Hypoxia-induced cell proliferation, angiogenesis and EMT may be involved in Benign prostatic hyperplasia (BPH) development. Puerarin is an extract of traditional Chinese medicine and has anti-oxidative stress, anti-inflammation and anti-tumor activities. We proposed to explore the therapeutic effect of Puerarin on BPH development and the possible mechanism of its action. HIF-1 signaling pathway molecules in human BPH samples were assayed. Hypoxia-induced cells model of BPH cells (BPH-1) as well as BPH model in vivo were established and the effect of Puerarin on cell proliferation was measured by EDU staining and CCK8. The level of ROS, SOD was detected using commercially available kits. Formation of HIF-1α/HIF-1β Dimers and HIF-1α-HIF-1β/ AKT1/AP-1 expression was measured and located using immunofluorescence, immunohistochemistry and wester blotting. Results indicated that Puerarin could inhibit cell proliferation, angiogenesis and EMT in hypoxia-induced BPH-1 and prostate of BPH mice. Mechanistically, Puerarin significantly downregulates the HIF-1α-HIF-1β/AKT1/AP-1 signaling axis under hypoxic conditions. These therapeutic effects were substantially attenuated by either the HIF-1α agonist deferoxamine (DFO) or genetic overexpression of HIF-1α/β. Notably, HIF-1β knockdown completely abolished HIF-1α-mediated pathological progression in BPH, including cellular proliferation, angiogenesis, and EMT processes. Our results suggested that hypoxia-induced cell proliferation, angiogenesis and EMT may positively correlate with BPH development and Puerarin might suppress BPH through regulated HIF-1α- HIF-1β/AKT1/ AP-1 especially dimer of HIF-1α and HIF-1β.

Personalized vaccines represent a promising approach for cancer treatment by eliciting tumor-specific immune responses. However, their development faces persistent challenges, including the laborious and costly process of neoantigen identification, which substantially delays vaccine production. Moreover, conventional platforms suffer from rapid systemic clearance and inefficient delivery to antigen-presenting cells (APCs), leading to only transient and weak immune activation. Here, we report a STING-agonist-integrated hydrogel system designed for localized delivery of tumor-derived extracellular vesicles (TEVs) to achieve robust and durable antitumor immunity. Upon subcutaneous administration, the in situ formed hydrogel vaccine acts as a depot for antigen-rich TEVs and STING agonists. We demonstrate that this vaccine promotes dendritic cells (DCs) recruitment and establishes an immune-permissive niche through spatiotemporal control over antigen-adjuvant distribution and prolonged APC-antigen engagement. Within this niche, DCs efficiently internalize and process TEVs under STING-mediated activation. These matured DCs subsequently migrate to draining lymph nodes, where they initiate potent and sustained tumor-specific T-cell responses. Our results show that rapidly producible personalized vaccines derived from melanoma TEVs effectively inhibit tumor growth. In a postoperative breast cancer model, patient-tailored TEV vaccines also markedly prevent tumor recurrence and metastasis. This readily customizable platform represents a robust and translatable strategy for personalized cancer immunotherapy.

Postoperative biochemical recurrence and local tumor relapse remain major clinical challenges in managing prostate cancer. Here, we report an injectable and sprayable supramolecular paclitaxel prodrug nanofiber (PF) co-loaded with a potent androgen receptor inhibitor darolutamide (ODM) for long-acting chemo-hormonal therapy against prostate cancer. Upon spraying, ODM/PF rapidly undergoes in situ gelation, forming a uniform hydrogel depot that coats irregular surgical surfaces and enables sustained, controlled drug release in response to the reductive tumor microenvironment. This dual-acting chemo-hormonal strategy produces potent therapeutic synergy by combining paclitaxel-induced mitotic arrest and apoptosis with suppression of androgen receptor signaling. In a murine model of incomplete tumor resection, postoperative spraying of ODM/PF effectively prevented local recurrence, significantly outperforming either agent alone while maintaining a favorable systemic safety profile. Our findings establish ODM/PF as an immediate postoperative adjuvant platform that maximizes local drug concentrations, minimizes systemic exposure, and enables early control of potential residual disease, thereby substantially reducing the likelihood of tumor recurrence.

