Cofilin 1 (CFL1) is a cytoskeletal protein and overexpression of the protein has been associated with aggressiveness in certain types of malignancies. The aim of the present study was to investigate the clinical implications of CFL1 expression in prostate cancer (PCa). Immunohistochemical analysis was performed using formalin‑fixed paraffin‑embedded tissue sections obtained from 111 patients with PCa and 47 patients with benign prostatic hyperplasia (BPH). In total, 78 (70.3%) out of 111 PCa tissues were found to express the CFL1 protein, while no expression was detected in BPH tissues. In addition, CFL1 was also observed to be significantly associated with the Gleason score (GS; <7 vs. ≥7; P<0.0001) and presence of lymph node metastasis (presence vs. absence; P<0.0001). However, there was no association between the expression of CFL1 and other clinicopathological variables, such as age (<69 years vs. ≥69 years; P=0.54), pre‑operative prostate specific antigen level (<20 ng/ml vs. ≥20 ng/ml; P=0.45) and pathological stage (T2 vs. ≥T3a; P=0.055). In addition, 35 tissues (31.5%) were observed to possess a CFL1‑positive mesenchyme. CFL1 expression was revealed to be an independent predictive factor for a high GS. The status of CFL1 expression in the mesenchyme also found to individually predict extraprostatic extension in PCa patients, based on multivariate analysis. The results of the present study indicated that CFL1 may specifically predict the development of PCa, and that the expression of CFL1 in the mesenchyme may be closely associated with the development of lymph node metastasis.

OBJECTIVES: This study was aimed to explore Cdc20 expression and its correlation with clinicopathological characteristics and biochemical recurrence (BCR) after laparoscopic radical prostatectomy (LRP) in clinically localized prostate cancer (PCa). T

The role of cell division cycle 20 (CDC20) was investigated in chemoresistance to decetaxel and the underlying mechanisms in metastatic castration-resistant prostate cancer (mCRPC). MTT assays were performed to determine effects of siRNA-mediated CDC20 knockdown on cell proliferation and anticancer activity of docetaxel. Western blot analyses were conducted to detect changes of Akt and Wnt signaling. Furthermore, in vivo growth of PCa was examined in nude mice treated with siCDC20 or docetaxel alone or in combination. CDC20 was overexpressed in mCRPC cells. Knockdown of CDC20 suppressed cell proliferation and enhanced anticancer effect of docetaxel with IC50 reducing from 0.358 to 0.188 µg/ml in PC3 cells and 0.307 to 0.162 µg/ml in DU145 cells (P<0.01). While no change of Akt signaling was observed, inhibition of Wnt/β-catenin signaling was detected upon CDC20 silencing. Xenograft tumor growth was significantly reduced in nude mice by CDC20 inhibition. The additional treatment of siCDC20 achieved better anticancer effects than that of docetaxel alone. Silencing of CDC20 may be a new strategy to improve chemosensitization to docetaxel in mCRPC.

The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.

The aim of the present study was to investigate the overexpression and significance of ribosomal L1 domain containing 1 (RSL1D1) in prostate cancer (PCA). The present study performed immunohistochemical analysis on the tissues of 138 patients with pathologically confirmed PCA. The patients were followed up for a median of 87 months. In addition, 50 patients with benign prostatic hyperplasia (BPH) were enrolled in the present study as a control group. Of the 138 PCA tissue samples, 124 (89.9%) expressed RSL1D1, while 4 out of the 50 (8.0%) BPH tissues expressed RSL1D1. The present study defined a high RSL1D1 expression level as the relative gene expression that was equal to or higher than the median, and low expression as the gene expression lower than the median. The pathological stage of patients with PCA (≥pT3a vs. pT2c) and the Gleason scores of patients (≥7 vs. <7) were associated with RSL1D1 expression (χ2=4.809 and 14.703; P=0.028 and P<0.0001, respectively) and a high expression of RSL1D1 (χ2=10.294 and 17.520; P=0.001 and P<0.0001, respectively). Kaplan‑Meier curve analysis demonstrated that the biochemical recurrence (BCR)‑free survival rate of the patients was increased in patients without RSL1D1 expression (P=0.0046), in those with low RSL1D1 expression (P<0.0001) and in those without RSL1D1 expression in the mesenchyme (P=0.006) compared with those patients with no expression, low expression and no mesenchymal expression, respectively. A high expression level of RSL1D1 was demonstrated to be an independent prognostic factor of BCR in patients with PCA using Cox regression analysis. Overall, the present study demonstrated that RSL1D1 expression was associated with PCA, and that it may aid in the improvement of diagnosis, prognosis and risk stratification of patients with PCA.