FHL2 affects the resistance of glioblastoma U87 cells against temozolomide via MGMT / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨干扰四个半LIM结构域蛋白2（FHL2）的表达对胶质母细胞瘤U87细胞中O6-甲基鸟嘌呤DNA甲基转移酶(MGMT) 表达的影响，以及对U87细胞替莫唑胺（TMZ）耐药性的影响。方法：利用慢病毒感染技术分别将携带不同FHL2干扰序列的慢病毒（shFHL2-1#、shFHL2-4#）及其阴性对照（shN）感染U87细胞，分别命名为shFHL2-1#、shFHL2-4#和shN组；采用siRNA转染技术将siMGMT-1#、siMGMT-4#和siN转染至U87细胞，为siMGMT-1#、siMGMT-4#和siN组，qPCR和WB法验证FHL2或MGMT的敲低效果。用TMZ处理上述各组细胞（以DMSO处理组为对照），随后以CCK-8法和细胞克隆形成实验检测TMZ处理前后FHL2或MGMT敲低组细胞的增殖情况，FCM检测TMZ处理前后FHL2敲低组细胞的凋亡情况，WB法和免疫荧光法检测敲低FHL2对U87细胞中MGMT表达的影响，WB法检测TMZ处理对各组细胞中FHL2和MGMT表达水平的影响。结果：成功构建敲低FHL2或MGMT表达的U87细胞。与shN组相比，shFHL2-1#、shFHL2-4#组U87细胞的增殖能力减弱、凋亡水平升高（均P<0.01），MGMT表达水平明显降低（均P<0.01）。经TMZ处理后，与相应的DMSO处理组相比，shN组细胞中FHL2和MGMT的表达水平显著升高（均P<0.05），而细胞的增殖和凋亡均无显著变化（均P>0.05）；shFHL2-1#、shFHL2-4#组细胞中FHL2和MGMT的表达水平无显著改变（均P>0.05），但细胞增殖能力进一步显著降低、凋亡水平进一步显著升高（均P<0.01）。敲低MGMT使U87细胞增殖减慢（P<0.01），而siMGMT-1#、siMGMT-4#组细胞经TMZ处理后增殖能力进一步降低（均P<0.01）。结论：干扰FHL2表达使得U87细胞增殖减慢而凋亡加剧、MGMT表达下调，提示FHL2可能通过影响MGMT的表达调控U87细胞对TMZ的耐药性。

Investigation of respiratory and dermal symptoms associated with metal working fluids at an aircraft engine manufacturing facility.

BACKGROUND: Each year, 1.2 million metalworkers are exposed to metalworking fluids (MWFs), which can cause dermal and respiratory disease. The National Institute for Occupational Safety and Health (NIOSH) conducted a health hazard evaluation of MWF exposures at an aircraft engine manufacturing facility. The objectives were to determine employee exposures to endotoxin and MWFs in the air, characterize symptoms experienced by employees working with MWFs, compare them to symptoms of employees unexposed to MWFs, and make recommendations for reducing exposures based on results. METHODS: Four hundred seven workers were categorized as MWF exposed or MWF unexposed and completed questionnaires. Estimated prevalence ratios (PR) of dermatitis, asthma, and work-related asthma (WRA) symptoms were calculated. Airborne concentrations of MWF and endotoxin were measured, and work practices observed. RESULTS: MWF exposed workers had a significantly higher prevalence of dermatitis on wrists/forearms (PR 2.59; 95% CI 1.22, 5.46), asthma symptoms (PR 1.49; 95% CI 1.05, 2.13), and WRA symptoms (PR 2.10; 95% CI 1.22, 3.30) than unexposed workers. Airborne concentrations of MWF were below the NIOSH recommended exposure limit (REL) for MWF aerosols (thoracic particulate mass). CONCLUSIONS: Despite MWF exposures below the NIOSH REL, exposed workers had a higher prevalence of asthma, WRA, and dermatitis symptoms than unexposed workers. Recommendations to reduce exposure included configuring mist collectors to automatically turn on when the machine is in use, and enforcing enclosure use.

Evaluation of potential noise exposures in hospital operating rooms.

The National Institute for Occupational Safety and Health received a health hazard evaluation request from West Virginia University Hospital, Morgantown, to evaluate noise exposures from surgical instruments in the OR. Four surgical technologists, four RNs, and one surgeon wore noise dosimeters to measure full-shift personal noise exposures during two days while they performed typical daily activities. Measurements did not exceed Occupational Safety and Health Administration or National Institute for Occupational Safety and Health noise exposure limits; however, area sound level measurements indicated that some intermittent activities can generate sound levels above 90 A-weighted decibels. Examples include surgery preparation, drilling or noise from other powered surgical instruments during surgeries, and clean up. Preventive maintenance of powered surgical instruments can reduce noise exposures, and noise output should be considered when selecting replacement instruments. Keeping music at a low level and using hearing protection are other interventions to consider to improve noise levels in an OR.

Ocular and respiratory symptoms among lifeguards at a hotel indoor waterpark resort.

OBJECTIVES: To determine the cause of eye and respiratory irritation symptoms among lifeguards at an indoor waterpark. METHODS: Investigators 1) performed environmental sampling for chloramine, endotoxin, and microbials; 2) administered symptom questionnaires; 3) reviewed ventilation system designs; and 4) reviewed water chemistry. RESULTS: Airborne trichloramine concentrations were found at levels reported to cause irritation symptoms in other studies. Some endotoxin concentrations were found at levels associated with cough and fever in previous studies. Exposed lifeguards were significantly more likely to report work-related irritation symptoms than unexposed individuals. The ventilation system may not have provided sufficient air movement and distribution to adequately capture and remove air contaminants at deck level. No water microbes were detected, and water chemistry met state standards. CONCLUSIONS: Indoor waterparks need to control water chemistry and ensure adequate air movement and distribution to control air contaminants and reduce health symptoms.