Matrix metalloproteinases （MMPs） and trophoblast invasion

MMPs and their natural tissue inhibitors TIMPs are crucial in coordinated breakdown and remodeling of the extracellular matrix (ECM) in physiological and pathological situations. Placentation is a key event of pregnancy in which MMPs/TIMPs system plays important roles in regulating the extravillus cytotrophoblast (EVTs) invasion. This paper focuses on expression patterns and regulatory mechanisms of MMPs/TIMPs family members during the process of placentation. Their implications in curing pregnancy-related diseases are also discussed.     

基质金属蛋白酶及其抑制剂与心、肾纤维化关系的研究进展

基质金属蛋白酶(MMPs)是降解细胞外基质(extracellular matrix,ECM)的重要酶类,组织金属蛋白酶抑制因子(TIMPs)是MMPs的内源性抑制物。业已证实,MMPs在各种生理、病理过程中,尤其是在心肌、肾脏纤维化的发生发展中发挥重要作用。本文就MMPs和TIMPs的分类、结构及其与心肌和肾脏纤维化的关系进行综述。     

Role of plasminogen activators and inhibitors in reproduction

The recent progress in the studies on the role of local and directed fibrinolysis controlled by plasminogen activators (PAs) and regulated by their inhibitors (PAIs) in reproduction is summarized. Hormone-induced coordinated expression of tissue type PA (tPA) and PAI type-1 (PAI-1) in the ovary is involved in the processes of ovulation and luteal regression; increases in urokinase type PA (uPA) and PAI-1 activity in the early stage of luteinized follicles may be responsible for ovarian tissue remodeling and angiogenesis; the PA system has been found to play an important role in spermatogenesis in testis and modulation of sperm maturation in epididymis. PA and matrix matalloproteanase (MMP) and their respective inhibitors have also been identified in trophoblast and uterus. The targeted proteolytic activity generated by the two systems may play an essential role in the processes of the cyclic uterine angiogenesis, implantation and placentation as well as parturition.     

基质金属蛋白酶与糖尿病性动脉粥样硬化

糖尿病并动脉粥样硬化（As）是糖尿病（DM）常见的慢性大血管并发症,DM死亡率中动脉粥样硬化占80%.基质金属蛋白酶（MMPs）与DM合并As的关系密切,MMPs在细胞外基质（ECM）动态平衡、组织重塑、修复等病理生理过程中起重要作用.DM合并As患者循环MMPs水平升高,提示MMPs在DM血管病变的发生、发展中起重要作用.应用干预措施降低MMPs产物活性有助于阻抑DM血管病变的发生、发展.     

基质金属蛋白酶家族在哺乳动物生殖过程中的作用

在成年灵长类的生活中,生殖器官在结构和功能特性上都在发生着明显的变化。这些由激素控制,并受到局部生长因子和细胞因子调节的变化,都广泛存在着结缔组织的重组。结缔组织的重组需要ECM(细胞外基质)成份的降解和重新合成两个过程。有许多酶可以ECM蛋白质的降解,但基质金属蛋白酶(MMPs)被认为是这一过程中起主要作用的酶。本文对MMP家族做一简要综述后,将着重讨论MMPs在不同生理状态(月经周期,着床,妊娠与分娩)下子宫中的表达及调控。     

Haemonectin, a bone marrow adhesion protein specific for cells of granulocyte lineage

There is substantial evidence that the haematopoietic microenvironment is crucial to the growth and differentiation of haematopoietic cells. This microenvironment is composed of stromal cells, soluble factors and extracellular matrix (ECM). We have shown that a complex extract of bone marrow ECM can stimulate the growth and differentiation of haematopoietic cells in vitro. Furthermore, the use of inhibitors or stimulators of ECM synthesis in long-term marrow culture affects cell proliferation. On a molecular level, however, the interactions between ECM and haematopoietic cells are not well understood. We have investigated the adhesion between specific bone marrow ECM components and haematopoietic cells, and found a protein, 'haemonectin', of relative molecular mass 60,000 in bone marrow ECM which is a lineage- and organ-specific attachment molecule for cells of granulocyte lineage. This specificity distinguishes haemonectin from previously described adhesion proteins which have a wider tissue distribution and cell type specificity.     

