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Journal of Vitreoretinal Diseases 2023To present a case of a chemotherapy regimen combining a fibroblast growth factor receptor (FGFR) and mitogen-activated protein kinase kinase (MEK) inhibitor leading to...
To present a case of a chemotherapy regimen combining a fibroblast growth factor receptor (FGFR) and mitogen-activated protein kinase kinase (MEK) inhibitor leading to serous retinopathy. A retrospective chart review of a single case was performed. A 67-year-old man with pancreatic and prostate cancer developed bilateral multifocal pockets of subretinal fluid while on an experimental chemotherapy regimen combining an MEK inhibitor (trametinib) and an FGFR inhibitor (erdafitinib). Given that FGFR lies upstream to the mitogen-activated protein kinase signaling pathway, retinal toxicity may be more severe and more common with FGFR-MEK combination therapy. Future studies are necessary to guide ophthalmic surveillance.
PubMed: 37927314
DOI: 10.1177/24741264231163393 -
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 -
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 -
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 -
The American Journal of Case Reports Oct 2023BACKGROUND Gelatinous pleural effusion, due to raised hyaluronic acid, can be associated with pleural infection and malignancies, such as tuberculosis, metastatic...
BACKGROUND Gelatinous pleural effusion, due to raised hyaluronic acid, can be associated with pleural infection and malignancies, such as tuberculosis, metastatic pleural disease, and mesothelioma. This report is of an 80-year-old man presenting with a gelatinous pleural effusion and diagnosis of pleural mesothelioma. CASE REPORT An 80-year-old man with diabetes mellitus, ischemic heart disease, metastatic prostate cancer, 30-pack-year smoking history, and 5-year history of asbestos exposure (during his 30s), presented with a 4-week history of breathlessness and was found to have right-sided pleural effusion. Thoracic computed tomography (CT) showed mild right-sided pleural thickening. Pleural tap revealed exudative fluid, with a pH of 7.4, and unremarkable cytology and microbiology analyses. The patient was treated for pneumonia and para-pneumonic effusion and discharged home. He came back 5 weeks later with worsening of symptoms and re-accumulation of pleural fluid. Repeated thorax CT showed extensive right-sided pleural lobular thickening. Pleural tap again yielded an exudative fluid, with a pH of 7.37. Cytology and microbiology did not reveal any positive signs for malignancy or infection. This time the pleural fluid appeared gelatinous in consistency. Pleural biopsy showed atypical epithelioid mesothelial cells arranged in trabeculae, with a tubulo-papillary configuration. Also, immunohistochemistry panel showed tumor cells expressed calretinin, EMA, WT1, and D2-40, with negative TTF1, CEA, and BerEp4. Final diagnosis was epithelioid mesothelioma. CONCLUSIONS This report has shown that a gelatinous pleural effusion can be associated with malignant and inflammatory pleural diseases. In this case, imaging and pleural biopsy with histopathology confirmed a diagnosis of pleural mesothelioma.
Topics: Male; Humans; Aged, 80 and over; Mesothelioma; Pleural Neoplasms; Pleural Effusion; Pleura; Asbestos; Pleural Diseases
PubMed: 37793939
DOI: 10.12659/AJCR.941263 -
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 -
Surgical Case Reports Sep 2023Thoracic duct cysts are extremely rare mediastinal tumors. We report a case of a thoracic duct cyst extending from the caudal aspect of the left main bronchus to the...
BACKGROUND
Thoracic duct cysts are extremely rare mediastinal tumors. We report a case of a thoracic duct cyst extending from the caudal aspect of the left main bronchus to the left renal artery that was safely and completely resected via bilateral thoracoscopic surgery in the prone position.
CASE PRESENTATION
A 77-year-old male was referred to our hospital for follow-up computed tomography (CT) of prostate cancer, which revealed a mediastinal tumor and fatty low-density along the posterior mediastinum of the para-aortic artery with a slightly high-density component. Magnetic resonance imaging revealed a T2-weighted image with high intensity. The preoperative radiological diagnosis was lipoma or well-differentiated liposarcoma. CT in the prone position suggested that the tumor could be resected from the thoracic cavity to the caudal side, and bilateral thoracoscopic surgery was performed in the prone position. Based on the surgical findings, the tumor was diagnosed as a thoracic duct cyst rather than a lipoma. Dissection around the thoracic duct cyst was performed using a vessel-sealing system to prevent leakage of the chyle, and reliable clipping was performed to resect the cisterna chyli. Histopathological examination revealed smooth muscle structures around the cyst, suggestive of a thoracic duct cyst. The diagnosis of a thoracic duct cyst was made based on a high triglyceride level of 1310 mg/dL on examination of the milky-white cyst fluid. The patient's postoperative course was uneventful, and he was discharged 4 days postoperatively. A CT scan performed 13 months after surgery showed no recurrence.
CONCLUSIONS
A rare thoracic duct cyst extending from the mediastinum to the cisterna chyli was safely and completely resected using bilateral thoracoscopic surgery, with the patient in the prone position.
PubMed: 37747542
DOI: 10.1186/s40792-023-01740-6 -
Biology of Reproduction Jan 2024Little is known about the non-neuronal spermic cholinergic system, which may regulate sperm motility and the acrosome reaction initiation process. We investigated the...
Little is known about the non-neuronal spermic cholinergic system, which may regulate sperm motility and the acrosome reaction initiation process. We investigated the presence of the key acetylcholine (ACh)-biosynthesizing enzyme, choline acetyltransferase (ChAT), and the acetylcholine-degrading enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and two ACh-receptors in human spermatozoa and seminal plasma. Fresh ejaculates were used for intra- and extracellular flow cytometric analysis of ChAT, AChE, BChE, and alpha-7-nicotinic and M1-muscarinic ACh-receptors in sperm. For determining the source of soluble enzymes, frozen seminal samples (n = 74) were selected on two bases: (1) from vasectomized (n = 37) and non-vasectomized (n = 37) subjects and (2) based on levels of alpha-glucosidase, fructose, or zinc to define sample subgroups with high or low fluid contribution from the epididymis and seminal vesicle, and prostate, respectively. Flow cytometric analyses revealed that ChAT was expressed intracellularly in essentially all spermatozoa. ChAT was also present in a readily membrane-detachable form at the extracellular membrane of at least 18% of the spermatozoa. These were also highly positive for intra- and extracellular BChE (>83%) and M1 (>84%) and α7 (>59%) ACh-receptors. Intriguingly, the sperm was negative for AChE. Analyses of seminal plasma revealed that spermatozoa and epididymides were major sources of soluble ChAT and BChE, whereas soluble AChE most likely originated from epididymides and seminal vesicles. Prostate had relatively minor contribution to the pool of the soluble enzymes in the seminal fluid. In conclusion, human spermatozoa exhibited a cholinergic phenotype and were one of the major sources of soluble ChAT and BChE in ejaculate. We also provide the first evidence for ChAT as an extracellularly membrane-anchored protein.
Topics: Humans; Male; Acetylcholinesterase; Acetylcholine; Butyrylcholinesterase; Semen; Sperm Motility; Spermatozoa; Cholinergic Agents
PubMed: 37741056
DOI: 10.1093/biolre/ioad127