Analysis of the role of PANoptosis in seizures via integrated bioinformatics analysis and experimental validation.

Background: Epilepsy is recognized as the most common chronic neurological condition among children, and hippocampal neuronal cell death has been identified as a crucial factor in the pathophysiological processes underlying seizures. In recent studies, PANoptosis, a newly characterized form of cell death, has emerged as a significant contributor to the development of various neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PANoptosis involves the simultaneous activation of pyroptosis, apoptosis, and necroptosis within the same population of cells. However, its specific role in the context of seizures remains to be fully elucidated. Further investigation is required to uncover the precise involvement of PANoptosis in the pathogenesis of seizures and to better understand its potential implications for the development of targeted therapeutic approaches in epilepsy. Methods: In this study, the gene expression data of the hippocampus following the administration of kainic acid (KA) or NaCl was obtained from the Gene Expression Omnibus (GEO) database. The PANoptosis-related gene set was compiled from the GeneCards database and previous literature. Time series analysis was performed to analyze the temporal expression patterns of the PANoptosis-related genes. Gene set variation analysis (GSVA), Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) were employed to explore potential biological mechanisms underlying PANoptosis and its role in seizures. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal gene modules and PANoptosis-related genes associated with the pathophysiological processes underlying seizures. To validate the expression of PANoptosis-related genes, Western blotting or quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. These experimental validations were performed in human blood samples, animal models, and cell models to verify the expression patterns of the PANoptosis-related genes and their relevance to epilepsy. Results: The GSVA analysis performed in this study demonstrated that PANoptosis-related genes have the potential to distinguish between the control group and KA-induced epileptic mice. This suggests that the expression patterns of these genes are significantly altered in response to KA-induced epilepsy. Furthermore, the Weighted gene co-expression network analysis (WGCNA) identified the blue module as being highly associated with epileptic phenotypes. This module consists of genes that exhibit correlated expression patterns specifically related to epilepsy. Within the blue module, 10 genes were further identified as biomarker genes for epilepsy. These genes include MLKL, IRF1, RIPK1, GSDMD, CASP1, CASP8, ZBP1, CASP6, PYCARD, and IL18. These genes likely play critical roles in the pathophysiology of epilepsy and could serve as potential biomarkers for diagnosing or monitoring the condition. Conclusion: In conclusion, our study suggests that the hippocampal neuronal cell death in epilepsy may be closely related to PANoptosis, a novel form of cell death, which provides insights into the underlying pathophysiological processes of epilepsy and helps the development of novel therapeutic approaches for epilepsy.

An angiogenesis-associated gene-based signature predicting prognosis and immunotherapy efficacy of head and neck squamous cell carcinoma patients.

OBJECTIVES: To develop a model that can assist in the diagnosis and prediction of prognosis for head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Data from TCGA and GEO databases were used to generate normalized gene expression data. Consensus Cluster Plus was used for cluster analysis and the relationship between angiogenesis-associated gene (AAG) expression patterns, clinical characteristics and survival was examined. Support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) analyzes and multiple logistic regression analyzes were performed to determine the diagnostic model, and a prognostic nomogram was constructed using univariate and multivariate Cox regression analyses. ESTIMATE, XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, CIBERSORT algorithms were used to assess the immune microenvironment of HNSCC patients. In addition, gene set enrichment analysis, treatment sensitivity analysis, and AAGs mutation studies were performed. Finally, we also performed immunohistochemistry (IHC) staining in the tissue samples. RESULTS: We classified HNSCC patients into subtypes based on differences in AAG expression from TCGA and GEO databases. There are differences in clinical features, TME, and immune-related gene expression between two subgroups. We constructed a HNSCC diagnostic model based on nine AAGs, which has good sensitivity and specificity. After further screening, we constructed a prognostic risk signature for HNSCC based on six AAGs. The constructed risk score had a good independent prognostic significance, and it was further constructed into a prognostic nomogram together with age and stage. Different prognostic risk groups have differences in immune microenvironment, drug sensitivity, gene enrichment and gene mutation. CONCLUSION: We have constructed a diagnostic and prognostic model for HNSCC based on AAG, which has good performance. The constructed prognostic risk score is closely related to tumor immune microenvironment and immunotherapy response.

