细胞衰老与慢性肝病及对肝纤维化的调节作用

衰老是生物界的普遍规律，细胞作为生物有机体的基本单位，也在不断地新生和衰老死亡。现在认为细胞衰老是由多种因素刺激，通过信号转导引起生长阻滞的一种稳定形式。目前除了衰老机理和老龄化引起的心脏病，心血管病等的研究外，有报道显示细胞衰老对肝损伤后肝纤维化有调节作用，因而受到人们的关注。     

端粒与糖尿病

端粒是真核细胞染色体的末端重复序列,在人类细胞核染色体中以TTAGGG形式串联重复出现,长度约为6~15 kb,其结构包括由数千碱基对组成的双链非编码DNA序列及单链3’末端序列,犹如＂帽子＂套在每个染色体的末端。端粒的生理功能主要是防止染色体末端融合及降解,避免复制过程中遗传信息丢失,对染色体起保护作用。由于端粒序列GGG含量丰富,容易遭受氧化应激损伤.     

端粒、端粒酶与癌症

端粒 ,端粒酶与癌症关系的研究是当前学术领域探索的热点[1] 。尤其自 1994年 ,Ｋｉｍ等[2 ] 建立ＴＲＡＰ方法检测到肿瘤细胞的端粒酶活性以来 ,使该领域的研究取得了长足的、稳定的进展 ,现将其研究进展概括如下。1　端粒 (ｔｅｌｏｍｅｒｅ)的概念端粒是指真核细胞线性染色体末端的蛋白质—ＤＮＡ特殊结构 ,即染色体末端ＤＮＡ序列的多个重复 ,其作用是保护和稳定染色体的末端 ,它由 2～ 2 0ｋｂ串联的短片段重复序列 (ＴＴＡＧＧＧ)ｎ及一些结合蛋白组成。四膜虫 (单细胞生物 )端粒的结构是 6个核苷酸5’ -ＴＴＧＧＧＧ - 3’序列的多次…     

端粒、端粒酶系统的调控与研究现状

端粒是指位于真核细胞线性染色体末端的特殊结构 ,由TTAGGG的DNA重复序列和端粒结合蛋白所构成的一种核蛋白复合体。端粒酶对端粒结构的稳定起着重要的作用 ,而端粒结构和端粒结合蛋白也影响端粒酶活性。在大多数组织端粒酶活性的抑制是在出生前由于hTERT转录水平的抑制 ,而在 90 %以上的癌细胞中通过hTERT表达上调被激活。端粒酶活性受多水平调控 ,本文从以下方面描述 :端粒酶活性和细胞分化、端粒酶活性的分子调节、端粒酶活性与细胞周期、端粒酶与肿瘤现状及端粒酶活性与其他因素 ,因此 ,可能在不同的细胞有不同的因素。     

端粒、端粒酶与癌变

端粒是真核细胞染色体末端的一种保护性结构，与端粒酶一起具有有维持基因组稳定和决定细胞寿命的作用。研究表明端粒酶激活是多种细胞癌形的一个重要环节，且该环节可处在整个癌变过程的早期或晚期，其作用在于维持癌变细胞的永生性。     

端粒-端粒酶系统与恶性血液病

<正>端粒-端粒酶在肿瘤发生发展中起着重要的作用,因而成为近年来生命科学研究的热点之一。端粒(Telomeres)是Muller根据黑腹果蝇染色体末端保护功能而于1938年首次定义。端粒酶(Telom-erase)则于1984年为Greider和Blackburn所发现。现就端粒-端粒酶系统及其在造血干细胞及血液系统恶性肿瘤中的表现综述如下。     

端粒、端粒酶与儿童白血病

端粒、端粒酶与肿瘤发生密切相关。本文阐述了端粒、端粒酶的生物学特性、功能 ;在造血系统的分布特征及其与白血病的关系     

端粒、端粒酶与肿瘤

临床上恶性肿瘤已成为威胁人类生命和健康的常见病之一,其发病率与死亡率正在逐年上升。目前,对大多数恶性肿瘤临床治疗方案中,仍首选是手术、放疗、药物治疗(包括化疗和中草药)以及免疫治疗。一些恶性肿瘤的早期诊断比较困难,治疗副作用大且愈后较差。随着端粒、端粒酶研究的不断深入,以端粒、端粒酶为靶分子的端粒酶抑制策略诊断治疗肿瘤已经引起临床的重视,因为,它不同于普通的具有细胞毒性的抗肿瘤治疗, 将有望成为更有效更安全的肿瘤诊治方案。     

端粒、端粒酶与卵巢癌的诊治进展

端粒长度是决定细胞增殖能力和寿命的分子标志，而端粒酶活化剂则是细胞恶化的共同通路。端粒酶是目前已知的最为广谱的肿瘤分子标记物，并可能成为肿瘤诊断和预后判断的新指标以及肿瘤治疗的新靶点。     

