共查询到20条相似文献,搜索用时 15 毫秒
1.
Laura Keglowich Michael Roth Maria Philippova Thérèse Resink Gavin Tjin Brian Oliver Didier Lardinois Sophie Dessus-Babus Reinoud Gosens Katrin Hostettler Haack Michael Tamm Peter Borger 《PloS one》2013,8(12)
Background
Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer. BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as an important source of inflammatory mediators and angiogenic factors.Objective
To compare the angiogenic potential of BSMC of asthmatic and non-asthmatic patients and to identify asthma-specific angiogenic factors.Methods
Primary BSMC were isolated from human airway tissue of asthmatic and non-asthmatic patients. Conditioned medium (CM) collected from BSMC isolates was tested for angiogenic capacity using the endothelial cell (EC)-spheroid in vitro angiogenesis assay. Angiogenic factors in CM were quantified using a human angiogenesis antibody array and enzyme linked immunosorbent assay.Results
Induction of sprout outgrowth from EC-spheroids by CM of BSMC obtained from asthma patients was increased compared with CM of control BSMC (twofold, p < 0.001). Levels of ENA-78, GRO-α and IL-8 were significantly elevated in CM of BSMC from asthma patients (p < 0.05 vs. non-asthmatic patients). SB 265610, a competitive antagonist of chemokine (CXC-motif) receptor 2 (CXCR2), attenuated the increased sprout outgrowth induced by CM of asthma patient-derived BSMC.Conclusions
BSMC isolated from asthma patients exhibit increased angiogenic potential. This effect is mediated through the CXCR2 ligands (ENA78, GRO-α and IL-8) produced by BSMC.Implications
CXCR2 ligands may play a decisive role in directing the neovascularization in the sub-epithelial cell layers of the lungs of asthma patients. Counteracting the CXCR2-mediated neovascularization by pharmaceutical compounds may represent a novel strategy to reduce airway remodelling in asthma. 相似文献2.
Background
Asthma is a chronic disease that is characterized by airway hyperresponsiveness and airway remodeling. The underlying mechanisms that mediate the pathological processes are not fully understood. Abl is a non-receptor protein tyrosine kinase that has a role in the regulation of smooth muscle contraction and smooth muscle cell proliferation in vitro. The role of Abl in airway hyperresponsiveness and airway remodeling in vivo is largely unknown.Methods
To evaluate the role of Abl in asthma pathology, we assessed the expression of Abl in airway tissues from the ovalbumin sensitized and challenged mouse model, and human asthmatic airway smooth muscle cells. In addition, we generated conditional knockout mice in which Abl expression in smooth muscle was disrupted, and then evaluated the effects of Abl conditional knockout on airway resistance, smooth muscle mass, cell proliferation, IL-13 and CCL2 in the mouse model of asthma. Furthermore, we determined the effects of the Abl pharmacological inhibitors imatinib and GNF-5 on these processes in the animal model of asthma.Results
The expression of Abl was upregulated in airway tissues of the animal model of asthma and in airway smooth muscle cells of patients with severe asthma. Conditional knockout of Abl attenuated airway resistance, smooth muscle mass and staining of proliferating cell nuclear antigen in the airway of mice sensitized and challenged with ovalbumin. Interestingly, conditional knockout of Abl did not affect the levels of IL-13 and CCL2 in bronchoalveolar lavage fluid of animals treated with ovalbumin. However, treatment with imatinib and GNF-5 inhibited the ovalbumin-induced increase in IL-13 and CCL2 as well as airway resistance and smooth muscle growth in animals.Conclusions
These results suggest that the altered expression of Abl in airway smooth muscle may play a critical role in the development of airway hyperresponsiveness and airway remodeling in asthma. Our findings support the concept that Abl may be a novel target for the development of new therapy to treat asthma. 相似文献3.
Background
Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response.Aims
The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells.Methods
Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells.Results
High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis.Conclusion
High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD. 相似文献4.
