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In Silico Structural Analysis and Characterization of Human Kiss-1 Receptor: A Metastasis Suppressor Protein in Melanomas and Breast Cancer 人类Kiss-1受体:黑色素瘤和乳腺癌转移抑制蛋白的硅结构分析和表征
Pub Date : 2012-12-01 DOI: 10.18519/JER/2012/V16/75930
S. S. Swain, S. Mohanty, D. Panda, S. Rout, P. Padhi
Metastasis, a major cause of death in cancer patients, involves the spread of a tumor or cancer to distant parts of the body as primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS1 is a metastasis-suppressor protein that suppresses metastases in malignant melanomas and in some breast carcinomas, without affecting tumorigenicity and also may be mediated in part by cell cycle arrest and induction of apoptosis in malignant cells. To understand the operational mechanism, structural model is always important. Therefore, in present study a complete structural analysis and three- dimensional (3D) modeling of KiSS-1 receptor, with a molecular weight of 42,586 kDa, of Homo sapiens was carried out. The 398 amino acid sequence of the KiSS-1 receptor protein was retrieved from Uniprot KB database (Acc. no: Q969F8). Based on the PDB Blast result and analysis the three-dimensional structure of KiSS-1R was predicted by using the SWISS MODEL, ESyPred 3D protein comparative modeling server. The predicted model was further assessed by Rampage, VERIFY-3D and PROCHECK graph with acceptable scores. The overall result provides evidence of good quality of model and furnishes an adequate foundation for functional analysis of experimentally derived crystal structures and also helps in understanding metastasis.
转移是癌症患者死亡的主要原因,包括肿瘤或癌症作为原发癌症扩散到身体的远处,侵犯周围组织,通过循环扩散,在远处器官再次侵袭和增殖。KiSS1是一种转移抑制蛋白,可抑制恶性黑色素瘤和某些乳腺癌的转移,但不影响致瘤性,也可能部分通过恶性细胞的细胞周期阻滞和诱导凋亡介导。为了理解其运行机制,结构模型总是很重要的。因此,本研究对分子量为42,586 kDa的智人KiSS-1受体进行了完整的结构分析和三维建模。从Uniprot KB数据库(Acc)中检索到KiSS-1受体蛋白的398个氨基酸序列。没有:Q969F8)。基于PDB Blast的结果和分析,利用SWISS MODEL、ESyPred三维蛋白比较建模服务器对KiSS-1R的三维结构进行了预测。通过Rampage、VERIFY-3D和PROCHECK图对预测模型进行进一步评估,得分可接受。结果表明模型质量良好,为实验导出的晶体结构的功能分析提供了充分的基础,也有助于理解转移。
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引用次数: 1
Functional Pleiotropy of Melatonin in the Regulation of Reproduction: An Overview 褪黑素在生殖调节中的功能多效性研究综述
Pub Date : 2012-06-01 DOI: 10.18519/JER/2012/V16/76136
P. Pal, Kazi Nurul Hasan, S. K. Maitra
This brief review covers recent important findings to form an informative pool depicting unique role of the pineal hormone melatonin in the regulation of reproductive axis in vertebrates. Since last decades, melatonin research witnessed an enormous progress in understanding the nature and mechanism of actions of this tiny, but versatile, product of tryptophan in the regulation of diverse body functions, especially reproduction in different groups of vertebrates. Demonstration of melatonin receptors on different peripheral organs and parts of brain essentially supported the contention of a hormonal effect of melatonin. Several lines of evidence suggest that melatonin regulates, rather modulates, vertebrate reproduction by two pathways- one through controlling the hypothalamo-hypophyseal- gonadal axis and another by inducing direct effect on the gonads through G-protein coupled MT1 and MT2 receptors. The conventional idea of the regulatory actions of melatonin on gonads via the hypothalamo-hypophyseal- gonadal axis involving gonadotrophic releasing hormone (GnRH) and gonadotrophins, has been greatly enriched by the discovery of other hypothalamic peptides like, gonadotrophic inhibitory hormone (GnIH) and kisspeptin. Additional findings that melatonin, due to its lipophilicity and potential antioxidant property, scavenges and detoxifies various free radicals, opened up a possibility of its significant contribution to the physiology of oocytes during growth and maturation. As an obvious outcome of unequivocal evidence suggesting pleiotropic functions of melatonin in the regulation of vertebrate reproduction, studies on the array of molecular events occurring at different sites of melatonin actions have emerged as a new exciting area of investigation.