To predict the pathological subdiagnosis of benign prostatic hyperplasia (BPH‐PS) with the overarching aim of mitigating finasteride overtreatment, we conducted a study integrating clinical, pathological, and radiomic data from BPH patients at our center. The study comprised a retrospective analysis of data and a prospective cohort of BPH patients undergoing pharmacological treatment for six months. Sixty patients (mean age: 68.5 ± 7.1 years) with 360 histopathological whole‐slide images (WSIs) were included in the retrospective cohort. Three gland recognition models were developed and trained to identify glandular structures in WSIs, facilitating the calculation of gland ratios. The optimal model, based on Artificial Neural Network—Multilayer Perceptron (ANN‐MLP), achieved an intraclass correlation coefficient (ICC) of .948 ( p < .001) compared to manual annotation. Radiomic features and habitat analysis were extracted from apparent diffusion coefficient (ADC). Patients were categorized into two groups, BPH with predominantly glandular hyperplasia (BPH‐G) and BPH with predominantly stromal hyperplasia (BPH‐S). An optimal ADC cut‐off value of 1.110×10 −3 mm 2 /s was determined to calculate the Habitat Score. The Habitat Score demonstrated superior predictive performance for BPH‐PS, with an area under the curve (AUC) value of .902. A total of 161 patients (mean age: 64.3 ± 7.0 years) were enrolled in a prospective cohort study. By comparing the changes in prostate volume under MRI before and after medication, it was found that the volume reduction rate of BPH‐G was significantly higher than that of BPH‐S ( p < .001). In conclusion, the ADC value was associated with the gland ratio and could be utilized to predict BPH‐PS, which suggested that the therapeutic efficacy of finasteride could be anticipated by diagnosing BPH‐PS.

Electrical pudendal nerve stimulation (EPNS) has been proposed as a clinic-based option for post-prostatectomy incontinence (PPI), but comparative evidence is limited. We conducted a retrospective cohort study across three medical centers (2018-2022) comparing EPNS (24 sessions over eight weeks) with pelvic-floor muscle training plus transrectal electrical stimulation (PFMT + TES). Primary outcomes were changes from baseline to end of treatment in the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score and 24-hr pad-test urine loss. The Incontinence Impact Questionnaire-7 (IIQ-7) score was assessed as a secondary outcome, and pad-free status was recorded at six months after treatment. In adjusted analyses using propensity-score overlap weighting of 389 men, EPNS was associated with larger improvements than PFMT + TES in ICIQ-UI SF (β - 4.34, 95% CI - 6.65 to - 2.02), 24-hr pad-test urine loss (β - 631.26 g, - 750.81 to - 511.70), and IIQ-7 (β - 2.86, - 5.14 to - 0.58). Unweighted within-group changes were directionally consistent. At the last follow-up, pad-free status was observed in 32.6% of men in the EPNS group versus 7.0% with PFMT + TES. These findings suggest that eight weeks of EPNS can reduce symptom burden and urine loss and yield patient-perceivable quality-of-life gains, although further studies are needed to evaluate the long-term effects.Trial registration: ClinicalTrial.gov (NCT06130306 Registration Date 11/05/2023).

