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Journal of the Science of Food and... Dec 2023Rapeseed bee pollen has been recognized as a critical treatment for chronic non-bacterial prostatitis (CNP) and it also can modulate gut microbiota and improve gut...
BACKGROUND
Rapeseed bee pollen has been recognized as a critical treatment for chronic non-bacterial prostatitis (CNP) and it also can modulate gut microbiota and improve gut health. This study aimed to explore the anti-prostatitis effects of rapeseed bee pollen with or without wall-disruption, and to investigate the connection between this treatment and gut microbiota.
RESULTS
The results reveal that rapeseed bee pollen can effectively alleviate chronic non-bacteria prostatitis by selectively regulating gut microbiota, with higher doses and wall-disrupted pollen showing greater efficacy. Treatment with a high dose of wall-disrupted rapeseed bee pollen (WDH, 1.26 g kg body weight) reduced prostate wet weight and prostate index by approximately 32% and 36%, respectively, nearly the levels observed in the control group. Wall-disrupted rapeseed bee pollen treatment also reduced significantly (p < 0.05) the expression of proinflammatory cytokines (IL-6, IL-8, IL-1β, and TNF-α), as confirmed by immunofluorescence with laser scanning confocal microscope. Our results show that rapeseed bee pollen can inhibit pathogenic bacteria and enhance probiotics, particularly in the Firmicutes-to-Bacteroidetes (F/B) ratio and the abundance of Prevotella (genus).
CONCLUSION
This is the first study to investigate the alleviation of CNP with rapeseed bee pollen through gut microbiota. These results seem to provide better understanding for the development of rapeseed bee pollen as a complementary medicine. © 2023 Society of Chemical Industry.
Topics: Humans; Male; Bees; Animals; Prostatitis; Gastrointestinal Microbiome; Brassica napus; Pollen; Bacteria; Brassica rapa
PubMed: 37486857
DOI: 10.1002/jsfa.12878 -
Cancer Research Communications Aug 2023Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for the treatment of advanced prostate cancer, a...
UNLABELLED
Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for the treatment of advanced prostate cancer, a significant subset of patients will progress with resistant disease including AR-negative tumors that display neuroendocrine features [neuroendocrine prostate cancer (NEPC)]. On the basis of RNA sequencing (RNA-seq) data from a clinical cohort of tissue from benign prostate, locally advanced prostate cancer, metastatic castration-resistant prostate cancer and NEPC, we developed a multi-step bioinformatics pipeline to identify NEPC-specific, overexpressed gene transcripts that encode cell surface proteins. This included the identification of known NEPC surface protein CEACAM5 as well as other potentially targetable proteins (e.g., HMMR and CESLR3). We further showed that cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) knockdown results in reduced NEPC tumor cell proliferation and migration . We provide data including laser capture microdissection followed by RNA-seq data supporting a causal role of CELSR3 in the development and/or maintenance of the phenotype associated with NEPC. Finally, we provide initial data that suggests CELSR3 is a target for T-cell redirection therapeutics. Further work is now needed to fully evaluate the utility of targeting CELSR3 with T-cell redirection or other similar therapeutics as a potential new strategy for patients with NEPC.
SIGNIFICANCE
The development of effective treatment for patients with NEPC remains an unmet clinical need. We have identified specific surface proteins, including CELSR3, that may serve as novel biomarkers or therapeutic targets for NEPC.
Topics: Humans; Male; Prostatic Neoplasms; Neuroendocrine Tumors; Prostate; Cell Membrane; Cadherins
PubMed: 37546702
DOI: 10.1158/2767-9764.CRC-22-0491 -
Frontiers in Immunology 2023Prostatitis is an inflammatory disease of the prostate gland, which affects 2-16% of men worldwide and thought to be a cause for prostate cancer (PCa) development....
BACKGROUND
Prostatitis is an inflammatory disease of the prostate gland, which affects 2-16% of men worldwide and thought to be a cause for prostate cancer (PCa) development. Carcinoembryogenic antigen-related cell adhesion molecules (CEACAMs) are deregulated in inflammation and in PCa. The role of CEACAMs in prostate inflammation and their possible contribution to the malignant transformation of prostate epithelial cells is still elusive. In this study, we investigated the expression of CEACAMs in an prostatitis model and their potential role in malignant transformation of prostate epithelial cells.
METHODS
Normal prostate epithelial RWPE-1 cells were treated with pro-inflammatory cytokines to achieve an inflammatory state of the cells. The expression of CEACAMs and their related isoforms were analyzed. Additionally, the expression levels of selected CEACAMs were correlated with the expression of malignancy markers and the migratory properties of the cells.
RESULTS
This study demonstrates that the pro-inflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferon-gamma (IFNγ), induce synergistically an up-regulation of CEACAM1 expression in RWPE-1 cells, specifically favoring the CEACAM1-L isoform. Furthermore, overexpressed CEACAM1-L is associated with the deregulated expression of JAK/STAT, NFκB, and epithelial-mesenchymal transition (EMT) genes, as well as an increased cell migration.
