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Ovarian cancer is the third most common gynecological malignancy worldwide and the fifth leading cause of cancer-related death among women. This may be attributed to difficulties in diagnosing early-stage ovarian cancer, as it is typically asymptomatic until metastases, and due to the ineffective management of patients with late-stage ovarian cancer. The aim of the present study was to investigate potential therapeutic targets for the treatment of ovarian cancer. Bioinformatics techniques were used to analyze the expression levels of tryptophan (Trp) metabolism-related genes in tissue samples from patients with ovarian cancer. Additionally, western blots, clonogenic assays, immunohistochemical staining, chromatin immunoprecipitation-quantitative PCR, cell co-culture assays, a xenograft model and high-performance liquid chromatography-tandem mass spectrometry were performed to evaluate the antitumor effects of genes identified from the bioinformatics analysis. Increased expression levels of the amino acid transporter, solute carrier family 7 member 5 (SLC7A5), in tissue samples from patients with ovarian cancer was demonstrated. Inhibition of SLC7A5 reduced ovarian cancer cell proliferation through G2/M cell cycle arrest and blocked intracellular aryl hydrocarbon receptor nucleus entry, which downregulated PD-L1 expression levels. Dysregulation of Trp metabolism in ovarian cancer tissue samples, as well as the upregulation of kynurenine expression levels in the plasma of patients with ovarian cancer, were demonstrated to be unfavorable prognostic factors for the progression-free survival of patients with ovarian cancer. The present study demonstrated that the dysregulation of Trp metabolism could potentially be used as a diagnostic biomarker for ovarian cancer, as well as the potential of targeting SLC7A5 for immunotherapeutic management of patients with ovarian cancer in the future. [ABSTRACT FROM AUTHOR]

Valsa canker, caused by fungal pathogens in Valsa species, is a fungal disease of apple and pear growing in China and even in Asia. Malectin-like kinases play crucial roles in plant recognition of the pathogen-induced signals and subsequent activation of partially host immune responses. However, the role of MEDOS1 (MDS1), a Malectin-like kinase, in plant immunity has not yet been extensively explored. Here, we found that the expression of the Malus domestica MDS (MdMDS1) gene, a homologous gene of the Catharanthus roseus Receptor-Like Kinase 1-like (CrRLK1L) family member MDS1 in Arabidopsis, could be inhibited by Valsa canker signals. Over-expression of MdMDS1 decreased Valsa canker resistance of apple and pear fruits, as well as 'Duli-G03' (Pyrus betulifolia) suspension cells. In response to Valsa pyri (Vp) signals in suspension cells, the up-regulation of MdMDS1 caused the inhibition of defense-related genes but activated the expression of cell wall-related genes. Among these, the pectin methylesterase gene PbePME1 was robustly induced. Further analysis confirmed that PbePME1, a negative regulator of Valsa canker resistance, was indispensable for MdMDS1's function. Our results enriched the recognization of the functions of CrRLK1L genes in host resistance against necrotrophics. We also provided a theoretical reference for the resistance breeding and comprehensive control of Valsa canker in both apples and pears., (© 2024 Scandinavian Plant Physiology Society.)