Sulfated Hyaluronan Binds to Heparanase and Blocks Its Enzymatic and Cellular Actions in Carcinoma Cells

We examined whether sulfated hyaluronan exerts inhibitory effects on enzymatic and biological actions of heparanase, a sole endo-beta-glucuronidase implicated in cancer malignancy and inflammation. Degradation of heparan sulfate by human and mouse heparanase was inhibited by sulfated hyaluronan. In particular, high-sulfated hyaluronan modified with approximately 2.5 sulfate groups per disaccharide unit effectively inhibited the enzymatic activity at a lower concentration than heparin. Human and mouse heparanase bound to immobilized sulfated hyaluronan. Invasion of heparanase-positive colon-26 cells and 4T1 cells under 3D culture conditions was significantly suppressed in the presence of high-sulfated hyaluronan. Heparanase-induced release of CCL2 from colon-26 cells was suppressed in the presence of sulfated hyaluronan via blocking of cell surface binding and subsequent intracellular NF-κB-dependent signaling. The inhibitory effect of sulfated hyaluronan is likely due to competitive binding to the heparanase molecule, which antagonizes the heparanase-substrate interaction. Fragment molecular orbital calculation revealed a strong binding of sulfated hyaluronan tetrasaccharide to the heparanase molecule based on electrostatic interactions, particularly characterized by interactions of (−1)- and (−2)-positioned sulfated sugar residues with basic amino acid residues composing the heparin-binding domain-1 of heparanase. These results propose a relevance for sulfated hyaluronan in the blocking of heparanase-mediated enzymatic and cellular actions.     

Acute T-Cell-Driven Inflammation Requires the Endoglycosidase Heparanase-1 from Multiple Cell Types

It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, since many redundant proteases can solubilise BM it has been difficult to prove that proteases aid cell migration, particularly in vivo. Recent studies also suggest that other mechanisms allow BM passage of cells. To resolve this issue we exploited heparanase-1 (HPSE-1), the only endoglycosidase in mammals that digests heparan sulfate (HS), a major constituent of BM. Initially we examined the effect of HPSE-1 deficiency on a well-characterised adoptive transfer model of T-cell-mediated inflammation. We found that total elimination of HPSE-1 from this system resulted in a drastic reduction in tissue injury and loss of target HS. Subsequent studies showed that the source of HPSE-1 in the transferred T cells was predominantly activated CD4⁺ T cells. Based on bone marrow chimeras, two cellular sources of HPSE-1 were identified in T cell recipients, one being haematopoiesis dependent and the other radiation resistant. Collectively our findings unequivocally demonstrate that an acute T-cell-initiated inflammatory response is HPSE-1 dependent and is reliant on HPSE-1 from at least three different cell types.     

基于光学成像技术的针灸镇痛机理研究

疼痛治疗是一个医学难题。虽然人们对痛觉感受机理的认识已达到细胞分子水平,但现代医学疗法对疼痛尤其是慢性疼痛的治疗仍无良策。针灸镇痛疗法因副作用小、疗效好而逐渐获得西方认可。尽管针灸镇痛在临床上得到了验证,但是其机理尚未明确。正电子发射断层扫描(PET)、单光子发射计算机断层扫描(SPECT)和功能核磁共振成像(fMRI)、免疫组织化学等技术已被应用于针灸镇痛机理的研究。然而,这些技术在分辨率或无损检测等方面存在局限性,限制了它们在针灸镇痛机理研究中的进一步应用。介绍了采用光学成像技术研究针灸镇痛的机理,其中重点评述激光扫描共聚焦显微成像术、光学相干层析成像术及活体动物光学成像术在针灸镇痛机理研究中的应用。     

DOT1L Methyltransferase Regulates Calcium Influx in Erythroid Progenitor Cells in Response to Erythropoietin

