Search

Abstract Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant with endocrine disrupting properties. As a plasticizer, DEHP can be leach from the plastic to transfer the external environment and thus enters the animal food chain, causing serious damage to the animal organs. The heat-shock response (HSR) comprising heat-shock protein (HSPs) and heat-shock transcription factor (HSFs) plays a pivotal role in various toxic stress conditions. For the sake of investigating the effects of DEHP exposure on cardiac toxicity and the regulation of HSR, male quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. Histopathological changes including cardiomyocyte swelling and muscle fiber dilatation were observed in the hearts exposed to DEHP. During the DEHP treatment, the mRNA expression of HSP60 and HSP70 were universally reduced, while the expression of other HSPs (HSP10, HSP25, HSP27, HSP40, HSP47, HSP90, HSP110) had different degrees of growth. In addition, the levels of HSF1, HSF2, and HSF3 were significantly increased. Given the facts above, DEHP exposure induced the toxic effects of quail heart. DEHP exposure did great harm to HSR via affecting the synthesis of HSFs to mediate the transcription of the HSPs. Ultimately, this study provided new evidence that DEHP-induced cardiotoxicity in quail was related to activation of HSR and playing a protective role. Graphical abstract Image 1 Highlights • DEHP exposure induced the renal injury in quail. • DEHP-induced cardiotoxicity is associated with the modulation of HSFs and HSPs. • DEHP exposure activated the HSR pathway responses in the heart. [ABSTRACT FROM AUTHOR]

Abstract A new naphthalene-quinoline based chemosensor L was prepared and structurally characterized. L exhibited excellent selectivity and sensitivity to Al3+ through distinct fluorescence enhancement (335-fold) and ratiometric detection in DMF/H 2 O (v/v, 1/9) based on the combined mechanisms of ESIPT and CHEF. The recognizing behavior of L toward Al3+ had been investigated in detail through Job's Plot, FT-IR, HNMR, and HRMS analysis. The limit of detection (LOD) for Al3+ was as low as and 3.67 × 10−8 M. L was successfully applied in real sample detection and construction of molecular logic gate. Moreover, L was verified to be of low cytotoxicity and good imaging characteristics for the detection of Al3+ in cells HSC. Graphical abstract Unlabelled Image Highlights • A naphthalene-quinoline based chemosensor L was prepared and structurally characterized. • L exhibited excellent selectivity and sensitivity to Al3+ through fluorescence enhancement (335-fold) and ratiometric detection. • The limit of detection (LOD) for Al3+ was determined as 3.67 × 10−8 M. • L was successfully applied in the detection of Al3+ in cells HSC. [ABSTRACT FROM AUTHOR]

Abstract Atrazine (ATR) is a most used herbicide which is believed as a pivotal determinant of environmental nephrosis, but potential mechanism is still largely unclear. This study intends to reveal a novel mechanism of ATR-induced nephrotoxicity. Quail were treated with 0, 50, 250 and 500 mg ATR/kg/d by oral gavage for 45 days. Kidney coefficient was decreased, biochemical and morphologic indices reflecting the kidney injury were significantly increased in ATR-exposed quail. ATR exposure upregulated the expression of proapoptotic factors (Bax, Caspase 3 and FasL) and downregulated antiapoptotic factor (Bcl-2). Notably, cristae of mitochondria decreased, mitochondrial malformation and mitochondrial vacuolar degeneration were observed in ATR-exposed quail. ATR induced the disorder of mitochondrial function related factors expressions and promoted oxidative damage. Furthermore, ATR induced toxicities in the expression of Nrf2 and Nrf2-target genes. In conclusion, ATR altered the microstructure and function of quail kidney. ATR induced renal damage via causing mitochondrial dysfunction, influencing mitochondrial function related genes expression, modulating Nrf2 signaling pathway. This study suggested ATR induced the nephrotoxicity via disturbing the transcription of mitochondrial function related factors and Nrf2 signaling pathway. Graphical abstract Graphical abstract illustrating the proposed mechanism by ATR-induced nephrotoxicity in quail. Nrf2 signaling pathway was blocked by ATR in kidney of quail. Mitochondria in quail kidney were the target organelles of ATR induced nephrotoxicity. ATR damaged mitochondrial function and morphology. It is deduced that ATR-induced nephrotoxicity is associated with mitochondrial dysfunction and interruption of Nrf2 signaling pathway. Image 1 Highlights • ATR decreased kidney coefficient, impaired histology and function of kidney. • ATR disturbed mitochondrial structure and function related genes expression. • ATR exposure stimulated apoptosis and oxidative stress. • ATR induced variation of Nrf2 signaling pathway and antioxidant response. [ABSTRACT FROM AUTHOR]

Di (2-ethyl hexyl) phthalate (DEHP) as a plasticizer can leach away from the plastic and hence entrances into the animal food chain which caused serious hazard in organs of animals, but there are few studies on DEHP kidney toxicity. The heat-shock response (HSR) consisting of the HSPs and HSFs plays an important role in various toxicity stress conditions. To investigate the influence on kidney toxicity and the modulation of HSR during DEHP exposure, female quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. The shrinkages of glomeruli and dilation of kidney tubule epithelia cells were observed in the kidney of DEHP-exposed quail. DEHP treatment could significantly decrease the expressions of HSP25, HSP27, HSP47, HSP60 , while the expressions of HSP10, HSP40, HSP70, HSP90, HSP110 were upregulated in the kidney. In addition, the expression levels of HSF1 and HSF3 were significantly increased under DEHP. This is the first study to demonstrate quail exposure to DEHP is in fact detrimental to bird kidney. Besides, DEHP could attack HSR by affecting the synthesis of HSFs to mediate the transcription of the HSPs resulting in kidney damage. [ABSTRACT FROM AUTHOR]

