Culture in low levels of oxygen enhances in vitro proliferation potential of satellite cells from old skeletal muscles

The proliferation ability of satellite cells (considered the 'stem cells' of mature myofibers) declines with increasing age when cultured under standard cell culture conditions of 21% oxygen. However, actual oxygen levels in the intact myofiber in vivo are an order of magnitude lower. No studies to date have addressed the issue of whether culturing satellite cells from old muscles under more 'physiologic' conditions would enhance their proliferation and/or differentiation ability. Therefore, we analyzed satellite cells derived from 31-month-old rats in standard cultures with 21% O₂ and in lowered (∼3%) O₂. Under the lowered O₂ conditions, we noted a remarkable increase in the percentage of large-sized colonies, activation of cell cycle progression factors, phosphorylation of Akt, and downregulation of the cell cycle inhibitor p27^Kip1. These data suggest that lower O₂ levels provide a milieu that stimulates proliferation by allowing continued cell cycle progression, to result ultimately in the enhanced in vitro replicative life span of the old satellite cells. Such a method therefore provides an improved means for the ex vivo generation of progenitor satellite cell populations for potential therapeutic stem cell transplantation. Received 20 April 2001; received after revision 28 May 2001; accepted 31 May 2001     

低氧环境下去势大鼠骨质疏松模型的骨吸收标志物观察

观察低氧条件下去势大鼠骨质疏松模型的骨吸收相关生化指标变化,探讨其在低氧条件下骨质疏松症诊断和监测中的应用。选用纯种SD雌性大白鼠72只,随机分为A组(低氧去卵巢组)、B组(常氧去卵巢组)、C组(低氧对照组)和D组(常氧对照组)。术后分别在低氧模拟环境下和正常环境下饲养。并于术后4周、12周和24周测量大鼠的腰椎骨密度和相关生化指标,包括血浆抗酒石酸盐酸性磷酸酶、尿羟脯氨酸、尿脱氧吡啶酚。12周时,去卵巢大鼠骨密度下降较为显著(P0.05),且低氧去卵巢组骨密度明显低于常氧去卵巢组(P0.05),对照组均无显著变化(P0.05)。24周,除常氧对照组骨密度无显著变化,其它三组骨密度均有显著降低,且低氧去卵巢组骨密度明显低于其它组,差异具有统计学意义(P0.05)。骨吸收指标检测发现,12周时,所有组尿羟脯氨酸浓度无显著性差异(P0.05),24周时,低氧去卵巢组血尿羟脯氨酸浓度显著高于其它三组(P0.05)。12周时,去势大鼠的血浆抗酒石酸盐酸性磷酸酶和尿脱氧吡啶酚含量显著高于对照组,而饲养于低氧环境后,这种差异更加显著(P0.01)。低氧环境可引起骨代谢异常,骨吸收增加,应用骨吸收生化指标检测有助于高空、高原低氧环境人群骨质疏松症的早期诊断。     

飞行员双人高空供氧方案实验评价

评价飞行员双人高空供氧方案的供氧防护性能。假人穿个体防护装备,采用新型供氧方案,先后在低压舱内完成4项试验:1分子筛产氧供氧性能实验;2气氧供混合氧性能实验;3气氧供纯氧性能实验;4加压供氧性能实验。结果氧气系统的供氧分压大于20.0 kPa(在12.0 km高度以下)和16.0 kPa(在12.0 km高度以上)。吸气阻力小于490 Pa(假人肺通气量20.0 L/min)和578 Pa(假人肺通气量30.0 L/min,1.8 km高度以上)。说明该高空供氧方案满足地面约18.0 km高度两名飞行员供氧防护要求。     

块菌保健功效的初步研究

本文通过动物实验,阐明了块菌能显著提高小鼠的常压耐缺氧能力,负重游泳能力,亚硝酸钠中毒存活率,小肠蠕动能力,以及耐寒能力,并成一定的剂量依赖关系。但是,对于小鼠的睡眠没有明显促进作用。急性毒性实验揭示块菌没有毒性。子宫和卵巢实验表明块菌并没有对雌性小鼠的生殖器官造成不良影响,反而使其子宫指数和卵巢指数增加,表明块菌具有雌激素样作用。此外,实验结果亦显示块菌对于雌性小鼠的常压耐缺氧能力,亚硝酸钠中毒存活率,和小肠蠕动能力的改善效果更优于雄性。本研究揭示块菌作为男性传统壮阳食用菌,对于女性也有很好的保健价值。     

Adenine nucleotide metabolism during anoxia and postanoxic recovery in insects

Severe hypoxia (anoxia), if maintained for more than a few minutes, causes irreversible damage in humans and other mammals. Why mammals are so vulnerable to anoxia is not fully understood. It is therefore of interest to study animals that are more tolerant of anoxia in order to identify physiological and metabolic properties that are correlated with a high tolerance of anoxia. Insects have high metabolic rates and their energy metabolism is dependent on aerobic ATP production. In insects, as in mammals, anoxia causes a rapid breakdown of physiological function, resulting in a state similar to rigor mortis. This is accompanied by a precipitous decrease in metabolic rate. In contrast to mammals, however, insects can survive anoxia for many hours and recover spontaneously and completely when air is again available. We have followed the metabolism of adenine nucleotides in locust tissues (mainly in the flight muscle) over 3 h of anoxia and during recovery from 1 h of anoxia. The content of ATP in the flight muscle dropped to 1% of normal during 2 h of anoxia. The main product was AMP which increased in content more than 20-fold. Some of the AMP was deaminated to IMP and this was further dephosphorylated to inosine. Altogether less than 30% of the total adenine nucleotides were degraded during 3 h of anoxia and this may contribute to the amazing ability of insects to recover from prolonged anoxia.     

