Inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by astragalus polysaccharide protects against transport stress-induced cardiac injury in chicks.

Transport stress (TS) not only weakens poultry performance but also affects animal welfare. Additionally, TS can evoke cardiac damage by triggering sterile inflammation in chicks, but the underlying mechanism is not fully understood. Here, we aimed to elucidate how TS induces sterile inflammation and heart injury and to clarify the antagonism effect of astragalus polysaccharides (APS). We randomly divided 60 chicks (one-day-old female) into 5 groups (n = 12): Control_0h (Con_0h) group (chicks were slaughtered at initiation), Control group (stress-free control), TS group (simulated TS exposure for 8 h), TS plus water (TS+W) group, and TS plus APS (TS+APS) group. Before simulation transport, the chicks of TS+W and TS+APS groups were, respectively, dietary with 100 µL of water or APS (250 µg/mL). H&E staining was employed for cardiac histopathological observation. ELISA assay was used to measure oxidative stress marker levels (GSH, GPX, GST, and MDA). A commercial kit was used to isolate the mitochondrial portion, and qRT-PCR was employed to measure the mitochondrial DNA (mtDNA) levels. Furthermore, we evaluated the activity of mtDNA-mediated NF-κB, NLRP3 inflammasome, and cGAS-STING inflammatory pathways and the expression of downstream inflammatory factors by Western Blotting or qRT-PCR. Our findings revealed that APS notably relieved TS-induced myocardial histopathological lesions and infiltrations. Likewise, the decrease in proinflammatory factors (TNF-α, IL-1ß, and IL-6) and IFN-ß by APS further supported this result. Meanwhile, TS caused severe oxidative stress in the chick heart, as evidenced by decreased antioxidant enzymes and increased MDA. Importantly, APS prevented mtDNA stress and leakage by reducing oxidative stress. Interestingly, TS-induced mtDNA leakage caused a series of inflammation events via mtDNA-PRRs pathways, including TLR21-NF-κB, NLRP3 inflammasome, and cGAS-STING signaling. Encouragingly, all these adverse changes related to inflammation events induced by mtDNA-PRRs activation were all relieved by APS treatment. In summary, our findings provide the first evidence that inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by APS could protect against TS-induced cardiac damage in chicks.

Melatonin inhibits atrazine-induced mitochondrial impairment in cerebellum of mice: Modulation of cGAS-STING-NLRP3 axis-dependent cell pyroptosis.

The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT.

Cadmium Transforms Astrocytes into the A1 Subtype via Inducing Gap Junction Protein Connexin 43 into the Nucleus.

Cadmium is highly toxic and present in the environment and can be accumulated among various levels of the food chain. Both humans and animals are at risk from toxicity associated with cadmium. However, the neurological endpoint caused by cadmium has not been revealed. The aim of our research is to explore the potential target of cadmium attack when causing neurotoxicity. 80 male chickens (one day old, weighing 36.49 ± 2.88 g) were randomly divided into four groups and independently treated with 0, 35, 70, or 140 mg/kg CdCl2 in diet for 90 days. The result showed that the striatum was damaged due to a high dose of cadmium in the brain, which was characterized by degeneration of neurons and astrocyte dysfunction. Transcriptome analysis demonstrated that striatal astrocytes were transformed into the A1 state under cadmium exposure. Deeper investigation revealed that the internalization of gap junction protein connexin 43 was responsible for this transformation. Eventually, we can conclude that the internalized gap junction protein connexin 43 of astrocytes is the target of cadmium anchoring, and this process was accompanied by the transformation of astrocytes into the A1 subtype. This study provides a new direction for exploring the effects of cadmium on the nervous system and the treatment of subsequent nervous system diseases.

Astragalus polysaccharide alleviates transport stress-induced heart injury in newly hatched chicks via ERS-UPR-autophagy dependent pathway.

Transport stress (TS) not only affects animal welfare but also eventually leads to higher morbidity and mortality. Moreover, TS could induce heart injury in animals, but the possible mechanism has yet to be fully explored. Astragalus polysaccharide (APS) is a main active component of Radix Astragali, which has an extensive anti-stress effect. However, the effect of APS on TS-induced heart injury has not yet been elucidated. In this study, a chick model of simulated TS was used. 240 newly hatched chicks were arranged into 4 groups: Control (Con), Transport group (T), Transport + water group (TW), and Transport + APS group (TA). Before transport, the chicks of the TW and TA groups were treated with deionized water and APS (0.25 mg/mL, 100 µL) by oral drops respectively. The histopathological analysis of myocardial tissue was assessed by hematoxylin and eosin staining. qRT-PCR and Western Blotting assays were employed to measure the expression of genes and proteins. Semiquantitative PCR was performed for the X box-binding protein-1 (XBP-1) mRNA splicing assay. The results indicated that APS significantly reduced TS-induced myocardial histopathological changes. Meanwhile, TS induced endoplasmic reticulum stress (ERS), evidenced by an activation of the unfolded protein response (UPR) signaling pathway and up-regulation of ERS-markers (P < 0.05). Moreover, TS markedly triggered autophagy induction by activating AMP-activated protein kinase (AMPK), reflected by augmented LC3-II/LC3-I, AMPK phosphorylation and autophagy-related genes (ATGs) expression (P < 0.05). Importantly, our study manifested that treatment of APS could reduce TS-induced ERS and AMPK-activated autophagy, accordingly alleviating heart injury of transported chicks. In summary, these findings indicate that TS induces heart injury in chicks via an ERS-UPR-autophagy-dependent pathway, and APS as an effective therapeutic method to alleviate it.

