Binbin Gong

Purpose: This study investigated how alcohol exacerbated chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and assessed gut microbiota-targeted therapeutic strategies. Methods: An alcohol‑treated experimental autoimmune prostatitis (EAP) mouse model was established to evaluate the exacerbating effect of alcohol on CP/CPPS. The involvement of gut microbiota was assessed by antibiotic depletion and fecal microbiota transplantation (FMT). 16S rRNA sequencing was applied to profile microbial alterations, particularly the abundance of Lactobacillus johnsonii (L. john). Oral administration of live L. john or intravenous injection of Lactobacillus johnsonii-derived extracellular vesicles (LjEVs) was tested as therapeutic interventions. Mechanistic studies were conducted in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophages using transcriptomics, qRT-PCR, Western blot, and flow cytometry. Results: Alcohol consumption aggravated pelvic tactile hypersensitivity and prostatic inflammation, increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and promoted M1 macrophage polarization in EAP mice. Fecal microbiota transplantation from alcohol-fed EAP mice reproduced the aggravated phenotype, confirming that gut microbiota mediates this effect. Alcohol specifically reduced the relative abundance of L. john. Oral L. john or intravenous LjEVs alleviated tactile hypersensitivity and inflammation, and inhibited M1 macrophage polarization in alcohol-fed EAP mice. In vitro, LjEVs were internalized by macrophages, suppressed LPS-induced M1 macrophage polarization and pro-inflammatory gene expression, and inhibited TNF-α/NF-κB signaling. Exogenous TNF-α reversed the inhibitory effects of LjEVs on M1 macrophage polarization. Conclusion: Alcohol exacerbated EAP by reducing L. john, which in turn promoted prostatic M1 macrophage polarization via the TNF-α/NF-κB pathway. Supplementation with L. john or LjEVs ameliorated the disease by suppressing this pathway, offering a microbiota-targeted therapy for alcohol-aggravated CP/CPPS.

Metastasis remains a significant challenge in the management of clear cell renal cell carcinoma (ccRCC), and a continued focus on its underlying mechanisms is crucial for improving patient outcomes and optimizing clinical therapies. The ovarian-tumor related protease (OTU) is involved in regulating critical cell signaling pathways, but the functions of most OTUs have yet to be explored. In this study, an unbiased RNAi screening revealed that ovarian tumor domain-containing 2 (YOD1) knockdown significantly promoted cell metastasis. YOD1 downregulation promoted ccRCC growth and metastasis both in vitro and in vivo. Notably, YOD1 knockdown stimulated the growth of organoids derived from ccRCC patients. Further investigation revealed that YOD1 directly interacted with and stabilized Zinc finger protein 24 (ZNF24) expression by deubiquitination in a manner dependent on its catalytic activity. YOD1 inhibition attenuated ZNF24 transcriptional repression of vascular endothelial growth factor A (VEGFA), thereby promoting VEGFA gene expression. Furthermore, ZNF24 was identified as a key mediator of YOD1 function. The expression of YOD1 and ZNF24 was significantly downregulated in tumor tissues, with a strong correlation between them. Importantly, reduced YOD1 and ZNF24 levels were strongly associated with poor clinical outcomes in ccRCC patients. Our results reveal the mechanism by which YOD1 regulates VEGFA transcription and suppresses tumorigenesis by deubiquitinating ZNF24, providing a therapeutic target in ccRCC.

Prostate cancer (PRAD) is recognized as having a significant effect on systemic illnesses. This study examined possible immune cells, metabolic pathways, and genes that may explain the interaction between PRAD and hip pain. We used information retrieved from the Cancer Genome Atlas and the Gene Expression Omnibus databases. To find common genes, we utilized differential expression analysis and weighted gene co-expression network analysis. The genes that were shared were subjected to pathway enrichment studies using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Additionally, hub genes were analyzed using LASSO regression, and a receiver operating characteristic curve was generated based on the screening outcomes. The genes for the nodes were chosen in a protein–protein interaction network that was built. Single-sample gene-set enrichment analysis was performed to identify the differentially expressed genes. Immunohistochemistry staining confirmed hub gene expression, and single-sample gene-set enrichment analysis assessed immune cell infiltration. We concluded by comparing MAX dimerization protein 3 (MXD3) and MAX interactor 1 (MXI1) expression in tumor tissues using Uniform Manifold Approximation and Projection and violin plots in the Tumor lmmune Single-cell Hub database. After analyzing the intersection of the differentially expressed genes and weighted gene co-expression network analysis-significant module genes, we determined that MXD3 was the best shared diagnostic biomarker for PRAD and hip pain. One potential predictor of PRAD development was the MXI1 node gene, which was found in the protein–protein interaction network. The analyses revealed that MXD3 had a relatively positive correlation with neutrophil and T-helper cell infiltration levels, whereas MXI1 had a negative correlation with mast and Tgd cell levels. Tumors had lower levels of MXI1 expression and higher levels of MXD3 expression compared to normal tissues. Endothelial cells, induced pluripotent stem cells, and smooth muscle cells were all found to express MXI1. This is the first study to investigate the close genetic link between hip pain and PRAD using bioinformatics technologies. The 2 most significant genes involved in crosstalk between PRAD and hip pain were MXD3 and MXI1. The immunological responses triggered by T cells, mast cells, and neutrophils may be crucial in the relationship between PRAD and hip pain.

Pursuing knowledge about circular RNA (circRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression profiles and their competing endogenous RNA (ceRNA) networks in hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) was the focus of this research. Expression patterns of circRNAs, lncRNAs, miRNAs, and mRNAs were searched for in relation to HBV-related HCC using whole-transcriptome sequencing. The expression levels of chosen circRNA, lncRNA, miRNA, and mRNA were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential connections and roles of ceRNA were deduced via bioinformatics research. The sum of 284 circRNAs, 2,927 lncRNAs, 693 miRNAs, and 5566 mRNAs were discovered to be expressed at considerably different levels in HBV-related HCC tissue and adjacent normal tissue. And the most significantly up- and down-regulated circRNAs, lncRNAs, miRNAs, and mRNAs were verified in HBV-related HCC by qRT-PCR. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of HBV-related HCC were established, and the ceRNA regulatory networks revealed the gene expression mechanisms controlled by ncRNAs. Collectively, we revealed the contribution of various circRNA, lncRNA, miRNA, and mRNA expression profiles and identified their ceRNA regulatory networks in HBV-related HCC, providing a theoretical basis for further exploration.