Abstract Di (2-ethylhexyl) phthalate (DEHP) is a widely distributed pollutant that is of great concern due to its negative health effects. However, whether DEHP exposure causes liver toxicity in birds remains unclear. To clarify the potential hepatotoxicity of DEHP, quails were exposed to 0, 250, 500 and 1000 mg/kg BW/day DEHP by gavage treatment for 45 days. The livers of DEHP-exposed quails showed histomorphological changes. DEHP exposure induced a significant increase in cytochrome P450 enzyme system (CYP450s) activity (including aniline-4-hydroxylase (AH), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND) and NADPH-cytochrome C reductase (NCR)) and in the contents of total cytochrome P450 (CYP450) and cytochrome b5 (Cyt b5) in quail liver. DEHP exposure also influenced the expression of nuclear xenobiotic receptors (NXRs) and CYP450 isoforms in the liver. The results suggested that DEHP-induced hepatotoxicity in quail liver is associated with activation of the NXRs pathway responses and disruption of CYP450s homeostasis. This study will help to further elucidate DEHP exposure-induced liver toxicity in quails. Graphical abstract DEHP exposure induced hepatic toxicity. DEHP disrupted hepatic CYP450s homeostasis via affecting the transcription of CYPs. DEHP-induced toxicity was associated with activating AHR/PXR/CAR pathway responses and disrupting the CYP450s homeostasis. Image 1 Highlights • DEHP exposure induces the hepatotoxicity in quail. • DEHP triggers the hepatic AHR/PXR/CAR pathway response. • DEHP disrupts the hepatic CYP450 homeostasis. • DEHP modulates the CYPs isoforms transcription via activating the NXRs pathway. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is one of the most extensively used herbicide that eventually leaches into groundwater and surface water from agricultural areas. Exposure to ATR does harm to the health of human and animals, especially the heart. However, ATR exposure caused cardiotoxicity in bird remains unclear. To evaluate ATR-exerted potential cardiotoxicity in heart, quail were exposed with 0, 50, 250, and 500 mg/kg BW/day ATR by gavage treatment for 45 days. Cardiac histopathological alternation was observed in ATR-induced quail. ATR exposure increased the Cytochrome P450s and Cytochrome b5 contents, Cytochrome P450 (CYP) enzyme system (APND, ERND, AH, and NCR) activities and the expression of CYP isoforms ( CYP1B1 , CYP2C18 , CYP2D6 , CYP3A4 , CYP3A7 , and CYP4B1 ) in quail heart. The expression of nuclear xenobiotic receptors (NXRs) was also influenced in the heart by ATR exposure. ATR exposure significantly caused the up-regulation of pro-inflammatory cytokines ( TNF-α, IL-6, NF-κB , and IL-8 ), down-regulation of anti-inflammatory cytokines ( IL-10 ) expression levels and increased NO content and iNOS activity. The present research provides new insights into the mechanism that ATR-induced cardiotoxicity through up-regulating the expression levels of GRP78 and XBP-1s , triggering ER stress, activating the expression of IRE1α/TRAF2/NF-κB signaling pathway related factors ( IRE1α , TRAF2 , IKK , and NF-κB ) and inducing an inflammatory response in quail hearts. In conclusion, ATR exposure could induce cardiac inflammatory injury via activating NXRs responses, disrupting CYP homeostasis and CYP isoforms transcription, altering NO metabolism and triggering ER stress and inflammatory response by activating IRE1α/TRAF2/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is easily found in the environment. Excessive daily exposure of it may lead to an increased risk of cardiovascular disease (CVD). Lycopene (LYC), as a natural carotenoid, has been shown to have the potential to prevent CVD. However, the mechanism of LYC on cardiotoxicity caused by DEHP exposure is unknown. The research was aimed to investigate the chemoprotection of LYC on the cardiotoxicity caused by DEHP exposure. Mice were treated with DEHP (500 mg/kg or 1,000 mg/kg) and/or LYC (5 mg/kg) for 28 d by intragastric administration, and the heart was subjected to histopathology and biochemistry analysis. The results indicated that DEHP caused cardiac histological alterations and enhanced the activity of cardiac injury indicators, and interfered with mitochondrial function and activating mitophagy. Notably, LYC supplementation could inhibit DEHP-induced oxidative stress. The mitochondrial dysfunction and emotional disorder caused by DEHP exposure were significantly improved through the protective effect of LYC. We concluded that LYC enhances mitochondrial function by regulating mitochondrial biogenesis and dynamics to antagonize DEHP-induced cardiac mitophagy and oxidative stress. DEHP exposure can cause heart damage and destroy the pathophysiological integrity of the mouse heart. LYC can alleviate this phenomenon. LYC can alleviate the heart oxidative stress damage induced by the imbalance of mitochondrial biogenesis and mitochondrial dynamics disorder DEHP. This study provides new insights and shows that LYC can prevent DEHP-induced heart damage by activating mitophagy, which may be the target molecule of DEHP toxicity and LYC effect mechanism in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel naphthalimide-based colorimetric and fluorescent turn-on chemosensor for Al3+ was synthesized and characterized with spectroscopic techniques. In MeOH solution, BPAM showed high selectivity and sensitivity to Al3+ by a 60-fold fluorescence enhancement and blue-shift absorption with visible color changes attributed to the contribution of chelation enhanced fluorescence (CHEF) and inhibition of intramolecular charge transfer (ICT). A 1:1 BPAM-Al3+ complex confirmed by job’s plot and HRMS with a binding constant of 6.37 × 104 M− 1, and the detection limit for Al3+ was as low as 1.59 × 10− 7 M. BPAM was successfully applied in real sample detection and assessing the existence of Al3+ by a colorimetric method on filter paper. Furthermore, the fluorescent signals of BPAM were designed to construct an INHIBIT molecular logic gate. [ABSTRACT FROM AUTHOR]

The burden and morbidity of environmental nephrosis is increasing globally. Atrazine (ATR) and degradation products in the environment are considered key determinants of nephrosis. However, the lack of highly effective treatments for environmental nephrosis creates an urgent need to better understand the preventive strategies and mechanisms. This study aimed to highlight the mechanism of ATR-induced environmental nephrosis and the chemoprotective potential of lycopene (LYC) against the renal injury and nephrosis. Male mice were treated with LYC (5 mg/kg) and/or ATR (50 mg/kg or 200 mg/kg) by gavage administration for 21 days. Histopathological changes and biochemical function, cytochrome P450 enzymes system (CYP450s), nuclear xenobiotic receptors (NXRs) response and the transcription of CYP isoforms (CYPs) were detected. ATR exposure caused the changes of the histopathological and biochemical function, activated the NXR response and disturbed the CYP450s homeostasis. Supplementary LYC significantly prevented ATR-induced nephrotoxicity and alleviated the alternation of histopathological and biochemical function via modulating the CYP450s homeostasis and the NXR response. The results demonstrated AHR, CAR, PXR, PPAR (α, γ), CYP1, CYP2, CYP3 and CYP4 superfamily play a vital role in LYC-ATR interaction. Our findings provide new evidence that ATR exposure can cause the environmental nephrosis via inducing the kidney injury. Supplementary LYC showed significant chemoprotective potential against ATR-induced renal injury and environmental nephrosis via regulating the NXR response and the CYP450s homeostasis. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a ubiquitously distributed trace metal and environmental pollutant that is highly toxic to liver. Selenium (Se) may provide chemoprotection against Cd-induced cytotoxicity by augmenting the cellular antioxidant capacity. However, the mechanism of Se chemoprotection against Cd-induced hepatotoxicity is unclear. The present study evaluated the ameliorative properties of Se against Cd-induced cytotoxicity in hepatocytes. Primary cells were exposed to 5 μM Cd and/or 1 μM Se for 24 h. Cellular morphology and function, antioxidant status, activation of Nrf2 pathway, autophagy and apoptosis were determined. These results indicated that Se ameliorated the cytotoxicity of Cd by recovering hepatocyte morphology and function, inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) production, reducing intracellular LDH release, autophagy and apoptosis, and increasing the major antioxidative activities (Total antioxidant capacity (T-AOC) and superoxide dismutase (SOD). In summary, Cd is a hepatotoxin that causes hepatocytes damage by inducing oxidative stress, excessive autophagy and apoptosis as a mechanism of toxicity. Moreover, Se supplement ameliorated these effects by enhancing antioxidant systems, decreasing excessive autophagy and apoptosis. These results suggested that Se triggers Nrf2-mediated protection as the mechanism of Se chemoprotection against Cd-induced autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a commercially available herbicide that is used worldwide. The intensive use of ATR poses potential risks to animals' and humans' health. Lycopene (LYC) is an anti-oxidative phytochemical that normalizes health hazards triggered by environmental factors. In this study, we aimed to investigate the toxic effects of ATR on the hippocampus and its amelioration by LYC. Male mice were exposed to ATR (50 mg/kg/day or 200 mg/kg/d) and/or LYC (5 mg/kg/d) for 21 days. The results showed that ATR exposure induced hippocampus-dependent learning and memory impairments. ATR-induced ferroptosis in hippocampal cells affects the homeostasis of lipid metabolism, whereas LYC ameliorates the neurotoxic effects of ATR in the hippocampus. LYC inhibited ATR-induced ferroptosis by increasing the expression of HO-1, Nrf2 and SLC7A11. Therefore, this study established that LYC ameliorates ATR-induced spatial learning and memory impairments by inhibiting ferroptosis in the hippocampus and also provides a novel approach for the treatment in contradiction of environmental pollutants. ATR is a kind of herbicide that spreads throughout the environment. Because of its biological activity, particularly antioxidant properties, LYC has attracted a lot of interest. According to our findings, LYC ameliorates ATR-induced spatial learning and memory impairments by inhibiting ferroptosis in the hippocampus of mice. This research may lead to a plausible molecular mechanism for LYC therapy of ATR-induced neurological damage. [Display omitted] • ATR caused spatial learning and memory impairments. • ATR induced ferroptosis in the hippocampus. • LYC can prevent ferroptosis and promote nerve cell repair. • LYC mitigated ATR-induced spatial learning and memory impairments. [ABSTRACT FROM AUTHOR]

