Roles of Nitric Oxide and Asymmetric Dimethylarginine in Pregnancy and Fetal Programming

Nitric oxide (NO) regulates placental blood flow and actively participates in trophoblast invasion and placental development. Asymmetric dimethylarginine (ADMA) can inhibit NO synthase, which generates NO. ADMA has been associated with uterine artery flow disturbances such as preeclampsia. Substantial experimental evidence has reliably supported the hypothesis that an adverse in utero environment plays a role in postnatal physiological and pathophysiological programming. Growing evidence suggests that the placental nitrergic system is involved in epigenetic fetal programming. In this review, we discuss the roles of NO and ADMA in normal and compromised pregnancies as well as the link between placental insufficiency and epigenetic fetal programming.     

Increased Placental Phospholipid Levels in Pre-Eclamptic Pregnancies

Physiological pregnancy is associated with an increase in lipids from the first to the third trimester. This is a highly regulated response to satisfy energy and membrane demands of the developing fetus. Pregnancy disorders, such as pre-eclampsia, are associated with a dysregulation of lipid metabolism manifesting in increased maternal plasma lipid levels. In fetal placental tissue, only scarce information on the lipid profile is available, and data for gestational diseases are lacking. In the present study, we investigated the placental lipid content in control versus pre-eclamptic samples, with the focus on tissue phospholipid levels and composition. We found an increase in total phospholipid content as well as changes in individual phospholipid classes in pre-eclamptic placental tissues compared to controls. These alterations could be a source of placental pathological changes in pre-eclampsia, such as lipid peroxide insult or dysregulation of lipid transport across the syncytiotrophoblast.     

Role of Melatonin in Schizophrenia

Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia’s biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.     

Melatonin Receptor Genes in Vertebrates

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.     

N-乙酰基-5-甲氧基色胺的化学合成

综合国内外大量文献,简单介绍N-乙酰基-5-甲氧基色胺(褪黑素)的化学合成的理化性质、生理活性、用途和化学合成工艺路线,并提出了一条以丙二酸二乙酯和丙烯腈为起始原料的适合工业生产的简便、经济的化学合成方法,该工艺具有原料易得、反应条件温和、质量好和收率高等特点。     

N-乙酰-5-甲氧基色胺的工艺研究进展

综述了N-乙酰-5-甲氧基色胺主要的合成方法,并对各路线的优缺点进行评价,提出了可行的改进方向.     

高效液相色谱-二极管阵列检测法快速测定化妆品中褪黑激素

建立了一种简单、快速测定化妆品中褪黑激素的分析方法。样品经甲醇提取后经反相C18柱(4.6×250 mm,5μm)分离,体积比65∶35的水-乙腈作为流动相,等度洗脱,流速为1.0 mL/min,二极管阵列检测器进行检测,检测波长为223 nm,外标法定量。在优化实验条件下,褪黑激素在0.5~100 mg/L范围内线性关系良好,在空白化妆品中添加0.5、5.0、50.0 mg/kg 3个浓度水平时,得到的回收率为91%~101%,相对标准偏差为2.1%~3.9%。方法的检出限(S/N=3)为1.0 mg/kg,定量限(S/N=10)为5.0 mg/kg。该方法简单、快速、准确,可满足化妆品中褪黑激素的检测要求。     

