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.

The combination of IT via Ommaya reservoir and WBRT may result in better survival in EGFR-mutant NSCLC patients with LM and represents a promising treatment strategy for this patient population.

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

Our data demonstrated that MTX-mediated activation of the ERK/KEAP1 signaling pathway significantly induced ferroptosis by inhibiting the NRF2/HO-1/SLC7A11/GPX4 axis, thereby suppressing OC progression. These findings suggest that MTX is a promising candidate for OC treatment, offering a meaningful and effective therapeutic-strategy.

P=N/A, N=20, Completed, Ohio State University Comprehensive Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2026 --> Dec 2025

This case illustrates a fulminant presentation of primary vitreoretinal lymphoma, characterized by rapidly progressive optic disc involvement and extensive serous retinal detachment. Despite the severity, early diagnostic vitrectomy followed by prompt intravitreal methotrexate enabled anatomical and functional recovery.

β-sitosterol was associated with reduced oxidative stress markers and lower hepatic TGF-β, STING and ERK-1 levels in this short-term MTX injury model. These findings suggest that β-sitosterol may have potential therapeutic value in mitigating MTX-related hepatotoxicity.