Di (2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in plastic products, and due to its unique chemical composition, it frequently dissolves and enters the environment. Lycopene as a natural carotenoid has been shown to have powerful antioxidant capacity and strong kidney protection. This study aimed to investigate the role of the interplay between oxidative stress and the classical pyroptosis pathway in LYC alleviating DEHP-induced renal injury. ICR mice were given DEHP (500 mg/kg/d or 1000 mg/kg/d) and/or LYC (5 mg/kg/d) for 28 days to explore the underlying mechanisms of this hypothesis. Our results indicated that DEHP caused the shedding of renal tubular epithelial cells, increased the content of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the tissue, the decrease of antioxidant activity markers and the increase of oxidative stress indexes. It is gratifying that LYC alleviates DEHP-induced renal injury. The expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2) and its downstream target genes is improved in DEHP induced renal injury through LYC mediated protection. Meanwhile, LYC supplementation can inhibit DEHP-induced Caspase-1/NLRP3-dependent pyroptosis and inflammatory responses. Taken together, DEHP administration resulted in nephrotoxicity, but these changes ameliorated by LYC may through crosstalk between the Nrf2/Keap-1/NLRP3/Caspase-1 pathway. Our study provides new evidence that LYC protects against kidney injury caused by DEHP. [Display omitted] [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental toxicant that is widely used in the whole world as a plasticizer that can enhance plastic properties. A number of reserarches have demonstrated that DEHP could cause varying degrees of damage to the normal function of nerve. The research aimed to investigate the mechanism of DEHP-induced cerebellar toxicity. In present study, we set DEHP-caused cerebellar injury models of quail and implied that DEHP induced cerebellar dysplasia by abnormity of Purkinje cell and reduction of cerebellar granule cell. Furthermore, the mitochondrial damage was confirmed by the swelling, cristae reduction, membrane rupture of mitochondria or even the occurrence of autophagic vacuole. To clarified DEHP-induced mitochondrial damage in cerebellum, we examined the relevant genes of mitochondrial biogenesis, mitochondrial dynamics, oxidative damage, the pathways related to Nrf2 and PINK1/Parkin in cerebellum. Based on data, it appeared that DEHP treatment had a damaging effect on the cerebellum and led to mitophagy as well as oxidative stress. In conclusion, the research indicated that DEHP-actuated mitochondrial injury has a directly relationship with mitophagy. DEHP-actuated reduced mitochondrial biogenesis and dysregulation of mitochondrial dynamics. The increase of oxidative stress damaged mitochondria, and the redundant ROS in damaged mitochondria that gave rise to cerebellar harm. [Display omitted] • DEHP leads to a block in Sirt1-PGC-1α-mediated mitochondrial biogenesis. • DEHP leads to mitochondrial dynamics unbalance. • DEHP stimulates PINK1/parking-mediated mitophagy leading to cerebellar injury. • DEHP induces the reinforcement of oxidative stress. [ABSTRACT FROM AUTHOR]

A new schiff-base receptor L based on naphthalimide had been investigated as a selective and sensitive chemosensor for Al 3+ in CH 3 OH. Upon addition of Al 3+ , L showed a 39-fold enhancement at 508 nm with colorimetric and fluorometric dual-signaling response which might be induced by the integration of ICT and CHEF. A 1:1 stoichiometry for the L -Al 3+ complex was formed with an association constant of 1.62×10 4 M −1 , and the limit of detection for Al 3+ was determined as 7.4 nM. In addition, the potential utility of L in sensing Al 3+ was also examined in real water samples. [ABSTRACT FROM AUTHOR]

Atrazine is well known to be a biologically hazardous substance with toxic effects, but atrazine-induced neurotoxicity remains unclear. The aim of this study was to investigate the mechanisms of atrazine-induced cerebellar toxicity. To determine atrazine-exerted potential neurotoxicity, quails were treated with 50, 250 and 500 mg/kg atrazine by gavage administration for 45 days. Notably, the changes of cytochrome P450 enzyme system (CYP450s) were observed in atrazine-exposed quails. The contents of cytochrome P450 (CYP450) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR), aminopyrin N-demethylase (APND) and aniline-4-hydeoxylase (AH) were increased and erythromycin N-demethylase (ERND) was decreased in quail cerebellum. Nuclear xenobiotic receptors (NXRs) and the transcriptions of NXRs-related target molecules were influenced in cerebellum. Atrazine disrupted the CYP450s balance in quail cerebellum. These results suggested that atrazine-induced cerebellar toxicity in birds was associated with activating PXR/CAR pathway responses and disrupting cytochrome P450 homeostasis. This study provided novel evidences that atrazine exposure induced cerebellar toxicity. [ABSTRACT FROM AUTHOR]

Phthalates are extensively used in the production of plastics products and have been verified to induce lung injury. Lycopene (LYC) has proved an effective preventive and can be utilized to prevent phthalates-induced toxicity. However, the role of phthalate in pathogenesis of lung injury remain poorly researched, and little work has been devoted whether LYC could alleviate phthalate-induced lung toxicity via modulating nuclear xenobiotic receptors (NXRs) response. Here, di (2-ethylhexyl) phthalate (DEHP) is used as the representative of phthalates for further studies on toxicity of phthalates and the antagonistic role of LYC in phthalates-induced lung injury. We found that DEHP exposure caused alveoli destruction and alveolar epithelial cells type II damage. Mechanistically, DEHP exposure increased nuclear accumulation of aryl hydrocarbon receptor (AHR) and its downstream genes level, including cytochrome P450-dependent monooxygenase (CYP) 1A1 and CYP1B1. Constitutive androstane receptor (CAR) and their downstream gene level, including CYP2E1 are also increased after phthalates exposure. Significantly, LYC supplementation relieves lung injury from DEHP exposure by inhibiting the activation of NXRs. We confirm that NXRs plays a key role in phthalates-induced lung injury. Our study showed that LYC may have a positive role in alleviating the toxicity effects of phthalates, which provides an effective strategy for revising phthalates-induced injury. DEHP activates xenobiotic-sensing nuclear receptors AHR and CAR signaling pathway, and thereby resulted in lung injury. LYC supplementation is a potential therapeutic strategy to attenuates phthalates-induced lung injury (By Figdraw). [Display omitted] • DEHP causes lung injury via activating AHR/CAR signaling pathway. • DEHP increases the nuclear accumulation of AHR and CAR. • DEHP causes vacuolization and electron density reduced of lamellar bodies. • AHR and CAR can be used as targets for LYC to attenuate DEHP-induced lung injury. [ABSTRACT FROM AUTHOR]

Stress or stress-induced intestinal disturbances, especially diarrhea, are the main triggers for inflammatory bowel disease and irritable bowel syndrome. Diarrhea and intestinal inflammatory disease afflict patients around the world, and it has become a huge burden on the global health care system. Drinking sodium metasilicate-based alkaline mineral water (SM-based AMW) exerts a potential therapeutic effect in gastrointestinal disorders, including gut inflammation, and diarrhea, but the supportive evidence on animal studies and mechanism involved remain unreported. The maternally separated (MS) piglet (Newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infant. This study aims to determine whether drinking SM-based AMW confers diarrhea resistance in maternally separated (MS) piglets under weaning stress and what the underlying mechanisms are involved. 240 newly weaned piglets were randomly divided into the Control group and the sodium metasilicate pentahydrate (SMP) group. A decreased diarrhea incidence was observed in SMP treatment piglets. The intestine injury and activated stress hormones (COR and ACTH) induced by weaning was alleviated by SM-based AMW. This may be related to the improvement of intestinal microflora structure and function by SMP, especially the increase of s_copri abundance. Meanwhile, SMP maintained the integrity of the duodenal mucus barrier in MS piglets. Importantly, by targeting NF-κB inhibition via the microbiota-gut interaction, SM-based AMW alleviated intestinal inflammation, maintained fluid homeostasis by modulating aquaporins and fluid transporter expression, and enhanced barrier integrity by suppressing MLCK/p-MLC signaling. Therefore, drinking metasilicate-based alkaline mineral water confers diarrhea resistance in MS piglets via the microbiota-gut interaction. [Display omitted] • Drinking SM-based AMW confers diarrhea resistance in MS piglets under weaning stress. • Drinking SM-based AMW alleviates intestinal injury in MS piglets. • Drinking SM-based AMW improves the structure of gut microbiota in MS piglets. • Anti-diarrhea effect of SM-based AMW is related to microbiota-gut interaction. • s_copri is the key community of SM-based AMW mediated microbiota-gut interaction. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a widely used herbicide with biologically toxic effects that can lead to neurotoxicity. Lycopene (LYC) is an antioxidant with chemoprotective properties. However, little know about the mechanisms of preventative interventions about LYC alleviated ATR-induced neurotoxicity. Male mice were treated with distilled water (C), 5 mg/kg BW/day LYC (L), 50 and 200 mg/kg BW/day ATR (A1, A2), respectively and LYC + ATR (A1+L, A2+L). ATR promoted oxidative stress and inflammatory damage, as showed by the effects on MDA, H 2 O 2 , IL-6 and TNF-α accumulation, and IL-10, SOD, CAT and GSH depletion, which caused neuronal swelling and mitochondrial vacuolar degeneration. ATR disrupted the CYP450s balance via increasing contents of CYP450 and cytochrome B5, enhancing activities of NCR and ERND and activating NXRs and NXRs-related transcription factors. However, all these effects were reversed by LYC pretreatment. Collectively, these data indicated that LYC inhibited ATR-induced oxidative damage through modulating xenobiotic-sensing nuclear receptors and CYP450s. [Display omitted] • LYC inhibits ATR exposure-induces neurotoxicity. • LYC alleviates ATR exposure-induces AHR/PXR/CAR pathway responses. • LYC alleviates ATR-induces the CYP450 homeostasis disorders and CYPs transcription. • LYC alleviates ATR exposure triggers oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]

