In our study SHH protein overexpression was significantly

In our study, SHH protein overexpression was significantly associated with lymph node metastasis which is in agreement with the study done by Marechal et al. wherein they have reported that SHH is a prognostic biomarker in PDAC and high levels correlate with lymph node metastasis (Maréchal et al., 2015). SHH is expressed in early PanIN lesions, with increasing levels as lesions advance to invasive PDAC (Morton and Lewis, 2007). Further supporting our statement is the observation that in Kashmir valley, PC is a dreadful malignancy with most patients being diagnosed at a terminal stage when lymph node metastasis has occurred and surgical intervention is not useful.
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Acknowledgements
Introduction The facial nerve and its associated musculature collectively mediate facial expression and essential facial functions, such as eye closure, oral competence, and phonation of labial sounds (Garcia et al., 2015). Facial nerve paralysis impairs an individual's ability to express emotion and communicate, affects quality of life and social functioning (Coulson et al., 2004), and causes significant psychological distress (Fu et al., 2011). Despite advances in the surgical management of facial palsy (Harris and Tollefson, 2015), the restoration of normal facial function is difficult to achieve, particularly after nerve transection injuries in which the three-dimensional architecture of the distal nerve is disrupted (Allodi et al., 2012). The cellular and molecular responses to nerve injury are complex, involving multiple cell types and overlapping signaling pathways. Upon injury, the distal nerve undergoes Wallerian degeneration, a process in which injury-activated Schwann SAR131675 (SCs) proliferate and recruit macrophages to clear the nerve of axonal and myelin debris (Allodi et al., 2012; Cattin and Lloyd, 2016; Arthur-Farraj et al., 2012). The neuronal soma switches to a pro-regenerative state, activating transcription factors that favor axonal regeneration (Allodi et al., 2012). In the case of a nerve transection injury, a gap is created in the nerve. To permit regenerating axons to cross this gap, a bridge containing inflammatory cells and fibroblasts forms between the distal and proximal nerve stumps (Cattin and Lloyd, 2016). Early neovascularization within the bridge works in concert with secreted factors, such as GDNF, to increase SC proliferation and migration from the proximal to the distal nerve stump (Allodi et al., 2012; Cattin et al., 2015). SC interaction with fibroblasts is mediated via the EphrinB ligand and the EphB2 receptor, resulting in collimation of SCs and fibroblasts into tube-like structures, the Bands of Büngner, that ensheath the regenerating axons (Parrinello et al., 2010). SCs interact directly with regenerating axons to mediate growth cone guidance and axonal elongation throughout this process (Namgung, 2014). Fibroblasts play a significant role in cell-cell signaling in the regenerating nerve, and are a critical component of normal nerve microarchitecture (Allodi et al., 2012). To date, the signaling cues that prompt fibroblasts to reorganize within the nerve after transection injury are not well understood. During embryogenesis, the Hedgehog (Hh) signaling pathway drives the formation of normal nerve connective tissue (Parmantier et al., 1999). This signaling family consists of three members – Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh) – all of which share a receptor (Patched) and a downstream pathway that involves the Gli family of transcription factors – Gli1, Gli2, and Gli3. SC-derived Desert Hedgehog (Dhh) is necessary for the development of peripheral nerve sheaths and for the proper formation of the nerve's three-dimensional structure (Parmantier et al., 1999). Additionally, Sonic Hedgehog (Shh) signaling is required for normal cranial nerve development, and its absence leads to facial nerve agenesis (Kurosaka et al., 2015).