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BackgroundFatty acid deposition in the liver can activate a number of pro-inflammatory signaling pathways such as the Toll-like receptor 4 (TLR4) pathway, which may be important in the pathogenesis of nonalcoholic steatohepatitis. 1,25(OH)2D3 downregulates the expression of TLR4 and may represent a novel treatment strategy for reducing hepatocyte injury. Therefore, in this study, we investigated the protective effects of 1,25(OH)2D3 on diabetic liver injury in vivo.MethodsStreptozotocin (STZ)-induced diabetic rats were randomly divided into five groups and treated with low-dose 1,25(OH)2D3 (0.025 μg/kg/day), medium-dose 1,25(OH)2D3 (0.15 μg/kg/day), high-dose 1,25(OH)2D3 (0.3 μg/kg/day), insulin (protamine zinc insulin 16 U/kg/day, subcutaneous injection), or no intervention (the control group). Sixteen weeks later, the rats were killed, and blood samples were obtained to test lipid profiles and hepatic function. The infiltration of inflammatory cells, the level of fibrosis, and the expression levels of TLR4, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-α (TNF-α) in the liver were analyzed. The hepatocytes were treated with vehicle control, LPS (100 ng), high fat [DMEM + FFA (0.1 mM: palmitic acid, oleic acid, 1:2)], LPS + high fat, vehicle + 1,25(OH)2D3 (10−7 M), LPS + 1,25(OH)2D3, high fat + 1,25(OH)2D3, or LPS + high fat + 1,25(OH)2D3. RNA and protein were extracted to detect the expression of TLR4 and downstream inflammatory factors such as NF-ΚB, TNF-α, and IL-6. Groups of data were compared by single factor variance analysis.ResultsHigh-dose 1,25(OH)2D3 administration for 16 weeks downregulated the expression of TLR4, NF-κB, and TNF-α in the liver tissue of diabetic rats and attenuated hepatic inflammation and fibrosis, as shown by immunohistochemical staining, hematoxylin and eosin staining, Masson’s trichrome staining, reverse transcription polymerase chain reaction (RT-PCR), and western blotting. In vitro, hepatocytes treated with high fat or LPS exhibited significantly increased expression of TLR4, NF-κB, and downstream inflammatory factors (P < 0.05). Intervention with 1,25(OH)2D3 decreased the expression of TLR4, NF-κB, and inflammatory factors (P < 0.05).Conclusions1,25(OH)2D3 exhibited protective effects against diabetes-related liver injury, possibly through downregulation of components of the TLR4 signaling pathway.

IL-1b/IL-1R/MyD88-signaling is critical in mediating neutrophil recruitment and host defense against S. aureus skin infections but the cells that respond to IL-1b to trigger the protective IL-1R-dependent immune response are unclear. To evaluate the relative contribution of different IL-1R-expressing cell types against a community-acquired methicillin-resistant S. aureus (CA-MRSA) skin infection, a CA-MRSA strain (USA300 LAC::lux; 3x10 7 CFU) was inoculated intradermally into cre/lox mice with specific deletion of IL-1R in which IL-1R-floxed mice (IL-1R fl/fl ) were bred to mice with cre-specific expression in keratinocytes (K14-cre), all T cells (Lck-cre), all CD4 + /CD8 + T cells (CD4-cre), dendritic cells (CD11c-cre) and neutrophils (S100A8-cre). Of note, only Lck-cre x IL-1R fl/fl mice, a marked defect in host defense was observed with increased bacterial burden at early time points (beginning on days 3-7) after infection (as measured by in vivo bioluminescence [BLI] imaging and ex vivo CFU counting), markedly increased skin lesion sizes and defective neutrophil recruitment as measured by histology and flow cytometry. Of interest, there was slightly increased bacterial burden (w5fold) as measured by in vivo BLI and ex vivo CFU at late time points after infection (beginning on days 7-10) in CD4-cre x IL-1R fl/fl and CD11c-cre x IL-1R fl/fl mice. Taken together, these results suggest that IL-1R-mediated host defense against S. aureus skin infections involved IL-1R expressing non-CD4/CD8 cells (potentially gd T cells and NK T cells) at early time points during the innate immune response whereas IL-1R-expressing CD4/CD8 T cells and dendritic cells were involved later on during the adaptive immune response to promote clearance of the CA-MRSA skin infection. 488Identification of differentially-expressed circular RNAs and circular RNA-targeted pathways in host cells affected by Chlamydia infection

Introduction A literature review demonstrated conflicting results with different lumbar spine surgery techniques for LSS in the elderly. Materials and Methods From 2004 to 2011, a total of 183 consecutive patients at least 65 years old with degenerative LSS underwent decompressive surgery. Patients were divided into two groups: open decompression (Group A, 85 patients) and selective decompression (Group B, 98 patients). All patients were followed for at least 1 year and clinical outcomes were assessed using Visual Analog Scale pain scores (VAS), Oswestry Disability Index (ODI), and MacNab criteria preoperatively, 6 months postoperatively, and at the final follow-up. Results A total of 161 patients met the study criteria. The two groups were similar in age, sex, involved levels, preoperative neurologic status distribution, and comorbidities. The mean follow-up period was 22.3 ± 6.7 months (Group A) versus 23.0 ± 7.1 months (Group B) ( p > 0.05). Operation time, blood loss, and duration of hospitalization were significantly lower in the selective decompression group. The clinical outcomes (VAS, ODI) were maintained preoperatively, 6 months postoperatively, and at the final follow-up. Mean VAS scores were 7.4 ± 1.7 versus 7.9 ± 1.8; 4.0 ± 2.0 versus 2.6 ± 1.4; and 2.9 ± 1.3 versus 2.5 ± 1.5, respectively. Mean ODI scores were 60.3% ± 11.0% versus 65.1% ± 11.5%; 39.6% ± 8.7% versus 33.0% ± 8.5%; and 42.5% ± 10.8% versus 31.2% ± 8.8%, respectively. Sixty-seven patients (83.8%) versus 74 patients (91.4%) had good to excellent results 6 months postoperatively and 62 patients (77.5%) versus 72 patients (88.9%) had good to excellent results at the final follow-up. There were no surgery-related complications and no deaths among the patients at the last follow-up. Conclusion Compared with the open decompression group, selective decompression provided satisfactory clinical outcomes with significant reductions in operation time, blood loss, and duration of hospitalization. Selective decompression of the nerve root canal under direct vision was a safe and effective alternative to microsurgical procedures for elderly patients with LSS. Disclosure of Interest None declared