AIM2 contributes to the maintenance of intestinal integrity via Akt and protects against Salmonella mucosal infection.

The mechanism regulating the gastrointestinal epithelial barrier remains poorly understood. We herein demonstrate that Absent in melanoma-2 (AIM2) contributes to the maintenance of intestinal barrier integrity and defense against bacterial infection. AIM2-deficient mice displayed an increased susceptibility to mucosal but not systemic infection by Salmonella typhimurium, indicating a protective role for AIM2 in the gastrointestinal tract. In a Salmonella colitis model, compared with wild-type mice, AIM2(-/-) mice exhibited more severe body weight loss, intestinal damage, intestinal inflammation, and disruption of basal and activated epithelial cell turnover. In vivo and in vitro data showed that AIM2 restricted the early epithelial paracellular invasion of Salmonella and decreased epithelial permeability. The decreased epithelial barrier in AIM2(-/-) mice might be attributed to the altered expression of tight junction proteins that contribute to epithelial integrity. AIM2 promoted the expression of tight junction proteins through Akt activation. Together, these results suggest that AIM2 is required for maintaining the integrity of the epithelial barrier.

Diagnostic performance of micropthalmia transcription factor for melanoma: a systematic review and meta-analysis.

BACKGROUND AND AIM: The diagnosis of melanoma is still a clinical challenge, many studies reported that micropthalmia transcription factor (MITF) plays a role in diagnosing melanoma, but with considerable inconsistent results. The present work aimed to summarize the overall performance of MITF in diagnosing melanoma. METHODS: A systematic literature search was performed in Pubmed and Embase for studies regarding the usefulness of MITF to diagnose melanoma. Data were retrieved and pooled sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were determined. The post-test probability was performed to evaluate clinical usefulness. A summary receiver operator characteristic curve and the area under the curve were used to summarize the overall diagnostic accuracy. RESULTS: Nine studies with 1,299 subjects (651 melanomas and 648 non-melanomas) were included for present meta-analysis. The pooled sensitivity and specificity of MITF for diagnosing melanoma were 0.84 (95% CI: 0.81-0.87) and 0.96 (95% CI: 0.95-0.98), respectively. The positive likelihood ratio was 17.73 (95% CI: 10.85-28.99), negative likelihood ratio was 0.18 (95% CI: 0.10-0.32) and diagnostic odds ratio was 221.56 (95% CI: 66.16-741.96). In a setting of 20% prevalence of melanoma, the probability of melanoma would be 92% if the MITF test was positive, and the probability of melanoma would be 1% if it was negative. The area under the summary receiver operator characteristic curve was 0.99. CONCLUSIONS: MITF may play a valuable role in the diagnosis of melanoma with a high specificity. Nevertheless, the results of MITF should be interpreted with the combination of other test results and clinical findings.

Potential role of anti-p53 antibody in diagnosis of lung cancer: evidence from a bivariate meta-analysis.

OBJECTIVES: The diagnosis of lung cancer remains a clinical challenge. Many studies have assessed the diagnostic potential of anti-p53 antibody in lung cancer patients but with controversial results. This study aims to summarize the overall diagnostic performance of anti-p53 antibody in lung cancer. MATERIALS AND METHODS: Based on a comprehensive search of the Pubmed and Embase, we identified outcome data from all articles estimating diagnostic accuracy of anti-p53 antibody for lung cancer. A summary estimation for sensitivity, specificity, and other diagnostic indexes were pooled using a bivariate model. The overall measure of accuracy was calculated using summary receiver operating characteristic curve and the area under curve (AUC) was calculated. RESULTS: According to our inclusion criteria, 16 studies with 4414 subjects (2249 lung cancers, 2165 controls) were included. The summary estimates were: sensitivity 0.20 (95% CI 0.15-0.27), specificity 0.97 (95% CI 0.95-0.98), positive likelihood ratio 6.64 (95% CI 4.34-10.17), negative likelihood ratio 0.83 (95% CI 0.77-0.89), diagnostic odds ratio 8.04 (95% CI 5.05-12.79), the AUC was 0.84. Subgroup analysis suggested that anti-p53 antibody had a better diagnostic performance for small cell lung cancer than non-small cell lung cancer. CONCLUSIONS: anti-p53 antibody can be an assistant marker in diagnosing lung cancer, but the low sensitivity limits its use as a screening tool for lung cancer. Further studies should be performed to confirm our findings.