As one of the most used phthalates, Di (2-ethylhexyl) phthalate (DEHP) is a widespread environmental contaminant. Extremely persistent plastic can enter the food chain of animals through the aquatic environment, affect metabolic pathways and cause damage to the digestive system. But the molecular mechanism of its toxic effects on the duodenum in birds has not been elucidated. To investigate the toxicity of phthalates in the duodenum, quails were gavaged with 250, 500, and 750 mg/kg doses of DEHP for 45 days, and water and oil control groups were retained. This study revealed that subchronic exposure to DEHP could lead to duodenal barrier defect in quail. The damage to duodenum was reflected in a reduction in V/C and tight junction proteins. Moreover, DEHP also led to a breakdown of antimicrobial defenses through the flora derangement, which acted as a biological barrier. The massive presence of Lipopolysaccharide (LPS) led to the activation of TLR4 receptors. In addition, DEHP activated oxidative stress, which synergized the inflammatory response induced by the TLR4-NFκB pathway, and further promoted duodenum damage. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction. DEHP (a commonly used phthalate) induced duodenal barrier defect and flora derangement of quail, which is sensitive to environmental pollutants. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction. [Display omitted] • Duodenal barrier defect disrupts microbiota-barrier-immune interaction. • DEHP causes duodenal flora derangement and dysbiosis of antimicrobial function. • Duodenal Proteobacteria increased most significantly after DEHP treatment. • DEHP induces duodenum damage and decreases V/C in quail. • DEHP activates duodenal oxidative stress and inflammation in quail. DEHP (a commonly used phthalate) is ubiquitous in the environment due to overuse. This study could warn of the health risks to animals exposed to phthalates and even humans. [ABSTRACT FROM AUTHOR]

As a plasticizer, di-2-ethylhexyl phthalate (DEHP) has been listed as a potential endocrine disruptor by The World Health Organization. The toxicity of DEHP has been widely studied, but its toxicity on the digestive tract of birds has not been clarified. Female quail were treated by gavage with DEHP (250, 500, 750 mg/kg), with the blank and vehicle control groups reserved. The result showed that DEHP raised the damage severity grade, and decreased the ratio of villus length to crypt depth. The content and activity of cytochrome P450 system (CYP450s) were increased by DEHP. DEHP interfered with the transcription of nuclear xenobiotic receptors (NXRs), CYP isoforms, and the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway. This study revealed DEHP could cause the imbalance in CYP450s mediated by NXRs, and then promote Nrf2 mediated antioxidant defense. This study provided new evidence about the mechanisms of DEHP-induced toxic effects on digestive tract. [Display omitted] • DEHP increases the damage severity grade and decreases the villus length/crypt depth. • DEHP-induced jejunal toxicity is associated with oxidative stress in quail. • DEHP destroys the steady state of the NXR and CYP response in the quail jejunum. • DEHP activates Nrf2-mediated antioxidant defense in the quail jejunum. [ABSTRACT FROM AUTHOR]

