Radiation-induced brain injury (RIBI) after radiotherapy has become an increasingly important factor affecting the prognosis of patients with head and neck tumor. With the delivery of high doses of radiation to brain tissue, microglia rapidly transit to a pro-inflammatory phenotype, upregulate phagocytic machinery, and reduce the release of neurotrophic factors. Persistently activated microglia mediate the progression of chronic neuroinflammation, which may inhibit brain neurogenesis leading to the occurrence of neurocognitive disorders at the advanced stage of RIBI. Fully understanding the microglial pathophysiology and cellular and molecular mechanisms after irradiation may facilitate the development of novel therapy by targeting microglia to prevent RIBI and subsequent neurological and neuropsychiatric disorders.

CCAAT/enhancer-binding homologous protein (CHOP), a transcriptional regulator induced by endoplasmic reticulum stress (ER stress) is a pivotal factor in the ER stress-mediated apoptosis pathway. Previous studies have shown that CHOP is involved in the formation of fibrosis in a variety of tissues and is associated with alternative macrophage activation. The role of CHOP in the pathologic effects of liver fibrosis in schistosomiasis has not been reported, and underlying mechanisms remain unclear. This study is aimed at understanding the effect of CHOP on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in vivo and clarifying its mechanism. C57BL/6 mice were infected with cercariae of S. japonicum through the abdominal skin. The liver fibrosis was examined. The level of IL-13 was observed. The expressions of CHOP, Krüppel-like factor 4 (KLF4), signal transducer and activator of transcription 6 (STAT6), phosphorylation STAT6, interleukin-13 receptor alpha 1 (IL-13Rα1), and interleukin-4 receptor alpha (IL-4Rα) were analysed. The eosinophilic granuloma and collagen deposition were found around the eggs in mice infected for 6 and 10 weeks. IL-13 in plasma and IL-13Rα1 and IL-4Rα in liver tissue were significantly increased. The phosphorylated STAT6 was enhanced while Krüppel-like factor 4 (KLF4) was decreased in liver tissue. The expression of CHOP and colocalization of CHOP and CD206 were increased. Overall, these results suggest that CHOP plays a critical role in hepatic fibrosis induced by S. japonicum, likely through promoting alternative activation of macrophages.

Schistosomiasis is a zoonotic parasitic disease that is endemic in Asia. Macrophages are mainly involved in the inflammatory response of late schistosoma infection. Our previous study found that C/EBP homologous protein (CHOP) expression is significantly increased, and M2 macrophages are activated in schistosome‐induced liver fibrosis mice. However, the role of CHOP in the regulation of macrophage polarization remains to be further studied. Western blotting or quantitative PCR revealed that IL‐4 increased the expression of arginase‐1, macrophage mannose receptor 1, phosphorylation signal transducer and activator of transcription 6 (p‐STAT6), Krüppel‐like factor 4 (KLF4), CHOP, and IL‐13 receptor alpha (IL‐13Rα) and induced M2 polarization in RAW264.7 as measured by flow cytometry. Inhibiting STAT6 phosphorylation (AS1517499) reduced the IL‐4‐induced expression of KLF4, CHOP, and IL‐13Rα and also the number of M2 macrophages. The overexpression of CHOP stimulated M2 polarization, but AS1517499 inhibited this effect. CHOP increased the protein expression of KLF4 but did not change the expression of p‐STAT6. Soluble egg antigen (SEA) could promote the IL‐4‐induced protein expression of p‐STAT6, CHOP, and KLF4. Overall, the findings show that SEA can promote the activation of M2 macrophages by causing increased CHOP‐induced KLF4 levels and activation of STAT6 phosphorylation.

Background: Centromeric protein A (CENP-A), an essential protein involved in chromosomal segregation during cell division, is associated with several cancer types. However, its role in gliomas remains unclear. This study examined the clinical and prognostic significance of CENP-A in gliomas.Methods: Data of patients with glioma were collected from the Cancer Genome Atlas. Logistic regression, the Kruskal–Wallis test, and the Wilcoxon signed-rank test were performed to assess the relationship between CENP-A expression and clinicopathological parameters. The Cox regression model and Kaplan–Meier curve were used to analyze the association between CENP-A and survival outcomes. A prognostic nomogram was constructed based on Cox multivariate analysis. Gene set enrichment analysis (GSEA) was conducted to identify key CENP-A-related pathways and biological processes.Results:CENP-A was upregulated in glioma samples. Increased CENP-A levels were significantly associated with the world health organization (WHO) grade [Odds ratio (OR) = 49.88 (23.52–129.06) for grade 4 vs. grades 2 and 3], primary therapy outcome [OR = 2.44 (1.64–3.68) for progressive disease (PD) and stable disease (SD) vs. partial response (PR) and complete response (CR)], isocitrate dehydrogenase (IDH) status [OR = 13.76 (9.25–20.96) for wild-type vs. mutant], 1p/19q co-deletion [OR = 5.91 (3.95–9.06) for no codeletion vs. co-deletion], and age [OR = 4.02 (2.68–6.18) for > 60 vs. ≤ 60]. Elevated CENP-A expression was correlated with shorter overall survival in both univariate [hazard ratio (HR): 5.422; 95% confidence interval (CI): 4.044–7.271; p < 0.001] and multivariate analyses (HR: 1.967; 95% CI: 1.280–3.025; p < 0.002). GSEA showed enrichment of numerous cell cycle-and tumor-related pathways in the CENP-A high expression phenotype. The calibration plot and C-index indicated the favorable performance of our nomogram for prognostic prediction in patients with glioma.Conclusion: We propose a role for CENP-A in glioma progression and its potential as a biomarker for glioma diagnosis and prognosis.

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