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Current Medicinal Chemistry Jan 2024Chronic prostatitis is a highly prevalent condition that significantly impacts the quality of life and fertility of men. Because of its heterogeneous nature, there is no...
Chronic prostatitis is a highly prevalent condition that significantly impacts the quality of life and fertility of men. Because of its heterogeneous nature, there is no definitive treatment, which requires ongoing research into its etiology. Additionally, the association between prostatitis and an elevated risk of prostate cancer highlights the importance of comprehending androgen involvement in prostatitis. This paper examines the current understanding of androgen signaling in prostatitis and explores contemporary therapeutic approaches. We reviewed Medline articles comprehensively, using keywords such as nonbacterial prostatitis, prostatitis infertility, androgen role in prostatitis, and chronic pelvic pain. Several cellular targets are linked to androgen signaling. Notably, the major tyrosine phosphatase activity (cPAcP) in normal human prostate is influenced by androgen signaling, and its serum levels inversely correlate with prostate cancer progression. Androgens also regulate membrane-associated zinc and pyruvate transporters transduction in prostate cells, suggesting promising avenues for novel drug development aimed at inhibiting these molecules to reduce cancer tumor growth. Various therapies for prostatitis have been evaluated, including antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha-blockers, 5α-reductase inhibitors, and androgen receptor antagonists. These therapies have demonstrated varying degrees of success in ameliorating symptoms. In conclusion, aging decreases circulating T and intraprostatic DHT, altering the proper functioning of the prostate, reducing the ability of androgens to maintain normal Zn2+ levels, and diminishing the secretion of citrate, PAcP, and other proteins into the prostatic fluid. The Zn2+-transporter decreases or is absent in prostate cancer, so the pyruvate transporter activates. Consequently, the cell ATP increases, inducing tumor growth.
PubMed: 38243983
DOI: 10.2174/0109298673279207231228070533 -
Biosensors & Bioelectronics Nov 2023A new photoelectrochemical immunoassay based on self-assembled p-n AgO@BiOS nanoflower heterojunction was designed and developed for quantitative monitoring of...
A new photoelectrochemical immunoassay based on self-assembled p-n AgO@BiOS nanoflower heterojunction was designed and developed for quantitative monitoring of prostate-specific antigen (PSA) in biological fluids. Primarily, self-assembled p-n AgO@BiOS nanoflower heterojunctions were served as the photoactive materials and coated onto the surface of electrodes. Subsequently, the glucose oxidase (GOx) was bound to the detection antibody (mAb) labeled gold nanoparticles (Au NPs) and then were employed to accomplish a sandwich-like immunoreaction to generate HO on a microplate incubated with monoclonal anti-PSA antibodies. In the presence of PSA, the product (HO) was catalyzed by the substrate, which was used as an electron sacrificial agent to improve signal conversion and capture of photogenerated electrons. Under optimum conditions, a wide linear range of 0.01-50 ng mL and a low detection limit of 5.3 pg mL were accomplished with the sensor, exhibiting an excellent photocurrent response. Moreover, the proposed sensor revealed satisfactory reproducibility, high selectivity, and acceptable accuracy for the real sample testing. Importantly, our work provides a novel strategy for high sensitivity detection of disease-associated biomarkers for the early diagnosis of cancers.
Topics: Male; Humans; Gold; Hydrogen Peroxide; Metal Nanoparticles; Reproducibility of Results; Biosensing Techniques; Antibodies; Immunoassay
PubMed: 37603986
DOI: 10.1016/j.bios.2023.115608 -
Pharmaceutics Dec 2023Nanomedicines engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or a short half-life, are targeted...
