IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus.

Interleukin- (IL-) 33 contributes to various inflammatory processes. IL-33/ST2 activation participates in systemic lupus erythematous via binding to the receptor of Suppression of Tumorigenicity 2 protein (ST2). However, whether IL-33/ST2 interferes with the nosogenesis of cutaneous lupus erythematosus (CLE) has not been reported so far. Herein, we proposed to disclose the impacts on IL-33/ST2 activation and Ro60 on CLE and their potential implications in the photosensitization of CLE cells. IL-33, ST2, and Ro60 in CLE patients' skin lesions were detected. Murine keratinocytes stimulated with or without IL-33 were irradiated by ultraviolet B (UVB), and the levels of Ro60 and inflammation markers were determined. Keratinocytes were cocultured with J774.2 macrophages and stimulated with IL-33 for analysis of chemostasis. The results identified that IL-33, ST2, and downstream inflammation markers were significantly upregulated in CLE lesions with Ro60 overexpression. Additionally, IL-33 treatment promoted the upregulation of Ro60 induced by UVB treatment in murine keratinocytes. Moreover, IL-33 stimulates keratinocytes to induce macrophage migration via enhancing the generation of the chemokine (C-C motif) ligands 17 and 22. Meanwhile, the silencing of ST2 or nuclear factor-kappa B (NF-κB) suppression abolished IL-33-induced upregulation of Ro60 in keratinocytes. Similarly, the inhibition of SOX17 expression was followed by downregulation of Ro60 in keratinocytes following IL-33 stimulation. In addition, UVB irradiation upregulated SOX17 in keratinocytes. Conclusively, the IL-33/ST2 axis interferes with Ro60-regulated photosensitization via activating the NF-κB- and PI3K/Akt- and SOX17-related pathways.

Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4/MyD88/NF-κB pathway.

BACKGROUND/AIMS: This study aimed to explore the therapeutic effects and underlying mechanism of berberine (BBR) on the non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD). MATERIALS AND METHODS: Rats were randomly divided into the following 4 groups: control (normal diet), model (HFD), polyene phosphatidylcholine HFD+PPC, and BBR (HFD+BBR) group. The NAFLD models were prepared by feeding with HFD for 12 weeks. The liver tissues were observed by oil red O staining. H-E staining was used to detect pathological changes in the liver tissues. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected by an automatic biochemical analyzer. ELISA was performed to observe the inflammatory cytokines (TNF-α, IL-6, and IL-1ß) expressions. The levels of TLR4, MyD88, and NF-κB p65 were analyzed using western blot and qRT-PCR, respectively. The nuclear translocation levels of NF-κB in the primary liver cells were measured using flow cytometry. RESULTS: BBR could significantly alleviate the liver tissue steatosis and inflammatory cell infiltration; reduce the NAFLD activity scores and serum levels of ALT, AST, TC, and LDL-C; decrease the levels of TNF-α, IL-6, and IL-1ß, and reduce the expression of TLR4, MyD88, and NF-κB in the liver tissues. BBR could also reverse the nuclear translocation of NF-κB in the primary liver cells. CONCLUSION: BBR alleviated the progress of NAFLD and liver damage, which might contribute to inhibit the nuclear translocation of NF-κB via the TLR4/MyD88/NF-κB pathway.

Chemical characterization of polysaccharides isolated from scrophularia ningpoensis and its protective effect on the cerebral ischemia/reperfusin injury in rat model.

This study was designed to investigate the chemical characterization of scrophularia ningpoensis polysaccharides (SNP) and its protective activity on the cerebral ischemia/reperfusin injury (CIRI) rats. SNP was successfully isolated and fractionated by anion exchange chromatography and gel filtration into different factions, namely SNP1, SNP2, SNP3, SNP2-A and SNP2-B. SNP2-A is consisted of mannose (Man), rhamnose (Rha), glucuronic Acid (Glu A), galacturonic Acid (Gal A), glucose (Glu), galactose (Gal), xylose (Xyl) and arabinose (Ara). The nervous defect symptoms, the brain infarct volume and brain water content of rats with CIRI were improved by pretreatment with SNP2-A. In addition, SNP2-A could increase SOD activities, but could reduce MDA, NO, NOS, IL-1ß and TNF-α levels in brain tissues of rats with CIRI. Additionally, the reductive ERK protein expression and the elevated JNK and p38 protein expression stimulated by CIRI were all ameliorated by pre-treatment of SNP2-A. The results indicate that the protective effect may be related to the improvement of SNP2-A on the antioxidant capacity of brain tissue, the inhibition of inflammatory cytokines overproduction and the amelioration of MAPK pathway such as JNK, p38 and ERK proteins. These data provided an information for mechanistic studies for polysaccharide neuroprotective effects in CIRI.

Association between CD14 SNP -159 C/T and gastric cancer: an independent case-control study and an updated meta-analysis.

PURPOSE: The association between CD14 -159C/T polymorphism and the susceptibility to gastric cancer (GC) has been reported. However, the results were inconclusive. In the present study, a case-control study and a meta-analysis were performed to assess the possible association between -159C/T in the CD14 gene and GC risk. PATIENTS AND METHODS: Relevant studies were searched in several databases including PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure database, and Wanfang database (last search was performed on December 30, 2015). In addition, a case-control study involving 164 GC cases and 169 controls was also performed in the analysis. Statistical analysis was performed by the software Revman5.3. RESULTS: A total of ten published studies and the present case-control study involving 2,844 GC and 3,983 controls were included for the meta-analysis. The analysis result indicated that the T allele of CD14 -159C/T polymorphism did not confer risk for GC (in our study: [P=0.93]; in the meta-analysis: T vs 2N odds ratio =1.28 and 95% confidence interval (CI) =0.95-1.24, [P=0.24]). However, we found a significant association in the recessive model (in our study: TT vs TC+CC [P=0.04]; in the meta-analysis: TT vs TC+CC odds ratio =1.12 and 95% CI =1.01-1.26, [P=0.04]). Furthermore, a subgroup analysis by ethnicity showed that TT genotype was significantly associated with GC in Asian (odds ratio =1.17 and 95% CI =1.02-1.34, [P=0.02]) but not in Caucasian. CONCLUSION: Our results highlight the TT genotype of CD14 -159C/T as a genetic susceptibility factor for gastric cancer, particularly, in Asians and population-based controls.