Protective effect of modified Huangqi Chifeng decoction on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway.

OBJECTIVE: To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction (, MHCD) in immunoglobulin A nephropathy (IgAN) rats. METHODS: To establish the IgAN rat model, the bovine serum albumin, lipopolysaccharide, and carbon tetrachloride 4 method was employed. The rats were then randomly assigned to the control, model, telmisartan, and high-, medium-, and low-dose MHCD groups, and were administered the respective treatments via intragastric administration for 8 weeks. The levels of 24-h urinary protein, serum creatinine (CRE), and blood urea nitrogen (BUN) were measured in each group. Pathological alterations were detected. IgA deposition was visualized through the use of immunofluorescence staining. The ultrastructure of the kidney was observed using a transmission electron microscope. The expression levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) were examined by immunohistochemistry and quantitative polymerase chain reaction. Levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) P65, were examined by immunohistochemistry, Western blotting, and quantitative polymerase chain reaction. RESULTS: The 24-h urine protein level in each group increased significantly at week 6, and worsen from then on. But this process can be reversed by treatments of telmisartan, and high-, medium-, and low-dose of MHCD, and these treatments did not affect renal function. Telmisartan, and high-, and medium-dose of MHCD reduced IgA deposition. Renal histopathology demonstrated the protective effect of high-, medium-, and low-dose of MHCD against kidney injury. The expression levels of MCP-1, IL-6, and TGF-ß1 in kidney tissues were downregulated by low, medium and high doses of MHCD treatment. Additionally, treatment of low, medium and high doses of MHCD decreased the protein and mRNA levels of TLR4, MyD88, and NF-κB. CONCLUSIONS: MHCD exerted nephroprotective effects on IgAN rats, and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway, thereby alleviating renal inflammation by inhibiting MCP-1, IL-6 expressions, and ameliorating renal fibrosis by inhibiting TGF-ß1 expression.

Nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure for preterm infants with respiratory distress syndrome: a meta-analysis and up-date.

OBJECTIVE: To evaluate whether nasal intermittent positive pressure ventilation (NIPPV) would decrease the requirement for endotracheal ventilation compared with nasal continuous positive airway pressure(NCPAP) for preterm infants with respiratory distress syndrome (RDS) and compare the related complications between these two noninvasive variations of respiratory support METHODS: A search of major electronic databases, including Medline (1980-2013) and the Cochrane Central Register of Controlled Trials, for randomized controlled trials that compared NIPPV versus NCPAP for preterm infants with RDS was performed. MAIN RESULTS: Six randomized controlled trials met selection criteria (n = 1,527). The meta-analyses demonstrated significant decrease in the need for invasive ventilation in the NIPPV group (RR:0.53; 95% CI, 0.33-0.85). In the subgroup of infants who received surfactant also demonstrated a significant rate of failure of nasal support in the NIPPV group (RR:0.57; 95% CI 0.42-0.78). However, the subgroup of infants whose gestational age (GA) ≤ 30 weeks or birth weight (BW) < 1,500 g showed no difference between the two groups (RR:0.59; 95% CI 0.27-1.26); and the subgroup of infants whose GA > 30 weeks or BW > 1,500 g also showed no difference between the two groups (RR:0.63; 95% CI 0.29-1.39). No differences in other outcome variables were observed between the two groups. CONCLUSIONS: Among preterm infants with RDS, there was a significant decrease in the need for invasive ventilation in the NIPPV group as compared with NCPAP group, especially for the infants who received surfactant. However, NIPPV could not decrease the need for invasive ventilation both in the subgroup of infants whose GA ≤ 30 weeks or BW < 1,500 g and the subgroup of infants with BW of >30 weeks or BW > 1,500 g. It is limited to analysis the primary outcome generally. Larger trials of this intervention are needed to assess the difference in this primary outcome and the related complications between both forms of noninvasive respiratory support.

Glycochenodeoxycholate induces rat alveolar epithelial type II cell death and inhibits surfactant secretion in vitro.

Bile acid-induced lung injury has become an important topic for neonatologists after the discovery of a high incidence of infant respiratory distress syndrome complicated from maternal intrahepatic cholestasis. To explore the molecular pathway of bile acid-induced lung injury, we investigated the cytotoxicity of the glycochenodeoxycholate (GCDC) to alveolar epithelial type II cells (AECII), as the main component of bile acid. The results demonstrated that glycochenodeoxycholate induced oxidative stress, mitochondrial damage, and increased caspase activity in the primary cultured AECII. Moreover, ROS scavengers and caspase inhibitors could rescue cell death induced by GCDC in rat AECII. Our results also indicated that GCDC inhibited AECII surfactant secretion. In conclusion, this study suggested that cell death prevention and cell therapy should be considered as therapeutic strategies for infant respiratory distress syndrome complicated from maternal intrahepatic cholestasis.