With the rising incidence of benign prostatic hyperplasia (BPH) due to societal aging, accurate and early diagnosis has become increasingly critical. The clinical challenges associated with BPH diagnosis, particularly the lack of specific biomarkers that can differentiate BPH from other causes of lower urinary tract symptoms (LUTS). Here, matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) metabolomic detection platform utilizing urine and serum samples is applied to explore metabolic information and identify potential biomarkers in designed cohort. The nanoparticle-assisted platform demonstrated rapid analysis, minimal sample consumption, and high reproducibility. Employing a two-step grouping screening approach, the identification of urinary metabolic patterns (UMPs) is automated to distinguish healthy individuals from LUTS group, followed by the use of serum metabolic patterns (SMPs) to accurately identify BPH cases within the LUTS cohort, achieving an area under the curve (AUC) of 0.830 (95% CI: 0.802-0.851). Furthermore, eight BPH-sensitive metabolic markers are identified, confirming their uniform distribution across age groups (p > 0.05). This research contributes valuable insights for the early diagnosis and personalized treatment of BPH, enhancing clinical practice and patient care.

Benign prostatic hyperplasia (BPH) is a prevalent condition characterized by nonmalignant proliferation of epithelial and stromal components in the prostate, frequently resulting in lower urinary tract symptoms in aging men. While receptor tyrosine kinase (RTK) signaling has been implicated in both benign proliferative disorders and malignant tumors, its role in BPH remains insufficiently defined. In this study, transcriptomic analyses of bulk and single-cell RNA sequencing data revealed consistent activation of RTK signaling in prostatic epithelial cells from BPH tissues. Pharmacological inhibition of this pathway using sunitinib suppressed epithelial proliferation in BPH cell lines, organoid models, and an androgen-induced BPH mouse model. Through target screening, colony-stimulating factor 1 receptor (CSF1R) was identified as a central mediator within the RTK signaling cascade. Functional experiments demonstrated that CSF1R promotes epithelial proliferation through activation of the PI3K/AKT/mTOR pathway. Mechanistic studies further showed that fibroblasts, which are expanded in BPH tissues, secrete CSF1 and IL34, both ligands of CSF1R, thereby enhancing downstream signaling and stimulating epithelial growth. Neutralization of these ligands or silencing of CSF1R reversed fibroblast-induced epithelial proliferation and clonogenicity. Clinical observations in patients treated with sunitinib confirmed a significant reduction in prostate volume and improvement in BPH-related urinary symptoms. Collectively, these findings establish a fibroblast/CSF1R/RTK signaling axis that contributes to BPH pathogenesis and support the potential of RTK inhibition as a therapeutic strategy.

Benign prostatic hyperplasia (BPH) affects aging men worldwide. Type 2 diabetes mellitus (T2DM) and BPH are aging related progressive diseases. High glucose (HG) promoted epithelial mesenchymal transformation (EMT) glucose-dependently in BPH cells. Arctigenin has multiple therapeutic functions as anti-tumor and anti-inflammatory. The role of Arctigenin in BPH and mechanism remain to be investigated. We proposed to explore the therapeutic effect of Arctigenin on BPH accompanied with T2DM and the molecular mechanism. EMT-related markers such as E-Cadherin and Vimentin along with Ki67 and MBOAT4/(acylated) Ghrelin/GHS-R in samples from BPH patients with euglycemia or T2DM were measured and the role of Arctigenin in cell proliferation, migration and vascular-like networks formation of BPH and vascular endothelial cells in HG culture and db/db mice (T2DM) with BPH were explored. Our results demonstrated that positive EMT-markers, MBOAT4/(acylated) Ghrelin/GHS-R and cell proliferation were found in HG samples of BPH patients, HG-induced cells and db/db mice. Arctigenin suppresses cell proliferation, cell migration and EMT, angiogenesis formation and attenuates BPH in mice under normal or HG condition. Our study suggested that Arctigenin might alleviate BPH companied with type 2 diabetes mellitus by inhibiting Ghrelin-induced EMT and cell proliferation through regulating MBOAT4/(acylated) Ghrelin/GHS-R.

