Therapeutic radiation of the pelvic region has been shown to cause damage to testicular germ cells. In this study we aimed to evaluate the effects of a low therapeutic dose of 1 Gy on the induction of cellular and histological damage in early-stage testicular germ cells and the impact of this radiation on offspring sex ratio. Unirradiated and irradiated male rats were mated with unirradiated female rats. Female rats were followed and the sex of the offspring was determined. The male rats were sacrificed at the end of the second week, and the testicular germ cells were subjected to genetic analysis along with cytological and histopathological examination. Sperm DNA was amplified with primers specific to testis-specific Y-linked protein, rat actin beta and testis-specific X-linked genes. The resulting products were separated by capillary electrophoresis. Histopathological changes were investigated by light microscopy along with the TUNEL assay and immunohistochemical staining for caspase-3. There was no significant difference between the two groups for sex ratio and size of offspring. The number of sperm cells bearing X or Y chromosomes’ did not differ significantly between these two groups. However, a 1 Gy dose of radiation caused significant cytopathological and histopathological changes in the testicular tissue. In the irradiated group, edematous regions were evident. The number of caspase-3 positive cells in the germinal epithelium of the seminiferous tubules was also significantly higher in the irradiated group. Our results showed that low-dose radiation induced apoptosis and caused significant cyto- and histopathological changes in the testicular tissue. Further research is required to fully elucidate their contribution to apoptosis and if low-dose radiation may potentially lead to long-term effects in the offspring. These results may also lead us to develop a new technique using the caspase-3 staining to monitor the susceptibility to low dose radiation.

Background/Objectives: Cancer is the second leading cause of death globally. Medicinal plants have emerged as fundamental sources of bioactive compounds with anticancer potential, largely attributed to their diverse secondary metabolites. This study aimed to investigate the cytotoxic effects of Helichrysum arenarium extracts from two distinct regions of Turkiye, Mersin, and Artvin, on cancerous (MDA-MB-231, RT4, T98G) and non-cancerous (ARPE-19, hGF) cell lines and to identify bioactive compounds responsible for these effects. Methods: H. arenarium plant extracts were prepared using ethanol and methanol as solvents, followed by lyophilization and dissolution in DMSO. The cytotoxic effects of the extracts were evaluated using Hoechst staining and MTS assays to assess cell viability. IC50 values and selectivity indices were calculated. Phytochemical composition was analyzed using Quadrupole Time-of-Flight mass spectrometry. Results: The ethanol extract from Mersin (HAE-M) demonstrated superior cytotoxicity, particularly against breast and bladder cancer cells, while showing minimal impact on non-cancerous cells. HAM-M, HAE-A, and HAM-A exhibited comparatively less potent effects. Phytochemical analysis of HAE-M identified 16 bioactive compounds, including Naringenin, Luteolin, and Quercitrin, known for their antioxidant and anticancer properties. Conclusions: These findings highlight the potential of H. arenarium extracts, particularly HAE-M, as a source of potent anticancer agents. This study is novel in its comprehensive analysis of different extraction methods and regional plant sources, combined with phytochemical profiling, to identify selective anticancer effects. Further investigations into the mechanisms of action of these extracts could contribute to the development of plant-derived anticancer therapies.

Improving the chemotherapy sensitivity of bladder cancer is a current clinical challenge. It is critical to seek out effective combination therapies that include low doses of cisplatin due to its dose-limiting toxicity. This study aims to investigate the cytotoxic effects of the combination therapy including proTAME, a small molecule inhibitor, targeting Cdc-20 and to determine the expression levels of several APC/C pathway-related genes that may play a role in the chemotherapy response of RT-4 (bladder cancer) and ARPE-19 (normal epithelial) cells. The IC20 and IC50 values were determined by MTS assay. The expression levels of apoptosis-associated (Bax and Bcl-2) and APC/C-associated (Cdc-20, Cyclin-B1, Securin, and Cdh-1) genes were assessed by qRT-PCR. Cell colonization ability and apoptosis were examined by clonogenic survival experiment and Annexin V/PI staining, respectively. Low-dose combination therapy showed a superior inhibition effect on RT-4 cells by increasing cell death and inhibiting colony formation. Triple-agent combination therapy further increased the percentage of late apoptotic and necrotic cells compared to the doublet-therapy with gemcitabine and cisplatin. ProTAME-containing combination therapies resulted in an elevation in Bax/Bcl-2 ratio in RT-4 cells, while a significant decrease was observed in proTAME-treated ARPE-19 cells. Cdc-20 expression in proTAME combined treatment groups were found to be decreased compared to their control groups. Low-dose triple-agent combination induced cytotoxicity and apoptosis in RT-4 cells effectively. It is essential to evaluate the role of APC/C pathway-associated potential biomarkers as therapeutic targets and define new combination therapy regimens to achieve improved tolerability in bladder cancer patients in the future.