MicroRNAs in hypoxia and acidic tumor microenvironment

MicroRNAs （miRNAs） are short non-coding RNAs of ,-22 nucleotides that play important roles in diverse biological functions including tumor adaption, survival, and metabolism homeostasis in specific tumor microenvironment, such as hypoxia and low pH. Hypoxia is a unique physiological condition during tumor development and progression, which alters a set of hypoxia-mediated miRNAs expression. These hypoxia-mediated miRNAs may exhibit either oncogenic activities or tumor-suppres sive activities, mainly through the regulation of cellular pathways including hypoxia-inducible factors signaling. Acidic tumor microenvironment develops in hypoxic solid tumors due to a combination of predominant glycolytic metabolism （Warburg effect） and poor fluid clearance due to incomplete vascularization. In this review, we summarize our current understanding of the emerging roles of miRNAs in hypoxia and acidic tumor microenvironment.     

雌激素对缺氧/复氧心肌钙离子的影响

雌激素对心肌细胞缺氧/复氧损伤具有保护作用,但其保护机制尚未完全阐明.缺氧/复氧可引起心肌细胞损伤,其中发生钙超载是心肌损伤的一个重要因素.进行了雌激素对缺氧/复氧心肌细胞内钙离子浓度的影响研究.结果显示:心肌细胞缺氧/复氧后细胞内钙离子浓度明显升高,呈复氧时间依赖性增加.雌激素有抑制缺氧/复氧心肌细胞内钙离子浓度升高...     

缺氧对冬眠刺猬激醒作用的初步观察

本文首次报告刺猬在冬眠状态下对缺氧反应的初步观察结果。观察指标为体温,心率和呼吸频率。6只刺猬在低压舱内一个大气压和环温2±2℃的条件下进入冬眠状态后,由低压舱模拟高空阶梯式低压缺氧。在模拟高度4000米、5000米及6000米阶段各停留30分钟,7000米停留2小时。结果表明:缺氧对处于冬眠状态的刺猬有促进其激醒的作用。     

Ghrelin通过诱导细胞自噬加剧H9c2细胞缺氧复氧损伤

用CoCl₂诱导H9c2细胞缺氧损伤24 h后,再将培养基换成新鲜培养基,以模拟心肌细胞体外缺血-再灌模型,并在此基础上通过ghrelin对细胞自噬的调节来评价ghrelin对心肌细胞缺氧-复氧损伤的调节作用.用流式细胞技术和LDH活性检测细胞凋亡和坏死.WST-1检测细胞活力;DCFH2-DA探针评估细胞内活性氧水平;用Western blotting检测细胞自噬.研究结果表明ghrelin处理的缺氧-复氧损伤细胞活力降低、LDH活性、细胞凋亡、ROS含量及自噬增加,用3MA处理后可明显抑制细胞自噬,并伴随细胞活力的显著升高,因此,ghrelin通过加强细胞自噬加剧了CoCl₂诱导的H9c2细胞缺氧-复氧损伤.     

基于低氧-免疫DNA甲基化标记在肺腺癌预后中的开发

为了探究缺氧和免疫联合分析DNA甲基化位点在肺癌预后中的作用，提高肺癌免疫治疗的有效性，本研究基于甲基化和转录组二维数据，构建了一个用于预后评估的风险评分模型．从TCGA数据库中下载了247个与缺氧、免疫状态相关的去冗余肺癌样本作为训练集．然后对低缺氧-强免疫状态的样本、高缺氧-弱免疫状态的样本进行了差异基因表达、甲基化位点和临床生存率分析．生存曲线分析显示，低缺氧状态-强免疫状态组中的肺腺癌患者的1、3、5年生存率均优于高缺氧状态-弱免疫状态组（log-rank检验，P<0.05、P<0.001、P<0.001）．使用LASSO回归构建的多基因预后模型包含9个甲基化位点，在肺腺癌测试数据集和验证数据集中均显示出良好的预后预测能力（AUC=0.83,0.80,0.82）．这9个甲基化位点分别分布在PEBP4、FLI1、HLA-DMB、MYO1F、ABCC2、AKNA、ETS1、CCR7和TXNRD1基因上．此外，我们从5年生存曲线中发现，在低缺氧-强免疫状态组中高表达的PEBP4、CCR7、FLI1、AKNA、HLA-DMB、MYO1F和低表达的ABCC2基因也可作为...