Background/Aims: To explore the protective effect of curcumin on renal ischemia-reperfusion injury (RIRI) in rats, and its influence on nephridial tissue’s NO and cGMP levels as well as downstream signaling pathway, to elucidate the possible mechanism of curcumin on RIRI. Methods: 36 Sprague Dawley rats (SD rats) were randomly divided into Sham group, Model group, curcumin (CUR +) Model group, 12 rats per group. They were all given RIRI model preparation by unilateral artery occlusion method. All groups’ β2-MG in urine in 24h, serum Cr and BUN were compared, and UAER were calculated. Nitric oxide synthase (NOS), cGMP-dependent protein kinase (PKG), Caspase-3 expression were all determined by western blot. Nitric oxide (NO), NOS and cGMP levels were also examined by using ELISA. All groups’ nephridial histomorphology and kidney tubules score were evaluated and compared. Results: β2-MG and UAER in urine, serum Cr and BUN, in renal tissue were all elevated in Model of RIRI, indicating the success of animal model of RIRI establishment, and above index in CUR + Model group were all lower than those in Model group. Furthermore, iNOS, NO, cGMP, PKG and Caspase-3 in renal tissue were all increased in Model of RIRI, indicating the NO signaling pathway was activated, which is one of the pathogenesis of RIRI, and above index in CUR + Model group were all lower than those in Model group, suggesting that inactivation of iNOS/NO/cGMP/PKG signaling pathway is one of the reasons that explain the protective effect of curcumin in RIRI. Conclusion: The activation of iNOS/NO/cGMP/PKG signaling pathway and the consequent promoted apoptosis of renal tubules are significantly involved in the pathogenesis of development of RIRI, and curcumin treatment could protect renal tubules against RIRI, at least partially, by suppressing the activated iNOS/NO/cGMP/PKG signaling pathway.

BackgroundThis study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats.MethodsExpression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were tested by QT-PCR and Western blot, and levels of 5-hydroxytryptamine (5-HT), KYN, TRY, 3-hydroxykynurenine (3-HK), and kynurenic acid (KA) in different brain regions were estimated using HPLC. Effects of the IDO direct inhibitor 1-methyl-l-tryptophan (1-MT) on cognitive, anxiety, and depressive-like behavior were evaluated in bile duct ligation (BDL) rats.ResultsIncreased serum TNF-α, IL-1β, and IL-6 levels were shown in rats 7 days after BDL, and these increases were observed earlier than those in the brain, indicating peripheral immune activation may result in central upregulation of proinflammatory cytokines. Moreover, BDL rats showed a progressive decline in memory formation, as well as anxiety and depressive-like behavior. Further study revealed that IDO expression increased after BDL, accompanied by a decrease of 5-HT and an increase of KYN, as well as abnormal expression of 3-HK and KA. The above results affected by BDL surgery were reversed by IDO inhibitor 1-MT treatment.ConclusionTaken together, these findings indicate that (1) behavioral impairment in BDL rats is correlated with proinflammatory cytokines; (2) TRY pathway of KYN metabolism, activated by inflammation, may play an important role in HE development; and (3) 1-MT may serve as a therapeutic agent for HE.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1037-9) contains supplementary material, which is available to authorized users.

BackgroundAcute lung injury (ALI) is a life-threatening clinical syndrome without effective treatment. Targeting delivery of glucocorticoid to lung shows potential efficacy for ALI based on their anti-inflammatory and anti-fibrotic properties, breaking through their clinical application limitation due to systemic side effects. This work was aimed to establish lung-targeted dexamethasone (DEX) loaded nanostructured lipid carriers (NLCs) with opposite surface charge and investigate their therapeutic effects on lipopolysaccharide (LPS)-induced ALI mice.ResultsThe diameter of anionic anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody-conjugated DEX-loaded NLCs (ICAM/DEX/NLCs) and the cationic ones with octadecylamine (ODA) modification (ICAM/DEX/ODA-NLCs) was about 249.9 and 235.9 nm. The zeta potential of ICAM/DEX/NLCs and ICAM/DEX/ODA-NLCs was about − 30.3 and 37.4 mV, respectively. Relative to the non-targeted control and ICAM/DEX/ODA-NLCs, ICAM/DEX/NLCs exhibited higher in vitro cellular uptake in LPS-activated human vascular endothelial cell line EAhy926 after CAM-mediated endocytosis, and stronger in vivo pulmonary distribution in the ALI model mice. In vivo i.v. administration of ICAM/DEX/NLCs significantly attenuated pulmonary inflammatory cells infiltration, and the production of pro-inflammatory cytokine TNF-α and IL-6 in ALI mice. H&E stain also revealed positive histological improvements by ICAM/DEX/NLCs.ConclusionsICAM/DEX/NLCs may represent a potential pulmonary endothelium targeted device, which facilitate translation of DEX into clinical ALI treatment.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0431-5) contains supplementary material, which is available to authorized users.