Cheryl V. Rahman Stuart J. Smith Paul S. Morgan Keith A. Langmack Phil A. Clarke Alison A. Ritchie Donald C. Macarthur Felicity R. Rose Kevin M. Shakesheff Richard G. Grundy Ruman Rahman 《PloS one》2013,8(10)
Introduction
Polymer-based delivery systems offer innovative intra-cavity administration of drugs, with the potential to better target micro-deposits of cancer cells in brain parenchyma beyond the resected cavity. Here we evaluate clinical utility, toxicity and sustained drug release capability of a novel formulation of poly(lactic-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) microparticles.Methods
PLGA/PEG microparticle-based matrices were molded around an ex vivo brain pseudo-resection cavity and analyzed using magnetic resonance imaging and computerized tomography. In vitro toxicity of the polymer was assessed using tumor and endothelial cells and drug release from trichostatin A-, etoposide- and methotrexate-loaded matrices was determined. To verify activity of released agents, tumor cells were seeded onto drug-loaded matrices and viability assessed.Results
PLGA/PEG matrices can be molded around a pseudo-resection cavity wall with no polymer-related artifact on clinical scans. The polymer withstands fractionated radiotherapy, with no disruption of microparticle structure. No toxicity was evident when tumor or endothelial cells were grown on control matrices in vitro. Trichostatin A, etoposide and methotrexate were released from the matrices over a 3-4 week period in vitro and etoposide released over 3 days in vivo, with released agents retaining cytotoxic capabilities. PLGA/PEG microparticle-based matrices molded around a resection cavity wall are distinguishable in clinical scanning modalities. Matrices are non-toxic in vitro suggesting good biocompatibility in vivo. Active trichostatin A, etoposide and methotrexate can be incorporated and released gradually from matrices, with radiotherapy unlikely to interfere with release.Conclusion
The PLGA/PEG delivery system offers an innovative intra-cavity approach to administer chemotherapeutics for improved local control of malignant brain tumors. 相似文献5.
Caio Cesar de Souza Alves Adam Collison Luke Hatchwell Maximilian Plank Matthew Morten Paul S. Foster Sebastian L. Johnston Cristiane Fran?a da Costa Mauro Vieira de Almeida Henrique Couto Teixeira Ana Paula Ferreira Joerg Mattes 《PloS one》2013,8(11)
Background
Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.Objective
To determine the anti-inflammatory potential of anthraquinones in-vivo.Methods
BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.Results
Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.Conclusion
Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT. 相似文献6.
Sylvia Moeckel Katharina Meyer Petra Leukel Fabian Heudorfer Corinna Seliger Christina Stangl Ulrich Bogdahn Martin Proescholdt Alexander Brawanski Arabel Vollmann-Zwerenz Markus J. Riemenschneider Anja-Katrin Bosserhoff Rainer Spang Peter Hau 《PloS one》2014,9(9)
Background
High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.Methods
In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a) to enrich specimens for brain tumor initiating cells and (b) to confront cells with a therapeutic agent before expression profiling.Results
As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.Conclusion
For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis. 相似文献7.
Ilona Rousalova Sulagna Banerjee Veena Sangwan Kristen Evenson Joel A. McCauley Robert Kratzke Selwyn M. Vickers Ashok Saluja Jonathan D’Cunha 《PloS one》2013,8(10)
Background
Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear.Methods
Cell viability was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections. Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA, APAF-1) was estimated by qRTPCR. Effect of Minnelide on proliferative cells in the tissue was estimated by Ki-67 staining of animal tissue sections.Results
In this study, we investigated in vitro and in vivo antitumor effects of triptolide/Minnelide in non-small cell lung carcinoma (NSCLC). Triptolide/Minnelide exhibited anti-proliferative effects and induced apoptosis in NSCLC cell lines and NSCLC mouse models. Triptolide/Minnelide significantly down-regulated the expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulated pro-apoptotic APAF-1 gene, in part, via attenuating the NF-κB signaling activity.Conclusion
In conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC. 相似文献8.
