Breast cancer patients often have a poor prognosis largely due to lack of effective targeted therapy. It is now well established that monosaccharide enhances growth retardation and chemotherapy sensitivity in tumor cells. We investigated whether d-arabinose has capability to restrict the proliferation of tumor cells and its mechanism. Here, we report that d-arabinose induced cytotoxicity is modulated by autophagy and p38 MAPK signaling pathway in breast cancer cell lines. The proliferation of cells was evaluated by CCK-8 and Colony formation assay. The distribution of cells in cell cycle phases was analyzed by flow cytometry. Cell cycle, autophagy and MAPK signaling related proteins were detected by western blotting. Mouse xenograft model was used to evaluate the efficacy of d-arabinose in vivo. The proliferation of cells was dramatically inhibited by d-arabinose exposure in a dose-dependent manner, which was relevant to cell cycle arrest, as demonstrated by G2/M cell cycle restriction and ectopic expression of cell cycle related proteins. Mechanistically, we further identified that d-arabinose is positively associated with autophagy and the activation of the p38 MAPK signaling in breast cancer. In contrast, 3-Ma or SB203580, the inhibitor of autophagy or p38 MAPK, reversed the efficacy of d-arabinose. Additionally, d-arabinose in vivo treatment could significantly inhibit xenograft growth of breast cancer cells. Our findings were the first to reveal that d-arabinose triggered cell cycle arrest by inducing autophagy through the activation of p38 MAPK signaling pathway in breast cancer cells.

This study aimed to explore factors contributing to the delays in the diagnosis and treatment of breast cancer (BC) in Ningxia Hui Autonomous Region. We conducted a cohort analysis of 1012 patients with BC diagnosed at the General Hospital of Ningxia Medical University between January 2018 and December 2019. Sociodemographic data were collected through questionnaires, and clinical data were gathered and analyzed from relevant databases. Furthermore, observations were made regarding delays in the diagnosis and treatment of BC, followed by an analysis of the correlations between patient delay and both sociological factors within the population and clinical factors specific to patients with BC. Subsequently, the factors associated with patient delay and system delay were examined using Cox regression analysis, along with the inclusion of neoadjuvant therapy. In the prevention and treatment of BC in Ningxia, the patient delay rate was 33.20%, the diagnosis delay rate was 17.89%, the treatment delay rate was 0.0099% and the system delay rate was 41.60%. There was a higher proportion of patient delay and system delay in aged patients (age ≥ 61 years) with rural registered permanent residence (RPR), multiple clinical symptoms (such as nipple spillage, axillary abnormalities, etc), a T4 tumor size classification, and the initial use of neoadjuvant therapy. Besides, significant positive correlations were observed between patient delay and system delay time with BC stage. Patients aged 51 to 60 and those with molecular types (Limanal1B: ki-67 > 14%, Limanal1B: HER-2 positive) were prone to patient delay, whereas molecular characteristics influenced system delay, unrelated to sociodemographic factors. The study identifies significant age, residency, and tumor molecular subtype correlations with diagnostic and treatment delays in Ningxia’s patients with BC, predominantly affecting women aged 41 to 60, especially urban dwellers. These findings underscore the need for targeted interventions to reduce delays and improve BC care in this region.

Astrocyte elevated gene-1 (AEG-1) has been characterized as an oncogene promoting the progression of various tumors. The role of AEG-1 in neurological diseases was highlighted by recent researches. However, the physiological function of AEG-1 remains elusive. Our study aimed to investigate the physiological role of AEG-1 in the central nervous system by generating a mouse model with specific deletion of Aeg-1 in the hippocampus and neocortex (Aeg-1 ^fl/flCre⁺ mice). Behavioral assessments revealed that Aeg-1 deficiency caused impaired learning and memory capabilities in juvenile and adult mice. Depressive-like behaviors were also observed in Aeg-1 ^fl/flCre⁺ mice. Gene Ontology (GO) enrichment analyses indicated that AEG-1 was involved in the neuronal morphogenesis. Interestingly, Aeg-1 knockout was irrelevant to the neuron loss but reduced the dendritic length and the dendritic spines density in hippocampus. Electrophysiological analyses showed a decreased response of paired-pulse facilitation (PPF) and a compromised efficiency of excitatory synaptic transmission following Aeg-1 deletion in hippocampus. In conclusion, our findings suggest that Aeg-1 deficiency in the hippocampus and neocortex leads to learning and memory impairments and depression in mice, which is mediated by the abnormalities of neuronal morphology and the impaired synaptic functions.

