Preliminary assessment of the Healthy Early Life Moments (HELMS) webinars in empowering Developmental Origins of Health and Disease (DOHaD) concept among healthcare professionals - a pragmatic serial cross-sectional study.

OBJECTIVES: The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge-practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars. METHODS: We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses. RESULTS: The median webinar attendance rate was 59.6 % (25th-75th percentile: 58.4-60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization. CONCLUSIONS: Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge-practice gap remains a crucial goal.

Metabolomic signatures and microbial community profiling of depressive rat model induced by adrenocorticotrophic hormone.

BACKGROUND: Adrenocorticotrophic hormone (ACTH)-treatment rat model has been utilized as a widely accepted model of treatment-resistant depression. Metabolomic signatures represent the pathophysiological phenotype of diseases. Recent studies in gut microbiota and metabolomics analysis revealed the dramatic role of microbiome in psychoneurological system diseases, but still, the mechanisms underlying gut microbiome-host interaction remain unclear. METHODS: Male Wistar rats were s.c. injection of ACTH fragment 1-24 for 14 days to induce treatment-resistant depression. Depression-related behavioral tests, analysis of serum monoamine neurotransmitters and hypothalamic-pituitary-adrenal (HPA) axis-related hormones were determined for assessment of ACTH-induced depression rat model. A gas chromatography-time-of-flight mass spectrometer based urinary metabolomic signatures integrated 16S rRNA sequence analysis based gut microbial profiling was performed, as well as Spearman's correlation coefficient analysis was used to manifest the covariation between the differential urinary metabolites and gut microbiota of genus level. RESULTS: Chronic injection of ACTH-induced depression-like phenotype (increased immobility time in forced swimming test and tail suspension test) was accompanied by peripheral serotonin down-regulation and HPA axis overactivation (ACTH and corticosterone up-regulation). Urinary metabolomics analysis indicated that pyruvic acid, L-threonine, mannitol, D-gluconic acid, 4-hydroxybenzoic acid, D-arabitol, myo-inositol and ascorbic acid levels were reduced in ACTH-treated rats' urine, while hippurate level was elevated. In addition, microbial community profiling revealed bacterial enrichment (e.g. Ruminococcus, Klebsiella) and reduction (e.g. Akkermansia, Lactobacillus) in the ACTH-induced depression rat model. Correlation analysis showed that Akkermansia and Lactobacillus were closely relevant to metabolites myo-inositol and hippurate, which were included in host inositol phosphate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. CONCLUSIONS: Depression rat model induced by ACTH is associated with disturbance of pyruvate metabolism, ascorbate and aldarate metabolism, inositol phosphate metabolism, glycine, serine and threonine metabolism, and glycolysis or gluconeogenesis, as well as changes in microbial community structure. Gut microbiota may participate in the mediation of systemic metabolomic changes in ACTH-induced depression model. Therefore, integrated metabolomic signatures and gut microbial community profiling would provide a basis for further studies on the pathogenesis of depression.

The Impact of Instant Coffee and Decaffeinated Coffee on the Gut Microbiota and Depression-Like Behaviors of Sleep-Deprived Rats.

Objective: Based on our previous research, chronic paradoxical sleep deprivation (PSD) can cause depression-like behaviors and microbial changes in gut microbiota. Coffee, as the world's most popular drink for the lack of sleep, is beneficial to health and attention and can eliminate the cognitive sequelae caused by poor sleep. The purpose of this study is to investigate the effects of coffee and decaffeinated coffee on PSD rats. Research Design and Methods: A total of 32 rats were divided into four groups: control group, PSD model group, conventional coffee group, and decaffeinated coffee group. Behavioral tests, including sucrose preference test, open field test, forced swimming test, and tail suspension test, as well as biochemical detection for inflammatory and antioxidant indexes were performed. The effects of coffee and decaffeinated coffee on the gut microbiota of PSD rats were investigated by 16S rRNA gene sequencing. Results: Coffee and decaffeinated coffee significantly improved the depression-like behaviors. Moreover, the serum levels of interleukin-6 and tumor necrosis factor alpha were decreased in both coffee and decaffeinated coffee groups, as well as the levels of superoxide dismutase and GSH-Px were increased. Gut microbiota analysis revealed that the abundance of S24-7, Lachnospiraceae, Oscillospira, and Parabacteroides were significantly increased in PSD rats, while the abundance of Akkermansia and Klebsiella were significantly decreased. After the treatment of coffee and decaffeinated coffee, the abundance of the above gut microbiota was all restored in different degrees. Coffee had relatively more significant effects on PSD-induced depressive-like behaviors, while the difference between coffee and decaffeinated coffee was not obvious in correcting the disorder of gut microbiota. Conclusions: These findings have shown that both coffee and decaffeinated coffee are effective for sleep deprivation-induced depression-like behaviors and the dysbiosis of gut microbiota and indicated that caffeine may be not the only key substance of coffee for regulating gut microbiota.

