miR-628-5p is a Potential Novel Prognosis Biomarker, Associated with Immune Infiltration in Bladder Urothelial Carcinoma.

BACKGROUND: microRNA-628-5p (miR-628-5p) has a significant impact on certain types of cancer. The precise function of miR-628-5p in the context of bladder urothelial carcinoma (BLCA) remains ambiguous. OBJECTIVE: We aimed to investigate the role of miR-628-5p in BLCA. METHODS: The samples were collected from The Cancer Genome Atlas (TCGA). Statistics were employed to evaluate the correlation and predictive significance of miR-628-5p. We analyzed the target genes and regulatory network of miR-628-5p and the correlation between miR-628-5p and immune infiltration. The expression of miR-628-5p in BLCA cells was confirmed by quantitative reverse-transcription PCR (qRT-PCR). RESULTS: miR-628-5p exhibited differential expression across various types of cancer. There was a significant association between high expression of miR-628-5p and primary therapy outcome (p < 0.05). High expression of miR-628-5p was observed to be associated with poorer overall survival (HR: 1.42; 95% CI: 1.06-1.90; p = 0.02), progress free survival (HR: 1.57; 95% CI: 1.17-2.11; p = 0.003), and disease specific survival (HR: 1.83; 95% CI: 1.28-2.62; p = 0.001) in BLCA. miR-628-5p was an independent prognostic factor in BLCA and may be involved in the development of the disease through various pathways, including focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway, and among others. miR-628-5p expression was significantly correlated with immune infiltration in BLCA patients. Compared to normal bladder epithelial cells, BLCA cell lines exhibited a significant upregulation of miR-628-5p. CONCLUSION: It is possible that miR-628-5p could serve as a hopeful therapeutic target and prognostic biomarker for individuals with BLCA.

Integrated microbiome and metabolome analysis reveals novel urinary microenvironmental signatures in interstitial cystitis/bladder pain syndrome patients.

BACKGROUND: The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) has not been elucidated, but urinary microorganisms and metabolites have been shown to be closely associated with the inflammatory response of IC/BPS. Nevertheless, the exact mechanisms related to this response have not been clarified. METHODS: 16S rRNA sequencing and untargeted metabolomics techniques were used to analyse the urinary microbial and metabolite profiles of 30 IC/BPS patients and 30 healthy controls, and correlation analyses were performed to explore the mechanisms by which they might be involved in the inflammatory response of IC/BPS. RESULTS: Twenty-eight differential genera, such as Lactobacillus and Sphingomonas, were identified. A total of 44 differential metabolites such as 1,3,7-trimethyluric acid and theophylline were screened. The abundance of Lactobacillus and Escherichia-Shigella was significantly higher in the urine of female IC/BPS patients and healthy controls compared to males, while Bacteroides and Acinetobacter were lower than in males. The results of the Pearson correlation analysis suggested that differential microorganisms may influence the composition of metabolites. The Lactobacillus genus may be a protective bacterium against IC/BPS, whereas Sphingomonas may be a pathogenic factor. The differential metabolite theophylline, as an anti-inflammatory substance, may downregulate the inflammatory response of IC/BPS. CONCLUSIONS: This study revealed microbial and metabolite profiles in the urine of IC/BPS patients versus healthy controls in both males and females. We also found some microorganisms and metabolites closely related to the inflammatory response of IC/BPS, which provided directions for future aetiological and therapeutic research.

Preliminary Exploration of a New Therapy for Interstitial Cystitis/Bladder Pain Syndrome: Botulinum Toxin A Combined with Sapylin.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease without long-term effective therapy. This study aims to evaluate the efficacy and safety of botulinum toxin A (BoNT/A) plus Sapylin, which might modulate the immune response of the bladder in the treatment of IC/BPS patients. We retrospectively investigated the clinical outcomes among 34 patients who accepted repeated Sapylin instillations after 200 U of BoNT/A submucosally injected into bladder walls (Mix group) and 28 patients who received BoNT/A alone (Control group). Each of the bladder walls (left, right, anterior and posterior) was injected six times with 8 U of BoNT/A per injection. The primary outcome measure was the global response assessment. The results showed that at 6 months post-injection, the response rate in the Mix group was remarkably higher than that in the Control group (58.8% vs. 28.6%, p < 0.05). The mean effective duration of the responders in the Mix group was apparently better than that in the Control group (27.5 (range 0-89) vs. 4.9 (range 0-11) months, p < 0.05). None of the patients experienced serious adverse events. In conclusion, repeated intravesical instillations of Sapylin after BoNT/A injection can produce significantly better clinical outcomes than BoNT/A alone in IC/PBS patients.