Effects of chronic low-level lead (Pb) exposure on cognitive function and hippocampal neuronal ferroptosis: An integrative approach using bioinformatics analysis, machine learning, and experimental validation.

Lead (Pb), a pervasive and ancient toxic heavy metal, continues to pose significant neurological health risks, particularly in regions such as Southeast Asia. While previous research has primarily focused on the adverse effects of acute, high-level lead exposure on neurological systems, studies on the impacts of chronic, low-level exposure are less extensive, especially regarding the precise mechanisms linking ferroptosis - a novel type of neuron cell death - with cognitive impairment. This study aims to explore the potential effects of chronic low-level lead exposure on cognitive function and hippocampal neuronal ferroptosis. This research represents the first comprehensive investigation into the impact of chronic low-level lead exposure on hippocampal neuronal ferroptosis, spanning clinical settings, bioinformatic analyses, and experimental validation. Our findings reveal significant alterations in the expression of genes associated with iron metabolism and Nrf2-dependent ferroptosis following lead exposure, as evidenced by comparing gene expression in the peripheral blood of lead-acid battery workers and workers without lead exposure. Furthermore, our in vitro and in vivo experimental results strongly suggest that lead exposure may precipitate cognitive dysfunction and induce hippocampal neuronal ferroptosis. In conclusion, our study indicates that chronic low-level lead exposure may activate microglia, leading to the promotion of ferroptosis in hippocampal neurons.

Tamizaje de niveles tensionales en individuos no hipertensos entre 18-65 años en la comunidad de pizarrete abajo, municipio nizao, provincia peravia, república dominicana, durante el período agosto-septiembre 2018 / Screening of blood pressure levels in non-hypertensive individuals between 18-65 years of age in the community of Pizarrete Abajo, Nizao municipality, Peravia province, Dominican Republic, during the period of august-september 2018

Introducción: la presión arterial elevada es el principal factor de riesgo de enfermedad global. En la República Dominicana el 31 % de la población padece de hipertensión arterial (HTA) y de este, un 60 % lleva tratamiento médico. Objetivo: determinar los niveles tensionales en individuos no hipertensos entre 18-65 años en la comunidad de Pizarrete Abajo, durante el período agosto-septiembre 2018. Metodología: estudio prospectivo, descriptivo y de corte longitudinal, en el que se analizaron 85 individuos que residen en la comunidad de Pizarrete Abajo, de los cuales 44 resultaron con niveles tensionales alterados. Resultados: el 51.7 % de los encuestados presentó niveles de tensión arterial alterados, sin haber sido anteriormente diagnosticado con hipertensión arterial. Un 24 % de las personas mostró niveles alterados una semana después de la primera toma de presión arterial. Conclusiones: en una muestra de 85 personas se encontraron niveles tensionales alterados en 44 individuos. Se procedió a una segunda toma de presión arterial una semana después de la primera y se observó que un 56.8 % correspondió a valores tensionales elevados, un 20.4 % a valores de HTA estadio 1 y un 18.1 % a valores de HTA estadio 2.

Introduction: High blood pressure is the main risk factor for global disease. In the Dominican Republic, 31% of the population suffers from arterial hypertension (HTN) and of these, 60% have medical treatment. Objective: To determine blood pressure levels in non-hypertensive individuals between 18-65 years of age in the community of Pizarrete Abajo during the period of August - September 2018. Methodology: Prospective, descriptive, and longitudinal study in which 85 individuals residing in the community of Pizarrete Abajo were analyzed, of which 44 resulted in altered blood pressure levels. Results: 51.7% of the individuals presented altered blood pressure levels without previously being diagnosed with hypertension. 24% of people showed altered levels one week after the first blood pressure measurement. Conclusions: In a sample of 85 people, altered blood pressure levels were found in 44 individuals. A second blood pressure measurement was carried out one week after the first measurement and it was observed that 56.8% corresponded to high blood pressure values, 20.4% corresponded to stage 1 HTN levels, and 18.1% corresponded to stage 2 HTN levels.