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New theory of uterovaginal embryogenesis 子宫-阴道胚胎发生的新理论
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2016-01-02 DOI: 10.1080/15476278.2016.1145317
Z. Makiyan
ABSTRACT Background: The explanation of uterine and vaginal embryogenesis in humans still poses many controversies, because it is difficult to assess early stages of an embryo. The literature review revealed many disagreements in Mullerian theory, inciting some authors to propose new embryological hypotheses. In the original Mullerian theory: the paramesonephral ducts form the Fallopian tubes, uterus and vagina; the mesonephral ducts regress in female embryos. Aims: The aim of this article is to investigate the development of Mullerian ducts in humans, using comparative analysis of fundamental embryological theory and various utero-vaginal anomalies. Material and methods: Between 1998 and 2015, 434 patients with various uterovaginal malformations had been operated on at the Scientific Centre of Obstetrics Gynaecology and Perynatology in Moscow. The anatomies of the uterovaginal malformations in these patients were diagnosed with ultrasound and MRI and then verified during surgical correction by laparoscopy. Results: A systematic comparison of uterovaginal malformations to those in the literature has allowed us to formulate a new theory of embryonic morphogenesis. The new theory is significantly different: ovary, ovarian ligamentum proprium, and ligamentum teres uteri derive from gonadal ridges; Fallopian tubes and vagina completely develop from mesonephral ducts. The uterus develops in the area of intersection between the mesonephral ducts with gonadal ridges by the fusion of the two. Conclusions: The new theory may to induce future embryological studies. The hypothetic possibility that the ovary and endometrium derive from the gonadal ridges could be the key to understanding the enigmatic aetiologies of extragenital and ovarian endometriosis.
背景:人类子宫和阴道胚胎发生的解释仍然存在许多争议,因为很难评估胚胎的早期阶段。文献综述揭示了缪勒理论中存在的诸多分歧,促使一些作者提出了新的胚胎学假说。在最初的缪勒氏理论中:肾旁管构成输卵管、子宫和阴道;在雌性胚胎中,中肾管退化。目的:本文的目的是通过对基础胚胎学理论和各种子宫阴道异常的比较分析来研究人类缪勒管的发育。材料和方法:1998年至2015年间,莫斯科妇产科科学中心对434名患有各种子宫阴道畸形的患者进行了手术。这些患者的子宫阴道畸形解剖是通过超声和MRI诊断的,然后在腹腔镜手术矫正中得到证实。结果:将子宫阴道畸形与文献中的畸形进行系统比较,使我们能够形成一种新的胚胎形态发生理论。新的理论有明显的不同:卵巢、卵巢固有韧带和子宫圆韧带起源于性腺脊;输卵管和阴道完全由肾系膜管发育而来。子宫发育在肾系管与性腺脊的交汇处,两者融合而成。结论:这一新理论可能为今后的胚胎学研究提供指导。卵巢和子宫内膜起源于性腺脊的假设可能是理解子宫外和卵巢子宫内膜异位症神秘病因的关键。
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引用次数: 19
Wnt-YAP interactions in the neural fate of human pluripotent stem cells and the implications for neural organoid formation Wnt-YAP在人类多能干细胞神经命运中的相互作用及其对神经类器官形成的影响
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2016-01-02 DOI: 10.1080/15476278.2016.1140290
Julie Bejoy, Liqing Song, Yan Li
ABSTRACT Human pluripotent stem cells (hPSCs) have shown the ability to self-organize into different types of neural organoids (e.g., whole brain organoids, cortical spheroids, midbrain organoids etc.) recently. The extrinsic and intrinsic signaling elicited by Wnt pathway, Hippo/Yes-associated protein (YAP) pathway, and extracellular microenvironment plays a critical role in brain tissue morphogenesis. This article highlights recent advances in neural tissue patterning from hPSCs, in particular the role of Wnt pathway and YAP activity in this process. Understanding the Wnt-YAP interactions should provide us the guidance to predict and modulate brain-like tissue structure through the regulation of extracellular microenvironment of hPSCs.
