CIA-II is associated with lower-grade glioma survival and cell proliferation.

BACKGROUND: The role of CIA-II has been clarified in several types of tumors; however, whether dysregulated CIA-II expression is also involved in the pathophysiology of lower-grade glioma (LGG) remains undisclosed. METHODS: A comprehensive pan-cancer analysis of the expression patterns and prognostic significance of CIA-II in miscellaneous tumors was undertaken. Subsequently, a detailed bioinformatics analysis was executed to identify putative correlations between CIA-II expression and clinical features, prognosis, biological functions, immunological characteristics, genomic alterations, and chemotherapeutics in LGG. In vitro studies were implemented to examine the potential roles of CIA-II in LGG. RESULTS: CIA-II expression was found to be abnormally elevated in a variety of tumors, including LGG. Additionally, patients with LGG with higher CIA-II expression owned worse prognosis. Importantly, the results declared that CIA-II expression was an independent prognostic indicator for LGG. Moreover, the expression of CIA-II was tightly interrelated with immune cell infiltration, gene mutations, and chemotherapeutics in LGG. In vitro studies revealed that CIA-II was increased and strongly related to the cell proliferation in LGG. CONCLUSION: CIA-II may be an independent prognostic factor and a serviceable therapeutic target in LGG.

DUSP10 is a novel immune-related biomarker connected with survival and cellular proliferation in lower-grade glioma.

OBJECTIVE: The role of dual-specificity phosphatase 10 (DUSP10) has been investigated in several types of cancer. Nevertheless, the underlying function of DUSP10 in lower-grade glioma (LGG) remains undetermined. METHODS: We entirely determined the expression features and prognostic significance of DUSP10 in numerous tumors by implementing a pan-cancer analysis. Adjacently, we thoroughly inspected the correlation between DUSP10 expression and clinicopathologic features, prognosis, biological processes, immune traits, gene variations, and treatment responses based on the expression features in LGG. In vitro studies were conducted to detect the underlying functions of DUSP10 in LGG. RESULTS: Unconventionally boosted DUSP10 expression and higher DUSP10 expression correlated with poorer prognosis were discovered in various tumors, including LGG. Fortunately, DUSP10 expression was proven to be an independent prognostic indicator of patients with LGG. Additionally, DUSP10 expression was tightly linked to the immune modulation, gene mutations, and response to immunotherapy/chemotherapy in LGG patients. In vitro studies illustrated that the DUSP10 was abnormally increased and pivotal for cell proliferation in LGG. CONCLUSIONS: Collectively, we verified that DUSP10 was an independent prognostic indicator and may become a novelty target of targeted therapy of LGG.

CNIH4: a novel biomarker connected with poor prognosis and cell proliferation in patients with lower-grade glioma.

Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) functions as an oncogene in several types of tumor. Nevertheless, the potential function of CNIH4 in lower-grade glioma (LGG) remains unclear. Pan-cancer analysis was implemented to comprehensively explore CNIH4 expression patterns and prognostic value in multiple cancers. Further, a systematic investigation of correlations between CNIH4 expression and clinical features, prognosis, biological functions, immune properties, genomic mutations, and treatment response was conducted, based on LGG expression patterns. CNIH4 expression levels and specific roles in LGG were also evaluated using in vitro experiments. Aberrant CNIH4 overexpression was detected in various tumors, and higher CNIH4 expression was linked with inferior prognosis, including in patients with LGG. Univariate and multivariate Cox regression analysis indicated that CNIH4 expression was an independent prognostic biomarker in patients with LGG. Our data also revealed that CNIH4 expression was strongly related to immune-associated signatures, immune cell infiltration, immune checkpoint genes, copy number alteration burden, tumor mutation burden, and treatment response in patients with LGG. In vitro experiments confirmed that CNIH4 was unusually elevated and crucial for cell proliferation, migration, invasion and cell cycle regulation in LGG. Together, our data validate CNIH4 may be an independent prognostic biomarker that could serve as a novel therapeutic target for improvement of prognosis in patients with LGG.

Melatonin-Driven NLRP3 Inflammation Inhibition Via Regulation of NF-κB Nucleocytoplasmic Transport: Implications for Postoperative Cognitive Dysfunction.

The aseptic inflammatory response of the central nervous system is one of the important causes of neurodegenerative diseases in individuals and is also recognized in postoperative cognitive dysfunction (POCD). Inflammasome is thought to be closely related to brain homeostasis. However, there are few drugs targeting the inflammasome to suppress inflammation in clinical practice. Here, we showed that the neuroinflammatory response mediated by the NLRP3 (NLR family, pyrin domain containing 3) inflammasome was involved in the pathological process of POCD. Melatonin protected mice from nerve damage by inhibiting activation of the NLRP3-caspase-1-interleukin 1 beta (IL-ß) pathway and thus reduced the secretion of IL-1ß inflammatory factors in microglia. Further research found that melatonin has a potential binding effect with NLRP3 protein, and at the same time could reduce the phosphorylation of nuclear factor kappa-B (NF-κB) and inhibit its nuclear translocation. The underlying mechanism was that melatonin inhibited the expression of acetylation of histone H3 and melatonin attenuated the binding of NF-κb to the NLRP3 promoter region 1-200 bp, where there are two potential binding target sites of NF-κb and NLRP3, namely the sequences 5'-GGGAACCCCC-3' and 5'-GGAAATCCA -3'. Therefore, we confirmed a novel mechanism of action of melatonin in the prevention and treatment of POCD.