Astragalus polysaccharide mitigates transport stress-induced hepatic metabolic stress via improving hepatic glucolipid metabolism in chicks.

In the modern poultry industry, newly hatched chicks are unavoidably transported from the hatching to the rearing foster. Stress caused by multiple physical and psychological stressors during transportation is particularly harmful to the liver. Astragalus polysaccharide (APS) possesses multiple benefits against hepatic metabolic disorders. Given that transport stress could disturb hepatic glucolipid metabolism and the role of APS in metabolic regulation, we speculated that APS could antagonize transport stress-induced disorder of hepatic glucolipid metabolism. Firstly, newly hatched chicks were transported for 0, 2, 4, and 8 h, respectively. Subsequently, to further investigate the effects of APS on transport stress-induced hepatic glucolipid metabolism disturbance, chicks were pretreated with water or APS and then subjected to transport treatment. Our study suggested that APS could relieve transport stress-induced lipid deposition in liver. Meanwhile, transport stress also induced disturbances in glucose metabolism, reflected by augmented mRNA expression of key molecules in gluconeogenesis and glycogenolysis. Surprisingly, APS could simultaneously alleviate these alterations via peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)/Sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway. Moreover, APS treatment regulated the level of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ), thereby alleviating transport stress-induced alterations of VLDL synthesis, cholesterol metabolism, lipid oxidation, synthesis, and transport-related molecules. These findings indicated that APS could prevent the potential against transport stress-induced hepatic glucolipid metabolism disorders via PGC-1α/SIRT1/AMPK/PPARα/PPARγ signaling system.

In the modern poultry industry, newly hatched chicks are unavoidably transported from the hatching to the rearing foster. During transportation, chicks are frequently subjected to various physical and psychological stressors, which can lead to alterations in blood composition, hormones, metabolites, enzymes, and behavior. These alterations adversely affect animal health and welfare. Stress caused by transportation is especially harmful to liver, which can cause significant effects on liver function, and disturb hepatic lipid metabolism and glucose metabolic. The current study demonstrated that Astragalus polysaccharide (APS) possesses multiple benefits against hepatic metabolic disorders. Administration of APS to chicks before transport could prevent transport-induced stress and hepatic glucolipid metabolism disorders.

Transport Stress Induced Cardiac NO-NOS Disorder Is Mitigated by Activating Nrf2/HO-1/NQO1 Antioxidant Defense Response in Newly Hatched Chicks.

With the development of the intensive poultry industry, the health problems of chickens caused by transportation have attracted more and more attention. Transport stress reduces performance, immune function, and meat quality in chicks, which has become one of the most important factors that endanger the development of the poultry industry. Currently, studies on the effects of transport stress have mainly focused on the performance of livestock and poultry to be slaughtered. However, the effects of transport stress on heart damage and oxidative stress in newborn chicks have not been reported. In this study, we selected newborn chicks as the object. This study was intended to explore the effects of transport stress on the heart damage of newly hatched chicks. The findings suggested that transport stress could cause oxidative stress in the hearts of newly hatched chicks by increasing the levels of malondialdehyde (MDA), hydrogen peroxide (H2O2) and decreasing the contents of Total antioxidant capacity (T-AOC), and the activities of antioxidant enzymes (SOD), together with increasing the activities of antioxidant enzymes (Catalase (CAT) and Glutathione S-transferase (GST)). Transport stress disrupted the balance between oxidation and antioxidant systems. The Nrf2 signaling pathway was activated by transport stress and triggered the transcription of antioxidant signaling. In short, transport stress-induced nitric oxide (NO)-nitric oxide synthases (NOS) system metabolic disorders and cardiac oxidative stress are mitigated by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase-1 (NQO1) antioxidant defense response in newly hatched chicks.

Di-2-ethylhexyl phthalate (DEHP) induced lipid metabolism disorder in liver via activating the LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathway.