CONCLUSION
We postulate that CEACAM1 isoform CEACAM1-4L may synergistically contribute to inflammation-induced oncogenesis in the prostate.
Topics: Male; Humans; Prostatitis; Prostate; Inflammation; Tumor Necrosis Factor-alpha; Transcription Factors; Cell Transformation, Neoplastic; Cytokines
PubMed: 37691945
DOI: 10.3389/fimmu.2023.1236343 -
International Journal of Molecular... Jul 2023Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed... (Review)
Review
Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.
Topics: Humans; Male; Biopsy; Oncogene Proteins, Fusion; Prostate; Prostatic Neoplasms; Serine Endopeptidases; Transcriptional Regulator ERG; p300-CBP Transcription Factors
PubMed: 37511059
DOI: 10.3390/ijms241411299 -
Pain Research & Management 2023Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of the male urological system while the etiology and treatment of CP/CPPS... (Review)
Review
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of the male urological system while the etiology and treatment of CP/CPPS remain a thorny issue. Cumulative research suggested a potentially important role of glial cells in CP/CPPS. This narrative review retrospected literature and grasped the research process about glial cells and CP/CPPS. Three types of glial cells showed a crucial connection with general pain and psychosocial symptoms. Microglia might also be involved in lower urinary tract symptoms. Only microglia and astrocytes have been studied in the animal model of CP/CPPS. Activated microglia and reactive astrocytes were found to be involved in both pain and psychosocial symptoms of CP/CPPS. The possible mechanism might be to mediate the production of some inflammatory mediators and their interaction with neurons. Glial cells provide a new insight to understand the cause of complex symptoms of CP/CPPS and might become a novel target to develop new treatment options. However, the activation and action mechanism of glial cells in CP/CPPS needs to be further explored.
Topics: Humans; Animals; Male; Chronic Disease; Prostatitis; Pelvic Pain; Central Nervous System; Neuroglia; Chronic Pain
PubMed: 38023826
DOI: 10.1155/2023/2061632 -
International Braz J Urol : Official... 2023To review and compare the effectivity of novel minimally invasive treatments (MITs) to transurethral resection of the prostate (TURP) for the treatment of lower urinary... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To review and compare the effectivity of novel minimally invasive treatments (MITs) to transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms (LUTS) in men.
METHODS
Medline, Embase, and Cochrane databases were searched from January 2010 to December 2022 for randomized controlled trials (RCTs) evaluating MITs, compared to TURP or sham, in men with LUTS. Studies were assessed by risk of bias tool, and evidence by GRADE. Functional outcomes by means of uroflowmetry and IPSS were the primary outcomes, safety and sexual function were secondary outcomes. As part of this review, a network meta-analysis (NMA) was conducted. MITs were ranked based on functional outcome improvement probability.
RESULTS
In total, 10 RCTs were included, evaluating aquablation, prostatic urethral lift, prostatic artery embolization (PAE), convective water vapor thermal treatment or temporary implantable nitinol device. All MITs showed a better safety profile compared to TURP. Functional outcome improvement following aquablation were comparable to TURP. In the NMA, aquablation was ranked highest, PAE followed with the second highest probability to improve functional outcomes. Other novel MITs resulted in worse functional outcomes compared to TURP. Level of evidence was low to very low.
CONCLUSIONS
Five MITs for treatment of LUTS were identified. Aquablation is likely to result in functional outcomes most comparable to TURP. Second in ranking was PAE, a technique that does not require general or spinal anesthesia. MITs have a better safety profile compared to TURP. However, due to high study heterogeneity, results should be interpreted with caution.
Topics: Male; Humans; Prostatic Hyperplasia; Network Meta-Analysis; Treatment Outcome; Prostate; Transurethral Resection of Prostate; Lower Urinary Tract Symptoms
PubMed: 37267609
DOI: 10.1590/S1677-5538.IBJU.2023.0016 -
JNCI Cancer Spectrum Aug 2023Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score,...
BACKGROUND
Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer.
METHODS
Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy.
RESULTS
A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84).
CONCLUSIONS
There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.
Topics: Male; Humans; United States; Risk Assessment; Prostatic Neoplasms; Prostate-Specific Antigen; Prostate; Genomics
PubMed: 37525535
DOI: 10.1093/jncics/pkad052 -
World Journal of Urology Oct 2023We developed a simple self-checkable screening tool for chronic prostatitis (S-CP) and internally validated it to encourage men (in the general population) with possible...
PURPOSE
We developed a simple self-checkable screening tool for chronic prostatitis (S-CP) and internally validated it to encourage men (in the general population) with possible chronic prostatitis to consult urologists.
METHODS
The expert panel proposed the S-CP, which comprises three domains: Area of pain or discomfort (6 components), accompanying Symptom (6 components), and Trigger for symptom flares (4 components). We employed logistic regression to predict chronic prostatitis prevalence with the S-CP. We evaluated the predictive performance using data from a representative national survey of Japanese men aged 20 to 84. We calculated the optimism-adjusted area under the curve using bootstrapping. We assessed sensitivity/specificity, likelihood ratio, and predictive value for each cutoff of the S-CP.
