Microglial AIM2 alleviates antiviral-related neuro-inflammation in mouse models of Parkinson's disease.

Inflammasome involvement in Parkinson's disease (PD) has been intensively investigated. Absent in melanoma 2 (AIM2) is an essential inflammasome protein known to contribute to the development of several neurological diseases. However, a specific role for AIM2 in PD has not been reported. In this study, we investigated the effect of AIM2 in the N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model by use of various knockout and bone marrow chimeric mice. The mechanism of action for AIM2 in PD was assessed by RNA-sequencing and in vitro primary microglial transfection. Results were validated in the A30P transgenic mouse model of PD. In the MPTP mouse model, AIM2 activation was found to negatively regulate neuro-inflammation independent of the inflammasome. Microglial AIM2 deficiency exacerbated behavioral and pathological features of both MPTP-induced and transgenic PD mouse models. Mechanistically, AIM2 reduced cyclic GMP-AMP synthase (cGAS)-mediated antiviral-related inflammation by inhibition of AKT-interferon regulatory factor 3 (IRF3) phosphorylation. These results demonstrate microglial AIM2 to inhibit the antiviral-related neuro-inflammation associated with PD and provide for a foundation upon which to identify new therapeutic targets for treatment of the disease.

Evaluation of the sensitivity of Microhyla fissipes tadpoles to aqueous cadmium.

Cadmium (Cd) exposure is harmful to amphibians in natural environments and the Cd concentration is a key parameter in water monitoring. Cd pollution has been a severe issue in the Yangtze River and its southern reaches in recent years. Acute toxicity assays were employed to determine the tolerance limits of Cd for Microhyla fissipes tadpoles and five different concentrations of Cd (0, 50, 100, 200 and 300 µg/L) were involved to detect its chronic effects on metamorphosis, growth, locomotion, genotoxicity and enzymatic activities of M. fissipes tadpoles. The results showed that the 24-h and 48-h LC50 values of Cd on M. fissipes tadpoles were 2591.3 µg/L and 1567.9 µg/L, respectively, and the presumable non-lethal concentration obtained was 172.2 µg/L. During the 70-day chronic toxicity assays, Cd showed negative impacts on survival, growth, metamorphosis and the frequency of erythrocytes nuclear abnormality of M. fissipes tadpoles. However, the Cd exposure caused the increased body size and condition of tadpoles at complete metamorphosis (GS46). The tadpoles exposed to 200 µg/L of Cd exhibited degraded locomotor performance at GS46. Weight increments of tadpoles were inhibited at Day 14 and massive deaths were observed over the next 14 days. The enzymatic activities of tadpoles experienced a shock response stage (GS30-GS35) and a complete recovery stage (GS36-GS41) in all treatments. However, the enzymatic activities (except alkaline phosphatase) of tadpoles at GS46 increased after Cd exposure, especially at high concentrations. In summary, Cd is a threat to M. fissipes tadpoles as that causes reduced fitness.

Altered long noncoding RNAs and survival outcomes in ovarian cancer: A systematic review and meta-analysis (PRISMA Compliant).

BACKGROUND: Previous studies investigating the association between altered long noncoding RNAs (lncRNAs) and survival outcomes in ovarian cancer have obtained controversial results. To comprehensively evaluate the association, we conducted a systematic review and meta-analysis of the studies published on the subject. METHODS: We performed a systematic search using the databases of the Cochrane Central Register of Controlled Trials, PubMed, and Embase to find all relevant articles from inception to May 7, 2017. Studies that evaluated the association between 1 specific lncRNA and survival outcomes in ovarian cancer were included. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) for overall survival, progression-free survival, and disease-free survival were calculated with a fixed-effects or random-effects model. RESULTS: A total of 15 studies involving 1333 patients with ovarian cancer were included in this meta-analysis. Altered lncRNAs were associated with decreased overall survival (HR: 2.29, 95% CI: 1.92-2.75) without heterogeneity (I = 0.0%) in ovarian cancer. Altered lncRNAs were also associated with decreased progression-free survival (HR: 2.77, 95% CI: 1.00-7.62, I = 76.6%) and disease-free survival (HR: 2.59, 95% CI: 0.89-7.57, I = 62.9%) in ovarian cancer. CONCLUSION: Our results supported the strong prognostic value of altered lncRNAs in ovarian cancer. Further large-scale studies should be carried out to verify the clinical applications of altered lncRNAs in the prognosis assessment of ovarian cancer.