Roles of clays in soils

In soil science, the term clay refers to all particles less than 2 μm in diameter. Thus it includes layer silicates, oxides and other minerals. Clays are the source of many of the chemical and physical properties of soils that make them a useful medium for the growth of plants and for the less common uses such as a medium for the disposal of wastes. Clays add much of the diversity found in soils. The minerals in soil clays frequently differ from their counterparts in commercial deposits. Also, the behavior of soil clays is influenced by the associated minerals in the coarser fractions. Organic matter is an important reactant with clays of some soils, but it is beyond the scope of this review.The cation exchange properties of clays are among their most important properties in retaining plant nutrient ions (e.g., NH₄⁺, K⁺, Ca²⁺, Mg²⁺, etc.). Cation selectivity of clays influences soils as a plant growth medium and as a disposal medium for wastes (e.g., radioactive and toxic metal ions). Native K in layer silicates of soils is the most important element provided to plants by illites and other micas. Clays contribute to the formation of soil structure by undergoing seasonal shrinking and swelling. Also, they are transported and form clay films that coat natural aggregates that characterize many friable soils. The dispersion and flocculation of clays are important reactions in the physical behavior of soils which in turn influence friability, water infiltration rate, erodibility and other behavioral properties.Vermiculite and smectite in soils frequently have Al³⁺ or polymeric Al on the cation exchange sites. Thus the behavior of these minerals is different from structurally similar minerals in natural deposits. The Fe oxides in soils occur largely as goethite and hematite. Yet they contain Al substituted in their structures, consequently the crystals are smaller and less soluble than their ideal counterparts. Iron oxides contribute to the color, aggregation, and adsorptive properties of soils. Manganese oxides in soils contribute to the retention of trace metals (Co, Zn, Ba, Ni, etc.) and to the oxidation of Fe. Lithiophorite forms in acid soils thus marking another group of minerals that occurs in soils and that is influenced by Al in the structure or in interlayer positions as a result of weathering.     

褪黑素的合成研究

通过对褪黑素合成工艺的研究与改进,使氮的烷基化反应中的二溴丙烷消耗降低了３７％;关环反应中１０％氯化氢的乙醇溶液用量减少了３５％;５－甲氧基色胺精制中避免了高成本六甲基二硅胺的使用;乙酰化反应与产品的精制在同一体系中进行,这样既得到了高纯度褪黑素,又简化了工艺操作。使原料总成本降低达２５％左右,生产工艺更适合于工业化生产。产品达到药用标准。     

褪黑激素(Melatonin)合成的研究

以吲哚为起始原料,经4步反应合成了褪黑激素(MLT),吲哚I在甲醇中羟基化得到5-羟基吲哚(Ⅱ)(7l％),Ⅱ与2-氯乙胺在乙酸乙酯中进行胺乙基化反应得到5-羟基色胺(Ⅲ)(73％),Ⅲ与硫酸二甲酯在甲苯中对羟基进行醚化,得到5-甲氧基色胺(Ⅳ)(78％),Ⅳ经乙酰化得到产物MLT,收率80％。     

褪黑素的化学合成方法

根据褪黑素的结构特点,综述了其不同的化学合成路线,并结合我国国情,提出了比较可行的3种褪黑素合成方法。     

Melatonin and Female Hormone Secretion in Postmenopausal Overweight Women

Estrogen deficiency is considered to be the main cause of increased appetite and increased weight in postmenopausal women. In this period, reduced secretion of melatonin (MEL) was also observed. The aim of the study was to evaluate the secretion of melatonin, 17-β estradiol and follicle-stimulating hormone (FSH) in relation to body mass index (BMI) in pre- and postmenopausal women. The study included 90 women divided into three equal groups: group I (control)—women without menstrual disorders, group II—postmenopausal women without change in appetite and body weight, group III—postmenopausal women experiencing increased appetite and weight gain. In each patient, serum melatonin, 17-β-estradiol, FSH and urine a 6-sulfatoxymelatonin (aMT6s) were determined. Compared to the control group, the level of melatonin and estradiol was statistically lower. The FSH level was higher than in the groups of postmenopausal women. No significant correlation was found in all groups between the level of melatonin and the levels of estradiol and FSH. A negative correlation was found between aMT6s excretion and BMI, and a positive correlation between the level of FSH and BMI, mainly in overweight women. The obtained results indicate a significant effect of melatonin deficiency on the process of weight gain in postmenopausal women and justify its use in treatment of these disorders.     

