从alpha干扰素向epsilon干扰素发展

一种新型的人干扰素已被Daman Biotech公司分离出来,据最近的欧洲专利透露。epsilon表示该干扰素来自上皮组织,而不是根据被发现的先后次序所定的序号。     

The alpha helix dipole: screened out?

Aligned alpha helix peptide dipoles sum to a "macroscopic" dipole parallel to the helix axis that has been implicated in protein folding and function. However, in aqueous solution the dipole is counteracted by an electrostatic reaction field generated by the solvent, and the strength of the helix dipole may reduce drastically from its value in vacuum. Here, using atomic-detail helix models and Poisson-Boltzmann continuum electrostatics calculations, the net effective dipole moment, mu(eff), is calculated. Some initially surprising results are found. Whereas in vacuum mu(eff) increases with helix length, the opposite is found to be the case for transmembrane helices. In soluble proteins, mu(eff) is found to vary strongly with the orientation and position of the helix relative to the aqueous medium. A set of rules is established to estimate of the strength of mu(eff) from graphical inspection of protein structures.     

大鼠Gs alpha亚基的原核表达和纯化

用 PCR的方法 ,在大鼠 Gs alpha亚基的 C端引入了 6个外源组氨酸 (即 6×His- Tag)并以此为纯化标记 .构成的表达载体 p QE60 /rat Gsα( L)在大肠杆菌 BL2 1 ( DE3)中获得了稳定的表达 .经 DEAE- Sephacel离子交换柱和 Ni- NTA Agarose亲和层析获得纯化的具有较高 [35S]- GTPγS结合活力的重组大鼠 Gs alpha亚基     

血管损伤的新靶点：平滑肌22 alpha

血管平滑肌细胞(vascular smooth muscle cell,VSMC)表型转化是血管损伤性疾病动脉粥样硬化、高血压和血管成形术后再狭窄等的共同病理生理过程.平滑肌22 alpha (smooth muscle 22 alpha, SM22α) 是一种VSMC分化标志物,其表达具有平滑肌组织特异性和细胞表型特异性. 该蛋白不仅作为一种肌动蛋白细胞骨架相关蛋白参与VSMC骨架组构和收缩调节,它还参与VSMC的增殖、炎症和氧化应激等进程. 本文就SM22α 的结构特征及其在VSMC血管损伤中的作用机制进行综述.     

肿瘤坏死因子alpha与子痫前期的关系

子痫前期是妊娠期特有疾病,是导致孕产妇及围生儿病死率的重要原因,其病因和发病机理仍未完全明确。目前,已被提出 和子痫前期的发生相关的因素包括遗传、氧化应激、异常滋养层细胞侵入、血管内皮细胞功能紊乱、营养缺乏、免疫缺陷等,其中 内皮细胞损伤导致的内皮细胞生理功能紊乱已经成为子痫前期病因学研究的热点。肿瘤坏死因子-alpha(tumor necrosis factor-alpha, TNF-alpha)在内皮细胞损害中发挥着重要作用,可能通过诱导炎性因子和血管内皮细胞黏附分子-1(VCAM-1)生成、抑制基质金属蛋 白酶(MMP)、影响血管活性物质、脂联素、瘦素和血管因子生成,介导子痫前期的发生。本文就TNF-琢与子痫前期发生的关系进行 综述。     

成纤维细胞激活蛋白alpha与肿瘤免疫抑制的研究进展

成纤维细胞激活蛋白alpha（Fibroblast activation protein-alpha,FAP-alpha）是一种跨膜丝氨酸蛋白酶,高度表达在90 %的上皮性肿瘤的 间质--肿瘤相关成纤维细胞（Tumor association fibroblast,TAF）上。FAPalpha在促进上皮性肿瘤的恶性进展中起着十分重要的作用, 近年来研究发现,FAP琢在肿瘤微环境中发挥免疫抑制的作用。研究FAPalpha在肿瘤免疫抑制中的作用,已成为肿瘤研究的新的热 点。为基于以FAP-alpha为靶标的抗肿瘤免疫治疗提供参考,本文围绕引起肿瘤免疫抑制的因素、FAPalpha与肿瘤免疫抑制的研究进展 以及FAP-alpha在肿瘤的发展进程的作用作一综述。     

HIF-1alpha在乳腺癌中的表达及临床意义

目的：分析乳腺癌患者HIF-1alpha的表达水平与临床病理的关系,探讨HIF-1alpha表达水平对于乳腺癌诊治的意义。方法：选取我 院收治的乳腺癌患者共46 例作为实验组,随机选取同期收治的42 例乳腺良性病变患者作为对照组,所有患者均采取手术治疗, 手术中留取病变的乳腺组织,应用免疫组织化学法对乳腺组织中的HIF-1alpha表达水平进行检测,同时分析HIF-1alpha表达水平与乳 腺癌临床病理特征的相关性,并应用统计学软件对结果进行分析。结果：①实验组患者病变乳腺组织中HIF-1alpha表达水平（95.65 %）显著高于对照组（2.50 %）,差异具有显著性（P<0.05）;②HIF-1alpha表达水平与乳腺癌的患者的年龄、肿瘤直径以及雌激素受体状 态无显著相关（P＞0.05）;③HIF-1alpha表达水平与乳腺癌的临床分期、组织学分级以及淋巴结转移情况具有显著相关性（P<0.05）。结 论：乳腺癌患者的HIF-1alpha表达异常升高,其表达水平与癌组织分级、分期以及淋巴结转移情况密切相关,对预后不良具有一定的 提示作用,值得临床深入探讨。     