BACKGROUND:Resistance to 5α-reductase inhibitors (5ARIs) represents a significant therapeutic challenge in benign prostatic hyperplasia (BPH) clinical management. While the c-Kit-mediated signaling has been implicated in various pathological conditions, its role in BPH and 5ARI resistance remains undefined. METHODS:Patient-derived organoids (PDOs) were established from BPH specimens and characterized through immunofluorescence, immunohistochemistry, and RT-qPCR analysis. Transcriptomic profiling was performed to identify differentially expressed genes between 5ARI-sensitive and resistant samples. The functional significance of c-Kit-mediated signaling was evaluated using selective inhibitor ISCK03. Further analysis identified cellular targets of c-Kit inhibition, and downstream signaling mechanisms were characterized through pathway analysis. RESULTS:RNA sequencing revealed differentially expressed genes between 5ARI-sensitive and resistant BPH PDOs, with significant enrichment in KIT and related genes. Enhanced c-Kit expression was confirmed in 5ARI-resistant specimens through multiple methodologies. Selective c-Kit inhibition with ISCK03 specifically suppressed 5ARI-resistant PDOs proliferation while sparing sensitive ones. Tests utilizing single-cell-derived organoids identified basal epithelial cells as primary targets of c-Kit inhibition. Mechanistic studies demonstrated that c-Kit maintains 5ARI resistance through the PI3K/AKT and Wnt/β-catenin signaling axis, with c-Kit inhibition significantly downregulating this pathway. CONCLUSIONS:c-Kit-mediated signaling is associated with 5ARI resistance in BPH, potentially through modulation of PI3K/AKT and Wnt/β-catenin pathways. These findings highlight c-Kit as a potential therapeutic target for overcoming 5ARI resistance.

Benign prostatic hyperplasia (BPH), characterized by the non-malignant enlargement of the prostate, exhibits a pronounced association with inflammation resulting from androgen receptor (AR) deficiency. Ferroptosis, a cell death mechanism triggered by iron-dependent lipid peroxidation and closely linked to inflammation, has yet to be fully understood in the context of BPH. Using RNA sequencing, we observed a significant elevation of taurine-upregulated gene 1 (TUG1) long noncoding RNA (lncRNA) in BPH tissues compared to normal prostate tissue. High levels of TUG1 exhibited a discernible correlation with both prostate volume and the extent of inflammatory infiltration in BPH patients. The suppression of TUG1 not only led to a reduction in prostate size but also ameliorated AR-deficiency-induced prostatic hyperplasia. Mechanistically, a decrease in AR in prostate luminal cells prompted macrophage aggregation and the release of IL-1β, subsequently fostering the transcription of TUG1 via MYC. Induced TUG1, through competitive binding with miR-188-3p, facilitated the expression of GPX4, thereby diminishing intracellular ROS levels and impeding ferroptosis in prostate luminal cells. Notably, the ferroptosis inducer JKE-1674 alleviated inflammation-induced prostatic hyperplasia in vivo. Together, these findings suggest that AR deficiency crucially inhibits ferroptosis, promoting BPH via the TUG1/miR-188-3p/GPX4 signaling axis, and making ferroptosis induction a promising therapeutic strategy for BPH patients with AR deficiency.

