Ferulic acid alleviates sciatica by inhibiting neuroinflammation and promoting nerve repair via the TLR4/NF-κB pathway.

INTRODUCTION: Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. METHODS: Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. RESULTS: RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1ß, IL-6, TNF-α, IL-8, and TGF-ß protein levels and IL-1ß, IL-6, TNF-α, TGF-ß, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1ß, iNOS, nNOS, COX2, and TLR4 expression was increased while S100ß and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1ß, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1ß, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1ß, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1ß, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1ß, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. CONCLUSION: Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.

Effect of Different Roasting Conditions and Coreopsis Extract on Heterocyclic Amine Formation in Roast Lamb Products.

ABSTRACT: Heterocyclic amines (HCAs), which are known carcinogens in thermally processed foods, were investigated in roast lamb patties under various time and temperature conditions. HCAs in lamb products roasted at some temperatures increased with roasting time. An exponential model with a time factor fit well for the production of HCAs. The mean pH and cooking loss at various temperatures were also determined. The mean pH decreased as the temperature increased. Coreopsis extract was added to lamb patties roasted at 230°C for 15 min per side. The amount of coreopsis extract added had a significant effect on HCA development. A weak positive relationship was observed between the antioxidant activity of the lamb patty with the coreopsis extract and the inhibitory effect of coreopsis extract on various HCAs, with a correlation coefficient of 0.14 to 0.44 (P > 0.05). Coreopsis extract containing flavonoids can be a beneficial additive for production of barbecue meat.

Microarray profiling of lung long non-coding RNAs and mRNAs in lipopolysaccharide-induced acute lung injury mouse model.

Long non-coding RNAs (lncRNAs) are involved in various biological processes as well as many respiratory diseases, while the role of lncRNAs in acute lung injury (ALI) remains unclear. The present study aimed to profile the expression of lung lncRNAs and mRNAs in lipopolysaccharide (LPS)-induced ALI mouse model. C57BL/6 mice were exposed to LPS or phosphate-buffered saline for 24 h, and lncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Bioinformatics analysis gene ontology including (GO) and pathway analysis and cell study in vitro was used to investigate potential mechanisms. Based on the microarray results, 2632 lncRNAs and 2352 mRNAs were differentially expressed between ALI and control mice. The microarray results were confirmed by the quantitative real-time PCR (qRT-PCR) results of ten randomized selected lncRNAs. GO analysis showed that the altered mRNAs were mainly related to the processes of immune system, immune response and defense response. Pathway analysis suggests that tumor necrosis factor (TNF) signaling pathway, NOD-like receptor pathway, and cytokine-cytokine receptor interaction may be involved in ALI. LncRNA-mRNA co-expression network analysis indicated that one individual lncRNA may interact with several mRNAs, and one individual mRNA may also interact with several lncRNAs. Small interfering RNA (siRNA) for ENSMUST00000170214.1, - ENSMUST00000016031.13 significantly inhibited LPS-induced TNF-α and interleukin (IL)-1ß production in murine RAW264.7 macrophages. Our results found significant changes of lncRNAs and mRNAs in the lungs of LPS-induced ALI mouse model, and intervention targeting lncRNAs may attenuate LPS-induced inflammation, which may help to elucidate the role of lncRNAs in the pathogenesis and treatment of ALI.

Telomerase activity assay for the diagnosis of malignant pleural effusion: A meta-analysis.

The telomerase activity assay has been established for the detection of malignant pleural effusion (MPE), however, the overall diagnostic accuracy of the telomerase activity assay for MPE remains unclear. We performed a systematic search in the Pubmed, Embase and Cochrane databases to identify published studies that have evaluated the diagnostic role of the telomerase activity assay for MPE. Sensitivity, specificity and other measures of accuracy of the telomerase activity assay in the diagnosis of MPE were pooled using the random effects models. A summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. A total of eight studies met the inclusion criteria for the meta-analysis. The pooled sensitivity and specificity for diagnosing MPE were 0.76 [95% confidence intervals (CI), 0.72-0.80] and 0.87 (95% CI, 0.83-0.91), respectively. The positive likelihood ratio was 5.19 (95% CI, 2.36-11.42), the negative likelihood ratio was 0.25 (95% CI, 0.11-0.53) and the diagnostic odds ratio was 23.18 (95% CI, 6.11-87.83). The area under the SROC curve was 0.92. The telomerase activity assay plays a role in the diagnosis of MPE with a relatively high specificity. The results of a telomerase activity assay should be interpreted together with the combination of other test results and clinical findings.