Nibrin, encoded by the NBN gene, participates in DNA repair. Mutations in the NBN gene lead to Nijemen breakage syndrome, which may result in several types of diseases, particularly susceptibility to cancer, including breast cancer. Polymorphic variants and defective mutations occurring in the NBN gene increase the risk of breast cancer through the double-stranded break repair mechanism. The aim of the present study was to investigate a possible association between breast cancer and NBN genetic variants, NBN 924 T>C, 8360 G>C and 30537 G>C, in women with breast cancer. Locus-specific primers were designed to study 3 genetic variants in DNA samples isolated from peripheral blood samples of 101 women with breast cancer and 115 healthy controls. Subsequently, 3 polymerase chain reaction-restriction fragment length polymorphism methods were performed and the obtained results were statistically analysed. The NBN gene 924 T>C variant was found to be significantly associated with breast cancer (χ2=5.722, P=0.017). There were no statistically significant differences between cases and controls in the NBN gene 8360 G>C variant (χ2=1,125, P=0.570) or the NBN gene 30537 G>C variant (χ2=4.301, P=0.116). In conclusion, the NBN gene 924 T>C variant may be a genetic risk factor for breast cancer development in women with breast cancer.

Background: In the last decade, there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases. Nigella sativa (N. sativa, family Ranunculaceae) is one of these plants that has attracted considerable interest. The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases, including cancer. Methods: The selection criteria for references were applied through Pubmed with “N. sativa and cancer”, “N. sativa and breast cancer”, “N. sativa and metastasis”, “N. sativa and cytotoxicity of natural killer cells”. The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes (Cyclin D1, P53, p21 protein (Cdc42/Rac) activated kinase 1 (PAK1), B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF)) in order to elucidate further potentially affected signaling pathways. Results: The aim of this review was to summarize studies regarding the effects of N. sativa in cancer generally, with a focus on breast cancer, its anti-metastatic effects, and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance. Conclusion: In summary, the data suggest that N. sativa might be used for its anti-cancer and antimetastatic properties and as an immune system activator against cancer.

This study aimed to investigate the antioxidant effect of Ellagic acid (EA) on wound healing in sodium hydroxide (NaOH)-induced corrosive esophageal burn injury. The interaction networks and functional annotations were conducted using Cytoscape software. A total of 24 Wistar albino rats were divided into control, corrosive esophageal burn (CEB) and CEB + EA groups. Burn injury was created by 20% NaOH and 30 mg/kg EA was per oral administered to rats. At the end of the 28-day experimental period, Malondialdehyde (MDA) content was measured. Esophageal tissue samples were processed for histological staining. The EA–target interaction network was revealed to be involved in regulating crucial cellular mechanisms for burn wound healing, with epidermal growth factor (EGF) identified as a central mediator. An increase in animal weight in the CEB + EA group was observed in the EA-treated group after CEB injury. Burn injury increased MDA content, but EA treatment decreased its level after CEB injury. Stenosis index, collagen degeneration, inflammation, fibrosis and necrosis levels were increased after CEB injury. EA treatment improved histopathology in the CEB + EA group compared to the CEB group. The expression of EGF was decreased in the CEB group but upregulated in the EA-treated group, suggesting a potential involvement of EA in cellular processes and tissue regeneration. EA, through its antioxidative and tissue regenerative properties, significantly contributes to alleviating the adverse effects of CEB injury, promoting wound healing.

The aim of this study was to investigate the antioxidant and anti-inflammatory effects of skimmianine on cerebral ischemia–reperfusion (IR) injury. Twenty-four female Wistar albino rats were randomly divided into three groups: Sham, Ischemia–Reperfusion (IR), and IR + Skimmianine (40 mg/kg Skimmianine). Cerebral ischemia was induced using a monofilament nylon suture to occlude the middle cerebral artery for 60 min. Following 23 h of reperfusion, the animals were sacrificed 14 days later. The effects of skimmianine on brain tissue post-IR injury were examined through biochemical and immunochemical analyses. In silico analysis using the Enrichr platform explored skimmianine’s potential biological processes involving IBA-1, IL-6, and NF-κB proteins. In the IR group, MDA levels increased, while SOD and CAT antioxidant enzyme activities decreased. In the IR + Skimmianine group, skimmianine treatment resulted in decreased MDA levels and increased SOD and CAT activities. Significant increases in IBA-1 expression were observed in the IR group, which skimmianine treatment significantly reduced, modulating microglial activation. High levels of IL-6 expression were noted in pyramidal neurons, vascular structures, and neuroglial cells in the IR group; skimmianine treatment reduced IL-6 expression, demonstrating anti-inflammatory effects. Increased NF-κB expression was observed in neurons and blood vessels in the gray and white matter in the IR group; skimmianine treatment reduced NF-κB expression. Gene Ontology results suggest skimmianine impacts immune and inflammatory responses via IBA-1 and IL-6, with potential effects on estrogen mechanisms mediated by NF-κB. Skimmianine may be a potential therapeutic strategy due to its antioxidant and anti-inflammatory effects on cerebral IR injury.

This study investigated the effects of zonisamide treatment on cerebellar tissues in an experimental alcohol addiction (AA) model and its potential mechanisms of action, particularly regarding apoptotic protease activating factor-1 (APAF-1) and tumor necrosis factor-alpha (TNF-α) expression. Thirty rats were divided into three groups: sham, ethanol (EtOH), and EtOH + zonisamide. AA was induced by administering 6 cc of EtOH orally every 8 h for 4 days. Zonisamide (100 mg/kg) was given to rats once daily before EtOH administration. Motor defects were evaluated using an open field maze. Serum TNF-α levels were measured from blood samples. Cerebellar sections were processed for histological examination and immunostained for APAF-1 and TNF-α. Protein interaction networks were constructed using Cytoscape, and functional annotations were performed with ShinyGO (version 0.80) software. The traveled area in the EtOH group was significantly reduced compared to the sham group (p = 0.0005). Rats in the EtOH + zonisamide group covered a larger area, with zonisamide treatment significantly improving locomotor ability compared to the EtOH group (p = 0.0463). Serum TNF-α levels were significantly elevated in the EtOH group compared to the sham group (p < 0.0001) and were significantly decreased in the EtOH + zonisamide group compared to the EtOH group (p = 0.0309). Regular cerebellar histological layers were observed in the sham group, while EtOH induction caused loss of cerebellar tissue integrity, neuronal degeneration, vascular dilatation and congestion, reduced myelin density, and neuropils in the EtOH group. Zonisamide treatment improved these pathologies, enhancing myelination and neuropil formation. Negative APAF-1 and TNF-α expressions were observed across cerebellar layers in the sham group. Due to EtOH toxicity, APAF-1 and TNF-α expression were upregulated in the EtOH group compared to the sham group (p < 0.001 for both). Zonisamide treatment downregulated these protein expressions in the EtOH + zonisamide group compared to the EtOH group (p < 0.001 and p = 0.0087, respectively). APAF-1 was primarily associated with AA through antifolate resistance, endopeptidases, and the interleukin-1 pathway, while TNF-α was predominantly enriched in infections and choline-binding, indicating zonisamide’s impact on immune and inflammatory pathways. In conclusion, zonisamide treatment significantly mitigated ethanol-induced cerebellar damage and inflammation in an AA model. Zonisamide improved locomotor function and reduced serum TNF-α levels, as well as APAF-1 and TNF-α expression in cerebellar tissues. These findings suggest that zonisamide exerts its protective effects by modulating immune and inflammatory pathways, thereby preserving cerebellar integrity and function.