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BACKGROUND: As a more common but easily neglected disorder, minimal depressive symptoms (MDS), it is unclear whether and why it increases the risk of cognitive progression in non-dementia elderly. METHODS: The Alzheimer's disease Neuroimaging Initiative (ADNI) database was used to assign 1065 non-dementia elderly into normal control (n = 380) and MDS (n = 685) groups via the Geriatric Depression Scale (GDS). Blood neutrophils, transcriptomics and metabolomics, cerebrospinal fluid (CSF) proteomics, and magnetic resonance imaging (MRI) data were analyzed. RESULTS: MDS was found to increase the risk of cognitive progression independently of multiple psychological symptoms. Increased levels of blood neutrophils were associated with cognitive progression in MDS, as supported by neutrophil-related pathways by transcriptomic enrichment analysis and multi-omics joint analysis. A disrupted frontolimbic circuit was associated with neutrophil activation in MDS. LIMITATIONS: The heterogeneity of the sample limited the generalizability of results, and the lack of follow-up data limited the research on the mechanism of neutrophil activation influencing cognitive function in MDS. CONCLUSIONS: Cognitive progression occurs as early as the MDS stage. And this phenomenon may attribute to the neutrophil activation and the related disrupted frontolimbic circuit.
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OBJECTIVE: To detect the expressions of transforming growth factor-ß (TGF-ß)-activated kinase (TAK1) and TGF-ß- activated protein kinase 1 (TAB1) in esophageal cancer tissues and explore their correlations with the clinicopathological features and prognosis of the patients. METHODS: The expressions of TAK1 and TAB1 in 84 esophageal cancer tissues and paired adjacent tissues was detected using immunohistochemical staining. The correlations of different patterns of TAK1 and TAB1 expressions (TAK1 alone, TAB1 alone, and both) with the clinicopathological features of the patients were analyzed. The correlation between TAK1 and TAB1 was assessed based on GEPIA datasets. Kaplan-Meier survival analysis was used to analyze the recurrence-free survival of the patients in relation with TAK1 and TAB1 expressions. RESULTS: TAK1 and TAB1 were highly expressed in 65.5% (55/84) and 52.4% (44/84) of the esophageal cancer tissues, respectively. The expression of TAK1, TAB1 and their co-expression were all correlated with tumor invasion depth, lymph node metastasis, and TNM staging (P < 0.05). A strong correlation was found between TAK1 and TAB1 expressions. A high expression of TAK1 and TAK1/TAB1 co-expression both predicted a poor recurrence-freed survival of the patients (P < 0.05). CONCLUSIONS: TAK1 and TAB1 are associated with the progression and prognosis of esophageal cancer and can serve as new prognostic biomarkers for esophageal cancer and as potential molecular targets for therapies.