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PLoS Neglected Tropical Diseases Oct 2023Trichomonas vaginalis is a human infective parasite responsible for trichomoniasis-the most common, non-viral, sexually transmitted infection worldwide. T. vaginalis...
Trichomonas vaginalis is a human infective parasite responsible for trichomoniasis-the most common, non-viral, sexually transmitted infection worldwide. T. vaginalis resides exclusively in the urogenital tract of both men and women. In women, T. vaginalis has been found colonizing the cervix and vaginal tract while in men it has been identified in the upper and lower urogenital tract and in secreted fluids such as semen, urethral discharge, urine, and prostatic fluid. Despite the over 270 million cases of trichomoniasis annually worldwide, T. vaginalis continues to be a highly neglected organism and thus poorly studied. Here we have developed a male mouse model for studying T. vaginalis pathogenesis in vivo by delivering parasites into the murine urogenital tract (MUT) via transurethral catheterization. Parasite burden was assessed ex-vivo using a nanoluciferase-based gene expression assay which allowed quantification of parasites pre- and post-inoculation. Using this model and read-out approach, we show that T. vaginalis can be found within MUT tissue up to 72 hrs post-inoculation. Furthermore, we also demonstrate that parasites that exhibit increased parasite adherence in vitro also have higher parasite burden in mice in vivo. These data provide evidence that parasite adherence to host cells aids in parasite persistence in vivo and molecular determinants found to correlate with host cell adherence in vitro are applicable to infection in vivo. Finally, we show that co-inoculation of T. vaginalis extracellular vesicles (TvEVs) and parasites results in higher parasite burden in vivo. These findings confirm our previous in vitro-based predictions that TvEVs assist the parasite in colonizing the host. The establishment of this pathogenesis model for T. vaginalis sets the stage for identifying and examining parasite factors that contribute to and influence infection outcomes.
Topics: Male; Humans; Female; Animals; Mice; Trichomonas vaginalis; Parasites; Trichomonas Infections; Vagina; Extracellular Vesicles
PubMed: 37871037
DOI: 10.1371/journal.pntd.0011693 -
Brain Structure & Function Jul 2023The first report of corpora amylacea (CA) is attributed to Morgagni, who described them in the prostate in the eighteenth century. Nearly a hundred years later, and... (Review)
Review
The first report of corpora amylacea (CA) is attributed to Morgagni, who described them in the prostate in the eighteenth century. Nearly a hundred years later, and following the lead started by Purkinje, Virchow described them in the brain. He made a detailed description of the most useful techniques to visualize them, but he failed to describe the cause of why CA do appear, why they are mainly linked with the elderly, and which is their clinical significance. Although in the last two centuries CA have received little attention, recent data have been able to describe that CA accumulate waste products and that some of them can be found in the cerebrospinal fluid and lymphatic nodes, after being released from the brain. Indeed, CA have been renamed to wasteosomes to underline the waste products they gather and to avoid confusion with the term amyloid used by Virchow, now widely related to certain protein deposits found in the brain. Here, after providing a commented English translation of Virchow's findings, we provide a recent update on these structures and their connection with the glymphatic system insufficiency, for which wasteosomes should be considered a hallmark, and how these bodies could serve as diagnostic or prognostic markers of various brain conditions.
Topics: Male; Humans; Aged; Brain; Brain Diseases; Amyloid; Waste Products
PubMed: 37358661
DOI: 10.1007/s00429-023-02664-5 -
Biology Aug 2023Extracellular vesicles (EVs) include exosomes, microvesicles, and apoptotic bodies. EVs are released by all cell types and are found in biological fluids including... (Review)
Review
Extracellular vesicles (EVs) include exosomes, microvesicles, and apoptotic bodies. EVs are released by all cell types and are found in biological fluids including plasma and urine. Urinary extracellular vesicles (uEVs) are a mixed population of EVs that comprise small EVs that are filtered and excreted, EVs secreted by tubular epithelial cells, and EVs released from the bladder, urethra, and prostate. The packaged cargo within uEVs includes bioactive molecules such as metabolites, lipids, proteins, mRNAs, and miRNAs. These molecules are involved in intercellular communication, elicit changes in intracellular signaling pathways, and play a role in the pathogenesis of various diseases including diabetes-associated hypertension and diabetic nephropathy. uEVs represent a rich source of biomarkers, prognosis markers, and can be loaded with small-molecule drugs as a vehicle for delivery.
PubMed: 37627022
DOI: 10.3390/biology12081138 -
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 -
Tumour Biology : the Journal of the... 2024Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells... (Review)
Review
BACKGROUND
Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells can either directly synthesize or induce the synthesis of TMs, and the release of these molecules into the bloodstream allows their quantification in biological fluids. Although very small concentrations of TMs are usually present in the serum or plasma of healthy subjects, increased concentrations may also be found in the presence of benign diseases or due to technical interference, producing false positive results.
