Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

FMNL1 down-regulation suppresses bone metastasis through reducing TGF-ß1 expression in non-small cell lung cancer (NSCLC).

Approximately 40% of patients with non-small cell lung cancer (NSCLC) develop bone metastasis. The formin protein formin-like 1 (FMNL1) plays a key role in the pathogenic processes of hematopoietic malignancies, and has been reported to be associated with the progression of multiple types of cancer. In the study, we found that FMNL1 expression was markedly up-regulated in primary NSCLC samples, and stronger expression of FNML1 was detected in bone metastasis. Reducing FMNL1 expression significantly suppressed cell proliferation in NSCLC cells. We also investigated the functional effects of FMNL1 knockdown on the inhibition of migration and invasion by meditating the expression of epithelial to mesenchymal transition (EMT)-associated signals in NSCLC cells. The transforming growth factor-ß1 (TGF-ß1)/SMADs signaling pathway was repressed in FMNL1-knockdown NSCLC cells. Further studies indicated that additional treatment with TGF-ß1 could markedly abrogate FMNL1 knockdown-induced suppression of migration and invasion in NSCLC cells. In addition, NSCLC cell-induced osteoclastogenesis was also inhibited by FMNL1 deletion, as evidenced by the down-regulated expression of tartrate-resistant acid phosphatase (TRAP) and NFATc1. In vivo studies confirmed the results that FMNL1 knockdown markedly limited tumor growth. Importantly, decreasing FMNL1 reduced bone metastasis ability in vivo. Therefore, our results demonstrated that suppressing FMNL1 expression could inhibit bone metastasis in NSCLC through blocking TGF-ß1 signaling, and FMNL1 might be a novel target for developing effective therapeutic strategy to limit the bone metastasis of NSCLC.