RESUMEN
Intervertebral disc degeneration (IVDD) severely affects the work and the quality of life of people. We previously demonstrated that silencing activation transcription factor 3 (ATF3) blocked the IVDD pathological process by regulating nucleus pulposus cell (NPC) ferroptosis, apoptosis, inflammation, and extracellular matrix (ECM) metabolism. Nevertheless, whether miR-874-3p mediated the IVDD pathological process by targeting ATF3 remains unclear. We performed single-cell RNA sequencing (scRNA-seq) and bioinformatics analysis to identify ATF3 as a key ferroptosis gene in IVDD. Then, Western blotting, flow cytometry, ELISA, and animal experiments were performed to validate the roles and regulatory mechanisms of miR-874-3p/ATF3 signalling axis in IVDD. ATF3 was highly expressed in IVDD patients and multiple cell types of IVDD rat, as revealed by scRNA-seq and bioinformatics analysis. GO analysis unveiled the involvement of ATF3 in regulating cell apoptosis and ECM metabolism. Furthermore, we verified that miR-874-3p might protect against IVDD by inhibiting NPC ferroptosis, apoptosis, ECM degradation, and inflammatory response by targeting ATF3. In vivo experiments displayed the protective effect of miR-874-3p/ATF3 axis on IVDD. These findings propose the potential of miR-874-3p and ATF3 as biomarkers of IVDD and suggest that targeting the miR-874-3p/ATF3 axis may be a therapeutic target for IVDD.
Asunto(s)
Factor de Transcripción Activador 3 , Ferroptosis , Degeneración del Disco Intervertebral , MicroARNs , Núcleo Pulposo , Factor de Transcripción Activador 3/metabolismo , Factor de Transcripción Activador 3/genética , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , MicroARNs/genética , MicroARNs/metabolismo , Animales , Humanos , Ratas , Ferroptosis/genética , Masculino , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Análisis de la Célula Individual/métodos , Apoptosis/genética , Transducción de Señal , Femenino , Persona de Mediana Edad , Ratas Sprague-Dawley , Análisis de Secuencia de ARN/métodos , Matriz Extracelular/metabolismo , Adulto , Regulación de la Expresión Génica , Modelos Animales de Enfermedad , Biología Computacional/métodosRESUMEN
The cognitive impairment of pituitary adenomas (PAs) has received increasing attention. Hyperprolactinemia and tumor mass effect are the potential causes. The aim of this study was to identify possible cognitive impairment and to further explore the correlation between these indices and prolactin (PRL) levels, based on the control of tumor size. Twenty-seven patients with prolactinomas (patient group) and twenty-six matched health control group (HC group) were enrolled in this study. All participants performed the flanker task while we continuously recorded electroencephalography data. On the behavioral performance level, patients showed a significantly slower reaction time (RT) in both flanker types. Concerning the event-related potentials level, patients elicited reduced P2 and enhanced N2 amplitudes compared with the HC group, suggesting an impairment of attentional processing (P2) and conflict monitoring (N2). Moreover, the patient group also induced lower P3 amplitudes relative to the HC group in both types, indicating that there were deficits in attentional resource allocation ability. We also found a significant correlation between the P3 amplitudes and incongruent condition RTs, as well as the subsequent PRL levels in the patient group. In conclusion, this is an innovative study that reveals the impaired cognition abilities in prolactinomas, and also proposes the possible cognitive toxicity of oversecreted PRL levels, which provides evidence for further research on the cognitive decline in PAs.
RESUMEN
Blast-induced traumatic brain injury (bTBI) is a leading cause of disability and mortality in soldiers during the conflicts in Iraq and Afghanistan. Although substantial clinical and animal studies have investigated the pathophysiology and treatments of bTBI, few effective therapies have been found, especially for the early rescue in the battlefield. The aim of this study is to evaluate neuroprotective effects of early normobaric hyperoxia (NBO) on bTBI. We established a rat model of bTBI caused by explosion in the cabin. It exhibited typical changes of mild bTBI, like impaired neurological function, brain edema, minor intracranial hemorrhage and neuron necrosis. The rats were divided into 4 groups (n = 12): Sham, Vehicle, hyperbaric oxygen (HBO) and NBO. Neurological function of the rats was assessed by the Neurological Severity Scores (NSS) at 24 h and 72 h after explosion. Serum interleukin-6 (IL-6), neuron specific enolase (NSE) and tau protein were measured at 24 h and 72 h after explosion. Brain water content was measured and Aquaporin-4 (AQP4) immunostaining was performed. Neuronal apoptosis was analyzed by TUNEL staining. NBO demonstrated curative effects on protecting the neurological function. Serum levels of NSE and tau protein were reduced at 24 h and 72 h after explosion. But the levels of IL-6 were not reduced significantly at both time points. Cerebral edema was alleviated. Simultaneously, AQP4 immunostaining of the hippocampus showed remarkably decreased expression after treatment. The number of apoptotic cells in hippocampus was also decreased. Compared with HBO, NBO is simple and convenient, and can be administered in remote areas. It may be a promising therapy for early rescue of bTBI in the battlefield.