癫痫发作间期alpha波的窄带相位同步分析

神经元同步化放电是癫痫发作的一个重要特征,作者提出并运用窄带相位同步技术对比分析了54个癫痫病人和10个正常成年人的脑电信号(EEG)数据.结果表明,相对于对照组,癫痫组的Alpha波的平均窄带相位同步值有显著下降(P=0.02058).为了更准确地刻画和衡量癫痫组和其对照组在同步模式上的差异,提出了一个新的具体的量化指标,即alpha波的窄带相位同步发散率.分析结果显示,对照组的窄带相位同步发散率明显低于癫痫组(P=0.003060),说明对照组的alpha波振子间互诱导强度更高.这可能反映了癫痫组窄带相位同步发散率的升高及所代表的alpha振子间互诱导强度的减弱与患者在癫痫发作间期的状态有密切的联系.     

Does injection of prostaglandin F(2alpha) (PGF2alpha) cause ovulation in anestrous Western White Face ewes?

In a previous study in our laboratory, treatment of non-prolific Western White Face (WWF) ewes with PGF(2 alpha) and intravaginal sponges containing medroxyprogesterone acetate (MAP) on approximately Day 8 of a cycle (Day 0 = first ovulation of the interovulatory interval) resulted in ovulations during the subsequent 6 days when MAP sponges were in place. Two experiments were performed on WWF ewes during anestrus to allow us to independently examine if such ovulations were due to the direct effects of PGF(2 alpha) on the ovary or to the effects of a rapid decrease in serum concentrations of progesterone at PGF(2 alpha)-induced luteolysis. Experiment 1: ewes fitted with MAP sponges for 6 days (n = 12) were injected with PGF(2 alpha) (n = 6; 15 mg im), or saline (n = 6) on the day of sponge insertion. Experiment 2: ewes received progesterone-releasing subcutaneous implants (n = 6) or empty implants (n = 5) for 5 days. Six hours prior to implant removal, all ewes received a MAP sponge, which remained in place for 6 days. Ewes from both experiments underwent ovarian ultrasonography and blood sampling once daily for 6 days before and twice daily for 6 days after sponge insertion. Additional blood samples were collected every 4 h during sponge treatment. Experiment 1: 4-6 (67%) PGF(2 alpha)-treated ewes ovulated approximately 1.5 days after PGF(2 alpha) injection; these ovulations were not preceded by estrus or a preovulatory surge release of LH, and resulted in transient corpora hemorrhagica (CH). The growth phase was longer (P < 0.05) and the growth rate slower (P < 0.05) in ovulating versus non-ovulating follicles in PGF(2 alpha)-treated ewes. Experiment 2: in ewes given progesterone implants, serum progesterone concentrations reached a peak (1.7 2 ng/mL; P < 0.001) on the day of implant removal and decreased to basal concentrations (<0.17 ng/mL; P < 0.001) within 24 h of implant removal. No ovulations occurred in either the treated or the control ewes. We concluded that ovulations occurring after PGF(2 alpha) injection, in the presence of a MAP sponge, could be due to a direct effect of PGF(2 alpha) at the ovarian level, rather than a sudden decline in circulating progesterone concentrations.     

HIF-1alpha信号通路在肿瘤细胞调控中的研究进展

缺氧诱导因子（HIF-1alpha）是肿瘤细胞生长过程中重要的调控因子,研究其作用机制有利于实现对肿瘤细胞增殖的抑制作用。 HIF-1alpha可引起多种基因转录,使肿瘤细胞耐受低氧环境,进而使癌症患者在治疗过程中产生耐受反应,最终影响治疗效果,甚至 放弃治疗。因此,以HIF-1alpha为靶点是治疗肿瘤的重要手段和方法。本文对HIF-1alpha的基本概况及其主要信号通路（PI3K 通路、 HSP90 通路及MAPK通路）以及不同通路抑制剂（如LY294002、17AAG、PD98059、U0126、SB203580、SP600125 等）进行综述,并 对HIF-1alpha的应用前景进行展望。     

番茄红素对胰腺alpha和beta细胞的差异作用

番茄红素是一种强抗氧化剂,在糖尿病的治疗实验中显示出对机体的保护作用,但是其细胞机制尚不明确。本研究采用不同浓度梯度的番茄红素处理胰腺alpha和beta细胞系,检测细胞的生长、凋亡、周期、活性氧、ATP水平和相关细胞因子的表达变化。结果显示,番茄红素不影响alpha细胞的生长、凋亡、周期、活性氧和ATP水平,但番茄红素可以促进beta细胞的生长、上调其S期比例、降低活性氧水平并提升ATP水平。与此同时,番茄红素可以提升beta细胞tnfα、tgfβ和hif1αmRNA的表达。这些结果表明番茄红素的作用具有细胞特异性,可以活化胰腺beta细胞,为其在糖尿病防治的临床应用提供数据支撑。     

Do free fatty acids induce insulin resistance in alpha cells?

