Cell Journal最新文献

Objective: This study aimed to develop a hybrid model for variable selection in high-dimensional survival analysis using a support vector regression (SVR), to identify prognostic biomarkers associated with survival in oral cancer (OC) patients through the analysis of gene expression data.

Materials and methods: In this retrospective cohort study, gene expression profiles (54,613 probes) related to 97 patients from the GSE41613 dataset from the GEO repository were used. First of all, martingale residuals were obtained using a Cox regression without covariates, and were used as pseudo-survival outcome. Then, the particle swarm optimization (PSO) and genetic algorithm (GA) were used in combination with SVR for selecting features related to pseudo-survival outcome. Concordance index (C-index), mean absolute error (MAE), mean squared error (MSE) and R-squares, were used to evaluate the performance of the models using selected features. Functional enrichment analysis was performed using DAVID database, and external validation utilized three independent datasets (GSE9844, GSE75538, GSE37991, GSE42743).

Results: The findings indicated that the PSO-based method outperformed the GA-based method, achieving a smaller MAE (0.061) and MSE (0.005), R-square (0.99) and C-index (0.973), selecting 291 probes from 1069 screened. A protein-protein interaction (PPI) network was constructed, including 200 nodes and 120 edges. Eleven key genes with the highest degree, including RBM25, SMC3, PRPF40A, POLE, SRRT, BCLAF1, PDS5B, HNRNPR, JAK1, MED23, and SULT1A1 were identified as significant biomarkers associated with OC survival.

Conclusion: The PSO-based hybrid model effectively improved SVR performance in survival prediction for OC patients and identified key prognostic biomarkers. Despite its promising results and validation on independent datasets, limitations in generalizability and signs of overfitting suggest the model is not yet ready for clinical use. Further studies with larger, diverse datasets are recommended.

Objective: The accumulation of amyloid plaques and disturbance of cholesterol homeostasis are implicated in the pathophysiology of Alzheimer's disease. Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) are key proteins involved in the efflux and metabolism of excess cholesterol, and small non-coding RNAs (miRNAs), can help to regulate the expression of the genes encoding these proteins. The aim of the present study was to investigate the alterations in the expression of APOE and CYP46A1 genes, as well as their respective regulatory miRNAs, in astrocytes treated with amyloid beta (Aβ).

Materials and methods: 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.

Results: The expression of APOE and CYP46A1 genes increased with Aβ treatment. MiR-33a-5p, as the negative regulator of the APOE gene exhibited significant decrease. Additionally, miR-let-7a-5p, as the positive regulator of the APOE gene, showed an increase in the Aβ treated group. Moreover, miR-98-5p, as the negative regulator of the CYP46A1 gene, showed a half-fold decrease. While, miR-27a-3p as the positive regulator of the CYP46A1 gene, increased significantly with Aβ treatment.

Conclusion: Alterations in the expression of APOE and CYP46A1 genes, as well as the expression of miRNAs regulating these genes, in astrocytes treated with Aβ suggests that the cell is attempting to modify the regulatory pathways of cholesterol homeostasis in the brain under pathological conditions, such as Alzheimer's disease.

Objective: 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.

Materials and methods: 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).

Results: 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.

Conclusion: 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.

Objective: 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 Alginate-coated Gold Nanoparticles (TAuNPs) for early prostate cancer diagnosis through molecular CT imaging.

Materials and methods: 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.

Results: 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.

Conclusion: 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 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.

Objective: Spermatogonial stem cell transplantation (SSCT) could be a helpful strategy for fertility restoration in patients with childhood cancer. Additionally, using metformin as an antioxidant may help mitigate damage caused by chemotherapy. This study aimed to evaluate the protective effects of metformin against oxidative stress caused by busulfan and cadmiuminduced damage while examining its role in enhancing spermatogenesis restoration following SSCT.

Materials and methods: In this experimental study, a long-term infertility mouse model was created using cadmium and busulfan treatment (BC, n=10). Cryopreserved SSCs were transplanted either alone (cryo+SSCT, n=10) or in combination with metformin (cryo+MET+SSCT, n=10). These experimental groups were compared to a control group (n=10). Flow cytometry was used to assess the protective effect of metformin against reactive oxygen species (ROS) production, and immunofluorescence evaluated proliferation and differentiation markers.

Results: The results of our study showed that ROS production decreased significantly in the cryopreservation group with metformin (P<0.05). The expression of proliferation and differentiation markers after transplantation was significantly increased in the cryopreservation group with metformin compared to the cryopreservation group containing a basic freezing medium (P<0.05).

