Objective To investigate the protective effect of berberine on acute hypoxia induced by sodium nitrite (NaNO2) in mice.MethodsThe animal model of acute hypoxia was established with NaNO2. Then the mice were treated with berberine by gavage in three different doses of 2.0 mg/kg, 4.0 mg/kg, and 8.0 mg/kg once everyday respectively for 6 days. The survival time according to the last breath, the breath time and open mouth times of animals were recorded. The superoxide dismutase (SOD), maleic dialdehyde (MDA), nitric oxide (NO) and lactic dehydrogenase (LDH) in brain tissue were tested. The pathological change was examined by HE staining.ResultsBerberine could significantly prolong the living time of acute hypoxia mice induced by NaNO2 and breath time after decapitation ( P<0.05, P<0.01), increase the activity of SOD and LDH, decrease the content of MDA and NO in brain tissue of hypoxia mice ( P<0.05, P<0.01). Under microscope, there were meningorrhagia, cellular necrosis in brain tissues of model animals, but no pathological changes found in berberine-treated animals.ConclusionBerberine has certain protective effect on acute hypoxia induced by NaNO2 in mice.

N1-methyladenosine(m1A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels.Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.

Cancer stem cell-like cells (CSCs) play an integral role in the heterogeneity, metastasis, and treatment resistance of head and neck squamous cell carcinoma (HNSCC) due to their high tumor initiation capacity and plasticity. Here, we identified a candidate gene named LIMP-2 as a novel therapeutic target regulating HNSCC progression and CSC properties. The high expression of LIMP-2 in HNSCC patients suggested a poor prognosis and potential immunotherapy resistance. Functionally, LIMP-2 can facilitate autolysosome formation to promote autophagic flux. LIMP-2 knockdown inhibits autophagic flux and reduces the tumorigenic ability of HNSCC. Further mechanistic studies suggest that enhanced autophagy helps HNSCC maintain stemness and promotes degradation of GSK3β, which in turn facilitates nuclear translocation of β-catenin and transcription of downstream target genes. In conclusion, this study reveals LIMP-2 as a novel prospective therapeutic target for HNSCC and provides evidence for a link between autophagy, CSC, and immunotherapy resistance.
Humans ; Autophagy ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Glycogen Synthase Kinase 3 beta/metabolism* ; Head and Neck Neoplasms/pathology* ; Neoplastic Stem Cells/pathology* ; Squamous Cell Carcinoma of Head and Neck/pathology* ; Lysosome-Associated Membrane Glycoproteins