Data from this pilot study indicate that more than 60% of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment, and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents.
Objective. Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Pristane-treated B6 mice develop severe DAH within 2 weeks of treatment. ) is a pleiotropic microRNA that plays a crucial role in the regulation of immune responses. Recent studies have revealed a pathogenic role of miR-155 in various autoimmune disorders. The purpose of this study was to examine the role of miR-155 in the development of DAH in pristane-induced lupus using miR-155-knockout (miR-155 2/2 ) mice and miR-155 antagomir to silence miR-155.Methods. DAH was induced by an intraperitoneal injection of 0.5 ml of pristane. MicroRNA-155 antagomir was administered intravenously to silence miR-155 expression. Lung tissues were collected for RNA extraction and were embedded in paraffin for sectioning. Gene expression profiling data were analyzed using Ingenuity Pathway Analysis. Real-time quantitative polymerase chain reaction analysis was used for single-gene validation. Luciferase reporter assay and argonaute 2 immunoprecipitation were performed for target validation.Results. MicroRNA-155 expression was significantly increased during the development of DAH. Disease progression was reduced in miR-155 2/2 mice as well as by in vivo silencing of miR-155 using a miR-155 antagomir. MicroRNA-155 silencing dampened pristaneinduced ectopic activation of multiple inflammatory pathways and reduced the expression of proinflammatory cytokines. Several negative regulators of NF-kB signaling were inhibited by pristane and were reactivated in miR-155 2/2 mice. In particular, the antiinflammatory factor peroxisome proliferator-activated receptor a was identified as a direct target of miR-155.Conclusion. MicroRNA-155 promotes pristaneinduced lung inflammation. It contributes to ectopic activation of NF-kB signaling pathways by targeting multiple negative regulators. MicroRNA-155 antagomir may be a promising therapeutic strategy for treating acute lung inflammation in lupus.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems. The clinical manifestations in lupus patients vary considerably, ranging from mild skin involvement to critical and life-threatening diseases of internal organs (1). The lungs are commonly affected in SLE, and can develop pleural, parenchymal, vascular, and airway dis-
Background: Peritoneal dialysis (PD) solutions contribute to peritoneal membrane damage. We investigated how conventional and biocompatible PD solutions with different glucose concentrations affect morphological and functional signs of peritoneal fibrosis as well as the TGF-β1/Smad signaling pathway in a chronic PD rat model. Methods: Non-uremic male Wistar rats (n = 28) were dialyzed thrice daily for 28 days with 20 ml of a conventional solution (Dianeal® 1.36%, D1, or 3.86%, D3) or a biocompatible solution (Physioneal® 1.36%, P1, or 3.86%, P3). A peritoneal equilibration test was performed. Six rats without dialysis served as controls. Results: The use of conventional solutions, particularly D3, resulted in expansion of the submesothelial compact zone, loss of mesothelial cell layer integrity, hypercellularity, accumulation of collagen I, increased vessel numbers and increased TGF-β1/Smad expression, but this did not significantly change fluid and solute peritoneal transport characteristics. In comparison with D1 and D3, the use of P1 and P3 was associated with less TGF-β1/Smad expression and less expansion of the submesothelial cell layer. Conclusions: Our findings indicate that biocompatible solutions with less glucose may decrease the rate of peritoneal fibrosis. The TGF-β1/Smad pathway is stimulated by PD solutions, representing a plausible pathophysiological mechanism.
Echocardiography and cardiac biomarkers, such as cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) are useful tools to evaluate cardiac dysfunction. Left ventricular systolic dysfunction (LVSD) is common in pediatric severe sepsis. The aim of this study is to evaluate the prognostic value of LVSD, cTnI, and NT-pro BNP for pediatric severe sepsis. A prospective, single center, observational study was conducted. Severe sepsis children were enrolled in the study from December 2015 to December 2016 in pediatric intensive care unit of Shanghai Children's Medical Center. Recorded general information, transthoracic echocardiography were performed at day 1, 2, 3, 7, and 10, using Simpson to measure left ventricular end-diastolic dimension and left ventricular end-systolic dimension, obtained echocardiography parameters: left ventricular ejection fraction (LVEF), left ventricular fractional shortening, left ventricular end-diastolic volume, left ventricular end- systolic volume, stroke volume, cardiac output. At the same time collecting the blood sample to measure cTnI, NT-pro BNP. The definition of LVSD was LVEF <50%. According to the prognosis of 28 days, children with severe sepsis were divided into survived group and nonsurvived group. Total of 50 pediatric patients who were diagnosed with severe sepsis (including septic shock) were enrolled, the incidence of LVSD was 52%. The 28-day mortality rate of severe sepsis was 34%. Multivariate logistic regression analyses for predictors of death in pediatric severe sepsis revealed that the 28-day mortality of severe sepsis was associated with mechanical ventilation (MV) within the first 6 hours of admission (odds ratio [OR], 0.01; 95% confidence interval [CI], 0.00–0.07) and total MV time (OR, 0.81; 95% CI, 0.68–0.97). The receiver operating characteristic curves LVEF (area under curve = 0.526), cTnI (area under curve = 0.480), and NT-pro BNP (area under curve = 0.624) were used to predict the 28-day mortality in pediatric severe sepsis. Follow-up echocardiography parameters for survived group and nonsurvived group showed no significant changes in LVEF, LVFS, stroke volume index, cardiac index (CI), left ventricular end-diastolic volume index and left ventricular end-systolic volume index at day 1, 2, 3, 7, and 10, except for CI at day 1 and 2. Kaplan–Meier plot of 28-day mortality and LVSD in pediatric severe sepsis showed there were no statistical differences ( χ 2 = 0.042, P = .837). LVSD occurs frequently in pediatric with severe sepsis. The 28-day mortality rate of severe sepsis was also high. In this study, none of LVSD, cTnI, and NT-proBNP was associated with the prognosis of pediatric severe sepsis.
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