卵泡分化排卵和黄体发生的分子基础

本文综述了近二十年来在雌性生殖研究领域中五个方面的研究进展。（1）原始卵泡的启动生长和分化：原始卵泡生长启动可能受卵巢内在因子,像生长因子的调控,而不是人所想象的FSH;启动生长的卵泡受生长因子,FSH,激活素,孤儿受体和其他卵巢旁分泌因子调控,并发展成“优势卵泡”;（2）优势卵泡和闭锁卵泡：FSH,激活素／抑制素,卵泡抑素和雌激素调节卵泡分化的趋向,它们的相互作用和平衡决定“优热卵泡”和“闭锁卵泡”的形成,其中雌激素在此起关键性作用;它一方面促进FSH对LH受体的诱导作用,增加GC上的LH受体数目;另一方面可促进GC芳香水酶的产生,使此卵泡进入良性循环,发展为优势卵泡;（3）两种细胞两种促性尕激素学说：在FSH和LH作用下,GC产生的孕酮可被膜细胞利用转化为雄激素;因此GC和TC相互作用是卵巢雌激素产生的前提;（4）排卵:GC主要产生tPA,而TC主要表达tPA的抑制因子PAI－1,在激素作用下,GC的tPA和TC的PAI－1相互作用,形成一个局部蛋白水解窗口,它对卵泡破裂起决定性作用;（5）黄体形成和萎缩：uPA和MMP／TIMP系统对黄体发生起重要作用;而tPA对黄体萎缩起关键作用。     

Viewpoints on the proinflammation state of leukemia

Proinflammation represents a pathophysiological state on the early stage of a number of diseases, especially the infectious and immunological ones. In recent years, proinflammation has attracted much attention, and the term 損roinflammation factors?appears frequently in the literature. While investigating leukemia and leukemic cells from the angle of 損roinflammation state? we got some intriguing findings, e.g. we detected the significantly elevated expression of proinflammation factor IL-18 in patients with acute myeloid leukemia (AML), which could up-regulate matrix metalloproteinases (MMP) and specific tissue inhibitors (TIMPs). The increased MMP may play a role in the aggressiveness of myeloid leukemic cells, and be associated with a poor prognosis. This phenomenon reflects an ignored aspect of leukemia. Investigations from the angle of 損roinflammation state?have broaden the fields of tumor and leukemia study.     

Role of plasminogen activator and plasminogen activator inhibitor type-1 in luteolysis——a minireview

This minireview summarized our recent studies on the role of plasminogen activator (PA) and inhibitor type-1 (PAI-1) in luteolysis. We have demonstrated that (1) both tissue type and urokinase type plasminogen activators (tPA and uPA) and a plasminogen activator inhibitor type-1 (PAI-1) were present in the corpus luteum of rat and rhesus monkey; (2) decrease in progesterone production in corpus luteum was well correlated with a sharp increase in tPA (but not uPA) and PAI-1 secretion; (3) exogenous tPA decreased luteal progesterone synthesis while monoclonal antibodies increased progesterone production; (4) interferon y inhibited luteal progesterone synthesis and stimulated tPA production while LH plus pro-lactin increased progesterone production and decreased tPA (but not uPA) activity in cultured luteal cells; (5) increase in proteolysis in the corpus luteum was also correlated with decrease in progesterone production in mouse. These data suggest that local degradation of extracellular matrix controlled by plasminogen activator and inhibitor is involved in the processes of luteolysis.     

Role of plasminogen activator and plasminogen activator inhibitor type-1 in luteolysis—a minireview

This minireview summarized our recent studies on the role of plasminogen activator (PA) and inhibitor type-1 (PAI-1) in luteolysis. We have demonstrated that (1) both tissue type and urokinase type plasminogen activators (tPA and uPA) and a plasminogen activator inhibitor type-1 (PAI-1) were present in the corpus luteum of rat and rhesus monkey; (2) decrease in progesterone production in corpus luteum was well correlated with a sharp increase in tPA (but not uPA) and PAI-1 secretion; (3) exogenous tPA decreased luteal progesterone synthesis while monoclonal antibodies increased progesterone production; (4) interferony inhibited luteal progesterone synthesis and stimulated tPA production while LH plus prolactin increased progesterone production and decreased tPA (hut not uPA) activity in cultured luteal cells; (5) increase in proteolysis in the corpus luteum was also correlated with decrease in progesterone production in mouse. These data suggest that local degradation of extracellular matrix controlled by plasminogen activator and inhibitor is involved in the processes of luteolysis.     