近年来,人类多能干细胞(hPSCs)显示出自组织成不同类型神经类器官的能力(如全脑类器官、皮质球类器官、中脑类器官等)。Wnt通路、Hippo/Yes-associated protein (YAP)通路和细胞外微环境诱导的外源性和内源性信号在脑组织形态发生中起着至关重要的作用。本文重点介绍了从hPSCs中提取神经组织模式的最新进展,特别是Wnt通路和YAP活性在这一过程中的作用。了解Wnt-YAP的相互作用将为我们通过调控hPSCs的细胞外微环境来预测和调节脑样组织结构提供指导。
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引用次数: 12
The role of endothelial cells on islet function and revascularization after islet transplantation 内皮细胞在胰岛移植后胰岛功能和血运重建中的作用
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2016-01-02 DOI: 10.1080/15476278.2016.1165378
A. del Toro-Arreola, A. K. Robles-Murillo, A. Daneri-Navarro, J. Rivas-Carrillo
ABSTRACT Islet transplantation has become a widely accepted therapeutic option for selected patients with type 1 diabetes mellitus. However, in order to achieve insulin independence a great number of islets are often pooled from 2 to 4 pancreata donors. Mostly, it is due to the massive loss of islets immediately after transplant. The endothelium plays a key role in the function of native islets and during the revascularization process after islet transplantation. However, if a delayed revascularization occurs, even the remaining islets will also undergo to cell death and late graft dysfunction. Therefore, it is essential to understand how the signals are released from endothelial cells, which might regulate both differentiation of pancreatic progenitors and thereby maintenance of the graft function. New strategies to facilitate islet engraftment and a prompt revascularization could be designed to intervene and might lead to improve future results of islet transplantation.
胰岛移植已成为1型糖尿病患者广泛接受的治疗选择。然而,为了实现胰岛素独立性,大量的胰岛通常由2到4个胰腺供体汇集。大多数情况下,这是由于移植后立即大量失去胰岛。内皮在天然胰岛的功能和胰岛移植后的血运重建过程中起着关键作用。然而,如果发生延迟的血运重建,即使是剩余的胰岛也会发生细胞死亡和晚期移植物功能障碍。因此,了解内皮细胞如何释放信号至关重要,这可能调节胰腺祖细胞的分化,从而维持移植物功能。促进胰岛移植和及时血运重建的新策略可以被设计用于干预,并可能导致改善未来胰岛移植的结果。
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引用次数: 22
Studies of gonadal sex differentiation 性腺性别分化的研究
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2016-01-02 DOI: 10.1080/15476278.2016.1145318
Z. Makiyan
ABSTRACT Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent embryonal differentiation stages. Between 1998 and 2015, 139 female patients with various (DSD) underwent operations at the Scientific Center of Obstetrics, Gynaecology and Perynatology in Moscow, Russia. Clinical investigations included karyotyping, ultrasound imaging, hormonal measurement and investigations of gonadal morphology. The male characteristics in the embryo are imposed by testicular hormones. When these are absent or inactive, the fetus may be arrested at between developmental stages, or stay on indifferent stage and become phenotypically female. A systematic analysis of gonadal morphology in DSD patients and a literature review revealed some controversies and led us to formulate a new hypothesis about sex differentiation. Proliferation of the mesonephric system (tubules and corpuscles) in the gonads stimulates the masculinization of gonads to testis. Sustentacular Sertoli cells of the testes are derived from mesonephric excretory tubules, while interstitial Leydig cells are derived from the original mesenchyme of the mesonephros. According of the new hypothesis, the original mesonephric cells (tubules and corpuscles) potentially persist in the ovarian parenchyma. In female gonads, some mesonephric excretory tubules regress and lose the tubular structure, but form ovarian theca interna and externa, becoming analogous to the sustentacular Sertoli cells in the testis. The ovarian interstitial Leydig cells are derived from intertubal mesenchyme of the mesonephros, similar to what occurs in male gonads (testis). Surprisingly, the leading determinative factor in sexual differentiation of the gonads is the mesonephros, represented by the embryonic urinary system.
