水飞蓟宾预防和治疗前列腺癌的作用机制

目的综述了水飞蓟宾预防和治疗前列腺癌的作用机制。方法对近几年国内外文献资料进行总结和归纳。结果水飞蓟宾是水飞蓟种子提取物水飞蓟素的主要有效成分,它可以通过改变细胞周期进程,抑制有丝分裂和细胞存活信号、抑制肿瘤细胞血管生成因子的分泌、以及促使上皮细胞凋亡等方式来抑制前列腺癌细胞的分化和生长。而且水飞蓟宾对化疗药物阿霉素表现协同作用,可以缓和前列腺特异抗原的升高。结论由于水飞蓟宾几乎没有毒性,现已被用作食品添加剂以预防前列腺癌。它也已进入临床试验,可望在不久的将来成为防治前列腺癌的药品。     

Epigenetic Mechanisms Are Involved in the Regulation of Ethanol Consumption in Mice

Background:

Repeated alcohol exposure is known to increase subsequent ethanol consumption in mice. However, the underlying mechanisms have not been fully elucidated. One postulated mechanism involves epigenetic modifications, including histone modifications and DNA methylation of relevant genes such as NR2B or BDNF.

Methods:

To investigate the role of epigenetic mechanisms in the development of alcohol drinking behavior, an established chronic intermittent ethanol exposure reinforced ethanol drinking mouse model with vapor inhalation over two 9-day treatment regimens was used. The DNA methyltransferase inhibitor, 5-azacytidine or the histone deacetylase inhibitor, Trichostatin A was administered (intraperitoneally) to C57BL/6 mice 30min before daily exposure to chronic intermittent ethanol. Changes in ethanol consumption were measured using the 2-bottle choice test.

Results:

The results indicated that systemic administration of Trichostatin A (2.5 µg/g) facilitated chronic intermittent ethanol-induced ethanol drinking, but systemic administration of 5-azacytidine (2 µg/g) did not cause the same effect. However, when 5-azacytidine was administered by intracerebroventricular injection, it facilitated chronic intermittent ethanol-induced ethanol drinking. Furthermore, the increased drinking caused by chronic intermittent ethanol was prevented by injection of a methyl donor, S-adenosyl-L-methionine. To provide evidence that chronic intermittent ethanol- or Trichostatin A-induced DNA demethylation and histone modifications of the NR2B promoter may underlie the altered ethanol consumption, we examined epigenetic modifications and NR2B expression in the prefrontal cortex of these mice. Chronic intermittent ethanol or Trichostatin A decreased DNA methylation and increased histone acetylation in the NR2B gene promoter, as well as mRNA levels of NR2B in these mice.

Conclusions:

Taken together, these results indicate that epigenetic modifications are involved in regulating ethanol drinking behavior, partially through altering NR2B expression.     

Impact of Epigenetic Dietary Compounds on Transgenerational Prevention of Human Diseases

The etiology of most human diseases involves complicated interactions of multiple environmental factors with individual genetic background which is initially generated early in human life, for example, during the processes of embryogenesis and fetal development in utero. Early embryogenesis includes a series of programming processes involving extremely accurate time-controlled gene activation/silencing expressions, and epigenetic control is believed to play a key role in regulating early embryonic development. Certain dietary components with properties in influencing epigenetic processes are believed to have preventive effects on many human diseases such as cancer. Evidence shows that in utero exposure to certain epigenetic diets may lead to reprogramming of primary epigenetic profiles such as DNA methylation and histone modifications on the key coding genes of the fetal genome, leading to different susceptibility to diseases later in life. In this review, we assess the current advances in dietary epigenetic intervention on transgenerational human disease control. Enhanced understanding of the important role of early life epigenetics control may lead to cost-effective translational chemopreventive potential by appropriate administration of prenatal and/or postnatal dietary supplements leading to early disease prevention.     