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: This study investigated the protective effect of Curcumin on renal ischemia-reperfusion injury (RIRI) as well as the mechanisms underlying the role of Curcumin. Selectivity of Curcumin in kidney in different doses and routes of administration was measured. In addition, the serum levels of β2-MG, UAER, BUN and creatinine were compared among the Sham, the RIRI model and the Curcumin + RIRI model groups. The expression of miR-146a iNOS, eNOS and nNOS, PKG, and caspase-3 among various groups was measured using real-time PCR and Western-blot analysis, while the levels of NO and cGMP in the samples were measured by ELISA. Finally, the effect of Curcumin on the transcriptional efficiencies of miR-146a, nNOS, eNOS and iNOS was studied using luciferase assay. The presence of mesoscale nanoparticles (MNPs) in the kidneys was safe. In addition, the accumulation of MNPs was in a dose-dependent manner and peaked at a dose of 25 mg/kg. The administration of Curcumin reduced the levels of serum β2-MG, UAER, BUN, creatinine as well as the score of renal tubule damage, therefore alleviating the symptoms induced by RIRI. Furthermore, the RIRI model group showed serious congestion and edema in the renal cortex and medulla, whereas the Curcumin + RIRI model group exhibited less renal tissue damage compared with that in the RIRI model group. Moreover, Curcumin enhanced miR-146a expression, while reducing the expression of nNOS, iNOS, cGPM, caspase-3 and PKG as well as the synthesis of NO. Curcumin may exert its effect by reducing the transcriptional efficiency of iNOS promoter, while increasing the transcriptional efficiency of miR-146a promoter. Furthermore, nNOS expression was negatively regulated by miR-146a. The protective effect of Curcumin against RIRI may be mediated by its regulation of cell apoptosis through the miR-146a/nNOS/NO/cGMP/PKG signaling pathway.

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The image resolution is the most important performance parameter for an aerial optoelectronic sensor. Existing thermal control methods cannot eliminate the sensor’s temperature gradient, making the image resolution difficult to further improve. This article analyzes the different impacts of temperature changes on the imaging resolution and proposes modifications. Firstly, the sensor was subjected to thermo-optical simulation by means of finite element analysis, and the different impacts of temperature changes on the imaging quality were analyzed. According to the simulation results, an active thermal control method is suggested to enhance the temperature uniformity of the sensor. Considering the impacts of active and passive thermal control measures, thermal optical analysis was carried out to predict the performance of the sensor. The results of the analysis show that the imaging quality of the sensor has been significantly improved. The experimental results show that the image resolution of the optoelectronic sensor improved from 47 to 59 lp/mm, which demonstrates that the sensor can produce a high image quality in a low-temperature environment.

In order to ensure the imaging performance of the aerial optoelectronic platform system in low temperature environment, an active-passive combined thermal control technology was studied. A thermal control finite element model of the aerial optoelectronic platform was established. Additionally, thermal control simulation analysis and experiments under extreme conditions were carried out respectively. The simulation and experimental results showed that the temperature level of the primary mirror is improved above 25 °C by the proposed thermal control technology effectively, meanwhile the temperature gradient of the primary and secondary mirrors are less than 5 °C. The successful implementation of this active-passive combined thermal control technology provides a technical support for the precision thermal control of aerial optoelectronic platforms.