这篇简短的综述涵盖了最近的重要发现,以形成一个信息库,描述松果体激素褪黑素在脊椎动物生殖轴调节中的独特作用。近几十年来,对褪黑素的研究取得了巨大进展,人们了解了这种微小但用途广泛的色氨酸产物在调节各种身体功能方面的性质和作用机制,特别是在不同脊椎动物群体中的繁殖。褪黑激素受体在不同外周器官和大脑部分的证明基本上支持褪黑激素激素效应的论点。一些证据表明,褪黑素通过两种途径调节脊椎动物的繁殖——一种是通过控制下丘脑-垂体-性腺轴,另一种是通过g蛋白偶联MT1和MT2受体对性腺产生直接影响。传统观点认为褪黑素通过下丘脑-垂体-性腺轴参与促性腺释放激素(GnRH)和促性腺激素对性腺的调节作用,随着其他下丘脑肽如促性腺抑制激素(GnIH)和kisspeptin的发现,这一观点得到了极大的丰富。另外的研究发现,褪黑素由于其亲脂性和潜在的抗氧化特性,清除和解毒各种自由基,开辟了其在卵母细胞生长和成熟过程中对生理的重要贡献的可能性。作为明确证据表明褪黑素在调节脊椎动物生殖中的多功能性的明显结果,对褪黑素作用的不同位点发生的一系列分子事件的研究已成为一个新的令人兴奋的研究领域。
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引用次数: 2
Melatonin, Insomnia and the Use of Melatonergic Drugs 褪黑激素、失眠和褪黑激素药物的使用
Pub Date : 2012-06-01 DOI: 10.18519/JER/2012/V16/76361
V. Srinivasan, R. Zakaria, Zahiruddin Othman, A. Brzezinski
Due to inconsistency among reports on the therapeutic efficacy of melatonin, attention has been focused on the development of more potent melatonin analogues with prolonged effects. Melatonergic drugs, ramelteon and agomelatine have been effective in treating either sleep disorders or sleep disturbances associated with depressive disorders. MT 1 and MT 2 melatonergic receptor agonist, ramelteon, was found effective in increasing total sleep time and sleep efficiency, and in reducing sleep latency in patients with insomnia. No reduction in its efficacy was found even after 6-12 months of continuous use. The mechanism of sleep promoting action of ramelteon is entirely different from that of conventional hypnotics that are in use today. Ramelteon's use is not associated with any adverse effects even after six months to one year after its continuous usage. Another melatonergic drug, agomelatine, has also been found effective in improving sleep efficiency and quality, and this action of agomelatine is suggested to be one of the major mechanism by which agomelatine ameliorates depressive symptoms in patients with major depressive disorders and bipolar disorders.
由于关于褪黑素治疗效果的报道不一致,人们一直关注于开发更有效的长效褪黑素类似物。褪黑激素药物,拉美替恩和阿戈美拉汀在治疗睡眠障碍或与抑郁症相关的睡眠障碍方面是有效的。发现mt1和mt2褪黑激素受体激动剂ramelteon可有效增加失眠患者的总睡眠时间和睡眠效率,并减少睡眠潜伏期。即使在连续使用6-12个月后,其疗效也没有下降。ramelteon促进睡眠的作用机制与目前使用的传统催眠药完全不同。即使在连续使用6个月至1年后,Ramelteon的使用也没有任何不良反应。另一种褪黑激素药物阿戈美拉汀也被发现能有效改善睡眠效率和质量,阿戈美拉汀的这种作用被认为是阿戈美拉汀改善重度抑郁症和双相情感障碍患者抑郁症状的主要机制之一。
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引用次数: 2
Eco-Immunology: Role of Melatonin in Avian Immune Defense 生态免疫学:褪黑素在禽类免疫防御中的作用
Pub Date : 2012-06-01 DOI: 10.18519/JER/2012/V16/76077
S. Yadav, C. Haldar
Avian immunology is a fascinating and growing field. Ecologists are now taking an interest in measuring immune-competence and determining its importance as a heritable trait for the survival of the wild species. Seasonally breeding animals encounter different environmental challenges throughout the year. In order to survive in specific environments these animals have developed various strategies that help them to find food, protect themselves from the tough environments, and also reproduce accordingly. Indeed, wild birds are continually challenged with different natural stressors such as shortage of food (during winter and rainy season), lack of water during summer, predator pressure in social system, sudden change in weather, season-bound diseases, infection (like avian influenza), etc. Only a few ecological studies have analyzed the stress and general immunity in wild birds that might have a link with the anti-stress hormone melatonin. Therefore, approaches improving our understanding of the stress-induced immune depression and their interrelationship in birds are most desirable. Unfortunately, our knowledge of the immune system has advanced at a much faster pace for mammals while immunology of wild birds received less attention. The purpose of this review is to bring together the current knowledge on the biological effects of melatonin on avian immune defense with special emphasis on new immerging area of neuro-immuno-endocrinology i.e., eco-immunology.