Nanomedicines engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or a short half-life, are targeted towards their cellular destination either passively or through various elements of cell membranes. The differences in the physicochemical properties of the cell membrane between tumor and nontumor cells have been reported, but they are not systematically used for drug delivery purposes. Thus, in this study, a new approach based on a match between the liposome compositions, i.e., membrane fluidity, to selectively interact with the targeted cell membrane was used. Lipid-based carriers of two different fluidities were designed and used to deliver 4()-4-F-Neuroprostane (F-NeuroP), a potential antitumor molecule derived from docosahexaenoic acid (DHA). Based on its hydrophobic character, F-NeuroP was added to the lipid mixture prior to liposome formation, a protocol that yielded over 80% encapsulation efficiency in both rigid and fluid liposomes. The presence of the active molecule did not modify the liposome size but increased the liposome negative charge and the liposome membrane fluidity, which suggested that the active molecule was accommodated in the lipid membrane. F-NeuroP integration in liposomes with a fluid character allowed for the selective targeting of the metastatic prostate cell line PC-3 vs. fibroblast controls. A significant decrease in viability (40%) was observed for the PC-3 cancer line in the presence of F-NeuroP fluid liposomes, whereas rigid F-NeuroP liposomes did not alter the PC-3 cell viability. These findings demonstrate that liposomes encapsulating F-NeuroP or other related molecules may be an interesting model of drug carriers based on membrane fluidity.
PubMed: 38140081
DOI: 10.3390/pharmaceutics15122739 -
Scientific Reports Jan 2024Knowledge of factors associated with semen quality may help in investigations of the aetiology and pathophysiology. We investigated the correlation between biomarkers...
Knowledge of factors associated with semen quality may help in investigations of the aetiology and pathophysiology. We investigated the correlation between biomarkers for testicular cell function (anti-müllerian hormone, AMH, Inhibin B, testosterone, free androgen-index (testosterone/sex-hormone binding globulin), insulin like peptide 3, INSL-3), alkaline phosphate (ALP), canine prostate-specific esterase (CPSE), and heterophilic antibodies with dog variables, semen quality, and fertility. Blood and semen were collected from 65 Bernese Mountain Dogs. We evaluated total sperm count, motility and morphological parameters. The semen quality ranged from poor to excellent, with an average total sperm count of 1.1 × 10 and 50% morphologically normal spermatozoa (MNS). Age and abnormal testicular consistency correlated with decreased motility and MNS. Higher ALP correlated with higher total sperm count. AMH could not be detected in seminal plasma. AMH in blood correlated with head defects and high AMH concentration correlated with a severe decline in several semen parameters. Testosterone was negatively and CPSE positively correlated with age. No correlations were found for INSL-3, inhibin B, or heterophilic antibodies. Our findings contribute to the understanding of factors associated with semen quality in dogs, particularly related to Sertoli cell function.
Topics: Male; Dogs; Animals; Semen Analysis; Semen; Anti-Mullerian Hormone; Body Fluids; Peptide Hormones; Testosterone; Antibodies, Heterophile; Esterases
PubMed: 38184699
DOI: 10.1038/s41598-024-51242-0 -
Environmental Pollution (Barking, Essex... Apr 2024The harmful effects of microplastics (MPs) on male fertility are receiving more and more attention. However, the impact of low-dose MPs exposure on the reproductive...
The harmful effects of microplastics (MPs) on male fertility are receiving more and more attention. However, the impact of low-dose MPs exposure on the reproductive function of male mice is still unclear. In this study, we exposed male mice to low-dose MPs (25-30 μg/kg body weight/day) or low-dose MPs combined with high-fat diet (HFD) feeding. Our results showed that low-dose MPs exposure or HFD feeding significantly reduced sperm quality and the number of offspring born, while low-dose MPs exposure combined with HFD feeding further enhanced the above effects. The combination of low-dose MPs exposure and HFD feeding resulted in a notable elevation of inflammatory level within the prostate of mice and induced apoptosis of prostate epithelium and a decrease in nutrients (zinc, citrate) in seminal plasma fluid. Our findings in this study could provide valuable clues for better understanding the influence of low-dose MPs exposure on the reproductive system under metabolic disorders and facilitate the development of the prevention of reproductive toxicity caused by MPs exposure.
Topics: Male; Humans; Polystyrenes; Microplastics; Plastics; Diet, High-Fat; Prostate; Semen; Fertility; Obesity
PubMed: 38367694
DOI: 10.1016/j.envpol.2024.123567 -
Cell Reports. Medicine Jun 2024Molecular phenotypic variations in metabolites offer the promise of rapid profiling of physiological and pathological states for diagnosis, monitoring, and prognosis....
