CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice

Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+CD25+Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+CD25+ Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy

Bee Venom Mitigates Cisplatin-Induced Nephrotoxicity by Regulating CD4 +

Cisplatin is used as a potent anticancer drug, but it often causes nephrotoxicity. Bee venom (BV) has been used for the treatment of various inflammatory diseases, and its renoprotective action was shown in NZB/W mice. However, little is known about whether BV has beneficial effects on cisplatin-induced nephrotoxicity and how such effects might be mediated. In the present study, the BV-injected group showed a significant increase in the population of Tregs in spleen. Although there was no significant difference in the numbers of Tregs 3 days after cisplatin injection between the BV- and PBS-injected groups, more migration of Tregs into the kidney was observed 6 hours after cisplatin administration in BV group than in PBS group. In addition, BV-injected mice showed reduced levels of serum creatinine, blood urea nitrogen, renal tissue damage, proinflammatory cytokines, and macrophage infiltration into the kidney 3 days after cisplatin administration. These renoprotective effects were abolished by the depletion of Tregs. The anticancer effect of repeated administrations of cisplatin was not affected by BV injection. These results suggest that BV has protective effects on cisplatin-induced nephrotoxicity in mice, at least in part, through the regulation of Tregs without a big influence on the antitumor effects of cisplatin

Participation in the urban project : the cases of the ZAC Paris Rive Gauche in Paris and the Gwanghwamun Square in Seoul

Cette thèse porte sur l'analyse des pratiques participatives des deux projets, la ZAC Paris Rive Gauche à Paris, l'aménagement du Gwanghwamun Square à Séoul. Alors que la « participation » dans le projet urbain est souvent annoncée comme l'objectif idéal, ce terme laisse une marge de traduction à chaque personne qui l'utilise. Cette thèse a pour objectif de comprendre le rôle de participation dans la fabrication de l'espace. Nous entamons d'abord l'étude du déroulement de ces deux projets urbains et de ses acteurs pour montrer leur place dans la démarche du projet. Ensuite, nous analysons la structure des dispositifs participatifs et leur fonctionnement. Il s'agit d'étudier la place des citoyens dans le projet urbain qui apparaissent à travers ces dispositifs et le lien qu'ils nouent éventuellement avec les acteurs. Qui sont-ils ? Pour répondre à cette question, nous analysons les figures des citoyens qui émergent lors de la participation. Nous avons retenu trois critères : 1) l'intensité de la participation, 2) l'intérêt qu'ils portent au projet et à l'espace, 3) la reconnaissance des savoirs citoyens. À partir de cette analyse sur la figure des citoyens, nous étudions comment des citoyens peuvent revendiquer leur présence dans la démarche du projet, et être reconnus par les acteurs ou non. Ce processus implique la mise en cause de la légitimité du projet et de l'autorité déléguée des acteurs. Si les acteurs du projet résistent à la réduction de leur portée dans la démarche du projet, qu'apporte la présence des citoyens dans l'aménagement de l'espace et à l'action publique collective ? Notre recherche montre que la dynamique participative n'est pas totalement malléable, malgré les difficultés de la prise de place des citoyens dans le jeu d'acteurs et de la reconnaissance de celle-ci. Nous avons essayé d'identifier les conditions de participation comme la possibilité de modifier la configuration des échanges, le partage des savoirs et la formation pour la participationThis thesis focuses on the analysis of participatory practices of two urban projects - the ZAC Paris Rive gauche in Paris and the creation of Gwanghwamun Square in Seoul. “Participation” in the urban project is often announced as the ideal objective. Its signification is disputable. The object of this thesis is to understand the role of participation in the making of spaces. For this, we start by describing the progress of these two urban projects as well as their stakeholders, to clarify their position in the project process. Then, the structure of the participating organizations and their functions are analyzed. By doing so, the place of citizens in the urban project as it appears in their relations with these organizations and their relations themselves with the stakeholders will be examined. Who are they? We analyze the types of citizens who emerge through citizen participation. Three criteria are selected: 1) the intensity of participation, 2) participants' interests, 3) recognition of citizens' knowledge. From these criteria, we research how citizens can claim their presence in the project, and be recognized by the stakeholders or not. If the stakeholders of the project resist the weakening of their influence in the project process caused by participation, what can the presence of these citizens bring to the space and to the public collective action? Our research shows that the dynamics of participation are not totally malleable, in spite of the citizens' difficulties in taking their place among stakeholders, and the recognition of their place. This research identifies the conditions of participation as the possibility of modifying the discussion situation, the knowledge sharing, and the learning to participat