Background: Controversial effect of sortilin on lipoprotein metabolism in the development of atherosclerosis reveals the need for more extensive researchObjectives: The aim of this study was to investigate the association between Sort1 gene expression and lipids, lipoprotein subfractions, and inflammation in CAD.Methods: The study population included 162 subjects with CAD and 49 healthy individuals. The Sort1 gene expression level was determined by qRT-PCR using Human Sortilin TaqMan Gene Expression Assays. Lipoprotein subclasses were analysed by the Lipoprint system. Serum levels of apolipoprotein and CRP were measured by autoanalyzer.Results: Sort1 gene expression and atherogenic subfraction (SdLDL) levels were significantly higher (p < 0.001) while atheroprotective subfraction (LbLDL) was lower in the subjects with CAD (p < 0.050). Also, increased Sort1 gene expression levels were observed in those with higher CRP values.Conclusions: Our findings reveal that the high Sort1 gene expression has a prominent linear relationship with both the atherogenic LDL phenotype and proinflammation, thereby might contribute to the occurrence of CAD.

In this study, La_0.25Fe_0.75FeO₃ (PNp)perovskite nanoparticle was synthesized using the sol–gel method. PNp-coated polyacrylonitrile (PAN) nanofibers were prepared by electrospinning on the pencil graphite electrode (PGE) surface. In another step, carcinoembryonic antigen (CEA) was loaded with CEA antibodies (Anti-CEA) as a biomarker receptor. Finally, PGE/PAN@PNp/Anti-CEA was used for CEA detection. Optimization steps and cell culture steps were performed using differential pulse voltammetry (DPV). The use of this composite system is a novel immunosensor development approach for label-free detection of CEA. Under optimum conditions, detection limit (LOD) of PGE/PAN@PNp/Anti-CEA immunosensor LOD 1.48 ng/mL, limit of quantification (LOQ) = 4.94 ng/mL, reproducibility 1.46% (n = 5) and R² = 0.9984 for antigen concentration within a linear working range of 0.1–10 ng/mL. Also, immunosensor recovery in real serum samples containing dopamine and ascorbic acid was found as 98.94 ± 7.43. It has great potential in clinical screening of different cancer biomarkers. The number of cells attached to the PGE/PAN@PNp/Anti-CEA/BSA(bovine serum)/CEA surface decreased in RT-4(bladder cancer), MDA-MB-231 (triple-negative breast adenocarcinoma cell line), and T98G cells (glioblastoma multiforme cell line), which are known as CEA-negative cell lines, whereas the number of MCF-7 cells (estrogen-sensitive human breast cancer cell line, known to be CEA positive) attached to the PGE/PAN@PNp/Anti-CEA/BSA/CEA surface increased, indicating higher affinity to the immunosensor surface. As a result, while MCF-7, which is CEA positive, can be determined best when using an immune-cytosensor, the cell that can be best determined with cytosensors was found to be RT-4.

Background: Acute myeloid leukemia (AML) is a malignancy characterized by the clonal expansion of hematopoietic stem and progenitor cells, often associated with mutations such as NPM1. DOT1L inhibitors have shown potential as new therapeutic opportunities for NPM1-mutant AML. The aim of this study was to investigate potential alternative targets of the small-molecule inhibitor EPZ004777, in addition to its primary target, DOT1L, using RNA sequencing data from the NCBI-GEO database (GSE85107). Methods: Differentially expressed genes (DEGs) were identified through bioinformatic analysis, followed by pathway enrichment analysis to uncover the relevant biological pathways. Additionally, molecular docking analysis was conducted to assess the binding affinity of EPZ004777 with the proteins CT45A3, HOXA4, SNX19, TPBG, and ZNF185, which were identified as significantly DEGs. The protein structures were obtained from AlphaFold and the Protein Data Bank. Results: EPZ004777 significantly altered gene expression. Oncofetal genes (CT45A3, TPBG) and genes associated with oncogenic pathways (HOXA4, ZNF185, SNX19) were downregulated, while the pro-apoptotic gene BEX3 was upregulated. Pathway enrichment analysis revealed the suppression of the Rap1 signaling pathway and cell adhesion molecules, which may reduce the invasiveness of AML cells. Additionally, upregulation of immune-related pathways suggests enhanced anti-tumor immune responses. Molecular docking analysis demonstrated that EPZ004777 has strong binding potential with SNX19, TPBG, and ZNF185 proteins. Conclusions: EPZ004777 has been identified as a potent modulator of SNX19, TPBG, and ZNF185 associated with apoptosis and tumor progression in AML.