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Life (Basel, Switzerland) Dec 2023Resistin is an adipokine with metabolic and inflammatory functions. Epidemiological and translational studies report that an increase in plasma levels and tissue...
Resistin is an adipokine with metabolic and inflammatory functions. Epidemiological and translational studies report that an increase in plasma levels and tissue expression of resistin increases the aggressiveness of prostate tumor cells. Extracellular vesicles (EVs) are secreted constitutively and induced by cytokines, growth factors, and calcium and are found in multiple biological fluids such as saliva, serum, semen, and urine. In particular, EVs have been shown to promote tumor progression through the induction of proliferation, growth, angiogenesis, resistance to chemotherapy, and metastasis. However, the role of resistin in the migration, invasion, and secretion of EVs in invasive prostate tumor cells remains to be studied. In the present study, we demonstrate that resistin induces increased migration and invasion in PC3 cells. In addition, these phenomena are accompanied by increased p-FAK levels and increased secretion of MMP-2 and MMP-9 in resistin-treated PC3 cells. Interestingly, EVs isolated from supernatants of PC3 cells treated with resistin induce an increase in migration and invasion accompanied by high MMP-2 and MMP-9 secretion in an autocrine stimulation model. In summary, our data for the first time demonstrate that resistin induces migration and invasion, partly through the secretion of EVs with pro-invasive characteristics in PC3 cells.
PubMed: 38137922
DOI: 10.3390/life13122321 -
Frontiers in Pharmacology 2023Chronic Bacterial Prostatitis (CBP) is inflammation of the prostate caused by bacterial infection. An estimated 8.2% of men have prostatitis, most commonly under the...
Chronic Bacterial Prostatitis (CBP) is inflammation of the prostate caused by bacterial infection. An estimated 8.2% of men have prostatitis, most commonly under the age of 50. Antibiotics often fail to treat CBP due to presence of bacterial biofilms and rising antibiotic resistance of pathogenic bacterial strains. The multidrug resistant (MDR) bacterial strains often implicated in cases of CBP include Extended Spectrum Beta Lactam resistant , Vancomycin resistant Enterococci, Gram-positive bacterial strains like Staphylococci and Streptococci, Enterobacteriaceae like and , and . CBP patients experience significant deterioration in quality of life, with impact on mental health comparable with patients of diabetes mellitus and chronic heart failure, leading patients to explore alternatives like phage therapy. We present the case of a patient diagnosed with and exhibiting typical symptoms of CBP. Tests of the prostatic and seminal fluids identified as the causative pathogen. The patient did not experience favourable long-term treatment outcomes despite repeated antibiotic courses administered over 5 years. This led him to seek phage therapy for treatment of his condition. The cultured strain of was tested against bacteriophage preparations developed by the Eliava Institute, Georgia. Preparations showing lytic activity against the strain were used for the patient's treatment at the Eliava Phage Therapy Center (EPTC). The patient underwent two courses of treatment with the EPTC. The first treatment course resulted in significant symptomatic improvement, followed by complete resolution of symptoms post the second course of phage therapy. Samples tested during treatment showed declining bacterial growth, corresponding with symptomatic improvement. Post-treatment cultures had no growth of pathogenic bacteria. This case illustrates the efficacy of bacteriophages in treating CBP, a condition that is often resistant to antibiotic therapies. Antibiotics such as ofloxacin, Fosfomycin, trimethoprim, nitrofurantoin and ceftriaxone were administered in multiple courses over 5 years, but the infection recurred after each course. After two courses of phage therapy, the patient experienced long-term symptom resolution and substantial reduction in bacterial load. Increasing numbers of such cases globally warrant further research into the potential for bacteriophages for treating MDR and chronic infections.
PubMed: 37790805
DOI: 10.3389/fphar.2023.1243824 -
Translational Andrology and Urology Nov 2023Lymphoceles, lymph fluid-filled collections within the body lacking epithelial lining, are a common complication after pelvic lymph node dissection (PLND) during...
BACKGROUND
Lymphoceles, lymph fluid-filled collections within the body lacking epithelial lining, are a common complication after pelvic lymph node dissection (PLND) during robot-assisted radical prostatectomy (RARP). In this study, we investigate the incidence of imaging confirmed symptomatic lymphoceles (SLC) in a centralized high-volume operating centre and assess predictive factors and treatment.
METHODS
We retrospectively analysed the incidence, risk factors and treatment of a consecutive series of patients who underwent PLND during RARP between September 2018 and January 2021 in a specialised operation clinic. We compared baseline patients' characteristics and pathological data between men who developed an SLC and those who did not. A multivariable model for the occurrence of an SLC was created using predetermined, clinically relevant variables to investigate predictive factors.
RESULTS
We analysed the records of 404 patients. The median follow-up length was 29 months. A total of 30 (7.4%) patients with an SLC were identified. The median time until SLC presentation was 12 weeks [interquartile range (IQR), 4-31 weeks], one-third of SLCs presented after 180 days. Percutaneous drainage was performed in 17 patients (57%). On multivariable analysis, only body mass index (BMI) significantly increased the odds of an SLC [per 5 odds ratio (OR) =1.7; 95% confidence interval (CI): 1.0-3.0, P=0.04].
