Objective A series of bioinformatics methods were used to identify ferroptosis related biomarkers in lupus nephritis (LN). Methods We retrieved sequencing data of GSE112943 from the GEO (Gene Expression Omnibus) database and screened LN differentially expressed genes. We searched for ferroptosis-related gene (FRG) through FerrDb database, and screened LN-FRG. We conducted enrichment analysis on the LN-FRGs using David online bioinformatics database and screened the core LN-FRG using cytoHubba. We used external data sets to verify the core LN-FRGs, constructed competing endogenous RNA networks, and conducted molecular docking analysis. Results A total of 37 LN-FRGs were selected through screening. These genes are mainly enriched in inflammation, immune regulation and ferroptosis related signaling pathways. Through the cytoHubba and external dataset validation, the key core LN-FRG of ATF3 (activating transcription factor 3) was ultimately identified, and its expression was significantly increased in LN (P<0.05). Molecular docking analysis showed that ATF3 was closely bound to SLC7A11 and NRF2, and may participate in the occurrence and development of LN through the microRNA-27-ATF3 regulation axis. Conclusion The pivotal gene ATF3 may participate in the inflammation and immune injury of LN through ferroptosis.
Objective To explore the expression and changes of serum irisin in adenine-induced chronic kidney disease (CKD) model, and the role of irisin and related pathway in CKD renal fibrosis. Methods Twenty male SD rats were randomly divided into a control group and a model group (CKD group) using a simple randomization method, with 10 rats in each group. At the end of the 2nd and 4th week, biochemical indicators, serum irisin and serum bone morphogenetic protein 7 (BMP7) levels, renal pathologic changes and interstitial fibrosis of renal tubules were measured in two groups of rats. The protein expression levels and messenger RNA (mRNA) expression levels of alpha-smooth muscle actin (α-SMA), collagen type I (Col-Ⅰ), BMP7, and Smad1 in rat kidney tissue were detected and compared. Results Compared with the control group at the end of the 2nd and 4th week, the CKD group showed that the serum creatinine (Scr), serum urea nitrogen (BUN), and 24-hour urinary protein level were increased (P<0.05), the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased (P<0.05), while the serum irisin and serum BMP7 were decreased (P<0.05), the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced (P<0.05). Compared with the end of the 2nd week, the CKD group at the end of the 4th week showed that the serum Scr, serum BUN, and 24-hour urinary protein level were increased (P<0.05), the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased (P<0.05), while the serum irisin and serum BMP7 were decreased (P<0.05), the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced (P<0.05). Compared to the control group, the renal tissue structure of the CKD group showed significant structural disorders and interstitial fibrosis of the renal tissue, which worsened over time. Serum irisin was negatively correlated with α- SMA and Col - Ⅰ (r=−0.917, −0.902, P<0.001) respectively, while serum irisin was positively correlated with serum BMP7 (r=0.842, P<0.001); Kidney tissue BMP7 was positively correlated with Smad1 (r=0.884, P<0.001). The cluster heat map showed that compared with the control group, BMP7 and recombinant fibronectin type Ⅲ domain containing were significantly decreased, α-SMA and Col-Ⅰ were significantly increased in CKD group; recombinant fibronectin type Ⅲ domain containing were positively correlated with BMP7, and negatively correlated with α-SMA and Col-Ⅰ. Conclusions irisin may be involved in the process of renal fibrosis in adenine-induced CKD via the BMP7/Smad1 axis. This will provide new ideas for the prevention and treatment of renal fibrosis.
ObjectiveTo analyze the influencing factors on clinical response to conbercept for diabetic macular edema (DME).MethodsA total of 51 patients (51 eyes) with DME who underwent intravitreal injection of conbercept were included in this retrospective study. The general information (age, sex, body mass index, smoking history, drinking history), blood glucose indicators (duration of diabetes, fasting blood glucose, HbA1c), blood pressure indicators (history of hypertension, systolic blood pressure, diastolic blood pressure), lipid indicators [total cholesterol (TC), high-density lipoprotein (HDL), apolipoprotein A (APOA)], biochemical indicators [neutrophil concentration, hemoglobin (HB), serum creatinine (Scr)] were collected. The best corrected visual acuity (BCVA) and macular central macular thickness (CMT) before and after treatment were comparatively analyzed. CMT reduced not less than 20% and BCVA increased by 2 lines as effective standards. Univariate analysis and multivariate logistic regression analysis were used to determine the factors affecting the efficacy of intravitreal injection of conbercept in patients with DME.ResultsUnivariate analysis showed that diastolic blood pressure, HDL, serum neutrophil concentration, baseline CMT and baseline BCVA were associated with edema regression (P＜0.05); HbA1c was associated with vision improvement (P＜0.05). Multivariate logistic regression analysis showed that there was a history of smoking (OR=0.122, 95% CI 0.017 − 0.887), low diastolic blood pressure (OR=0.850, 95%CI0.748 − 0.966), low HDL (OR=0.007, 95%CI 0.000 1 − 0.440), thin baseline CMT (OR=0.986, 95%CI0.977 − 0.995) were independent risk factors for failure outcome of edema regression (P＜0.05); long duration of diabetes (OR=1.191, 95%CI 1.011 − 1.404), high APOA (OR=1.007, 95% CI 1.000 − 1.013) were independent risk factors for failure outcome of vision improvement. Age, fasting blood glucose, systolic blood pressure, TC, HB, Scr and other indicators had no effect on the efficacy of edema regression and vision improvement after treatment (P＞0.05).ConclusionsSmoking history, long duration of diabetes, low diastolic blood pressure, low HDL level, high APOA level and thin baseline CMT are independent risk factors for the treatment of DME with intravitreal injection of conbercept.