MATERIAL AND METHODS AND RESULTS
Our review analyses the causes of false positives described between January 1970 to February 2023 for the TMs most frequently used in clinical practice: α-fetoprotein (AFP), β2-microglobulin (β2-M), cancer antigen 15-3 (CA 15-3), cancer antigen CA 19-9 (CA 19-9), cancer antigen CA 72-4 (CA 72-4), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), chromogranin A (CgA), choriogonadotropin (hCG), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), human epididymis protein 4 (HE4), serum HER2 (sHER2), squamous cell carcinoma antigen (SCCA), protein induced by vitamin K absence-II (PIVKA-II), Pro-gastrin-releasing peptide (Pro-GRP), prostate-specific antigen (PSA), Protein S-100 (S-100) and thyroglobulin (Tg). A total of 247 references were included.
CONCLUSIONS
A better understanding of pathophysiological processes and other conditions that affect the concentration of TMs might improve the interpretation of results and their clinical application.
Topics: Male; Humans; Biomarkers, Tumor; Lung Neoplasms; Antigens, Neoplasm; Keratin-19; Carcinoembryonic Antigen; Prostate-Specific Antigen; Phosphopyruvate Hydratase; CA-125 Antigen
PubMed: 38517826
DOI: 10.3233/TUB-220023 -
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 -
Alternative Therapies in Health and... Mar 2024Diminished ovarian reserve (DOR) can lead to amenorrhea, infertility, and even the development of premature ovarian insufficiency, severely affecting the quality of life...
BACKGROUND
Diminished ovarian reserve (DOR) can lead to amenorrhea, infertility, and even the development of premature ovarian insufficiency, severely affecting the quality of life for women. Therefore, it is important to determine the main components of Tonifying Yang Formula, analyze the active substances and effective targets for treating DOR using Tonifying Yang Formula, and explore its potential mechanisms of action.
OBJECTIVE
The study is aim to determine the main components of Tonifying Yang Formula, analyze the active substances and effective targets for treating DOR using Tonifying Yang Formula, and explore its potential molecular mechanisms of action, providing important theoretical basis for clinical application.
METHODS
The main active components of Tonifying Yang Formula and their potential therapeutic targets for DOR were searched using the Chinese Medicine Systems Pharmacology Database and Analysis Platform, BATMAN-TCM, GeneCards, OMIM, and Uniprot databases. The protein-protein interaction network of shared targets between drugs and diseases was constructed using the STRING database. The shared targets of drugs and diseases were subjected to GO analysis and KEGG pathway enrichment analysis using the DAVID database. AutoDock Vina was used to perform molecular docking between the active substances and key targets of the drug to validate their interaction activities.
RESULTS
The key chemical components in the Tonifying Yang Formula for DOR treatment include quercetin, luteolin, beta-sitosterol, stigmasterol, and kaempferol. The 164 key targets for treating DOR with Tonifying Yang Formula included AKT1, TNF, JUN, TP53, IL6, IL1B, EGFR, VEGFA, INS, and CASP3, among others. GO enrichment analysis revealed that the Tonifying Yang Formula mainly regulates gene expression positively, negatively regulates the apoptotic process, and affects signal transduction. KEGG pathway enrichment analysis showed that Tonifying Yang Formula is mainly involved in cancer-related pathways, the AGE-RAGE signaling pathway in diabetic complications, prostate cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway. Molecular docking results indicated that the core components of the Tonifying Yang Formula had higher docking energies and stable binding with targets such as AKT1, IL6, JUN, TNF, and TP53. This study selected the PI3K/AKT signaling pathway for validation. Through experimental research, we found that Tonifying Yang Formula could improve ovarian reserve function by activating the PI3K/AKT signaling pathway.
CONCLUSIONS
The potential mechanism of Tonifying Yang Formula therapy for DOR may be related to the influence of Chinese herbal compounds on pathways such as AKT1, IL6, JUN, TNF, and TP53, regulating the proliferation and apoptosis of ovarian granulosa cells, maintaining the function of the ovarian corpus luteum, regulating the secretion of related hormones, and alleviating ovarian tissue inflammation.
Topics: Female; Humans; Drugs, Chinese Herbal; Network Pharmacology; Ovarian Reserve; Molecular Docking Simulation; Protein Interaction Maps
PubMed: 37883761
DOI: No ID Found -
Biomedicines Dec 2023Prostate cancer is among the top five cancer types according to incidence and mortality. One of the main obstacles in prostate cancer management is the inability to... (Review)
Review
Prostate cancer is among the top five cancer types according to incidence and mortality. One of the main obstacles in prostate cancer management is the inability to foresee its course, which ranges from slow growth throughout years that requires minimum or no intervention to highly aggressive disease that spreads quickly and resists treatment. Therefore, it is not surprising that numerous studies have attempted to find biomarkers of prostate cancer occurrence, risk stratification, therapy response, and patient outcome. However, only a few prostate cancer biomarkers are used in clinics, which shows how difficult it is to find a novel biomarker. Cell adhesion to the extracellular matrix (ECM) through integrins is among the essential processes that govern its fate. Upon activation and ligation, integrins form multi-protein intracellular structures called integrin adhesion complexes (IACs). In this review article, the focus is put on the biomarker potential of the ECM- and IAC-related molecules stemming from both body fluids and prostate cancer tissue. The processes that they are involved in, such as tumor stiffening, bone turnover, and communication via exosomes, and their biomarker potential are also reviewed.
PubMed: 38255186
DOI: 10.3390/biomedicines12010079