RESULTS
Data were collected for 5,010 men-71 (1.4%) had a chronic prostatitis diagnosis. The apparent and adjusted area under the curve for the S-CP was 0.765 [95% confidence interval (CI) 0.702, 0.829] and 0.761 (0.696, 0.819), respectively. When the cutoff was two of the three domains being positive, sensitivity and specificity were 62.0% (95% CI 49.7, 73.2) and 85.4% (95% CI 84.4, 86.4), respectively. The positive/negative likelihood ratios were 4.2 (95% CI 3.5, 5.2) and 0.45 (95% CI 0.33, 0.60), respectively. The positive/negative predictive values were 5.7 (95% CI 4.2, 7.6) and 99.4 (95% CI 99.1, 99.6), respectively.
CONCLUSION
The reasonable predictive performance of the S-CP indicated that patients (in the general population) with chronic prostatitis were screened as a first step. Further research would develop another tool for diagnostic support in actual clinical settings.
Topics: Male; Humans; Prostatitis; Pelvic Pain; Chronic Disease; Predictive Value of Tests; Logistic Models
PubMed: 37712967
DOI: 10.1007/s00345-023-04574-x -
Biochimica Et Biophysica Acta.... Oct 2023Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. The six transmembrane epithelial antigen of the prostate 1 (STEAP1) protein is...
Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. The six transmembrane epithelial antigen of the prostate 1 (STEAP1) protein is overexpressed in several types of human tumors, particularly in PCa. Our research group has demonstrated that STEAP1 overexpression is associated with PCa progression and aggressiveness. Therefore, understanding the cellular and molecular mechanisms triggered by STEAP1 overexpression will provide important insights to delineate new strategies for PCa treatment. In the present work, a proteomic strategy was used to characterize the intracellular signaling pathways and the molecular targets downstream of STEAP1 in PCa cells. A label-free approach was applied using an Orbitrap LC-MS/MS system to characterize the proteome of STEAP1-knockdown PCa cells. More than 6700 proteins were identified, of which a total of 526 proteins were found differentially expressed in scramble siRNA versus STEAP1 siRNA (234 proteins up-regulated and 292 proteins down-regulated). Bioinformatics analysis allowed us to explore the mechanism through which STEAP1 exerts influence on PCa, revealing that endocytosis, RNA transport, apoptosis, aminoacyl-tRNA biosynthesis, and metabolic pathways are the main biological processes where STEAP1 is involved. By immunoblotting, it was confirmed that STEAP1 silencing induced the up-regulation of cathepsin B, intersectin-1, and syntaxin 4, and the down-regulation of HRas, PIK3C2A, and DIS3. These findings suggested that blocking STEAP1 might be a suitable strategy to activate apoptosis and endocytosis, and diminish cellular metabolism and intercellular communication, leading to inhibition of PCa progression.
Topics: Male; Humans; Prostate; Proteomics; Chromatography, Liquid; Tandem Mass Spectrometry; Prostatic Neoplasms; RNA, Small Interfering; Antigens, Neoplasm; Oxidoreductases
PubMed: 37315586
DOI: 10.1016/j.bbamcr.2023.119522 -
Oncogene Jul 2023Tuft cells are chemosensory epithelial cells that increase in number following infection or injury to robustly activate the innate immune response to alleviate or...
Tuft cells are chemosensory epithelial cells that increase in number following infection or injury to robustly activate the innate immune response to alleviate or promote disease. Recent studies of castration resistant prostate cancer and its subtype, neuroendocrine prostate cancer, revealed Pou2f3+ populations in mouse models. The transcription factor Pou2f3 is a master regulator of the tuft cell lineage. We show that tuft cells are upregulated early during prostate cancer development, and their numbers increase with progression. Cancer-associated tuft cells in the mouse prostate express DCLK1, COX1, COX2, while human tuft cells express COX1. Mouse and human tuft cells exhibit strong activation of signaling pathways including EGFR and SRC-family kinases. While DCLK1 is a mouse tuft cell marker, it is not present in human prostate tuft cells. Tuft cells that appear in mouse models of prostate cancer display genotype-specific tuft cell gene expression signatures. Using bioinformatic analysis tools and publicly available datasets, we characterized prostate tuft cells in aggressive disease and highlighted differences between tuft cell populations. Our findings indicate that tuft cells contribute to the prostate cancer microenvironment and may promote development of more advanced disease. Further research is needed to understand contributions of tuft cells to prostate cancer progression.
Topics: Male; Mice; Humans; Animals; Prostate; Protein Serine-Threonine Kinases; Signal Transduction; Prostatic Neoplasms; Epithelial Cells; Tumor Microenvironment; Doublecortin-Like Kinases
PubMed: 37386128
DOI: 10.1038/s41388-023-02743-1