Our previous studies have shown that microRNA-383 (miR-383) expression is downregulated in the testes of infertile men with maturation arrest (MA). However, the underlying mechanisms of miR-383 involved in the pathogenesis of MA remain unknown. In this study, we showed that downregulation of miR-383 was associated with hyperactive proliferation of germ cells in patients with mixed patterns of MA. Overexpression of miR-383 in NT2 (testicular embryonal carcinoma) cells resulted in suppression of proliferation, G1-phase arrest and induction of apoptosis, whereas silencing of miR-383 reversed these effects. The effects of miR-383 were mediated through targeting a tumor suppressor, interferon regulatory factor-1 (IRF1), and miR-383 was negatively correlated with IRF1 protein expression in vivo. miR-383 inhibited IRF1 by affecting its mRNA stability, which subsequently reduced the levels of the targets of IRF1, namely cyclin D1, CDK2 and p21. Downregulation of IRF1 or cyclin D1, but not that of CDK2, enhanced miR-383-mediated effects, whereas silencing of p21 partially inhibited the effects of miR-383. Moreover, miR-383 downregulated CDK4 by increasing proteasome-dependent degradation of CDK4, which in turn resulted in an inhibition of phosphorylated retinoblastoma protein (pRb) phosphorylation. These results suggest that miR-383 functions as a negative regulator of proliferation by targeting IRF1, in part, through inactivation of the pRb pathway. Abnormal testicular miR-383 expression may potentiate the connections between male infertility and testicular germ cell tumor.

Background Psoriasis has been linked to cardiovascular co-morbidities in cross-sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease (CVD) is limited. Objective To prospectively evaluate the association between psoriasis and risk of incident non-fatal CVD. Methods 96,008 participants were included from the Nurses’ Health Study II, and followed for 18 years. Information on physician-diagnosed psoriasis was obtained by self-report and diagnosis was confirmed by supplementary questionnaires. We included 2,463 individuals with self-reported psoriasis and a subsample of 1,242 with validated psoriasis. The main outcome was incident non-fatal CVD events (non-fatal myocardial infarction (MI) and non-fatal stroke), ascertained by biennial questionnaires and confirmed. Results During 1,709,069 person-years of follow-up, 713 incident non-fatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate-adjusted hazard ratio (HR) of non-fatal CVD, 1.55 (95% confidence interval (CI): 1.04-2.31). HRs for non-fatal MI and stroke were 1.70 (95% CI: 1.01-2.84) and 1.45 (95% CI: 0.80-2.65) respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR = 2.06, 95% CI: 1.31-3.26). For individuals with concomitant psoriatic arthritis, the risk of non-fatal CVD was even higher (HR 3.47; 95% CI: 1.85-6.51). Women diagnosed with psoriasis <40 years age or with duration of psoriasis ≥9 years had substantial elevations in CVD risk; HR 3.26 (95% CI: 1.21-8.75) and 3.09 (95% CI: 1.15-8.29) respectively. Conclusions Psoriasis is an independent predictor for non-fatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis.

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We did not find evidence of a positive association between AD and subsequent hypertension, T2D, MI or stroke; AD was inversely associated with these outcomes in our study. Given our findings and the conflicting literature, AD is likely not a major risk factor for cardiovascular disease.