Carbonic anhydrases (CAs) are acid–base regulatory proteins that modulate a variety of physiological functions. Recent findings have shown that CAIX is particularly upregulated in glioblastoma multiforme (GBM) and is associated with a poor patient outcome and survival rate. An analysis of the GSE4290 dataset of patients with gliomas showed that CAIX was highly expressed in GBM and was negatively associated with prognosis. The expression of CAIX under hypoxic conditions in GBM significantly increased in protein, mRNA, and transcriptional activity. Importantly, CAIX upregulation also regulated GBM motility, monocyte adhesion to GBM, and the polarization of tumor-associated monocytes/macrophages (TAM). Furthermore, the overexpression of CAIX was observed in intracranial GBM cells. Additionally, epidermal growth factor receptor/signal transducer and activator of transcription 3 regulated CAIX expression under hypoxic conditions by affecting the stability of hypoxia-inducible factor 1α. In contrast, the knockdown of CAIX dramatically abrogated the change in GBM motility and monocyte adhesion to GBM under hypoxic conditions. Our results provide a comprehensive understanding of the mechanisms of CAIX in the GBM microenvironment. Hence, novel therapeutic targets of GBM progression are possibly developed.

Objective: Intervertebral disc (IVD) degeneration and disc herniation are major causes of lower back pain, which involve the presence of inflammatory mediators and tissue invasion by immune cells. Intercellular adhesion molecule 1 (ICAM1, also termed CD54) is an adhesion molecule that mediates cell-cell interactions, particularly between immune cells and target tissue. The aim of this study was to examine the intracellular signaling pathways involved in inflammatory stimuli-induced ICAM1 expression in human anulus fibrosus (AF) cells. Methods: Quantitative reverse transcription-polymerase chain reaction (qPCR), western blotting, and flow cytometry were performed to dissect the roles of different signaling pathways in inflammatory stimuli-mediated ICAM1 expression. Results: Using qPCR and western blot analyses, a significant increase in ICAM1 expression was observed in AF cells after stimulation of lipopolysaccharide (LPS) plus interferon-gamma (IFNγ) in a time-dependent manner. Flow cytometry revealed ICAM1 upregulation on the surface of AF cells. Importantly, LPS plus IFNγ treatment also significantly promoted Chemokine ligand (CCL)2 expression, but not CCL3. The enhanced ICAM1 expression was abolished after incubation with antibody against CCL2. In AF cells, treatment with LPS plus IFNγ activated the FAK/ERK/GSK3 signaling pathways, promoted a time-dependent increase in PKCδ phosphorylation, and promoted PKCδ translocation to the nucleus. Treatment with the pharmacological PKCδ inhibitor; rottlerin, effectively blocked the enhanced productions of ICAM1 and CCL2. Conclusions: Inflammatory stimuli in AF cells are part of a specific pathophysiology in IVD degeneration and disc herniation that modulates CCL2/ICAM1 activation through the FAK/ERK/GSK3 and PKCδ signaling pathways in AF cells.

Objectives: Despite the remarkable advances in critical care management of acute brain injury for the past 20 years, the prognoses remain poor. However, numerous reports indicate the efficacy of Traditional Chinese Medicine (TCM) therapy in stroke rehabilitation. This study aimed to determine the efficacy and safety of integrated TCM (Wendan decoction [WDD]) in patients with acute brain injury as a combination therapy in the early stages. Design: Prospective randomized controlled trial. Setting: Single-center study. Subjects: Sixty patients diagnosed with acute brain injury were randomly assigned to intervention and control groups, equally, and 41 patients completed the study. Interventions: All patients were treated by conventional neurologic intensive care. The 23 patients in the intervention group were administered with an integrated WDD in the early stages three times daily; combination treatment was initiated within 14 days and lasted >1 month. Outcome measures: Duration of ventilator use, intensive care unit stays, Glasgow Coma Scale (GCS) scores, motor response, the best muscle power, disability rating scale (DRS) scores, modified Rankin scale (mRS) scores, and the mortality rate for the first month. The other outcome measures were GCS scores, motor response, the best muscle power, DRS, mRS, and Barthel index (BI) scores 6 months later. Results: There was no mortality in the intervention group, but the rate was 39% in the control group for first month. Comparisons between groups showed significant differences (p < 0.05) in GCS, DRS, mRS, and BI scores, indicating improvements in the intervention group after 6 months. Conclusions: In the early stages of acute brain injury, combination treatment with WDD was found to be safe. Furthermore, this treatment may improve neurologic functional outcomes after 6 months.