Modulation of glutaredoxin-1 expression in a mouse model of allergic airway disease

Glutaredoxins (GRX) are antioxidant enzymes that preferentially catalyze the reduction of protein-glutathione mixed disulfides. The formation of mixed disulfides with GSH is known as S-glutathionylation, a post-translational modification that is emerging as an important mode of redox signaling. Since asthma is a disease that is associated with increased oxidative stress and altered antioxidant defenses, we investigated the expression of GRX in a murine model of allergic airway disease. Sensitization and challenge of C57BL/6 mice with ovalbumin resulted in increased expression of GRX1 mRNA, as well as increased amounts of GRX1 protein and total GRX activity in the lung. Because GRX1 expression is prominent in bronchial epithelium, we isolated primary epithelial cells from mouse trachea to investigate the presence of GRX. Primary tracheal epithelial cells were found to express both GRX1 and 2 mRNA and detectable GRX activity. Treatment with IFN-gamma increased the expression of GRX1 and overall GRX activity, resulting in attenuation of protein S-glutathionylation. In contrast, TGF-beta1 caused decreased GRX1 expression and overall GRX activity, leading to markedly enhanced protein S-glutathionylation. GRX1 joins the cadre of antioxidant defenses known to be modulated during allergic airway inflammation.     

一个男运动员的性腺机能低下与富含胡萝卜素饮食的关系(英文)

目的:报道了一个年轻男运动员大量摄入胡萝卜素后引发性腺机能低下的独特病例。病例报告:一名20岁的患者,在先前一年里坚持自己设计的高胡萝卜素、低动物脂肪的饮食,就诊时症状为肌肉逐渐萎缩、身体活动能力以及性欲减低、勃起功能下降。临床上,他表现出明显的胡萝卜素过量的体征:掌心和脚底都呈黄色。当他的饮食正常化二周后,胡萝卜素 B 值达到了正常范围的上限。方法:在恢复均衡饮食前和恢复均衡饮食3、6和12个月后,分别进行下丘脑、垂体和睾丸功能的重复刺激测试。结果:在均衡饮食数月后,促性腺激素和性腺类固醇由最初测得的非常低的基础值和刺激值逐渐恢复正常,并且胡萝卜素 B 值也有所恢复。诊断9—12个月后,荷尔蒙分泌物和性反应完全恢复。结论:这是第一个与摄入过量胡萝卜素有关的下丘脑式性腺机能低下的病例。     

Wound healing: immunological aspects

Wound healing is a complex biological process, comprised of a series of a sequential events aiming to repair injured tissue. The role of the immune system in this process is not only to recognise and combat the newly presented antigens at the site of injury, but also to participate in the debridement of the damaged area and to contribute to the process of healing. In this review, we discuss the molecules and cells of the immune system that participate in tissue repair. We describe the mechanisms of immune recognition during initial insult and the innate and adaptive immune responses to injury. Finally, we address the role of the immune system in regeneration and repair.     

Multidisciplinary therapy of locally far-advanced or inflammatory breast cancer with fixed perioperative sequence of epirubicin, vinorelbine, and Fluorouracil chemotherapy, surgery, and radiotherapy: long-term results

BACKGROUND: Based on phase II data in advanced breast cancer (BC), the fluorouracil, epirubicin, and vinorelbine (FEN) combination was assessed as perioperative chemotherapy, integrated in a multidisciplinary treatment for locally advanced BC. PATIENTS AND METHODS: Patients with newly diagnosed inoperable (stage IIIB or inflammatory) BC. Multimodality treatment protocol consisted of four preoperative courses of fluorouracil (600 mg/m(2) day 1), epirubicin (75 mg/m(2) day 1), and vinorelbine (25 mg/m(2) day1 and day 8), all i.v. every 21 days, followed by radical or conservative surgery according to clinical response and four postoperative identical chemotherapy courses aimed to eradicate micrometastatic disease. Locoregional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonotherapy according to hormone receptor status. The primary end points of the study were: (a) clinical and pathological response, (b) downstaging and conversion to operable disease, and (c) recurrence-free survival (RFS) and overall survival (OS). RESULTS: Forty-eight women, one stage IIIA, 27 (56.2%) stage IIIB, two stage IIIC (4.1%), and 12 (25%) with inflammatory BC, aged 34-75 years (median, 52), were accrued. Thirty-eight and 34 patients completed the planned pre- and postoperative chemotherapy, respectively. Totals of 175 and 135 cycles were administered pre- and postoperatively, respectively. Toxicity of both phases, mainly hematologic, was in general acceptable without treatment-related death. Venous reactions were a frequent problem. All but three tumors were converted to operable, 31.3% with breast conservation. The clinical response rate (RR) was 77.7% (22.2% complete) and pathological RR was 73.3% (complete, 20% in both primary and axilla). After a median follow-up of 72 months, 62.5% and 16.7% of patients remain relapse free at 3 and 5 years, respectively, while 83% and 58.3% were alive 3 and 5 years, respectively, after the start of chemotherapy. Median RFS and OS have not yet been reached, and are currently 37+ and 62+ months, respectively. CONCLUSION: This fixed number of FEN perioperative courses schedule followed by radiotherapy is safe and highly active in inducing both local and distant control of locally far-advanced BC. This strategy is at least not inferior to other established regimens or strategies for locally far-advanced BC, while the integration of taxanes or new targeted agents may help show its true value for this challenging clinical entity.     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.