血小板相关因子在血栓性疾病中的作用

血栓性疾病(thrombotic disease)已成为全球人类死亡的主要原因,每年约720万人死于该病。而血小板(blood platelet)的功能与血栓性疾病的发生发展密切相关,如血小板相关组织因子(tissue factor,TF)、Toll样受体(Toll-like receptors,TLRs)、血小板表面Fc受体γ链(Fc receptor gamma-chain)、平均血小板体积(mean platelet volume,MPV)、P选择素(p-selectin)、血小板膜糖蛋白V(glycoprotein V,GPV)以及血小板内皮细胞黏附分子-1(platelet endothelial cell adhesion molecule-1,PECAM-1)等均参与血栓形成过程。本文就血小板相关因子在血栓性疾病中的作用作一综述,为临床心血管疾病的治疗提供参考。     

离聚体在聚合物共混中的特殊作用

共混方法是获得新型功能高聚物的常用、有效,也是最经济的方法之一,文章结合实例介绍了离聚体在聚合物共混过程中的各种特殊作用.     

Emerging Roles of Claudins in Human Cancer

Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism remains unclear. The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of claudins as predictors of tumor recurrence. The critical role of epigenetic mechanisms in the regulation of claudin expression indicates the possible application of epigenetic therapy to target claudins. A better understanding of the emerging role of claudins in CSC/TICs and chemoresistance may help to develop therapies against recurrent cancers.     

Quantification and Application of Potential Epigenetic Markers in Maternal Plasma of Pregnancies with Hypertensive Disorders

The aim of this study was to evaluate quantitative aberrations of novel fetal-specific epigenetic markers in maternal plasma of pregnancies with hypertensive disorders. We compared the concentrations of DSCR3, RASSF1A, and SRY as cell-free fetal DNA markers in 188 normal pregnancies, 16 pregnancies with early-onset preeclampsia (EO-PE), 47 pregnancies with late-onset preeclampsia (LO-PE), and 29 pregnancies with gestational hypertension (GH). The concentrations of all markers were significantly correlated with gestational age (p < 0.001 for all). Strong positive correlations were also observed between DSCR3 and SRY (r = 0.471, p < 0.001), as well as between RASSF1A and SRY (r = 0.326, p = 0.015) and between DSCR3 and RASSF1A (r = 0.673, p < 0.001). The concentrations of DSCR3 and RASSF1A in the EO-PE were significantly higher at 24–32 weeks and onwards (p < 0.05 for both). In the LO-PE, DSCR3 and RASSF1A concentrations were significantly higher only at 33–41 weeks compared with the controls. The concentrations of all markers in the GH group were not significantly different from those in the control group. This study is the first demonstration that DSCR3 is a novel epigenetic marker that can be an alternative to the RASSF1A for the prediction of EO-PE.     

Expression of the MT1 Melatonin Receptor in Ovarian Cancer Cells

Ovarian cancer (OC) is the leading cause of death among women with genital tract disorders. Melatonin exhibits oncostatic properties which it may effect through binding to its membrane receptor, MT1. The aim of this study was to determine the expression of MT1 in OC cells and to correlate this with clinical and pathological data. Immunohistochemistry was performed on 84 cases of OC. Normal ovarian epithelial (IOSE 364) and OC (SK-OV-3, OVCAR-3) cell lines were used to examine the MT1 expression at protein level using the western blot and immunofluorescence technique. The expression of MT1 was observed as cytoplasmic-membrane (MT1_CM) and membrane (MT1_M) reactions. A positive correlation between MT1_CM and MT1_M was found in all the studied cases. There were no significant differences between the expression of MT1_CM, MT1_M, and histological type, staging, grading, presence of residual disease, or overall survival time. Immunofluorescence showed both MT1_M and MT1_CM expression in all the tested cell lines. Western blot illustrated the highest protein level of MT1 in IOSE 364 and the lowest in the OVCAR-3. The results indicate the limited prognostic significance of MT1 in OC cells.     

Melatonin Promotes Superovulation in Sika Deer (Cervus nippon)

In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1 ± 2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98 ± 0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p < 0.05). The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p > 0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed.