-
Journal of Nanobiotechnology May 2024Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic...
Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.
Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.
Topics: Animals; Humans; Male; Mice; Dual-Specificity Phosphatases; Epithelial Cells; Exosomes; Inflammation; MAP Kinase Signaling System; MicroRNAs; Pelvic Pain; Prostate; Prostatitis; Stromal Cells; Chemokine CCL2
PubMed: 38724995
DOI: 10.1186/s12951-024-02513-5 -
Ecotoxicology and Environmental Safety Jun 2024Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of...
Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of light on metabolism, we studied Sprague-Dawley rats chronically exposed to red or blue light during daytime or nighttime. Rats in the experimental group were exposed to extended light for 4 hours during daytime or nighttime to simulate the effects of excessive light usage. Strikingly, we found systemic metabolic alterations only induced by blue light during daytime. Furthermore, we conducted metabolomic analyses of the cerebrospinal fluid, serum, heart, liver, spleen, adrenal, cerebellum, pituitary, prostate, spermatophore, hypothalamus and kidney from rats in the control and blue light exposure during daytime. Significant changes in metabolites have been observed in cerebrospinal fluid, serum, hypothalamus and kidney of rats exposed to blue light during daytime. Metabolic alterations observed in rats encompassing pyruvate metabolism, glutathione metabolism homocysteine degradation, phosphatidylethanolamine biosynthesis, and phospholipid biosynthesis, exhibit analogous patterns to those inherent in specific physiological processes, notably neurodevelopment, cellular injury, oxidative stress, and autophagic pathways. Our study provides insights into tissue-specific metabolic changes in rats exposed to blue light during the daytime and may help explain potential mechanisms of photopathogenesis.
Topics: Animals; Rats, Sprague-Dawley; Male; Light; Rats; Circadian Rhythm; Metabolomics; Oxidative Stress; Kidney; Blue Light
PubMed: 38723383
DOI: 10.1016/j.ecoenv.2024.116436 -
American Journal of Translational... 2024Osteoporosis (OP) stands as a prevalent bone ailment affecting the elderly, globally. The identification of reliable diagnostic markers crucially aids OP clinical...
BACKGROUND
Osteoporosis (OP) stands as a prevalent bone ailment affecting the elderly, globally. The identification of reliable diagnostic markers crucially aids OP clinical management.
METHODS
Utilizing the GEO database (GSE35959), we acquired expression profiles for OP and normal samples. Differential expression genes (DEGs) and hub genes were pinpointed through STRING, GEO2R, and Cytoscape. The competing endogenous RNA (ceRNA) network was constructed using miRTarBase, miRDB, and MiRcode databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed via DAVID. Validation involved clinical OP samples from the Pakistani population, with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) assessing hub gene expression.
RESULTS
A total of 2124 differentially expressed genes (DEGs) were identified between OP and normal samples in GSE35959. The selected hub genes among these DEGs were Splicing Factor 3a Subunit 1 (SF3A1), Ataxin 2 Like (ATXN2L), Heat Shock Protein 90 Beta Family Member 1 (HSP90B1), Cluster of Differentiation 74 (CD74), DExH-Box Helicase 29 (DHX29), ALG5 Dolichyl-Phosphate Beta-Glucosyltransferase (ALG5), NudC Domain Containing 2 (NUDCD2), and Ras-related protein Rab-2A (RAB2A). Expression validation of these genes on the Pakistani OP patients revealed significant up-regulation of SF3A1, ATXN2L, and CD74 and significant (P < 0.05) down-regulation of HSP90B1, DHX29, ALG5, NUDCD2, and RAB2A in OP patients. Receiver operating characteristic (ROC) analysis demonstrated that these hub genes displayed considerable diagnostic accuracy for detecting OP. The ceRNA network analysis of the hub genes revealed some important hub genes' regulatory miRNAs and lncRNAs. Via KEGG analysis, hub genes were found to be enriched in N-Glycan biosynthesis, Thyroid hormone synthesis, IL-17 signaling pathway, Prostate cancer, AMPK signaling pathway, Spliceosome, Estrogen signaling pathway, and Fluid shear stress and atherosclerosis, etc., pathways.
CONCLUSION
The identified eight hub genes in the present study could reliably distinguish OP patients from normal individuals, which may provide novel insight into the diagnostic research of OP.
