Gene expression insights: Chronic stress and bipolar disorder: A bioinformatics investigation

Bipolar disorder (BD) is a psychiatric disorder that affects an increasing number of people worldwide. The mechanisms of BD are unclear, but some studies have suggested that it may be related to genetic factors with high heritability. Moreover, research has shown that chronic stress can contribute to the development of major illnesses. In this paper, we used bioinformatics methods to analyze the possible mechanisms of chronic stress affecting BD through various aspects. We obtained gene expression data from postmortem brains of BD patients and healthy controls in datasets GSE12649 and GSE53987, and we identified 11 chronic stress-related genes (CSRGs) that were differentially expressed in BD. Then, we screened five biomarkers (IGFBP6, ALOX5AP, MAOA, AIF1 and TRPM3) using machine learning models. We further validated the expression and diagnostic value of the biomarkers in other datasets (GSE5388 and GSE78936) and performed functional enrichment analysis, regulatory network analysis and drug prediction based on the biomarkers. Our bioinformatics analysis revealed that chronic stress can affect the occurrence and development of BD through many aspects, including monoamine oxidase production and decomposition, neuroinflammation, ion permeability, pain perception and others. In this paper, we confirm the importance of studying the genetic influences of chronic stress on BD and other psychiatric disorders and suggested that biomarkers related to chronic stress may be potential diagnostic tools and therapeutic targets for BD

Sulfuric acid-amine nucleation in urban Beijing

New particle formation (NPF) is one of the major sources of atmospheric ultrafine particles. Due to the high aerosol and trace gas concentrations, the mechanism and governing factors for NPF in the polluted atmospheric boundary layer may be quite different from those in clean environments, which is however less understood. Herein, based on long-term atmospheric measurements from January 2018 to March 2019 in Beijing, the nucleation mechanism and the influences of H2SO4 concentration, amine concentrations, and aerosol concentration on NPF are quantified. The collision of H2SO4-amine clusters is found to be the dominating mechanism to initialize NPF in urban Beijing. The coagulation scavenging due to the high aerosol concentration is a governing factor as it limits the concentration of H2SO4-amine clusters and new particle formation rates. The formation of H2SO4-amine clusters in Beijing is sometimes limited by low amine concentrations. Summarizing the synergistic effects of H2SO4 concentration, amine concentrations, and aerosol concentration, we elucidate the governing factors for H2SO4-amine nucleation for various conditions.Peer reviewe

Continuous and comprehensive atmospheric observations in Beijing : a station to understand the complex urban atmospheric environment

Peer reviewe

Prevotella Induces the Production of Th17 Cells in the Colon of Mice

Th17-mediated mucosal inflammation is related to increased Prevotella bacterial abundance. The actual involvement of Prevotella in the development and accumulation of intestinal Th17 cells at a steady state, however, remains undefined. Herein, we investigated the role of Prevotella in inducing intestinal Th17 cells in mice. Mice were treated with a combination of broad-spectrum antibiotics (including ampicillin, neomycin sulfate, vancomycin hydrochloride, and metronidazole) in their drinking water for 4 weeks and then gavaged with Prevotella for 4 weeks. After inoculation, 16S rDNA sequencing was used to verify the colonization of Prevotella in the colon of mice. The IL-17A as well as IL-17A-expressing T cells was localized and quantified by an immunofluorescence assay (IFA) of colon sections. Th17 cells in the mesenteric lymph nodes of mice were counted by flow cytometry. Systemic immune response to Prevotella colonization was evaluated based on the serum levels of IL-6, TNF-α, IL-1β, IL-17A, IL-10, IL-4, IFN-γ, and IL-2. Th17-polarizing cytokines (IL-6, TNF-α, IL-1β, and IL-2) induced by Prevotella were evaluated by stimulation of bone marrow-derived dendritic cells (BMDCs). Results revealed that after inoculation, Prevotella successfully colonized the intestine of mice and induced the production and accumulation of colonic Th17 cells in the colon. Moreover, Prevotella elevated some of the Th17-related cytokines in the serum of mice. And Th17-polarizing cytokines (IL-6 and IL-1β) produced by BMDCs were mediated mainly through the interaction between Prevotella and Toll-like receptor 2 (TLR2). In conclusion, our data suggest that Prevotella induces the production of Th17 cells in the colon of mice, thus highlighting the potential role of Prevotella in training the intestinal immune system

Modeling the epidemiological impact and cost-effectiveness of a combined schoolgirl HPV vaccination and cervical cancer screening program among Chinese women