Male infertility is an attracting growing concern owing to decline in sperm quality of men worldwide. Phthalates, in particular to di (2-ethylhexyl) phthalate (DEHP) or its main metabolite mono-2-ethylhexyl phthalate (MEHP), affect male reproductive development and function, which mainly accounts for reduction in male fertility. Lycopene (LYC) is a natural antioxidant agent that has been recognized as a possible therapeutic option for treating male infertility. Testosterone (T)/androgen receptor (AR) signaling pathway is involved in maintaining spermatogenesis and male fertility. How DEHP causes spermatogenesis disturbance and whether LYC could prevent DEHP-induced male reproductive toxicity have remained unclear. Using in vivo and vitro approaches, we demonstrated that DEHP caused T biosynthesis reduction in Leydig cell and secretory function disorder in Sertoli cell, and thereby resulted in spermatogenic impairment. Results also showed that MEHP caused mitochondrial damage and oxidative damage, which imposes a serious threat to the progress of spermatogenesis. However, LYC supplement reversed these changes. Mechanistically, DEHP contributed to male infertility via perturbing T/AR signaling pathway during spermatogenesis. Overall, our study reveals critical role for T/AR signal transduction in male fertility and provides promising insights into the protective role of LYC in phthalate-induced male reproductive disorders. [Display omitted] • DEHP caused testosterone synthesis decline in Leydig cells. • DEHP resulted in secretory function disorder in Sertoli cells. • DEHP led to spermatogenic disorders by disrupting testosterone/androgen pathway. • LYC prevented DEHP-induced sperm parameters decline and spermiogenesis impairment. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment, with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage. Exposure to persistent environmental pollutants such as di(2-ethylhexyl) phthalate (DEHP) has been involved in multiple health disorders, including splenic diseases. In this study, we clarified the potential protective effect of lycopene on DEHP-induced splenic injury. The results showed that Lyc inhibited DEHP induced oxidative damage by regulating the P62-Keap1-NRF2 signaling pathway, indicating that Lyc could alleviate the toxic effects of DEHP and may be helpful in reducing spleen injury. [Display omitted] • Lyc alleviated DEHP exposure-induced splenic injury. • Lyc alleviated the DEHP exposure-induced redox imbalance. • Lyc mitigated the inhibition of P62-Keap1-NRF2 pathway induced by DEHP exposure. • Lyc alleviated the splenic cell mitochondrial injuries induced by DEHP exposure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a widely used heavy metal which is reported to exert extensive harm to the environment and human health. Owing to Cd being an element it is continuously enriched in the environment. The mechanism of splenic toxicity by Cd, however, is not yet clear. In order to explore the toxic mechanism of Cd exposure to the spleen, we added 0, 35, 70 and 140 mg/kg of Cd to the diet of chicken and fed them this diet for 90 days. Analysis of histopathological sections showed that Cd exposure damaged the spleen structure, the spleen red pulp, the white pulp boundary disappeared and the number of lymphocytes decreased significantly, suggesting that Cd exposure leads to organ injury to the spleen. Particularly, Cd-induced anoikis - a special form of programmed cell death caused by the loss of contact between cells and extracellular matrix and other cells - is associated with integrin-related cell detachment and activation of apoptotic signaling pathways. Moreover, Cd exposure leads to an increase in free radicals content and affects the activity of antioxidant enzymes resulting in oxidative stress. Simultaneously, Cd activated the body's antioxidant defense system mediated by the Nuclear factor related factor 2 (Nrf2) signaling pathway. Based on our results Cd-induced splenic lymphocytes anoikis is not mitigated by Nrf2-mediated antioxidative defense response. Cd exposure induced the toxic effects on spleen and triggered anoikis through changing the expression of Integrin and apoptotic factor in the spleen. Cd can activate Nuclear factor related factor 2 (Nrf2) signaling pathway and to a certain extent inhibit oxidative stress. [Display omitted] • Cd exposure induces the spleen injury. • Cd exposure causes splenic lymphocyte anoikis. • Nuclear factor related factor 2(Nrf2)can be activated by Cd. • Cd reduces oxidative stress injury by triggered the Nrf2 signaling pathway. • Cd induced anoikis is not mitigated by activating Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether closed suction drainage ( CSD) is associated with early recovery of knee function in patients undergoing total knee arthroplasty ( TKA). Methods Between January 2015 and September 2015, 80 consecutive patients were prospectively randomized into two groups: a CSD group (40 cases; average age, 66.9 ± 8.6 years; male, 8; female, 32) and a non- CSD group (40 cases; average age, 66.8 ± 10.1 years; male, 9; female, 31). Local inflammation outcomes (assessed by a visual analog scale [ VAS], swelling and skin temperature), calculated total blood loss ( CBL), hidden blood loss ( HBL), blood transfusion requirements and hemoglobin concentrations were recorded. Hospital for Special Surgery ( HSS) knee scores, range of motion ( ROM), limb swelling, tension vesicles, ecchymosis, time to regaining straight leg raising and duration of hospital stay were documented. All surgeries were performed by the same surgeon and followed up for 3 months. Results The peri-wound skin temperature and knee VAS pain scores were lower in the non- CSD group. Patients in the non- CSD group had significantly better knee ROM ( P = 0.028). The time to regaining active straight leg raising was significantly shorter in the non- CSD group N than in the CSD group ( P = 0.014). In addition, patients in the non- CSD group had a shorter length of hospital stay ( P = 0.004) than those in the CSD group, indicating earlier recovery of knee function. HBL was significantly less in the CSD group than the non- CSD group ( P = 0.006) on postoperative day ( POD) 5. However, CBL did not differ significantly between the two groups on POD5. There were no significant differences between two groups in all other assessed variables. Conclusion In this randomized study, primary TKA without CSD was associated with faster recovery related to less local inflammation and better early knee function. Furthermore, use of a drain had no significant advantage with respect to other outcome measures and may have increased costs. Based on these data, CSD after primary TKA is not routinely indicated. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the possible chemoprotective role of lycopene (LYC) against atrazine (ATR)-induced ionic disorder and hepatotoxicity in mice. Male kunming mice were treated with LYC (5mg/kg) and/or ATR (50mg/kg or 200mg/kg) by lavage administration for 21days. Ionic disorder was assessed by determining the Na(+), K(+) and Ca(2+) content and the alteration in ATP enzymes (ATPases) including Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase and the mRNA levels of ATPase's subunits in liver. ATR caused the increases of alanine aminotransferase and aspartate aminotransferase activities and histological changes. LYC pretreatment significantly protected liver against ATR-caused alternation. The significant effect of ATR and LYC on the K(+) and Mg(2+) content in liver was not observed, but ATR increased hepatic Na(+)-K(+)-ATPase activity and decreased Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity. The mRNA expressions of Na(+)-K(+)-ATPase subunits were regulated significantly by ATR. A significant increase of Ca(2+) content and seven down-regulated mRNA expressions of Ca(2+)-ATPase subunits and a decrease of Ca(2+)-ATPase activity were observed in the ATR-treated mice. Notably, LYC modulated these ATR-induced alterations of ATPase activity and mRNA expression of their subunits. These results suggest that ATR presents hepatotoxicity via regulating hepatic ATPase's activities and their subunit transcriptions and inducing ionic disorder. LYC protects liver against ATR-induced hepatotoxicity, significantly. LYC modulated hepatic ionic homeostasis disturbance via regulation of ATPase activities and their subunits' (1a1, 1b3, 1b4 and 2b4) transcriptions. In summary, these effects play a critical role of LYC-mediated chemoprevention against ATR-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Selenium (Se), a nutritionally essential mineral for humans and animals, has a significant antagonistic effect on heavy metal cadmium (Cd) biotoxicity. Still, the impact of different Se sources on alleviating Cd toxicity has received only limited attention. Therefore, the purpose of the current study was to assess the mitigation level of Cd-induced cardiotoxicity by different sources such as nanoparticles of Se, Se-rich yeast, and sodium selenite (SS). The results evidenced that the presence of Cd led to a significant increase in biochemical parameters such as lactate dehydrogenase and creatine kinase, as well as histopathological lesions in the heart of chickens. Cd exposure also resulted in more extensive effects on phase I metabolism enzymes and transcript cytochrome P450 isoforms, elevated the levels of malondialdehyde (MDA), glutathione (GSH), and hydrogen peroxide (H2O2) and depressed total superoxide dismutase (T-SOD), copper-zinc SOD (Cu-Zn SOD), total antioxidant capacity (T-AOC) and catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-S-transferase (GST) activities. The expression of nuclear receptors, aryl hydrocarbon receptor (AHR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) was declined, down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets in the Cd-treat group. Notably, Se sources application alleviated Cd toxicity by triggering AHR/CAR/PXR/Nrf2 signaling pathway to promote restoring antioxidant defense system and phase I metabolism enzymes system. However, when compared to the effectiveness of antagonism, the nanoparticles of Se were superior in relieving Cd-induced cardiotoxicity via AHR/CAR/PXR/Nrf2 pathway activation than other Se-sources. [ABSTRACT FROM AUTHOR]

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-1β , 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. This research showed that DEHP could induce lipid metabolism disorder and inflammatory response via LXR / SREBP-1c / PPARα / γ / NF-κB signal pathways. This study provides new evidence for the mechanisms of DEHP-induced hepatotoxicity. [Display omitted] • DEHP exposure caused hepatotoxicity. • DEHP induced lipid metabolism disorders in liver. • DEHP disrupted lipid metabolism to induce lipotoxicity in liver. • DEHP exposure caused inflammation response in liver. [ABSTRACT FROM AUTHOR]

Despite the intense efforts in searching for stroke therapies, an urgent need still exists to explore novel neuroprotective agents for ischemic stroke that have high efficacy and wide therapeutic time-window. Here, we provide the first demonstration that 28 -O-caffeoyl betulin (B- CA), a novel derivative of naturally occurring caffeoyl triterpene, could significantly alleviate brain infarction and neurological deficit when given as late as 6 h after transient middle cerebral artery occlusion in the rat. Moreover, post-ischemia B- CA administration exhibited long-term (14 days post stroke) protective effects on both brain infarction and functional (i.e., motor and sensory) deficits. Protective B- CA effects correlated with decreased inflammatory responses as indicated by inhibition of microglia and astrocyte activation [stained with ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) antibody, respectively], as well as suppression of tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 overproduction in the ipsilateral cortex of ischemic rat. B- CA administration caused significant hypothermia in the focal cerebral ischemic rat, which may contribute to its ameliorative effects on brain damage and inflammation. In view of its potency in wide therapeutic time-window, robust anti-inflammatory and hypothermic effects, this novel caffeoyl triterpene derivative may lead toward the development of effective therapeutic strategies for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background. Interferon-γ release assays (IGRAs) have been widely used for the diagnosis of latent and active tuberculosis in adults, but their role in diagnosing latent tuberculosis infection (LTBI) in children younger than 5 years remains unclear. Objective. To evaluate the diagnostic performance of IGRAs for LTBI in children younger than 5 years. Methods. We searched the PubMed, EMBASE, Cochrane Library, and Web of Knowledge databases. According to inclusion criteria, the diagnostic studies of IGRAs for LTBI in children younger than 5 years were included. The study quality was assessed using the 14-item Quality Assessment of Diagnostic Accuracy Studies instrument. The Meta-Analyst software was used to analyze the data. Results. Seven studies (627 patients) were included. Meta-analysis showed that compared with tuberculin skin test (TST), the pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), accuracy and diagnosis odds ratio (DOR), and summary receiver operating characteristic (SROC) curve of QuantiFERON-TB (values in parentheses are 95% confidence intervals) were 0.841 (0.733-0.911), 0.895 (0.861-0.922), 8.046 (5.953-10.876), 0.192 (0.113-0.326), 0.622 (0.527-0.709), 0.970 (0.946-0.983), 0.891 (0.861-0.916), 50.718 (24.201-106.287), and 0.809 respectively. The pooled Sen, Spe, PLR, NLR, PPV, NPV, accuracy, DOR, and SROC curve of T-SPOT.TB test were 0.931 (0.760-0.983), 0.767 (0.684-0.833), 3.947 (2.854-5.459), 0.095 (0.026-0.354), 0.523 (0.398-0.645), 0.977 (0.914-0.994), 0.806 (0.737-0.860), 65.270 (13.463-316.434), and 0.855, respectively. Conclusion. This meta-analysis showed that the sensitivity and specificity of IGRAs were slightly higher than TST and can be used as supporting tools to detect LTBI in children younger than 5 years. The methodological quality of diagnostic test needs to be improved. [ABSTRACT FROM PUBLISHER]

