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Acta Biomaterialia Sep 2023Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN)...
Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN) during prostatectomy is the main cause of postoperative erectile dysfunction (ED). In this study, the capability of a personalized bioactive fibrous membrane to regenerate injured CN was investigated. The fibrous membrane bioactivity is conferred by the selectively bound nerve growth factor (NGF) present in the rat urine. In a rat model of bilateral CN crush, the implanted bioactive fibrous membrane induces CN regeneration and restoration of erectile function, showing a significantly increased number of smooth muscle cells and content of endothelial and neuronal nitric oxide synthases (eNOS; nNOS). In addition, the bioactive fibrous membrane promotes nerve regeneration by increasing the number of myelinated axons and nNOS-positive cells, therefore reversing the CN fibrosis found in untreated rats or rats treated with a bare fibrous membrane. Therefore, this personalized regenerative strategy could overcome the recognized drawbacks of currently available treatments for CN injuries. It may constitute an effective treatment for prostate cancer patients suffering from ED after being subject to radical prostatectomy. STATEMENT OF SIGNIFICANCE: The present work introduces a unique strategy to address post-surgical ED resulting from CN injury during pelvic surgery (e.g., radical prostatectomy, radical cystoprostatectomy, abdominoperineal resection). It comprises a bioactive and cell-free fibrous implant, customized to enhance CN recovery. Pre-clinical results in a rat model of bilateral CN crush demonstrated that the bioactive fibrous implant can effectively heal injured CN, and restore penile structure and function. This implant selectively binds NGF from patient fluids (i.e. urine) due to its functionalized surface and high surface area. Moreover, its local implantation reduces adverse side effects. This tailored regenerative approach has the potential to revolutionize the treatment of ED in prostate cancer patients following radical prostatectomy, overcoming current treatment limitations.
Topics: Male; Humans; Rats; Animals; Rats, Sprague-Dawley; Nerve Growth Factor; Penile Erection; Erectile Dysfunction; Penis; Prostatectomy; Prostatic Neoplasms; Disease Models, Animal
PubMed: 37467838
DOI: 10.1016/j.actbio.2023.07.015 -
American Journal of Translational... 2021To study the effect of Qianliekang tablets on the clinical efficacy, immune function, and inflammatory factor levels in the prostatic fluid of elderly chronic...
The effect of Qianliekang tablets on the clinical efficacy, immune function, and inflammatory factor levels in the prostatic fluid of elderly chronic prostatitis patients.
PURPOSE
To study the effect of Qianliekang tablets on the clinical efficacy, immune function, and inflammatory factor levels in the prostatic fluid of elderly chronic prostatitis (CP) patients.
METHODS
106 elderly CP patients admitted to our hospital between June 2018 and June 2020 were recruited as the study cohort and randomly divided into a regular group and an observation group. The regular group was administered tamsulosin hydrochloride, and the observation group was administered a combination of tamsulosin hydrochloride and Qianliekang tablets. After a course of treatment, the clinical efficacy, the changes in the patients' symptoms, the function scores, the prostate ultrasound indicators, the changes in the T lymphocyte subsets, and the inflammatory factor expression levels in the prostatic fluid before and after the treatment were measured and compared in the two groups. The occurrence of adverse effects during the treatment was statistically analyzed.
RESULTS
The overall effectiveness rate in the observation group was superior to the overall effectiveness rate in the regular group (94.34% vs. 75.47%, P < 0.05). There were no significant differences in the patient clinical data before the treatment in the two groups (P > 0.05). After the treatment, the CD /CD immune function indicators, the prostatic fluid inflammatory factor levels, the symptom function scores, and the prostate ultrasound indicators in the observation group were better than they were in the regular group (all P < 0.05). No significant differences were found in the incidence of adverse effects between the two groups (P > 0.05).
CONCLUSION
Qianliekang tablets can improve the curative effect in elderly CP patients, enhance their immune function, and reduce the inflammatory factor expression levels in their prostatic fluid.
PubMed: 34306506
DOI: No ID Found -
World Journal of Clinical Oncology Aug 2020Advancing knowledge of the transcriptome has revealed that circular RNAs (circRNAs) are widely expressed and evolutionarily conserved molecules that may serve relevant... (Review)
Review
Advancing knowledge of the transcriptome has revealed that circular RNAs (circRNAs) are widely expressed and evolutionarily conserved molecules that may serve relevant biological roles. More interesting is the accumulating evidence which demonstrates the implication of circRNAs in diseases, especially cancers. This revelation has helped to form the rationale for many studies exploring their utility as clinical biomarkers. CircRNAs are highly stable due to their unique structures, exhibit some tissue specificity, and are enriched in exosomes, which facilitate their detection in a range of body fluids. These properties make circRNAs ideal candidates for biomarker development in many diseases. This review will outline the discovery, biogenesis, and proposed functions of circRNAs.
