At birth, ventilation and oxygenation immediately decrease pulmonary vascular resistance (PVR) and increase pulmonary blood flow (PBF); more gradual changes occur over the next several hours. Nitric oxide, produced by endothelial nitric oxide synthase (eNOS), mediates these gradual changes. To determine how ventilation and oxygenation affect eNOS gene expression, 12 fetal lambs were ventilated for 8 h without changing fetal descending aortic blood gases or pH (rhythmic distension) or with 100% oxygen (O 2 ventilation). Vascular pressures and PBF were measured. Total RNA, protein, and tissue sections were prepared from lung tissue for RNase protection assays, Western blotting, and in situ hybridization. O 2 ventilation increased PBF and decreased PVR more than rhythmic distension ( P Ͻ 0.05). Rhythmic distension increased eNOS mRNA expression; O 2 ventilation increased eNOS mRNA expression more and increased eNOS protein expression ( P Ͻ 0.05). To define the mechanisms responsible for these changes, ovine fetal pulmonary arterial endothelial cells were exposed to 1, 21, or 95% O 2 or to shear stress. 95% O 2 increased eNOS mRNA and protein expression ( P Ͻ 0.05). Shear stress increased eNOS mRNA and protein expression ( P Ͻ 0.05). Increased oxygenation but more importantly increased PBF with increased shear stress induce eNOS gene expression and contribute to pulmonary vasodilation after birth. (

Background/Aims: The activation of cannabinoid receptor 2 (CB2) has the beneficial effect of reducing neuroinflammatory response in the treatment of Alzheimer's disease (AD) and is suggested to trigger the peroxisome proliferator-activated receptor-γ (PPARγ) pathway; agonists of both receptors improve AD. Recently, the plant metabolite β-caryophyllene was shown to selectively bind to CB2 receptor and act as a full agonist. Methods: In this study, we examined the anti-inflammatory effect of β-caryophyllene in a transgenic APP/PS1 AD model and analyzed whether this effect was mediated by CB2 and PPARγ. Results: β-Caryophyllene, given orally, prevented cognitive impairment in APP/PS1 mice, and this positive cognitive effect was associated with reduced β-amyloid burden in both the hippocampus and the cerebral cortex. Moreover, β-caryophyllene reduced astrogliosis and microglial activation as well as the levels of COX-2 protein and the mRNA levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the cerebral cortex. The use of the CB2 antagonist AM630 or the PPARγ antagonist GW9662 significantly reversed the protective effects of β-caryophyllene on APP/PS1 mice. Conclusion: These results demonstrate that the anti-inflammatory effect of the sesquiterpene β-caryophyllene involves CB2 receptor activation and the PPARγ pathway and suggest β-caryophyllene as an attractive molecule for the development of new drugs with therapeutic potential for the treatment of AD.

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BackgroundThis study aims to analyze the computed tomography (CT) and magnetic resonance imaging(MRI) characteristics of hepatic epithelioid hemangioendothelioma (HEHE).MethodsEleven patients with histopathologically confirmed HEHE via surgical excision or biopsy were included. Imaging findings of these 11 patients were retrospectively analyzed (CT images obtained from all patients and MR images from five patients). Patterns of growth, characteristics of distribution, density/signal features, patterns of contrast enhancement, and changes of adjacent tissues were evaluated.ResultsHEHE is characterized by multiple lesions in the liver. HEHE could be further categorized as three types when considering patterns of growth: nodular type(5 cases), coalescent type(1 case) and mixed type(5 cases). In this study, a total of 312 lesions were detected, 214(74.3 %) of which were subcapsular. All lesions appeared as hypodense while round lower density were found within 10 lesions(<2 cm) on unenhanced CT images. On MRI, all lesions demonstrated low signal intensity on T1 weighted images and high heterogeneous signal intensity on T2 weighted images when compared to the normal liver parenchyma. Other imaging features included “lollipop sign”(6 cases) and capsular retraction(6 cases). On contrast-enhanced CT and MRI, lesions smaller than 2.0 cm mostly showed mild homogeneous enhancement (214/227, 94.3 %); lesions measuring 2.0–3.0 cm in diameter showed ring-like enhancement (16/53,30.2 %) and heterogeneous delayed enhancement (29/53,54.7 %); lesions larger than 3.0 cm demonstrated heterogeneous delayed enhancement (26/32, 81.3 %).ConclusionThe imaging findings of HEHE showed some typical imaging features and size-dependent patterns with contrast enhancement on both CT and MR images, these features can be used for accurate imaging diagnosis of HEHE.

BackgroundCerebral hypoperfusion is a pivotal risk factor for vascular dementia (VD), for which effective therapy remains inadequate. Persistent inflammatory responses and excessive chemotaxis of microglia/macrophages in the brain may accelerate the progression of VD. Endocannabinoids are involved in neuronal protection against inflammation-induced neuronal injury. Cannabinoids acting at cannabinoid receptor 2 (CB2R) can decrease inflammation. Based on the identification of paeoniflorin (PF) as a CB2R agonist, we investigated the neuroprotective and microglia/macrophages M1 to M2 polarization promoting effects of PF in a permanent four-vessel occlusion rat model.MethodsOne week after surgery, PF was intraperitoneally administered at a dose of 40 mg/kg once a day for 28 successive days. The effects of PF on memory deficit were investigated by a Morris water maze test, and the effects of PF on hippocampal neuronal damage were evaluated by light microscope and electron microscope. The mRNA and protein expression levels of key molecules related to the M1/M2 polarization of microglia/macrophages were assessed by RT-qPCR and Western blotting, respectively.ResultsAdministration of PF could significantly attenuate cerebral hypoperfusion-induced impairment of learning and memory and reduce the morphological and ultrastructural changes in the hippocampal CA1 region of rats. Moreover, PF promoted an M1 to M2 phenotype transition in microglia/macrophages in the hippocampus of rats. In addition to its inhibitory property against proinflammatory M1 mediator expression, such as IL-1β, IL-6, TNF-α and NO, PF dramatically up-regulated expression of anti-inflammatory cytokines IL-10 and TGF-β1. Importantly, CB2R antagonist AM630 abolished these beneficial effects produced by PF on learning, memory and hippocampus structure in rats, as well as the polarization of microglia/macrophages to the M2 phenotype. Additionally, PF treatment significantly inhibited cerebral hypoperfusion-induced mTOR/NF-κB proinflammatory pathway and enhanced PI3K/Akt anti-inflammatory pathway. Effects of PF on these signaling pathways were effectively attenuated when rats were co-treated with PF and AM630, indicating that the mTOR/NF-κB and PI3K/Akt signaling pathways were involved in the PF effects through CB2R activation.ConclusionThese findings demonstrated PF exerts its neuroprotective effect and shifts the inflammatory milieu toward resolution by modulation of microglia/macrophage polarization via CB2R activation.Electronic supplementary materialThe online version of this article (10.1186/s13020-018-0173-1) contains supplementary material, which is available to authorized users.