Background: Accumulated evidence suggest that tumor microenvironment (TME) plays a crucial role in breast cancer (BRCA) progression and therapeutic effects. Objective: This study aimed to characterize immune-related BRCA subtypes in TME, and identify genes with prognostic value. Methods: RNA sequencing profiles with corresponding clinical data from The Cancer Genome Atlas (TCGA) database of BRCA patients were downloaded to evaluate immune infiltration using the single-sample gene set enrichment (ssGAEA) algorithm. Further, BRCA was clustered according to immune infiltration status by consensus clustering analysis. Using Venn analysis, differentially expressed genes (DEGs) were overlapped to obtain candidate genes. Kaplan–Meier (K-M) analysis was performed to identify prognostic genes, and the results were verified in the GEO and METABRIC datasets. RT-qPCR was conducted to detect the mRNA expression of prognostic genes. Results: In the TCGA database, 3 immune-related BRCA subtypes were identified [cluster1 (C1), cluster2 (C2), and cluster3 (C2)]. The C2 subtype had better overall survival (OS) compared to the C1 subtype. Higher levels of immune markers and checkpoint protein were found in the C2 subtype than in others. By combining DEGs between BRCA and normal tissues, with the C1 and C2 subtypes associated with different OS, 25 BRCA candidate genes were identified. Among these, 8 genes were identified as prognostic genes for BRCA. RT-qPCR showed that the expressions of 2 genes were significantly elevated in BRCA tissues, while that of other genes were decreased. Conclusion: Three BRCA subtypes were identified with the immune index, which may help design advanced treatment of BRCA. The data code used for the analysis in this article was available on GitHub (https://github.com/tangzhn/BRCA1.git).

Objective Triple-negative breast cancer lacks effective targeted therapies, necessitating novel treatment approaches.To evaluate the antitumor efficacy and molecular mechanisms of l-rhamnose in TNBC. Methods We employed an integrated approach combining in vitro cell-based assays and in vivo xenograft models. TNBC cell lines (MDA-MB-231, Hs578T) were treated with l-rhamnose to assess proliferation and colony formation. Molecular docking predicted the binding between l-rhamnose and GSTM5. GSTM5 gain- and loss-of-function experiments were performed to confirm its functional role. The in vivo efficacy was evaluated using MDA-MB-231 nude mouse xenografts. Ferroptosis dependency was confirmed using Ferrostatin-1. Results l-rhamnose dose- and time-dependently inhibited TNBC proliferation and colony formation. Intraperitoneal administration (5 g/kg) significantly suppressed tumor growth without affecting mouse body weight. Fer-1 attenuated l-rhamnose-mediated tumor suppression both in vitro and in vivo. Mechanistically, l-rhamnose downregulated GSTM5 protein levels, concomitant with GPX4 reduction and lipid peroxide accumulation. GSTM5 overexpression rescued l-rhamnose-induced cell death and restored GPX4, whereas GSTM5 knockdown sensitized cells to ferroptosis. Molecular docking predicted a potential interaction between l-rhamnose and the GSTM5 protein, with a calculated binding energy of -5.341 kcal/mol, which guided our subsequent functional investigations. Conclusion l-rhamnose suppresses TNBC growth by inducing ferroptosis, a process associated with the downregulation of GSTM5. Our findings reveal that GSTM5 is a key mediator modulating ferroptosis sensitivity in TNBC. These results position l-rhamnose as a candidate for further investigation in TNBC therapy.