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In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI. Acute lung injury (ALI) is a critically severe, life-threatening condition in ICU, characterized by high mortality of approximately 40% 1 . ALI, along with its more severe form, acute respiratory distress syndrome, often results from a massive insult to the lung, whether be the direct alveolar infiltration or the indirect effects of systemic inflammatory response syndrome or multiple organ dysfunction syndromes 2 . An effective treatment of this life-threatening disorder calls for a better understanding of the molecular pathophysiology of ALI. The intestine is recognized to be one of the largest immune barrier systems and to be the source of bacteria and endotoxins in the body 3 . Previous reports indicate that the intestinal organ plays a crucial role in the development of ALI 4 . Mesenteric artery ischemia, a commonly seen critical state during small bowel transplantation or trauma, may lead to intestinal ischemia/reperfusion (I/R) injury. During the process of intestinal I/R injury, local bacteria overgrow and translocate, gastrointestinal mobility decreases, and mucosal permeability increases, all of which subsequently lead to the local intestine damage or distant lung injuries through the activation of systemic inflammatory response syndrome or multiple organ dysfunction syndromes 5,6 . Intestinal I/R is, therefore, a useful model for the investigation of pathophysiological mechanism of indirect ALI. Fenofibrate is known as an agonist of the peroxisome proliferator-activated receptor -α (PPARα ), the nuclear receptor superfamily member 7 . As a nuclear receptor activator, fenofibrate up-regulates or down-regulates genes that are involved in many pathophysiological processes, such as oxidative stress, inflammation, and leukocyte endothelium interactions 8, 9 . Recent studies have demonstrated an anti-oxidant, anti-inflammatory, and anti-ischemic role of fenofibrate to attenuate I/R injury in kidney 10,11 , liver 12 , brain 13,14 and heart 15 . But to date there are no literatures reporting the protective effects of fenofibrate in I/R injury in the organ of intestine. Moreover, the functional significance of fenofibrate in the intestinal I/R-induced ALI remains unclear. Therefore, this experiment is aimed to investigate whether fenofibrate administration would ameliorate the lung injury and inflammation in the model of intestinal I/R injury. Animals. The male C57BL/6 mice (8-10-wk-old; 20 ± 2 g) were purchased from Charles River (Beijing, China). Mice were kept in a temperature (21 ± 2 °C) and humidity (60 ± 5%) controlled room on a 12-hour light/dark cycle. They were fed a standard mice chow and water ad liblitum. All experiments were performed in accordance with the Declaration of Helsinki and were approved by the Institutional Animal Ethical Committee of the Peking Union Medical College Hospital.
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Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice OPEN


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We previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, however, improving neurological function. The clinical use of EPO has been cautioned most recently due to serious safety concerns arising from an increased mortality in acute stroke patients treated with EPO and simultaneously receiving systemic thrombolysis [2]. Carbamylated EPO (cEPO) is an EPO derivative without erythropoietic activity and devoid of the EPO side eff ects, but with apparently well maintained cytoprotective qualities [3]. We therefore tested the hypothesis whether cEPO may be equally effi cient as EPO in reducing morphological as well as functional aortic occlusion-induced spinal cord I/R injury. Methods In a randomized and blinded trial pigs received either vehicle (control, n = 9), EPO or cEPO, respectively (n = 9 each; 5,000 IU/kg over 30 minutes before and during the fi rst 4 hours of reperfusion). Animals underwent 30 minutes of thoracic aortic balloon occlusion with catheters placed immediately downstream of the A. subclavia and upstream of the aortic trifurcation. Spinal cord function was assessed by motor evoked potentials (MEP as percentage of the amplitude before aortic occlusion) and lower limb refl exes (assessed as the subjective strength of response) for a period of 10 hours after reperfusion. Tissue damage was evaluated using Nissl staining. Results Both EPO-treated and cEPO-treated animals presented with attenuated spinal cord injury in the Nissl staining (median (quartile) percentage of damaged neurons in the thoracic segments: control 27 (25,44), cEPO 8 (4,10), and EPO 5 (5,7), P <0.001 