We predicted potential therapeutic small molecular drugs by targeting subtype-specific oncogenic pathways and validated drug sensitivity (C1-GBM: Methotrexate and Cisplatin; C2-GBM: Cytarabine) by assessing IC50 values against GBM cell lines (divided into C1/C2 subtypes based on the nine hub genes) from the Genomics of Drug Sensitivity in Cancer database. This study introduces a pathway-based prognostic molecular classification of GBM with "hot" (C1-GBM) and "inherent driving" (C2-GBM) tumor subtypes, providing a prediction model based on hub biomarkers and potential therapeutic targets for treatments.

This study presents a method to improve the therapeutic effect of methotrexate against rheumatoid arthritis using the Exo/MTX/HA.

In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA.

In the pre-biologic era, immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate (MTX) were widely used as first-line maintenance therapies in Crohn's disease. In light of evolving treatment goals that prioritize safety, cost-effectiveness, and individualized care, this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations. The survey underscores a persistent gap between guidelines and real-world practice, reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn's disease management.

Rats were randomly divided into five groups: healthy control (Control), untreated RA model (Model), SIL (25 mg/kg/day), SIL (50 mg/kg/day), and methotrexate (7.6 mg/kg/day) groups, with 10 mice in each group...SIL effectively mitigates myocardial fibrosis and oxidative stress in adjuvant-induced RA rats, primarily through inhibition of IRAK4-mediated inflammatory signaling. These findings highlight SIL as a promising therapeutic candidate for RA-related cardiac injury.

Collectively, our findings uncover that METTL3-mediated m6A modification of CACNA1E contributes to OS progression and chemoresistance through enhancing WNT7B-mediated non-canonical Wnt/Ca2+ signaling. Targeted inhibition of CACNA1E in combination with MTX may be a promising alternative therapeutic strategy for patients with MTX-resistant OS.

CAEO considerably alleviated the oxidative and nitrosative stress, mitochondrial dysfunction, inflammatory and apoptosis responses caused by MTX. This shielding effect may be due to the decline in JAK2/STAT3/NF-κB and the triggering in Nrf2/HO-1/NQO1 pathways.

The congruence between bioinformatics and experimental validation findings strongly highlighted API as a promising therapeutic candidate for alleviating METX cardiotoxicity. While the current data reveals key underlying molecular mechanisms for API's cardioprotective effect, further comprehensive studies across diverse cardiotoxicity models are essential to fully elucidate cardioprotective effect of API.

Concurrent methotrexate use was found to exacerbate VCR-induced neurotoxicity. VCR-induced neurotoxicity remains a significant challenge in ALL therapy. Standardized neurotoxicity assessment tools and prospective studies are needed to improve early detection and optimize management strategies, ultimately balancing treatment efficacy with minimizing neurological morbidity.

The mice were randomly divided into a CIA model group (MO group), melittin acupoint subcutaneous injection group (ST group), melittin acupoint intramuscular injection group (IT group), and methotrexate group (MTX group), with an additional normal control group (NC group) established...WB analysis showed elevated levels of Unc-51-like autophagy activating kinase 1 (ULK1), beclin-1 (P<0.01), and microtubule-associated protein 1 light chain 3 II (LC3II) (P<0.05), and reduced phosphorylation of PI3K, AKT, and mTOR (P<0.05). MAI alleviates RA symptoms by inhibiting the PI3K/AKT/mTOR pathway and promoting autophagy.

In addition, the STING activator DMXAA attenuated the inhibitory effect of TP combined with MTX on LPS-induced RAW264.7 cell viability and inflammatory response(P<0.05). In conclusion, TP combined with MTX synergistically inhibited LPS-induced proliferation of RAW264.7 cells, and its mechanism of action may be related to the down-regulation of the cGAS-STING pathway and the influence on macrophage migration and invasion, which provides further evidence for the treatment of rheumatoid arthritis with TP combined with MTX.

P2, N=27, Terminated, AHS Cancer Control Alberta | Trial completion date: Nov 2029 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Jan 2026 --> Jun 2025; Challenges in meeting the enrollment target