Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with very poor prognosis despite recent progress in multimodal treatments. Within glioma tissue, various niche cells such as macrophages and neutrophils form a unique glioma immune microenvironment (GIME) by interacting with heterogenous cancer cells, and this has been implicated in disease progression and responsiveness to immunomodulatory therapies. This study explores novel potential prognostic markers associated with the GIME using integrated bioinformatics analyses, including single-cell RNA-sequencing (scRNA-seq), and spatial transcriptome (ST) datasets of clinical GBM specimens. We first identified 42 genes as being associated with poor prognosis in GBM from 5 different cohorts, GBM vs. nontumor tissue, grade IV vs. grade II gliomas, isocitrate dehydrogenase (IDH)-wild-type vs. IDH-mutant variants, mesenchymal vs. proneural and classical subtypes, and hazard ratio for overall survival. Among these, 32 genes were positively correlated with ESTIMATEScore, infiltration of various immune cell types, expression of known immune-related genes, and representative immune-associated biological signals. On scRNA-seq analysis, 7 genes were relatively concentrated in tumor-associated macrophages rather than in malignant cells. ST analysis revealed that Collagen beta(1-O)galactosyltransferase 1 (COLGALT1), Integrin subunit beta 2 (ITGB2), and Myosin light chain 12A (MYL12A) were distributed in the interface between the tumor and the peritumoral area, overlapping with the expression of representative immune-related genes. These findings support the potential of COLGALT1, ITGB2 and MYL12A as biomarkers for predicting the prognosis and immune responses of GBM, which can help in the development of potential immunotherapeutic strategies for GBM.

Adropin is a 43-amino acid peptide that is highly conserved among mammals. First identified in the mouse liver in 2008, adropin is broadly expressed throughout the body and has been implicated in various pathological conditions, including obesity, altered food intake, insulin resistance, glucose intolerance, and other disorders related to energy metabolism. However, its precise physiological role remains unclear. In this study, we developed a specific competitive enzyme-linked immunosorbent assay (ELISA) for adropin using an in-house generated anti-adropin polyclonal antibody. We then examined plasma adropin levels in mice under different energy metabolic conditions: fed a normal diet, subjected to short-term fasting, and fed a long-term high-fat diet. In addition, we assessed hepatic and hypothalamic expression of Enho mRNA, which encodes adropin. We observed a wide range of plasma adropin levels, spanning from those in normal healthy mice on a high-fat diet to preclinical and obese diabetic mice. Both plasma adropin concentrations and hepatic Enho mRNA expression increased in response to feeding and high-fat diet intake. Multiple regression analysis revealed a significant negative correlation between plasma adropin and plasma glucagon concentrations. These findings suggest that adropin secretion is modulated by the peripheral hormone glucagon and may contribute to the maintenance of energy metabolic homeostasis. In conclusion, the ELISA developed in this study provides a useful and reliable tool for investigating the mechanisms underlying energy metabolism.

Parthanatos is a noncanonical form of regulated cell death mediated by the overactivation of poly(ADP-ribose) polymerase-1, yet its regulatory mechanisms are not fully understood. To fully elucidate its regulatory mechanisms, it is necessary to establish useful research tools to investigate parthanatos. We have previously identified the human fibrosarcoma HT1080 cells as highly sensitive cells to parthanatos, and cefotaxime, a 3rd-generation cephem antibiotic, as the parthanatos inducer. In this study, we comprehensively characterized the ability of various cephem antibiotics, including cephalothin (also called cefalotin) (CET), cefoxitin, ceftriaxone, cefoperazone, ceftezole, and cefalexin, to induce parthanatos. Among them, CET exhibited the lowest LD₅₀. Therefore, our results show that CET works as the more potent and useful parthanatos inducer.

Allergic contact dermatitis (ACD) is a common skin disorder caused by contact with allergens. ACD treatment is based on patient education to avoid contact with allergens. However, sometimes patients may not be able to avoid the allergen because of its close proximity to their living environment. Thus, a novel therapeutic strategy that does not involve the avoidance of allergens is required. We previously reported that methionine, an essential amino acid, significantly suppressed ACD development caused by the repeated application of 1-fluoro-2,4-dinitrobenzene (DNFB). However, the magnitude of this suppressive effect of methionine depended on the mouse strain used to establish ACD, and the mechanism of this difference was still unclear in past studies. In this study, we investigated the mechanism underlying these strain differences and found that a lack of selenium-binding protein 1 (SBP1) enhanced the ACD-suppressive effect of methionine. The lack of SBP1 does not affect ACD progression; however, it reduces the hepatic beta-homocysteine methyltransferase (Bhmt) expression suppression by ACD. In support of this hypothesis, the lack of SBP1 reduced the suppression of hepatic dimethylglycine (DMG) production by ACD. These results suggest that the lack of SBP1 enhances the suppressive effects of methionine on ACD by suppressing DMG production.

The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system plays an important role in defense against oxidative stress, and its involvement has been implicated in body weight reduction under obese conditions. While the effect on white adipose tissue (WAT) has been intensely studied, focusing on the anti-inflammatory and anti-oxidative stress effects exerted by Nrf2 activation, the involvement of skeletal muscle has not been investigated. We assessed the body weight changes induced by Nrf2 activation by comparing its effect on WAT with those on skeletal muscle. We evaluated TBE-31, a potent Nrf2 activator, in a high-fat diet (HFD)-induced obesity model. Notably, TBE-31 significantly suppressed HFD-induced body weight gain compared with vehicle treatment. While treatment with TBE-31 induced a significant WAT weight decrease compared with vehicle, skeletal muscle weight was not affected. In addition, body weight changes were significantly correlated with WAT but not with skeletal muscle. Lipid deposition was remarkably improved in the adipose tissue, but muscle histology was not affected. A gene expression analysis revealed that Ucp-1 was upregulated and Il-6 downregulated by TBE-31 treatment in an Nrf2-dependent manner. Taken together, these findings suggest that pharmacological activation of Nrf2 suppressed HFD-induced body weight gain by affecting WAT.