Anatomical Importance Between Neural Structure and Bony Landmark: Clinical Importance for Posterior Endoscopic Cervical Foraminotomy

Objective Posterior endoscopic cervical foraminotomy (PECF) is a well-established, minimally invasive surgery for cervical radiculopathy, but have the more chances of neural structure damage due to the limited visibility and steeper learning curve. So, the anatomical understanding of the nerve associated with the bony structure will be an essential surgical guideline. Methods We measured the distance between the bilateral dura lateral edge and bilateral V-point on axial cuts of cervical magnetic resonance imaging and 3-dimensional spine computed tomography imaging, respectively, from 80 patients. We then calculate the distance and position between the dura lateral edge and the V-point as surgically critical width (SCW). Transverse interdural distance (TIDW), transverse inter-V-point distance, and anatomical facet joint width were measured. Results The mean TIDW decreased as the levels down in the 40s–60s but increased at the C4–5, C5–6, and C6–7 levels in the 70s. Statistically significant difference was shown at the C6–7 level between the 40s and the 70s. The mean anatomical inter-V-point distance markedly decreased at C5–6 and continued till the C7–Tl level at all age groups. Moreover, a statistically significant difference was shown at the C3–4 and C4–5 level between the 40s and the 70s. The mean negative values of SCW increased from the 40s to 70s at the C5–6 and C6–7 levels (C5–6: -0.60 ± 1.10 mm to -1.63 ± 1.56 mm; C6–7: -0.90 ± 0.74 mm to -2.18 ± 1.25 mm). There were statistically significant differences between the 2 aged groups at the C3–4, C4–5, C5–6, and C6–7 levels. Conclusion A prediction of the correlated position between the lateral dura edge and the V-point is essential for the PECF not to injure the neural structure. In the case of a performing the PECF at the C5–6 and C6–7 level in the old-aged patient, it should be considered the laterally moved dura edge, and more extended bony remove is needed for less neural structure damage

ISG15 modification of filamin B negatively regulates the type I interferon-induced JNK signalling pathway

Interferon (IFN)-induced signalling pathways have essential functions in innate immune responses. In response to type I IFNs, filamin B tethers RAC1 and a Jun N-terminal kinase (JNK)-specific mitogen-activated protein kinase (MAPK) module—MEKK1, MKK4 and JNK—and thereby promotes the activation of JNK and JNK-mediated apoptosis. Here, we show that type I IFNs induce the conjugation of filamin B by interferon-stimulated gene 15 (ISG15). ISGylation of filamin B led to the release of RAC1, MEKK1 and MKK4 from the scaffold protein and thus to the prevention of sequential activation of the JNK cascade. By contrast, blockade of filamin B ISGylation by substitution of Lys 2467 with arginine or by knockdown of ubiquitin-activating enzyme E1-like (UBEL1) prevented the release of the signalling molecules from filamin B, resulting in persistent promotion of JNK activation and JNK-mediated apoptosis. These results indicate that filamin B ISGylation acts as a negative feedback regulatory gate for the desensitization of type I IFN-induced JNK signalling

Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH2-terminal Kinase Signaling Pathway

Type I interferons (IFNs) activate Janus tyrosine kinase-signal transducer and activator of transcription pathway for exerting pleiotropic biological effects, including antiviral, antiproliferative, and immunomodulatory responses. Here, we demonstrate that filamin B functions as a scaffold that links between activated Rac1 and a c-Jun NH2-terminal kinase (JNK) cascade module for mediating type I IFN signaling. Filamin B interacted with Rac1, mitogen-activated protein kinase kinase kinase 1, mitogen-activated protein kinase kinase 4, and JNK. Filamin B markedly enhanced IFNα-dependent Rac1 activation and the sequential activation of the JNK cascade members. Complementation assays using M2 melanoma cells revealed that filamin B, but not filamin A, is required for IFNα-dependent activation of JNK. Furthermore, filamin B promoted IFNα-induced apoptosis, whereas short hairpin RNA-mediated knockdown of filamin B prevented it. These results establish a novel function of filamin B as a molecular scaffold in the JNK signaling pathway for type I IFN-induced apoptosis, thus providing the biological basis for antitumor and antiviral functions of type I IFNs