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1.
Horm Metab Res ; 55(8): 555-562, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37399835

RESUMO

This study was designed to assess the role and mechanism of circRNA SCAR in human retinal microvascular endothelial cells (hRMVECs) treated with high glucose. Quantitative real-time polymerase chain reaction (qRT-PCR) and cell counting kit 8 (CCK-8) were used to detect the effects of different concentrations of glucose on circRNA SCAR expression and cell proliferation in hRMVECs. Cell viability, levels of oxygen species (ROS), malondialdehyde (MDA) and adenosine triphosphate (ATP), as well as activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the transfected hRMVECs in each group were detected using CCK-8 and their corresponding detection kits. Changes in mtDNA copy number in high-glucose-induced hRMVECs were observed by qRT-PCR. Additionally, western blot was applied to detect effect of overexpressing circRNA SCAR on the expression levels of mitochondrial function-related proteins (Drp1 and Fis1) and cell permeability-related proteins (claudin-5, occludin and ZO-1) in hRMVECs under high-glucose concentration. According to experimental results, high glucose significantly downregulated circRNA SCAR expression and inhibited cell proliferation in hRMVECs. Instead, overexpression of this circRNA SCAR promoted cell proliferation, reduced levels of ROS, MDA and ATP, and increased SOD and CAT activities in hRMVECs under high-glucose concentration. Also, circRNA SCAR overexpression reversed the high-glucose-induced decrease in mtDNA copy number as well as, high-glucose-induced upregulation of Drp1 and Fis1 protein expression and downregulation of claudin-5, occludin and ZO-1 protein expression in hRMVECs. In summary, circRNA SCAR promotes the proliferation of hRMVECs under high-glucose concentration, alleviates oxidative stress induced by high glucose, and improves mitochondrial function and permeability damage.


Assuntos
Células Endoteliais , RNA Circular , Humanos , Trifosfato de Adenosina/metabolismo , Apoptose , Claudina-5/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Células Endoteliais/metabolismo , Glucose/metabolismo , Mitocôndrias/metabolismo , Ocludina/metabolismo , Estresse Oxidativo , Permeabilidade , Espécies Reativas de Oxigênio/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Superóxido Dismutase
2.
Int Ophthalmol ; 39(4): 745-752, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29691696

RESUMO

PURPOSE: To investigate the influence of trabeculectomy and phacotrabeculectomy on the ocular surface. DESIGN: Retrospective, case-control study. METHODS: Eighty-one samples without dry eyes were recruited and divided into three groups, including phacoemulsification group (N = 30) as control group, trabeculectomy group (N = 27) and phacotrabeculectomy group (N = 24) as study groups. Ocular surface parameters, including noninvasive keratograph first (NifBUT) and average (NiaBUT) tear film breakup time, tear meniscus height (TMH) and corneal fluorescein stain (CFS), were estimated preoperatively, at 3 days, 1 month and 3 months postoperatively using oculus keratograph. RESULTS: No significant difference was observed in ocular surface parameters at baseline among three groups (p > 0.05). The magnitude of NifBUT and NiaBUT was reduced at 3 days and 1 month postoperatively in phacotrabeculectomy group, but greater than that in the other two groups (All p < 0.001). In all the groups, both the NifBUT and NiaBUT tended to recover at 1 and 3 months postoperatively, whereas both of them did not recover to baseline at 3 months postoperatively in trabeculectomy (NifBUT, p = 0.001; NiaBUT, p < 0.001) and phacotrabeculectomy group (NifBUT, p < 0.001; NiaBUT, p = 0.020). TMH was raised at 3 days postoperatively and restored to the baseline level at 1 and 3 months postoperatively for three groups (p > 0.05). CFS was elevated at 3 days postoperatively and different in recovery at 1 and 3 months postoperatively for three groups. CONCLUSIONS: The influence of phacotrabeculectomy on ocular surface is worse than that of trabeculectomy for the short run and is not distinct different for a long time.


Assuntos
Córnea/patologia , Técnicas de Diagnóstico Oftalmológico/instrumentação , Glaucoma de Ângulo Fechado/cirurgia , Facoemulsificação/métodos , Lágrimas/fisiologia , Trabeculectomia/métodos , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Optometria/instrumentação , Estudos Retrospectivos
3.
PLoS One ; 7(5): e37693, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22666381

RESUMO

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa.


Assuntos
Antineoplásicos/farmacologia , Diterpenos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Endopeptidases/genética , Endopeptidases/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fenantrenos/farmacologia , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisteína Endopeptidases , Progressão da Doença , Compostos de Epóxi/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Masculino , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/genética , Transcrição Gênica/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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