胸主动脉夹层相关的危险因素认识现状

胸主动脉夹层是一种病情变化快的灾难性疾病,其特点是发病急、病情复杂、急诊诊断困难、进展迅速、误诊率高、病死率高、易引起医疗纠纷.即便如此,形成胸主动脉夹层详细的原因还不明确,许多危险因素与胸主动脉夹层的发生有关,包括高血压、性别(男性)、主动脉的正常老化、吸食毒品、动脉粥样硬化、遗传性疾病和炎性疾病等.     

Fish-oil emulsion (omega-3 polyunsaturated fatty acids) attenuates acute lung injury induced by intestinal ischemia–reperfusion through Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 pathway

Background

Activated macrophage infiltration into the lungs is paramount in the pathogenesis of acute lung injury (ALI) induced by intestinal ischemia–reperfusion (I/R). Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a potent activator of the Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 (AMPK/SIRT1) pathway against macrophage inflammation. We aimed to evaluate whether ω-3 PUFAs may protect against ALI induced by intestinal I/R via the AMPK/SIRT1 pathway.

Methods

Ischemia in male Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of fish-oil emulsion (FO emulsion, containing major ingredients as ω-3 PUFAs) or normal saline (control) was administered by intraperitoneal injection for three consecutive days to each animal. All animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analysis.

Results

Intestinal I/R caused intestinal and lung injury, evidenced by severe lung tissue edema and macrophage infiltration. Pretreatment with FO emulsion improved the integrity of microscopic structures in the intestine and lungs. Intestinal I/R induced the expression of macrophage-derived mediators (macrophage migration inhibitory factor and macrophage chemoattractant protein-1), inflammatory factors (nuclear factor κB, tumor necrosis factor α, interleukin 6, and interleukin 1β), and proapoptosis factor p66shc. There was a decrease in the expression of AMPK, SIRT1, and claudin 5. FO emulsion significantly inhibited macrophage infiltration into the lungs, inflammatory factor expression, and p66shc phosphorylation. Importantly, FO emulsion restored AMPK, SIRT1, and claudin 5 in the lungs.

Conclusions

Pretreatment with ω-3 PUFAs effectively protects intestinal and lung injury induced by intestinal I/R, reduces macrophage infiltration, suppresses inflammation, inhibits lung apoptosis, and improves the lung endothelial barrier after intestinal I/R in a manner dependent on AMPK/SIRT1. Thus, there is a potential for developing AMPK/SIRT1 as a novel target for patients with intestinal I/R–induced ALI.     

The interaction between Toll-like receptor 4 signaling pathway and hypoxia-inducible factor 1α in lung ischemia–reperfusion injury

Background

Lung ischemia–reperfusion injury (LIRI) is the life-threatening complication occurring after lung transplantation. Toll-like receptor 4 (TLR4) signaling pathway and hypoxia-inducible factor-1α (HIF-1α) are intimately involved in the development and progression of various inflammatory and hypoxia diseases; however, the relationship of them in LIRI in vivo is still far from clear.

Materials and methods

Forty-five Sprague–Dawley rats were randomly distributed in nine groups: (1) Sham group, (2) LIRI group, (3) LIRI + saline control group, (4) LIRI + dimethyl Sulfoxide control group, (5) LIRI + lipopolysaccharide group, (6) LIRI + TAK-242 group (TAK-242 is a TLR4 inhibitor, ethyl (6R)-6- [N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate), (7) LIRI + thioredoxin group (thioredoxin is an apoptosis signal–regulating kinase 1 (ASK1) inhibitor), (8) LIRI + SB203580 group (SB203580 is a p38 inhibitor), and (9) LIRI + chetomin group (chetomin is a HIF-1α inhibitor). The interaction between TLR4 signaling pathway (including TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR-domain-containing adapter-inducing interferon-β (TRIF), ASK1, and p38) and HIF-1α and the role of TLR4-dependent HIF-1α were analyzed.

Results

In LIRI, HIF-1α accumulation was induced in a TLR4-dependent fashion, and MyD88, but not TRIF, and activation of ASK1 and p38 were found to be critical for TLR4-mediated HIF-1α accumulation. HIF-1α protein played a critical role in TLR4-mediated lung injury of LIRI (including inflammation, cell apoptosis, and lung damage). HIF-1α protein upregulated TLR4 expression of LIRI in a positive feedback manner.

Conclusions

We identify that the TLR4-HIF-1 loop may be existed in LIRI. Therefore, we suggest that the interaction between them may represent a novel therapeutic target for the development of novel target-based therapies of LIRI.     

Targeted thrombolysis strategies for neuroprotective effect

Stroke is usually treated by systemic thrombolytic therapy if the patient presents within an appropriate time window. There is also widespread interest in the development of thrombolytic agents that can be used in cases of delayed presentation. Current agents that can be used in cases of delayed presentation of nerve damage by thrombus. Current systemic thrombolytic therapy is associated with adverse effects such as fibrinogenolysis and bleeding. In an attempt to increase the efficacy, safety, and specificity of thrombolytic therapy, a number of targeted thrombolytic agents have been studied in recent years. This review focuses on the concepts underlying targeted thrombolytic therapy and describes recent drug developments in this field.     

Cognitive empathy modulates the processing of pragmatic constraints during sentence comprehension

Previous studies have shown that brain regions for mentalizing, including temporoparietal junction (TPJ) and medial prefrontal cortex (mPFC), are activated in understanding the nonliteral meaning of sentences. A different set of brain regions, including left inferior frontal gyrus (IFG), is activated for dealing with pragmatic incongruence. Here we demonstrate that individuals’ cognitive empathic ability modulates the brain activity underlying the processing of pragmatic constraints during sentence comprehension. The lian … dou … construction in Chinese (similar to English even) normally describes an event of low expectedness; it also introduces a pragmatic scale against which the likelihood of an underspecified event can be inferred. By embedding neutral or highly likely events in the construction, we created underspecified and incongruent sentences and compared both with control sentences in which events of low expectedness were described. Imaging results showed that (i) left TPJ was activated for the underspecified sentences, and the activity in mPFC correlated with individuals’ fantasizing ability and (ii) anterior cingulate cortex (ACC) was activated for the incongruent sentences, and the activity in bilateral IFG correlated with individuals’ perspective taking ability. These findings suggest that brain activations in making pragmatic inference and in dealing with pragmatic failure are modulated by different components of cognitive empathy.