PubMed: 32879844
DOI: 10.5306/wjco.v11.i8.563 -
Frontiers in Medicine 2021Extracellular vesicles (EVs) are natural nanoparticles secreted by cells in the body and released into the extracellular environment. They are associated with various... (Review)
Review
Extracellular vesicles (EVs) are natural nanoparticles secreted by cells in the body and released into the extracellular environment. They are associated with various physiological or pathological processes, and considered as carriers in intercellular information transmission, so that EVs can be used as an important marker of liquid biopsy for disease diagnosis and prognosis. EVs are widely present in various body fluids, among which, urine is easy to obtain in large amount through non-invasive methods and has a small dynamic range of proteins, so it is a good object for studying EVs. However, most of the current isolation and detection of EVs still use traditional methods, which are of low purity, time consuming, and poor efficiency; therefore, more efficient and highly selective techniques are urgently needed. Recently, inspired by the nanoscale of EVs, platforms based on nanomaterials have been innovatively explored for isolation and detection of EVs from body fluids. These newly developed nanotechnologies, with higher selectivity and sensitivity, greatly improve the precision of isolation target EVs from urine. This review focuses on the nanomaterials used in isolation and detection of urinary EVs, discusses the advantages and disadvantages between traditional methods and nanomaterials-based platforms, and presents urinary EV-derived biomarkers for prostate cancer (PCa) diagnosis. We aim to provide a reference for researchers who want to carry out studies about nanomaterial-based platforms to identify urinary EVs, and we hope to summarize the biomarkers in downstream analysis of urinary EVs for auxiliary diagnosis of PCa disease in detail.
PubMed: 35096890
DOI: 10.3389/fmed.2021.800889 -
American Journal of Translational... 2024Liquid biopsy is an innovative approach that provides a more complete understanding of treatment response and prognosis in monitoring metastatic prostate cancer. It... (Review)
Review
Liquid biopsy is an innovative approach that provides a more complete understanding of treatment response and prognosis in monitoring metastatic prostate cancer. It complements invasive tissue biopsy and involves the assessment of various biomarkers in body fluids such as blood, semen, and urine. Liquid biopsy analyzes circulating tumor cells, extracellular vesicles, circulating tumor DNA, and the secretome. This is particularly important given the heterogeneity of prostate cancer and the need for better prognostic biomarkers. Liquid biopsy can personalize the treatment of homonosensitive and castration-resistant metastatic prostate cancer by acting as a predictive and prognostic tool. This review discusses various biomarkers, assay techniques, and potential applications in daily clinical practice, highlighting the exciting possibilities that this emerging field holds for improving patient outcomes.
PubMed: 38883349
DOI: 10.62347/DICU9510 -
International Journal of Molecular... Dec 2021Increasing evidence suggests that tumor development requires not only oncogene/tumor suppressor mutations to drive the growth, survival, and metastasis but also... (Review)
Review
Increasing evidence suggests that tumor development requires not only oncogene/tumor suppressor mutations to drive the growth, survival, and metastasis but also metabolic adaptations to meet the increasing energy demand for rapid cellular expansion and to cope with the often nutritional and oxygen-deprived microenvironment. One well-recognized strategy is to shift the metabolic flow from oxidative phosphorylation (OXPHOS) or respiration in mitochondria to glycolysis or fermentation in cytosol, known as Warburg effects. However, not all cancer cells follow this paradigm. In the development of prostate cancer, OXPHOS actually increases as compared to normal prostate tissue. This is because normal prostate epithelial cells divert citrate in mitochondria for the TCA cycle to the cytosol for secretion into seminal fluid. The sustained level of OXPHOS in primary tumors persists in progression to an advanced stage. As such, targeting OXPHOS and mitochondrial activities in general present therapeutic opportunities. In this review, we summarize the recent findings of the key regulators of the OXPHOS pathway in prostate cancer, ranging from transcriptional regulation, metabolic regulation to genetic regulation. Moreover, we provided a comprehensive update of the current status of OXPHOS inhibitors for prostate cancer therapy. A challenge of developing OXPHOS inhibitors is to selectively target cancer mitochondria and spare normal counterparts, which is also discussed.
Topics: Antineoplastic Agents; Citric Acid Cycle; Drug Delivery Systems; Humans; Male; Mitochondria; Oxidative Phosphorylation; Prostatic Neoplasms; Signal Transduction
PubMed: 34948229
DOI: 10.3390/ijms222413435 -
Frontiers in Immunology 2021Numerous types of viruses have been found in human semen, which raises concerns about the sexual transmission of these viruses. The overall effect of semen on viral...
