Bilirubin level is decreased in patients with allergic rhinitis.

BACKGROUND: There are limitations in detecting methods for early diagnosis and screening of allergic rhinitis. Considering the anti-inflammatory and anti-oxidative effects of bilirubin, this study aims to explore the relationship between bilirubin and allergic rhinitis and to identify bilirubin-related candidate urinary protein biomarkers associated with allergic rhinitis. METHODS: 63 allergic rhinitis patients (AR group) and 86 healthy controls (NC group) were enrolled. Venous blood was obtained to measure serum total IgE levels and bilirubin parameters. Patients in the AR group were then classified into the AR1 group (IgE > 125 IU/mL) and the AR2 group (IgE ≤ 125 IU/mL). After randomly selecting ten urine samples from the AR1 group, ten samples were chosen from the AR2 and the NC groups, respectively, according to age and gender matching. We employed a Tandem Mass Tag-Based liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics approach and targeted parallel-reaction monitoring(PRM) to identify and validate urinary biomarkers for allergic rhinitis. RESULTS: Compared with the NC group, the bilirubin levels of the AR group, AR1 group, and AR2 group were significantly lower. Although the bilirubin level of the AR1 group was lower than that of the AR2 group, the difference was not significant. Further urinary proteomics analysis found that the expression levels of proteins related to bilirubin metabolism and transportation in the AR1 and AR2 groups, including ABCC1, GSTA1, GSTO1, GSTM3, GSTM5, and BLVRB, were significantly higher than those in the NC group. By PRM-based quantification, GSTA1 and GSTO1 showed significant differences in different degrees of Allergic Rhinitis groups and healthy controls. The AUC of the combined diagnosis of GSTA1 and GSTO1 was 0.79 (95% CI 0.583-0.997, P = 0.007), and the sensitivity and specificity were 100% and 60.0%, respectively. CONCLUSIONS: Bilirubin levels are associated with allergic rhinitis. Our study revealed that urine proteomics has a specific value for exploring the pathophysiological mechanism of bilirubin changes in AR patients and screening possible biomarkers.

Chlorogenic acid attenuates inflammation in LPS-induced Human gingival fibroblasts via CysLT1R/Nrf2/NLRP3 signaling.

Periodontitis is a chronic periodontal inflammatory disease and its etiology remains not fully understood. Chlorogenic acid (CA) is an ingredient isolated from nature product and exerts anti-inflammatory property. The purpose of the present study was to estimate the effect of CA on LPS-induced Human gingival fibroblasts (HGFs) and explore its mechanism. The CysLT1R inhibitor montelukast, Nrf2 inhibitor ML385, NLRP3 inhibitor MCC950 were employed to investigate the mechanism. As a result, the bioinformatic analysis indicated that CysLT1R, Nrf2, NLRP3 in the affected site of periodontitis patients gingival tissues were notably altered compared with those in unaffected site of healthy donors gingival tissues. The treatment with CA inhibited the contents of IL-1ß, IL-18 both in LPS-induced HGFs. CA ameliorated the expressions of CysLT1R, Nrf2, HO-1, NLRP3, ASC, pro-caspase-1, active caspase-1 in vitro. CA treatment promoted the nuclear translocation of Nrf2, suppressed oxidative stress and elevated mitochondrial membrane potential. The co-treatment with montelukast, ML385, MCC950 proved that CysLT1R, Nrf2, NLRP3 participated in the CA-mediated anti-inflammatory reaction. Molecular docking showed that CA might combine with CysLT1R. In conclusion, our data suggested that CA could attenuate inflammation in HGFs, which was possibly through CysLT1R/Nrf2/NLRP3 signaling.

MicroRNA-153 functions as a tumor suppressor in gastric cancer via targeting Kruppel-like factor 5.

[This retracts the article DOI: 10.3892/etm.2018.6226.].

Fisetin attenuates periodontitis through FGFR1/TLR4/NLRP3 inflammasome pathway.

The purpose of the present study was to investigate the pharmacological effect of Fisetin on experimental periodontitis in rats and explore its potential mechanism. The ligature/LPS method was used to induce periodontitis in rats. LPS was employed to cause inflammation in Human gingival fibroblasts (HGF). The transfections with FGFR1 SiRNA, NLRP3 SiRNA and the selective TLR4 inhibitor TAK242 were used to investigate the mechanism of Fisetin-mediated inflammatory reaction in LPS-induced HGF. As a result, Fisetin reduced the alveolar bone gap, reversed histopathological lesion and inhibited serum inflammatory cytokine concentration in periodontitis rats. Fisetin decreased the inflammatory cytokine contents in the supernatant of LPS-induced HGF. The inhibitory effect of Fisetin might be attributed to FGFR1/TLR4/NLRP3 inflammasome pathway both in vivo and in vitro. The suppressions of FGFR1, TLR4 and NLRP3 proved that FGFR1/TLR4/NLRP3 signaling was involved in the Fisetin-mediated inflammatory response. Fisetin also inhibited NLRP3 priming. The data demonstrated that Fisetin attenuated periodontitis by inhibiting inflammatory reaction via FGFR1/TLR4/NLRP3 inflammasome pathway.

MicroRNA-153 functions as a tumor suppressor in gastric cancer via targeting Kruppel-like factor 5.

Various microRNAs (miRs) have been demonstrated to serve important roles in gastric cancer (GC). miR-153 in particular has been reported to serve a suppressive role in GC; however, the underlying mechanism remains unclear. In the present study Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to examine the mRNA and protein expression of Kruppel-like factor 5. An MTT, wound healing and transwell assay were used to study cell proliferation, migration and invasion, respectively. In the present study, quantitative polymerase chain reaction data indicated that miR-153 was significantly downregulated in GC tissues compared with the adjacent non-tumor tissues. In addition, the reduced expression of miR-153 was significantly associated with GC aggressiveness and poor prognosis of patients. The expression of miR-153 was also reduced in GC cell lines, including KATO III, NCI-N87, SNU-16 and SNU-5, when compared with normal gastric epithelial GES-1 cells. Overexpression of miR-153 in the GC SNU-5 cells by miR-153 mimic transfection significantly inhibited the cell proliferation, migration and invasion. Furthermore, KLF5 was identified as a target gene of miR-153 in SNU-5 cells by bioinformatics prediction. It was observed that KLF5 was significantly upregulated in GC tissues and cell lines, and its expression was negatively regulated by miR-153 in SNU-5 cells. Overexpression of KLF5 impaired the suppressive effects of miR-153 on the proliferation, migration and invasion of SNU-5 cells. In conclusion, the present study demonstrated that miR-153 serves a tumor suppressive role in GC, at least partly, through directly targeting KLF5, thus highlighting the clinical significance of miR-153 in GC.