Molecular and Cellular Basis of Regeneration and Tissue Repair

Although early after birth the central nervous system is more plastic than in the adult, it already displays limited regenerative capability. This becomes severely impaired at specific stages of embryonic development; however, the precise cellular and molecular basis of this loss is not fully understood. The chick embryo provides an ideal model for direct comparisons of regenerating and non-regenerating spinal cord within the same species because of its accessibility in ovo, the extensive knowledge of chick neural development and the molecular tools now available. Regenerative ability in the chick is lost at around E13, a relatively advanced stage of spinal cord development. This is most likely due to a complex series of events: there is evidence to suggest that developmentally regulated changes in the early response to injury, expression of inhibitory molecules and neurogenesis may contribute to loss of regenerative capacity in the chick spinal cord.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Nymphs of hemimetabolous insects such as cockroaches and crickets exhibit a remarkable capacity for regenerating complex structures from damaged legs. Until recent years, however, approaches to elucidate the molecular mechanisms underlying the leg regeneration process have been lacking. Taking the cricket Gryllus bimaculatus as a model, we found that a phenotype related to regeneration frequently appears during leg regeneration, even though no phenotype is induced by RNA interference (RNAi) in the cricket nymph, designated as regeneration-dependent RNAi. Since then, we have investigated the functions of various genes encoding signaling factors and cellular adhesion proteins like Fat and Dachsous during leg regeneration. In this review, we summarize the classical knowledge about insect leg regeneration and introduce recent advances concerning the signaling cascades required for regenerating a leg. Our results provide clues to the mechanisms of regeneration which are relevant to vertebrate systems.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Cell plasticity and mesenchymal-epithelial interactions are regarded as a hallmark of embryonic development and are not believed to occur extensively in the adult. Recently, adult mesenchymal stem cells were reported to differentiate in culture into a variety of mature cell types, including epithelial cells. Progress in stem and progenitor cell biology and recognition of the unique properties of such cells may enable intelligent bioengineering design of replacement skin which allows regeneration to occur in vivo. Ideally, a scaffold-free environment which stimulates skin stem cells in situ to initiate cell signals that result in regeneration rather than scar formation is required. Various skin progenitor cell types are considered along with the signalling cascades that they affect. We also discuss a mammalian model of scar-free regeneration. Many of these mechanisms, if fully understood, could be harnessed after injury to perfectly restore the skin.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

The Xenopus tadpole is a favourable organism for regeneration research because it is suitable for a wide range of micromanipulative procedures and for a wide range of transgenic methods. Combination of these techniques enables genes to be activated or inhibited at specific times and in specific tissue types to a much higher degree than in any other organism capable of regeneration. Regenerating systems include the tail, the limb buds and the lens. The study of tail regeneration has shown that each tissue type supplies the cells for its own replacement: there is no detectable de-differentiation or metaplasia. Signalling systems needed for regeneration include the BMP and Notch signalling pathways, and perhaps also the Wnt and FGF pathways. The limb buds will regenerate completely at early stages, but not once they are fully differentiated. This provides a good opportunity to study the loss of regenerative ability using transgenic methods.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Recent experiments on gene expression during lens regeneration in adult newts have revealed that both the regeneration-competent dorsal iris and the regeneration-incompetent ventral iris are quite active in expressing important regulatory genes. In this paper we outline some of the issues pertaining to this dorsal/ventral specificity and identity.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Upon amputation of the urodele limb, the epidermal cells surrounding the amputation plane migrate to heal the wound. The resulting wound epidermis (WE) induces the regeneration process, resulting in blastema formation, cell division, and ultimately repatterning into a new limb. Despite its central role in the initiation of limb regeneration, little is known about how the WE forms. Here we discuss various models of WE formation and the experimental data in support of each.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Tissue repair and regeneration are very complex biological events, whose successful attainment requires far more than mere cell division. However, almost unavoidably they entail cell proliferation as a fundamental premise. Full regeneration or repair cannot be achieved without replacing cells lost to disease or injury, replacement that can only take place via proliferation of surviving cells. This review endeavors to outline the molecular bases of exit from and reentry into the cell cycle. In recent years, the decision to proliferate or not has been seen as mostly the concern of cyclins and cyclin-dependent kinases. This account tries to show that cell cycle inhibitors are as important as the positive regulators in the making of this decision. Finally, the authors wish to suggest that the molecular knowledge of the cell cycle can be harnessed to the benefit of many aspects of regenerative medicine.     

