ABSTRACT
We investigated aging-related changes in nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the spinal cord of aged dogs. At all levels of the spinal cord examined, NADPH-d activities were observed in neurons and fibers in the superficial dorsal horn (DH), dorsal gray commissure (DGC) and around the central canal (CC). A significant number of NADPH-d positive macro-diameter fibers, termed megaloneurites, were discovered in the sacral spinal cord (S1-S3) segments of aged dogs. The distribution of megaloneurites was characterized from the dorsal root entry zone (DREZ) into the superficial dorsal horn, along the lateral collateral pathway (LCP) to the region of sacral parasympathetic nucleus (SPN), DGC and around the CC, but not in the cervical, thoracic and lumbar segments. Double staining of NADPH-d histochemistry and immunofluorescence showed that NADPH-d positive megaloneurites co-localized with vasoactive intestinal peptide (VIP) immunoreactivity. We believed that megaloneurites may in part represent visceral afferent projections to the SPN and/or DGC. The NADPH-d megaloneurites in the aged sacral spinal cord indicated some anomalous changes in the neurites, which might account for a disturbance in the aging pathway of the autonomic and sensory nerve in the pelvic visceral organs.
Subject(s)
NADPH Dehydrogenase , Nitric Oxide Synthase , Dogs , Animals , NADPH Dehydrogenase/metabolism , NADP/metabolism , Nitric Oxide Synthase/metabolism , Spinal Cord/metabolism , Spinal Cord Dorsal Horn/metabolism , AgingABSTRACT
ABSTRACT: The pyrroline-5-carboxylate reductase 1 (PYCR1) plays important roles in cancers, but its contribution to adenocarcinoma of the kidney (AK) and the potential mechanism remain to be clarified. In this study, we aimed to demonstrate the relationship between PYCR1 mRNA and AK based on The Cancer Genome Atlas database.PYCR1 mRNA in AK and normal tissues was compared using Wilcoxon rank sum test. The relationship between PYCR1 mRNA and clinicopathological characters was evaluated using logistic regression. The association between PYCR1 mRNA and survival rate was evaluated using Kaplan-Meier test and Cox regression of univariate and multivariate analysis. Additionally, Gene Set Enrichment Analysis was conducted to annotate the biological function of PYCR1 mRNA.Increased PYCR1 mRNA was found in AK tissues. Increased PYCR1 mRNA was related to high histologic grade, clinical stage, and lymph node and distant metastasis. Kaplan-Meier survival analysis and univariate analysis showed that AK patients with increased PYCR1 mRNA had worse prognosis than those without. PYCR1 mRNA remained independently associated with overall survival (HR: 1.34; 95% CI: 1.07-1.66; Pâ=â.009) in multivariate analysis. The Gene Set Enrichment Analysis suggested that ribosome, proteasome, inhibition of p53 signaling pathway, extracellular matrix receptor interaction, and homologous recombination were differentially enriched in increased PYCR1 mRNA phenotype.Increased PYCR1 mRNA is a potential marker in patients with AK. More importantly, p53 pathway, ribosome, proteasome, extracellular matrix receptor interaction, and homologous are differentially enriched in AK patients with increased PYCR1 mRNA.
