Larsenjohansson6980

Exposure to ambient fine particulate matter (PM2.5) elicits various abnormalities in glycaemic control and thus correlates with type 2 diabetes. Intermittent fasting is an emerging treatment for type 2 diabetes. This study, therefore, tested whether intermittent fasting ameliorates PM2.5 exposure-induced abnormalities in glycaemic control. To this end, C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) for 16 weeks and concurrently subject to ad libitum feeding or intermittent fasting. The food intake assessment showed that CAP exposure transiently reduced food intake in ad libitum fed mice, but persistently reduced food intake in intermittently fasted mice. In contrast, CAP exposure persistently promoted mouse weight gain in ad libitum fed mice, while intermittent fasting blocked this CAP exposure-induced weight gain. The glucose homeostasis assessments revealed that CAP exposure elicited insulin resistance and glucose intolerance and meanwhile increased glucose-induced insulin secretion (GIIS). The insulin resistance and glucose intolerance, but not the increase in GIIS, induced by CAP exposure were blocked by intermittent fasting. Analysis of Akt phosphorylation, the indicator of local insulin signaling, showed that CAP exposure reduced insulin signaling in the liver and adipose tissues but not in the skeletal muscle. Intermittent fasting blocked CAP exposure-induced insulin resistance in the liver but not in the adipose tissues. The present study demonstrates that intermittent fasting ameliorates PM2.5 exposure-induced insulin resistance and glucose intolerance, strongly supporting that it may be used to prevent type 2 diabetes due to exposure to PM2.5.Extensive literature has demonstrated that acute myeloid leukaemia (AML) cells show enhanced mitochondrial biogenesis and increased reliance on oxidative phosphorylation (OXPHOS) compared with normal hematopoietic progenitors, and one hallmark of AML leukaemia blasts is myeloid differentiation blockade. However, relatively few reports have linked these processes. Recent studies have indicated that therapies that overcome differentiation arrest represent an effective treatment strategy. Here, we identified that the disruption of the mitochondrial mass and energy metabolism promotes leukaemia cellular myeloid differentiation. In this study, we showed that acute monocytic leukaemia (AML-M5) cells package mitochondria in microvesicles (MVs) when MVs shed from membranes. Additionally, during myeloid differentiation, we report for the first time that differentiated leukaemia cells release more MVs than undifferentiated leukaemia cells. Targeting the formation of MVs using a specific inhibitor (Y-27632) restrained myeloid differentiation, suggesting that the increased release level of MVs plays an important role in regulating myeloid differentiation. Furthermore, the intracellular mitochondria and ATP levels were decreased after leukaemia cells overcame the differentiation blockade. Moreover, rotenone, which is used to inhibit the respiratory chain and ATP production, had a strong effect on myeloid differentiation in monocytic leukaemia cells. Collectively, these studies uncovered the relationship between mitochondrial function and myeloid differentiation and may provide more insight into the diagnosis and treatment of AML.

Forkhead box f1 (FoxF1), a transcription factor, was implicated in lung development. However, the molecular mechanism of FoxF1 in lung injury, specifically in injury caused by paraquat (PQ), one of the most frequently used herbicides, is unknown. Accordingly, we performed this study to investigate whether FoxF1 attenuates PQ-induced lung injury and to determine the possible mechanism.

We used PQ-treated Beas-2B cells to measure the expression of FoxF1. Later, ChIP-qPCR was applied to detect the levels of histone acetylation in cells, followed by the validation of the relationship between histone deacetylase-2 (HDAC2) and FoxF1. Subsequently, the correlation between FoxF1 and microRNA (miR)-342 and the downstream mechanism of miR-342 were evaluated by bioinformatics analysis. The apoptosis and the content of reactive oxygen species (ROS) in PQ-treated cells were detected to evaluate the roles of HDAC2, FoxF1 and miR-342 in vitro. Finally, a rat model was developed to evaluate the effects of HDAC2, miR-342 and Krüppel-like factor 5 (KLF5) on PQ-induced lung injury in vivo.

PQ treatment significantly enhanced FoxF1 promoter deacetylation, thereby inhibiting FoxF1 expression. After inhibition of HDAC2 activity, apoptosis and oxidative stress induced by PQ were significantly reversed. Nevertheless, further inhibition of miR-342 or overexpression of KLF5 promoted apoptosis and oxidative stress induced by PQ, and IκB/NF-κB p65 signaling was significantly activated after PQ treatment.

PQ treatment inhibited miR-342 expression by promoting HDAC2-induced deacetylation of the FoxF1 promoter, thereby promoting KLF5 expression and the IκB/NF-κB p65 signaling activation, and finally exacerbating PQ-induced lung injury in rats.

PQ treatment inhibited miR-342 expression by promoting HDAC2-induced deacetylation of the FoxF1 promoter, thereby promoting KLF5 expression and the IκB/NF-κB p65 signaling activation, and finally exacerbating PQ-induced lung injury in rats.

The purpose of this study was to evaluate serum cardiac troponin I and serum N-terminal (NT) pro-brain natriuretic peptide (pro-BNP) levels and the utility of tissue Doppler imaging in assessing cardiovascular changes following left ventricular (LV) dysfunction in children with beta-thalassemia major (β-TM). Selleckchem CDK inhibitor In children with β-TM who depend on regular blood transfusion, cardiac iron toxicity is a common serious complication. The most common cause of death among these patients is congestive heart failure.

This is a cross-sectional study which included 50 patients with β-TM and 50 healthy controls. Tissue Doppler imaging was performed and levels of serum ferritin, cardiac troponin I, and NT pro-BNP were estimated for all included patients.

Serum NT pro-BNP and cardiac troponin (cTnI) showed a significant increase in patients with β-TM (p<.001). In patients with β-TM, LV dimensions (LV end systolic diameter) and (LV end diastolic diameter) were large (p<.01); LV mass (p<.01), E wave, and E/A ratio (p<.