Revisiting the astrocyte-oligodendrocyte relationship in the adult CNS

The lineages of both astrocytes and oligodendrocytes have been popular areas of research in the last decade. The source of these cells in the mature CNS is relevant to the study of the cellular response to CNS injury. A significant amount of evidence exists to suggest that resident precursor cells proliferate and differentiate into mature glial cells that facilitate tissue repair and recovery. Additionally, the re-entry of mature astrocytes into the cell cycle can also contribute to the pool of new astrocytes that are observed following CNS injury. In order to better understand the glial response to injury in the adult CNS we must revisit the astrocyte-oligodendrocyte relationship. Specifically, we argue that there is a common glial precursor cell from which astrocytes and oligodendrocytes differentiate and that the microenvironment surrounding the injury determines the fate of the stimulated precursor cell. Ideally, better understanding the origin of new glial cells in the injured CNS will facilitate the development of therapeutics targeted to alter the glial response in a beneficial way.     

PCOS患者子宫内膜白血病抑制因子的表达及意义

目的:探讨多囊卵巢综合征(PCOS)患者不同组织学分期的子宫内膜白血病抑制因子(LIF)的表达与子宫内膜容受性的关系。方法:20例已婚PCOS患者(PCOS组)和26例已婚不孕症患者(对照组)在月经周期第5￣14日及排卵后7￣8 d采集其子宫内膜标本,经HE染色判定内膜组织学分期,采用免疫组织化学法检测内膜LIF的表达。结果:PCOS组间质反应不良和分泌反应欠佳的发生率均高于对照组,差异有统计学意义(χ2=5.000,P<0.05;χ2=7.219,P<0.01)。LIF的表达以腺上皮细胞的胞质为主,其在分泌中期子宫内膜的表达水平均高于增生期(P<0.01)。LIF在PCOS组增生期和分泌中期子宫内膜的表达水平均低于其相应的对照组(P<0.01)。结论:PCOS患者着床窗口期LIF的低表达可能影响着床的多个环节,参与了PCOS患者内分泌紊乱纠正后仍出现妊娠率低、流产率高的发生、发展过程。     

LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway

Leukemia inhibitory factor (LIF) is a multi-functional cytokine protein. The role of LIF in tumorigenesis is not well-understood. Here, we found that LIF promotes tumorigenesis and metastasis of breast cancer. LIF promotes cell proliferation and anchorage-independent growth of breast cancer cells in vitro, and the growth of xenograft breast tumors in vivo. LIF also promotes invasion and migration of breast cancer cells in vitro and metastasis of breast cancer in vivo. We found that LIF activates the AKT-mTOR signaling pathway to promote tumorigenesis and metastasis of breast cancer. Inhibiting the AKT activity can largely block the activation of the mTOR pathway by LIF, suggesting that LIF activates the mTOR pathway through AKT. Inhibiting the AKT activity as well as inhibiting the mTOR activity largely block the promoting effect of LIF on tumorigenesis and metastasis. Furthermore, overexpression of LIF is significantly associated with a poorer relapse free survival in breast cancer patients. Taken together, our data strongly suggest that LIF plays an important role in the tumorigenesis and metastasis of breast cancer, and could be an important prognostic marker for breast cancer.     

Axotomy induced changes in neuronal plasticity of sympathetic chain ganglia (SChG) neurons supplying descending colon in the pig

Sympathetic neurons are capable of extensive regeneration following axonal injury. To investigate the response to axotomy of colon-projecting neurons (CPN) localized in the porcine sympathetic chain ganglia (SChG), the retrograde Fast Blue (FB) tracer, axonal transection and double immunohistochemistry methods were applied. The CPN were localized exclusively in the lumbar SChG and displayed a predominantly catecholaminergic [i.e. Tyrosine Hydroxylase (TH)/Dopamine β Hydroxylase (DβH)] and Neuropeptide Y (NPY) positive phenotype under physiological conditions. Axotomy led to a significant decrease in TH/DβH production and a simultaneous increase in the neuropeptides Galanin (GAL) and Somatostatin (SOM), but not NPY or Vasoactive Intestinal Peptide (VIP) expression in retrogradely traced perikarya. Furthermore, the decrease in density of TH-/DβH-, VIP-, Leu⁵-Enkephalin (LENK)-, Choline Acetyltransferase (ChAT)-immunoreactive (-IR) nerve fibers occurred after axotomy. These data suggest a species-specific response to axonal damage of the CPN localized in porcine SChG. Since the SChG neurons supervise the vasculature of gut both in physiological and pathological conditions, and since pig is a more accurate animal model of human gut than a rodent (Swindle et al., 1992), these data may contribute to the understanding of the pathology of several gut illnesses, like Crohn Disease and Irritable Bowel Syndrome which commonly affect western populations.     

Effects of 5-fluorouracil and gemcitabine on a breast cancer cell line (MCF-7) via the JAK/STAT pathway

Aberrant activation of the JAK/STAT pathway may predispose to malignancy as a consequence of the deregulation of cell proliferation, differentiation or apoptosis such as in cancer of the blood, head and neck, and breast. In our study we aimed to investigate the effects of 5-fluorouracil (5-FU) and gemcitabine on a breast cancer cell line (MCF-7 cells) via the JAK/STAT pathway. Distribution of JAK1, JAK2, JAK3 and STAT2, STAT3, STAT4, STAT5 were evaluated on MCF-7 cells following gemcitabine and 5-FU treatment and in the absence of drug treatment by an indirect immunohistochemical method. It was observed that JAK1, JAK3, STAT5 and particularly STAT2 activation were more effective than the other JAK/STATs in breast cancer progression. Following treatment with 5-FU, JAK1 and STAT5 immunoreactivities were decreased in MCF-7 cells in comparison with both gemcitabine-treated and non-treated groups. These results suggest that the JAK/STAT pathway plays an important role in breast cancer pathogenesis and may be more affected after 5-FU treatment rather than gemcitabine. Drugs which block STAT5 may provide a novel therapeutic approach for the treatment of breast cancer.     