性腺分化对人类胚胎的性发育具有决定性的影响。性发育障碍(DSD)与持续的胚胎分化阶段有关。1998年至2015年期间,139名患有各种(DSD)的女性患者在俄罗斯莫斯科的妇产科科学中心接受了手术。临床检查包括核型、超声成像、激素测量和性腺形态检查。胚胎中的男性特征是由睾丸激素决定的。当这些缺失或不活跃时,胎儿可能会在发育阶段之间停滞不前,或停留在无关阶段并成为表型上的女性。通过对DSD患者性腺形态的系统分析和文献回顾,我们发现了一些争议,并提出了一个关于性别分化的新假设。性腺中肾系统(小管和小体)的增生刺激性腺向睾丸的男性化。睾丸的支撑支持细胞来源于中肾排泄小管,而间质间质细胞来源于中肾原有的间质。根据新的假说,原来的中肾细胞(小管和小体)可能存在于卵巢薄壁组织中。在雌性性腺中,一些肾中排泄小管退化并失去管状结构,但形成卵巢内膜和外膜,变得类似于睾丸中的支撑性支持细胞。卵巢间质间质细胞来源于中肾的管间质,类似于男性性腺(睾丸)。令人惊讶的是,性腺性别分化的主要决定因素是中肾,以胚胎泌尿系统为代表。
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引用次数: 25
The role of stem cells in limb regeneration 干细胞在肢体再生中的作用
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2016-01-02 DOI: 10.1080/15476278.2016.1163463
Elizabeth R. Zielins, R. C. Ransom, Tripp Leavitt, M. Longaker, D. Wan
ABSTRACT Limb regeneration is a complex yet fascinating process observed to some extent in many animal species, though seen in its entirety in urodele amphibians. Accomplished by formation of a morphologically uniform intermediate, the blastema, scientists have long attempted to define the cellular constituents that enable regrowth of a functional appendage. Today, we know that the blastema consists of a variety of multipotent progenitor cells originating from a variety of tissues, and which contribute to limb tissue regeneration in a lineage-restricted manner. By continuing to dissect the role of stem cells in limb regeneration, we can hope to one day modulate the human response to limb amputation and facilitate regrowth of a working replacement.
肢体再生是一个复杂而迷人的过程,在许多动物物种中观察到一定程度,尽管在尾纲两栖动物中看到它的全部。通过形成形态一致的中间体——胚基,科学家们长期以来一直试图确定能够使功能性附属物再生的细胞成分。今天,我们知道胚基由多种来自多种组织的多能祖细胞组成,并以谱系限制的方式促进肢体组织再生。通过继续研究干细胞在肢体再生中的作用,我们可以希望有一天能够调节人类对肢体截肢的反应,并促进工作替代物的再生。
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引用次数: 14
From hacking the human genome to editing organs 从破解人类基因组到编辑器官
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2015-10-02 DOI: 10.1080/15476278.2015.1120047
Takamasa Tobita, J. Guzman‐Lepe, Alexandra Collin de l'Hortet
ABSTRACT In the recent decades, human genome engineering has been one of the major interesting research subjects, essentially because it raises new possibilities for personalized medicine and biotechnologies. With the development of engineered nucleases such as the Zinc Finger Nucleases (ZFNs), the Transcription activator-like effector nucleases (TALENs) and more recently the Clustered Regularly Interspaced short Palindromic Repeats (CRISPR), the field of human genome edition has evolved very rapidly. Every new genetic tool is broadening the scope of applications on human tissues, even before we can completely master each of these tools. In this review, we will present the recent advances regarding human genome edition tools, we will discuss the numerous implications they have in research and medicine, and we will mention the limits and concerns about such technologies
近几十年来,人类基因组工程一直是一个重要的有趣的研究课题,主要是因为它为个性化医疗和生物技术提供了新的可能性。随着工程核酸酶如锌指核酸酶(ZFNs)、转录激活因子样效应核酸酶(TALENs)和最近的聚集规则间隔短回语重复序列(CRISPR)的发展,人类基因组编辑领域发展非常迅速。每一种新的基因工具都在扩大人类组织的应用范围,甚至在我们完全掌握这些工具之前。在这篇综述中,我们将介绍关于人类基因组编辑工具的最新进展,我们将讨论它们在研究和医学中的众多影响,我们将提到这些技术的限制和关注
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引用次数: 5
Cell Therapy Strategies to Combat Immunosenescence 对抗免疫衰老的细胞治疗策略
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2015-10-02 DOI: 10.1080/15476278.2015.1120046
E. Stahl, B. Brown
abstract Declining function of the immune system, termed “immunosenescence,” leads to a higher incidence of infection, cancer, and autoimmune disease related mortalities in the elderly population.1 Increasing interest in the field of immunosenescence is well-timed, as 20% of the United States population is expected to surpass the age of 65 by the year 2030.2 Our current understanding of immunosenescence involves a shift in function of both adaptive and innate immune cells, leading to a reduced capacity to recognize new antigens and widespread chronic inflammation. The present review focuses on changes that occur in haematopoietic stem cells, macrophages, and T-cells using knowledge gained from both rodent and human studies. The review will discuss emerging strategies to combat immunosenescence, focusing on cellular and genetic therapies, including bone marrow transplantation and genetic reprogramming. A better understanding of the mechanisms and implications of immunosenescence will be necessary to combat age-related mortalities in the future.
