-
American Journal of Reproductive... Feb 2021Extracellular vesicles (EVs) are secreted cell-derived membrane structures present in all organisms across animal, bacterial, and plant phyla. These vesicles play... (Review)
Review
Extracellular vesicles (EVs) are secreted cell-derived membrane structures present in all organisms across animal, bacterial, and plant phyla. These vesicles play important roles in cell-cell communication in many processes integral to health and disease. Recent studies demonstrate that EVs and their cargo have influential and conserved roles in male reproduction. While EVs have been isolated from virtually all specialized tissues comprising the male reproductive tract, they are best characterized in the epididymis (epididymosomes) and seminal fluid (seminal fluid extracellular vesicles or prostasomes). Broadly speaking, EVs promote reproductive success through supporting sperm development and function, as well as influencing the physiology of female reproductive tract cells after mating. In this review, we present current knowledge on the composition and function of male reproductive tract EV populations in both normal physiology and pathology, and argue that their functions identify them as critical regulators of fertility and fecundity.
Topics: Animals; Cell Communication; Epididymis; Extracellular Vesicles; Female; Fertility; Humans; Male; Prostate; Reproduction; Sperm Motility; Spermatozoa
PubMed: 32885533
DOI: 10.1111/aji.13338 -
International Journal of Molecular... Sep 2023Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their... (Review)
Review
Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.
Topics: Male; Humans; Carcinoma, Renal Cell; Prostate; Prostatic Neoplasms, Castration-Resistant; Clinical Relevance; Kidney Neoplasms; Neoplasm Recurrence, Local; Extracellular Vesicles; Exosomes
PubMed: 37834162
DOI: 10.3390/ijms241914713 -
World Journal of Urology Mar 2022Transurethral endoscopic procedures using bipolar current, or laser energy are nowadays widely accepted and have replaced the traditional monopolar resection. A major... (Review)
Review
PURPOSE
Transurethral endoscopic procedures using bipolar current, or laser energy are nowadays widely accepted and have replaced the traditional monopolar resection. A major advantage of these techniques is the utilization of isotonic saline as irrigation solution, which minimizes side effects such as symptoms associated to classical transurethral resection syndrome (TUR-syndrome). Nonetheless, clinically significant IFA also occurs with saline and is determined by pressure gradients, systemic resistance and by the amount of irrigation fluid. We aimed to investigate the extend of IFA and symptoms due to volume overload during bipolar transurethral resection (bTUR) and laser procedures of the prostate.
METHODS
We performed a systematic literature search using PubMed, restricted to original English-written articles, including animal, artificial model, and human studies. Search terms were TUR, transurethral, laser, HoLEP, ThuLEP, greenlight, enucleation, fluid absorption, fluid uptake, and TUR-syndrome.
RESULTS
Mean and maximum IFA during bTURP ranges between 133 and 915 ml and 1019 ml and 2166 ml, respectively. Absorption during laser procedures can be significant with maximum values up to 4579 ml and mainly occurs during prostate vaporization techniques. Incidence of moderate to severe symptoms from iso-osmolar volume overload reaches 9%.
CONCLUSIONS
Irrigation fluid absorption during bTUR and laser surgery of the prostate is not negligible. Iso-osmolar overhydration with development of non-classical TUR-syndrome should be identified peri- and postoperatively and surgical teams should be aware of complications. Breath ethanol, venous pH, serum chloride, and bicarbonate could be markers for detecting dangerous events of IFA with saline.