Critical Role for Cold Shock Protein YB-1 in Cytokinesis.

High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, ß-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division.

Chronic paradoxical sleep deprivation-induced depression-like behavior, energy metabolism and microbial changes in rats.

AIMS: Given the lasting impact of chronic paradoxical sleep deprivation (PSD) on behavior and organism metabolic alternations, along with the role of the microbiome in neurobehavioral development and metabolism, we sought to examine the relationship between the microbiota and chronic PSD-induced behavioral and metabolic changes. MATERIALS AND METHODS: Psychological status of 7-day PSD (7d-PSD) male rats was tested by behavioral method, serum inflammatory cytokines and hypothalamic-pituitary-adrenal (HPA) axis-related hormones. In addition, GC-MS based urine metabolomics and 16S rRNA gene sequencing approaches were applied to estimate the influences of chronic PSD on host metabolism and gut-microbiota. Furtherly, microbial functional prediction and Spearman's correlation analysis were implemented to manifest the relations between the differential urinary metabolites and gut microbiota. KEY FINDINGS: 7d-PSD rats displayed depression-like behavior, metabolic and microbial changes. By integrating differential gut bacteria with indicators of depression and differential metabolites, we found that the alterations of Akkermansia, Oscillospira, Ruminococcus, Parabacteroides, Aggregatibacter and Phascolarctobacterium were closely related to abnormalities of depression symptoms and inflammatory cytokines. These bacteria also had close connections with host energy metabolism concerning arginine and proline metabolism, glycine, serine and threonine metabolism, and glyoxylate and dicarboxylate metabolism, pyruvate metabolism, which overlapped with the results of 16S rRNA gene function annotation. SIGNIFICANCE: These data suggest that a specific situation of circadian disturbance, chronic PSD-induced alterations in gut microbiota and related host changes in metabolism may be the pathogenesis of depression.

Modulation of gut microbiota by chlorogenic acid pretreatment on rats with adrenocorticotropic hormone induced depression-like behavior.

Gut microbiota dysbiosis has been implicated as a vital element in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, we investigate the effects of chlorogenic acid (CGA) on gut microbiota in a rat model of MDD. Depression was induced by the adrenocorticotropic hormone (ACTH, 100 µg per rat) in male Wistar rats, which were intervened with using saline or CGA (500 mg kg-1). Behavioral changes and serum parameters were assessed and fecal samples were analyzed by 16S rRNA gene sequencing. Our studies demonstrated that CGA pretreatment ameliorated depression-like behavior (SPT, FST, TST, and OFT) and serum biochemical levels (5-HT, DA, IL-6, and TNF-α) in ACTH-induced depression rats. In addition, CGA ameliorated the decrease in fecal microbiota diversity in ACTH-treated rats. In particular, at the genus level, the changes in the relative abundance of some key bacteria such as Desulfovibrionales, Desulfovibrio, Klebsiella, Burkholderiales, and Bifidobacterium were modulated by CGA pretreatment. These results indicated that CGA could modify the gut microbial community structure, which may contribute to its antidepressant effects.

A urinary metabolomics (GC-MS) strategy to evaluate the antidepressant-like effect of chlorogenic acid in adrenocorticotropic hormone-treated rats.