PubMed: 38715824
DOI: 10.62347/TAYD3318 -
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 -
Current Problems in Diagnostic Radiology Apr 2024Seminal vesicles play a crucial role in the male reproductive system, as they are responsible for secreting a fluid that forms most of the ejaculate. Seminal vesicles'... (Review)
Review
Seminal vesicles play a crucial role in the male reproductive system, as they are responsible for secreting a fluid that forms most of the ejaculate. Seminal vesicles' pathology can present with non-specific symptoms, making imaging diagnosis essential for proper patient management. Various imaging modalities can be used to evaluate these glands, with MRI beneficial in illustrating the spectrum of seminal vesicle disease. Typical seminal vesicles appear as elongated fluid-containing structures, but congenital anomalies, inflammatory conditions, and neoplastic disorders can alter their appearance. Furthermore, differentiating mimics from actual pathology can be challenging but crucial for proper management. This article aims to provide an overview of the typical imaging appearance of the seminal vesicles and illustrate the principal imaging characteristics of conditions involving these structures. It will review the imaging characteristics of common and uncommon lesions involving the seminal vesicles by exploring congenital, infectious, and neoplastic in detail. As the seminal vesicles are often evaluated incidentally during prostate imaging, radiologists should be aware of the variability of normal findings and recognize the principal pathologies affecting these structures to ensure proper patient management.
PubMed: 38692935
DOI: 10.1067/j.cpradiol.2024.04.006 -
Frontiers in Endocrinology 2024Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA).... (Review)
Review
Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.
Topics: Humans; Male; Sperm Retrieval; Azoospermia; Biomarkers; Infertility, Male; Semen; Spermatogenesis
PubMed: 38689732
DOI: 10.3389/fendo.2024.1349000 -
Veterinary Radiology & Ultrasound : the... Apr 2024Canine prostatic carcinoma (PC) has incompletely defined CT features. The purpose of this multicenter retrospective case series was to assess prostatic, regional, and...
Canine prostatic carcinoma (PC) has incompletely defined CT features. The purpose of this multicenter retrospective case series was to assess prostatic, regional, and distant findings of PC. Thirty dogs were enrolled. Consistent prostatic features included postcontrast heterogeneity with hypoattenuating, nonenhancing areas (30/30), capsular distortion (29/30), prostatic urethral effacement, displacement, or invasion (28/30), precontrast heterogeneity (27/30), and mineralization (24/30) which was always within or at the margin of the hypoattenuating areas. Consistent extraprostatic features included medial iliac lymph node enlargement (20/30), internal iliac lymph node enlargement (15/30), and periprostatic fat streaking or fluid (15/29). In a minority of dogs, there was lymph node mineralization, bladder trigone invasion, ureteral dilation, ductus deferens invasion, and bony changes consistent with hypertrophic osteopathy. Strongly suspected and potential bony metastases were noted infrequently (8/26), all in vertebrae regional to the prostate. In conclusion, these findings provide guidance on the expected CT features of canine PC.
PubMed: 38687009
DOI: 10.1111/vru.13375 -
G3 (Bethesda, Md.) Apr 2024The Drosophila melanogaster male accessory gland is a functional analog of the mammalian prostate and seminal vesicles containing two secretory epithelial cell types,...
The Drosophila melanogaster male accessory gland is a functional analog of the mammalian prostate and seminal vesicles containing two secretory epithelial cell types, termed main and secondary cells. This tissue is responsible for making and secreting seminal fluid proteins and other molecules that contribute to successful reproduction. The cells of this tissue are bi-nucleate and polyploid, due to variant cell cycles that include endomitosis and endocycling during metamorphosis. Here we provide evidence of additional cell cycle variants in this tissue. We show that main cells of the gland are connected by ring canals that form after the penultimate mitosis and we describe an additional post-eclosion endocycle required for gland maturation that is dependent on juvenile hormone signaling. We present evidence that the main cells of the Drosophila melanogaster accessory gland undergo a unique cell cycle reprogramming throughout organ development that results in step-wise cell cycle truncations culminating in cells containing two octoploid nuclei with under-replicated heterochromatin in the mature gland. We propose this tissue as a model to study developmental and hormonal temporal control of cell cycle variants in terminally differentiating tissues.
PubMed: 38683731
DOI: 10.1093/g3journal/jkae089 -
Pharmaceutics Mar 2024Enzalutamide (ENZ), marketed under the brand name Xtandi as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for...
Enzalutamide (ENZ), marketed under the brand name Xtandi as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.
PubMed: 38675118
DOI: 10.3390/pharmaceutics16040457 -
BioRxiv : the Preprint Server For... Apr 2024During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling...
During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations - including large populations of macrophages, dendritic cells, T cells, and NKT cells - which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.
PubMed: 38645090
DOI: 10.1101/2024.04.08.588538