类胰岛素生长因子-1何以折叠成2种高级结构的分子基础

胰岛素和IGF-1属于同一超家族,具有共同的结构模体和非常类似的三维结构,但两者的折叠行为却迥然不同。胰岛素和单链胰岛素（PIP）折叠成唯一的热力学稳定的三维结构,而IGF-1则折叠成两种热力学稳定的三维结构。即是说：IGF-1的同一序列编码两种折叠信息。是序列中的什么部位决定胰岛素／PIP和IGF-1具有不同的折叠行为？这是一个极为有趣且长期为人们所困惑的问题。本实验室在PIP和mini—IGF-1工作的基础上,用蛋白质工程技术先后设计表达了一系列胰岛素和IGF-1的杂交分子,阐明了胰岛素和IGF-1不同折叠行为的分子基础。此外,还研究了文昌鱼胰岛素类似肽（aILP）的体外再折叠,结果提示胰岛素和IGF-1的不同折叠行为是由它们的祖先分子aILP分支进化而来的。     

Regeneration of feline ventral roots

Résumé On démontre la capacité de régénération des racines ventrales des nerfs spinaux dont la résection a été pratiquée dans une série de 23 chats. Il y a eu récupération anatomique et fonctionnelle après l'anastomose des racines ventrales innervant des muscles striés et lisses.     

Regeneration of feline dorsal roots

Résumé La régénération des racines postérieures, précédemment sectionées, a lieu exclusivement dans leur parties neurilemmales. Se servant d'une méthode modifiée d'anastomose des racines, leur régénération fonctionelle est démonstrée par des techniques électrophysiologiques.     

Cellular and molecular mechanisms of alcohol-induced osteopenia

Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.     

Cellular and molecular aspects of Lyme arthritis

Lyme disease is a multisystem illness initiated upon infection with the spirochete Borrelia burgdorferi. Whereas the majority of patients who develop Lyme arthritis may be successfully treated with antibiotic therapy, about 10% go on to develop arthritis which persists for months to years, despite antibiotic therapy. Development of what we have termed treatment-resistant Lyme arthritis has previously been associated with both the presence of particular major histocompatibility complex class II alleles and immunoreactivity to the spriochetal outer surface protein A (OspA). Recently, we showed that patients with treatment-resistant Lyme arthritis, but not patients with other forms of arthritis, generate synovial fluid T cell responses to an immunodominant epitope of OspA and a highly homologous region of the human-lymphocyte-function-associated antigen-1α _L chain. Identification of a bacterial antigen capable of propagating an autoimmune response against a self-antigen provides a model of molecular mimicry in the pathogenesis of treatment-resistant Lyme arthritis. Received 21 December 1999; received after revision 10 April 2000; accepted 11 April 2000     

持久性有机污染物及修复技术

持久性有机污染物（POPs）具有致癌、致畸和致突变作用,对人类健康造成严重危害：本文介绍了持久性有机污染源的控制技术,以及土壤在受到污染后,所采用的生态修复方法,并详细介绍了物理修复、化学修复和生物修复技术及发展趋势。     

Cellular regulation and molecular interactions of the ferritins

Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA (mRNA) structures, signaling pathways and protein catalysts. Ferritin, a protein nanocage around an iron/oxy mineral, centralizes the control. Complementary DNA (antioxidant responsive element/Maf recognition element) and mRNA (iron responsive element) responses regulate ferritin synthesis rates. Multiple iron-protein interactions control iron and oxygen substrate movement through the protein cage, from dynamic gated pores to catalytic sites related to di-iron oxygenase cofactor sites. Maxi-ferritins concentrate iron for the bio-synthesis of iron/heme proteins, trapping oxygen; bacterial mini-ferritins, DNA protection during starvation proteins, reverse the substrate roles, destroying oxidants, trapping iron and protecting DNA. Ferritin is nature’s unique and conserved approach to controlled, safe use of iron and oxygen, with protein synthesis in animals adjusted by dual, genetic DNA and mRNA sequences that selectively respond to iron or oxidant signals and link ferritin to proteins of iron, oxygen and antioxidant metabolism. Received 25 June 2005; received after revision 17 October 2005; accepted 25 November 2005