Paeonol, a Major Compound of Moutan Cortex, Attenuates Cisplatin-Induced Nephrotoxicity in Mice

Cisplatin is an effective chemotherapeutic agent that is used for the treatment of a variety of cancers; however, its nephrotoxicity limits the use of this drug. In the present study, we examined whether paeonol, a major compound of Moutan Cortex, has protective effects on cisplatin-induced acute renal failure in mice. To accomplish this, Balb/c mice (6 to 8 wk of age, weighing 20 to 25 g) were administered, Moutan Cortex (300 mg/kg) or paeonol (20 mg/kg) once a day. At day 4, mice received cisplatin (30, 20, or 10 mg/kg) intraperitoneally. The paeonol-treated group showed marked attenuation of serum creatine and blood urea nitrogen levels as well as reduced levels of proinflammatory cytokines and nitric oxide when compared to the control group. In addition, the paeonol-treated group showed prolonged survival and marked attenuation of renal tissue injury. Taken together, these results demonstrated that paeonol can prevent the renal toxic effects of cisplatin

Effects of Ag Nanoparticle Coated Metal Electrodes on Electrochemical CO2 Reduction in Aqueous KHCO3

Electrochemical CO2 reduction is crucial for developing a sustainable closed-carbon-cycle society; however, the factors determining product selectivity have not been fully established, especially when the reaction is carried out over metal cathodes. The selectivity of the CO2 reduction pathway can be improved by modifying the cathode’s catalyst surface. This can be achieved by using specific surface of single crystal or by alloying through the addition of an impurity. In this study, the products of electrochemical CO2 reduction were evaluated in an aqueous KHCO3 system at various applied currents and with various metal cathodes. The metal cathodes were coated by Ag nanoparticles, as the Ag cathode was determined to yield the best Faradaic efficiency for CO production in an aqueous KHCO3 system. Our results suggest that some Ag coated cathodes enhance CO2 reduction, and thus the reduction products are tunable through surface modification

CD4+CD25+ regulatory T cell depletion modulates anxiety and depression-like behaviors in mice.

Stress has been shown to suppress immune function and increase susceptibility to inflammatory disease and psychiatric disease. CD4(+)CD25(+) regulatory T (Treg) cells are prominent in immune regulation. This study was conducted to determine if anti-CD25 antibody (Ab) mediated depletion of Treg cells in mice susceptibility to stress-induced development of depression-like behaviors, as well as immunological and neurochemical activity. To accomplish this, an elevated plus-maze test (EPM), tail suspension test (TST), and forced swim test (FST) were used to examine depression-like behaviors upon chronic immobilization stress. Immune imbalance status was observed based on analysis of serum cytokines using a mouse cytometric bead array in conjunction with flow cytometry and changes in the levels of serotonin (5-HT) and dopamine (DA) in the brain were measured by high performance liquid chromatography (HPLC). The time spent in the open arms of the EPM decreased significantly and the immobility time in the FST increased significantly in the anti-CD25 Ab-treated group when compared with the non stressed wild-type group. In addition, interlukin-6 (IL-6), tumor necrosis factor-á (TNF-á), interlukin-2 (IL-2), interferon-gamma (IFN-γ), interlukin-4 (IL-4) and interlukin-17A (IL-17A) concentrations were significantly upregulated in the stressed anti-CD25 Ab-treated group when compared with the non stressed wild-type group. Furthermore, the non stressed anti-CD25 Ab-treated group displayed decreased 5-HT levels within the hippocampus when compared with the non stressed wild-type group. These results suggest that CD4(+)CD25(+) Treg cell depletion modulated alterations in depressive behavior, cytokine and monoaminergic activity. Therefore, controlling CD4(+)CD25(+) Treg cell function during stress may be a potent therapeutic strategy for the treatment of depression-like symptoms

Herbal Formula, PM014, Attenuates Lung Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD), which is characterized by airway obstruction, leads to, as the two major forms of COPD, chronic bronchitis and emphysema. This study was conducted to evaluate the effects of herbal formula, PM014, in a murine model of COPD. Balb/c mice were treated once with each herb extract in PM014 or PM014 mixture via an oral injection. Lipopolysaccharide (LPS) or elastase/LPS were administrated to the mice to induce a disease that resembles COPD. PM014 treatment significantly attenuated the increased accumulation of immune cells in bronchoalveolar lavage fluid (BALF) compared to control mice. In addition, the TNF-α and IL-6 levels in BALF were decreased in the PM014 mice. Furthermore, histological analysis demonstrated that PM014 attenuated the hazardous effects of lung inflammation. These data suggest that PM014 exerts beneficial effects against forms of COPD such as lung inflammation