某地区部队官兵皮肤病的调查分析及防治对策

目的调查长白地区部队皮肤病发生情况,分析其发病原因,为防止提供科学依据。方法采用普查法,对986例长白部队官兵进行皮肤病流行病学调查。结果检测出皮肤病190例,发病率为19%。感染性皮肤病、皮肤附属器疾病及真菌性皮肤病发病率最高。结论部队官兵常见皮肤病为感染性皮肤病、皮肤附属器疾病及真菌性皮肤病;驻地环境、高强度训练及皮肤病防治知识缺乏时长白地区部队皮肤病发生的主要原因;应加强皮肤病的防治宣传,采取有效科学方法进行防治,提高部队军医的皮肤诊治水平是主要的防治措施。     

Molecular Targets and Mechanisms of Cancer Prevention and Treatment by Withaferin A, A Naturally Occurring Steroidal Lactone

The plants used in Ayurvedic medicine, which has been practiced in India for thousands of years for the treatment of a variety of disorders, are rich in chemicals potentially useful for prevention and treatment of cancer. Withania somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is one such medicinal plant whose anticancer value was realized over four decades ago after isolation of a crystalline steroidal compound (withaferin A) from the leaves of this shrub. The root and leaf extracts of W. somnifera are shown to confer protection against chemically-induced cancers in experimental rodents, and retard tumor xenograft growth in athymic mice. Anticancer effect of W. somnifera is generally attributable to steroidal lactones collectively referred to as withanolides. Withaferin A (WA) appears most active against cancer among structurally divergent withanolides isolated from the root or leaf of W. somnifera. Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models. This review summarizes the key in vivo preclinical studies demonstrating anticancer effects of WA. Molecular targets and mechanisms likely contributing to the anticancer effects of WA are also discussed. Finally, challenges in clinical development of WA for the prevention and treatment of cancer are highlighted.     

标准化皮肤护理对乳腺癌放疗后皮损的疗效评价

目的探究标准化皮肤护理对乳腺癌放疗后皮损的临床效果。方法本次选取乳腺癌放疗后皮损患者120例作为研究对象,收治时间2015年6月17日至2017年9月17日,分为对照组(给予常规护理)、观察组(在对照组的基础上给予标准化皮肤护理);并对120例患者的皮肤护理效果及总体健康状况评分、生活质量(心理职能、生理功能、疾病治疗、社会功能)进行观察及评估。结果两组乳腺癌放疗后皮损患者在皮肤护理效果对比中存在一定差异,P<0.05。两组乳腺癌放疗后皮损患者在总体健康状况评分对比中存在一定差异,P<0.05。观察组与对照组患者在生活质量评估对比中存在明显差异,即观察组数据高于对照组数据,P值<0.05。结论标准化皮肤护理对乳腺癌放疗后皮损具有较高的应用价值,不仅可以改善皮肤损伤程度,并且还能提高患者的生活质量及耐受性,临床上值得应用及推广。     

自黏性软聚硅酮薄膜敷料预防乳腺癌术后急性放射性皮炎的研究

目的探讨自黏性软聚硅酮薄膜敷料(美菲)对乳腺癌患者急性放射性皮炎的防护效果。方法选取我院84例乳腺癌术后患者为研究对象,随机分为对照组42例、试验组42例,对照组行常规放疗皮肤护理,试验组在放疗前予美菲膜贴于照射野皮肤表面。分别使用RTOG及RISRAS评分表评估放疗期间及放疗后2周急性放射性皮炎的严重程度。结果 RTOG评分显示,试验组Ⅰ、Ⅱ、Ⅲ级放射性皮炎发生率分别为78.6%、16.7%、4.7%,对照组Ⅰ、Ⅱ、Ⅲ级放射性皮炎发生率分别为16.7%、59.5%、23.8%,差异有统计学意义(P<0.001);与对照组相比较,试验组Ⅰ、Ⅱ、Ⅲ级放射性皮炎发生时间更长,当发生相同等级放射性皮炎时,试验组累积放疗剂量更大(P<0.05)。RISRAS评分显示试验组较对照组显著降低,差异有统计学意义(P<0.001)。对照组总治疗时间较试验组延长(P<0.005)。结论乳腺癌术后患者在放疗前及全过程中使用美菲,可以显著降低急性放射性皮炎的发生。     