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in agricultural and industrial plastic products. Many researchers have demonstrated that DEHP can cause varying degrees of harm to the heart. This research investigated the mechanism by which DEHP causes heart damage in quail. The quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day or 750 mg/kg BW/day) for 45 days. The present study suggested that DEHP could cause varying levels of heart damage, including disordered myocardial fiber arrangements, myocardial fiber breakage and myocardial cell swelling. The results showed that DEHP induced mitochondrial damage, such as cavitation lesions and mitochondrial crest breakage. DEHP damaged mitochondria and inhibited nuclear respiratory factor 1 (Nrf1)-mediated mitochondrial biogenesis, which led to mitochondrial damage. DEHP caused oxidative stress in the heart and activated the defense mechanism of the nuclear factor red blood cell 2 related factor 2 (Nrf2) system. DEHP-induced mitophagy was related to a decline in mitochondrial biogenesis and disordered mitochondrial dynamics. The data indicated that DEHP exposure damaged cardiac mitochondria and caused mitophagy and cardiotoxicity. Of note, this study showed that DEHP-induced mitophagy and mitochondrial damage are associated with the dysregulation of mitochondrial biogenesis. This study showed that DEHP exposure can cause cardiotoxicity, which was closely related to mitochondrial damage. DEHP inhibited Nrf1-mediated mitochondrial biogenesis and caused an imbalance in mitochondrial dynamics. DEHP exposure increased the level of Nrf2 because it induced oxidative stress and activated the Nrf2 signaling pathway. DEHP-induced mitochondrial damage leads to the occurrence of mitophagy, which ultimately leads to cardiotoxicity. This study provided new evidence for the effect of DEHP on the cardiotoxicity of quail. [Display omitted] • DEHP caused an Nrf1-mediated decline in mitochondrial biogenesis. • DEHP-induced cardiac oxidative stress damage activates the Nrf2 signaling pathway. • DEHP caused disordered mitochondrial dynamics in the heart of quail. • DEHP-induced mitophagy was associated with reduced mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is one of the toxic environmental heavy metals that poses health hazard to animals due to its toxicity. Nano-Selenium (Nano-Se) is a Nano-composite form of Se, which has emerged as a promising therapeutic agent for its protective roles against heavy metals-induced toxicity. Heat shock proteins (HSPs) play a critical role in cellular homeostasis. However, the potential protective effects of Nano-Se against Cd-induced cerebellar toxicity remain to be illustrated. To investigate the toxic effects of Cd on chicken's cerebellum, and the protective effects of Nano-Se against Cd-induced cerebellar toxicity, a total of 80 male chicks were divided into four groups and treated as follows: (A) 0 mg/kg Cd, (B) 1 mg/kg Nano-Se (C) 140 mg/kg Cd + 1 mg/kg Nano-Se (D) 140 mg/kg Cd for 90 days. We tested heat shock protein pathway-related factors including heat shock factors (HSFs) HSF1, HSF2, HSF3 and heat shock proteins (HSPs) HSP10, HSP25, HSP27, HSP40, HSP60, HSP70 and HSP90 expressions. Histopathological results showed that Cd treatment caused degradation of Purkinje cells. In addition, HSFs and HSPs expression decreased significantly in the Cd group. Nano-Se co-treatment with Cd enhanced the expression of HSFs and HSPs. In summary, our findings explicated a potential protective effect of Nano-Se against Cd-induced cerebellar injury in chicken, suggesting that Nano-Se is a promising therapeutic agent for the treatment of Cd toxicity. Cd can be absorbed to chickens through the food chain, eventually caused cerebellar injury. However, Nano-Se attenuated cerebellar injury induced by Cd. This study indicated that the cerebellum is the target organ of Cd-induced cerebellar injury. Chronic and high-dose Cd treatment caused blurring nucleolus and degradation of Purkinje cell. In addition, HSFs and HSPs expression were decreased significantly, However, supplementation of Nano-Se exerts protective function against chronic Cd-induced cerebellar injury through activating heat shock protein pathway. [Display omitted] • Cerebellum is the target organ of Cd toxicity. • Cd inhibited heat shock protein pathway in cerebellum. • Nano-Se activated the heat shock protein pathway that alleviated cerebellar injury. • Nano-Se is a promising candidate for the treatment of Cd toxicity. [ABSTRACT FROM AUTHOR]

In this paper, we addressed the immune adjuvant effects of interleukin(IL)-21 on DNA vaccine constructs expressing mycobacterium tuberculosis (TB) Ag85A and compared immune responses induced in mice inoculated DNA vaccine constructs expressing Ag85A and IL-21 with mice inoculated DNA vaccine constructs expressing Ag85A alone or Bacillus Galmette-Guérin(BCG.). In this experiment, the gene of IL-21 was firstly amplified from plasmid pcDNA3.1-mIL21 by PCR and cloned into the plasmid pRSC, forming recombinant plasmid pRSC-IL21. Then, the gene of Ag85A was amplified from the plasmid pIRES-Ag85A by PCR and cloned into the recombinant pRSC-IL21 again, finally forming co-expression DNA vaccine constructs pRSC-IL21-Ag85A. It was identified by the analysis of endonuclease digestion, DNA sequencing, the IL-21 and Ag85A expression in SP2/0 cells. Mice were i.m. immunized with BCG, DNA vaccine constructs pRSC-Ag85A or pRSC-IL21-Ag85A respectively, and the immune responses induced in mice was compared with other vaccines. The results showed that the DNA vaccine constructs pRSC-IL21-Ag85A was successfully constructed since the Ag85A and IL-21 was correctly expressed in SP2/0 cells respectively, and it elicited stronger immune responses in Balb/c mice than that of mice immunized with pRSC-Ag85A and the efficiency was as BCG did. We concluded that the IL-21 was a promising immune adjunctive modality to enhance immunigenicity of DNA vaccine containing Ag85A and the study provided the possibility of further development of immune accessory effect of IL-21 on DNA vaccine against TB. [ABSTRACT FROM AUTHOR]

Abstract: This study examines the concentrations of air pollutants in passenger carriages on a number of lines of the Beijing railway transit system differentiating between services with and without air conditioning. In-train air quality monitoring found PM10 concentrations are extremely high compared with other cities. Integrated factor assessment results show that the in-train air quality in the ground railway transit system where there is air conditioning is more acceptable than in the underground system. [Copyright &y& Elsevier]

Abstract: SrRuO3 thin films have been grown on singular (100) MgO substrates using pulsed laser deposition (PLD) in 30Pa oxygen ambient and at a temperature of 400–700°C. Ex situ reflection high-energy electron diffraction (RHEED) as well as X-ray diffraction (XRD) θ/2θ scan indicated that the films deposited above 650°C were well crystallized though they had a rough surface as shown by atom force microscopy (AFM). XRD Φ scans revealed that these films were composed of all three different types of orientation domains, which was further confirmed by the RHEED patterns. The heteroepitaxial relationship between SrRuO3 and MgO was found to be [110] SRO//[100] MgO and 45°-rotated cube-on-cube [001] SRO//[100] MgO. These domain structures and surface morphology are similar to that of ever-reported SrRuO3 thin films deposited on the (001) LaAlO3 substrates, and different from those deposited on (001) SrTiO3 substrates that have an atomically flat surface and are composed of only the [110]-type domains. The reason for this difference was ascribed to the effect of lattice mismatch across the film/substrate interface. The room temperature resistivity of SrRuO3 films fabricated at 700°C was 300μΩcm. Therefore, epitaxial SrRuO3 films on MgO substrate could serve as a promising candidate of electrode materials for the fabrication of ferroelectric or dielectric films. [Copyright &y& Elsevier]