Hironori Kusano Jun Akiba Sachiko Ogasawara Sakiko Sanada Makiko Yasumoto Masamichi Nakayama Keiko Ueda Kosuke Ueda Takashi Kurita Keita Todoroki Yumi Umeno Osamu Nakashima Hirohisa Yano 《PloS one》2013,8(12)
Purpose
We investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells.Methods
The effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0–4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined.Results
PEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 μg/kg, 0.06 μg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control.Conclusions
Although in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC. 相似文献9.
10.
Background
Several human malignancies are associated with Epstein-Barr virus (EBV) and more than 95% of the adult human population carries this virus lifelong. EBV efficiently infects human B cells and persists in this cellular compartment latently. EBV-infected B cells become activated and growth transformed, express a characteristic set of viral latent genes, and acquire the status of proliferating lymphoblastoid cell lines in vitro. Because EBV infects only primate cells, it has not been possible to establish a model of infection in immunocompetent rodents. Such a model would be most desirable in order to study EBV''s pathogenesis and latency in a suitable and amenable host.Methodology/Principal Findings
We stably introduced recombinant EBV genomes into mouse embryonic stem cells and induced their differentiation to B cells in vitro to develop the desired model. In vitro differentiated murine B cells maintained the EBV genomes but expression of viral genes was restricted to the latent membrane proteins (LMPs). In contrast to human B cells, EBV''s nuclear antigens (EBNAs) were not expressed detectably and growth transformed murine B cells did not arise in vitro. Aberrant splicing and premature termination of EBNA mRNAs most likely prevented the expression of EBNA genes required for B-cell transformation.Conclusions/Significance
Our findings indicate that fundamental differences in gene regulation between mouse and man might block the route towards a tractable murine model for EBV. 相似文献11.
Vicente Plaza David Ramos-Barbón Ana María Mu?oz Ana María Fortuna Astrid Crespo Cristina Murio Rosa Palomino 《PloS one》2013,8(10)
Background
The measurement of fractional nitric oxide concentration in exhaled breath (FeNO), a noninvasive indicator of airway inflammation, remains controversial as a tool to assess asthma control. Guidelines currently limit asthma control assessment to symptom and spirometry based appraisals such as the Asthma Control Questionnaire-7 (ACQ-7). We aimed at determining whether adding FeNO to ACQ-7 improves current asthma clinical control assessment, through enhanced detection of not well controlled asthma.Methods
Asthmatic subjects, classified as not well controlled as per ACQ-7 on regular clinical practice, were included in a prospective, multicenter fashion, and had their maintenance treatment adjusted on visit 1. On follow-up (visit 2) four weeks later, the subjects were reevaluated as controlled or not well controlled using ACQ-7 versus a combination of FeNO and ACQ-7.Results
Out of 381 subjects enrolled, 225 (59.1%) had not well controlled asthma on visit 2 as determined by ACQ-7, and 264 (69.3%) as per combined FeNO and ACQ-7. The combination of FeNO to ACQ-7 increased by 14.8% the detection of not well controlled asthma following maintenance therapy adjustment.Conclusions
The addition of FeNO to ACQ-7 increased the detectability of not well controlled asthma upon adjustment of maintenance therapy. Adding a measure of airway inflammation to usual symptom and spirometry based scores increases the efficacy of current asthma clinical control assessment. 相似文献12.
