These data suggest that the increased mRNA expression of FTO could be responsible for the reduction of m(6)A in T2DM, which may further increase the risk of complications of T2DM. Low m(6)A should be investigated further as a novel potential biomarker of T2DM.

The aim of the present study was to evaluate the role of placental apoptosis in mediating the reproductive and developmental toxicity of caffeine in rodents. Female Kunming mice were treated with caffeine (60, 120 and 240 mg/kg per day) before and during pregnancy. The conception rate, maternal bodyweight gain, placental weight and indices of fetal developmental, including the rate of intrauterine growth retardation (IUGR; i.e. the actual number of fetuses exhibiting IUGR as a percentage of the total number of fetuses), were determined on gestational day (GD) 18. Female Wistar rats were treated with caffeine (20, 60 and 180 mg/kg per day) from GD11 to GD20. The IUGR rate, maternal plasma angiotensin (Ang) II and prolactin concentrations, placental pathology, expression of angiotensin AT(1) and AT(2) receptors and apoptosis-related proteins were measured on GD20. In mice, caffeine treatment dose-dependently reduced the total conception rate, delayed conception and decreased maternal bodyweight gain, placental weight, fetal bodyweight and fetal body and tail lengths, whereas the IUGR rate was increased. In rats, caffeine treatment dose-dependently decreased placental weight and fetal bodyweight and increased the IUGR rate. Abnormal placental structures and decreased maternal plasma prolactin concentrations were observed following 180 mg/kg per day caffeine treatment, which resulted in increases in renin-angiotensin system (RAS) activity, including maternal plasma AngII concentrations and placental AT(1B) and AT(2) receptor expression, and Bax and p53 expression, but decreases in placental Bcl-2 expression. On the basis of the results of the present study, it appears that caffeine ingestion has detrimental effects on the reproductive system and fetal development in rodents that are associated with chronic activation of the maternal and placental RAS, and induction of p53-dependent placental apoptosis.

Objective: Electronic cigarette (e-cig) use has recently been implicated in promoting atherosclerosis. In this study, we aimed to investigate the mechanism of e-cig exposure accelerated atherosclerotic lesion development. Approach and Results: Eight-week-old ApoE −/− mice fed normal laboratory diet were exposed to e-cig vapor (ECV) for 2 hours/day, 5 days/week for 16 weeks. We found that ECV exposure significantly induced atherosclerotic lesions as examined by Oil Red O staining and greatly upregulated TLR9 (toll-like receptor 9) expression in classical monocytes and in the atherosclerotic plaques, which the latter was corroborated by enhanced TLR9 expression in human femoral artery atherosclerotic plaques from e-cig smokers. Intriguingly, we found a significant increase of oxidative mitochondria DNA lesion in the plasma of ECV-exposed mice. Administration of TLR9 antagonist before ECV exposure not only alleviated atherosclerosis and the upregulation of TLR9 in plaques but also attenuated the increase of plasma levels of inflammatory cytokines, reduced the plaque accumulation of lipid and macrophages, and decreased the frequency of blood CCR2 + (C-C chemokine receptor type 2) classical monocytes. Surprisingly, we found that cytoplasmic mitochondrial DNA isolated from ECV extract-treated macrophages can enhance TLR9 activation in reporter cells and the induction of inflammatory cytokine could be suppressed by TLR9 inhibitor in macrophages. Conclusions: E-cig increases level of damaged mitochondrial DNA in circulating blood and induces the expression of TLR9, which elevate the expression of proinflammatory cytokines in monocyte/macrophage and consequently lead to atherosclerosis. Our results raise the possibility that intervention of TLR9 activation is a potential pharmacological target of ECV-related inflammation and cardiovascular diseases.

Aim: The aryl hydrocarbon receptor (AhR)-ligand axis has been shown to be involved in inflammatory diseases and bone homeostasis. However, the activation of AhR signalling pathway and the possible functions of AhR ligands in periodontitis are underexplored. This study investigated the expression of the AhR target gene cytochrome P450 subfamily B member 1 (CYP1B1) and the functions and mechanisms of the AhR ligand 6 formylindolo[3,2-b]carbazole (FICZ) in periodontitis. Materials and Methods: CYP1B1 expression was detected in human periodontitis samples, mice with ligature-induced periodontitis and lipopolysaccharide (LPS)-induced inflammation in periodontal ligament cells (PDLCs) in vitro. FICZ was administered topically or systemically. The therapeutic functions of FICZ were detected via qPCR, micro-computed tomography and immunohistochemistry. Finally, the mechanisms of AhR signalling in periodontitis were investigated by cell assays. Results: CYP1B1 expression was downregulated in periodontitis. FICZ rescued the alveolar bone loss and mitigated the inflammatory cytokines in periodontitis mice. In vitro, FICZ pre-treatment reduced the LPS-induced inflammation in PDLCs via the increased phosphorylation of STAT3. Additionally, FICZ prompted the mineralization of PDLCs via activation of the Wnt/β-catenin signalling pathway. Conclusion: AhR signalling pathway is suppressed in periodontitis and the AhR ligand FICZ can prevent periodontitis. K E Y W O R D S AhR signalling, CYP1B1, FICZ, inflammation, periodontitis | 883 HUANG et Al.

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Previously, we identified YueF as a novel Hepatitis B virus X protein (HBx)-interacting protein. Herein, we studied the functions of YueF and HBx in hepatocarcinogenesis. YueF was expressed at high levels in normal human hepatic cells and tissues, but scarcely found in hepatoma cells or other tumor tissues. Over-expression of YueF, or YueF and HBx could induce cell apoptosis and enhance p53 expression in hepatoma cells, whereas over-expression of HBx alone behaved contrarily. These results indicate that YueF has tumor suppressor activity and affects the functions of HBx in cell apoptosis and p53 expression in hepatoma cells.

FICZ/AhR axis might be a potential target to achieve optimal bone regeneration for both BMSCs and primed cartilage templates.

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