Molecular phenotypic variations in metabolites offer the promise of rapid profiling of physiological and pathological states for diagnosis, monitoring, and prognosis. Since present methods are expensive, time-consuming, and still not sensitive enough, there is an urgent need for approaches that can interrogate complex biological fluids at a system-wide level. Here, we introduce hyperspectral surface-enhanced Raman spectroscopy (SERS) to profile microliters of biofluidic metabolite extraction in 15 min with a spectral set, SERSome, that can be used to describe the structures and functions of various molecules produced in the biofluid at a specific time via SERS characteristics. The metabolite differences of various biofluids, including cell culture medium and human serum, are successfully profiled, showing a diagnosis accuracy of 80.8% on the internal test set and 73% on the external validation set for prostate cancer, discovering potential biomarkers, and predicting the tissue-level pathological aggressiveness. SERSomes offer a promising methodology for metabolic phenotyping.
Topics: Humans; Prostatic Neoplasms; Spectrum Analysis, Raman; Male; Phenotype; Metabolomics; Metabolome; Biomarkers, Tumor; Cell Line, Tumor
PubMed: 38776910
DOI: 10.1016/j.xcrm.2024.101579 -
Anticancer Research Sep 2023Testosterone is essential for prostate cancer development and growth. This study aimed to investigate the relationship between testosterone in seminal vesicles and...
BACKGROUND/AIM
Testosterone is essential for prostate cancer development and growth. This study aimed to investigate the relationship between testosterone in seminal vesicles and prostate cancer incidence and its malignant phenotype.
PATIENTS AND METHODS
After obtaining institutional review board approval, seminal vesicle fluid samples were collected from patients who underwent prostatectomy or cystectomy. Pathological review demonstrated that 26 patients had benign prostate tissue and 149 had prostate cancer. First, testosterone levels in seminal vesicle fluid from benign prostate and prostate cancer samples were compared. Next, the relationship between pathological stage, International Society of Urological Pathology (ISUP) score, and testosterone concentrations in seminal vesicle fluid in the prostate cancer group were examined.
RESULTS
Testosterone in seminal vesicles was significantly higher in the prostate cancer group [median (range), 1.94 (0.17-4.32) ng/ml] than in the benign prostate group (mainly bladder cancer) [1.45 (0.60-2.78) ng/ml] (p=0.001). Testosterone in seminal vesicles showed no difference in relation to pathological stage (pT2 vs. pT3) or ISUP score (12 vs. 345) (p=0.480 and p=0.964, respectively). Neoadjuvant chemotherapy for other cancers (e.g., bladder or rectal cancer) significantly reduced testosterone in seminal vesicles (p=0.013). Multivariate regression analysis revealed that testosterone in seminal vesicles was significantly correlated with prostate cancer, and not with neoadjuvant chemotherapy (p=0.023, p=0.457, respectively).
CONCLUSION
Testosterone in seminal vesicles may contribute to prostate cancer incidence, but has no relationship with pathological grading.
Topics: Male; Humans; Seminal Vesicles; Prostatic Neoplasms; Testosterone; Prostate; Urinary Bladder Neoplasms
PubMed: 37648320
DOI: 10.21873/anticanres.16618 -
The association between zinc and prostate cancer development: A systematic review and meta-analysis.PloS One 2024Prostate cancer is affecting males globally, with several complications. Zinc can play roles in cancers. We aimed to clarify the association between zinc levels or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prostate cancer is affecting males globally, with several complications. Zinc can play roles in cancers. We aimed to clarify the association between zinc levels or intake with prostate cancer development.
METHODS
We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science until May 1, 2023. We included case-controls and cross-sectionals that measured zinc level and/or intake in patients with prostate cancer or cohorts that evaluated the association between zinc and prostate cancer development. Studies that did not have a healthy control group were excluded. Joanna Briggs Institute was used for quality assessment. Publication bias was evaluated using Egger's and Begg's tests and funnel plot.
RESULTS
Overall, 52 studies (n = 44 case controls, n = 4 cohorts, and n = 4 cross sectionals) with a total number of 163909 participants were included. Serum (standardized mean difference (SMD): -1.11; 95% confidence interval (CI): -1.67, -0.56), hair (SMD: -1.31; 95% CI: -2.19, -0.44), and prostatic fluid or tissue zinc levels (SMD: -3.70; 95% CI: -4.90, -2.49) were significantly lower in prostate cancer patients. There were no significant differences in nail zinc level and zinc intake between those with prostate cancer and healthy controls. There was no publication bias except for serum and hair zinc levels based on Begg's and Egger's tests, respectively. The mean risk of bias scores were 4.61 in case-controls, eight in cohorts, and seven in cross-sectionals.
