalyx and SARS-CoV-2. The endothelial glycocalyx is a dynamic grid overlying the surface of the endothelial cell (EC) lumen and consists of membrane-bound proteoglycans and glycoproteins. The role of glycocalyx has been determined in the regulation of EC permeability, adhesion, and coagulation. SARS-CoV-2 is an enveloped, single-stranded RNA virus belonging to ß-coronavirus that causes the outbreak and the pandemic of COVID-19. Through the respiratory tract, SARS-CoV-2 enters blood circulation and interacts with ECs possessing angiotensin-converting enzyme 2 (ACE2). Intact glycolyx prevents SARS-CoV-2 invasion of ECs. When the glycocalyx is incomplete, virus spike protein of SARS-CoV-2 binds with ACE2 and enters ECs for replication. In addition, cytokine storm targets glycocalyx, leading to subsequent coagulation disorder. Therefore, it is intriguing to develop a novel treatment for SARS-CoV-2 infection through the maintenance of the integrity of glycocalyx. This review aims to summarize state-of-the-art knowledge of glycocalyx and its potential function in SARS-CoV-2 infection.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Glicocálix , Enzima de Conversão de Angiotensina 2 , Coagulação Sanguínea
3.
Analyst ; 148(18): 4421-4428, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37552510

RESUMO

Coincidental realization of broadband spectral coverage and high resolution in one spectrometer system has always been a challenge. Here, we report the development of a high-resolution visible CCD spectrometer based on the virtually imaged phase array (VIPA) technique. By using a thin glass plate and a reflective grating, a two-dimensional cross-dispersion was realized. A broadband coverage of ∼14.94 THz and a high resolution of ∼1 GHz at 632.996 nm were achieved with a simple structure. The effects of the surface quality of VIPA etalon, the pixel size of the CCD camera, the pinhole size of the input beam, and the focal length of the imaging lens on the resolution of the spectrometer and the transverse spot size on the detector plane were considered. A comparison between the experimental results by changing the imaging lens and the theoretical calculation results proved a better simulation of these two parameters, which is a helpful contribution to the design and construction of a VIPA spectrometer. The developed spectrometer will provide a useful tool for the study of high-resolution spectroscopy and for simultaneous multi-species trace detection.

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