Specificity of peripheral nerve regeneration: interactions at the axon level

Peripheral nerves injuries result in paralysis, anesthesia and lack of autonomic control of the affected body areas. After injury, axons distal to the lesion are disconnected from the neuronal body and degenerate, leading to denervation of the peripheral organs. Wallerian degeneration creates a microenvironment distal to the injury site that supports axonal regrowth, while the neuron body changes in phenotype to promote axonal regeneration. The significance of axonal regeneration is to replace the degenerated distal nerve segment, and achieve reinnervation of target organs and restitution of their functions. However, axonal regeneration does not always allows for adequate functional recovery, so that after a peripheral nerve injury, patients do not recover normal motor control and fine sensibility. The lack of specificity of nerve regeneration, in terms of motor and sensory axons regrowth, pathfinding and target reinnervation, is one the main shortcomings for recovery. Key factors for successful axonal regeneration include the intrinsic changes that neurons suffer to switch their transmitter state to a pro-regenerative state and the environment that the axons find distal to the lesion site. The molecular mechanisms implicated in axonal regeneration and pathfinding after injury are complex, and take into account the cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules and their receptors. The aim of this review is to look at those interactions, trying to understand if some of these molecular factors are specific for motor and sensory neuron growth, and provide the basic knowledge for potential strategies to enhance and guide axonal regeneration and reinnervation of adequate target organs.     

In vivo Angiotensin II AT1 receptor blockade selectively inhibits LPS-induced innate immune response and ACTH release in rat pituitary gland

Systemic lipopolysaccharide (LPS) administration induces an innate immune response and stimulates the hypothalamic–pituitary–adrenal axis. We studied Angiotensin II AT₁ receptor participation in the LPS effects with focus on the pituitary gland. LPS (50 μg/kg, i.p.) enhanced, 3 h after administration, gene expression of pituitary CD14 and that of Angiotensin II AT_1A receptors in pituitary and hypothalamic paraventricular nucleus (PVN); stimulated ACTH and corticosterone release; decreased pituitary CRF₁ receptor mRNA and increased all plasma and pituitary pro-inflammatory factors studied.The AT₁ receptor blocker (ARB) candesartan (1 mg/kg/day, s.c. daily for 3 days before LPS) blocked pituitary and PVN AT₁ receptors, inhibited LPS-induced ACTH but not corticosterone secretion and decreased LPS-induced release of TNF-α, IL-1β and IL-6 to the circulation. The ARB reduced LPS-induced pituitary gene expression of IL-6, LIF, iNOS, COX-2 and IκB-α; and prevented LPS-induced increase of nNOS/eNOS activity. The ARB did not affect LPS-induced TNF-α and IL-1β gene expression, IL-6 or IL-1β protein content or LPS-induced decrease of CRF₁ receptors. When administered alone, the ARB increased basal plasma corticosterone levels and basal PGE₂ mRNA in pituitary.Our results demonstrate that the pituitary gland is a target for systemically administered LPS. AT₁ receptor activity is necessary for the complete pituitary response to LPS and is limited to specific pro-inflammatory pathways. There is a complementary and complex influence of the PVN and circulating cytokines on the initial pituitary response to LPS. Our findings support the proposal that ARBs may be considered for the treatment of inflammatory conditions.     

白血病抑制因子对非小细胞肺癌细胞增殖和侵袭的影响及其机制

目的 探讨非小细胞肺癌（NSCLC）中白血病抑制因子（leukemia inhibitory factor, LIF）对细胞增殖和侵袭的影响及其作用机制。方法 采用荧光定量PCR和Western blot检测LIF在人NSCLC组织和癌旁组织中的表达;应用重组LIF因子处理非小细胞肺癌细胞系A549和Z793, MTT技术检测重组LIF因子对细胞增殖的影响; Transwell实验检测重组LIF因子对细胞侵袭的影响;Western blot检测重组LIF因子对肿瘤细胞中AKT/mTOR信号通路的影响。结果 LIF在肺癌组织中的表达水平较正常癌旁组织显著上调（P=0.0078）。重组LIF处理A549和Z793细胞后,肿瘤细胞增殖较对照组明显增加（P<0.01）;肿瘤细胞的侵袭能力较对照组明显增强（P<0.01）;AKT蛋白的磷酸化水平明显增加,且其下游底物mTOR的表达显著上调。结论 LIF在非小细胞肺癌中表达上调,并通过激活AKT/mTOR信号通路促进非小细胞肺癌细胞的增殖和侵袭。     

白血病抑制因子在女性生殖系统的表达及调控

白血病抑制因子是具有抑制多项生长潜能的胚胎细胞分化并保持其增殖能力的细胞因子。越来越多的研究发现白血病抑制因子影响生殖活动的各个环节,它表达于生殖系统的各个部位,是胚泡着床时所必须的。对白血病抑制因子的理化性质、分子量、生物活性进行综述,探讨其在生殖领域的作用。