Identification of a Novel Glycolysis-Related LncRNA Signature for Predicting Overall Survival in Patients With Bladder Cancer.

BACKGROUND: Both lncRNAs and glycolysis are considered to be key influencing factors in the progression of bladder cancer (BCa). Studies have shown that glycolysis-related lncRNAs are an important factor affecting the overall survival and prognosis of patients with bladder cancer. In this study, a prognostic model of BCa patients was constructed based on glycolysis-related lncRNAs to provide a point of reference for clinical diagnosis and treatment decisions. METHODS: The transcriptome, clinical data, and glycolysis-related pathway gene sets of BCa patients were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Set Enrichment Analysis (GSEA) official website. Next, differentially expressed glycolysis-related lncRNAs were screened out, glycolysis-related lncRNAs with prognostic significance were identified through LASSO regression analysis, and a risk scoring model was constructed through multivariate Cox regression analysis. Then, based on the median of the risk scores, all BCa patients were divided into either a high-risk or low-risk group. Kaplan-Meier (KM) survival analysis and the receiver operating characteristic (ROC) curve were used to evaluate the predictive power of the model. A nomogram prognostic model was then constructed based on clinical indicators and risk scores. A calibration chart, clinical decision curve, and ROC curve analysis were used to evaluate the predictive performance of the model, and the risk score of the prognostic model was verified using the TCGA data set. Finally, Gene Set Enrichment Analysis (GSEA) was performed on glycolysis-related lncRNAs. RESULTS: A total of 59 differentially expressed glycolysis-related lncRNAs were obtained from 411 bladder tumor tissues and 19 pericarcinomatous tissues, and 9 of those glycolysis-related lncRNAs (AC099850.3, AL589843.1, MAFG-DT, AC011503.2, NR2F1-AS1, AC078778.1, ZNF667-AS1, MNX1-AS1, and AC105942.1) were found to have prognostic significance. A signature was then constructed for predicting survival in BCa based on those 9 glycolysis-related lncRNAs. ROC curve analysis and a nomogram verified the accuracy of the signature. CONCLUSION: Through this study, a novel prognostic prediction model for BCa was established based on 9 glycolysis-related lncRNAs that could effectively distinguish high-risk and low-risk BCa patients, and also provide a new point of reference for clinicians to make individualized treatment and review plans for patients with different levels of risk.

The study on the function and cell source of interleukin-6 in interstitial cystitis/bladder painful syndrome rat model.

OBJECTIVE: The elevated expression of interleukin-6 (IL-6) in patients with interstitial cystitis/bladder painful syndrome (IC/BPS) has been demonstrated, but the role of IL-6 in IC/BPS and its source remain to be explored. METHODS: IC/BPS rat model was created in female rats by using long-term intermittent intravesical hyaluronidase (0.5 ml, 4 mg/ml). After modeling, IL-6 stimulation group, and anti-IL-6R group were treated with recombinant rat IL-6 and tocilizumab, respectively. Symptomatic changes were detected by Vonfrey pain score and urodynamics, and hematoxylin-eosin (HE) staining, mast cell staining and Masson staining were used to evaluate the changes of inflammation in the bladder tissue of rats. Cell sources of IL-6 was explored through enzyme linked immunosorbent assay (ELISA) test, reverse transcription polymerase chain reaction (RT-PCR), and western-blot test on the supernatant of coculturing rat bladder epithelial cells and rat macrophages. RESULTS: The Vonfrey pain scores of the model group and IL-6 stimulation group were significantly higher than those of the control group, while the anti-IL-6R group were significantly lower (p < .05). Compared with the blank control group, urodynamic results showed that the urination interval of the model group and IL-6 stimulation group was significantly shortened, and the maximum bladder capacity was significantly reduced (p < .05), and anti-IL-6R treatment significantly alleviated the inflammatory response of bladder tissue. The results of HE, Mast cell staining, and Masson staining showed that the inflammatory response of bladder tissue after anti-IL-6R treatment was significantly reduced. Through cells coculture, the relative expression of IL-6 from model group was found significantly higher than blank control group by RT-PCR, ELISA, and western blot test (p < .05). CONCLUSIONS: IL-6 played an essential role in the development of IC/BPS rat model as a proinflammation cytokine. Further evidence from coculture proved that macrophages are the cell resource of IL-6 in IC/BPS.