Long-term chronic exposure to di-(2-ethylhexyl)-phthalate induces obesity via disruption of host lipid metabolism and gut microbiota in mice.

BACKGROUND: Numerous epidemiological findings have shown that di-(2-ethylhexyl)-phthalate (DEHP), one of industrial plasticizers with endocrine-disrupting properties, positively contributes to high incidence of obesity. However, potential pathogenesis of dietary DEHP exposure-induced obesity remains largely unknown. METHODS: Chronic DEHP exposure at different doses (0.05 and 5 mg/kg body weight) to mice had been continuously lasted for 14 weeks through the diet. A combination of targeted quantitative metabolomics (LC/GC-MS) with global 1H NMR-based metabolic profiling to explore the effects of dietary DEHP exposure with different doses on host lipid metabolism of mice. Metagenomics (16S rRNA gene sequencing) was also employed to examine the alterations of gut microbiota composition in the cecal contents of mice after dietary DEHP exposure. RESULTS: Dietary exposure to DEHP at both doses induced weight gain and hepatic lipogenesis of mice by promoting the uptake of fatty acids and disrupting phospholipids and choline metabolism. Dietary DEHP exposure altered the gut microbiota community with disruption of intestinal morphology and reduction of Firmicutes to Bacteroidetes ratio in the cecal contents of mice. Furthermore, DEHP exposure activated gut microbiota fermentation process producing excess short chain fatty acids of mice. CONCLUSION: These findings provide systematic evidence that long-term chronic DEHP exposure induces obesity through disruption of host lipid metabolism and gut microbiota in mice, which not only confirm the epidemiological results, but also expand our understanding of metabolic diseases caused by environmental pollutants exposure.

Relevant Factors and Intervention Measures of Psychological Stress-Induced Hyperthermia among Medical Staff in Temporary COVID-19 Negative Pressure Wards.

Background: Medical staff working in COVID-19 wards must be isolated and observed for 14 days upon the occurrence of psychological stress-induced hyperthermia (PSH). Such measures could result in great psychological pressure and incur considerable losses in anti-disease resources. Methods: In this study, the psychological conditions of medical staff were assessed over a period of 7 days in COVID-19 isolation wards of the People's Hospital of Guangxi Zhuang Autonomous Region, China and 7 days after leaving the wards by using the Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Impact of Event Scale-Revised (IES-R), and Post-traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C). The relevant factors of PSH were analyzed by t- and rank sum tests. Results: A total of 10 females with an average body temperature of 37.36 ± 0.07 °C were included in the PSH group. Another 103 females and 53 males with an average body temperature of 36.66 ± 0.21 °C were included in the control group. The PSQI, GAD-7, PHQ-9, IES-R, and PCL-C scores of the PSH group were higher than those of the control group. Binary regression analysis indicated that the odds ratios of the PSQI and GAD-7 scores were 12.98 and 3.81, respectively (P < 0.05). After positive intervention, the body temperature and psychological scale scores of both groups returned to normal ranges. Conclusion: Working in COVID-19 wards could cause susceptible medical staff to suffer from PSH. Female sex, somnipathy, and GAD are independent risk factors of PSH.

Epidemiology and Serum Metabolic Characteristics of Acute Myocardial Infarction Patients in Chest Pain Centers.

BACKGROUND: We aimed to find a potential earlier diagnostic strategy for acute myocardial infarction (AMI) by investigating the epidemiology and serum metabolic characteristics of AMI patients in comparison with those of chest pain controls (CPCS). METHODS: We conducted this prospective, non-randomized, observational study of patients with acute chest pain symptoms presenting to the Emergency Rooms (ER) in The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Province, China from January 2015 to July 2016. We included a cohort of 45 patients with AMI together with 45 age- and sex-matched CPCS. The epidemiology of AMI was collected, and the phenotypic characteristics of the serum metabolite composition of AMI patients were determined using a combination of 1H nuclear magnetic resonance (NMR)-based metabolomics and clinical assays. RESULTS: The epidemiology showed that elderly AMI patients with chest pain syndrome presenting to ER have little awareness of their physical condition and compliance with medication. Significant serum metabolic differences observed between AMI patients and CPCS were highlighted by system differentiations in multiple metabolic pathways including anaerobic glycolysis, gluconeogenesis, tricarboxylic acid cycle (TCA cycle), protein biosynthesis, lipoprotein changes, choline and fatty acid metabolisms and intestinal microbial metabolism. CONCLUSION: The epidemiology and serum metabolic phenotypes observed here demonstrated that integration of metabolomics with other techniques could be useful for better understanding the biochemistry of AMI and for potential AMI molecular diagnosis. We should improve the general public's awareness of AMI, including early symptoms, risk factors, emergency responses, and treatments for related comorbidities.

A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 (DISC1), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation. Interestingly, prenatal interruption of mouse Disc1 function in NPCs leads to abnormal depression-like deficit in adult mice. Here we took a novel unbiased metabonomics approach to identify brain-specific metabolites that are significantly changed in DN-DISC1 mice. Surprisingly, the inhibitory neurotransmitter, GABA, is augmented. Consistently, parvalbumin (PV) interneurons are increased in the cingulate cortex, retrosplenial granular cortex, and motor cortex. Interestingly, somatostatin (SST) positive and neuropeptide Y (NPY) interneurons are decreased in some brain regions, suggesting that DN-DISC1 expression affects the localization of interneuron subtypes. To further explore the cellular mechanisms that cause this change, DN-DISC1 suppresses proliferation and promotes the cell cycle exit of progenitors in the medial ganglionic eminence (MGE), whereas it stimulates ectopic proliferation of neighboring cells through cell non-autonomous effect. Mechanistically, it modulates GSK3 activity and interrupts Dlx2 activity in the Wnt activation. In sum, our results provide evidence that specific genetic insults on NSCs at a short period of time could lead to prolonged changes of brain metabolism and development, eventually behavioral defects.

A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors.

BACKGROUND: Nonsense mediated mRNA decay (NMD) is an RNA surveillance mechanism that controls RNA stability and ensures the speedy degradation of erroneous and unnecessary transcripts. This mechanism depends on several core factors in the exon junction complex (EJC), eIF4A3, RBM8a, Magoh, and BTZ, as well as peripheral factors to distinguish premature stop codons (PTCs) from normal stop codons in transcripts. Recently, emerging evidence has indicated that NMD factors are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). However, the mechanism in which these factors control embryonic brain development is not clear. RESULT: We found that RBM8a is critical for proliferation and differentiation in cortical neural progenitor cells (NPCs). RBM8a is highly expressed in the subventricular zone (SVZ) of the early embryonic cortex, suggesting that RBM8a may play a role in regulating NPCs. RBM8a overexpression stimulates embryonic NPC proliferation and suppresses neuronal differentiation. Conversely, knockdown of RBM8a in the neocortex reduces NPC proliferation and promotes premature neuronal differentiation. Moreover, overexpression of RBM8a suppresses cell cycle exit and keeps cortical NPCs in a proliferative state. To uncover the underlying mechanisms of this phenotype, genome-wide RNAseq was used to identify potential downstream genes of RBM8a in the brain, which have been implicated in autism and neurodevelopmental disorders. Interestingly, autism and schizophrenia risk genes are highly represented in downstream transcripts of RBM8a. In addition, RBM8a regulates multiple alternative splicing genes and NMD targets that are implicated in ASD. Taken together, this data suggests a novel role of RBM8a in the regulation of neurodevelopment. CONCLUSIONS: Our studies provide some insight into causes of mental illnesses and will facilitate the development of new therapeutic strategies for neurodevelopmental illnesses.