有机锗可延缓细胞衰老

中国古代神话小说《白蛇传》中 白娘子为救她的夫君许仙去昆仑山盗取灵芝，现代研究认为，灵芝之所以“灵”，是因为它含有丰富的锗。锗是一种金属元素，对人体的生理功能有着卓越的贡献．却迟迟不为人知。     

人胚肺成纤维细胞衰老过程中胰岛素样生长因子2表观遗传活化作用

目的观察体外培养人胚肺成纤维细胞复制性衰老过程中及过氧化氢诱导早衰持续阶段胰岛素样生长因子2(IGF2)表观遗传学修饰。方法荧光定量PCR检测IGF2的mRNA表达,甲基化特异PCR检测其启动子区甲基化改变,染色质免疫沉淀结合定量PCR检测组蛋白修饰,包括组蛋白H3、H4乙酰化,H3(Lys4)及H4(Lys20)甲基化修饰。结果细胞复制性衰老过程中,中年细胞组及复制性衰老细胞组IGF2的mRNA表达升高,早衰持续组升高显著;细胞衰老过程中,仅复制性衰老细胞组在启动子区-658～-456bp具有一定的甲基化水平;复制性衰老细胞组的组蛋白修饰在启动子区-856～-634bp以H4乙酰化,H3甲基化修饰为主;+9～+145bp的修饰,复制性衰老细胞组受组蛋白H3及H4甲基化联合修饰,早衰持续组以H3甲基化修饰为主。结论细胞衰老过程中,IGF2启动子区组蛋白修饰联合调控其mRNA表达,复制性衰老与早衰的调控机制存在差异。     

The Interplay of Vitamin D Deficiency and Cellular Senescence in The Pathogenesis of Obesity-Related Co-Morbidities

This scoping review aims to clarify the interplay between obesity, vitamin D deficiency, cellular senescence, and obesity-related metabolic consequences, mainly subclinical atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Obesity is a significant global health problem that involves cellular, environmental, behavioral, and genetic elements. The fundamental cause of obesity throughout all life stages is an energy imbalance, and its consequences are countless and, foremost, very common. Obesity has been comprehensively studied in the literature given its association with low serum vitamin D, with many proposed mechanisms linking the two conditions. Moreover, markers of exaggerated cellular senescence have been proven to accumulate in obese individuals. Subclinical atherosclerosis initiates an early stage that ends in serious cardiac events, and obesity, low vitamin D, and senescent cells largely contribute to its associated chronic low-grade inflammation. Furthermore, NAFLD signifies the hepatic manifestation of metabolic syndrome, and studies have highlighted the important role of obesity, vitamin D deficiency, and cellular senescence in its development. Therefore, we outlined the most important mechanisms tying these conditions to one another.     

Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity,Skin Health and Cellular Senescence

The role of the microbiome in human aging is important: the microbiome directly impacts aging through the gastrointestinal system. However, the microbial impact on skin has yet to be fully understood. For example, cellular senescence is an intrinsic aging process that has been recently associated with microbial imbalance. With age, cells become senescent in response to stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation of senescent cells has been linked to various aging and chronic pathologies due to an overexpression of the senescence-associated secretory phenotype (SASP) comprised of proinflammatory cytokines, chemokines, growth factors, proteases, lipids and extracellular matrix components. In particular, dermatological disorders may be promoted by senescence as the skin is a common site of accumulation. The gut microbiota influences cellular senescence and skin disruption through the gut-skin axis and secretion of microbial metabolites. Metabolomics can be used to identify and quantify metabolites involved in senescence. Moreover, novel anti-senescent therapeutics are warranted given the poor safety profiles of current pharmaceutical drugs. Probiotics and prebiotics may be effective alternatives, considering the relationship between the microbiome and healthy aging. However, further research on gut composition under a senescent status is needed to develop immunomodulatory therapies.     

人胚肺成纤维细胞复制性衰老及过氧化氢诱导的早衰研究

目的研究关于人胚肺成纤维细胞复制性衰老及过氧化氢诱导的早衰。方法常规传代培养人胚肺二倍体成纤维细胞及应用过氧化氢染毒诱导细胞早衰发生,利用细胞衰老综合指标进行评价,包括细胞形态学改变、生长曲线、寿命周期、细胞周期分布及衰老相关β-半乳糖苷酶染色等,同时检测细胞衰老不同阶段增殖细胞核抗原PCNA的mRNA和蛋白水平表达变化。结果人胚肺二倍体成纤维细胞于52PDL(群体倍增水平)处于细胞复制性衰老状态,400μmol/L过氧化氢可短期内诱导细胞过早衰老,衰老的细胞变大扁平,饱和度降低,细胞不可逆的阻滞于G1期,衰老相关β-半乳糖苷酶染色阳性率增加,PCNA表达随着衰老程度的增加而逐渐下降。结论400μmol/L过氧化氢以一定方式作用于细胞可以诱导早衰发生,细胞复制性衰老与细胞早衰具有相同的生物学特征和增殖能力。     