CONCLUSIONS
SLCs present significant consequences, as more than half of patients with an SLC were treated with percutaneous drainage. Many patients presented later than the centralized surgeons' postoperative follow-up, a drawback of centralized care. An increased BMI was a significant predictor for SLC.
PubMed: 38106676
DOI: 10.21037/tau-23-416 -
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 -
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 -
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 -
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 -
Global Spine Journal Jul 2023Systematic Review and Meta-analysis. (Review)
Review
STUDY DESIGN
Systematic Review and Meta-analysis.
OBJECTIVE
Postoperative urinary retention (POUR) is a common complication following lumbar spine surgery (LSS) and timely recognition is imperative to avoid long-term consequences. The aim of the current meta-analysis was to systematically review the literature in order to identify risk factors associated with POUR after LSS.
METHODS
In accordance with PRISMA guidelines, a systematic review of the literature was performed using Pubmed, EMBASE, and MEDLINE database for articles on POUR following LSS. A meta-analysis was performed comparing patients with and without POUR; and the factors associated with this adverse event were analyzed. The pooled data were reported as mean differences with 95% confidence intervals (CI; < .05). Heterogeneity among the studies was evaluated using the I statistic.
RESULTS
The meta-analysis included 10 studies compromised of 30,300 patients. Based on our analysis, patients who were male, were older in age, underwent instrumented fusion, had diabetes mellitus, coronary artery disease, or benign prostatic hypertrophy had significantly higher risk of developing POUR. Additionally, patients in who developed POUR had significantly longer surgical times and higher volumes of intra-operative fluid administration, as compared with non-POUR patients. The POUR patients also had a significantly higher association with urinary tract infection. Prior surgery, BMI, length of stay, and smoking status did not reveal any statistical association with POUR.
CONCLUSIONS
Risk factors associated with POUR following LSS include male gender, older age, longer surgical times, fusion procedures, larger volumes of intraoperative infusions, and associated comorbidities like DM, CAD, and BPH.
PubMed: 36562179
DOI: 10.1177/21925682221146493 -
Neurology(R) Neuroimmunology &... Jul 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical,...
OBJECTIVES
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical, MRI, immunopathology, and treatment response in a person with MOGAD and melanoma.
METHODS
This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center.
RESULTS
A 52-year-old man presented with progressive encephalomyelitis that led to identification of metastatic melanoma. Investigations revealed positive MOG-IgG at high titers in serum (1:1,000; normal, <1:20) and CSF (1:4,096; normal, <1:2). MRI demonstrated multifocal T2 lesions with enhancement in the brain and spine. Brain biopsy showed demyelination and inflammation. MOG immunostaining was not present in the tumor tissue. He initially improved with methylprednisolone, plasmapheresis, prolonged oral steroid taper, and cancer-directed treatment with BRAF and MEK 1/2 inhibitors, but then developed bilateral optic neuritis. IV immunoglobulin (IVIG) was initiated. Five months later, he developed metastases and immune checkpoint inhibitor (ICI) treatment was started, which precipitated optic neuritis and myelitis despite IVIG and prednisone. Tocilizumab, an interleukin-6 receptor blocker, was started with excellent and sustained clinical and radiologic response.
DISCUSSION
This case revealed a presentation of MOGAD concurrent with melanoma without tumor MOG immunostaining. We highlight tocilizumab as a dual-purpose treatment of MOGAD and the neurologic immune-related adverse effect of ICI.
Topics: Humans; Male; Melanoma; Middle Aged; Myelin-Oligodendrocyte Glycoprotein; Immune Checkpoint Inhibitors; Autoantibodies; Demyelinating Autoimmune Diseases, CNS
PubMed: 38696737
DOI: 10.1212/NXI.0000000000200249 -
Journal of Cancer Research and Clinical... Jul 2023Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal...
PURPOSE
Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal cells, and have great potential to be used as markers for disease initiation, progression, and response to treatment. This under-utilised tool provides insights into a better understanding of prostate cancer.
METHODS
EV from serum and urine of healthy men and castration-resistant prostate cancer (CRPC) patients were isolated and characterised by transmission electron microscopy, particle size analysis, and western blot. Proteomic and cholesterol liquid chromatography-mass spectrometry (LC-MS) analyses were conducted.
RESULTS
There was a successful enrichment of small EV/exosomes isolated from serum and urine. EV derived from biological fluids of CRPC patients had significant differences in composition when compared with those from healthy controls. Analysis of matched serum and urine samples from six prostate cancer patients revealed specific EV proteins common in both types of biological fluid for each patient.
CONCLUSION
Some of the EV proteins identified from our analyses have potential to be used as CRPC markers. These markers may depict a pattern in cancer progression through non-invasive sample collection.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Proteomics; Extracellular Vesicles; Exosomes; Body Fluids
PubMed: 36222898
DOI: 10.1007/s00432-022-04391-6