Abstract: This study examined the concentrations of carbon monoxide, carbon dioxide, TVOC, TSP, PM10, PM2.5, PM1, benzene, toluene and xylene in passenger cars of the Beijing Ground Railway Transit System (Line No. 13). This system connects the northern suburb and downtown, and is equipped with air-conditioned passenger cars. In-train air quality monitoring was performed in both summer (July and August) and winter (December). To obtain representative data, the sampling design considered both rush and regular hours, urban and suburban areas, as well as the number of passengers. Meanwhile, questionnaires were distributed to the passengers. The monitoring results indicated that, overall, the air quality in the passenger cars was acceptable with a few exceptions, which is consistent with the passengers'' perception. Concentrations of some air pollutants showed significant seasonal variations and had the significant difference between rush hour and regular hour. Furthermore, the in-train air quality was greatly influenced by the number of passengers. This paper describes the experimental design, and presents the preliminary results. [Copyright &y& Elsevier]

Abstract: A series of metallic LaNiO3 (LNO) thin films were deposited on MgO (100) substrates by pulsed laser deposition (PLD) under the oxygen pressure of 20Pa at different substrate temperatures from 450 to 750°C. X-ray diffraction (XRD) was used to characterize the crystal structure of LNO films. θ–2θ scans of XRD indicate that LNO film deposited at a substrate temperature of 700°C has a high orientation of (l l 0). At other substrate temperatures, the LNO films have mixed phases of (l l 0) and (l 00). Furthermore, pole figure measurements show that LNO thin films, with the bicrystalline structure, were epitaxially deposited on MgO (100) substrates in the mode of LNO (110)//MgO (100) at 700°C. Reflection high-energy electric diffraction (RHEED) and atomic force microscopy (AFM) were also performed to investigate the microstructure of LNO films with the high (l l 0) orientation. RHEED patterns clearly confirm this epitaxial relationship. An atomically smooth surface of LNO films at 700°C was obtained. In addition, bicrystalline epitaxial LNO films, fabricated at 700°C, present a excellent conductivity with a lower electrical resistivity of 300μΩcm. Thus, the obtained results indicate that bicystalline epitaxial LNO films could serve as a promising candidate of electrode materials for the fabrication of ferroelectric or dielectric films. [Copyright &y& Elsevier]

Bone size, which has strong genetic determination, is an important determinant of bone strength and a risk factor of osteoporotic fractures. We previously reported an approximately 10-cm genome-wide linkage scan in 630 subjects from 53 US Caucasian pedigrees. The strongest evidence of linkage was obtained on chromosome 17q22 near the marker D17S787, with a two-point LOD score of 3.98 and a multipoint maximum LOD score (MLS) of 3.01. Additionally, suggestive linkages (1.54 < MLS < 2.83) were found at the other four chromosomal regions. In the present study, with an attempt to further examine our previous findings, we perform a follow-up linkage analysis in an expanded sample of 79 pedigrees with 1816 subjects. The total sample contains >80,000 informative relative pairs for linkage analyses, including 3846 sib pairs. Fifteen markers covering the above five promising regions are genotyped, narrowing the average genomic distance from approximately 10 to 5 cm. In the total 79 pedigrees, support of linkage was achieved for the wrist bone size at 17q22 with a two-point LOD score of 2.27 (P = 0.0006) and MLS of 1.78 (P = 0.002). The genomic region 17q22 includes COL1A1, a strong candidate gene that is significantly associated with osteoporotic fracture risk. Our data suggest that this region is promising for further exploratory studies. [Copyright &y& Elsevier]

An ultra-thick nitrided layer (>80 μm) was formed by hot wire enhanced plasma-assisted nitriding of AISI 316L austenitic stainless steel under the higher pulsed bias to investigate the structure and the corrosion performance. The phase structure, the cross-sectional morphology, the element distribution, hardness and modulus, as well as the corrosion behavior of the nitrided layer were investigated by XRD, SEM, EDS, nano-indentation tester and electrochemical workstation, respectively. The results showed that the nitrided layer was divided into two sub-layers: the upper thick layer composed of N-expanded austenite and CrN, and the lower thin layer mainly composed of γ N with a trace of CrN precipitate. Nitrided at −400 V, CrN and high N-expanded austenite formed in the upper layer, which exhibited a high hardness and an excellent corrosion resistance. As the bias increased to −500 V, more nitrogen atoms precipitated as CrN phase and low N-expanded austenite phase began to form, the thickness of nitrided layer reached a maximum of 84 μm. To −600 V, high N-expanded austenite almost completely transformed to low N-expanded austenite, accompanied by the increase of CrN, which caused the thickness and hardness of the nitrided layer to decrease, and the pitting corrosion occurred at −4.1 mV. • An ultra-thick nitrided layer (>80 μm) was formed by hot wire enhanced PAN. • The phase structure of this novel surface layer was analyzed by XRD. • The nitrided layer exhibits excellent corrosion resistance. • The out-diffusion of Cr compensates the depletion of free-Cr in expanded austenite. • The nitrided layer shows high hardness. [ABSTRACT FROM AUTHOR]

An increasing number of epidemiologic studies show that women have a special exposure profile to phthalates, and the exposures have attracted attention regarding their potential health hazards. Here, we developed a model for studying the ovarian action of di-(2-ethylhexyl) phthalate (DEHP) and its major metabolite monoethylhexyl phthalate (MEHP). In vivo, treatment with DEHP (250, 500, and 1000 mg kg^-1) induced decreased thickness of ovarian granulosa cell layer and mitochondrial damage in quail, caused oxidative stress, interfered with the transcription of hypothalamic-pituitary-ovarian axis (HPOA) steroid hormone-related factors (increased transcription of StAR , 3β-HSD , P450scc , and LH and decreased transcription of 17β-HSD , P450arom, FSH , and ERβ), and blocked the secretion of steroid hormones (decreased FSH, E 2 , and T levels and increased LH, P, and PRL levels). In vitro, granulosa cells were cultured with MEHP (50, 100, and 200 μM), activator of PPARγ (rosiglitazone, 50 μM), or antagonist of PPARγ (GW9662, 10 μM) for 24 h and gene and protein expression were analyzed by real time RT-PCR and western blot. Rosiglitazone, like MEHP, significantly decreased mRNA and protein levels of P450arom. Antagonist GW9662 partially blocked the suppression of P450arom by MEHP, suggesting that MEHP acts through PPARγ, but not exclusively. Our model shows that MEHP acts on granulosa cells in quail by stimulating PPARs, which leads to decreased gene and protein expression of P450arom. Therefore, the environmental endocrine disruptor DEHP and its major metabolite MEHP act through a receptor-mediated signaling pathway to inhibit the production of estradiol, interfere with the modulation of HPOA, suppress the synthesis of sex hormones, and cause sex hormone secretion disorders, resulting in severe toxicity in the female reproductive system. A framework for an adverse outcome pathway of DEHP/MEHP-induced ovarian toxicity was constructed, which can facilitate an improved understanding of the mechanism of female reproductive toxicity. The environmental contaminant DEHP and its metabolite MEHP act through a receptor-mediated signaling pathway to suppress estradiol production in the ovary, interfere with the regulation of the hypothalamus-pituitary-ovarian gonadal axis, hinder the synthesis of sex hormones, and trigger sex hormone secretion disorders, leading to serious dose-dependent toxicity of the reproductive system. A framework for an adverse outcome pathway of DEHP/MEHP-induced ovarian toxicity was constructed, which can facilitate an improved understanding of the mechanism of female reproductive toxicity. Unlabelled Image • Exposure to DEHP induced ovarian developmental disorders in quail. • DEHP disrupted sex hormone levels by interfering with the regulation of HPOA. • MEHP decreased aromatase level in the granulosa cell by activating the PPARs. • DEHP and its metabolite MEHP lead to toxicity on the reproductive system. • A framework for an AOP of DEHP/MEHP-induced ovarian toxicity was constructed. [ABSTRACT FROM AUTHOR]