禽免疫学是一个迷人的和不断发展的领域。生态学家现在对测量免疫能力和确定其作为一种遗传特征对野生物种生存的重要性很感兴趣。季节性繁殖的动物全年都会遇到不同的环境挑战。为了在特定的环境中生存,这些动物已经发展出各种各样的策略来帮助它们寻找食物,保护自己免受恶劣环境的侵害,并相应地繁殖。事实上,野生鸟类不断受到各种自然压力的挑战,如食物短缺(冬季和雨季),夏季缺水,社会系统中的捕食者压力,天气的突然变化,季节性疾病,感染(如禽流感)等。只有少数生态学研究分析了野生鸟类的压力和一般免疫力,这可能与抗应激激素褪黑激素有关。因此,改善我们对鸟类应激性免疫抑制及其相互关系的理解的方法是最可取的。不幸的是,我们对哺乳动物免疫系统的了解发展得更快,而野生鸟类的免疫学却很少受到关注。本文综述了褪黑素对禽类免疫防御生物学作用的最新研究进展,重点介绍了神经免疫内分泌学的新领域,即生态免疫学。
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引用次数: 2
Melatonin: Circadian Regulation of Biomarkers of Oxidative Stress 褪黑素:氧化应激生物标志物的昼夜节律调节
Pub Date : 2012-06-01 DOI: 10.18519/JER/2012/V16/76307
S. Chakravarty, S. Rizvi
Melatonin, released primarily from the pineal gland, controls the 24 hour biological clock. It is now known that melatonin also controls circannual reproductive cycles in animals and plays a role in neuroprotection, tumor-suppression, and immunomodulation. The hormone is also a potent antioxidant. This review is an attempt to document the pleiotropic biological effects of melatonin.
褪黑素主要由松果体释放,控制着24小时的生物钟。现在已经知道,褪黑素还控制着动物的年度生殖周期,并在神经保护、肿瘤抑制和免疫调节方面发挥作用。这种激素也是一种有效的抗氧化剂。本文综述了褪黑素的多效生物学效应。
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引用次数: 0
Impact of Sewage Effluents on Osmoregulation in a Freshwater Teleost, Anabas testudineus 污水对淡水硬骨鱼(Anabas testudineus)渗透调节的影响
Pub Date : 2011-06-01 DOI: 10.18519/JER/2011/V15/76850
R. Binitha, S. Soorya, C. A. Devi, F. Sunny
This study investigated the impact of sewage effluents of the polluted river, Parvathyputhenar in Trivandrum city, Kerala, India, on the activities of osmoregulatory enzymes such as Na + /K + and Ca 2+ ATPases, the concentration of sodium and potassium ion content in the gill and on the chloride cells (CCs) and pavement cells (PCs) that regulate ions transport in the gill epithelium of a freshwater fish. The results indicate a significant (P<0.05) decrease in the activity of branchial Na + /K + ATPase and Ca 2+ ATPase in the fish exposed to sewage effluents for 7, 14 and 28 days and the fish caught from the polluted river. When the fish caught from the polluted river were kept in normal pond water in the laboratory for 30, 60 and 90 days, the enzyme's activities were gradually increased and almost restored to the control level. Scanning electron microscopic analysis of gill epithelium showed noticeable changes in the surface area morphology of CCs and PCs in the fish exposed to sewage effluents. Exposure to the sewage effluents drastically altered the size and characteristic "finger print" pattern of PCs and also reduced number of CCs in the gill epithelium. As the ATPases play an important role in maintenance of functional integrity of gill epithelium it is suggested that measurement of the activities of ATPases may be used as a biomarker of exposure to sewage effluents. This work is highly pertinent in the context of increased level and effect of endocrine disrupting chemicals present in the aquatic systems, which are increasing day by day.
