Search

The identification of novel age‐related biomarkers represents an area of intense research interest. Despite multiple studies associating DNA damage with aging, there is a glaring paucity of DNA damage‐based biomarkers of age, mainly due to the lack of precise methods for genome‐wide surveys of different types of DNA damage. Recently, we developed two techniques for genome‐wide mapping of the most prevalent types of DNA damage, single‐strand breaks and abasic sites, with nucleotide‐level resolution. Herein, we explored the potential of genomic patterns of DNA damage identified by these methods as a source of novel age‐related biomarkers using mice as a model system. Strikingly, we found that models based on genomic patterns of either DNA lesion could accurately predict age with higher precision than the commonly used transcriptome analysis. Interestingly, the informative patterns were limited to relatively few genes and the DNA damage levels were positively or negatively correlated with age. These findings show that previously unexplored high‐resolution genomic patterns of DNA damage contain useful information that can contribute significantly to both practical applications and basic science. [ABSTRACT FROM AUTHOR]

Cell therapy represents a promising treatment modality. A critical component in the production of cell therapy products is maintaining the sterility of cell therapy clean rooms (CTCRs). This study aimed to evaluate the environmental microbial load within CTCRs. We systematically monitored microbial load in CTCRs, following established guidelines. Cultured microbial samples underwent metagenomic sequencing, and alpha and beta diversity analyses, functional annotation, and resistance gene profiling were performed using various bioinformatics tools to assess microbial diversity and function. From November 2023 to January 2024, we collected 42 environmental microbial colony samples from various sources within the CTCR and performed metagenomic sequencing on 39 samples. Alpha diversity analysis revealed no significant differences among surface, settle_plate, and airborne categories, but significant disparities within surface subgroups were revealed. Beta diversity analysis showed notable differences between surface and airborne categories and among surface subgroups. Species distribution analysis identified Bacillus as the predominant genus on surfaces. Functional annotation and resistance gene analysis indicated distinct resistance patterns, with significant variations between subgroups, such as microscopes and transfer windows, and hands and other Grade_B environments. Resistance to hydrogen peroxide was notably higher in the transfer window group. These findings highlight the importance of stringent disinfection protocols and enhanced hand hygiene to maintain sterility in CTCRs. These findings provide valuable insights for implementing effective measures to maintain cleanliness throughout CTCRs. The annotation and study of resistance genes can help rapidly identify methods to control cellular contamination under circumstances of environmental microbial pollution.IMPORTANCEMaintaining the sterility of cell therapy clean rooms (CTCRs) is crucial for the production of safe and effective cell therapy products. Our study systematically evaluated the environmental microbial load within CTCRs, revealing significant microbial diversity and distinct resistance patterns to disinfection methods. These findings underscore the need for stringent disinfection protocols and enhanced hand hygiene practices to ensure CTCR sterility. By identifying key microbial species and their resistance genes, our research provides essential insights into controlling contamination and safeguarding the production environment, ultimately contributing to the reliability and success of cell therapy treatments.

Background: Inactivation of members of the OVO-like family of C2H2 zinc-finger transcription factor 2 (OVOL2) is increased after colorectal cancer (CRC) metastasis. This study investigated the functional roles and clinical relevance of OVOL2 and its downstream factors in colorectal carcinogenesis., Methods: Transcriptome RNA sequencing (RNA-seq) of HCT116 cells overexpressing OVOL2 and SW480 cells silencing OVOL2 were conducted. We cross-checked the Chromatin Immunoprecipitation sequencing (ChIP-seq, GSM1239518) positive peaks and RNA-seq differential expression genes (DEGs). In vitro functional assays, including wound-healing assay and transwell assay, were performed. The RNA expression (n = 597) and protein expression (n = 93) of OVOL2- mitogen-activated protein kinase kinase kinase 8 (MAP3K8)-C-X-C Motif Chemokine Ligand 16 (CXCL16) were evaluated in human CRC and adjacent normal tissues. CXCL16 levels in cell culture supernatants and serum samples obtained from 29 colon polyps patients and 24 CRC patients were measured using ELISA., Results: We found that OVOL2 inhibited the migration and epithelial mesenchymal transition (EMT) of CRC cells by blocking the MAP3K8/AKT/NF-κB signaling pathway, and also decreased levels of CXCL16, a chemokine downstream of the MAP3K8/AKT/NF-κB signaling pathway. Furthermore, patient tumor tissue samples showed a lower level of in situ OVOL2 (P = 0.005) and higher CXCL16 (P = 0.001) levels, compared to adjacent normal tissues. Survival analyses revealed that both OVOL2 (logrank P = 0.063) and CXCL16 (logrank P = 0.048) were associated with overall survival (OS) and were independent prognostic factors for CRC. Additionally, OVOL2 and CXCL16 were found to be prognostically relevant (logrank P = 0.038). CXCL16 may serve as a potential diagnostic biomarker for CRC (P = 0.010)., Conclusions: The OVOL2/ MAP3K8/CXCL16 axis is a key player in colonic tumorigenesis and metastasis, and may be a potential diagnostic and prognostic biomarker., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Evidence suggests that DNA repair capacity manifested by intact functional base excision repair and mismatch repair (MMR) pathways is related to the prognosis of multiple cancer types. Aldolase B (ALDOB) is well known for its role in metabolism and glycolysis. The expression of ALDOB in colon adenocarcinoma and the relationship between its expression and colon adenocarcinoma prognosis remain controversial; in addition, the potential role of ALDOB in DNA MMR has not yet been reported. In this study, we identified a cluster of DNA repair-related proteins that interact with ALDOB in the colon adenocarcinoma cell line HCT116. Expression analysis of colon adenocarcinoma data from the Cancer Genome Atlas (TCGA-COAD data, n = 551) indicated that ALDOB mRNA expression was significantly higher in specimens with microsatellite instability (MSI) than in specimens with microsatellite stability (MSS). Regarding prognosis, colon adenocarcinoma patients with high ALDOB mRNA expression had longer overall survival (OS). Higher expression of ALDOB protein was significantly correlated with MMR deficiency (d-MMR) in formalin-fixed paraffin-embedded (FFPE) patient specimens. The expression of ALDOB was significantly elevated in colon adenocarcinoma cell lines. Further evidence indicated that rather than affecting proliferation, ALDOB overexpression induced the functional loss of MMR proteins and in turn caused irreversible DNA damage via disrupting EZH2-Rad51 expression and then caused apoptosis by ERK inactivation. Overall, our study demonstrates that high ALDOB expression impairs DNA MMR and induces apoptosis in colon adenocarcinoma. ALDOB may be a new biomarker associated with d-MMR and an independent prognostic factor for colon adenocarcinoma., (Copyright © 2019 Elsevier GmbH. All rights reserved.)