Erythropoietin (EPO) signaling plays a vital role in erythropoiesis by regulating proliferation and lineage-specific differentiation of murine hematopoietic progenitor cells (HPCs). An important downstream response of EPO signaling is calcium (Ca²⁺) influx, which is regulated by transient receptor potential channel (TRPC) proteins, particularly TRPC2 and TRPC6. While EPO induces Ca²⁺ influx through TRPC2, TRPC6 inhibits the function of TRPC2. Thus, interactions between TRPC2 and TRPC6 regulate the rate of Ca²⁺ influx in EPO-induced erythropoiesis. In this study, we observed that the expression of TRPC6 in KIT-positive erythroid progenitor cells was regulated by DOT1L. DOT1L is a methyltransferase that plays an important role in many biological processes during embryonic development including early erythropoiesis. We previously reported that Dot1l knockout (Dot1l^KO) HPCs in the yolk sac failed to develop properly, which resulted in lethal anemia. In this study, we detected a marked downregulation of Trpc6 gene expression in Dot1l^KO progenitor cells in the yolk sac compared to the wild type (WT). The promoter and the proximal regions of the Trpc6 gene locus exhibited an enrichment of H3K79 methylation, which is mediated solely by DOT1L. However, the expression of Trpc2, the positive regulator of Ca²⁺ influx, remained unchanged, resulting in an increased TRPC2/TRPC6 ratio. As the loss of DOT1L decreased TRPC6, which inhibited Ca²⁺ influx by TRPC2, Dot1l^KO HPCs in the yolk sac exhibited accelerated and sustained elevated levels of Ca²⁺ influx. Such heightened Ca²⁺ levels might have detrimental effects on the growth and proliferation of HPCs in response to EPO.     

APT废水中氨氮的测定

APT废水中氨氮主要以铵盐的形式存在,采用蒸馏滴定法测定其氨氮的总量,方法以20 g/L硼酸溶液为吸收液,吸收蒸馏出的NH3,用甲基红--亚甲基蓝为指示剂,硫酸标准溶液滴定.方法的标准平均偏差为1.9%,回收率为99%～105%.     

X射线荧光光谱熔片分析的校准曲线与玻璃片质量校正

在铁合金和铁矿石的X射线荧光光谱(XRF)熔片分析中,存在着样品直接灼烧和熔融质量变化不同产生的误差,常用的稀释比校正无法校正这种误差。实验提出在固定质量(体积)的熔剂中熔入系列被测组分的氧化物制备出质量(体积)相同的玻璃片标准系列,建立X射线荧光强度与玻璃片中被测组分体积浓度的函数曲线,使用样品玻璃片质量与校准曲线玻璃片的质量比校准分析结果,即质量校正代替稀释比校正。以纯物质(SiO₂、CaCO₃、Al₂O₃和Fe₂O₃)为标准,用选定的仪器工作条件,建立了硅钙合金分析用Si、Ca、Fe、Al质量分数对荧光强度的校准曲线,其线性相关系数分别为0.9990、0.9993、0.9994、0.9995。用标准样品考察了校准曲线的准确度。t检验结果表明,当玻璃片的质量变化较大时,不使用质量校正测量结果偏差较大,正确度差。     

氟离子促进石煤提钒浸出过程的热力学研究

讨论了含氟化钙的主要含钒矿物为金云母的石煤直接酸浸过程中可能发生的化学反应,并进行热力学分析和建立浸出反应模型。结果表明,氟离子强化石煤提钒浸出的机理是氟与铝、硅生成AlF52-和SiF62-,从而降低金云母被破坏的自由能,使其更易溶解,其破坏过程是分步进行的。     

硫铝酸钙改性硅酸盐水泥应用研究进展

硫铝酸钙改性硅酸盐水泥熟料兼具硅酸盐水泥熟料和硫铝酸盐水泥熟料的优良性能,同时该种水泥熟料对粉煤灰等火山灰类材料具有超强的活性激发效果,这使得硫铝酸钙改性硅酸盐水泥具有广阔的应用前景。主要概括了硫铝酸盐改性硅酸盐水泥的性能及水化特性,综述了该种水泥与不同矿物掺合料的复合性能以及与化学外加剂的适应性,提出了硫铝酸钙改性硅酸盐水泥存在的问题及改善措施。     

助剂对CaSO_4载氧体化学链燃烧的影响

在固定床实验台架上,研究了CaSO4和添加助剂的CaSO4与气体燃料发生反应的特性。结果表明:助剂可大幅度地提高CaSO4的反应活性,缩短反应时间。在950℃下,所有复合载氧体的转化率均超过95%。在还原和氧化过程中,载氧体释放的SO2曲线呈单峰特性,且随温度显著增大;温度对COS的释放没有明显的影响作用。含Ni-Fe的载氧体等转化率下硫的损失率最小。通过程序升温还原、X射线衍射和场发射扫描电镜等表征分析,研究了样品的反应性能,成分与结构变化,并提出了一个可能的催化还原反应和硫释放机制。