RESUMO
Objective: Psoriasis is a disease with an immunogenetic background in which cytokines have important effects on its prevalence and incidence. The present meta-analysis evaluated the relationship between tumor necrosis factor-alpha (TNF-α) polymorphisms (rs361525, rs1800629, rs1799724, 1800630, and rs1799964) and psoriasis risk in studies following Hardy-Weinberg equilibrium (HWE). Materials and methods: Four databases were searched to retrieve relevant studies reporting the distributions of TNF-α polymorphisms in psoriasis cases compared to controls. The effect sizes were the 95% confidence intervals (CIs) and odds ratios (ORs). Subgroup analysis, sensitivity analyses, publication bias, trial sequential analysis (TSA), and meta-regression were performed on the initial pooled results of TNF-α polymorphisms. Results: Thirty-six articles with 71 studies were included in the meta-analysis (twenty-six: rs361525, twenty-seven: rs1800629, nine: rs1799724, four: 1800630, and five: rs1799964). The pooled ORs for -238 G/A rs361525 polymorphism were 2.33 (p < 0.00001), 2.79 (p < 0.0001), 2.35 (p < 0.00001), 2.44 (p < 0.00001), and 2.45 (p < 0.00001), as well as 1.57 (p < 0.00001), 1.98 (p = 0.01), 1.61 (p < 0.00001), 1.64 (p < 0.00001), and 1.79 (p < 0.00001) for -857 C/T rs1799724 polymorphism in allelic, homozygous, heterozygous, dominant, and recessive models, respectively. Ethnicity, psoriasis type, and sample size affected the pooled results of rs361525, rs1800629, and rs1799724 polymorphisms. Based on TSA, there were just sufficient cases for -238 G/A rs361525 polymorphism in five genetic models and -857C/T rs1799724 polymorphism in allelic, heterozygous, and dominant models. Conclusions: The A allele and GA and GG genotypes of -238 G/A rs361525 polymorphism and T allele, TT and CT genotypes of -857C/T rs1799724 polymorphism were related to increased risks in psoriasis cases. Well-designed studies (with no deviation from HWE in controls) with more cases are recommended in the future.
RESUMO
The aim of this study was to analyze the single and combined effects of N-acetyl cysteine (NAC) and doxycycline (Dox) on the inflammatory and angiogenic factors in the rat model of alkali-burned cornea. Rats were treated with a single and combined 0.5% NAC and 12.5 µg/mL Dox eye drops and evaluated on days 3, 7, and 28. In the corneas of various groups, the activity of Catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes was assessed. The expression of inflammatory factors (TNF-α, Rel-a, and CXCL-1) and angiogenic factors (VEGF-a, MMP2, and MMP9) was measured using real-time polymerase chain reaction. The antioxidant enzyme activities decreased substantially 3 days after injury with sodium hydroxide (NaOH). NAC and combined NAC+ Dox topical treatments increased the SOD enzyme activity on day 28 (P < 0.05). The expression of TNF-α and Rel-a genes following single and combined treatment of NAC and Dox decreased significantly on days 7 and 28 (P < 0.05). The mRNA level of angiogenic factors and corneal neovascularization (CNV) level declined in NaOH-injured rats treated with Dox (P < 0.05). The topical treatment of Dox could attenuate inflammation and CNV complications. However, NAC treatment may not reduce the expression of angiogenic genes.
