Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.

Association between yogurt and dietary supplements containing probiotic consumption with sleep disturbance in US adults: Results from NHANES, 2009-2018.

Purpose: Sleep disorders are common globally. Probiotics may improve human microbial diversity, offering potential benefits for sleep disturbances by enhancing sleep quality and reducing disorders. We aimed to use a population-based study to investigate the association between yogurt (a probiotic food) and probiotic consumption with sleep disturbances in US adults. Methods: A total of 49,693 adults from the 2009-2018 National Health and Nutrition Examination Survey (NHANES) were included in the analyses. Sleep disorders and sleep duration were assessed according to the Sleep Disorders Questionnaire. The Dietary Questionnaire evaluated yogurt and dietary supplements containing probiotic consumption. After adjusting for confounding factors, weighted multivariable logistic regression and subgroup analyses were used to assess the association between yogurt and probiotic consumption and sleep status. Results: Of the study cohort, 3535 (14.24 %) participants consumed yogurt and/or dietary supplements containing probiotics. The prevalence of sleep disorders was 16.22 %. Only 53.51 % of the participants achieved the recommended amount of sleep (7-9 h), with 6.10 % and 33.48 % having excessive and insufficient sleep duration, respectively. Weighted Logistic regression models indicated a significant association of probiotic intake with a decreased risk of sleep disturbances compared with those without yogurt or probiotic consumption after adjustments. (For sleep disorders: OR: 0.96, 95 % CI 0.94-0.98, P < 0.001; for sleep duration: OR: 0.98, 95 % CI 0.96-1.00, P = 0.081) Moreover, the effect size of the probiotic intake on sleep was especially significant in sex, race, and BMI subgroups. Conclusion: The present study first indicated that yogurt and probiotic consumption were associated with a reduced risk of sleep disturbances in US adults, particularly among males, whites, and those with a normal BMI. Incorporating yogurt or probiotics into the diet could serve as a public health strategy for improving sleep disturbances, though further investigation into the underlying mechanisms is needed.