Conclusion: Transplantation of SSCs combined with metformin significantly enhances spermatogenesis and improves the homing efficiency of transplanted SSCs. This approach holds great potential for restoring fertility in clinical settings, particularly in childhood cancer survivors.

Objective: This study aims to investigate the effects of sodium hydrogen sulphide (NaHS) supplementation, a hydrogen sulphide (H2S) donor, on oxidant and antioxidant markers, as well as sperm function in rats with experimentally induced varicocele.

Materials and methods: In this experimental study, 55 male Wistar rats were assigned to varicocele (n=25), control (n=20), and sham (n=10) groups. In the varicocele group, five rats received NaHS treatment immediately after surgery for four months and ten rats were treated two to four months after surgery. The remaining ten rats in the varicocele group received no treatment. Similar protocols were followed for the control groups. At the end of four months, all rats were sacrificed, and assessments were made for sperm parameters that included function tests, and testicular malondialdehyde (MDA) and total antioxidant capacity (TAC).

Results: Varicocele induction significantly impaired sperm parameters and sperm function tests. NaHS treatment for two months increased sperm concentrations, while treatment for two and four months improved motility, chromatin status, and intracellular reactive oxygen species (ROS) compared to untreated varicocele rats. After four months, NaHS treatment reduced testicular MDA levels. Testicular TAC significantly increased after two months but decreased after four months of treatment in the varicocele group (P<0.05).

Conclusion: NaHS treatment improved sperm parameters and reduced oxidative stress in varicocele rats. The observed effects depended on the treatment duration.

Objective: High glucose (HG)-induced oxidative stress is a metabolic stimulus for hepatic impairment in diabetes. Natural phytochemicals may alleviate HG-induced complications. We aimed to examine the impact of citronellol (CT) on oxidative stress and inflammation in the human hepatocellular liver carcinoma (HepG2) cell line under HG conditions.

Materials and methods: In this experimental study, the HepG2 cells were exposed to HG concentrations of 50 mM and co-treated with or without CT at concentrations of 10, 20, and 40 μg/ml for 48 hours. The impact of treatments on the levels of malondialdehyde (MDA), glutathione (GSH), and the enzyme's activity of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) was explored. We used quantitative reverse transcription polymerase chain reaction (qRTPCR) to evaluate the gene expression of nuclear factor-κβ (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and dipeptidyl peptidase-4 (DPP-4).

Results: Co-treatment with CT (20 and 40 μg/ml) significantly reduced (P<0.05) HG-induced cell death (9.73 and 10.56%, respectively) and MDA production (16 and 26.78%, respectively) compared to untreated HG control group. Meanwhile, CT (10, 20, and 40 μg/ml) substantially increased (P<0.05) GSH content (35.61, 55.24, and 69.75%, respectively), GPx (48.32, 61.75, and 75.10%, respectively), and CAT activity (20.25, 25.09, 30.16%, respectively) dose-dependently comparison to untreated ones. TNF-α and IL-6 gene expression were also modulated significantly (P<0.05) by 40 μg/ml CT (47.75 and 32.44%, respectively) as compared to the HG control group. Moreover, CT at 20 and 40 μg/ml attenuated (P<0.05) NF-κB gene expression (30.41 and 39.93%, respectively), and at all doses, made a considerable reduction (P<0.05) in DPP-4 gene expression (18.77, 18.78, and 44.61%, respectively) dose-dependently comparison to untreated ones.

Conclusion: Our research suggested that CT with greater effectiveness at 40 μg/ml might shield hepatocytes exposed to HG by lowering oxidative stress and inhibiting inflammatory reactions; however, more research is needed.

Endometriosis, a benign gynecological disorder affecting 10-15% of women during their reproductive years, is characterized by the growth of endometrial tissue outside the uterus. Despite its prevalence, the exact pathophysiology of this disease remains poorly understood. Current treatments, including surgery and hormonal therapies, often have limited efficacy and may be associated with significant side effects. In recent years, drug repurposing has emerged as a promising strategy for managing endometriosis. This approach capitalizes on the molecular similarities between endometriosis and certain cancers, particularly the role of proteins such as fibronectin. By targeting these shared molecular pathways, researchers are exploring the potential of repurposing existing drugs, especially anticancer agents, to treat endometriosis. This strategy promises to provide more effective and less invasive treatment options for patients with endometriosis. Preliminary studies have shown the potential of anticancer drugs in inhibiting disease progression and alleviating symptoms. However, further clinical trials are necessary to confirm these findings and establish the precise role of anticancer drugs in the management of endometriosis.