Major depressive disorder (MDD) is a chronic recurring illness that seriously affects human health. Chlorogenic acid (CGA), an important polyphenol extracted from Eucommia ulmoides Oliver bark, has been reported to have anti-depression, neuroprotection, memory improvement and other pharmacological effects. However, little is known about the underlying mechanisms of CGA on the treatment of depression. Here, we investigated the antidepressant-like effects of CGA on an adrenocorticotropic hormone (ACTH)-treated rat model. Thirty-two male Wistar rats were randomly divided into four groups: normal diet group (N), ACTH-treated model group (M), memantine positive control group (M + Mem) and CGA intervened group (M + CGA). Sucrose preference tests (SPTs) and open-field tests (OFTs) were performed to evaluate depressive-like behaviors. Memantine (30 mg kg-1) and CGA (500 mg kg-1) administration dramatically increased hedonic behaviors of the rats in SPT. The scores of crossing and rearing were significantly increased in the M + Mem group and M + CGA group. These results of the behaviour tests might be suggestive of antidepressant-like effects. Moreover, memantine and CGA reversed the levels of serum 5-hydroxytryptamine (5-HT), ACTH, corticotropin-releasing hormone (CRH), and dopamine (DA) that were altered in ACTH-treated rats. Based on a GC-MS metabolomic approach, significant differences in the metabolic profile were observed in ACTH-treated rats compared with the control group, as well as the M + CGA group and M + Mem group compared with the ACTH-treated group. A total of 19 metabolites were identified for the discrimination of normal rats and ACTH-treated rats, and 12 out of 19 differential metabolites were reversed with CGA intervention. Combined with pattern recognition and bioinformatics, nine perturbed metabolic pathways, including energy metabolism, neurotransmitter metabolism, and amino acid metabolism, were identified based on these metabolites. These integrative studies might give a holistic insight into the pathophysiological mechanism of the ACTH-treated depressive rat model, and also showed that CGA has antidepressant-like activities in ACTH-treated rats, providing an important drug candidate for the prevention and treatment of tricyclic anti-depressant treatment-resistant depression.

Urinary Metabolomic Study of Chlorogenic Acid in a Rat Model of Chronic Sleep Deprivation Using Gas Chromatography-Mass Spectrometry.

The urinary metabolomic study based on gas chromatography-mass spectrometry (GC-MS) had been developed to investigate the possible antidepressant mechanism of chlorogenic acid (CGA) in a rat model of sleep deprivation (SD). According to pattern recognition analysis, there was a clear separation among big platform group (BP), sleep deprivation group (SD), and the CGA (model + CGA), and CGA group was much closer to the BP group by showing a tendency of recovering towards BP group. Thirty-six significantly changed metabolites related to antidepressant by CGA were identified and used to explore the potential mechanism. Combined with the result of the classic behavioral tests and biochemical indices, CGA has significant antidepressant effects in a rat model of SD, suggesting that the mechanism of action of CGA might be involved in regulating the abnormal pathway of nicotinate and nicotinamide metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine and proline metabolism. Our results also show that metabolomics analysis based on GC-MS is a useful tool for exploring biomarkers involved in depression and elucidating the potential therapeutic mechanisms of Chinese medicine.

A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota.

Resveratrol and quercetin, widely found in foods and vegetables, are plant polyphenols reported to have a wide range of biological activities. Despite their limited bioavailabilities, both resveratrol and quercetin are known to exhibit anti-inflammation and anti-obesity effects. We hypothesized that gut microbiota may be a potential target for resveratrol and quercetin to prevent the development of obesity. The aim of this research was to confirm whether a combination of quercetin and resveratrol (CQR) could restore the gut microbiota dysbiosis induced by a high-fat diet (HFD). In this study, Wistar rats were divided into three groups: a normal diet (ND) group, a HFD group and a CQR group. The CQR group was treated with a HFD and administered with a combination of quercetin [30 mg per kg body weight (BW) per day] and resveratrol [15 mg per kg body weight (BW) per day] by oral gavage. At the end of 10 weeks, CQR reduced the body weight gain and visceral (epididymal, perirenal) adipose tissue weight. Moreover, CQR also reduced serum lipids, attenuated serum inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1] and reversed serum biochemical parameters (adiponectin, insulin, leptin, etc.). Importantly, our results demonstrated that CQR could modulate the gut microbiota composition. 16S rRNA gene sequencing revealed that CQR had an impact on gut microbiota, decreasing Firmicutes (P < 0.05) and the proportion of Firmicutes to Bacteroidetes (P = 0.052). CQR also significantly inhibited the relative abundance of Desulfovibrionaceae (P < 0.01), Acidaminococcaceae (P < 0.05), Coriobacteriaceae (P < 0.05), Bilophila (P < 0.05), Lachnospiraceae (P < 0.05) and its genus Lachnoclostridium (P < 0.001), which were reported to be potentially related to diet-induced obesity. Moreover, compared with the HFD group, the relative abundance of Bacteroidales_S24-7_group (P < 0.01), Christensenellaceae (P < 0.001), Akkermansia (P < 0.01), Ruminococcaceae (P < 0.01) and its genera Ruminococcaceae_UCG-014 (P < 0.01), and Ruminococcaceae_UCG-005 (P < 0.01), which were reported to have an effect of relieving HFD-induced obesity, was markedly increased in the CQR group. Overall, these results indicated that administration of CQR may have beneficial effects on ameliorating HFD-induced obesity and reducing HFD-induced gut microbiota dysbiosis.