AKR1C1 (Aldo-Keto Reductase Family 1 Member C1)

In 3D spheroids, both agents disrupted tumor architecture and reduced viability, alone or in combination with carboplatin. Our findings highlight that platinum resistance in HGSOC can be tackled by repurposing MEF and MPA that act also as AKR1C inhibitors.

In 19Del/T790M/C797S mutant cells, SG-55 elevated the reduced/oxidized nicotinamide adenine dinucleotide phosphate (NADPH/NADP+) ratio, decreased the reduced/oxidized glutathione (GSH/GSSG) ratio, induced DNA double-strand breaks, and synergized with Osimertinib to suppress proliferation, clonogenicity, and survival. This combination therapy demonstrated efficacy in xenograft models and exhibited favorable pharmacokinetics in mice, thereby validating AKR1C3 blockade as a "metabolism-targeted" strategy to overcome resistance mediated by the EGFR C797S mutation.

ADMET profiling confirmed SFN's high intestinal absorption and blood-brain barrier non-permeability. Thus, integrating SFN as a natural AKR1B10 inhibitor into ER-negative BC treatment regimens may enhance early malignancy management and support its development as a nutraceutical adjunct.

AKR1Cs are not only significantly overexpressed in pancreatic cancer, but also closely associated with poor clinical grading, clinical chemoresistance and poor immune response in pancreatic cancer.Moreover, regulating the expression of AKR1C1 in pancreatic cancer cells will affect its proliferation, migration, invasion and the occurrence of epithelial-mesenchymal transformation (EMT). Our findings are expected to establish AKR1Cs, especially AKR1C1 as a promising therapeutic target for the clinical treatment of pancreatic cancer.

This review consolidates current findings on the molecular characteristics, brain region-specific expression, and neurophysiological functions of AKR1C enzymes, and discusses their emerging roles in central nervous system disorders. By presenting these insights, this review offers a valuable framework for researchers to explore new directions in the development of neuroprotective and neuroregenerative strategies.

Our findings suggest that ZnS inhibits autophagy, promotes ferroptosis, and enhances sensitivity to sorafenib in HCC cells through the lncRNA TCONS-00026762/AKR1C1 axis.

Our findings demonstrate that MAFF promotes tumorigenesis by suppressing ferroptosis and nominates MAFF as a promising therapeutic target for pancreatic cancer.

The results of this study suggest that the use of common anti-inflammatory medications may have significant implications for the risk and progression of oral diseases. These findings offer new insights into the clinical management of oral health and warrant further investigation into the underlying genetic mechanisms and drug-target interactions.

Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significant up-regulate genes including GLDC,LINC01595,IL-27,ANGPTL3,CYP7A1,and AKR1C1;the significant down-regulate genes including P2RY2,LIPC,and ECHDC3. A biobank of patient-derived organoids of BTC has been established,which demonstrating its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

Functional validation demonstrated that DDX39B may represent a new therapeutic target for TNBC. Moreover, we identified a series of highly selective covalent probes targeting ARK1C1, PDIA1, and ALDH1A1, which could serve as valuable tools for detecting the expression and activity of these critical proteins.

Furthermore, POE reduced the expression of pro-inflammatory and pro-coagulant markers (VCAM-1, ICAM-1, TF) and partially reversed TNF-α-induced endothelial activation. These findings suggest that POE exerts anti-angiogenic effects through a multitargeted mechanism, supporting its potential as a natural therapeutic agent for diseases characterized by aberrant angiogenesis.

Human plasma contains mostly sulfate/glucuronided steroids (2.4-6% non-sulfate/glucuronided), whereas male rats exhibit much higher free steroid levels (29-56%), likely due to the absence of zona reticularis. These findings highlight tissue-specific enzymatic differences, which may impact neurosteroid regulation and CNS disorders.