You have accessJournal of UrologyProstate Cancer: Advanced (Including Drug Therapy) III (MP60)1 May 2024MP60-01 HYDROGEL-ENCAPSULATED EXOSOME VACCINE AS A NOVEL IMMUNOTHERAPEUTIC APPROACH AND ITS ROLE IN ENHANCING IMMUNOTHERAPY FOR PROSTATE CANCER Qi Chen, Zehong Peng, Yang Ge, Xinxing Du, Feihu Wang, Liang Dong, and Wei Xue Qi ChenQi Chen , Zehong PengZehong Peng , Yang GeYang Ge , Xinxing DuXinxing Du , Feihu WangFeihu Wang , Liang DongLiang Dong , and Wei XueWei Xue View All Author Informationhttps://doi.org/10.1097/01.JU.0001008804.84010.ec.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Due to the low immune cell infiltration and the suppressive tumor immune microenvironment (TIME), the efficacy of immunotherapy for prostate cancer is currently quite limited. This study aims to design a cancer vaccine using supramolecular peptide hydrogel encapsulated with ex vivo tumor tissue-derived exosomes (TEXs) and adjuvants to inhibit the growth and recurrence of prostate cancer, as well as improve the effect of immune checkpoint inhibitors. METHODS: Here, we design an amphiphilic self-assembling peptide, KKFE8, capable of forming hydrogels in situ after subcutaneous injection. TEXs are extracted through the lysis and ultracentrifugation of tumor tissue collected from prostate cancer patients. The positively charged self-assembler KKFE8 can adsorb negatively charged TEXs, CDA (a STING agonist), and GM-CSF through electrostatic interactions to create the Gel-Vaccine system. We characterize the controlled release of the vaccine components through the gel by in vitro and in vivo experiments. We then assess the therapeutic effects and related molecular mechanisms of gel vaccines in different mouse models of prostate cancer. RESULTS: Significant tumor regression was observed in mice vaccinated with the Gel-Vaccine across multiple mouse models of prostate cancer. This effect was even more pronounced in mice treated with the combination of aPD-1. We detected a higher number of DC aggregates at the site of gel vaccination, with an increased presence of mature and migratory DCs. Furthermore, we observed an elevated count of mature DCs, along with an increased presence of CD4+ and CD8+ T lymphocytes in the lymph nodes. Additionally, a greater number of CD8+ T cells with cytotoxic capabilities and fewer regulatory T cells infiltrates were detected within the tumor tissue. CONCLUSIONS: TEXs are enriched with tumor antigens, making them potential stimulators of anti-tumor immune responses. After subcutaneous inoculation, the exosome-gel scaffold can be triggered in situ to form an artificial secondary lymphoid organ, continuously recruiting antigen-presenting cells and achieving highly efficient antigen processing. This process can induce immune infiltration in the TIME. When combined with aPD-1, it triggers a potent and long-lasting tumor-specific immune response, effectively inhibiting prostate cancer growth and recurrence. This innovative approach suggests a new strategy for treating prostate cancer: customized gel vaccines from individual tumor-derived exosomes, offering personalized therapies. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e999 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Qi Chen More articles by this author Zehong Peng More articles by this author Yang Ge More articles by this author Xinxing Du More articles by this author Feihu Wang More articles by this author Liang Dong More articles by this author Wei Xue More articles by this author Expand All Advertisement PDF downloadLoading ...

Background: Dietary nutrient intake contributes to urination; however, the association between dietary nutrient intake, especially that of fat, and urinary incontinence (UI) is not well understood. The most common types of UI include stress UI (SUI) and urgency UI (UUI). Objective: To investigate the potential effect(s) of dietary fat intake on UI and explore its mechanism of action in relation to body mass index (BMI). Methods: A cross-sectional survey of data from 15,121 individuals (20–85 years of age) from the National Health and Nutrition Examination Survey (2001–2008), a random population-based sample, was performed. Data regarding dietary nutrient intake were collected through 24 h dietary recall interviews. UI and covariate data were collected through in-person interviews. UI was assessed according to the American Urological Association Symptom Index. The odds ratio (OR) for SUI and UUI were calculated using multivariate logistic regression analysis. The mediation effect was estimated using observational mediation analysis. Results: Higher total fat intake was positively associated with increased odds for developing UI (OR 1.44 [95% confidence interval (CI) 1.08–1.93]). Females who consumed more saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were more likely to develop SUI. BMI partially explained the association between total fat, SFA, MUFA, and PUFA and SUI; the proportions of the mediation effect of BMI were 14.7%, 13.0%, 18.7%, and 16.3%, respectively. Conclusions: Results of this study emphasize the key role of dietary fat intake in the prevalence of UI. Higher fat intake was positively associated with UI and BMI partially mediated the effect of fat intake on SUI.

