Prognostic Significance of Notch-4, SATB-2, and Glutaminase-1 in Colorectal Adenocarcinoma

Background: Neurogenic locus notch homology 4 (Notch-4) is crucial in maintaining stem cells. Special AT-rich sequence-binding protein 2 (SATB-2) is a transcription factor that binds to the nuclear matrix and serves various functions, including brain development. Glutaminase-1 (GLS-1) plays a pivotal role in cancer cell metabolism, growth, and proliferation. This study aims to assess the expression of these markers in colorectal cancer, establishing correlations with clinicopathological characteristics and patient survival.Method: In this retrospective study, we retrieved and analyzed 68 formalin-fixed, paraffin-embedded blocks of primary colorectal adenocarcinoma, not otherwise specified cases, and adjacent normal mucosa. Notch-4, SATB-2 and GLS-1 expressions were analyzed using immunohistochemistry at the Zagazig School of Medicine, Egypt.Results: High expressions of Notch-4 and GLS-1 and low expression of SATB-2 were observed in colonic adenocarcinoma but not in adjacent non-neoplastic mucosa (P < 0.001). High expressions of Notch-4 and GLS-1, along with low expression of SATB-2, were associated with a higher tumor grade, advanced stage (P < 0.001), lymphovascular invasion, lymph node metastasis, and poor disease-free survival and overall survival rates (P < 0.001).Conclusion: High expression of Notch-4 and GLS-1 is correlated with a poor prognosis in colorectal cancer, while high expression of SATB-2 is associated with a favorable prognosis for colorectal carcinoma. These markers can aid in predicting tumor prognosis and guiding targeted therapy for colorectal carcinoma

Betanin improves motor function and alleviates experimental Parkinsonism via downregulation of TLR4/MyD88/NF-κB pathway: Molecular docking and biological investigations

Parkinson’s disease (PD) is a progressive neuroinflammatory and degenerative disease. In this study, we investigated the neuroprotective action of betanin in the rotenone-induced Parkinson-like mice model. Twenty-eight adult male Swiss albino mice were divided into four groups: Vehicle, Rotenone, Rotenone + Betanin 50 mg/kg, and Rotenone + Betanin 100 mg/kg. Parkinsonism was induced by subcutaneous injection of 9 doses of rotenone (1 mg/kg/48 h) plus betanin at 50 and 100 mg/kg/48 h in rotenone + betanin groups for twenty days. Motor dysfunction was assessed after the end of the therapeutic period using the pole, rotarod, open-field, grid, and cylinder tests. Malondialdehyde, reduced glutathione (GSH), Toll-like receptor 4 (TLR4), myeloid differentiation primary response-88 (MyD88), nuclear factor kappa- B (NF-κB), neuronal degeneration in the striatum were evaluated. In addition, we assessed the immunohistochemical densities of tyrosine hydroxylase (TH) in Str and in substantia nigra compacta (SNpc). Our results showed that rotenone remarkably decreased (results of tests), increased decreased TH density with a significant increase in MDA, TLR4, MyD88, NF-κB, and a decrease in GSH (p < 0.05). Treatment with betanin significantly results of tests), increased TH density. Furthermore, betanin significantly downregulated malondialdehyde and improved GSH. Additionally, the expression of TLR4, MyD88, and NF-κB was significantly alleviated. Betanin’s powerful antioxidative and anti-inflammatory properties can be related to its neuroprotective potential as well as its ability to delay or prevent neurodegeneration in PD