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.

Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates the anticancer and immunomodulatory potential of skimmianine in breast cancer through a comprehensive approach, integrating biochemical, histopathological, immunohistochemical, and bioinformatics analyses. Methods: Thirty-six female Wistar albino rats were divided into three groups: control, 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer, and DMBA + skimmianine (n = 12/group). Breast cancer was induced with a single oral dose of 50 mg/kg DMBA in sesame oil. After 16 weeks, skimmianine (40 mg/kg) was administered intraperitoneally for four weeks. Serum CA15-3 levels were measured via enzyme-linked immunosorbent assay (ELISA). Histopathological assessment was performed using hematoxylin and eosin (H&E) staining, and proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) were evaluated immunohistochemically. Pathway and hub gene analyses were performed using Cytoscape, functional annotation with Enrichr, and immune analyses via the Tumor and Immune System Interaction Database (TISIDB) and Sangerbox. Results: The tumor burden in the animals increased after DMBA induction compared to the control groups (0.00 ± 0.00% vs. 89.00 ± 6.60%, respectively, p < 0.001), while skimmianine treatment significantly reduced the tumor burden in the animals (49.00 ± 9.40%, vs. DMBA group, p = 0.191). Histopathological analysis showed DMBA-induced structural disorganization and malignant clustering, whereas skimmianine preserved ductal structures and mitigated the damage. Compared to the control group, DMBA administration markedly elevated serum CA15-3 levels (0.23 ± 0.06 ng/mL vs. 8.57 ± 1.01 ng/mL, respectively), along with PCNA (13.0 ± 3.0% vs. 25.0 ± 4.0%, respectively) and TNF-α (8.4 ± 1.7% vs. 34.0 ± 5.3%, respectively) expression, indicating active tumor progression. Skimmianine treatment significantly reduced CA15-3 (3.72 ± 0.58 ng/mL), PCNA (20.0 ± 4.1%), and TNF-α (25.0 ± 3.9%) levels (p < 0.001). In silico analyses indicated skimmianine’s effects on PCNA influence cell cycle pathways, while TNF-α suppression impacts toll-like receptor (TLR) signaling (adjusted p < 0.05). PCNA- and TNF-α-related anticancer effects were especially notable in basal molecular and C2 immune subtypes (p < 0.05). Related hub proteins may regulate immune dynamics by reducing immunosuppression and tumor-promoting inflammation (p < 0.05). Conclusions: Skimmianine shows promise as a breast cancer therapy by simultaneously targeting tumor growth and immune regulation, with PCNA and TNF-α identified as potential key players.

Background: Peripheral nerve injuries frequently result in incomplete recovery despite advances in microsurgical repair. Both pharmacological and rehabilitative strategies have been investigated to enhance regeneration. Dexamethasone, a potent anti-inflammatory corticosteroid, and aerobic exercise, such as swimming, may promote repair through distinct but complementary mechanisms. Methods: A standardized rat sciatic nerve crush model was used to evaluate the effects of local dexamethasone administration (2 mg/kg/day, perineural for 10 days), swimming exercise (20 min/session, three times per week for 21 days), and their combination. Functional recovery was assessed by the Sciatic Functional Index (SFI), oxidative stress by MDA, GPX, and MPO assays, and structural recovery by histological, MBP immunohistochemical, and TEM analyses. Results: The injury group exhibited markedly elevated MDA and MPO levels and reduced GPX activity, indicating oxidative stress. Both dexamethasone and swimming exercise significantly improved these parameters, while the combination group showed values approaching controls (p < 0.001 for all comparisons vs. injury). Histological and immunohistochemical findings confirmed greater myelin preservation and higher MBP expression in treated groups, particularly in the combination group, whose g-ratio and myelin thickness were statistically indistinguishable from controls. SFI analysis revealed progressive motor improvement, with the combination therapy achieving near-normal function by day 28. Conclusions: This study demonstrates that dexamethasone and swimming exercise each contribute to peripheral nerve recovery and that their combined application provides additive benefits in terms of functional, biochemical, and structural regeneration. These results are limited to the specific dose and exercise regimen tested but support the potential of integrating anti-inflammatory pharmacotherapy with controlled physical exercise as a multimodal approach to enhance peripheral nerve repair.