You have accessJournal of UrologyProstate Cancer: Detection & Screening IV (MP49)1 May 2024MP49-07 DEFINING HIGH GLEASON SCORE PROSTATE CANCER BY PROSTATE FLUID METABOLIC FINGERPRINT BASED MULTI-MODAL DIAGNOSIS Zehong Peng, Yuning Wang, Xinrui Wu, Xingxing Du, Cong Hu, Qi Chen, Yang Ge, Yanhao Dong, Kun Qian, Liang Dong, and Wei Xue Zehong PengZehong Peng , Yuning WangYuning Wang , Xinrui WuXinrui Wu , Xingxing DuXingxing Du , Cong HuCong Hu , Qi ChenQi Chen , Yang GeYang Ge , Yanhao DongYanhao Dong , Kun QianKun Qian , Liang DongLiang Dong , and Wei XueWei Xue View All Author Informationhttps://doi.org/10.1097/01.JU.0001008696.31772.28.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer with high Gleason score remains a key challenge in healthcare due to its rapid progression and poor prognosis. This study aims to make rapid and early diagnosis of high Gleason score prostate cancer by using the metabolic fingerprint of prostate fluid. METHODS: we enrolled 108 patients and then classified the patients into two groups: PCa (n=45) and BPH (n=63).We then developed a ferric nanoparticle-assisted laser desorption/ionization mass spectrometry (FeNPALDI-MS) detection platform to identify the metabolomics in prostate fluid. By employing various machine learning algorithms, we combined the metabolomics with prostate-specific antigen (PSA) to establish a multi-modal recognition approach for prostate cancer with high Gleason score(n=11). Additionally, we selected key metabolites from the metabolomics and combined them with PSA to enhance the efficiency of diagnosis. Simultaneously, we discovered several metabolic pathways associated with the progression of prostate cancer. RESULTS: We successfully constructed the metabolic fingerprint of prostate fluid and developed a multi-modal identification system. This system can accurately diagnose prostate cancer with high Gleason score , with an area under the curve (AUC) of 0.83 in the training group and 0.87 in the test group. Additionally, from the prostate fluid metabolic fingerprint (PSF-MF), we identified six metabolites as biomarkers and their associated metabolic pathways. The panel composed of these metabolites also demonstrated good clinical predictive ability for prostate cancer with high Gleason score, with an AUC of 0.89 in the training group and 0.87 in the test group. CONCLUSIONS: In this study, we were able to achieve a non-invasive and rapid diagnosis of prostate cancer with high Gleason score by developing a multi-modal recognition using the metabolic fingerprint of prostate fluid. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e785 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Zehong Peng More articles by this author Yuning Wang More articles by this author Xinrui Wu More articles by this author Xingxing Du More articles by this author Cong Hu More articles by this author Qi Chen More articles by this author Yang Ge More articles by this author Yanhao Dong More articles by this author Kun Qian More articles by this author Liang Dong More articles by this author Wei Xue More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD35)1 May 2024PD35-05 M2-LIKE MACROPHAGE PROMOTES PROSTATE CANCER METASTASIS BY HORIZONTAL TRANSFER OF TXNDC5 MRNA VIA EXTRACELLULAR VESICLES Cong Hu, Tianyang Wu, Xinxing Du, Zehong Peng, Qi Chen, Yinjie Zhu, Baijun Dong, Jiahua Pan, Liang Dong, and Wei Xue Cong HuCong Hu , Tianyang WuTianyang Wu , Xinxing DuXinxing Du , Zehong PengZehong Peng , Qi ChenQi Chen , Yinjie ZhuYinjie Zhu , Baijun DongBaijun Dong , Jiahua PanJiahua Pan , Liang DongLiang Dong , and Wei XueWei Xue View All Author Informationhttps://doi.org/10.1097/01.JU.0001009396.21455.74.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The incidence of prostate cancer (PCa) is on the rise worldwide, and metastatic PCa remains incurable. Tumor-associated macrophages in PCa tend to be M2 phenotype, which promote cancer metastasis, but the mechanism is not clear. Whether extracellular vesicles (EVs), as a means of intercellular communication, can mediate the above process needs to be further elucidated. METHODS: We explored the infiltration of M2-like macrophage in metastatic and non-metastatic PCa primary foci by single-cell sequencing, which was verified by immunohistochemistry and immunofluorescence in patient samples. EVs were separated from M2-like macrophages polarized from THP-1cell line, with differential ultracentrifugation. M2-derived EVs were co-incubated with PCa cell lines Du145 and PC3, and changes in invasion and migration ability were observed by Transwell and wound-healing assay. Differential genes that were co-altered were identified by RNA sequencing of the EVs-treated cells. Overexpression and knockdown of the differential gene were carried out to observe if they could change the metastatic ability of PCa cell. The above cell lines were injected through the tail vein of mice to observe systemic metastasis. GFP-tagged differential gene in EVs was applied to see if they can be delivered directly to target cells via EVs and translated into functional proteins to promote PCa metastasis. RESULTS: In our own patient cohort, single-cell sequencing demonstrated more M2-like macrophages infiltration of primary foci in metastatic PCa compared to non-metastatic PCa. Immunohistochemistry and immunofluorescence confirmed these results. Wound-healing assay and Transwell demonstrated enhanced migration and invasion of M2 EVs-treated DU145 and PC3. The RNA sequencing data of treated Du145 and PC3 revealed a common differential gene, TXNDC5. Overexpression and knocked-down of TXNDC5 in DU145 and PC3 verified its regulation of migration and invasion in vivo and in vitro. The presence of TXNDC5 gene in M2-derived EVs was further verified by qRT-PCR, and the fusion gene fused with GFP was found to be successfully translated in target cells with confocal microscopy and flow cytometry. CONCLUSIONS: Our study successfully demonstrated that TXNDC5 mRNA in M2-derived EVs is able to regulate PCa migration and invasion through horizontal delivery. Source of Funding: The National Natural Science Foundation of China (82103485) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e726 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Cong Hu More articles by this author Tianyang Wu More articles by this author Xinxing Du More articles by this author Zehong Peng More articles by this author Qi Chen More articles by this author Yinjie Zhu More articles by this author Baijun Dong More articles by this author Jiahua Pan More articles by this author Liang Dong More articles by this author Wei Xue More articles by this author Expand All Advertisement PDF downloadLoading ...

Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because of a lack of a durable response, especially in advanced disease states. Extracellular vesicles (EVs) are lipid-bilayer encircled nanoscale vesicles that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating the transfer of information. The past decade has witnessed a wide range of EV applications in both diagnostics and therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers in various clinical scenarios to guide treatment; EVs can facilitate the grading and staging of patients for appropriate treatment selection. Second, EVs play a pivotal role in pathophysiological processes via intercellular communication. Targeting key molecules involved in EV-mediated tumor progression (e.g., proliferation, angiogenesis, metastasis, immune escape, and drug resistance) is a potential approach for curbing PCa. Third, EVs are promising drug carriers. Naïve EVs from various sources and engineered EV-based drug delivery systems have paved the way for the development of new treatment modalities. This review discusses the recent advancements in the application of EV therapies and highlights EV-based functional materials as novel interventions for PCa.

Abstract. Background. The goal of this study was to determine the safety and efficacy of endoscopic combined intrarenal surgery (ECIRS) performed in the prone split-leg position for the treatment of complex renal stones. Materials and methods. A mature ECIRS protocol was designed. Retrospective analysis was conducted of medical records between January 2020 and December 2021 of patients with complex renal stones at one center who underwent ECIRS by 2 skilled surgeons using retrograde flexible ureteroscopy and mini-percutaneous nephrolithotomy in the prone split-leg position. Results. A total of 44 patients were included in this study. Mean stone size was 26.1 ± 12.7 mm, and the number of calyces involved was 4.36 ± 2.09. Mean operative time was 71.1 ± 21.8 minutes. Postoperative decline in hemoglobin was 15.8 ± 9.8 g/L. Seventy-five percent of patients achieved stone-free status. The mean number of residual stones was 2.8 ± 2.3, and the mean residual stone size was 10.30 ± 4.76 mm. Six patients (13.6%) developed postoperative complications, including 4 with fever during the first 2 days postoperatively and 2 patients with transient postoperative pain. No patients developed severe complications. Conclusions. Endoscopic combined intrarenal surgery in the prone split-leg position can be performed safely by experienced surgeons using retrograde flexible ureteroscopy in conjunction with mini-percutaneous nephrolithotomy as a successful technique for the treatment of complex renal stones.

