6,6-二溴青霉烷酸甲酯的合成

以6-氨基青霉烷酸(6-APA)为原料,在非均相反应体系中加入催化剂聚乙二醇,使氨基取代和a-H的取代同时完成,制得6,6-二溴青霉烷酸．再以三氯化铝作催化剂,用工业甲醇与6,6-二溴青霉烷酸进行酯化反应．同时讨论了时间、温度、投料比和催化剂用量对酯化反应条件的影响．工业甲醇／6,6-二溴青霉烷酸(质量比)为4,三氯化铝5％(以6,6-二溴青霉烷酸的质量计),最佳反应温度为27℃,最佳反应时间为6h,产率达到96．2％．     

Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis

Osteoarthritis is a chronic joint disease characterized by pain and immobility due to a gradual loss of cartilage. Current treatments are palliative; there is no cure. With a growing interest in alternative therapies, due in part to safety issues regarding pharmacological treatments like Celebrex, safe dietary compounds that help the body regenerate cartilage tissue are of great clinical importance. The dietary supplement S-adenosylmethionine (SAMe) shows such potential. Clinical trials have shown reduced pain and stiffness while in vitro and animal studies have shown SAMe can stimulate the production of cartilage which is critical in reversing the disease process. The author examines many potential mechanisms of action including: reduction of inflammatory mediators; increasing levels of glutathione; direct or indirect signaling of cartilage synthesis or survival; maintenance of DNA methylation. Research into the mechanisms of supplemental SAMe in osteoarthritis is necessary to evaluate the clinical effectiveness and safety of this dietary supplement.     

表观遗传修饰-他莫昔芬耐药机制研究的新方向

他莫昔芬(tamoxifen,TAM)为人工合成的非甾体类抗雌激素药物,被广泛用于雌激素受体(estrogen receptor,ER)阳性的乳腺癌患者的治疗。但是仍有约40%的ER阳性乳腺癌患者对TAM产生继发性耐药。目前对TAM耐药机制研究众多,而表观遗传学是最新的研究方向。在本综述中,我们将从表观遗传调控方面阐述当前对TAM耐药机制研究的新进展,以便更好地了解TAM耐药,并为乳腺癌治疗提供新的策略。     

丙戊酸钠抗抑郁作用涉及改善氧化应激平衡和提升脑源性神经营养因子表达

目的: 探讨丙戊酸钠减轻慢性不可预见刺激(CUS)致大鼠抑郁行为是否与改善机体氧化应激功能及脑源性神经营养因子(BDNF)表达有关。方法: 雄性SD大鼠60只,随机分为对照组(CG),模型组(MG),丙戊酸钠灌胃正常组(VAPC)和丙戊酸钠灌胃模型组(VAPM)。以开场试验和强迫游泳试验评价大鼠焦虑抑郁行为;采用常规生物化学方法测定大脑皮质丙二醛(MDA)含量及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活力;荧光定量PCR和Western blot检测海马脑源性神经营养因子(BDNF)mRNA和蛋白表达。结果: 与CG组相比,MG组大鼠开场试验水平得分和垂直得分明显降低,强迫游泳试验不动时间显著延长,MDA含量升高,SOD及CAT活力明显下降,海马BDNF mRNA和蛋白表达均明显降低。给予丙戊酸钠可明显阻遏上述变化,但对正常大鼠无明显影响。结论: CUS致大鼠焦虑抑郁行为与体内氧化及抗氧化失衡,海马BDNF表达减少有关;丙戊酸钠能阻遏这种变化,从而显示减轻CUS所致大鼠焦虑抑郁行为作用。     

Effects of Prenatal Phthalate Exposure and Childhood Exercise on Maternal Behaviors in Female Rats at Postpartum: A Role of Oxtr Methylation in the Hypothalamus

Both the detrimental effect of prenatal exposure to di-(2-ethylhexyl)-phthalate (DEHP) and the beneficial effects of physical exercise on brain functions have been reported. The oxytocin pathway has been implicated in the onset of maternal behaviors. Epigenetic modification of the oxytocin receptor gene (OXTR) through DNA methylation has been associated with the pathogenesis of neuropsychiatric disorders. The purpose of this study was to investigate the effects of prenatal DEHP exposure on oxytocin-regulated maternal behaviors and to examine the protective effect of exercise. Pregnant rats (F0) were fed with vehicle or DEHP during gestation and the offspring females (F1) were assessed for their maternal behaviors by pup retrieval test at postpartum. The results showed that reduced pup retrieval activities without significant alteration of stress responses were observed in the prenatally DEHP-exposed females. Prenatal DEHP exposure decreased the expressions of oxytocin, Oxtr mRNA, and oxytocin receptor, and increased Oxtr methylation in the hypothalamus of postpartum female rats. There were no significant effects of exercise on behavioral, biochemical, and epigenetic measurements. These results suggest that prenatal DEHP exposure has a long-term adverse effect on maternal behaviors; Oxtr hyper-methylation may be a potential epigenetic mechanism for this alteration, which cannot be prevented by physical exercise during childhood.     

浅谈高吸水性树脂的研制及应用

简述了淀粉的接枝共聚,纤维素接枝共聚,交联合成树脂等高吸水树脂的合成方法,并介绍了在日用化工,农业及医用方面的多种应用,指出了淀粉接枝共聚方法是一种原料丰富,成本低廉,产物可自然分解的首选方法。     

高血压表观遗传药理学研究进展

伴随着遗传药理学的发展,人们逐渐认识到基因多态性不能完全解释降压药物疗效的个体差异。在分子水平上,高血压药物相关代谢酶、受体、转运体都受到基因表达调控的影响,并在降压疗效差异中起着重要的作用。因此,从表观遗传学的角度研究遗传因素与降压药物之间的关系,将有助于更好地解释临床上药物反应产生的个体差异。本文综述总结了DNA甲基化、组蛋白修饰和microRNAs等表观遗传调控方式对高血压相关药物编码基因的影响。