Effects of arginine vasopressin on the transcriptome of prefrontal cortex in autistic rat model.

Our previous studies have also demonstrated that AVP can significantly improve social interaction disorders and stereotypical behaviours in rats with VPA-induced autism model. To further explore the mechanisms of action of AVP, we compared the PFC transcriptome changes before and after AVP treatment in VPA-induced autism rat model. The autism model was induced by intraperitoneally injected with VPA at embryonic day 12.5 and randomly assigned to two groups: the VPA-induced autism model group and the AVP treatment group. The AVP treatment group were treated with intranasal AVP at postnatal day 21 and for 3 weeks. The gene expression levels and function changes on the prefrontal cortex were measured by RNA-seq and bioinformatics analysis at PND42 and the mRNA expression levels of synaptic and myelin development related genes were validated by qPCR. Our results confirmed that AVP could significantly improve synaptic and axon dysplasia and promote oligodendrocyte development in the prefrontal cortex in VPA-induced autism models by regulating multiple signalling pathways.

A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the fastest-rising causes of cancer-related death worldwide, but its deficiency of specific biomarkers and therapeutic targets in the early stages lead to severe inadequacy in the early diagnosis and treatment of HCC. Covalently closed circular RNA (circRNA), which was once considered an aberrant splicing by-product, is now drawing new interest in cancer research because of its remarkable functionality. Beneath the surface of the dominant functional proteins events, a hidden circRNA-centric noncoding regulatory RNAs network active in the very early stage of HCC is here revealed by a genome-wide analysis of mRNA, circRNA, and microRNA (miRNA) expression profiles. Circ-CDYL (chromodomain Y like) is specifically up-regulated in the early stages of HCC and therefore contributes to the properties of epithelial cell adhesion molecule (EPCAM)-positive liver tumor-initiating cells. Circ-CDYL interacts with mRNAs encoding hepatoma-derived growth factor (HDGF) and hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by acting as the sponge of miR-892a and miR-328-3p, respectively. Subsequently, activation of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase-mechanistic target of rapamycin kinase complex 1/ß-catenin and NOTCH2 pathways, which promote the expression of the effect proteins, baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto-oncogene, is influenced by circ-CDYL. A treatment incorporating circ-CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem-like characteristics and tumor growth in HCC. Finally, we demonstrated that circ-CDYL expression or which combined with HDGF and HIF1AN are both independent markers for discrimination of early stages of HCC with the odds ratios of 1.09 (95% confidence interval [CI], 1.02-1.17) and 124.58 (95% CI, 13.26-1170.56), respectively. Conclusion: These findings uncover a circRNA-centric noncoding regulatory RNAs network in the early stages of HCC and thus provide a possibility for surveillance and early treatment of HCC.

Dual regulation of HMGB1 by combined JNK1/2-ATF2 axis with miR-200 family in nonalcoholic steatohepatitis in mice.

In the context of diabetes, obesity, and metabolic syndrome, the inflammatory signaling has critical roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain poorly delineated. Herein, early and persistently elevated, proinflammatory cytokine HMGB1 expression was detected in a high-fat diet (HFD)-induced NAFLD model in C57BL/6 mice. The expression and extracellular release of HMGB1 was rapidly and dramatically induced by saturated palmitic acid in vitro. HFD-induced inflammatory response and liver function impairment were both mitigated after the inhibition of endogenous HMGB1 by neutralizing antibody in vivo. The up-regulation of HMGB1 was thought to be modified by dual channels: in the transcriptional level, it was regulated by JNK1/JNK2-ATF2 axis; post-transcriptionally, it was regulated by the microRNA (miR)-200 family, especially miR-429. miR-429 liver conditional knockout mice (miR-429Δhep), fed either a normal diet or an HFD, showed severe liver inflammation and dysfunction, accompanied by greater expression of HMGB1. Intriguingly, the up-regulation and release of HMGB1 could in turn self-activate TLR4-JNK1/JNK2-ATF2 signaling, thus forming a positive feedback. Our findings reveal a novel mechanism by which HMGB1 expression was regulated by both the JNK1/2-ATF2 axis and the miR-200 family, which provides a potential new approach for the treatment of NAFLD.-Chen, X., Ling, Y., Wei, Y., Tang, J., Ren, Y., Zhang, B., Jiang, F., Li, H., Wang, R., Wen, W., Lv, G., Wu, M., Chen, L., Li, L., Wang, H. Dual regulation of HMGB1 by combined JNK1/2-ATF2 axis with miR-200 family in nonalcoholic steatohepatitis in mice.