Introduction: The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) and to provide a basis for clinical prevention of recurrence of NMIBC. Methods: From January 2012 to December 2020, 592 patients with NMIBC who underwent TURBT attending the Second Affiliated Hospital of Xi’an Jiaotong University were retrospectively included in this study. Patients were divided into relapse and relapse-free groups according to whether relapse occurred within 2 years. Ultimately, 72 patients were included in the relapse group and 350 patients were included in the relapse-free group. Observation indicators included age, sex, smoking, underlying disease (hypertension, diabetes, coronary heart disease), two or more lesions, tumor size, hematuria, pathology grading (low, medium, high), staging (Ta, T1), muscular invasion in initial pathology, tumor base (sessile, pedunculated), use of intravesical drug (pirarubicin, bacillus Calmette-Guerin [BCG], mitomycin, hydroxycamptothecin, gemcitabine). Results: In this study, the 2-year recurrence rate of NMIBC patients after TURBT was 17.06%. There were significant differences in comparison of pirarubicin, BCG, and mitomycin treatment between the two groups (p < 0.05). To avoid missing risk factors for recurrence, factors with p < 0.1 were analyzed. The results of univariate logistic regression analysis showed that NMIBC patients with BCG treatment (OR = 5.088, 95% CI = 1.444–17.73, p = 0.012), high pathology grading (OR = 0.415, 95% CI = 0.197–0.880, p = 0.023), T1 stage (OR = 2.097, 95% CI = 0.996–4.618, p = 0.059), mitomycin treatment (OR = 5.029, 95% CI = 1.149–21.77, p = 0.031), and pirarubicin treatment (OR = 1.794, 95% CI = 1.079–3.030, p = 0.024) had significantly higher risk of recurrence within 2 years after TURBT. The results of multivariate logistic regression analysis showed that NMIBC patients with high pathology grading (OR = 0.4030, 95% CI = 0.1702–0.8426, p = 0.0241), pirarubicin treatment (OR = 1.961, 95% CI = 1.159–3.348, p = 0.0125), and BCG treatment (OR = 6.201, 95% CI = 1.275–29.73, p = 0.0190) had significantly higher risk of recurrence within 2 years after TURBT. Conclusion: Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of mitomycin and BCG on recurrence rates.

Benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PC) have similar symptoms, making it challenging to differentially diagnose these two conditions. The study used Weighted Gene Co-Expression Network Analysis, as well as two machine learning strategies to identify BPH-specific biomarkers based on an integrated transcriptome data from 922 samples. Eight prognostic genes (ALCAM, COL6A2, CRISP2, FOXF2, IGF1, PTN, SCN7A, and UAP1) were identified to be BPH-specific biomarkers with high accuracy and specificity. Moreover, we constructed a seven-gene diagnostic classifier to distinguish BPH from PC. The infiltrations of plasmacytoid dendritic cells and neutrophil cells showed distinct differences between BPH and non-BPH groups. Additionally, ursolic acid can reverse transcriptional features associated with the occurrence and progression of BPH. Both in vivo and in vitro experiments have confirmed that it induces apoptosis of BPH cells and inhibits cell proliferation by promoting cell cycle S-phase arrest. The diagnostic biomarkers, microenvironment characteristics, and therapeutic effect of ursolic acid explored in this study offer new diagnostic and therapeutic strategies for BPH.