本研究调查了印度喀拉拉邦特里vandrum市Parvathyputhenar污染河流的污水对淡水鱼鳃上皮中调节离子运输的氯细胞(CCs)和铺装细胞(PCs)渗透调节酶(如Na + /K +和ca2 + atp酶)活性的影响,以及鳃中钠和钾离子含量的浓度。结果表明,污水处理7、14和28 d的鱼和污染河流捕获的鱼鳃Na + /K + atp酶和ca2 + atp酶活性显著(P<0.05)降低。从污染河流捕获的鱼在实验室的正常池塘水中饲养30、60和90天后,酶的活性逐渐增加,几乎恢复到对照水平。鳃上皮的扫描电镜分析显示,接触污水的鱼的cc和pc的表面积形态发生了明显的变化。暴露于污水中大大改变了pc的大小和特征“指纹”模式,也减少了鳃上皮中cc的数量。由于atp酶在维持鳃上皮的功能完整性方面起着重要作用,因此建议测量atp酶的活性可作为污水暴露的生物标志物。这项工作是高度相关的背景下增加水平和影响内分泌干扰化学物质存在于水生系统,这是日益增加的。
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引用次数: 0
Effect of Mammalian Gonadotropins (FSH & LH) on Regressed Testis of the Snake Enhydris enhydris Schneider 哺乳动物促性腺激素(FSH和LH)对蛇退化睾丸的影响
Pub Date : 2011-06-01 DOI: 10.18519/JER/2011/V15/76951
R. Jadhav, A. S. Padgaonkar
Aadministration of mammalian gonadotropins (FSH & LH during the regressed phase of testes of the snake Enhydris enhydris induced spermatogenesis, and caused hypertrophy of Leydig cells. The results indicate that the testis of Enhydris enhydris is not refractory to gonadotropin stimulation during regressed phase of the reproductive cycle. It is further suggested that all aspects of testicular function in snakes may be accounted for by a single FSH-like gonadotropin.
在Enhydris enhydra的睾丸退化期给予哺乳动物促性腺激素(FSH和LH)可诱导精子发生,并引起睾丸间质细胞肥大。结果表明,在生殖周期退行期,雌雄大鼠睾丸对促性腺激素的刺激并不难耐受。这进一步表明,蛇类睾丸功能的所有方面都可能由一种类似fsh的促性腺激素来解释。
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引用次数: 0
Seasonal Male Reproductive Cycle of the Estuarine Snake Enhydris enhydris Schneider 河口蛇Enhydris Enhydris Schneider的季节性雄性生殖周期
Pub Date : 2011-06-01 DOI: 10.18519/JER/2011/V15/76867
R. Jadhav, A. S. Padgaonkar
The testis of Enhydris enhydris undergoes a definite seasonal reproductive cycle. Breeding takes place during the month of October, following which the testes regress. There is definite arrest of spermatogenesis till the next breeding season. Based on the histological examination of the seminiferous epithelium, the testicular activity is divided into four phases, recrudescent, breeding, degenerate and regressed. Recrudescence begins in the month of June. The testis becomes spermatogenically functional at the beginning of October. The testicular weight and gonado-somatic index show a gradual increase during the recrudescent phase (June -Sep) reaching the peak in the month of October. At the onset of degenerative phase the testicular weight and gonado-somatic index start decreasing. A corresponding seasonal variation is reflected in the ductus epididymidis and ductus deferens as observed from the epithelial cell height and the diameter of the respective ducts. On the other hand the sexual segment of kidney never reaches peak and does not indicate any seasonal cycle.
