白藜芦醇对人角膜上皮细胞炎症和氧化应激损伤的保护作用

目的：探讨白藜芦醇(RSV)对人角膜上皮细胞(HCECs)炎症和氧化应激损伤的保护作用。

方法：用肿瘤坏死因子-α(TNF-α)诱导HCECs发生炎症反应，设对照组、TNF-α组、RSV+TNF-α组； 用H₂O₂诱导HCECs发生氧化应激反应，设正常组、H₂O₂组、RSV+H₂O₂组。采用MTT法检测细胞活力； RT-qPCR及酶联免疫吸附测定(ELISA)法检测相关炎症因子IL-1、IL-6、IL-8的表达； 免疫荧光染色法及Western blot法检测核因子-κB p65(NF-κB p65)的核转位； 2''，7''-二氯荧光黄双乙酸盐(DCFH-DA)荧光探针法检测细胞内活性氧(ROS)水平。

结果：在HCECs炎症反应中，RT-qPCR及ELISA结果均显示，与对照组相比，TNF-α组的HCECs IL-1、IL-6、IL-8的表达水平均显著升高。RSV预处理细胞后，以上指标较TNF-α组显著下降； 免疫荧光染色及Western blot结果均显示，TNF-α组NF-κB p65核转位增加，而RSV预处理细胞后NF-κB p65核转位受到抑制。在HCECs氧化应激反应中，MTT和DCFH-DA荧光探针染色结果分别显示，H₂O₂刺激使HCECs活力显著下降，HCECs内ROS的产生增多。而RSV 预处理后，细胞活力显著上升，且RSV抑制了H₂O₂诱导的HCECs内ROS的产生。

结论：RSV对HCECs的炎症和氧化应激反应具有抑制作用，RSV通过抑制NF-κB通路激活以抑制炎症反应。     

Extraskeletal osteosarcoma of penis: A case report

Extraskeletal osteosarcoma (EOS) is rare and commonly arises in the retroperitoneum, limbs, head and neck. There is no significant difference between EOS and other malignant tumors in soft tissue. Localized pain and swelling are the common presenting symptoms. Clinical diagnosis of EOS is difficult, imaging techniques may be helpful and careful, and the histopathological analysis is necessary. The common histological variants of EOS include: osteoblastoma, chondroblastoma, and fibroblastoma, and other unusual subtypes were reported occasionally. It should be distinguished with myositis ossificans, malignant mesenchymoma, giant cell tumor and parosteal osteosarcoma. We present an EOS arising in the penis. The primary site and histological category of the tumor were extremely rare. We hope the case will be helpful to the recognition of clinical signs, iconography and histopathology of EOS.     

The protective effect of melatonin on smoke‐induced vascular injury in rats and humans: a randomized controlled trial

Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke‐induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke‐induced vascular injury. 32 male rats and a double‐blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10 mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested two weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule‐1 (CD31), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and endothelin‐1 (ET‐1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2‐related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO‐1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase‐1 (HO‐1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after two weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM‐1, VCAM‐1 and ET‐1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO‐1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggest that melatonin could ameliorate smoke‐induced vascular injury.     

Day-to-Day Variation in Food Intake and Energy Expenditure in Healthy Women: The Dietitian II Study

Because day-to-day food intake varies, we tested the hypothesis that ad libitum food intake and energy expenditure show corrective responses over periods of 1 to 10 days in healthy young women. Food intake and accelerometry measurements were collected daily for 17 days in 15 young women. Total daily energy expenditure (TDEE) using doubly labeled water was also measured. The daily deviations in macronutrient and energy intake and energy expenditure from the average values were compared with the deviations observed over succeeding intervals to estimate the corrective responses. The intraindividual coefficients of variation for energy intake averaged ±25%, ranging from 16% to 34%. TDEE had a coefficient of variation of 8.3%, and accelerometry had a coefficient of variation of 8.4% (range=4.6% to 16.4%). Energy expenditure by accelerometry (2,087±191 kcal/day) was not significantly different from TDEE (2,128±177 kcal/day), but reported daily energy intake was 20.4% lower (1,693±276 kcal/day). There were significant corrective responses in energy from fat and total energy intake. This occurred from Days 3 to 6, with a peak at Day 5 that disappeared when data were randomized within each subject. Human beings show corrective responses to deviations from average energy and macronutrient intakes with a lag time of 3 to 6 days, but not 1 to 2 days. These corrective responses are likely to play a role in bringing about weight stability.     

微小RNA-29a通过沉默信息调节因子2相关酶类1基因调控肝细胞脂肪变性的机制

目的探讨人肝细胞株L02脂肪变性时微小RNA-29a(miR-29a)的表达变化及其靶向沉默信息调节因子2相关酶类1(silent mating type information regulation 2 homolog-1,Sirt1)调节脂肪肝细胞脂肪沉积的机制。方法采用油酸和棕榈酸混合物诱导建立非酒精性脂肪肝细胞模型,验证模型成功后,PCR检测miR-29a和Sirt1的表达变化;生物学预测miR-29a的靶基因;分别转染miR-29a模拟物和抑制剂,过表达miR-29a和抑制miR-29a后再建立人脂肪肝细胞模型。油红O染色观察细胞中脂质蓄积情况并测定甘油三酯含量,荧光定量PCR和免疫印迹法检测Sirt1基因和蛋白表达变化。结果脂肪肝细胞模型组miR-29a相对表达量和甘油三酯含量显著高于对照组(P<0.01),Sirt1相对表达量显著低于对照组(P<0.01);生物学预测Sirt1是miR-29a的靶基因,过表达miR-29a后,细胞内脂滴明显增多,脂肪沉积加重,甘油三酯含量显著增加(P<0.05),细胞中miR-29a的表达显著上调(P<0.01),而Sirt1 mRNA表达显著下调(P<0.05),Sirt1蛋白表达呈下降趋势;与之相反,抑制miR-29a后,细胞中脂滴相对减少,脂肪沉积减轻,甘油三酯含量显著下降(P<0.05),细胞中miR-29a的表达被有效抑制(P<0.01),而Sirt1 mRNA的表达显著上调(P<0.05),Sirt1蛋白表达较对照组呈上升趋势。结论 miR-29a在非酒精性脂肪肝细胞中表达显著上调,miR-29a通过表达上调负调控Sirt1表达从而促进脂肪肝细胞中脂肪沉积。     

The tumour–stroma ratio in colon cancer: the biological role and its prognostic impact

The tumour microenvironment consists of a complex mixture of non‐neoplastic cells, including fibroblasts, immune cells and endothelial cells embedded in the proteins of the extracellular matrix. The tumour microenvironment plays an active role in tumour behaviour. By interacting with cancer cells, it influences disease progression and the metastatic capacity of the tumour. Tumours with a high amount of stroma correspond to poor patient prognosis. The tumour–stroma ratio (TSR) is a strong independent prognostic tool in colon cancer and provides additional value to the current clinically used tumour–node–metastasis classification. The TSR is assessed on conventional haematoxylin and eosin‐stained paraffin sections at the invasive front of the tumour. Here we review studies demonstrating the prognostic significance of the TSR in solid epithelial tumours with a focus on colon cancer. Moreover, the biological role of the tumour microenvironment during tumour progression and invasion will be discussed, as well as the attempts to target the tumour stroma for therapeutic purposes. We suggest that the TSR can be implemented with little effort and without additional costs in current routine pathology diagnostics owing to its simplicity and reliability.