Topics: Humans; Laser Therapy; Lasers; Male; Prostate; Prostatic Hyperplasia; Therapeutic Irrigation; Transurethral Resection of Prostate; Urologic Surgical Procedures
PubMed: 34191108
DOI: 10.1007/s00345-021-03769-4 -
Frontiers in Cell and Developmental... 2023Small extracellular vesicles (sEVs) are minute vesicles secreted by various cells that are capable of transporting cargo, including microRNAs, between donor and... (Review)
Review
Small extracellular vesicles (sEVs) are minute vesicles secreted by various cells that are capable of transporting cargo, including microRNAs, between donor and recipient cells. MicroRNAs (miRNAs), small non-coding RNAs approximately 22 nucleotides in length, have been implicated in a wide array of biological processes, including those involved in tumorigenesis. Emerging evidence highlights the pivotal role of miRNAs encapsulated in sEVs in both the diagnosis and treatment of urological tumors, with potential implications in epithelial-mesenchymal transition, proliferation, metastasis, angiogenesis, tumor microenvironment and drug resistance. This review provides a brief overview of the biogenesis and functional mechanisms of sEVs and miRNAs, followed by a summarization of recent empirical findings on miRNAs encapsulated in sEVs from three archetypal urologic malignancies: prostate cancer, clear cell renal cell carcinoma, and bladder cancer. We conclude by underscoring the potential of sEV-enclosed miRNAs as both biomarkers and therapeutic targets, with a particular focus on their detection and analysis in biological fluids such as urine, plasma, and serum.
PubMed: 37333986
DOI: 10.3389/fcell.2023.1192937 -
Magma (New York, N.Y.) Aug 2022Molecular interactions in prostatic fluid are of biological interest and may affect MRI and MRS of the prostate. We investigated the existence of interactions between...
INTRODUCTION
Molecular interactions in prostatic fluid are of biological interest and may affect MRI and MRS of the prostate. We investigated the existence of interactions between the major components of this fluid: spermine, citrate and myoinositol, metal ions, including zinc, and proteins.
MATERIALS AND METHODS
Solutions of 90 mM citrate, 18 mM spermine and 6 mM myo-inositol, mimicking expressed prostatic fluid, were investigated by 1H NMR using changes in T2 relaxation and chemical shift as markers for interactions.
RESULTS AND DISCUSSION
Adding to this metabolite mixture the ions Na , K, Ca, Mg and Zn, decreased the T2 relaxation times of citrate and spermine protons by factors of 3 and 2, respectively, with Zn++ causing the largest effect, indicating ion-metabolite interactions. The T2 of 18 mM spermine dropped by a factor of 2 upon addition with 90 mM citrate, but no effect on T2 was seen with myo-inositol pointing to a specific citrate-spermine interaction. Moreover, the T2 of citrate in the presence of spermine decreased by adding metal ions and increasing amounts of Zn, indicating complexation of citrate and spermine with metal ions, particularly with Zn. The addition of bovine serum albumin (BSA), as an index protein, substantially further decreased the T2 of spermine and citrate implying the formation of a transient spermine-metal ion-citrate-BSA complex. Finally, we found that the T2 of citrate in extracellular fluid of prostate cancer cells, as a mimic of fluid in cancerous prostates, decreased by adding fetal calf serum, indicating protein binding.
Topics: Citrates; Citric Acid; Humans; Inositol; Magnetic Resonance Imaging; Male; Prostatic Neoplasms; Proton Magnetic Resonance Spectroscopy; Protons; Spermine
PubMed: 34919194
DOI: 10.1007/s10334-021-00983-4 -
Frontiers in Chemistry 2021Expressed prostatic secretions (EPS), also called post digital rectal exam urines, are proximal fluids of the prostate that are widely used for diagnostic and prognostic...
Expressed prostatic secretions (EPS), also called post digital rectal exam urines, are proximal fluids of the prostate that are widely used for diagnostic and prognostic assays for prostate cancer. These fluids contain an abundant number of glycoproteins and extracellular vesicles secreted by the prostate gland, and the ability to detect changes in their N-glycans composition as a reflection of disease state represents potential new biomarker candidates. Methods to characterize these N-glycan constituents directly from clinical samples in a timely manner and with minimal sample processing requirements are not currently available. In this report, an approach is described to directly profile the N-glycan constituents of EPS urine samples, prostatic fluids and urine using imaging mass spectrometry for detection. An amine reactive slide is used to immobilize glycoproteins from a few microliters of spotted samples, followed by peptide N-glycosidase digestion. Over 100 N-glycan compositions can be detected with this method, and it works with urine, urine EPS, prostatic fluids, and urine EPS-derived extracellular vesicles. A comparison of the N-glycans detected from the fluids with tissue N-glycans from prostate cancer tissues was done, indicating a subset of N-glycans present in fluids derived from the gland lumens. The developed N-glycan profiling is amenable to analysis of larger clinical cohorts and adaptable to other biofluids.
