激活素A与肝脏疾病

激活素A是一种具有广泛生物学作用的细胞因子,在肝脏其作用主要表现为抑制细胞增殖、诱导细胞凋亡、促进细胞外基质合成分泌、抑制肿瘤细胞增殖及转移.研究发现急、慢性肝炎、肝纤维化、肝硬化、肝癌及肝功能衰竭等疾病发生发展中均有激活素A表达异常,提示激活素A信号异常可能参与了这些肝脏疾病的发生发展过程.     

脂联素对子宫内膜癌细胞生长抑制和细胞凋亡的影响

观察脂联素对子宫内膜癌细胞株HEC-1-A和RL95-2细胞计数、细胞凋亡和细胞周期的影响,检测脂联素对细胞p-AMPK/AMPKα表达的影响.结果提示脂联素对子宫内膜癌细胞具有抑制生长和诱导细胞凋亡发生的作用,其作用机制可能与AMPK激活有关.     

激活素A信号调控与肝脏疾病

激活素A是一种多功能细胞因子,具有广泛生物学作用,其在肝脏的作用主要表现为抑制细胞增殖、诱导细胞凋亡、促进细胞外基质分泌、抑制肿瘤细胞增殖及转移。在慢性肝炎、肝纤维化、肝癌及肝功能衰竭等疾病发生发展过程中均有激活素A表达异常,提示激活素A信号异常可能参与了肝脏疾病发生发展过程。     

激活素和肝纤维化

激活素是转化生长因子-β多肽类生长因子大家族成员之一,近来研究表明激活素有致肝纤维化作用,作用机制与转化生长因子-β相似,但又不完全相同。本文扼要综述了激活素致纤维化作用机制。抑制激活素表达可能是防治肝纤维化的新途径。     

血管生成素1通过核因子κB传导通路调节内皮祖细胞炎症因子表达

目的探讨血管生成素1调节内皮祖细胞炎症因子的可能的信号传导通路。方法采用肿瘤坏死因子α诱导内皮祖细胞炎症,以慢病毒为载体将血管生成素1导入内皮祖细胞中,使用特异性抑制剂吡咯烷二硫代氨基甲酸盐抑制核因子κB,通过Western blot检测内皮祖细胞中血管生成素1蛋白和核因子κB蛋白的表达情况,随后采用荧光定量聚合酶链反应、酶联免疫吸附法检测各组内皮祖细胞中黏附分子细胞间黏附分子1、血管细胞黏附分子1的表达水平。结果转染血管生成素1基因内皮祖细胞中能够成功表达血管生成素1蛋白,而经吡咯烷二硫代氨基甲酸盐抑制后核因子κB蛋白未见明显表达。与肿瘤坏死因子α组相比,血管生成素1组、吡咯烷二硫代氨基甲酸盐组、血管生成素1+吡咯烷二硫代氨基甲酸盐组细胞间黏附分子1、血管细胞黏附分子1的mRNA和蛋白表达水平均明显下调(P<0.05),三组间无明显差异(P>0.05)。结论血管生成素1可能通过核因子κB信号传导通路影响肿瘤坏死因子α诱导的内皮祖细胞的炎症反应。     

TNF-α对3T3-L1脂肪细胞PPAR-γ2 mRNA表达及脂联素分泌的影响

用肿瘤坏死因子α（TNF-α）分别处理未分化、已分化的3T3-L1细胞，检测培养细胞过氧化物酶体增殖物激活受体γ2（PPAR-γ2）mRNA的表达和脂联素的分泌。结果表明TNF-α可明显抑制3T3-L1脂肪细胞的PPAR-γ2 mRNA表达和脂联素的分泌（P〈0.05或P〈0.01），提示TNF-α可能通过PPAR-γ影响脂联素的分泌。     