免疫系统功能的下降,被称为“免疫衰老”,导致老年人感染、癌症和自身免疫性疾病相关死亡率的升高人们对免疫衰老领域的兴趣日益浓厚,因为预计到2030年,20%的美国人口将超过65岁。我们目前对免疫衰老的理解包括适应性和先天免疫细胞功能的改变,导致识别新抗原的能力下降和广泛的慢性炎症。目前的综述主要集中在造血干细胞、巨噬细胞和t细胞中发生的变化,利用从啮齿动物和人类研究中获得的知识。这篇综述将讨论对抗免疫衰老的新策略,重点是细胞和基因治疗,包括骨髓移植和基因重编程。更好地了解免疫衰老的机制和影响将是必要的,以对抗年龄相关的死亡在未来。
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引用次数: 55
3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration. 生物3D打印:神经组织再生治疗策略的新见解。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2015-01-01 DOI: 10.1080/15476278.2015.1123360
Fu-Yu Hsieh, Shan-hui Hsu

Acute traumatic injuries and chronic degenerative diseases represent the world's largest unmet medical need. There are over 50 million people worldwide suffering from neurodegenerative diseases. However, there are only a few treatment options available for acute traumatic injuries and neurodegenerative diseases. Recently, 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. In this commentary, the newly developed 3D bioprinting technique involving neural stem cells (NSCs) embedded in the thermoresponsive biodegradable polyurethane (PU) bioink is reviewed. The thermoresponsive and biodegradable PU dispersion can form gel near 37 °C without any crosslinker. NSCs embedded within the water-based PU hydrogel with appropriate stiffness showed comparable viability and differentiation after printing. Moreover, in the zebrafish embryo neural deficit model, injection of the NSC-laden PU hydrogels promoted the repair of damaged CNS. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden constructs. Therefore, the newly developed 3D bioprinting technique may offer new possibilities for future therapeutic strategy of neural tissue regeneration.

急性创伤性损伤和慢性退行性疾病是世界上最大的未满足医疗需求。全世界有超过5000万人患有神经退行性疾病。然而,只有少数治疗方案可用于急性创伤性损伤和神经退行性疾病。最近,3D生物打印正被应用于再生医学,以满足对适合移植的组织和器官的需求。在这篇评论中,新开发的3D生物打印技术涉及神经干细胞(NSCs)嵌入热响应生物可降解聚氨酯(PU)生物墨水。热响应性和可生物降解的PU分散体可以在37℃附近形成凝胶,不需要任何交联剂。在水性PU水凝胶中嵌入具有适当硬度的NSCs,在打印后显示出相当的活力和分化。此外,在斑马鱼胚胎神经缺损模型中,注射含有nsc的PU水凝胶可促进受损中枢神经系统的修复。此外,在植入3d打印的装载nsc的构建体后,创伤性脑损伤的成年斑马鱼的功能得以恢复。因此,新开发的生物3D打印技术可能为未来神经组织再生的治疗策略提供新的可能性。
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引用次数: 81
Meckel Gruber syndrome, A case report. 梅克尔-格鲁伯综合征,一例报告。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2015-01-01 Epub Date: 2015-06-02 DOI: 10.1080/15476278.2015.1055431
Kiper Aslan, Elif Külahçı Aslan, Adnan Orhan, Mehmet Aral Atalay

Introduction: Meckel-Gruber Syndrome was first described by J R Meckel in 1822. It is an autosomal recessive disorder, and is caused by the failure of mesodermal induction. The typical triad of Meckel-Gruber Syndrome (MGS) involves meningo-encephalocele, polycystic kidneys and postaxial polydactyly. The worldwide incidence varies from 1 in 1.300 to 1 in 140.000 live births.

