糖尿病大血管病变的表观遗传学标志物

表观遗传学是指在不改变核苷酸序列的情况下,基因的表达活性发生了可遗传的变化,它包括DNA甲基化、组蛋白修饰、miRNA等.表观遗传学在糖尿病大血管病变的发生、发展过程发挥了重要的作用.近年来研究发现了一些反映糖尿病大血管病变的表观遗传学标志物,包括LINE-1甲基化、Alu甲基化、DDAH2启动子甲基化;Sirt1与SET7等组蛋白修饰相关酶;miRNA-126、miRNA-21、miRNA-125b等.随着表观遗传改变检测手段的改进,表观遗传学标志物有可能成为糖尿病大血管病变新的诊断手段.     

表观遗传调控在胰岛β细胞功能调控中的研究进展

表观遗传是指在DNA序列不发生改变情况下,基因表达发生可遗传性改变的现象.表观遗传在疾病发生发展中发挥重要作用,其机制十分复杂,包括DNA甲基化、组蛋白修饰和非编码RNA等.2型糖尿病是一种由遗传和环境因素共同作用而发生的复杂多基因遗传性疾病,其病因和发病机制目前尚未完全阐明.近年研究发现,表观遗传直接或间接调控胰岛β细胞的发育、分化、分泌功能以及机体对胰岛素的敏感性,参与2型糖尿病的发生和发展.对表观遗传调控的研究将为阐明2型糖尿病发病机制,及预防和治疗2型糖尿病提供新的思路和靶点.     

表观遗传修饰在糖尿病代谢记忆中的作用

糖尿病患者在血糖得到控制后,糖尿病并发症仍然持续发展的现象提示了以前暴露于高血糖导致的“代谢记忆”.近来的研究提示“代谢记忆”可能归因于靶细胞的表观遗传改变.许多实验证据显示:组蛋白乙酰基转移酶(HATs)、组蛋白去乙酰化酶(HDACs)、组蛋白甲基转移酶(HMTs)、组蛋白赖氨酸去甲基化酶(KDMs)以及microRNA在调节几种与糖尿病并发症相关的关键基因表观遗传修饰中发挥了重要作用.进一步阐明表观遗传修饰在糖尿病“代谢记忆”中的作用机制以及明确相应的细胞信号通路,对于糖尿病及其并发症的防治有重要意义.     

糖尿病肾病足细胞损伤的表观遗传调控

表观遗传修饰是糖尿病肾病的重要机制之一,足细胞损伤是疾病进展的核心事件。不同表观遗传修饰方式可通过单独作用或交叉对话,改变足细胞结构和功能、促进足细胞凋亡及上皮间充质转化、影响足细胞自噬,以及参与足细胞内质网应激和线粒体功能障碍等过程,参与足细胞损伤。表观遗传是可逆的,通过治疗干预改变表观遗传修饰可能是防治糖尿病肾病的一个重要方向。     

表观遗传学与糖尿病肾病

表观遗传调控主要包括DNA甲基化、组蛋白修饰和微小RNA(miRNA)等.糖尿病肾病(DN)是糖尿病主要的慢性并发症之一.一些特定基因的启动子区甲基化水平异常,组蛋白乙酰化与去乙酰化及miRNA等都参与了DN的发生、发展.对表观遗传学与DN关系的研究,可为进一步认识和治疗DN提供一种新的途径.     

N6-甲基腺嘌呤RNA修饰在糖尿病及其并发症中的研究进展

糖尿病是常见的慢性病之一,可引发多个系统的并发症。表观遗传失调在疾病的发生中至关重要,对mRNA的可逆化学修饰是控制基因表达的重要调控机制。N6-甲基腺嘌呤（m 6A）修饰的失调与糖尿病及其并发症的发生相关。笔者对m 6A调控在糖尿病和相关并发症中的最新发现进行综述。     

表观遗传学和肾脏疾病

表观遗传学是研究基因的核苷酸序列不发生改变的情况下发生可遗传修饰的一门学科。表观遗传机制包括DNA甲基化、组蛋白修饰、基因组印记、母体效应、基因沉默和非编码RNA的调控作用等。目前,对于表观遗传学的研究主要集中在DNA甲基化、组蛋白修饰和非编码RNA的调控上,其机制在肾脏疾病的发生和发展中亦起重要作用。     

早期发育营养与成年期糖代谢异常的表观遗传学机制

尽管人们普遍认为基因与生活方式是糖尿病风险增加的主要因素,但基因改变只能部分解释糖尿病患病风险增加的原因.早期发育环境（营养状况）能显著影响成年期发生糖尿病的风险.表观遗传学与糖尿病、代谢综合征、癌症等慢性病的发病关系密切,由于表观遗传可以受到环境的刺激而发生变化,而改变的表观遗传特性可在细胞分裂中得以保持并存在,因此,表观遗传很可能是早期发育环境异常与导致成年期糖代谢紊乱这一现象的重要分子基础.另外越来越多的动物模型和大型临床研究数据显示表观遗传学机制在成年期糖代谢异常的发生发展的过程中起着十分关键的作用[1].本文将简要介绍如下.     

表观遗传修饰在糖尿病慢性并发症中的研究进展

探讨表观遗传学对糖尿病主要并发症发生发展的作用机制。基于表观遗传学改变的可逆性，良好的饮食习惯和适当的运动将会一定程度遏制糖尿病并发症的发展，同时可在修饰的相关靶点进行有针对性的药物靶向干预，帮助患者更好的防止和控制并发症，减少致残率和病死率。     

表观遗传学与肺癌

表观遗传学是指无DNA序列变化、可遗传的基因表达的改变.表观遗传学的分子机制主要包括DNA甲基化及组蛋白修饰,这些生物大分子的修饰在细胞周期,基因组印记、X染色体的失活中起重要作用.表观遗传学的改变与肿瘤及肺癌的发生、发展密切相关,它在疾病中的重要性越来越受到关注,表观遗传学的改变有可能成为新的诊断、监测及治疗的工具.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.