RÉSUMÉ
Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.
Sujet(s)
Émodine , Fibrose , Mitochondries , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes , Insuffisance rénale chronique , Animaux , Émodine/pharmacologie , Émodine/usage thérapeutique , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/métabolisme , Insuffisance rénale chronique/traitement médicamenteux , Insuffisance rénale chronique/métabolisme , Insuffisance rénale chronique/anatomopathologie , Fibrose/traitement médicamenteux , Mitochondries/effets des médicaments et des substances chimiques , Mitochondries/métabolisme , Mâle , Rats , Rat Sprague-Dawley , Homéostasie/effets des médicaments et des substances chimiques , Rein/anatomopathologie , Rein/effets des médicaments et des substances chimiques , Rein/métabolisme , Obstruction urétérale/anatomopathologie , Obstruction urétérale/traitement médicamenteux , Facteur de croissance transformant bêta-1/métabolisme , Lignée cellulaireRÉSUMÉ
BACKGROUND: The 2017 Oxford classification of immunoglobulin A nephropathy (IgAN) recently reported that crescents could predict a worse renal outcome. Early prediction of crescent formation can help physicians determine the appropriate intervention, and thus, improve the outcomes. Therefore, we aimed to establish a nomogram model for the prediction of crescent formation in IgA nephropathy patients. METHODS: We retrospectively analyzed 200 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator(LASSO) regression and multivariate logistic regression was applied to screen for influencing factors of crescent formation in IgAN patients. The performance of the proposed nomogram was evaluated based on Harrell's concordance index (C-index), calibration plot, and decision curve analysis. RESULTS: Multivariate logistic analysis showed that urinary protein ≥ 1 g (OR = 3.129, 95%CI = 1.454-6.732), urinary red blood cell (URBC) counts ≥ 30/ul (OR = 3.190, 95%CI = 1.590-6.402), mALBU ≥ 1500 mg/L(OR = 2.330, 95%CI = 1.008-5.386), eGFR < 60ml/min/1.73m2(OR = 2.295, 95%CI = 1.016-5.187), Serum IgA/C3 ratio ≥ 2.59 (OR = 2.505, 95%CI = 1.241-5.057), were independent risk factors for crescent formation. Incorporating these factors, our model achieved well-fitted calibration curves and a good C-index of 0.776 (95%CI [0.711-0.840]) in predicting crescent formation. CONCLUSIONS: Our nomogram showed good calibration and was effective in predicting crescent formation risk in IgAN patients.
Sujet(s)
Glomérulonéphrite à dépôts d'IgA , Humains , Glomérulonéphrite à dépôts d'IgA/diagnostic , Études rétrospectives , Nomogrammes , Rein , CalibrageRÉSUMÉ
AIM: To evaluate the effects of ultrasound-guided percutaneous transluminal angioplasty (PTA) on the arteriovenous fistula (AVF) stenosis of hemodialysis graft. MATERIALS AND METHODS: A total of 189 patients with AVF dysfunction who underwent ultrasound-guided PTA were enrolled. Their baseline data were collected. The Log-rank test, Kaplan-Meier survival analysis and univariate Cox proportional risk regression analysis were performed to compare the primary and secondary patency rates and to explore the related influencing factors. RESULTS: A total of 256 sites of stenosis were found by ultrasonography, including 80 sites in anastomotic segment, 28 in supply artery segment, 60 in drainage vein segment and 88 in proximal segment of the internal fistula vein. The mean length of stenosis was 22.4 mm, and the mean degree was 93.4%. The success rate of surgery was 96.09%, with the postoperative residual stenosis of >30% in 3.91% of patients. The clinical success rate was 97.66% and complications occurred in 2.34% of patients. The mean follow-up time was 30.2 months, and vascular patency was observed in 25.93% of patients. The primary patency rates in 1st, 2nd and 3rd years after surgery were 84.66%, 60.85% and 21.69%, respectively, and the patients with diabetes (P=0.002) and old age (P<0.001) had lower rates. The secondary patency rates in 1st, 2nd and 3rd years after surgery were 91.00%, 74.07% and 32.80%, respectively, and a lower secondary patency rate was significantly correlated with diabetes (P=0.019), old age (P<0.001), long stenosis segment (P<0.001) and high degree of residual stenosis (P=0.012). CONCLUSIONS: Vascular patency can be maintained in hemodialysis patients with AVF dysfunction through repeated intervention, and there is no need to shorten the venous segment by surgery. Ultrasound-guided PTA is a promising substitute for traditional surgery. KEY WORDS: Arteriovenous Fistula, Hemodialysis, Ultrasound, Percutaneous Transluminal Angioplasty.