Case: In this report, we present a case of MGS in which the diagnosis was made at 19 weeks of gestation based on ultrasonographic findings of the typical triad of the disease (encephalocele, polycystic kidneys, and polydactyly) These features were suggestive of the diagnosis of Meckel Gruber Syndrome (MGS). She had also placenta previa totalis. The patient was counselled regarding the lethal outcome of MGS. Unfortunately, the family did not approve the termination of pregnancy. At the 32nd week, she referred to hospital with complaints of vaginal bleeding and uterine contractions. An emergency cesarean section was perfomed due to plasental malposition. A 1380 gr, female fetus was delivered. First and 5th minute Apgar scores were 1 and 0, respectively. Consequently, the baby died after 45 minutes of neonatal resuscitation.

Conclusion: MGS is a lethal disorder. One cannot speak about survival of the fetus because of the pulmonary hypoplasia. The parents should be counseled about prognosis of the fetus and the outcome. Counselers should strictly give information about the recurrence risk for the next pregnancies.

简介:Meckel- gruber综合征是由J R Meckel于1822年首次描述的。它是一种常染色体隐性遗传病,是由中胚层诱导失败引起的。典型的梅克尔-格鲁伯综合征(MGS)包括脑膜-脑膨出、多囊肾和轴后多指畸形。全世界的发病率从1 / 1300到1 / 14万活产不等。病例:在本报告中,我们报告一例妊娠19周时诊断为MGS的病例,超声检查显示该疾病的典型三联征(脑膨出、多囊肾和多指畸形),这些特征提示诊断为梅克尔-格鲁伯综合征(MGS)。她还有完全性前置胎盘。患者被告知MGS的致命后果。不幸的是,家人不同意终止妊娠。在第32周时,她因阴道出血和子宫收缩的主诉转诊到医院。由于产妇体位不正,急诊剖宫产。一个1380克的女性胎儿诞生了。第1分钟和第5分钟Apgar得分分别为1和0。结果,婴儿在45分钟的新生儿复苏后死亡。结论:MGS是一种致死性疾病。由于肺发育不全,胎儿不能存活。应告知父母胎儿的预后和结局。咨询师应严格告知下次妊娠的复发风险。
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引用次数: 16
Wnt signaling induces epithelial differentiation during cutaneous wound healing. Wnt信号在皮肤伤口愈合过程中诱导上皮分化。
IF 2.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2015-01-01 DOI: 10.1080/15476278.2015.1086052
Khosrow S Houschyar, Arash Momeni, Malcolm N Pyles, Zeshaan N Maan, Alexander J Whittam, Frank Siemers

Cutaneous wound repair in adult mammals typically does not regenerate original dermal architecture. Skin that has undergone repair following injury is not identical to intact uninjured skin. This disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development and thus we seek a deeper understanding of the role that Wnt signaling plays in the mechanisms of skin repair in both fetal and adult wounds. The influence of secreted Wnt signaling proteins in tissue homeostasis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. Wnt signaling is activated by wounding and participates in every subsequent stage of the healing process from the control of inflammation and programmed cell death, to the mobilization of stem cell reservoirs within the wound site. Endogenous Wnt signaling augmentation represents an attractive option to aid in the restoration of cutaneous wounds, as the complex mechanisms of the Wnt pathway have been increasingly investigated over the years. In this review, we summarize recent data elucidating the roles that Wnt signaling plays in cutaneous wound healing process.

成年哺乳动物的皮肤伤口修复通常不会再生原有的皮肤结构。受伤后进行修复的皮肤与未受伤的完整皮肤是不一样的。这种差异可能是由于与胚胎皮肤发育相比,出生后皮肤伤口修复的调节机制存在差异,因此我们寻求更深入地了解Wnt信号在胎儿和成人伤口皮肤修复机制中所起的作用。分泌的Wnt信号蛋白对组织稳态的影响促使人们努力识别靶向Wnt介导的细胞反应的小分子。Wnt信号被损伤激活,并参与愈合过程的每个后续阶段,从控制炎症和程序性细胞死亡,到伤口部位干细胞库的动员。内源性Wnt信号增强是帮助皮肤伤口修复的一个有吸引力的选择,因为Wnt通路的复杂机制近年来已经得到越来越多的研究。在这篇综述中,我们总结了最近阐明Wnt信号在皮肤伤口愈合过程中所起作用的数据。
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引用次数: 71
期刊
Organogenesis
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