Human papillomavirus (HPV) infection is common in women and also the main cause of cervical cancer. Based on a dynamic compartmental model, we aimed to evaluate the population impact and cost-effectiveness of strategies that combined cervical cancer screening and HPV schoolgirl vaccination for Chinese women. The effectiveness of interventions was assessed by comparing modeled scenarios to the status quo, where a 3-y cervical cancer screening program remained at a 20% coverage and without a universal HPV vaccination program. Our study demonstrated that increasing screening coverage from 20% to 50% would reduce the high-risk HPV (HR-HPV) prevalence to 5.4%, whereas a universal schoolgirl vaccination program using the quadrivalent vaccine (qHPV) with a coverage of 50% would reduce the prevalence to 2.9% by 2069. Scaling-up the cervical screening coverage to 50% will prevent 16,012 (95% CI: 8,791 to 25,913) Disability-Adjusted Life-Years (DALYs) per year, with an incremental cost-effectiveness ratio (ICER) of US$10,958 (95$169 to $26,973)/DALY prevented. At the current qHPV price, vaccinating 50$ 83,043, 95% CI: $52,234 to$138,025) exceeds cost-effectiveness threshold (i.e., 3 times GDP per-capita of China: $30,792). The qHPV vaccine requires at least a 50% price reduction to be cost-effective. Vaccinating schoolgirls will result in a large population health benefit in the long term, but such a universal HPV vaccination program can only be cost-effective with a substantial price reduction

Effect of Xiaoyao San on the brain-gut axis in rats after chronic immobilization stress

Objective: To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (CIS). Methods: Rats were divided into control, model, and treatment groups. The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days, during which they were administered Xiaoyao San decoction [3.854 g/(kg·d)] or vehicle by gavage, and their body weight gain, food intake and water intake were monitored. The rats were subsequently subjected to the open field test (OFT) and d-xylose absorption test, and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA), radioimmune analysis, or real-time fluorescence quantitative polymerase chain reaction. Gastric mucosal morphology was also assessed. Results: The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS, abnormalities signified by decreases in food intake, reductions in digestive absorption, decreases in body weight, decreases in the total distances traveled and increases in the time in the central zone during the OFT, gastric mucosal lesion development and decreases in gastrointestinal hormone secretion. These changes were reversed after treatment with Xiaoyao San, which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides. Specifically, the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5, which are secreted by the hypothalamus and promote digestive function, were increased in the Xiaoyao San-treated group compared with the model group. Furthermore, the levels of pro-opiomelanocortin (POMC) and its receptor, melanocortin-4 receptor (MC4R), which are secreted by the hypothalamus and inhibit digestive function, were significantly decreased in the treatment group compared with the model group. However, the levels of ghrelin (GHRL), gastrin (GAS) and motilin (MTL), which are secreted by the stomach, were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P < .05 vs. the model group). Conclusion: Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT), suggesting that its effects are associated with the brain-gut axis

Metabolomics-based alleviation of depression by Xiaoyaosan through regulation of XDH and GRIA2

Background: Xiaoyaosan is gradually gaining acceptance and recognition within the international scientific community. However, it still lacks appropriate methodological and theoretical descriptions that adhere to modern scientific standards. The development of omics technologies, particularly metabolomics, has facilitated the characterization of body physiology and can be used to guide clinical intervention. Aim of this study: This study explored the therapeutic mechanism of Xiaoyaosan from a metabolomics perspective. Methods: We recruited a total of 30 patients with mild to moderate depression and 15 healthy individuals, and collected urine samples from these participants for non-targeted metabolomics analysis. To establish a depressed rat model, we used chronic unpredictable mild stress in combination with orphan, and collected urine samples from the depressed rats for untargeted metabolomics analysis. Differential metabolites (DMs) were analyzed using multivariate data methods, and the biological pathways of DMs were analyzed using MetaboAnalyst 5.0. We comprehensively analyzed the urine metabolic fingerprints of depressed patients and rats to explore common characteristics of metabolic pathways and markers. We also analyzed the key targets of Xiaoyaosan in the treatment of depression and compared them to the targets of metabolic biomarkers. Finally, we verified the regulatory effects of Xiaoyaosan on key targets using real-time quantitative PCR and Western blot. Results: In the treatment of depression patients with Xiaoyaosan, we identified 243 DMs and 22 metabolic pathways. For depressed rats treated with Xiaoyaosan, we found 44 DMs and 9 metabolic pathways. Our comprehensive analysis of the urinary metabolic fingerprint revealed 7 important biological pathways and 6 crucial metabolic markers in the treatment of depression with Xiaoyaosan. The key targets of Xiaoyaosan in the treatment of depression were identified as XDH and GRIA2. Real-time quantitative PCR results demonstrated that Xiaoyaosan upregulated XDH expression in the brain's prefrontal cortex and GRIA2 expression in the brain's prefrontal cortex and hippocampus of depressed rats. Western blot results indicated that Xiaoyaosan upregulated XDH expression in the hypothalamus, prefrontal cortex, and hippocampus, as well as GRIA2 expression in the prefrontal cortex and hippocampus of depressed rats. Conclusions: Our study demonstrated that Xiaoyaosan regulates the metabolic disorders of depression and plays an antidepressant role through regulation of the expression of XDH and GRIA2 in the brain tissues of CUMS rats