Axonal growth inhibitors and their receptors in spinal cord injury:from biology to clinical translation

Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.

Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis

AIM: To investigated the molecular cause of very early-onset ulcerative colitis (UC) in an 18-mo-old affected child.

NHL患者血清TNF-α、LDH水平及与血沉的相关性研究

目的探讨非霍奇金淋巴瘤(NHL)患者血清TNF-αs、TNFRI、LDH、球蛋白、白蛋白水平及血沉的变化和意义。方法严格选取25例初诊NHL患者和26例正常人为研究对象,采用ELISA法测定血清TNF-α及sTNFRI水平,采用OLYMPUS 600血生化仪测定血清LDH、球蛋白及白蛋白水平,采用魏氏法测定血沉。结果NHL患者血清TNF-αs、TNFRI、LDH、球蛋白水平及血沉值均高于对照组,且血清TNF-αs、TNFRI、LDH、球蛋白水平与血沉值均具有相关性;两组血清白蛋白水平差异无显著性,NHL患者血清白蛋白水平血沉值成负相关。结论NHL患者TNF-α、sTN-FRI、LDH、球蛋白、白蛋白改变与血沉增快均有关系,其中TNF-α、白蛋白及LDH作用较大。