硫氧还蛋白和硫氧还蛋白相互作用蛋白与糖尿病及其并发症关系的研究进展

硫氧还蛋白系统是由硫氧还蛋白、NADPH和硫氧还蛋白还原酶三部分组成的氧化还原敏感的多功能小分子蛋白系统。硫氧还蛋白系统在细胞内外行使着多种功能,如调节细胞氧化还原状态以对抗氧化应激,激活转录因子如NF-κB和AP-1促生长,以及与ASK-1作用抑制细胞凋亡等。硫氧还蛋白相互作用蛋白\硫氧还蛋白结合蛋白2\维生素D3上调蛋白1为硫氧还蛋白结合蛋白之一,是硫氧还蛋白功能和表达的一种负性调节因子,通过抑制硫氧还蛋白系统功能而发挥介导氧化应激、诱导细胞凋亡及对抗细胞增殖等作用。高糖可以通过相互作用蛋白启动子上的CREs(碳水化合物反应元件)刺激硫氧还蛋白相互作用蛋白的产生而抑制硫氧还蛋白,进而促进氧化应激,损伤胰岛B细胞;诱导B细胞凋亡增加,促进糖尿病及其并发症的发生。因此,硫氧还蛋白相互作用蛋白或许在糖毒性和B细胞凋亡、糖尿病及其并发症之间起着重要作用。     

细胞外硫氧还蛋白的作用

硫氧还蛋白(thioredoxin,Trx)是具有多种生物学功能的一种小分子蛋白质.它和硫氧还蛋白还原酶及NADPH组成硫氧还蛋白系统,具有抗氧化、促细胞生长、抗细胞凋亡和调节转录因子活性作用.近年研究发现,Trx可以分泌到细胞外,而胞外Trx与许多疾病有关.胞外Trx抑制中性粒细胞到炎症反应部位,抑制促炎因子的表达释放.因此,胞外Trx即可作为一些疾病的标志,同时又具有重要的免疫调节作用.     

硫氧还蛋白系统在骨质疏松症中的作用

越来越多的研究表明氧化应激与骨质疏松症的发生密切相关,而硫氧还蛋白(Trx)系统其中一个重要作用就是参与调节细胞氧化还原状态以对抗氧化应激,其是由Trx、硫氧还蛋白还原酶(TrxR)和还原型辅酶Ⅱ(NADPH)以及硫氧还蛋白相互作用蛋白(TXNIP)组成的多功能小分子蛋白系统,因此在骨质疏松症的发生发展中扮有重要角色。本文综述了硫氧还蛋白系统和骨质疏松症之间的联系。     

硫氧还蛋白与肝脏疾病

硫氧还蛋白(thioredoxin,Trx)是一种低分子质量、进化上高度保守的有还原双硫键活力的蛋白质,主要功能是调节细胞胞内氧化还原平衡,参与氧应激诱导的细胞凋亡,并与肿瘤的发生密切相关.Trx与脂肪性肝病、病毒性肝炎、肝纤维化、肝硬化、肝癌等的发生发展及预后密切相关,此文综述Trx与肝脏疾病的关系.     

硫氧还蛋白生物活性及其与人类疾病的关系

硫氧还蛋白(thioredoxin，Trx)、硫氧还蛋白还原酶(thioredoxin reductase，TR)和还原型辅酶Ⅱ(NADPH)一起构成硫氧还蛋白系统(Trx系统)。这是一个广泛分布的NADPH依赖性二硫化物还原酶系统。Trx在TR的作用下可以从氧化型转变为还原型，还原型的Trx可以催化许多有二硫键暴露的蛋白质的还原反应。研究发现Trx除了基本的氧化还原调节功能，还有许多其他生物学活性，因而其与人类疾病的关系日益受到人们的重视。     

硫氧还蛋白系统调控细胞周期的研究进展

硫氧还蛋白系统除了调节机体内氧化还原反应,还具有多种生物学活性.在癌症组织细胞中硫氧还蛋白表达增高,提示硫氧还蛋白系统与肿瘤有关.最近研究表明硫氧还蛋白系统在细胞周期中起到重要调节作用,本文论述了硫氧还蛋白系统调控细胞周期的研究进展.     

硫氧还蛋白与癌症相关蛋白的关系

<正>癌症发病机制十分复杂,与许多基因有关,这些基因在癌症的发生、发展及转移过程中起着不同的作用,最终赋予了癌细胞两大基本的特征:细胞周期失去调控使得癌细胞无限增殖;癌细胞具有浸润性和扩散性。硫氧还蛋白(TRX)是氧化还原调节蛋白,在多种癌组织中表达增高,与癌症发生有着密切关系,具有调节多种癌症相关蛋白作用。本文综述了硫氧还蛋白与癌症相关蛋白的研究进展。见图1。     

硫氧还蛋白与肝脏疾病

硫氧还蛋白（thioredoxin,Trx）是一种低分子质量、进化上高度保守的有还原双硫键活力的蛋白质,主要功能是调节细胞胞内氧化还原平衡,参与氧应激诱导的细胞凋亡,并与肿瘤的发生密切相关。Trx与脂肪性肝病、病毒性肝炎、肝纤维化、肝硬化、肝癌等的发生发展及预后密切相关,此文综述Trx与肝脏疾病的关系。     

硫氧还蛋白结合蛋白-2与肿瘤的关系

尽管目前研究肿瘤的报导很多,肿瘤发病的分子机制仍不清楚.硫氧还蛋白结合蛋白-2(TRX-binding protein-2,TBP-2)又被称为维生素D3上调蛋白1(Vitamin D3 up-regulated protein1,VDUP1)或硫氧还蛋白相互作用蛋白(Thioredoxin-interacting protein,Txnip),它与硫氧还蛋白(thioredoxin,TRX)的活性部位结合,抑制其活性,除了参与多种氧化应激反应,还具有多种生物学功能.最近的研究显示:TBP-2与肿瘤密切相关,有些肿瘤组织中,TBP-2表达降低或缺失.TBP-2表达增高时,细胞周期停滞,肿瘤细胞繁殖受到抑制.因此,它已成为近年肿瘤研究的重要靶点.     

硫氧还蛋白对缺血再灌注保护机制研究进展

硫氧还蛋白与缺血再灌注相互作用:心肌缺血再灌注下调硫氧还蛋白表达并抑制其活性.硫氧还蛋白在细胞质、线粒体、细胞核及细胞外作用,平衡氧化还原状态、抗凋亡、抗炎、保护心肌细胞.     

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.     

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.     

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.     

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.