Enhydris Enhydris的睾丸有一定的季节性生殖周期。繁殖发生在10月份,之后睾丸退化。到下一个繁殖季节,精子的发生肯定会停止。根据精原上皮组织学检查,睾丸活动可分为复发期、繁殖期、退化期和退行期四个阶段。六月开始复发。睾丸在10月初开始具有生精功能。睾丸重量和性腺指数在复发期(6 - 9月)逐渐增加,在10月达到高峰。在退行期开始时,睾丸重量和性腺指数开始下降。从上皮细胞的高度和各自导管的直径来看,附睾导管和异管也有相应的季节变化。另一方面,肾的性征部分从未达到峰值,也没有任何季节周期。
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引用次数: 3
Effects of follicle stimulating hormone (FSH) on the regressed testes of the snake Enhydris enhydris (Schneider) 促卵泡激素(FSH)对蛇退化睾丸的影响
Pub Date : 2010-06-01 DOI: 10.18519/JER/2010/V14/77698
R. Jadhav, A. S. Padgaonkar
Administration of FSH (1IU/day) to the snake Enhydris enhydris for 14, 28 and 42 days resulted in increase in diameter of the seminiferous tubules of the regressed testes. Proliferation of spermatogonia and increase in abundance of primary spermatocytes were also observed. But the treatment failed to induce the spermatogenic cells to meiotic division. The interstitial cells in the testes between control and FSH-treated snakes did not show any difference. The failure to complete the process of spermatogenesis after FSH treatment indicates that role by a second hormone is necessary for the completion of spermatogenic process. The second hormone may be either LH or androgen.
FSH (1IU/d)连续14、28和42天使退行性睾丸精管直径增加。同时还观察到精原细胞增殖和原代精母细胞丰度的增加。但该处理不能诱导生精细胞进行减数分裂。对照组和fsh处理蛇的睾丸间质细胞没有任何差异。FSH治疗后不能完成生精过程表明第二激素的作用是完成生精过程所必需的。第二种激素可能是黄体生成素或雄激素。
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引用次数: 0
Melatonin and Methoxytryptophol have Temporal Effect on Tail Elongation but not Methoxytryptamine: Studies on Tail Regeneration in Hemidactylus flaviviridis 褪黑素和甲氧基色氨酸对尾伸长有时间效应,而甲氧基色氨酸对尾伸长无时间效应——黄绿半毛驴尾再生的研究
Pub Date : 2010-06-01 DOI: 10.18519/JER/2010/V14/77697
A. Kurup, A. Ramachandran
In order to evaluate the time-specific influence of pineal indoles on tail regeneration in lizards, melatonin (M), methoxytryptophol (ML) and methoxytryptamine (MT) were administered intraperitonealy to different groups of lizards at morning 7:00 hrs (m) or in the evening at 17:00 hrs (e). The Mm and MLe groups of lizards showed a delay in the attainment of various arbitrary stages of regeneration like wound healing, pre-blastema, blastema and initiation of growth while the Me and MLm groups of lizards showed hastened attainment. However, MTm and MTe treatments did not bring about any difference compared to the controls. The total length of tail regenerated and percentage replacement at the end of 30 days were significantly less in Mm and MLe groups of lizards. MTm and MTe treatments, however, did not affect the regeneration process. The results indicate that M and ML have opposite time-specific effects on regeneration, while MT has no effect. Apparently, M and ML are part of the photoperiodic and neuro-endocrine transduction mechanisms related to regenerative growth in lizards.
为了评估松果体吲哚对蜥蜴尾巴再生的时间特异性影响,我们分别在早上7点(M)和晚上17点(e)给不同组的蜥蜴腹腔注射褪黑素(M)、甲氧基色氨酸(ML)和甲氧基色胺(MT)。Mm和MLe组的蜥蜴在伤口愈合、胚前、而Me组和MLm组则表现出更快的发育。然而,与对照组相比,MTm和MTe处理没有带来任何差异。Mm组和MLe组30 d尾再生总长度和替换率显著低于MLe组。然而,MTm和MTe处理不影响再生过程。结果表明,M和ML对再生具有相反的时间特异性作用,而MT对再生没有影响。显然,M和ML是与蜥蜴再生生长相关的光周期和神经内分泌转导机制的一部分。
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引用次数: 2
期刊
Journal of Endocrinology and Reproduction
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