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The aminopeptidase activity (AP) of the leukotriene A4 hydrolase (LTA4H) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTA4H AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTA4H modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTA4H AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates. Differential modulation of LTA4H by 4MDM was probed in a murine model of acute lung inflammation, which showed that 4MDM modulates the host neutrophilic response independent of clearing PGP. X-ray crystallography showed that 4MDM and PGP bind at the zinc binding pocket and no allosteric binding was observed. We then determined that 4MDM modulation is not dependent on the allosteric binding of the ligand, but on the N-terminal side chain of the peptide. In conclusion, our study revealed that a peptidase therapeutic target can interact with its substrate and ligand in complex biochemical mechanisms. This raises an important consideration when ligands are designed to explain some of the unpredictable outcomes observed in therapeutic discovery targeting LTA4H. [ABSTRACT FROM AUTHOR]

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The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch ( J -NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO 2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J -NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.

Background: RNA methylation is a significant form of post-transcriptional modification that has been implicated in various diseases, including cancers. One prominent type of RNA methylation is 5-Methylcytosine (m 5 C), which primarily regulates RNA stability, transcription, and translation. However, the role of m 5 C-related gene regulation in cell adhesion within uterine corpus endometrial carcinoma (UCEC) remains unexplored. Therefore, the objective of this study was to investigate the association between RNA m 5 C methylation and UCEC and develop a prognostic predictive model to forecast survival outcomes in UCEC patients., Methods: The RNA datasets were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The dataset was used to explore the interaction relationships of m 5 C regulators in UCEC. Unsupervised clustering analysis identified clusters with distinct m 5 C modification patterns. Different clusters underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment level analysis to investigate the effects of pathways related to m 5 C methylation, which were further validated through in vitro cellular experiments. A prognostic predictive model was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis., Results: Two clusters with distinct m 5 C modification patterns were identified using unsupervised cluster analysis. Furthermore, the prognosis of cluster 2 was found to be worse. Enrichment analysis showed alterations in cell adhesion-related pathways in both clusters, as well as differences between the clusters. Through this analysis, we identified 25 genes with significant prognostic value. Finally, a prognostic predictive model comprising NSUN2 and YBX1 was constructed., Conclusions: In conclusion, diverse m 5 C modification patterns display distinct cell adhesion properties in UCEC, which are correlated with prognosis and offer significant potential as prognostic markers for UCEC assessment. We developed a prognostic predictive model to accurately predict the prognosis of UCEC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-742/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Objective: To observe the effects of human umbilical cord mesenchymal stem cells (UC-MSCs) on the proliferation and apoptosis of human ovarian cancer cell SKOV3.
 Methods: Transwell co-culture was used to observe the targeted homing effect of UC-MSCs on ovarian cancer cells. MTT assay was used to detect the inhibitory effect of UC-MSCs conditioned medium on SKOV3 proliferation, and Annexin V-FITC/PI double staining was used to detect the apoptotic rate. Real-time PCR was used to detect the expression levels of Ki-67, Bcl-2 and Bax genes-relevant to proliferation and apoptosis of SKOV3 cells.
 Results: UC-MSCs targeted SKOV3 cells in vitro. MTT assay showed that UC-MSCs conditioned medium significantly inhibited the proliferation of SKOV3 cells (P<0.01). Annexin V-FITC/PI double staining showed that the apoptotic rate in the 75% conditioned medium group was significantly higher than that in the control group (P<0.05). Real-time PCR showed that the expression of proliferation-related gene Ki-67 decreased significantly (P<0.01). The apoptosis-related gene Bcl-2 expression was decreased dramatically (P<0.01), and Bax expression was increased significantly (P<0.01).
 Conclusion: UC-MSCs can target ovarian cancer cells in vitro, inhibit the proliferation of SKOV3 cells by regulating the expression of Ki-67, and promote the apoptosis of SKOV3 cells by regulating the expression of Bcl-2 and Bax.

Special AT-rich sequence binding protein 1 (SATB1) is a master chromatin organizer that has recently been reported to directly upregulate metastasis-associated genes and downregulate tumor suppressor genes. However, its clinical significance in the case of ovarian cancer remains unclear. In the current study, we assessed the expression levels of SATB1 in ovarian cancer and aimed to show whether it may be a conventional clinicopathological parameter. Epithelial ovarian cancer (n=91), borderline cystadenoma (n=13) and normal ovarian background tissues (n=8) were collected immediately following excision during surgery. The mRNA expression levels of SATB1, VEGF-A and MMP-9 were determined using real-time quantitative PCR. Western blotting and immunohistochemical staining were carried out to detect the protein expression levels of SATB1. Expression levels within the ovarian cancer specimens were compared to the normal background tissues and analyzed against FIGO stage, lymph node involvement and histological type. SATB1 mRNA in malignant and borderline ovarian cystadenoma tissues was 6.74- and 5.70-fold higher compared with normal ovarian tissue, respectively (P<0.01). Western blot analysis revealed that a strong positive band of SATB1 expression was present in ovarian cancer tissues. Immunohistochemical staining showed that the positive expression rates of SATB1 in ovarian cancer, borderline ovarian cystadenoma and normal ovarian tissues were 69.2, 61.5 and 0% (P<0.01), respectively. SATB1 expression increased concomitantly with increasing FIGO stage and lymph node involvement. Survival curves showed that a higher SATB1 expression was correlated with shorter survival. Our results provide evidence that SATB1 expression is significantly associated with progression, metastasis and prognosis of epithelial ovarian cancer. SATB1 may therefore serve as a conventional clinicopathological parameter of ovarian cancer.