Kyoung-Nam Kim Jin Hee Kim Ho-Jang Kwon Soo-Jong Hong Byoung-Ju Kim So-Yeon Lee Yun-Chul Hong Sanghyuk Bae 《PloS one》2014,9(10)
Background
Although the effect of bisphenol A on various health outcomes has been extensively examined, few studies have investigated its effect on asthma.Objective
We hypothesized that exposure to bisphenol A in school-age children was associated with wheezing and asthma.Methods
Participants included 127 children aged 7–8 years without a previous asthma diagnosis in an elementary school in Seoul, Korea. Three surveys were conducted, each 2 years apart. Bisphenol A concentration was measured at the baseline survey, and PC20, which is defined as the methacholine concentration that induces a decrease in FEV1 of 20% from baseline, was measured at every survey. Associations between bisphenol A concentration at 7–8 years of age and wheezing, asthma, and PC20 at ages up to 11–12 years were examined using generalized estimating equations, a marginal Cox regression model, and a linear mixed model.Results
The log-transformed creatinine-adjusted urinary bisphenol A concentration at 7–8 years was positively associated with wheezing (odds ratio, 2.48; 95% confidence interval, 1.15–5.31; P = .02) and asthma (hazard ratio, 2.13; 95% confidence interval, 1.51–3.00; P<.001) at ages up to 11–12 years. Bisphenol A was also negatively associated with PC20 (ß = −2.33; P = .02). When stratified by sex, the association between bisphenol A and asthma remained significant only in girls (hazard ratio, 2.45; 95% confidence interval, 2.18–2.76; P<.001).Conclusion
Increased urinary bisphenol A concentrations at 7–8 years old were positively associated with wheezing and asthma and negatively associated with PC20 at ages up to 11–12 years. 相似文献13.
John Axelsson Javaid-ur Rehman Torbjorn Akerstedt Rolf Ekman Gregory E. Miller Caroline Olgart H?glund Mats Lekander 《PloS one》2013,8(12)
Background
Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion.Methods
Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 – 07.00 h) followed by 5 days with restricted sleep (03.00 – 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed.Results
5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p’s<.05). In addition, all variables varied across the 24 h day.Conclusions
5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences. 相似文献14.
Lau JY Oliver BG Baraket M Beckett EL Hansbro NG Moir LM Wilton SD Williams C Foster PS Hansbro PM Black JL Burgess JK 《PloS one》2010,5(10):e13360
Background
The extracellular matrix is a dynamic and complex network of macromolecules responsible for maintaining and influencing cellular functions of the airway. The role of fibronectin, an extracellular matrix protein, is well documented in asthma. However, the expression and function of fibulin-1, a secreted glycoprotein which interacts with fibronectin, has not been reported. Fibulin-1 is widely expressed in basement membranes in many organs including the lung. There are four isoforms in humans (A–D) of which fibulin-1C and 1D predominate. The objective of this study was to study the expression of fibulin-1 in volunteers with and without asthma, and to examine its function in vitro.Methodology/Principal Findings
We used immunohistochemistry and dot-blots to examine fibulin-1 levels in bronchial biopsies, bronchoalveolar lavage fluid and serum. Real-time PCR for fibulin-1C and 1D, and ELISA and western blotting for fibulin-1 were used to study the levels in airway smooth muscle cells. The function of fibulin-1C was determined by assessing its role, using an antisense oligonucleotide, in cell proliferation, migration and wound healing. A murine model of airway hyperresponsiveness (AHR) was used to explore the biological significance of fibulin-1. Levels of fibulin-1 were significantly increased in the serum and bronchoalveolar lavage fluid of 21 asthmatics compared with 11 healthy volunteers. In addition fibulin-1 was increased in asthma derived airway smooth muscle cells and fibulin-1C contributed to the enhanced proliferation and wound repair in these cells. These features were reversed when fibulin-1C was suppressed using an antisense oligomer. In a mouse model of AHR, treatment with an AO inhibited the development of AHR to methacholine.Conclusions
Our data collectively suggest fibulin-1C may be worthy of further investigation as a target for airway remodeling in asthma. 相似文献15.
Background
Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR).Methods
Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro.Results
Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro.Conclusion
Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. 相似文献16.
