Background: The global rise in ultra-processed food (UPF) consumption and the persistent burden of mental disorders have raised growing public health concerns. Emerging evidence suggests that unfavorable dietary patterns, particularly with high UPF intake, contribute to the development of mental disorders. Objective: To assess the associations of UPF-related metabolic signatures and mental disorders. Methods: In this population-based cohort study of 30,059 participants from the UK Biobank, we first identified a plasma metabolic signature associated with UPF intake leveraging nuclear magnetic resonance metabolomics. We then applied Cox and logistic regression models to investigate the associations of both UPF consumption and its metabolic signature with incident mental disorders and specific psychological symptoms, respectively. Results: Higher UPF intake was significantly associated with increased risks of overall mental disorder (hazard ratio per 10% increment [95% confidence interval]: 1.04 [1.02, 1.06]), depressive disorder (1.14 [1.08, 1.20]), anxiety disorder (1.12 [1.06, 1.18]), and substance use disorder (1.06 [1.01, 1.11]), as well as several psychological symptoms including suicidal ideation (odds ratios [95% confidence interval]: 1.12 [1.03, 1.16]) and anxiety feeling (1.05 [1.01, 1.09]). Similarly, the UPF-related metabolic signature was independently associated with elevated risks of these mental health outcomes and partially mediated the associations between UPF intake and mental disorders. Conclusions: These findings highlighted the potential metabolic pathways underlying the neuropsychiatric risks of UPF consumption and underscored the importance of dietary quality in mental health.

Background: Polyunsaturated fatty acids (PUFAs) are promising nutrients for the prevention and management of psychiatric disorders. Both animal experiments and cohort studies have demonstrated the antidepressant effects of PUFAs, especially omega-3 PUFAs. However, inconsistent reports about specific types of PUFAs, such as the omega-3 and omega-6 PUFAs, still exist. Objectives: To assess the effects of specific PUFAs on mental disorders and related symptoms and explore the potential mechanisms involving white matter microstructure. Methods: Leveraging 102,252 residents from the UK Biobank, the effects of five PUFA measures on depressive disorder and anxiety disorder were explored through Cox regression models with full adjustment for possible confounders. Furthermore, the effects on related psychiatric symptoms and brain white matter microstructures were also estimated using logistic regression models and multiple linear regression models, respectively. Results: In this study, plasma levels of five PUFAs measured in quartile 4 were associated with lower risks of incident depressive disorder compared with the lowest quartile, with hazard ratios of 0.80 [95% confidence interval] = [0.71, 0.90] for total PUFAs, 0.86 [0.76, 0.97] for omega-3 PUFAs, 0.80 [0.71, 0.91] for docosahexaenoic acid, 0.79 [0.70, 0.89] for omega-6 PUFAs, and 0.77 [0.69, 0.87] for linoleic acid. Similar associations were observed between PUFAs and the incident risk of anxiety disorder. In addition, high plasma PUFA levels were also related to lower risks of occurrence of several adverse psychological symptoms, especially omega-3 PUFAs and DHA. Among the included participants, 8780 individuals with brain imaging information were included in further neuroimaging analyses, and significant associations with white matter microstructures were observed. Conclusions: Thus, this study provides population-based evidence to support the value of interventions to target PUFAs (specifically omega-3 PUFAs) for the prevention and improvement of mental health.

Background: Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy, ranking third in incidence and second in cancer-related mortality. Despite therapeutic advances, challenges such as chemotherapy toxicity and drug resistance persist. Thus, there is an urgent need for novel CRC treatments. However, developing new drugs is time-consuming and resource-intensive. As a more efficient approach, drug repurposing offers a promising alternative for discovering new therapies. Methods: In this study, we screened 1068 small molecular compounds from an FDA-approved drug library in CRC cells. Menadione was selected for further study based on its activity profile. Mechanistic analysis included a cell death pathway PCR array, differential gene expression, enrichment, and network analysis. Gene expressions were validated by RT-qPCR. Results: We identified menadione as a potent anti-tumor drug. Menadione induced three programmed cell death (PCD) signaling pathways: necroptosis, apoptosis, and autophagy. Furthermore, we found that the anti-tumor effect induced by menadione in CRC cells was mediated through a key gene: MAPK8. Conclusions: By employing methods of cell biology, molecular biology, and bioinformatics, we conclude that menadione can induce multiple forms of PCD in CRC cells by activating MAPK8, providing a foundation for repurposing the “new use” of the “old drug” menadione in CRC treatment.