PubMed: 34646811
DOI: 10.3389/fchem.2021.734280 -
Oncology Letters Dec 2022Prostate cancer (PCa) is the second most frequently diagnosed solid tumor and the fifth leading cause of cancer mortality among men worldwide. The prostate specific...
Prostate cancer (PCa) is the second most frequently diagnosed solid tumor and the fifth leading cause of cancer mortality among men worldwide. The prostate specific antigen (PSA) test for PCa remains controversial. Therefore, the development of more effective non-invasive biomarkers for PCa is necessary. The present study evaluated the diagnostic value of microRNA (miR)-20b-5p in PCa. Tissue miR-20b-5p expression levels and their correlation with clinical parameters were assessed using The Cancer Genome Atlas (TCGA) datasets, and the diagnostic value of the miR-20b-5p expression levels in PCa tissues was assessed using receiver operating characteristic curve analysis. Reverse transcription-quantitative PCR (RT-qPCR) was used to assess the relative expression levels of miR-20b-5p in PCa tissues compared with benign prostate hyperplasia (BPH) tissues. In addition, miR-20b-5p expression levels in PCa cell lines and non-tumorigenic prostate epithelial cells were compared. In this study, exosomes were extracted from the prostatic fluid as a source of liquid biopsy for the detection of PCa. The prostatic fluid exosomal miR-20b-5p expression levels between patients with PCa and the biopsy-negative patients were compared, and the diagnostic efficiency of prostatic fluid exosomal miR-20b-5p expression levels in PCa was compared with PSA and with the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator. The mechanism by which miR-20b-5p may function in PCa was assessed using bioinformatic analysis and validation experiments. miR-20b-5p was expressed at a markedly higher level in PCa tissues compared with normal prostate tissues with high diagnostic efficiency (area under the curve: 0.826). The expression levels of miR-20b-5p were also significantly higher in PCa tissues compared with BPH tissues; similarly, miR-20b-5p was more highly expressed in PCa cells compared with non-tumorigenic prostate epithelial cells. Prostatic fluid exosomal miR-20b-5p expression levels in patients with PCa were significantly higher compared with confirmed to be biopsy-negative, and the diagnostic performance of miR-20b-5p was superior to PSA and ERSPC risk calculator. The results of RT-qPCR and western blotting following transfection of DU145 cells with miR-20b-5p mimics and inhibitor showed that miR-20b-5p reduced the expression of retinoblastoma-associated protein 1 (RB1). Therefore, RB1 may be a significant target gene for miR-20b-5p. In conclusion, the present study demonstrated that miR-20b-5p was upregulated in PCa at the tissue and cellular levels, as well as in prostatic fluid exosomes. Therefore, miR-20b-5p may be a promising early diagnostic biomarker for PCa and an important tool to guide the decision-making of prostate biopsy.
PubMed: 36311688
DOI: 10.3892/ol.2022.13546 -
Archivum Immunologiae Et Therapiae... Sep 2021Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by chronic pain in the perineum or lower abdomen regions, is a frequent disorder in men.... (Review)
Review
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by chronic pain in the perineum or lower abdomen regions, is a frequent disorder in men. Previous studies demonstrated that the immune mediators, including interleukin (IL)-1β, IL-6, interferon-γ, tumor necrosis factor-α, and immunoglobulins, are elevated in the expressed prostate secretions and seminal fluid of CP/CPPS men. The memory T, T helper 1 (Th1), Th17, and Th22 cells increase in the peripheral blood of CP/CPPS men. Additionally, prostate antigens specific-autoreactive T cells are identified in CP/CPPS patients. After generally reviewing and comparing the inflammatory responses in autoimmune diseases and CP/CPPS, we presumed that CP/CPPS is more likely to be defined as an autoimmune disease. Thus, a better understanding of autoimmune diseases would contribute to a deeper understanding of the CP/CPPS and provide new inspirations for the treatment of this disease.