人凝血酶反应素-1的结构与功能

人凝血酶反应素 (TSP) - 1属糖蛋白 ,广泛分布在血液及心、肺、肾等组织中 ,受血清及多种生长因子的调节 ,具有抗凝血、抗血管生成等作用 ,近来有研究表明 ,它可明显抑制血管平滑肌细胞的增殖 ,可能与再狭窄发生机制有关。本文就人 TSP的结构、组织分布、表达调控和功能研究予以介绍。     

膜表面核仁素对内毒素所致THP-1细胞炎症介质表达的影响

目的探讨THP-1细胞膜定位核仁素作为寡糖链受体在脂多糖所致炎症反应中的作用。方法采用间接免疫荧光、流式细胞术以及细胞膜蛋白免疫印迹等技术证实核仁素在人THP-1细胞膜表面表达。以无血清状态下脂多糖刺激THP-1细胞为炎症细胞模型，采用逆转录聚合酶链反应及酶联免疫吸附测定法等检测核仁素抗体对炎症介质肿瘤坏死因子α和白细胞介素1β的表达与分泌的影响。结果间接免疫荧光、流式细胞术以及免疫印迹证实核仁素可在人THP-1细胞膜表面表达。逆转录聚合酶链反应结果发现，在无血清条件下，500μg/L脂多糖刺激1h、2h、3h或4h后可以明显促进肿瘤坏死因子α和白细胞介素1βmRNA表达，而核仁素抗体处理1h后再用脂多糖刺激1h、2h、3h或4h，肿瘤坏死因子α和白细胞介素1βmRNA表达明显受到抑制。而先用正常IgG体处理1h后再用脂多糖刺激1h、2h、3h或4h，肿瘤坏死因子α和白细胞介素1βmRNA表达与单用脂多糖刺激水平相当。另外单用正常IgG或核仁素抗体处理1～4h，肿瘤坏死因子α和白细胞介素1βmRNA表达与对照组比较无差异。酶联免疫吸附测定法检测发现，核仁素抗体处理1h后能明显抑制脂多糖所致肿瘤坏死因子α和白细胞介素1β的分泌，而IgG则没有这种作用。结论THP-1细胞膜表面核仁素参与了脂多糖所致炎症反应，提示核仁素可能是脂多糖的一种新受体。     

心肌素抑制血管平滑肌细胞表型转换改善动脉粥样硬化

动脉粥样硬化(As)是一种涉及多种细胞并由多种因素诱导的慢性疾病,血管平滑肌细胞(VSMC)的增殖、迁移对As的发生和发展有着不可忽视的影响,包括促进斑块的生成及诱发斑块的不稳定等。VSMC由收缩表型向合成表型转换是其增殖和迁移的基础,维持VSMC的收缩表型,抑制其合成表型的形成有助于抑制其异常增殖和As斑块的形成。心肌素作为VSMC收缩标志基因的关键转录因子,能与血清反应因子结合来激活VSMC收缩标志基因的表达。多种功能因子,如雌激素受体α、组蛋白修饰、DNA甲基化和microRNA等,都可以与心肌素联合作用调节血管的功能并抑制VSMC的表型转换;多种作用途径,例如转化生长因子β1、血小板衍生生长因子BB等信号通路,可增加心肌素表达,抑制VSMC的增殖和迁移。因此,心肌素在As发展过程中有着至关重要的保护作用。调控心肌素影响VSMC的表型转换可能成为未来治疗As乃至心血管疾病的新策略。     

E-钙粘附素和α-链接素的表达与大肠癌分化、转移、分期及预后的关系

寻找肿瘤特异性预后指标一直是肿瘤研究的热点,但迄今为止大肠癌与其他恶性肿瘤一样尚无理想的预后指标.E-钙粘附素是钙依赖性的具有细胞与细胞粘附特征的转膜糖蛋白.α-链接素可与E-钙粘附素形成复合物,与E-钙粘附素粘附功能密切相关,在上皮细胞间聚集和粘附中起关键作用.多种肿瘤转移与E-钙粘附素和α-链接素表达异常有关.本研究旨在探讨E-钙粘附素和α-链接素的表达与大肠癌分化、转移、分期及预后的关系.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.