CONCLUSIONS
Overall, high zinc levels might have a protective role in prostate cancer, which can be used as a therapeutic or preventive intervention. Future large-scale studies are needed to confirm the association.
Topics: Male; Humans; Zinc; Prostatic Neoplasms; Health Status; Nutritional Status; PubMed
PubMed: 38507438
DOI: 10.1371/journal.pone.0299398 -
Frontiers in Molecular Biosciences 2023Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification,...
Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification, and active surveillance. In recent years, liquid biopsies have emerged as a promising non-invasive approach to complement or even replace traditional tissue biopsies. Extracellular vesicles (EVs), nanosized membranous structures released by various cells into body fluids, have gained substantial attention as a source of cancer biomarkers due to their ability to encapsulate and transport a wide range of biological molecules, including RNA. In this study, we aimed to validate 15 potential RNA biomarkers, identified in a previous EV RNA sequencing study, using droplet digital PCR. The candidate biomarkers were tested in plasma and urinary EVs collected before and after radical prostatectomy from 30 PCa patients and their diagnostic potential was evaluated in a test cohort consisting of 20 benign prostate hyperplasia (BPH) and 20 PCa patients' plasma and urinary EVs. Next, the results were validated in an independent cohort of plasma EVs from 31 PCa and 31 BPH patients. We found that the levels of NKX3-1 ( = 0.0008) in plasma EVs, and tRF-Phe-GAA-3b ( < 0.0001) tRF-Lys-CTT-5c ( < 0.0327), piR-28004 ( = 0.0081) and miR-375-3p ( < 0.0001) in urinary EVs significantly decreased after radical prostatectomy suggesting that the main tissue source of these RNAs is prostate and/or PCa. Two mRNA biomarkers-GLO1 and NKX3-1 showed promising diagnostic potential in distinguishing between PCa and BPH with AUC of 0.68 and 0.82, respectively, in the test cohort and AUC of 0.73 and 0.65, respectively, in the validation cohort, when tested in plasma EVs. Combining these markers in a biomarker model yielded AUC of 0.85 and 0.71 in the test and validation cohorts, respectively. Although the PSA levels in the blood could not distinguish PCa from BPH in our cohort, adding PSA to the mRNA biomarker model increased AUC from 0.71 to 0.76. This study identified two novel EV-enclosed RNA biomarkers-NKX3-1 and GLO1-for the detection of PCa, and highlights the complementary nature of GLO1, NKX3-1 and PSA as combined biomarkers in liquid biopsies of PCa.
PubMed: 38099195
DOI: 10.3389/fmolb.2023.1279854 -
Frontiers in Veterinary Science 2023A 1-year-old male intact Miniature Schnauzer mix was presented for chronic intermittent hematuria. Abdominal ultrasonography revealed a large, fluid-filled cystic...
A 1-year-old male intact Miniature Schnauzer mix was presented for chronic intermittent hematuria. Abdominal ultrasonography revealed a large, fluid-filled cystic structure extending cranially and dorsally to the prostate. Computed tomography scan images revealed that the fluid-filled cavity resembled a uterus, with both horns entering the scrotum through the inguinal canal adjacent to the testes. On cytogenetic analysis, the dog was found to have a homozygote mutation on consistent with persistent Müllerian duct syndrome (PMDS). A gonadohysterectomy was performed, and surgical and histologic findings confirmed the presence of a uterus, oviducts, vagina, and testes in this dog. Additionally, an intraoperative fluoroscopy exam revealed a communication between the uterus and the bladder via an enlarged utricle, explaining the hematuria and urine in the reproductive tract (urometra). To our knowledge, this is the first clinical report of a phenotypically intact male dog with PMDS and urometra due to an enlarged prostatic utricle. This case illustrates a combination of a disorder of sex and urogenital sinus development.
PubMed: 37470070
DOI: 10.3389/fvets.2023.1185621