The protective effect of vitexinin septic encephalopathy by reducing leukocyte-endothelial adhesion and inflammatory response.

BACKGROUND: Despite advances in therapeutic strategies and critical care management, septic encephalopathy (SE) is still a leading cause of infection-associated death in intensive care units (ICUs). Vitexin, a flavonoids compound, exerts and anti-inflammatory effect through inhibition of proinflammatory cytokines and signaling pathways. This study aimed to explore the anti-inflammatory effects of vitexin in SE and the underlying mechanisms. METHODS: An SE-inducedC57BL/6 mouse model was established via cecal ligation and puncture (CLP). Western blotting was performed to evaluate the protein expression levels of Chemokine (C-X-C motif) ligand 1 (CXCL1), fractalkine (CX3CL1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, NF-κB p65, p-NF-κB p65, and tumor necrosis factor-α (TNF-α). Flow cytometry was used to detect the expressions ofCD11a/CD18, CD11b/CD18, ICAM-1, and adherent leukocyte. The expression of ICAM-1 was detected by immunohistochemistry. An enzyme-linked immunosorbent assay was performed to evaluate the expression of monocyte chemotactic protein-1 (MCP-1), Interleukin (IL)-6, IL-8, and IL-10. RESULTS: In this study, we found that vitexin significantly downregulated the expression of brain endothelial chemokines CXCL1 and CX3CL1 in CLP mice, exerting a potential anti-inflammatory against SE. Our data also showed that vitexin alleviated SE primarily by relying on reducing leukocyte-endothelial adhesion via the mediation of adhesion molecules. Moreover, vitexin suppressed the expression of proinflammatory cytokines, such as MCP-1, IL-6, IL-8, TNF-α, and NF-κB p65, in the CLP mice, while the expression of the anti-inflammatory cytokine IL-10 was elevated. CONCLUSIONS: Overall, our study demonstrated the protective effect vitexin exerts in SE by reducing leukocyte-endothelial adhesion and inflammatory response. These findings offer a molecular basis for the potential application of vitexin in the treatment of SE and other inflammatory-mediated and immunemediated disorders.

p300 promotes differentiation of Th17 cells via positive regulation of the nuclear transcription factor RORγt in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) has been the major cause of acute respiratory failure in critical patients and one of the leading causes of death worldwide for several decades. Th17 cells are involved in the occurrence and progression of ARDS. Furthermore, histone acetyltransferase (HAT) p300 is a transcriptional coactivator, and its activity is closely related to cancer and inflammatory diseases. p300 and histone deacetylase 1 (HDAC1) interact with and stabilize the nuclear transcription factor retinoic acid-related orphan receptor gamma t (RORγt) and participate in the regulation of RORγt-mediated IL-17 transcription in T helper 17 (Th17) cell differentiation by acetylation and deacetylation. However, the effect of p300 on RORγt and Th17 cells in ARDS is not well reported. Therefore, we aimed to investigate the clinical features of p300 and its effect on RORγt and Th17 cells in patients with ARDS as well as in lipopolysaccharide-induced acute lung injury (ALI) mouse models. Overexpression of p300 and RORγt mRNA was found in the peripheral blood mononuclear cells from patients with ARDS, especially among non-survivors, compared to that in healthy individuals (P < 0.05). Moreover, the decline of FOXP3 mRNA level correlated with survival and increased RORγt mRNA levels corelated with infection (P < 0.05). Immunohistochemical analysis revealed high p300 and RORγt expression in ALI mouse lung tissues. Inhibitor-mediated knockdown of p300 reduced lung tissue inflammation and lung injury score (P < 0.05). Western blotting and ELISA revealed that p300 inhibitor caused a decrease in the mRNA and protein levels of RORγt as well as interleukin 17 (IL-17) production in ALI mouse lung tissues (P < 0.05). Thus, our findings suggest that p300 may play a key role in ARDS by positively regulating RORγt transcription and is a potential new immunotherapy target for ARDS.

[Effectiveness of U-shape titanium screw-rod fixation system with bone autografting for lumbar spondylolysis of young adults].

OBJECTIVE: To investigate the effectiveness of U-shape titanium screw-rod fixation system with bone autografting for lumbar spondylolysis of young adults. METHODS: Between January 2008 and December 2011, 32 patients with lumbar spondylolysis underwent U-shape titanium screw-rod fixation system with bone autografting. All patients were male with an average age of 22 years (range, 19-32 years). The disease duration ranged from 3 to 24 months (mean, 14 months). L3 was involved in spondylolysis in 2 cases, L4 in 10 cases, and L5 in 20 cases. The preoperative visual analogue scale (VAS) and Oswestry disability index (ODI) scores were 8.0 +/- 1.1 and 75.3 +/- 11.2, respectively. RESULTS: The operation time was 80-120 minutes (mean, 85 minutes), and the blood loss was 150-250 mL (mean, 210 mL). Primary healing of incision was obtained in all patients without complications of infection and nerve symptom. Thirty-two patients were followed up 12-24 months (mean, 14 months). Low back pain was significantly alleviated after operation. The VAS and ODI scores at 3 months after operation were 1.0 +/- 0.5 and 17.6 +/- 3.4, respectively, showing significant differences when compared with preoperative ones (t = 30.523, P = 0.000; t = 45.312, P = 0.000). X-ray films and CT showed bone fusion in the area of isthmus defects, with the bone fusion time of 6-12 months (mean, 9 months). During follow-up, no secondary lumbar spondyloly, adjacent segment degeneration, or loosening or breaking of internal fixator was found. CONCLUSION: The U-shape titanium screw-rod fixation system with bone autografting is a reliable treatment for lumbar spondylolysis of young adults because of a high fusion rate, minimal invasive, and maximum retention of lumbar range of motion.