Stroke, a leading cause of death and disability, includes ischemic (IS), hemorrhagic (HS), and subarachnoid subtypes. While the triglyceride-glucose index (TyG) has been linked to cerebrovascular diseases, studies focus on single subtypes and lack ICU data. The prognostic roles of the atherogenic index of plasma (AIP) and total cholesterol-to-HDL ratio (TC_HDL) in critically ill stroke patients’ all-cause mortality (ACM) remain unexplored. This study investigates these indices’ associations with ACM in critically ill stroke patients. We screened 3247 ICU-admitted stroke patients from the eICU-CRD, stratified by TyG, AIP, and TC_HDL quartiles. Endpoints were in-hospital and ICU mortality. Analyses used Cox regression, Kaplan–Meier curves, and restricted cubic splines. In-hospital and ICU mortality rates were 17.2% and 9.7%, respectively. Multivariate Cox analysis showed elevated TyG correlated with higher ICU mortality [HR 1.528, 95% CI 1.252–1.771, *P* = 0.002] and in-hospital mortality [HR 1.434, 95% CI 1.04–1.619, *P* = 0.013]. Elevated AIP associated with higher ICU [HR 1.342, *P* = 0.021] and in-hospital mortality [HR 1.631, *P* = 0.005]. TC_HDL showed no significant associations. Kaplan–Meier curves confirmed TyG’s links to both mortalities and AIP’s association with in-hospital mortality. Restricted cubic splines revealed increasing risk with higher TyG. TyG shows stronger correlations with short-term ICU and in-hospital mortality in critically ill stroke patients compared to AIP and TC_HDL. Monitoring TyG may aid prognostic assessment and risk stratification, supporting optimized treatment strategies and aligning with prior research on TyG and stroke outcomes.

Introduction: Hyperbaric oxygen enhances glioma chemosensitivity, but the mechanism remains unclear. Hypoxia is common in gliomas, and as the main effector molecules of hypoxia, HIF1α and HIF2α promote the malignant progression by inhibiting cell apoptosis and maintaining stemness. ABCG2 is a marker protein of tumor stem cells and drug efflux transporter protein. This study aims to reveal the detailed mechanism of hyperbaric oxygen promote both proliferation and chemosensitization.Methods: Under hyperbaric oxygen and hypoxic conditions, we investigated the differences in cell cycle, proliferation, apoptosis, LDH release, and the expression of proteins and mRNA. We also conducted studies on transcriptional regulation and performed in vivo experiments.Results: It revealed that under hypoxic conditions, HIF1α, HIF2α, and ABCG2 are highly expressed, and both HIF1α and HIF2α promote ABCG2 expression. After hyperbaric oxygen treatment, the expression of HIF1α, HIF2α, and ABCG2 decreased, both cell proliferation and chemosensitivity increased. After knocking out HIF1α and HIF2α, cell proliferation and chemosensitivity increased, but the expression of stem cell marker proteins decreased. ChIP-qPCR revealed that HIF1α and HIF2α target the ABCG2 promoter. Gain-and loss-of-function experiments suggested that ABCG2 can promote the expression of stem cell marker proteins, inhibit cell apoptosis, and promote tumor progression.Conclusion: This study confirmed that hyperbaric oxygen can inhibit ABCG2 expression through HIF1α and HIF2α, thereby promoting the proliferation and chemosensitization of gliomas.

Background: This study investigates whether Hypoxia-Inducible Factor 1 alpha (HIF1α) and Hypoxia-Inducible Factor 2 alpha (HIF2α) coordinately regulate insulin-like growth factor 1 receptor (IGF1R) expression, thereby influencing chemosensitivity in glioblastoma multiforme (GBM).Methods: We analyzed the expression and correlation of HIF1α, HIF2α, and IGF1R in glioma using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Immunohistochemistry (IHC) was performed to detect the expression of HIF1α, HIF2α, and IGF1R in GBM tissues and cells, as well as oxygen tension. Cell cycle analysis, apoptosis assays, lactate dehydrogenase (LDH) release measurements, Western blotting, and xenograft tumor models were employed to explore the synergistic regulation of IGF1R by HIF1α and HIF2α, focusing on activation of the PI3K/AKT signaling pathway and its contribution to GBM drug resistance. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and dual-luciferase reporter assays were used to investigate the binding sites of HIF1α and HIF2α involved in regulating IGF1R.Results: Our study demonstrated that HIF1α and HIF2α were highly expressed in GBM tissues and hypoxia-cultured cells, and their expression positively correlated with IGF1R expression. Simultaneous knockout of HIF1α and HIF2α in GBM cells resulted in the highest LDH release and apoptosis rates under hypoxic conditions, accompanied by the most significant decrease in IGF1R, p-PDK1, and p-AKT levels. Knockout of IGF1R in tumor cells under hypoxia led to an increas of LDH release and apoptosis rates, and reduced phosphorylation of PDK1 and AKT. In addition, we demonstrated that HIF1α and HIF2α promoted IGF1R expression by binding to a specific hypoxia response element (HRE) sequence (5′-GAACGTGCCT-3′) within the IGF1R promoter using dual-luciferase reporter system.Conclusion: Glioblastoma cells, residing within a hypoxic microenvironment, exhibit high expression of HIF1α and HIF2α. These transcription factors promote the upregulation of IGF1R, which subsequently activates the PI3K/AKT signaling pathway. This activation, in turn, promotes cell proliferation and chemoresistance, ultimately contributing to tumor malignancy.