Cellular phones and traffic accidents

Cellular phone use in motor vehicles is becoming an increasing world-wide phenomenon. Using data obtained from traffic accidents reported between 1992 and 1995 in the state of Oklahoma, USA, this study examined statistical rate-ratios of accident characteristics between drivers with or without cellular phones. Rates were calculated between cellular phone involvement and reported accident causes, types of collision, driver actions immediately prior to the accident, location of the accident, the extent of fatalities, and age and gender of drivers. Results indicated a significant increased rate among drivers with cellular phones for inattention, unsafe speed, driving on wrong side of road, striking a fixed object, overturning their vehicle, swerving prior to the accident, and running off the roadway. People with phones stood an increased risk of being killed in an accident over persons without phones. Males with phones had a significantly higher rate than females for many of accident characteristics mentioned above. Rate-ratios of some accident characteristics and fatalities increased as age increased, with the exception of drivers under age 20 yrs, who had the highest fatality rate. Limitations of the study and possible prevention alternatives are discussed.     

细胞电生理与膜片钳技术

本讲座介绍细胞电生理的基本知识及其基本方法。包括细胞的简单结构、细胞膜的化学组成和生物电信号的产生机制。膜片钳技术是现代电生理研究的基本方法,它涉及实验系统的组建和实验过程中的关键技术。     

MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells

The mammalian target of rapamycin (mTOR) is a sensor of nutrient status and plays an important role in cell growth and metabolism. Although inhibition of mTOR signaling promotes tumor cell death and several mTOR inhibitors have been used clinically, recent reports have shown that co-treatment with MHY1485, an mTOR activator, enhances the anti-cancer effects of anti-PD-1 antibody and 5-fluorouracil. However, it remains unclear whether MHY1485 treatment alters the effects of radiation on tumor cells. In this study, the radiosensitizing effects of MHY1485 were investigated using murine CT26 and LLC cell lines. We examined mTOR signaling, tumor cell growth, colony formation, apoptosis, senescence, oxidative stress, p21 accumulation and endoplasmic reticulum (ER) stress levels in cells treated with MHY1485 and radiation, either alone or together. We found that MHY1485 treatment inhibited growth and colony formation in both cell lines under irradiation and no-irradiation conditions, results that were not fully consistent with MHY1485’s known role in activating mTOR signaling. Furthermore, we found that combined treatment with MHY1485 and radiation significantly increased apoptosis and senescence in tumor cells in association with oxidative stress, ER stress and p21 stabilization, compared to radiation treatment alone. Our results suggested that MHY1485 enhances the radiosensitivity of tumor cells by a mechanism that may differ from MHY1485’s role in mTOR activation.     

Ageing and immunity: Addressing immune senescence to ensure healthy ageing

Among the greatest achievements of the 20th century, prolongation of life expectancy has been the result of improved health conditions, decreased childhood mortality, lower incidence of infectious diseases. The consequence is the rapid ageing of the world population, with the elderly representing over 25% of the entire population by the year 2030, of which 75% living in less developed countries. Ageing thus represents one of the major public health challenges of the 21st century. Indeed, unhealthy ageing and frailty of the aged population has an important impact on the economic development and social costs of a country, a problem even more acute in less developed countries. A better knowledge of immune senescence and the design of customised vaccination strategies for the elderly are the immediate challenges posed to scientists and physicians. The conference “Ageing and immunity”, recently held in Siena (Italy), has addressed these issues and defined the global strategic priorities for research and health policies aimed at ensuring healthy ageing.     

过继性细胞基因疗法与类风湿关节炎

类风湿关节炎（Rheumatoid arthritis,RA）是一种常见的以滑膜炎及关节软骨破坏为特征的累及全身多关节的慢性自身免疫性疾病,患病率及致残率高,严重影响患者的健康和生活质量,给家庭和社会带来沉重的负担。目前,RA的病因仍不十分明确,针对的治疗选择很有限,其治疗方法主要依靠药物治疗,血浆置换,造血干细胞移植及外科手术治疗等。且目前最好的治疗方法都不能从根本上改变RA患者的病情状态。所以治疗RA需要一个新颖的方法-过继性细胞基因疗法。本文就RA治疗现状和进展作一综述,并对各种方法比较其利弊。     

Cellular responses to high ascorbic acid intake by normally nourished and undernourished mice

Swiss albino mice were reared in litters of 8 or 14 pups each to produce normally nourished or undernourished pups, respectively. Litter size was maintained 26 days postnatally when several mice were sacrificed. The undernourished mice weighed less and had lower ascorbic acid contents in their livers and adrenals than normally nourished mice. They also had lighter brains, livers, and kidneys, and fewer cells (DNA) in those tissues. Animals remaining in both size litters were allowed free access to a stock diet and either untreated drinking water or drinking water containing 250 mg ascorbic acid per 100 ml for 28 days, when they were sacrificed. Suplementary ascorbic acid had no effect on cell number (DNA) or cell size (protein/DNA) in tissues of either normally nourished or early undernourished mice. Undernourished mice, however, retained fewer cells in their tissues than normally nourished mice.