肝细胞的三维受控组装

为解决肝病救治中肝供体缺乏的问题,采用基于快速成形技术的细胞组装机,将肝细胞和海藻酸钠与明胶复合材料的共混物作为成形对象,通过细胞材料直接三维受控组装技术,实现了堆积成形具有一定三维结构和预定义孔隙的肝组织前体。常规体外培养条件下,肝细胞存活并保持生物学活性达12d之久。这一技术有望成为肝脏及其他人体组织器官人工构造的新途径。     

月经周期中情绪冲突Stroop效应研究

探讨正常育龄妇女月经周期对情绪冲突的影响,以及不同时期的情绪注意偏向.研究采用重复测量设计的词-面孔Stroop任务,分析比较了21名被试在卵泡期和黄体期完成情绪判断任务和性别判断任务的正确率和反应时.结果发现:被试在两个任务中均表现出明显的情绪Stroop效应;在情绪判断任务中,月经周期对情绪冲突Stroop任务的影响有统计学意义(p0.01),在黄体期被试的情绪Stroop效应更加明显,对负性和正性情绪面孔识别的正确率和反应时均存在统计学意义(p0.01);在性别判断任务中发现,与黄体期相比,女性在卵泡期对男性面孔的识别正确率较高,反应时较短.研究结果表明:女性在黄体期的认知控制能力较卵泡期下降,同时对负性情绪表现出明显的注意偏向;卵泡期女性对男性面孔的偏好大于黄体期女性.     

The universality and biological significance of signal molecules with intracellular-extracellular compatible functions

Generally, cell signal molecules are classified into the extracellular signal molecules (the first messengers) and the intracellular signal ones (the second messengers). Cyclic adenosine monophosphate (CAMP), calcium ions and calmodulin (CaM) are the traditional intracellular messengers, but they are also present in extracellular matrix (ECM). Some of them have been discovered to act as the first messengers through cell surface receptors. Other second messengers, such as cyclic guanosine monophosphate (cGMP), cyclic adenosine diphosphate ribose (cADPR) and annexin, are also found existing outside animal and plant cells. The existence of these messengers with intracellular-extracellular compatible functions in cells may be a regular biological phenomenon. These compatible messengers might be the communication factors between intracellular and extracellular regions or among the cell populations, and are also important in regulating cell development procedure.     

Immunoreactive beta-endorphin in sheep ovary

Although the ovarian production of sex steroids is of obvious physiological importance, recent studies suggest that peptides such as oxytocin, relaxin and inhibin are also synthesized in the ovary. We report here the presence of immunoreactive (ir) beta-endorphin, ir-adrenocorticotropic hormone (ACTH) and presumptive high molecular weight forms of both in extracts of sheep ovary, consistent with ovarian production from a common precursor. Our findings suggest that beta-endorphin and ACTH are produced and secreted by the follicular cells, and that their production may be related to the oestrous cycle.     

Growth-cone attraction to netrin-1 is converted to repulsion by laminin-1.

Growing axons are guided by both diffusible and substrate-bound factors. Growth cones of retinal neurons exhibit chemoattractive turning towards the diffusible factor netrin-1 in vitro and are guided into the optic nerve head (ONH) by localized netrin-1. Here we report that, in Xenopus, laminin-1 from the extracellular matrix (ECM), converts netrin-mediated attraction into repulsion. A soluble peptide fragment of laminin-1 (YIGSR) mimics this laminin-induced conversion. Low levels of cyclic AMP in growth cones also lead to the conversion of netrin-induced attraction into repulsion, and we show that the amount of cAMP decreases in the presence of laminin-1 or YIGSR, suggesting a possible mechanism for laminin's effect. At the netrin-1-rich ONH, where axons turn sharply to leave the eye, laminin-1 is confined to the retinal surface. Repulsion from the region in which laminin and netrin are coexpressed may help to drive axons into the region where only netrin is present, providing a mechanism for their escape from the retinal surface. Consistent with this idea, YIGSR peptides applied to the developing retina cause axons to be misdirected at the ONH. These findings indicate that ECM molecules not only promote axon outgrowth, but also modify the behaviour of growth cones in response to diffusible guidance cues.     

Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands

Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression. Whereas the mechanism of hypoxia-driven angiogenesis is well understood, the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure. Here we show that the end products of lipid oxidation, ω-(2-carboxyethyl)pyrrole (CEP) and other related pyrroles, are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 or scavenger receptors on endothelial cells, leading to an angiogenic response that is independent of vascular endothelial growth factor. CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Taken together, these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.     

植物激素脱落酸的药理作用与药用前景

综述脱落酸(abscisic acid,ABA)在人和动物细胞中的存在和分泌、对各种组织细胞的作用及其信号途径等方面的研究进展.从海绵动物到多种哺乳动物的各种白细胞、胰岛细胞和干细胞等都能产生或分泌ABA,通过激活质膜上的G蛋白偶联复合受体,激活细胞内的腺苷二磷酸核糖环化酶,使细胞环腺苷二磷酸核糖升高,从而导致细胞内C...