Cell Journal (Yakhteh)
Volume:26 Issue: 11, Nov 2024

Nanocomplexes, as targeted contrast agents, have been developing for diagnostic imaging, especially in computed tomography (CT). The present study aimed to investigate a novel approach using Triptorelin-conjugated-coated Gold Nanoparticles (TAuNPs) for early prostate cancer diagnosis through molecular CT imaging. In the current experimental study, AuNPs and TAuNPs were synthesized and then characterized using transmission electron microscopy (TEM), fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS), and the AuNPs cytotoxicity and the cell viability were also assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The intensity of X-ray attenuation and contrast to noise ratio (CNR) for nontargeted and targeted nanoparticles were measured for tube voltages of 90.0, 120.0, and 140.0 kVp at different mAs, and the four different concentrations, including 25.0, 50.0, 75.0, and 100.0 μg/ml. The synthesized TAuNPs are non-toxic within the concentration range of 25-100 μg/ml, at tube potentials of 90.0, 120.0, and 140.0 kVp, and 145.0 as well as 266.0 mA. Also, the X-ray attenuation of targeted cells was 1.74, 2.23, and 2 times higher, respectively, than that of non-targeted cells for a concentration of 100 μg/ml. Furthermore, the CNR values for TAuNPs compared to AuNPs at tube potentials of 90.0, 120.0, and 140.0 kVp, and 266.0 mA, were 1.65, 3.35, and 2.57 c/ϭ, respectively. The current study demonstrates that synthesized TAuNPs are emerged as a contrast agent, which is targeted for molecular CT imaging of prostate cancer cells, expressing the gonadotropin-releasing hormone (GnRH) receptor.

The accumulation of amyloid plaques and disturbance of cholesterol homeostasis are implicated in thepathophysiology of Alzheimer’s disease. Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) are keyproteins involved in the efflux and metabolism of excess cholesterol, and small non-coding RNAs (miRNAs), can helpto regulate the expression of the genes encoding these proteins. The aim of the present study was to investigatethe alterations in the expression of APOE and CYP46A1 genes, as well as their respective regulatory miRNAs, inastrocytes treated with amyloid beta (Aβ). In this experimental study, isolated astrocyte cells were cultured and treated with Aβ for 24 hours. Changes in the expression of APOE and CYP46A1 genes, as well as their regulating miRNAs, were assessed using the realtime polymerase chain reaction (PCR) technique. The expression of APOE and CYP46A1 genes increased with Aβ treatment. MiR-33a-5p, as the negativeregulator of the APOE gene exhibited significant decrease. Additionally, miR-let-7a-5p, as the positive regulator ofthe APOE gene, showed an increase in the Aβ treated group. Moreover, miR-98-5p, as the negative regulator of theCYP46A1 gene, showed a half-fold decrease. While, miR-27a-3p as the positive regulator of the CYP46A1 gene,increased significantly with Aβ treatment. Alterations in the expression of APOE and CYP46A1 genes, as well as the expression of miRNAsregulating these genes, in astrocytes treated with Aβ suggests that the cell is attempting to modify the regulatorypathways of cholesterol homeostasis in the brain under pathological conditions, such as Alzheimer’s disease.

Granulosa cell tumor (GCT) is a sex cord-stromal rare malignancy; and is associated with infertility. Extracellular vesicles (EVs) are small secreted vesicles containing proteins, mRNA, and miRNA, therefore modulating signaling pathways potentially in recipient cells and in this way, they can help cancer spread through intercellular communication. In this research, the capability of ovarian cancer-derived EVs for inducing proliferation and metastasis in GCs is investigated. In the experimental study, EVs were isolated by ultracentrifugation from A2780 human ovarian cancer cell-conditioned. Mouse GCs were mechanically isolated from 8 female mice. ovarian cancer-derived EVs were then added to the GCs (experimental groups: untreated GCs (control group), GCs treated with concentrations of 10, 25, and 50 μg/ml), and cell viability, migration, apoptosis, and estrogen hormone measurements were assessed by MTT, scratch assay, propidium iodide (PI) staining, annexin-V-FITC/PI and ELISA assay respectively. Gene's expression of Amh, Foxl2, Gdf-9, and Igf-1r were determined using real-time polymerase chain reaction (PCR). GCs treated with ovarian cancer EVs indicate an increase in cell viability compared to the control cells (P<0.05). Also, ovarian cancer EVs showed an increase in the migration potency. The other results this experimental study showed that ovarian cancer EVs increase in the estrogen secretion level (P<0.001) and reduce the apoptosis of GCs compared to the control group. It is further showed that EVs isolated from ovarian cancer (A2780 cell line) can induce the RNA expression level of several genes in recipient GCs, such as Amh, Foxl2, and Igf-1r (P<0.01, P<0.001), respectively, while the RNA expression level of Gdf-9 gene was decreased in comparison with the control. To sum up, the research here provides a novel insight into the role of ovarian cancer EVs in proliferation and metastasis in GCs and prevention of infertility caused by granulosa cancer.

Isoflavones are phytoestrogen compounds that can regulate the growth of prostate cancer (PCa) cells. While most studies indicate phytoestrogens mediate their biological effects by activating estrogen receptors (ERs) ERα and ERβ, recent research suggests that they also activate the G-protein coupled ER (GPER). This study aimed to investigate the effects of genistein and daidzein on cell migration and invasion processes in LNCaP and PC3 human PCa cell lines. Furthermore, the role of GPER as a mediator of the effects of these two isoflavones was evaluated using the specific receptor antagonist G15. LNCaP and PC-3 were pre-treated with G15 (1 μM) before phytoestrogens (50 μM) treatments. Following treatment, cell lines were cultured in Matrigel-uncoated Transwell inserts for migration assays and coated inserts for invasion assays. Treatments with genistein and daidzein significantly decrease cell migration and invasion in LNCaP and PC-3. Additionally, the GPER antagonist G15 suppresses the effects of genistein and daidzein, restoring the migratory and invasive capacities in both cell lines. Based on the results, we suggest that GPER regulates cell migration and invasion of LNCaP and PC-3 mediated by genistein and daidzein. Further research is needed to elucidate the signaling pathways involved to evaluate its role and potential as a therapeutic intervention target in PCa.

The potential application of extracellular vesicles (EVs) in regenerative and personalized medicine has attracted substantial interest in recent years, highlighting the need for standardized protocols for their administration in preclinical and clinical settings. EVs, which play critical roles in intercellular communication and have significant therapeutic potential, have prompted extensive research and advancements in their clinical applications. However, the rapid evolution of this field has also revealed variability in how EVs are isolated, characterized, and used across different studies. Over the past decade, organizations such as the International Society for Extracellular Vesicles (ISEV) and the International Society for Cell and Gene Therapy (ISCT) have actively worked to address these challenges by proposing frameworks for standardizing EV-related research. As the clinical evaluation of therapeutic EVs becomes increasingly commonplace, there is a need for practical guidelines and assessment tools that can aid in evaluating their efficacy and safety. In this context, we propose a comprehensive checklist designed to guide researchers and clinicians in considering critical aspects when designing and conducting biomedical and clinical studies involving EVs. This checklist aims to enhance the standardization of trials and therapeutic procedures, ensuring that clinical reports are prepared with adequate detail. By controlling reproducibility and transparency in research, we believe that our proposed guidelines will contribute significantly to advancing the application of EVs in clinical practice.