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Epidemiology suggests ambient temperature is the triggers and potential activator of asthma. The role of high and low temperatures on airway inflammation of asthma, and the underlying molecular mechanism are not yet understood. A mouse model of asthma was adopted in our experiment. The BALB/c mice were exposed at different temperature for 4 h (2 h in the morning and 2 h in the afternoon) on weekday. The exposure temperatures were 10 °C, 24 °C and 40 °C. Ovalbumin (OVA) was used to sensitize the mice on days 14, 18, 22, 26, and 30, followed by an aerosol challenge for 30 min from day 32–38. After the final OVA challenge, lung function, serum protein and pulmonary inflammation were assessed. Comparing the OVA with the saline group at 24 °C, we saw a significant increase in: serum Total-IgE (p < 0.05); OVA-sIgE (p < 0.01); IL-4 (p < 0.05); IL-1β (p < 0.01); IL-6 (p < 0.01); TNF-α (p < 0.01); and the ratio of IL-4/IFN-γ (p < 0.01). At the same time, there was a significant decrease in IFN-γ (p < 0.01). As the temperature increase, there is a U shape for immune proteins and pro-inflammatory factors with a peak value at 24 °C, exception for IFN-γ (inverted U-shape). After the high and low temperature exposure, the Ri and Re increased significantly, while Cldyn decreased significantly compared with the 24 °C group. Histopathological analysis of the OVA groups showed airway remodeling, airway wall thickening and deforming, and subepithelial fibrosis. More obvious changes were found in the high and low temperature exposure groups. The immunohistochemistry suggested that TRPs changed with temperatures. High and low temperatures can aggravate airway inflammation in a mouse model of asthma. TRPs play an important role in temperature aggravation of allergic asthma. The results suggest that asthmatics should avoid exposure to high and low temperatures for too long time. Image 1 • Temperatures induced asthma in mouse model was successful. • High and low temperatures can aggravate airway inflammation of asthma. • Different indicators followed a U-shaped or inverse-U-shaped curve with temperatures increase. • TRPs play an important role in temperature aggravation of allergic asthma. [ABSTRACT FROM AUTHOR]

Abstract Diisodecyl phthalate (DIDP) is a new type of phthalate used in the coating of pharmaceutical pills and in plastic food wrappers. This research was conducted to investigate whether DIDP could cause learning and memory impairment in mice, using formaldehyde (FA) to construct a positive control. Behavioral analysis showed that oral administration of 15 mg kg−1·d−1 DIDP combined with inhalation of 1 mg m−3 FA led to learning and memory impairment in mice. Histopathological observations of the brain showed that the pathological alterations in the hippocampi. Detection of testosterone (T) and estradiol (E2) levels in the brain and serum showed that E2 levels were associated with learning and memory disorders. Reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) revealed the increased oxidative stress levels. Detection of caspase-3, NF-κB, the phosphorylated cAMP response-element binding protein (p-CREB) and the brain derived neurotrophic factor (BDNF) showed that the protective effect mediated by BDNF, is reduced. However, some of these effects were blocked by the administration of Vitmin E (VitE, 100 mg kg−1·d−1) or 17β-estradiol (17β-E2, 100 μg kg−1). These data suggest that DIDP may aggravate the FA-exposure-induced learning and memory impairment in mice, and that 17β-E2 could be utilized to avoid these adverse effects. Graphical abstract Image 1 Highlights • DIDP aggravates the FA-exposure-impaired learning and memory via oxidative stress. • DIDP causes learning and memory disabilities in mice by abnormal estradiol levels. • 17β-E2 could be utilized to avoid DIDP-induced learning and memory impairment. [ABSTRACT FROM AUTHOR]

