Polystyrene nanoplastics exposure causes erectile dysfunction in rats.

Polystyrene nanoplastics (PS-NPs), emerging and increasingly pervasive environmental contaminants, have the potential to cause persistent harm to organisms. Although previous reports have documented local accumulation and adverse effects in a variety of major organs after PS-NPs exposure, the impact of PS-NPs exposure on erectile function remains unexplored. Herein, we established a rat model of oral exposure to 100 nm PS-NPs for 28 days. To determine the best dose range of PS-NPs, we designed both low-dose and high-dose PS-NPs groups, which correspond to the minimum and maximum human intake doses, respectively. The findings indicated that PS-NPs could accumulate within the corpus cavernosum and high dose but not low dose of PS-NPs triggered erectile dysfunction. Moreover, the toxicological effects of PS-NPs on erectile function include fibrosis in the corpus cavernous, endothelial dysfunction, reduction in testosterone levels, elevated oxidative stress and apoptosis. Overall, this study revealed that PS-NPs exposure can cause erectile dysfunction via multiple ways, which provided new insights into the toxicity of PS-NPs.

Unraveling CCL20's role by regulating Th17 cell chemotaxis in experimental autoimmune prostatitis.

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well-being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL-17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF-κB/MAPK/PI3K pathway. The interplay between IL-17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges.

PEGylated Manganese-Zinc Ferrite Nanocrystals Combined with Intratumoral Implantation of Micromagnets Enabled Synergetic Prostate Cancer Therapy via Ferroptotic and Immunogenic Cell Death.

Therapeutic efficacy for prostate cancer is highly restricted by insufficient drug accumulation and the resistance to apoptosis and immunogenic cell death (ICD). Although enhanced permeability and retention (EPR) effect of magnetic nanomaterials could benefit from external magnetic field, it falls off rapidly with increased distance from magnet surface. Considering the deep location of prostate in pelvis, the improvement of EPR effect by external magnetic field is limited. In addition, apoptosis resistance and cGAS-STING pathway inhibition-related immunotherapy resistance are major obstacles to conventional therapy. Herein, the magnetic PEGylated manganese-zinc ferrite nanocrystals (PMZFNs) are designed. Instead of providing external magnet, micromagnets into tumor tissues are intratumorally implanted to actively attract and retain intravenously-injected PMZFNs. As a result, PMZFNs accumulate in prostate cancer with high efficacy, depending on the established internal magnetic field, which subsequently elicit potent ferroptosis and the activation of cGAS-STING pathway. Ferroptosis not only directly suppresses prostate cancer but also triggers burst release of cancer-associated antigens and consequently initiates ICD against prostate cancer, where activated cGAS-STING pathway further amplifies the efficacy of ICD by generating interferon-ß. Collectively, the intratumorally implanted micromagnets confer a durable EPR effect of PMZFNs, which eventually achieve the synergetic tumoricidal efficacy with negligible systemic toxicity.

Signature for Prostate Cancer Based on Autophagy-Related Genes and a Nomogram for Quantitative Risk Stratification.

Background: Prostate cancer (PCa) ranks as the most common malignancy and the second leading cause of cancer-related death among males worldwide. The essential role of autophagy in the progression of PCa and treatment resistance has been preliminarily revealed. However, comprehensive molecular elucidations of the correlation between PCa and autophagy are rare. Method: We obtained transcription information and corresponding clinicopathological profiles of PCa patients from TCGA, MSKCC, and GEO datasets. LAASO analysis was employed to select gene signatures and estimate the autophagy score for each patient. Correlations between the signature and prognosis of PCa were investigated by K-M and multivariate Cox regression analyses. A nomogram was established on the basis of the above results. Further validations relied on ROC, calibration analysis, decision curve analysis, and external cohorts. Variable activated signaling pathways were revealed using GSVA algorithms, and the genetic alteration landscape was elucidated via the oncodrive module from the "maftools" R package. In addition, we also examined the therapeutic role of the signature based on phenotype data from GDSC 2016. Result: Six autophagy-related genes were eventually selected to establish the signature, including ULK1, CAPN10, FKBP5, UBE2T, NLRC4, and BNIP3L. We used these genes and corresponding coefficients to calculate an autophagy score (AutS) for each patient in this study. A high AutS group and a low AutS group were divided on the mean AutS of the patients. Longer overall survival, higher Gleason score and PSA, and better response to ADT were observed in patients with high AutS. Meanwhile, we found that high AutS PCa was related to more proliferation-associated signaling activation and higher genetic mutation frequencies, manifesting a poor prognosis. A nomogram was constructed based on GS, T stage, PSA, and AutS as covariates. Its discriminative efficacy and clinical value were validated using robust statistical methods. Finally, we tested its prognostic value through two external cohorts and six published signatures. Conclusion: The autophagy-related gene signature is a highly discriminative model for risk stratification and drug therapy in PCa, and a nomogram incorporating AutS might be a promising tool for precision medicine.