Integrative analysis of single-cell RNA-seq and gut microbiome metabarcoding data elucidates macrophage dysfunction in mice with DSS-induced ulcerative colitis.

Ulcerative colitis (UC) is a significant inflammatory bowel disease caused by an abnormal immune response to gut microbes. However, there are still gaps in our understanding of how immune and metabolic changes specifically contribute to this disease. Our research aims to address this gap by examining mouse colons after inducing ulcerative colitis-like symptoms. Employing single-cell RNA-seq and 16 s rRNA amplicon sequencing to analyze distinct cell clusters and microbiomes in the mouse colon at different time points after induction with dextran sodium sulfate. We observe a significant reduction in epithelial populations during acute colitis, indicating tissue damage, with a partial recovery observed in chronic inflammation. Analyses of cell-cell interactions demonstrate shifts in networking patterns among different cell types during disease progression. Notably, macrophage phenotypes exhibit diversity, with a pronounced polarization towards the pro-inflammatory M1 phenotype in chronic conditions, suggesting the role of macrophage heterogeneity in disease severity. Increased expression of Nampt and NOX2 complex subunits in chronic UC macrophages contributes to the inflammatory processes. The chronic UC microbiome exhibits reduced taxonomic diversity compared to healthy conditions and acute UC. The study also highlights the role of T cell differentiation in the context of dysbiosis and its implications in colitis progression, emphasizing the need for targeted interventions to modulate the inflammatory response and immune balance in colitis.

A Retrospective View of the Triple-Negative Breast Cancer Microenvironment: Novel Markers, Interactions, and Mechanisms of Tumor-Associated Components Using Public Single-Cell RNA-Seq Datasets.

Triple-negative breast cancer (TNBC) is a significant clinical challenge due to its aggressive nature and limited treatment options. In search of new treatment targets, not only single genes but also gene pairs involved in protein interactions, we explored the tumor microenvironment (TME) of TNBC from a retrospective point of view, using public single-cell RNA sequencing datasets. A High-resolution Cell type Annotation Tool, HiCAT, was used first to identify the cell type in 3-level taxonomies. Tumor cells were then identified based on the estimates of copy number variation. With the annotation results, differentially expressed genes were analyzed to find subtype-specific markers for each cell type, including tumor cells, fibroblast, and macrophage. Cell-cell interactions were also inferred for each cell type pair. Through integrative analysis, we could find unique TNBC markers not only for tumor cells but also for various TME components, including fibroblasts and macrophages. Specifically, twelve marker genes, including DSC2 and CDKN2A, were identified for TNBC tumor cells. Another key finding of our study was the interaction between the DSC2 and DSG2 genes among TNBC tumor cells, suggesting that they are more tightly aggregated with each other than those of other subtypes, including normal epithelial cells. The overexpression of DSC2 in TNBC and its prognostic power were verified by using METABRIC, a large bulk RNA-seq dataset with clinical information. These findings not only corroborate previous hypotheses but also lay the foundation for a new structural understanding of TNBC, as revealed through our single-cell analysis workflow.

Cervical Cancer Screening and Its Associated Factors Among North Korean Defectors Living in South Korea.

North Korean defectors (NKD) have many health problems related to insufficient nutrition, trauma from escaping, and being exposed to infectious diseases, but little research exists on their cancer screening. A total of 638 NKD participated in this cross-sectional survey. South Korean natives (SKN) who participated in the Korean National Health and Nutrition Examination Survey V were selected using age matching to each NKD. Fisher's exact tests and logistic regression were used for data analysis. The cervical cancer screening rate of NKD was significantly lower than for SKN (42 and 70 %, respectively; P < .001). The adjusted proportions of cervical cancer screening for NKD in all age groups under 60 years (P < .01) and having education beyond high school (P < .001) were significantly lower than that of SKN. NKD who had education under a high school level were more likely to have cervical cancer screening compared to NKD with education beyond a high school level (OR 1.81, 95 % CI 1.12-2.93). NKD were less likely to receive appropriate cervical cancer screening compared to SKN, especially those aged 30-39 years or married. Tailored interventions for NKD are needed to improve cervical cancer screening compliance.

Factors Associated With Self-reported and Medically Diagnosed Urinary Incontinence Among Community-Dwelling Older Women In Korea.

PURPOSE: The purpose of this study was to examine the prevalence of urinary incontinence (UI) in community-dwelling Korean women 60 years or older, and to identify factors associated with self-reported and medically diagnosed UI. METHODS: This study was a secondary analysis of data from the 2008 Actual Living Condition of the Elderly and Welfare Need Survey, which used a stratified two-stage cluster sampling method to select a representative sample of 8,961 elderly Korean women. RESULTS: Of the 8,961 women in this study, 579 (6.5%) had self-reported UI, and 209 (2.3%) were medically diagnosed with UI. As patient age and exercise ability of the upper extremities increased, risk for self-reported UI decreased (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; OR, 0.99; 95% CI, 0.98-0.99, respectively). In contrast, as the number of limited instrumental activities of daily living (IADL) increased, the risk for self-reported UI increased (OR, 1.30; 95% CI, 1.24-1.35). Overweight women were 1.94 times more likely to have self-reported UI compared to underweight women. Women with a history of stroke or asthma were more likely to have self-reported UI compared to women with no history. Also, women who reported being in good health were less likely to have UI, compared to women who reported being in poor health (OR, 0.47; 95% CI, 0.31-0.70). Medically diagnosed UI was negatively associated with the number of limited IADL and exercise ability scores for the lower extremities (OR, 0.86; 95% CI, 0.80-0.92; OR, 0.98; 95% CI, 0.97-0.99, respectively). In contrast, as the exercise ability score for the upper extremities increased, so did the risk for medically diagnosed UI (OR, 1.02; 95% CI, 1.01-1.03). CONCLUSIONS: An interventional program for home visit health services is needed for incontinent women who are highly dependent on others for IADL.