Epidemiological evidence indicates a significant relationship between exposure to diisononyl phthalate and allergic asthma. Despite this, the mechanism underlying this association remains unclear. Previous toxicological researches have suggested that the development of allergic asthma may involve the activation of endoplasmic reticulum stress (ERS) and the nuclear factor κ-B (NF-κB) pathways. Nevertheless, it is currently unknown whether these specific signaling pathways are implicated in diisononyl phthalate (DINP)-induced allergic asthma. The objective of this research was to understand how DINP exacerbates allergic asthma in Balb/c mice through ERS and NF-κB pathways. To systematically examine the aggravated effects of DINP in Balb/c mice, we measured airway hyperresponsiveness (AHR), lung tissue pathology, cytokines, and ERS and NF-κB pathway biomarkers. Additionally, we applied the ERS antagonist phenylbutyric acid (4-PBA) or the NF-κB antagonist pyrrolidine dithiocarbamate (PDTC) to verify the mediating effects of ERS and NF-κB on DINP-exacerbated allergic asthma. The results of our experiment show that oral DINP exposure may exacerbate airway hyperresponsiveness and airway remodeling. This deterioration is accompanied by an imbalance in immunoglobulin levels, Th17/Treg cells, ERS, and NF-κB biomarkers, leading to the activation of pro-inflammatory pathways. Furthermore, our study found that the blocking effect of 4-PBA or PDTC can inhibit the Th17/Treg imbalance and effectively alleviate symptoms resembling allergic asthma. In conclusion, ERS and NF-κB signaling pathways play an important role in regulating DINP-induced allergic asthma exacerbations. [Display omitted] • Exposure to diisononyl phthalate aggravates allergic asthma in Balb/c mice. • Endoplasmic reticulum stress and NF-κB pathway is involved in allergic asthma exacerbated by diisononyl phthalate. • Exposure to diisononyl phthalate triggers Th17/Treg immune imbalance in Balb/c mice. • 4-PBA or PDTC treatment can alleviate allergic asthma caused by combined exposure to ovalbumin and diisononyl phthalate. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of “Shaoyang syndrome” has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression. Materials and methods Male C57 BL/6 J mice (aged 4 weeks after weaning) were reared isolatedly for 8 weeks and XCHT (0.8, 2.3, 7.0 g/kg) were given by gavage once a day. Forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated-plus maze test (EPM) and intruder-induced aggression test were used to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice after administration of XCHT for 6 weeks. HPLC-MS/MS was performed to quantify the levels of neurotransmitters in the hippocampus by in vivo microdialysis, while western immunoblotting was used to evaluate the action of XCHT on the synthesis, transport and degradation of monoamine neurotransmitters. Immunofluorescence was used to study the effects of XCHT on neurogenesis and neurotrophin expression, including Ki-67, DCX, BrdU and BDNF. Results Our results showed that administration of XCHT (0.8, 2.3 and 7.0 g/kg) for 6 weeks significantly attenuated the increase in immobility time in TST and FST, improved the anxiety-like behaviors in OFT and EPM, and improved the aggressive behaviors of SI-reared mice. XCHT significantly elevated monoamine neurotransmitters levels and inhibited 5-HT turnover (5-HIAA/5-HT) in hippocampal microdialysates of SI-reared mice. In addition, we found XCHT enhanced monoamine neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin transporter (SERT) expression and decreased monoamine neurotransmitter degradation enzyme (MAO A ) expression in the hippocampus of SI-reared mice for the first time. Moreover, XCHT significantly augmented hippocampal neurogenesis and BDNF expression in hippocampus of SI-reared mice. Conclusions Our results showed for the first time that XCHT improved depressive/anxiety-like behaviors of SI-reared mice by regulating the monoaminergic system, neurogenesis and neurotrophin expression. The findings indicate that XCHT may have a therapeutic application for early-life stress model of depression and in turn provide further evidence supporting XCHT a novel potential antidepressant from a distinct perspective. [ABSTRACT FROM AUTHOR]

Among all phthalate esters, dibutyl phthalate (DBP) is only second to di-(2-ethylhexyl) phthalate (DEHP) in terms of adverse health outcomes, and its potential cerebral neurotoxicity has raised concern in recent years. DBP exposure has been reported to be responsible for neurobehavioral effects and related neurological diseases. In this study, we found that neurobehavioral changes induced by DBP may be mediated by oxidative damage in the mouse brain, and that the co-administration of Mangiferin (MAG, 50 mg/kg/day) may protect the brain against oxidative damage caused by DBP exposure. The results of ethological analysis (elevated plus maze test and open-field test), histopathological examination of the brain, and assessments of oxidative stress (OS) in the mouse brain showed that there is a link between oxidative stress and anxiety-like behavior produced by DBP at higher doses (25 or 125 mg/kg/day). Biomarkers of oxidative stress encompass reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA) and DPC coefficients (DPC). MAG (50 mg/kg/day),administered as an antioxidant,can attenuatetheanxiety-like behavior of the tested mice. [ABSTRACT FROM AUTHOR]

Previously, we reported that exposure to diisononyl phthalate (DINP) resulted in cognitive deficits and anxiety in mice (https://doi.org/10.1038/srep14676). Artificial light at night (ALAN) is now recognized as being a potential threat to human health. However, toxicological evidence concerning exposure to a combination of ALAN and DINP in vivo is limited. To this end, mice were orally exposed to different concentrations of DINP for 28 consecutive days, and ALAN (intensity 150 lux, every night for 12 h). The results showed that oxidative stress levels increased with increasing DINP exposure concentrations, which triggered apoptosis (Bcl-2 levels decreased, Bax levels increased), resulting in nerve cell damage and a decline in the learning and memory abilities of mice. The combined effects of ALAN and DINP exposure on the learning ability and memory of mice are more serious than for DINP exposure alone. The antioxidant vitamin E was shown to have a certain antagonistic effect on the oxidative damage caused by ALAN and DINP exposure. These results highlight a previously unknown relationship between exposure to ALAN and DINP-induced learning and memory impairment, and provide evidence that ALAN may be exacerbating the effects of DINP. [Display omitted] • ALAN exacerbates DINP-induced oxidative damage and apoptosis in the hippocampus. • Combined ALAN and DINP exposure on mouse behavior was more seriously than DINP alone. • VitE reduces pathological changes and oxidative stress caused by ALAN and DINP. [ABSTRACT FROM AUTHOR]