Di-2-ethylhexyl phthalate (DEHP) has been widely used in many fields (agricultural products, medical instruments, and food packing). As an environmental contaminant, DEHP has a negative impact on human and animal health, and thus toxicity caused by DEHP is increasingly serious health concern. Nevertheless, DEHP-induced liver damage in quail remains unclear. To investigate the mechanism of liver damage caused by DEHP, male quail were treated with DEHP (250, 500, and 750 mg/kg) by gavage. Notably, DEHP exposure results in increased blood lipids and the accumulation of triglycerides (TG), total cholesterol (TC), and non-esterified fatty acid (NEFA) in the liver. Histopathological analysis showed that steatosis and inflammatory cell infiltration were observed in the liver tissue of quails exposed to DEHP. The results of Oil Red O staining displayed that DEHP induced lipid storage in the liver. Moreover, DEHP induced lipid metabolism disorders by activating the LXR/SREBP-1c and PPARα/γ signaling pathway. DEHP exposure obviously caused the up-regulation of pro-inflammatory cytokines (NF-κB, IL-6, IL-8, IL-1ß, and TNF-a). This study showed that DEHP could induce lipid metabolism disorders and inflammatory response via LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathways.

Gap Junction Protein Connexin 43 as a Target Is Internalized in Astrocyte Neurotoxicity Caused by Di-(2-ethylhexyl) Phthalate.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in plastic products, consumer products, and packaging materials. It is of great health concern in both animals and humans as it released into the environment and entered into the body from plastic products over time, thereby resulting in neurotoxicity. As a pivotal regulator of the central nervous system (CNS), astrocytes, are crucial for maintaining brain homeostasis. Nevertheless, the underlying reason for astrocyte neurotoxicity due to DEHP exposure remains incompletely understood. Here, using an in vivo model of neurotoxicity in quail, this study summarizes that Cx43 is internalized by phosphorylation and translocated to the nucleus as a consequence of DEHP exposure in astrocytes. This study further demonstrated that astrocytes transformed to pro-inflammatory status and induced the formation of autophagosomes. Of note, integrated immunofluorescent codetection approaches revealed an overexpression of the glial fibrillary acidic protein (GFAP) and down-expression of Cx43 in astrocytes. Therefore, in terms of neurotoxicity, this experiment in vivo models directly linked Cx43 internalization to autophagy and neuroinflammation and ultimately locked these changes to the astrocytes of the brain. These findings unveil a potential approach targeting Cx43 internalization for the treatment of neurodegeneration caused by DEHP exposure in astrocytes.

[Meteorological mechanism for the formation of a serious pollution case in Beijing in the background of northerly flow at upper levels].

There is a kind of serious air pollution case occurring in the situation of northerly flow at the levels above 850 hPa in Beijing area. Meteorological data, NCEP reanalysis data and PM2.5 concentration survey were used to analyze the roles of meteorological mechanism in this kind of air pollution case. The results showed that the stable stratification did not exist all the time during the gradual increase of PM2.5 concentration. The favorable meteorological conditions in PM2.5 accumulation came from the layered structure of vertical speed and convergence in vertical direction. From the surface to the middle level of troposphere, the vertical velocity showed an updraft-downdraft-updraft distribution. And the divergence displayed a convergence-divergence-convergence structure. The convergence at lower levels led to the gathering of the polluted air from the surrounding and the ascending current brought it upwards. However, the polluted air could not go further up due to the prolonged downdraft layer above. As the result, PM2.5 near the surface was concentrated gradually. The vertical speed in layer structure was attributed to the high level northerly flow without invading into the boundary layer. In such case, the wind was still in southerly direction or kept calm at the surface. The weak cold air or no cold air at all was the main reason that the northerly flow could not hit the surface. The developed downdraft layer was relative to the convergence above which was resulted from the wind speed pulses in the northerly flow at upper levels. In conclusion, the air dynamical effect played a key role in the pollution type of northerly flow at upper levels. Therefore, it will be beneficial to enhance our capability in the analysis and forecasting of this kind of pollution case by focusing on 24 hours temperature variation at the middle and lower troposphere as well as the vertical distribution of vertical velocity and divergence.

[Observation study on aerosol optical properties and radiative forcing using the ground-based and satellite remote sensing at background station during the regional pollution episodes].

The significant effect of anthropogenic pollutants transportation on the physical and optical properties of regional background atmospheric aerosol was studied by using ground-based and satellite remote sensing data obtained at the atmospheric background station (Shangdianzi, Beijing) of North China during October 1 to 15 in 2011. The aerosol mass concentration and reactive gases concentration increased obviously during periods of October 4-5, October 7-9, and October 11-12. Comparing with the background period of October 1-3, volume concentration increased by a factor of 3-6 for reactive gases such as NO(x), and CO, and a factor of 10-20 for SO2. Mass concentration of PM2.5 was about 200 microg x m(-3) on October 9. During haze period, the AOD at 500 nm varied between 0.60 to 1.00. The single scattering albedo (SSA) was lower than 0.88. And the black carbon concentration increased 4-8 times, which suggested the aerosol absorption was very strong during this pollution episode. The absorption of aerosol particles could cause 100-400 W x m(-2) increase of atmospheric radiation. The surface radiation decreased by about 100-300 W x m(-2) due to the aerosol scattering and absorption. This could cause higher stability of atmosphere, which will significantly affect the cloud and precipitation, and thus the regional weather and climate.