Serum Vaspin Levels in Gestational Diabetes Mellitus: A Meta-Analysis.

The objective of this study was to evaluate the potential relationship between serum vaspin levels and gestational diabetes mellitus (GDM). The PubMed, EBSCO, Web of Science, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) database were searched for articles published before December 2022. The publication language was restricted to English and Chinese. A meta-analysis was conducted by combining all studies that met the inclusion and exclusion criteria. Twenty-two studies (1990 women with GDM and 1597 pregnant women without GDM) were ultimately included in this meta-analysis. The meta-analysis showed that the serum vaspin levels are significantly higher in GDM compared with the controls (standardized mean difference: 0.720, 95% confidence interval: 0.440-1.000, Z = 5.041, P < 0.001). Subgroup analyses by stage of pregnancy and body mass index showed results similar to the overall outcome. No publication bias was identified, and the sensitivity analysis confirmed the robustness of the final result. Our results show that the serum vaspin levels are significantly higher in GDM. These findings suggest that high vaspin concentration is closely related to GDM and the serum vaspin levels might be a potential biomarker to indicate risk of GDM, more randomized control trials comparing the expression levels of vaspin between early and standard diagnosis of GDM are needed to strengthen our findings.

PSMD10/gankyrin induces autophagy to promote tumor progression through cytoplasmic interaction with ATG7 and nuclear transactivation of ATG7 expression.

Although autophagy is most critical for survival of cancer cells, especially in fast-growing tumors, the mechanism remains to be fully characterized. Herein we report that PSMD10/gankyrin promotes autophagy in hepatocellular carcinoma (HCC) in response to starvation or stress through 2 complementary routes. PSMD10 was physically associated with ATG7 in the cytoplasm, and this association was enhanced by initial nutrient deprivation. Subsequently, PSMD10 translocated into the nucleus and bound cooperatively with nuclear HSF1 (heat shock transcription factor 1) onto the ATG7 promoter, upregulated ATG7 expression in the advanced stage of starvation. Intriguingly, the type of PSMD10-mediated autophagy was independent of the proteasome system, although PSMD10 has been believed to be an indispensable chaperone for assembly of the 26S proteasome. A significant correlation between PSMD10 expression and ATG7 levels was detected in human HCC biopsies, and the combination of these 2 parameters is a powerful predictor of poor prognosis. The median survival of sorafenib-treated HCC patients with high expression of PSMD10 was much shorter than those with low expression of PSMD10. Furthermore, PSMD10 augmented autophagic flux to resist sorafenib or conventional chemotherapy, and inhibition of autophagy suppressed PSMD10-mediated resistance. We conclude that these results present a novel mechanism involving modulation of ATG7 by PSMD10 in sustaining autophagy, promoting HCC cell survival against starvation or chemotherapy. Targeting of PSMD10 might therefore be an attractive strategy in HCC treatment by suppressing autophagy and inducing HCC cell sensitivity to drugs.

Ultra-fast fabrication of colloidal photonic crystals by spray coating.

An ultra-fast fabrication of large-scale colloidal PCs via spray coating was demonstrated. The latex spheres with hydrophobic core and hydrophilic shell were designed, and the latex shell with abundant COOH groups resulted in strong hydrogen bonding interaction among latex spheres, which boosted latex arrangement during the spray procedure. The resultant samples with area of 7 × 12 cm(2) were easily fabricated within 1 min on different substrates. This ultra-fast fabrication procedure would be of great importance for the practical application of PCs for optic devices and functional coatings.