Topics: Autoimmune Diseases; Chronic Disease; Chronic Pain; Humans; Male; Pelvic Pain; Prostatitis
PubMed: 34523016
DOI: 10.1007/s00005-021-00628-3 -
Cells Aug 2021The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various... (Review)
Review
The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.
Topics: Animals; Body Fluids; Embolism; Extracellular Traps; Humans; Inflammation; Neutrophils; Prospective Studies; Thrombosis
PubMed: 34571857
DOI: 10.3390/cells10092208 -
Gynecological Endocrinology : the... Oct 2023Polycystic ovary syndrome (PCOS) was known as the common endocrine disease in women, featured as hyperandrogenism, ovulation disorders, etc. Fat mass and...
BACKGROUND
Polycystic ovary syndrome (PCOS) was known as the common endocrine disease in women, featured as hyperandrogenism, ovulation disorders, etc. Fat mass and obesity-associated protein (FTO), a m6A demethylase, is abnormal in the occurrence of ovarian diseases. However, the mechanism of FTO in the pathogenesis of PCOS is still unclear.
METHODS
The level of FTO in clinical samples, PCOS rat with hyperandrogenism and granulosa cells (GCs) lines effected by DHT were investigated by ELISA, qRT-PCR, WB, and IHC, while m6A RNA methylation level was studied by m6A Colorimetric and androgen level was tested through ELISA. Changes in steroid hormone synthetase and androgen receptor (AR)/prostate-specific antigen (PSA) levels were visualized by WB after transient transfection silenced FTO. The effect of DHT combined with FTO inhibitor meclofenamic acid (MA) on FTO, AR/PSA, and AKT phosphorylation were also demonstrated by WB. The co-localization of FTO and AR in KGN cells was analyzed by confocal microscopy, and the physiological interaction between FTO and AR was studied by Co-IP assay. The effect of FTO-specific inhibitor MA, AKT phosphorylation inhibitor LY294002, and the combined them on GCs proliferation and cell cycle were evaluated by drug combination index, EDU assay, and flow cytometry analysis.
RESULTS
FTO expression was upregulated in follicular fluid and GCs in PCOS patients clinically. The high FTO expression in patients was negative with the level of m6A, but positive with the level of androgen. The upregulation of FTO was accompanied with a decrease in the level of m6A in PCOS rat with hyperandrogenism. Dihydrotestosterone (DHT) promoted the FTO expression and inhibited m6A content as a dose-dependent way . In contrast, suppression of FTO with siRNA attenuated the expression of steroid hormone synthetase such as CYP11A1, CYP17A1, HSD11B1, HSD3B2 except CYP19A1 synthetase, ultimately inducing the decrease of androgen level. Suppression of FTO also decreased the biological activity of androgen through downregulation AR/PSA. MA treatment as the specific FTO antagonist decreased cell survival in time- and dose-dependent way in GCs lines. Correspondingly, MA treatment decreased the expression of FTO, AR/PSA expression, and AKT phosphorylation in the presence of DHT stimulation. Additionally, we also speculate there is a potential relation between FTO and AR according to FTO was co-localized and interacted with AR in KGN cells. Compared with AKT phosphorylation inhibitor LY294002 or MA alone, LY294002 combined with MA synergistically inhibited cell survival and increased G2/M phase arrest in GC line.
CONCLUSIONS
We first evaluated the correlation of FTO and m6A in PCOS clinically, and further explored the mechanism between FTO and hyperandrogenism in PCOS animal and cell models. These findings contributed the potential therapy by targeting the FTO for hyperandrogenism in PCOS.
Topics: Animals; Female; Humans; Rats; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Androgens; Dihydrotestosterone; Granulosa Cells; Hyperandrogenism; Ligases; Polycystic Ovary Syndrome; Prostate-Specific Antigen; Proto-Oncogene Proteins c-akt
PubMed: 37931646
DOI: 10.1080/09513590.2023.2276167