Anhui Medical University

Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function. Cystine-glutamate transporter SLC7A11 is essential for maintaining cellular redox homeostasis and resisting ferroptosis. However, the mechanisms underlying neuronal ferroptosis caused by SLC7A11 downregulation following spinal cord injury remain unclear. Herein, we provide evidence that tumor protein 53, a negative regulator of SLC7A11, was significantly upregulated post-spinal cord injury. Transcriptomic analysis indicated that tumor protein 53 was associated with injury severity. We subsequently confirmed that tumor protein 53 inhibition restored the expressions of SLC7A11 and glutathione peroxidase 4, alleviated neuronal ferroptosis, and improved neurological function in a contusion spinal cord injury rat model. The regulatory effects of tumor protein 53 on the transcription and ubiquitination of SLC7A11 were further elucidated using chromatin immunoprecipitation polymerase chain reaction and cleavage under targets and tagmentation techniques. Additionally, Kelch-like protein 4, an E3 ubiquitin ligase adaptor, was demonstrated to play an important role in the tumor protein 53-mediated ubiquitination of SLC7A11. In summary, the present study elucidated the possible mechanisms of tumor protein 53-mediated neuronal ferroptosis in spinal cord injury, thereby providing potential targets and insights for clinical translation.

Hematologic malignancies remain a significant public health concern in the United States, affecting over 1.5 million individuals. Although chemotherapy remains a foundational component of treatment, the emergence of novel therapeutic strategies has transformed the treatment landscape. This review examines the development, mechanism of action, expanding clinical applications, and barriers to care associated with chimeric antigen receptor T-cell (CAR T-cell) therapy. Relevant data was found via a literature search across major biomedical databases focusing on current clinical implementation of CAR T-cell therapies. To date, seven CAR T-cell therapies have received U.S. Food and Drug Administration approval, demonstrating robust response rates and effective clearance of malignant cells in hematologic malignancies, including B-cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia. Despite these promising outcomes, CAR T-cell therapy faces significant challenges, including manufacturing timelines, geographic access limitations, and substantial financial burden. As the field continues to evolve, this review aims to provide clinicians with an updated synthesis of clinical outcomes, treatment-related toxicities, and persistent barriers to equitable access.

Pharyngeal squamous cell carcinoma (PSCC) is an aggressive subtype of head and neck squamous cell carcinoma (HNSCC) with poor prognosis and low survival rates. Immune checkpoint inhibitors (ICIs) show promise, but less than 20% of HNSCC patients respond positively. Targeted radionuclide therapy (TRT) combines radionuclides with monoclonal antibodies to target tumor cells. This study created a reliable animal model of PSCC for evaluating the therapeutic efficacy of 131I-aPD-L1. Nude mice were subcutaneously implanted with FaDu cells-a human PSCC cell line characterized by high PD-L1 expression. The synthesis of 131I-aPD-L1 was optimized by varying labeling conditions, achieving a labeling efficiency of over 90%. Mice were divided into experimental and control groups; the experimental group received a single intravenous injection of 500 μCi 131I-aPD-L1. Accumulation of 131I-aPD-L1 in tumor tissues was confirmed by animal single-photon emission computed tomography (SPECT). Tumor volume and mouse body weight were measured every 3 days for 30 days. At the end of the study, tumor tissues were stained for histological examination and immunohistochemical analysis of Bcl-2 and Caspase-3 expression levels. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was also performed on tumor tissues. SPECT verified a significant accumulation of 131I in FaDu tumor tissue. The experimental group exhibited significantly slower tumor volume increase compared to the control group (t = 2.37, p < 0.05). Additionally, a significant reduction in body weight was observed in the 131I-aPD-L1 group compared to the control group (t = 5.624, p < 0.01). HE staining showed extensive tumor necrosis in the experimental group. Immunohistochemical analysis revealed negative Bcl-2 expression and higher caspase-3 expression in the experimental group, indicating enhanced apoptosis and necrosis in tumor cells. Furthermore, TUNEL assay further confirmed that 131I exerted cytotoxic effects by inducing DNA fragmentation. Collectively, our findings demonstrate the promising therapeutic potential of 131I-aPD-L1 for PSCC, particularly in patients with drug resistance or recurrent head and neck tumors. However, the use of nude mice may have impacted the full therapeutic efficacy and synergistic potential observed with immunotherapy. Future studies should utilize immunocompetent models to better assess the probe's therapeutic impact and to explore its synergistic effects with immunotherapy and reduce the dose of 131I to mitigate its toxic effects.