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Background. CRC is the third most common cancer globally. The tumor immune microenvironment is closely associated with the overexpressed lncRNA ZEB1-AS1. However, in individuals with CRC, the ZEB1-AS1 gene’s ability to predict immune response is a mystery. Materials and Methods. The ZEB1-AS1 gene’s prognostic potential was thoroughly investigated. We analyzed and included into the TCGA database all ZEB1-AS1 and ZEB1-AS1-related genes using LASSO-Cox regression. Researchers examined the link among ZEB1-AS1 and the tumor immune microenvironment, immune checkpoint, and tumor mutation burden (TMB) in CRC through the TCGA database. Using a predictive model, researchers were able to determine the link between ZEB1-AS1 and NUDT3 and CRC prognosis. Result. According to our findings, individuals with reduced ZEB1-AS1 expression had a better prognosis in CRC. Based on the expression of two genes in the TCGA database, patients were divided into two cohorts. The B lymphocytes and macrophages are less likely to be recruited by tissues with a low-risk score. TMB and immunological checkpoints were shown to have a connection. Based on these genes, a predictive nomogram was built and confirmed, with a C-index of 0.78. Conclusion. Prognostic models based on ZEB1-AS1 and ZEB1-AS1-related genes are more accurate for CRC patients when it comes to the prognosis and immune checkpoint responsiveness.

Mas-related gene (Mrg) C receptors are exclusively expressed in the trigeminal and dorsal root ganglia (DRG). However, their functional roles are poorly understood. This study was aimed to determine the effect of MrgC receptors on pain hypersensitivity in the early phase of neuropathic pain and its underlying mechanisms. Intrathecal (i.t.) administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) at 1 or 10nmol attenuated mechanical allodynia one day after L5 spinal nerve ligation (SNL) surgery. I.t. BAM8-22 (10 nmol) inhibited SNL-induced microglia activation in the spinal dorsal horn on day 2 post-SNL. The BAM8-22 treatment also abolished SNL-induced upregulation of neuronal nitric oxide synthesis (nNOS) in the dorsal root ganglia (DRG). On the other hand, SNL, but not sham, surgery reduced the expression of MrgC receptor mRNA in the injured L5 DRG without changing thier levels in the adjacent uninjured L4 or L6 DRG on day 2 following the surgery. These results suggest that the activation of MrgC receptors can relieve pain hypersensitivity by the inhibition of nNOS increase in DRG neurons and microglia activation in the spinal dorsal horn in the early time following peripheral nerve injury. This study provides evidence that MrgC receptors could be targeted as a novel therapy for neuropathic pain with limited unwanted effects.

We have previously shown that intrathecal administration of the adrenomedullin (AM) receptor antagonist AM(22-52) produces a long-lasting anti-hyperalgesia effect. This study examined the hypothesis that AM recruits other pronociceptive mediators in complete Freund's adjuvant (CFA)-induced inflammation. Injection of CFA in the hindpaw of rat produced an increase in the expression of nNOS in dorsal root ganglion (DRG) and the spinal dorsal horn. An intrathecal administration of AM(22-52), but not the CGRP antagonist BIBN4096BS, abolished the CFA-induced increase of nNOS. Moreover, AM-induced increase of CGRP was inhibited by the nNOS inhibitors L-NAME and 7-nitroindazole in cultured ganglion explants. Addition of AM to ganglion cultures induced an increase in nNOS protein, which was attenuated by the PKA inhibitor H-89. Treatment with AM also concentration-dependently increased cAMP content and pPKA protein level, but not its non-phosphorylated form, in cultured ganglia. In addition, nNOS was shown to be co-localized with the AM receptor components calcitonin receptor-like receptor and receptor activity-modifying protein 2- and 3 in DRG neurons. The present study suggests that the enhanced activity of nitric oxide (NO) mediates the biological action of AM at the spinal level and that AM recruits NO-CGRP via cAMP/PKA signaling in a mechanistic pathway underlying CFA-induced hyperalgesia.