Numerous types of viruses have been found in human semen, which raises concerns about the sexual transmission of these viruses. The overall effect of semen on viral infection and transmission have yet to be fully investigated. In the present study, we aimed at the effect of seminal plasma (SP) on viral infection by focusing on the mumps viral (MuV) infection of HeLa cells. MuV efficiently infected HeLa cells . MuV infection was strongly inhibited by the pre-treatment of viruses with SP. SP inhibited MuV infection through the impairment of the virus's attachment to cells. The antiviral activity of SP was resistant to the treatment of SP with boiling water, Proteinase K, RNase A, and DNase I, suggesting that the antiviral factor would not be proteins and nucleic acids. PNGase or PLA2 treatments did not abrogate the antiviral effect of SP against MuV. Further, we showed that the prostatic fluid (PF) showed similar inhibition as SP, whereas the epididymal fluid and seminal vesicle extract did not inhibit MuV infection. Both SP and PF also inhibited MuV infection of other cell types, including another human cervical carcinoma cell line C33a, mouse primary epididymal epithelial cells, and Sertoli cell line 15P1. Moreover, this inhibitory effect was not specific to MuV, as the herpes simplex virus 1, dengue virus 2, and adenovirus 5 infections were also inhibited by SP and PF. Our findings suggest that SP contains a prostate-derived pan-antiviral factor that may limit the sexual transmission of various viruses.
Topics: Animals; Antiviral Agents; Cell Line, Tumor; Cells, Cultured; Chlorocebus aethiops; Epithelial Cells; HeLa Cells; Host-Pathogen Interactions; Humans; Male; Mice, Inbred C57BL; Mumps virus; Semen; Vero Cells; Viruses; Mice
PubMed: 33679733
DOI: 10.3389/fimmu.2021.580454 -
Translational Research : the Journal of... Nov 2018Liquid biopsies examine tumor cells or tumor genomic content in circulating fluids. In advanced prostate cancer which metastasizes frequently to the bone, it is... (Review)
Review
Liquid biopsies examine tumor cells or tumor genomic content in circulating fluids. In advanced prostate cancer which metastasizes frequently to the bone, it is difficult to evaluate underlying and evolving genomic heterogeneity of skeletal metastases for effecting clinical care for which reason liquid biopsies offer an alternate approach. In this review, we will summarize the current state of a wide variety of liquid biopsy-based biomarker assays currently being investigated and developed for managing prostate cancer. We will also highlight technical and clinical challenges and opportunities for translating liquid biopsies into clinical applications.
Topics: Biomarkers; Cell-Free Nucleic Acids; Humans; Liquid Biopsy; Male; Neoplasm Staging; Neoplastic Cells, Circulating; Prostatic Neoplasms
PubMed: 29936077
DOI: 10.1016/j.trsl.2018.05.004 -
PloS One 2015Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in...
BACKGROUND
Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood.
METHODS/PRINCIPAL FINDINGS
We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests.
CONCLUSIONS
Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs.
Topics: Antibodies, Monoclonal; Endothelial Cells; Epididymis; Epitope Mapping; Humans; Lung; Male; Peptidyl-Dipeptidase A; Prostate; Semen
PubMed: 26600189
DOI: 10.1371/journal.pone.0143455 -
Frontiers in Oncology 2017Prostate cancer (PCa) is one of the most frequently diagnosed cancer among men in the western societies. Many PCa patients bear tumors that will not threat their lives... (Review)
Review
Prostate cancer (PCa) is one of the most frequently diagnosed cancer among men in the western societies. Many PCa patients bear tumors that will not threat their lives if left untreated or if treatment is delayed. Our inability for early identification of these patients has resulted in massive overtreatment. Therefore, there is a great need of finding biomarkers for patient stratification according to prognostic risk; as well as there is a need for novel targets that can allow the development of effective treatments for patients that progress to castration-resistant PCa. Most biomarkers in cancer are proteins, including the widely-used prostate-specific antigen (PSA). Recent developments in mass spectrometry allow the identification and quantification of thousands of proteins and posttranslational modifications from small amounts of biological material, including formalin-fixed paraffin-embedded tissues, and biological fluids. Novel diagnostic and prognostic biomarkers have been identified in tissue, blood, urine, and seminal plasma of PCa patients, and new insights in the ethology and progression of this disease have been achieved using this technology. In this review, we summarize these findings and discuss the potential of this technology to pave the way toward the clinical implementation of precision medicine in PCa.
PubMed: 29164064
DOI: 10.3389/fonc.2017.00267