AKT1 (V-akt murine thymoma viral oncogene homolog 1)

Thirty-eight pharmaceuticals demonstrated significant associations with cheilitis, with isotretinoin being the most frequently reported (ROR = 42.61) and crisaborole exhibiting the most pronounced signal (ROR = 550.48)...Molecular docking studies indicated strong binding affinities (ranging from -8.1 to -6.2 kcal/mol), particularly for the afatinib-EGFR and capecitabine-IL-6 interactions...ADMET profiling predicted a high risk of drug-induced liver injury for four compounds, while lamotrigine demonstrated a favorable safety profile. This integrative framework connects population-level indicators with mechanistic forecasts, providing a translational model for comprehending, predicting, and managing drug-induced cheilitis.

Although less potent than the nanomolar-range reference drug Epothilone B (IC50 < 0.1 μM), rugulosin A showed submicromolar-to-low micromolar efficacy with notable selectivity toward cancer cells, which is considered significant for an unoptimized natural product scaffold. Its antiproliferative activity against K562 cells (GI50 = 3.69 μM), benchmarked against Imatinib (GI50 = 0.373 μM), also falls within the active range of natural product leads...Molecular docking revealed strong binding energies (-10.1, -9.8, and -11.0 kcal/mol), along with a stable molecular dynamics simulations data. These findings highlight rugulosin A (3) as a promising anticancer lead that modulates major apoptosis signaling pathways.

Fusion transcript analysis identified 91 recurrent fusions, including novel partners with ERBB2, MED1, and CDK12, suggesting the possibility of unique molecular events. Interpretation and conclusions This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.

Based on our experimental data, we propose a translational pathway, from preclinical intraperitoneal validation to clinically feasible local delivery (e.g., endoscopic submucosal injection or retention enema), with dose translation and follow-up endpoint suggestions. This study demonstrates the potential of advanced biomaterials and nucleic acid therapeutics for genetic/rare diseases, providing a basis for personalized FAP prevention.

The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.

Pathway analysis revealed predominant WNT/β-catenin signaling in EBTs versus RAS-MEK-ERK pathway alterations in SMBTs resembling the seromucinous variant of ovarian endometrioid carcinoma, with additional involvement of PI3K-PTEN-AKT-mTOR and SWI/SNF chromatin remodeling pathways in both. These findings demonstrate that EBTs and SMBTs possess distinct morphologic and molecular profiles, expanding the molecular characterization of early ovarian endometrioid-type neoplasms.

P3, N=256, Active, not recruiting, Laekna Limited | Recruiting --> Active, not recruiting

Mechanistically, UA was associated with modulation of the AKT/mTOR signaling pathway to limit tumor progression and with alterations in AKT1-related signaling, including changes in the P-AKT1/FOXO1 axis and increased expression of cytotoxic effector molecules such as GZMB, thereby contributing to antitumor immune activation and remodeling of the tumor immune microenvironment. This study proposes a working model of a diet-microbiota-AKT1-immunity axis, which may provide conceptual insights into CRC prevention and immunotherapeutic strategies.

This study comprehensively explores the multi-target mechanisms of TKM against TNBC using network pharmacology, molecular pharmacology, and metabolomics approaches. These findings provide a foundation for future mechanistic investigations and may support the further preclinical development of TKM-based strategies for TNBC.

ADME profiling confirmed favorable drug-likeness of α-cedrol. These results suggest that J. chinensis L. seed essential oil, particularly as a complex phytochemical mixture containing α-cedrol, holds promise as a natural source for antimicrobial and anticancer agents.

Acacetin alleviates loperamide-induced FC by inhibiting P53-mediated apoptosis in colonic epithelial cells, providing new insights into the therapeutic mechanisms of traditional Chinese herbal medicine YWL in treating constipation.

This study identifies SAA1 as a potential target in BPA-induced dermatomyositis, highlighting the impact of BPA on immune regulation and providing a foundation for understanding associated health risks and developing mitigation strategies. Given the limited research on dermatomyositis, further experimental validation is essential to elucidate the pathogenic mechanisms of BPA.