Xiao-yuan Liu Li Zhang JianPing Wu Lei Zhou Yi-Jie Ren Wei-Qiong Yang Zi-Jun Ming Bo Chen Jianrong Wang Yi Zhang Jin-Ming Yang 《PloS one》2013,8(11)
Background
Glioblastoma multiforme (GBM), the most common form of brain cancer with an average survival of less than 12 months, is a highly aggressive and fatal disease characterized by survival of glioma cells following initial treatment, invasion through the brain parenchyma and destruction of normal brain tissues, and ultimately resistance to current treatments. Temozolomide (TMZ) is commonly used chemotherapy for treatment of primary and recurrent high-grade gliomas. Nevertheless, the therapeutic outcome of TMZ is often unsatisfactory. In this study, we sought to determine whether eEF-2 kinase affected the sensitivity of glioma cells to treatment with TMZ.Methodology/Principal Findings
Using RNA interference approach, a small molecule inhibitor of eEF-2 kinase, and in vitro and in vivo glioma models, we observed that inhibition of eEF-2 kinase could enhance sensitivity of glioma cells to TMZ, and that this sensitizing effect was associated with blockade of autophagy and augmentation of apoptosis caused by TMZ.Conclusions/Significance
These findings demonstrated that targeting eEF-2 kinase can enhance the anti-glioma activity of TMZ, and inhibitors of this kinase may be exploited as chemo-sensitizers for TMZ in treatment of malignant glioma. 相似文献17.
Background
Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure. Oxidative stress, apoptosis and inflammation play crucial roles in CIN. Renalase is a newly discovered monoamine oxidase from the kidney. We hypothesize that renalase could protect against CIN through anti-oxidation, anti-inflammation and anti-apoptosis pathways.Methods
We tested our hypothesis in vivo with a rat model of Ioversol-induced CIN and in vitro. Sprague-Dawley rats were divided into 4 groups (n = 6 per group): control group, Ioversol group (rats subjected to Ioversol-induced CIN), Ioversol plus vehicle group (CIN rats pretreated with vehicle) and Ioversol plus renalase group (CIN rats pretreated with 2 mg/kg recombinant renalase). HK2 cells were treated with Ioversol or H2O2.Results
The results showed that pretreatment with renalase attenuated the deterioration of renal function, tubular necrosis, oxidative stress, apoptosis and inflammation (P<0.05). Furthermore, renalase protected HK2 cells against the cytotoxicity of Ioversol and suppressed Caspase-3 activity, oxidative stress and apoptosis induced by H2O2.Conclusion
Recombinant renalase protected CIN in rats through anti-oxidation, anti-apoptosis and anti-inflammation mechanisms. 相似文献18.
Peng Lu Marie-Chantal Struijs Jiaping Mei Janneke Witte-Bouma Anita M. Korteland-van Male Adrianus C. J. M. de Bruijn Johannes B. van Goudoever Ingrid B. Renes 《PloS one》2013,8(10)
Background
Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) play important roles in chronic intestinal inflammation. Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants and is characterized by acute intestinal inflammation and necrosis. The objective of the study is to investigate the role of ER stress and the UPR in NEC patients.Methods
Ileal tissues from NEC and control patients were obtained during surgical resection and/or at stoma closure. Splicing of XBP1 was detected using PCR, and gene expression was quantified using qPCR and Western blot.Results
Splicing of XBP1 was only detected in a subset of acute NEC (A-NEC) patients, and not in NEC patients who had undergone reanastomosis (R-NEC). The other ER stress and the UPR pathways, PERK and ATF6, were not activated in NEC patients. A-NEC patients showing XBP1 splicing (A-NEC-XBP1s) had increased mucosal expression of GRP78, CHOP, IL6 and IL8. Similar results were obtained by inducing ER stress and the UPR in vitro. A-NEC-XBP1s patients showed altered T cell differentiation indicated by decreased mucosal expression of RORC, IL17A and FOXP3. A-NEC-XBP1s patients additionally showed more severe morphological damage and a worse surgical outcome. Compared with A-NEC patients, R-NEC patients showed lower mucosal IL6 and IL8 expression and higher mucosal FOXP3 expression.Conclusions
XBP1 splicing, ER stress and the UPR in NEC are associated with increased IL6 and IL8 expression levels, altered T cell differentiation and severe epithelial injury. 相似文献19.