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1.
Macromol Biosci ; 24(6): e2300496, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38359399

RESUMO

The contact between the dialysis membrane and blood can induce oxidative stress and thrombosis, causing oxidative organ damage and impaired toxin clearance. To date, the selection of anticoagulants has focused on mechanisms inhibiting white, but not red (erythrocytes) thrombus formation. In the present study, polyethersulfone (PES) membranes are modified with the antioxidant drug tiopronin; the physicochemical properties and dialysis performance of the Tio-PES membranes are evaluated. The effects on erythrocyte thrombosis are evaluated in terms of erythrocyte morphology, prothrombotic properties (adhesion, aggregation, viscosity, sedimentation, and hemolysis), and fibrinogen (FIB)-erythrocyte interactions. The regular anticoagulant and antiplatelet properties are also assessed. Superoxide dismutase, malondialdehyde, plasma protein, and complement C3a are further determined. Finally, the biosafety of the Tio-PES membranes is evaluated both in vitro and in vivo. The Tio-PES membranes exhibit excellent physicochemical properties and improved dialysis performance. It is found that the Tio-PES membranes stabilize erythrocyte morphology, reduce erythrocyte prothrombotic properties, decrease FIB adsorption, and prevent red thrombus formation. In addition, the Tio-PES membranes exhibit excellent antioxidant properties and show biosafety in primary toxicity studies. Thus, Tio-PES membranes hold promise as novel, safe, and effective dialysis materials for potential clinical application.


Assuntos
Antioxidantes , Eritrócitos , Teste de Materiais , Membranas Artificiais , Polímeros , Sulfonas , Trombose , Sulfonas/química , Sulfonas/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Polímeros/química , Polímeros/farmacologia , Trombose/prevenção & controle , Humanos , Animais , Hemólise/efeitos dos fármacos , Anticoagulantes/farmacologia , Anticoagulantes/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Fibrinogênio/química , Fibrinogênio/metabolismo
2.
Genes Dis ; 10(5): 2137-2150, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37492709

RESUMO

Aptamers, short single DNA or RNA oligonucleotides, have shown immense application potential as molecular probes for the early diagnosis and therapy of cancer. However, conventional cell-SELEX technologies for aptamer discovery are time-consuming and laborious. Here we discovered a new aptamer BC-3 by using an improved rapid X-Aptamer selection process for human bladder carcinoma, for which there is no specific molecular probe yet. We show that BC-3 exhibited excellent affinity in bladder cancer cells but not normal cells. We demonstrate that BC-3 displayed high selectivity for tumor cells over their normal counterparts in vitro, in mice, and in patient tumor tissue specimens. Further endocytosis pathway analysis revealed that BC-3 internalized into bladder cancer cells via clathrin-mediated endocytosis. Importantly, we identified ribosomal protein S7 (RPS7) as the binding target of BC-3 via an integrated methodology (mass spectrometry, colocalization assay, and immunoblotting). Together, we report that a novel aptamer BC-3 is discovered for bladder cancer and its properties in the disease are unearthed. Our findings will facilitate the discovery of novel diagnostic and therapeutic strategies for bladder cancer.

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