Specificity of peripheral nerve regeneration: interactions at the axon level

Peripheral nerves injuries result in paralysis, anesthesia and lack of autonomic control of the affected body areas. After injury, axons distal to the lesion are disconnected from the neuronal body and degenerate, leading to denervation of the peripheral organs. Wallerian degeneration creates a microenvironment distal to the injury site that supports axonal regrowth, while the neuron body changes in phenotype to promote axonal regeneration. The significance of axonal regeneration is to replace the degenerated distal nerve segment, and achieve reinnervation of target organs and restitution of their functions. However, axonal regeneration does not always allows for adequate functional recovery, so that after a peripheral nerve injury, patients do not recover normal motor control and fine sensibility. The lack of specificity of nerve regeneration, in terms of motor and sensory axons regrowth, pathfinding and target reinnervation, is one the main shortcomings for recovery. Key factors for successful axonal regeneration include the intrinsic changes that neurons suffer to switch their transmitter state to a pro-regenerative state and the environment that the axons find distal to the lesion site. The molecular mechanisms implicated in axonal regeneration and pathfinding after injury are complex, and take into account the cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules and their receptors. The aim of this review is to look at those interactions, trying to understand if some of these molecular factors are specific for motor and sensory neuron growth, and provide the basic knowledge for potential strategies to enhance and guide axonal regeneration and reinnervation of adequate target organs.     

粘附分子与冠心病发病机制研究进展

细胞粘附分子（CAMs）被认为在导致动脉粥样斑块形成的各个炎症反应阶段均起到了重要作用,文章从同型半胱氨酸诱导CAMs表达的机制,CD40-CD40L与CAMs的表达,核转录因子与CAMs的表达,C-反应蛋白与CAMs的表达,血管紧张素与CAMs的表达4个方面,阐述了细胞粘附分子与冠心病之间的发病机制研究进展。     

Electron tomography of paranodal septate-like junctions and the associated axonal and glial cytoskeletons in the central nervous system

The polarized domains of myelinated axons are specifically organized to maximize the efficiency of saltatory conduction. The paranodal region is directly adjacent to the node of Ranvier and contains specialized septate-like junctions that provide adhesion between axons and glial cells and that constitute a lateral diffusion barrier for nodal components. To complement and extend earlier studies on the peripheral nervous system, electron tomography was used to image paranodal regions from the central nervous system (CNS). Our three-dimensional reconstructions revealed short filamentous linkers running directly from the septate-like junctions to neurofilaments, microfilaments, and organelles within the axon. The intercellular spacing between axons and glia was measured to be 7.4 ± 0.6 nm, over twice the value previously reported in the literature (2.5-3.0 nm). Averaging of individual junctions revealed a bifurcated structure in the intercellular space that is consistent with a dimeric complex of cell adhesion molecules composing the septate-like junction. Taken together, these findings provide new insight into the structural organization of CNS paranodes and suggest that, in addition to providing axo-glial adhesion, cytoskeletal linkage to the septate-like junctions may be required to maintain axonal domains and to regulate organelle transport in myelinated axons.     

Association between precystectomy epithelial tumor marker response to neoadjuvant chemotherapy and oncological outcomes in urothelial bladder cancer

Introduction and Objectives

We previously reported that elevated precystectomy serum levels of epithelial tumor markers predict worse oncological outcome in patients with invasive bladder cancer (BC). Herein, we evaluated the effect of neoadjuvant chemotherapy (NAC) on elevated tumor marker levels and their association with oncological outcomes.

Intentions and willingness to use complementary and alternative medicines: What potential patients believe about CAMs

This paper explores the intentions and willingness of a sample of Australian consumers (N = 356) to use complementary and alternative medicine (CAM). Participants considered using CAMs at least once in the next 2 months and rated the likelihood of certain consequences of CAM use, whether important others would approve, and if barriers would prevent them from using CAMs. People intending to use CAMs (high intenders) were more likely than those low on intention (low intenders) to endorse positive outcomes of CAM use and believe that important others would support their CAM use. High intenders were less likely than low intenders to believe that barriers would prevent use. Low intenders (n = 200) were also asked to consider their response to a free CAM trial. Those willing to accept a trial were more likely than those unwilling to believe that CAMs could improve health and less likely to believe that laziness would prevent use. These results identify important beliefs which may influence people's decisions to use CAMs.     

Diet quality and markers of endothelial function: The CARDIA study

Background and aimDietary patterns are associated cross-sectionally with cellular adhesion molecules (CAMs). We studied prospective associations of three dietary patterns with CAMs.Methods and resultsIn the Coronary Artery Risk Development in Young Adults (CARDIA) study, diet was assessed at years 0 (1985–86) and 7 (1992–93) examinations. Four circulating CAMs (E-selectin, P-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and vascular cellular adhesion molecule (VCAM)) were assayed at years 7 and 15 (2000–01). We created one index score “A Priori Diet Quality Score” and derived dietary patterns using principal components analysis (PCA). Multivariable linear regression models predicted year 15 CAMs from averaged (year 0/7) dietary patterns. The A Priori Diet Quality Score rated 46 food groups beneficial, neutral or adverse based on hypothesized health effects. We derived two PCA dietary patterns: “fruit and vegetables (FV)” (high intakes of fruit, vegetables, and whole grains) and “meat” (high intakes of red meat, refined grain, and butter). All dietary patterns were related to E-selectin and sICAM-1. P-selectin was not related to the FV dietary pattern. VCAM was only related to the A Priori Diet Quality Score. Strongest associations were for the meat dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the A Priori Diet Quality Score with sICAM-1 (effect size 34% of an SD (−15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (−45.1/170.3 ng/mL)).ConclusionThis prospective analysis suggests that dietary patterns are associated with CAMs.     

PSA-NCAM in mammalian structural plasticity and neurogenesis

Polysialic acid (PSA) is a linear homopolymer of alpha2-8-N acetylneuraminic acid whose major carrier in vertebrates is the neural cell adhesion molecule (NCAM). PSA serves as a potent negative regulator of cell interactions via its unusual biophysical properties. PSA on NCAM is developmentally regulated thus playing a prominent role in different forms of neural plasticity spanning from embryonic to adult nervous system, including axonal growth, outgrowth and fasciculation, cell migration, synaptic plasticity, activity-induced plasticity, neuronal-glial plasticity, embryonic and adult neurogenesis. The cellular distribution, developmental changes and possible function(s) of PSA-NCAM in the central nervous system of mammals here are reviewed, along with recent findings and theories about the relationships between NCAM protein and PSA as well as the role of different polysialyltransferases. Particular attention is focused on postnatal/adult neurogenesis, an issue which has been deeply investigated in the last decade as an example of persisting structural plasticity with potential implications for brain repair strategies. Adult neurogenic sites, although harbouring all subsequent steps of cell differentiation, from stem cell division to cell replacement, do not faithfully recapitulate development. After birth, they undergo morphological and molecular modifications allowing structural plasticity to adapt to the non-permissive environment of the mature nervous tissue, that are paralled by changes in the expression of PSA-NCAM. The use of PSA-NCAM as a marker for exploring differences in structural plasticity and neurogenesis among mammalian species is also discussed.