Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Molecular hydrogen has been considered a preventive and therapeutic medical gas in many diseases including cancer. In our study, we sought to assess the potential role of molecular hydrogen on GBM. The in vivo studies were performed using a rat orthotopic glioma model and a mouse subcutaneous xenograft model. Animals inhaled hydrogen gas (67%) 1 h two times per day. MR imaging studies were performed to determine the tumor volume. Immunohistochemistry (IHC), immunofluorescence staining, and flow cytometry analysis were conducted to determine the expression of surface markers. Sphere formation assay was performed to assess the cancer stem cell self-renewal capacity. Assays for cell migration, invasion, and colony formation were conducted. The in vivo study showed that hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM. IHC and immunofluorescence staining demonstrated that hydrogen treatment markedly downregulated the expression of markers involved in stemness (CD133, Nestin), proliferation (ki67), and angiogenesis (CD34) and also upregulated GFAP expression, a marker of differentiation. Similar results were obtained in the in vitro studies. The sphere-forming ability of glioma cells was also suppressed by hydrogen treatment. Moreover, hydrogen treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.

Introduction: The tumor microenvironment (TME) is crucial for the development of head and neck squamous cell carcinoma (HNSCC). However, the correlation of the characteristics of the TME and the prognosis of patients with HNSCC remains less known.Methods: In this study, we calculated the immune and stromal cell scores using the “estimate” R package. Kaplan-Meier survival and CIBERSORT algorithm analyses were applied in this study.Results: We identified seven new markers: FCGR3B, IGHV3-64, AC023449.2, IGKV1D-8, FCGR2A, WDFY4, and HBQ1. Subsequently, a risk model was constructed and all HNSCC samples were grouped into low- and high-risk groups. The results of both the Kaplan-Meier survival and receiver operating characteristic curve (ROC) analyses showed that the prognosis indicated by the model was accurate (0.758, 0.756, and 0.666 for 1-, 3- and 5-year survival rates). In addition, we applied the CIBERSORT algorithm to reveal the significant differences in the infiltration levels of immune cells between the two risk groups.Discussion: Our study elucidated the roles of the TME and identified new prognostic biomarkers for patients with HNSCC.

MYSM1, a deubiquitinating enzyme, plays a pivotal role in diverse biological processes. Both MYSM1 knockout mice and patients with Mysm1 gene mutations exhibit developmental abnormalities across multiple tissues and organs. Serving as a crucial regulator, MYSM1 influences stem cell function, immune responses, and the pathogenesis of diverse diseases. This review comprehensively details MYSM1’s deubiquitinating activities in both the nucleus and cytoplasmic compartments, its effects on stem cell proliferation, differentiation, and immune cell function, and its involvement in cancer, aging, and depression. The high sequence homology between murine and human MYSM1, along with similar phenotypes observed in Mysm1-deficient models, provides valuable insights into the etiology of human Mysm1-deficiency syndromes. This review aims to offer a foundation for future comprehensive research on MYSM1.

Radiation-induced brain injury (RBI) is a severe complication of cranial radiotherapy that poses a significant clinical challenge due to a lack of effective treatments. Ferroptosis, an oxidative stress-driven cell death pathway, has been implicated in its pathogenesis. Here, we report that 75% ethanol (GBF-8), a novel subfraction isolated from male Ginkgo biloba flowers, confers significant protection against RBI. In a murine RBI model, GBF-8 administration restored cognitive function and alleviated neuroinflammation. We demonstrated that this neuroprotective effect is mechanistically linked to ferroptosis inhibition. Integrated proteomic and metabolomic profiling identified the Solute carrier family 7 member 11 (Slc7a11)–Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (Eif4ebp1) axis as the primary target of GBF-8. This work not only establishes GBF-8 as a promising therapeutic candidate but also delineates a previously unrecognized regulatory axis for combating ferroptosis in RBI.

Background: Necroptosis has emerged as a critical regulator in tumor progression and therapeutic response, yet its prognostic significance and influence on the tumor microenvironment (TME) in gastric cancer (GC) remain poorly characterized. Therefore, it is needed to unveil the intricate relationship between GC and necroptosis. Methods: We conducted an integrative analysis of bulk and single-cell data to delineate the prognostic landscape of necroptosis in GC. A necroptosis-related (NR) model was established using transcriptomic data from the TCGA cohort and validated in an external GEO cohort. To translate this model into clinical practice, a prognostic nomogram incorporating NR scores and clinical parameters was constructed. The molecular mechanisms underlying NR variations were investigated through stemness analysis, pathway enrichment, immune cell infiltration profiling, and intercellular communication networks. Results: Consensus clustering analysis revealed pronounced heterogeneity in GC by stratifying patients into two survival-associated NR clusters (cluster 1 and cluster 2) with differences in TME characteristics. Employing machine learning approaches, a NR model was developed and validated, which demonstrated predictive ability for survival outcomes. Meanwhile, the nomogram demonstrated clinically relevant predictive accuracy, with time-dependent area under curve (AUC) values of 0.701 (1-year), 0.715 (3-year), and 0.753 (5-year). Notably, this NR model enabled robust stratification of GC patients into two distinct subgroups, both in bulk and single-cell datasets. Single-cell resolution analysis revealed patients with varying NR scores were characterized by aberrant enrichment of endothelial cells, epithelial cells, and fibroblasts, highlighting the profound impact of necroptosis on cellular composition within the TME. Conclusions: Our novel NR model deciphers the dynamic interplay between necroptosis and TME remodeling in GC, enabling robust patient stratification across both bulk and single-cell data and revealing a necroptosis-driven environment characterized by aberrant expansion of endothelial cells, epithelial cells, and fibroblasts. The clinically applicable nomogram offers a precision medicine framework for risk assessment.