放射性皮肤损伤的药物防护现状

肿瘤放射治疗过程中发生放射性皮肤损伤是不可避免的,放射性皮肤损伤会导致患者舒适度的改变,降低患者生活质量,甚至被迫中断治疗,影响肿瘤放射治疗的效果,对于放射性皮肤损伤,目前没有统一的防治标准,为了减轻和降低放射性皮肤损伤,许多学者对其防治进行了大量研究,本文拟就其研究现状进行综述。     

Selective ��4��2 Nicotinic Acetylcholine Receptor Agonists Target Epigenetic Mechanisms in Cortical GABAergic Neurons

Nicotine improves cognitive performance and attention in both experimental animals and in human subjects, including patients affected by neuropsychiatric disorders. However, the specific molecular mechanisms underlying nicotine-induced behavioral changes remain unclear. We have recently shown in mice that repeated injections of nicotine, which achieve plasma concentrations comparable to those reported in high cigarette smokers, result in an epigenetically induced increase of glutamic acid decarboxylase 67 (GAD₆₇) expression. Here we explored the impact of synthetic α₄β₂ and α₇ nAChR agonists on GABAergic epigenetic parameters. Varenicline (VAR), a high-affinity partial agonist at α₄β₂ and a lower affinity full agonist at α₇ neuronal nAChR, injected in doses of 1–5 mg/kg/s.c. twice daily for 5 days, elicited a 30–40% decrease of cortical DNA methyltransferase (DNMT)1 mRNA and an increased expression of GAD₆₇ mRNA and protein. This upregulation of GAD₆₇ was abolished by the nAChR antagonist mecamylamine. Furthermore, the level of MeCP₂ binding to GAD₆₇ promoters was significantly reduced following VAR administration. This effect was abolished when VAR was administered with mecamylamine. Similar effects on cortical DNMT1 and GAD₆₇ expression were obtained after administration of A–85380, an agonist that binds to α₄β₂ but has negligible affinity for α₃β₄ or α₇ subtypes containing nAChR. In contrast, PNU–282987, an agonist of the homomeric α₇ nAChR, failed to decrease cortical DNMT1 mRNA or to induce GAD₆₇ expression. The present study suggests that the α₄β₂ nAChR agonists may be better suited to control the epigenetic alterations of GABAergic neurons in schizophrenia than the α₇ nAChR agonists.     

金粉蕨素体外诱导人宫颈癌HeLa 细胞凋亡的机制

目的：探讨金粉蕨素（ONY）体外诱导人宫颈癌HeLa细胞凋亡的作用及其分子机制。方法体外培养人宫颈癌HeLa、CaSki、SiHa、ME180细胞,采用MTT法检测ONY对人宫颈癌HeLa、CaSki、SiHa、ME180细胞生长抑制率的影响;Hoechst33258染色检测ONY对人宫颈癌HeLa细胞凋亡的形态学变化;流式细胞术（FCM）检测ONY对HeLa细胞凋亡率的影响;DNA琼脂糖电泳检测HeLa细胞凋亡的DNA条带;Western blot分析凋亡相关蛋白表达变化。结果 ONY对人宫颈癌HeLa、CaSki、SiHa、ME180细胞生长有较强的抑制作用,呈剂量和时间依赖性,以HeLa细胞对ONY最为敏感,作用24 h的IC50值为10.48μg·mL-1。经ONY作用于HeLa细胞24 h后,细胞出现典型的凋亡形态学改变,表现出典型的凋亡特征的亚二倍体峰,且呈剂量依赖性,同时出现典型的凋亡DNA条带;同时,cytochrome c、caspase-9和caspase-3蛋白表达增加,bcl-2蛋白表达下调,而bax蛋白表达不变, Bcl-2/Bax比值下调（P〈0.05）。结论 ONY可能通过调控线粒体途径相关蛋白抑制宫颈癌HeLa细胞增殖并诱导其凋亡。