Temozolomide (TMZ) resistance remains a major obstacle to achieving durable treatment responses in glioblastoma (GBM), yet its microenvironmental associations remain incompletely defined. While most studies have focused on tumor-intrinsic mechanisms, the contribution of the tumor microenvironment (TME) to TMZ resistance is less well characterized. Here, by performing transcriptomic profiling of matched control and TMZ-resistant glioma cells based on previously publised result, we identified a prognostic gene signature representing resistant glioma stem-like cells. Projection of this signature onto large-scale single-cell RNA-seq datasets enabled stratification of tumor cells into distinct transcriptional subpopulations with varying resistance profiles. Resistant clusters exhibited enhanced crosstalk with multiple immune cell types compared with non-resistant clusters, with the strongest signals directed toward microglia/macrophages (MG) and a uniquely enriched CXCL2/3-CXCR2 chemotactic axis engaging neutrophils, as revealed by CellChat analysis. Functional assays confirmed that conditioned media from resistant glioma cells promoted neutrophil migration and reactive oxygen species (ROS) production, effects that were attenuated by CXCR2 inhibition. Together, these results define a resistance-associated gene signature that delineates discrete cellular states within gliomas and uncover a specific tumor-neutrophil communication circuit linked to TMZ resistance, highlighting CXCL2/3-CXCR2 signaling as a potential therapeutic target for overcoming treatment resistance.

Background: Data regarding the association between anthropometric factors and meningioma risk are inconsistent. Our aim was to investigate the association of body mass index (BMI), height, waist to hip ratio (WHR), waist circumference, and meningioma risk through a comprehensive meta-analysis. Methods: An extensive review of literature was conducted in PubMed and Embase databases. Random-effects models were used to pool the study-specific relative risk estimates (RRs) and 95% confidence intervals (CIs). Moreover, we employed a dose-response meta-analysis with a one-stage robust error meta-regression (REMR) model. Results: We included nine prospective studies for four anthropometric factors listed above and meningioma risk. Compared with normal weight, both overweight (RR:1.11, 95% CI: 1.04, 1.19; P = 0.003, I² = 0.0%) and obesity (RR: 1.38, 95% CI:1.16, 1.64; P < 0.001, I² = 54.7%) were statistically significantly associated with meningioma risk. Dose-response analysis showed a nonlinear relationship between BMI and meningioma risk (P = 0.038). For height, a positive association was identified for men (RR:1.30, 95% CI:1.08, 1.56; P = 0.005, I² = 0.0%) but not women (RR:1.13, 95% CI: 0.94,1.36; P = 0.186, I² = 49.8%). Highest vs. lowest levels analyses also showed a positive association between meningioma risk and waist circumference (RR:1.89, 95% CI:1.34, 2.66; P < 0.001, I² = 0.0%) and WHR (RR:1.40, 95% CI:1.00, 1.94; P = 0.048, I² = 0.0%). Conclusion: Our meta-analysis indicates greater height (in men) and excess weight and body fat mass were associated with an increased risk of meningioma. Further prospective studies with particular attention to sex disparity and dose-response analysis are warranted to confirm our observation.

Intracerebral hemorrhage (ICH) is a life-threatening neurological disorder characterized by spatiotemporally evolving pathological cascades, necessitating interventions that dynamically adapt to its multiphasic injury progression. Here, we report modular polymer (PPP)-based nanotherapeutics engineered for stage-specific therapy of ICH through sequential pharmacological actions. The PPP architecture integrates a hydrophilic segment and a hydrophobic, reactive oxygen species (ROS)-responsive motif onto a polyamine scaffold, enabling ROS-triggered programmed dissociation, on-demand anti-inflammatory agent release, and iron chelation. This design confers spatiotemporal therapeutic precision: during the hyperacute phase, PPP nanoparticles promote rapid hemostasis and efficiently scavenge cell-free DNA (cfDNA); in the acute phase, they attenuate neuroinflammation through ROS-mediated hydrolysis and subsequent release of polyamine domains; and in the subacute phase, the exposed polyamines neutralize cytotoxic aldehydes and sequester iron ions to suppress ferroptosis. In vitro, PPPs demonstrated multimodal cytoprotection by attenuating oxidative stress and inflammation in microglial cells under hemin/cfDNA challenge, thereby preserving neuronal viability, and directly inhibiting neuronal ferroptosis via downregulating heme oxygenase-1 and activating glutathione peroxidase 4/solute carrier family 7 member 11. In vivo, PPPs conferred comprehensive neuroprotection, significantly limiting hematoma expansion, reducing oxidative stress and neuroinflammation, and preventing iron-mediated neuronal death. By precisely interfacing with dynamic pathophysiology of ICH, this tunable nanotherapeutic platform represents a paradigm shift in targeted neurovascular injury management.