Thirty years ago, Unger and Orci proposed the bihormonal-abnormality hypothesis, which highlighted that both deficient insulin secretion and excessive glucagon levels contributed to the hyperglycemic state in type 2 diabetes. The plasma free fatty acid (FFAs) concentrations are higher in patients with diabetes and prediabetes, suggesting that FFAs may be involved in the pathophysiology of diabetes. In type 2 diabetes, at least in the obese form, insulin does not seem to correct the exaggerated alpha cell responses. This phenomenon suggests that the inability of insulin to suppress the glucagon level could be caused by alpha cell insulin resistance. However, it has remained unclear whether alpha cell insulin resistance is caused by FFAs. Recent studies have demonstrated that long-term exposure to elevated FFA levels leads to hypersecretion of glucagon and accumulation of triglycerides (TG) in clonal alpha-TC1-6 cells, but the mechanism of FFA-induced alpha cell insulin resistance is unclear. We hypothesize that long-term exposure to FFAs reduces AMP-activated protein kinase (AMPK) activity and increases TG accumulation in alpha cells, leading to impaired insulin signaling of alpha cells and hypersecretion of glucagon. This hypothesis provides the first detailed examination of the effects of FFAs on alpha cells with glucagon hypersecretion. It potentially suggests that improving alpha cell insulin resistance as well as reversing lipotoxicity will normalize alpha cell function and may benefit glucose control. Consequently, AMPK and insulin-related pathways in alpha cells could be potential targets for controlling glucagon secretion and glucose counter-regulation.     

Mammalian {alpha}-mannosidases--multiple forms but a common purpose?

Previously,     

Cancer progression: is inhibin alpha from Venus or Mars?

The inhibin field has been perplexed by the information that inhibin alpha is a tumour suppressor in mice yet is elevated in women with ovarian cancer. Furthermore, we have consistently observed a down-regulation or loss of inhibin alpha in prostate cancer patient samples and cell lines. However, our latest data have prompted us to re-evaluate the role of inhibin alpha in prostate and other cancers. Using the analogy of TGF-beta as a springboard for our hypothesis, we offer a unifying model whereby the previously conflicting observations in mice, men and women can be explained. We propose that initially inhibin alpha is tumour-suppressive and is expressed in benign and early-stage primary cancers. Tumour-suppressive inhibin alpha is then silenced as the tumour progresses but is reactivated as a pro-metastatic factor in advanced, aggressive cancers.     

Does prothymosin alpha affect the phosphorylation of elongation factor 2?

Prothymosin alpha is a small, acidic, essential nuclear protein that plays a poorly defined role in the proliferation and survival of mammalian cells. Recently, Vega et al. proposed that exogenous prothymosin alpha can specifically increase the phosphorylation of eukaryotic elongation factor 2 (eEF-2) in extracts of NIH3T3 cells (Vega, F. V., Vidal, A., Hellman, U., Wernstedt, C., and Domínguez, F. (1998) J. Biol. Chem. 273, 10147-10152). Using similar lysates prepared by four methods (detergent lysis, Dounce homogenization, digitonin permeabilization, and sonication) and three preparations of prothymosin alpha, one of which was purified by gentle means (the native protein, and a histidine-tagged recombinant prothymosin alpha expressed either in bacteria or in COS cells), we failed to find a response. A reconstituted system composed of eEF-2, recombinant eEF-2 kinase, calmodulin, and calcium was also unaffected by prothymosin alpha. However, unlike our optimized buffer, Vega's system included a phosphatase inhibitor, 50 mM fluoride, which when evaluated in our laboratories severely reduced phosphorylation of all species. Under these conditions, any procedure that decreases the effective fluoride concentration will relieve the inhibition and appear to activate. Our data do not support a direct relationship between the function of prothymosin alpha and the phosphorylation of eEF-2.     

HIF-1alpha and p53: the ODD couple?

Tumor hypoxia activates hypoxia-inducible factor-1 (HIF-1) and induces the accumulation of the tumor suppressor p53. HIF-1 signaling stimulates angiogenesis and mediates cellular adaptation to hypoxia, whereas p53 promotes hypoxia-induced apoptosis. A recent article provides in vitro biophysical evidence supporting a direct interaction between p53 and the oxygen-dependent degradation domain of the HIF-1alpha subunit. The article identifies potential structural parameters required for this interaction and suggests an alternative mechanism by which p53 might impact tumor response to therapy.