-
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 -
Proteins Feb 2024Iroquois Homeobox 4 (IRX4) belongs to a family of homeobox TFs having roles in embryogenesis, cell specification, and organ development. Recently, large scale...
Iroquois Homeobox 4 (IRX4) belongs to a family of homeobox TFs having roles in embryogenesis, cell specification, and organ development. Recently, large scale genome-wide association studies and epigenetic studies have highlighted the role of IRX4 and its associated variants in prostate cancer. No studies have investigated and characterized the structural aspect of the IRX4 homeodomain and its potential to bind to DNA. The current study uses sequence analysis, homology modeling, and molecular dynamics simulations to explore IRX4 homeodomain-DNA recognition mechanisms and the role of somatic mutations affecting these interactions. Using publicly available databases, gene expression of IRX4 was found in different tissues, including prostate, heart, skin, vagina, and the protein expression was found in cancer cell lines (HCT166, HEK293), B cells, ascitic fluid, and brain. Sequence conservation of the homeodomain shed light on the importance of N- and C-terminal residues involved in DNA binding. The specificity of IRX4 homodimer bound to consensus human DNA sequence was confirmed by molecular dynamics simulations, representing the role of conserved amino acids including R145, A194, N195, S190, R198, and R199 in binding to DNA. Additional N-terminal residues like T144 and G143 were also found to have specific interactions highlighting the importance of N-terminus of the homeodomain in DNA recognition. Additionally, the effects of somatic mutations, including the conserved Arginine (R145, R198, and R199) residues on DNA binding elucidated the importance of these residues in stabilizing the protein-DNA complex. Secondary structure and hydrogen bonding analysis showed the roles of specific residues (R145, T191, A194, N195, R198, and R199) in maintaining the homogeneity of the structure and its interaction with DNA. The differences in relative binding free energies of all the mutants shed light on the structural modularity of this protein and the dynamics behind protein-DNA interaction. We also have predicted that the C-terminal sequence of the IRX4 homeodomain could act as a potential cell-penetrating peptide, emphasizing the role these small peptides could play in targeting homeobox TFs.
Topics: Male; Humans; Transcription Factors; Homeodomain Proteins; Genome-Wide Association Study; HEK293 Cells
PubMed: 37861198
DOI: 10.1002/prot.26604 -
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 -
Analytica Chimica Acta Oct 2023Detecting cancer biomarker levels in body fluids is essential for medical diagnosis. Enzyme-linked immunosorbent assay (ELISA) has been broadly used to detect cancer...
BACKGROUND
Detecting cancer biomarker levels in body fluids is essential for medical diagnosis. Enzyme-linked immunosorbent assay (ELISA) has been broadly used to detect cancer biomarkers. However, colorimetric ELISA based solely on nanoparticles (NPs) are susceptible to environmental influences, which often results in the detection inaccuracy, being limited in clinical applications. In this regard, the dual-mode approach would add signal diversity to the detection, making the results more reliable.
RESULTS
We present colorimetric and photothermal immunosensor that enables direct reading of the color and temperature of the solution. A core-satellite nanoprobe constructed by polydopamine (PDA) as the core and gold seeds as satellites is rationally designed as the signal reporter. When ascorbic acid is present in the solution, PDA can cooperate with ascorbic acid to reduce chloroauric acid and mediate the growth of gold seeds on the PDA surface, inducing a redshift of the localized surface plasmon resonance peak of the nanosensor and the change in photothermal conversion efficiency. The method is further combined with the sandwiched immunoassay to construct an alkaline phosphatase based colorimetric and photothermal ELISA for the highly sensitive and accurate evaluation and detection of prostate-specific antigen (PSA). The linear range was from 0.05 to 100 ng mL with a detection limit of 6.71 pg mL for the colorimetric detection, while the linear range was from 0.5 to 90 ng mL with a detection limit of 0.13 ng mL in the photothermal analysis. The accurate detection of PSA levels in serum samples was well demonstrated with the dual-mode approach.
SIGNIFICANCE
The presented immunoassay allows straightforward, sensitive, and selective readout by color and temperature without advanced instrumentation. Particularly, the LOD was much lower than the threshold in clinical trials for PSA. Therefore, this method has a great prospect in the early diagnosis of cancer biomarkers based on a dual-mode multifunctional platform.
Topics: Male; Humans; Prostate-Specific Antigen; Biomarkers, Tumor; Gold; Biosensing Techniques; Immunoassay; Colorimetry; Neoplasms; Ascorbic Acid; Metal Nanoparticles; Limit of Detection
PubMed: 37827632
DOI: 10.1016/j.aca.2023.341775 -
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 -
Practical Radiation Oncology 2024The aim of this study was to evaluate the application of a radiopaque viscous spacer (RVS) for prostate cancer radiation therapy (RT), including injection procedure,...
PURPOSE
The aim of this study was to evaluate the application of a radiopaque viscous spacer (RVS) for prostate cancer radiation therapy (RT), including injection procedure, toxicity, treatment planning, image guidance, and imaging results up to 12 months after RT.
METHODS AND MATERIALS
RVS (median, 10 mL) was injected between prostate and rectal wall in 30 patients. Cone beam computed tomography (CT) was performed during the course of RT, a magnetic resonance imaging 3 and 12 months after RT. Injection and treatment tolerability were analyzed. The resulting distribution was compared with a control group of 30 patients with an initially fluid spacer.
RESULTS
Procedure- or device-related adverse events were not observed. Signs of hydrogel migration were not found in any case. The volume decreased by 25% at 3 months after RT, and small residues were detected at 12 months after RT in 3 cases (10%). The median rectal volume percentage within the 90% isodose was 3.0% (interquartile range, 1.5%-4.5%). Acute and late gastrointestinal toxicities were found in 17% and 3%, respectively (all grade 1). The median distance between prostate and rectum at the base/midplane/apex was greater for RVS in comparison to initially fluid spacer (14/12/11 mm vs 12/10/10 mm, respectively), the gel symmetry (right vs left from midline) was comparable. The application was assessed to be easier to control by the users, and visibility in cone beam CT as good.
CONCLUSIONS
The injection of a radiopaque viscous hydrogel spacer resulted in a prostate-rectum distance of >10 mm in most cases. The resulting rectum volume within the high-dose region and RT toxicity were very low. Advantages in comparison to the conventional hydrogel spacer are predominantly an improved placement control during the injection process and good visibility on CT.
Topics: Male; Humans; Prostate; Hydrogels; Prospective Studies; Prostatic Neoplasms; Radiotherapy Dosage; Rectum
PubMed: 37791943
DOI: 10.1016/j.prro.2023.05.013 -
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