vs control group; in the lumbar segments: control 26 (19,32), cEPO 7 (5,13), EPO 8 (5,10), P <0.001 vs control group). However, while only cEPO treatment was associated with recovery of the MEP amplitude to pre-occlusion values when compared with the control group (P <0.05), lower limb refl ex response was comparably restored stronger in both treatment groups (P <0.05 vs control). Conclusions In a clinically relevant porcine model mimicking aortic crossclamping during vascular surgery repair of thoracic aortic aneurysm, cEPO protected spinal cord function and integrity as eff ective as EPO when applied at equipotent doses. Acknowledgements Supported by the Deutsche Forschungs gemeinschaft (SCHE 899/2-2). Figure 1 (abstract P2). Phenylbutyrate reduced the unfolded protein response. Introduction In awake, spontaneously breathing mice, inhaling hydrogen sulfi de (H 2 S) induced a hibernation-like metabolic state characterised by reduced energy expenditure and hypothermia [1], which protected against otherwise lethal hypoxia [2] and hemorrhage [3] as a result of impaired cellular energy metabolism [4]. Therefore, we investigated the metabolic eff ects of inhaled H 2 S in our model of resuscitated murine septic shock. Methods Sixteen hours after induction of sepsis by cecal ligation and puncture (CLP) or sham operation, anesthetized and mechanically ventilated mice received 100 ppm H 2 S or vehicle over 5 hours at body temperatures of 38 and 27°C, respectively. During the observation period, hyperdynamic hemodynamics were maintained by colloid resuscitation and noradrenaline infusion [5]. Endogenous glucose production was calculated from blood 13 C6-glucose isotope enrichment derived from the rate of appearance of stable, non-radioactive labeled 1,2,3,4,5,6-13 C6 glucose during continuous isotope infusion [6]. Whole-body glucose oxidation rate was derived from the total CO 2 -production rate, the mixed expiratory 13 CO 2 / 12 CO 2 isotope ratio and the 13 C6-glucose infusion rate after the steady state was achieved. Results While endogenous glucose production was not aff ected by hypothermia, it was signifi cantly higher in the septic animals when compared with the corresponding sham operated groups, most likely due to the ongoing noradrenaline infusion. In contrast, despite the catecholamine infusion and higher glucose release, whole body glucose oxidation was signifi cantly reduced in normothermic septic animals. During hypothermia, H 2 S shifted substrate towards preferential glucose utilisation, but this eff ect disappeared in the septic mice. Conclusions H 2 S inhalation alone does not infl uence glucose metabolism once temperature is maintained at normothermic levels in anesthetised and mechanically ventilated mice. The H 2 S-related shift of energy metabo lism towards preferential carbohydrate oxidation present during hypothermia is blunted during sepsis, possibly as a result of the ongoing catecholamine treatment.
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P1 Comparison of carbamylated versus recombinant erythropoietin during spinal cord ischemia/reperfusion injury P2 Sodium 4-phenylbutylate protects against myocardial ischemia-reperfusion injury by reducing unfolded protein response-mediated apoptosis in mice P3 Time-dependent eff ects of intravenous H 2 S during long-term, resuscitated porcine hemorrhagic shock


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Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus. DMVs is why they exist in the first place. In this study, we looked at thousands of infected cells and identified two coronavirus mutants that made half as many organelles as normal and two others that made typical numbers but smaller organelles. Despite differences in DMV size and number, all four mutants replicated as efficiently as wild-type virus. To better understand the relative importance of replicative organelles, we carried out competitive fitness experiments. None of these viruses was found to be significantly less fit than wild-type, and two were actually fitter in tests in two kinds of cells. This suggests that viruses have evolved to have tremendous plasticity in the ability to form membraneassociated replication complexes and that large and numerous DMVs are not exclusively associated with efficient coronavirus replication. Citation Al-Mulla HMN, Turrell L, Smith NM, Payne L, Baliji S, Züst R, Thiel V, Baker SC, Siddell SG, Neuman BW. 2014. Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions. mBio 5(2):e01107-13.
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Competitive Fitness in Coronaviruses Is Not Correlated with Size or Number of Double-Membrane Vesicles under Reduced-Temperature Growth Conditions