Calycosin promotes axon growth by inhibiting PTPRS and alleviates spinal cord injury.

Our former studies have identified the alleviating effect of Calycosin (CA) on spinal cord injury (SCI). In this study, our purpose is to explore the influence of CA on SCI from the perspective of promoting axon growth. The SCI animal model was constructed by spinal cord compression, wherein rat primary cortex neuronal isolation was performed, and the axonal growth restriction cell model was established via chondroitin sulfate proteoglycan (CSPG) treatment. The expressions of axon regeneration markers were measured via immunofluorescent staining and western blot, and the direct target of CA was examined using silver staining. Finally, the expression of the protein tyrosine phosphatase receptor type S (PTPRS) was assessed using western blot. CA treatment increased neuronal process outgrowth and the expressions of axon regeneration markers, such as neurofilament H (NF-H), vesicular glutamate transporter 1 (vGlut1), and synaptophysin (Syn) in both SCI model rats and CSPG-treated primary cortical neurons, and PTPRS levels were elevated after SCI induction. In addition, PTPRS was the direct target of CA, and according to in vivo findings, exposure to CA reduced the PTPRS content. Furthermore, PTPRS overexpression inhibited CA's enhancement of axon regeneration marker content and neuronal axon lengths. CA improves SCI by increasing axon development through regulating PTPRS expression.

Clinical Efficacy of Epidural Injections of Local Anesthetic Alone or Combined with Steroid for Neck Pain: A Systematic Review and Meta-Analysis.

Aims: To compare the effectiveness of cervical epidural injections of local anesthetic with vs. without a steroid. Methods: Three databases (PubMed, Embase, and Cochrane library) were used to search and assess all clinical randomized controlled trials regarding the clinical efficacy of epidural injections from January 01, 2009, to October 31, 2020. Cochrane review criteria and the Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment instrument were used to evaluate the methodologic quality of the included studies. Qualitative and quantitative analyses were performed according to best evidence synthesis principles and by single-arm meta-analysis, respectively. Results: Based on the search criteria, 4 RCTs were qualitatively and quantitatively analyzed in the single-arm meta-analysis. Treatment with lidocaine alone or with the steroid resulted in decreases of 4.46 and 4.29 points, respectively, in pain scores and of 15.8 and 14.46 points, respectively, in functional scores at 6 months. Similar trends were observed at the 1-year follow-up: pain scores decreased by 4.27 and 4.14 points, while functional scores decreased by 15.94 and 14.44 points in patients with neck pain who received lidocaine without or with the steroid, respectively. In the 3 studies that reported 2-year follow-up data, patients with neck pain treated with lidocaine or lidocaine + steroid showed 4.2- and 4.14-point decreases, in pain score and 15.92- and 14.89-point decreases, respectively, in functional scores. Conclusions: The studies showed level I (strong) evidence for short- and long-term improvements in pain relief and functionality with cervical epidural injections of local anesthetic alone or with a steroid in the management of neck pain.

Pseudogene PA2G4P4 promotes oncogene PA2G4 expression and nuclear translocation to affect glioblastoma cell viability and apoptosis.

Dysregulation of pseudogenes is involved in the progression of various types of cancer, including glioblastoma (GBM). Proliferation associated-2G4 (PA2G4) pseudogene 4 (PA2G4P4) has been shown to play an oncogenic role in bladder cancer development. Our study aimed to explore the role and mechanism of PA2G4P4 in GBM progression. PA2G4P4 and PA2G4 expression in GBM tissues was analyzed using the GEPIA database. Cell viability, apoptosis, and activities of caspase-3 and caspase-9 in GBM cells were explored by CCK-8, flow cytometry analysis, and colorimetric activity assay kits, respectively. GEPIA database showed that PA2G4P4 and PA2G4 were both upregulated in GBM tissues. PA2G4P4 expression was also boosted in GBM cells. Knockdown of PA2G4P4 or PA2G4 inhibited cell viability, induced apoptosis, and increased caspase-3 and caspase-9 activities in GBM cells. Data from UALCAN database showed that among top 15 genes correlated with PA2G4P4, PA2G4 had the highest correlation coefficient. Additionally, knockdown of PA2G4P4 inhibited PA2G4 expression and nuclear translocation in GBM cells. Overexpression of PA2G4 abolished the functions of PA2G4P4 knockdown on viability and apoptosis in GBM cells. Summarily, pseudogene PA2G4P4 promotes oncogene PA2G4 expression and nuclear translocation to affect cell viability and apoptosis in GBM cells.