A series of benzothiazole-based compounds were synthesized and characterized. Among them, probe Z showed significant dual-functional performance which was capable of sensing pH change and Cu2+. Probe Z displayed fluorescent turn-on under alkaline conditions due to deprotonation of the hydroxyl group along with the obviously color change from colorless to mint green. Interestingly, it further achieved in ratiometric detection of Cu2+ through absorbance or fluorescence signals in strong alkaline condition. The limit of detection was calculated correspondingly as 0.37 μM and 1.35 μM, respectively. Especially, the combination of the XNOR and INHIBIT logic gates could be used to confirm that one medium was in neutrality or alkalinity condition. Moreover, Z was successfully used in real water samples and test paper for fast identification of Cu2+, respectively. Unlabelled Image • A dual-functional chemosensor Z was synthesized and characterized. • Z was successfully in sensing pH change through significant color chang. • Z was achieved in ratiometric detection of Cu2+ with detection limit as low as 1.35 μM. • Z was successfully used in real water samples and test paper for fast identification of Cu2+. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has been implicated in the pathogenesis of inflammation, myocardial infarction, angiocardiopathy, even cancers. However, it is unknown that Cd-induced cardiac toxicity through Nrf2-mediate antioxidant defense and Cytochrome P450 (CYP450) system. To ascertain the chemoprevention of Cd-induced cardiac toxicity, total 60 newborn chicks were fed with different doses of Cd (0 mg/kg, 35 mg/kg and 70 mg/kg) for a period of 90 days feed administration. Results indicated Cd exposure caused cardiac histopathology changed and functions abnormal, induced NOS activities raised and cardiac inflammation, triggering inflammation factors (IL-6, IL-8, TNF-α, and NF-κb) upregulation and inhabitation of IL-10. Cd caused increase of total CYP450 and Cytochrome b 5 (Cyt b 5) contents, while erythromycin N-demethylase (ERND), aminopyrin N-demethylase (APND), aniline-4-hydeoxylase (AH) and NADPH-cytochrome c reductase (NCR) indicated opposite situations with different degrees of reduction in microsomes. The mRNA level of most CYP450s isoforms (CYP1A1, CYP1A2, CYP1A5, CYP1B1, CYP2C18, CYP2C45, CYP3A4, CYP3A7 and CYP3A9) were significantly increase but CYP2D6 expression level changed not obvious. Furthermore, Cd treatment caused increased the peroxidation product (MDA) and H 2 O 2 over accumulation, the decreased of T-AOC accompanied by decreased activity of antioxidant enzymes (T-SOD, GST and GPX). Over accumulation of Cd lead to oxidative stress and activated Nrf2 signal pathway through upregulating pivotal target genes (HO-1, NQO1, GCLC, GCLM and SOD). These findings suggested Cd exposure caused cardiotoxicity through CYP450s enzymes homeostasis disturbance and Nrf2-mediated oxidative stress signal pathways defense. These results may provide new evidence on molecular mechanism of Cd-induced cardiac toxicity. Cadmium (Cd) enters the heart through cell membranes and disrupts the metabolic system. Findings from the present study provide new evidence that Cd exposure affects the modulation of Cytochrome P450 Systems and Nrf2 mediated antioxidant defense in the heart. Cd exposure resulted in oxidative stress via disrupting the homeostasis of CYP450s, activating Nrf2 signaling. All data supplied in the present study contribute to broadening knowledge on the mechanisms of Cd-induced cardiotoxicity. Image 1 • Cadmium exposure caused cardiotoxicity. • Cadmium induced cardiac inflammation. • Cadmium disturbed the Cytochrome P450 homeostasis in heart. • Cadmium induced oxidative stress via affecting Nrf2 mediated antioxidant defense. [ABSTRACT FROM AUTHOR]

A dual-function probe BHMH was synthesized and characterized functioned with benzothiazole as signal unit for the simultaneous detection of Zn2+ and Al3+ DMF/H 2 O (1/1, v/v, 0.01 M HEPES, pH = 6.0). Probe BHMH achieved in the recognition of Zn2+ and Al3+ both through obvious fluorescence turn-on and absorbance ratiometric response. The limit of detection (LOD) according to the titration of fluorescence for Zn2+ and Al3+ were 1.27 × 10−7 M and 1.42 × 10−7 M, respectively. Furthermore, the significant color changes could be detected by naked eye whatever under ultraviolet-lamp or daylight. According to Job plot, the binding ratio of BHMH with Zn2+ and Al3+ were determined as 1:1 and 2:1, respectively. The binging detail was further confirmed by 1H NMR titration and ESI-MS analysis as well. Moreover, probe BHMH was successfully applied in the detection Zn2+ and Al3+ in real sample and test stripe. Unlabelled Image • Chemosensor BHMH with benzothiazole fluorophore was synthesized and characterized. • BHMH exhibits highly selective to Zn2+ and Al3+ with significant fluorescence turn-on and color change. • Limit of detection (LOD) for Zn2+ and Al3+ were all reached the level of 10−8 M. • BHMH was successfully applied in the detection of Zn2+ and Al3+ in test paper. [ABSTRACT FROM AUTHOR]

Metastasis is regarded as the fatal hallmark for colon cancer, but molecular mechanisms responsible for it have remained poorly defined. Glucocorticoid receptor (GR) within the tumor microenvironment mediates the effects of stress hormones which are used in clinics for their inflammation-modulatory and immunosuppressive properties. Further, epigenetic activation of GR promotes tumor heterogeneity and metastasis. Here, we sought to investigate the correlation between GR activation and proliferation and invasion in metastatic colon cancer microenvironment. We used proliferation/invasion assays, western blot, RT-qPCR, immunofluorescence staining and quantitative methylation to study glucocorticoid-GR signaling, including the involvement of CDK1, in human colon adenocarcinoma cell lines HT29 and T84 (a representative metastatic cell line). Nuclear expression levels of GR were significantly upregulated in metastatic T84 cells, and glucocorticoid derivative, dexamethasone (DEX) treatment caused increased proliferation and invasion in T84 cell, compared to HT29 cell. DEX treatment induced CDK1 expression which was accompanied by reduced CDK1 methylation, indicating epigenetic regulation. Depletion of GR suppressed proliferation of metastatic colon carcinoma cells and depletion of CDK1 had similar suppressing effects on proliferation as well as invasion of metastatic cells. Our study suggests that glucocorticoid-GR-CDK1 signaling induces proliferation and invasion of colon cancer cells and therapies involving the use of glucocorticoids need to exercise caution and re-evaluation. [ABSTRACT FROM AUTHOR]

Background: In endemic areas, placental malaria due to Plasmodium falciparum is most frequent and severe in first-time mothers, and increases the risk of infant mortality in their offspring. Placental malaria may increase the susceptibility of infants to malaria parasitemia, but evidence for this effect is inconclusive.Methods and Findings: During 2002-2004, we monitored parasitemia in 453 infants, including 69 who were born to mothers with placental malaria, in a region of northeastern Tanzania where malaria transmission is intense. We used a Cox proportional hazards model to evaluate the time from birth to first parasitemia, and a generalized estimating equations logistic regression model to evaluate risk of any parasitemia throughout the first year of life. Compared with infants whose mothers did not have placental malaria at delivery ("PM-negative"), offspring of mothers with placental malaria at delivery ("PM-positive") were 41% more likely to experience their first parasitemia at a younger age (adjusted hazard ratio [AHR] = 1.41, 95% confidence interval [CI] 1.01-1.99). The odds of parasitemia throughout infancy were strongly modified by the interaction between placental malaria and gravidity (p for interaction = 0.008, Type 3 likelihood ratio test). Offspring of PM-negative primigravidae had lower odds of parasitemia during infancy (adjusted odds ratio [AOR] = 0.67, 95% CI 0.50-0.91) than offspring of PM-negative multigravidae, and offspring of PM-positive primigravidae had the lowest odds (AOR = 0.21, 95% CI 0.09-0.47). In contrast, offspring of PM-positive multigravidae had significantly higher odds of parasitemia (AOR = 1.59, 95% CI 1.16-2.17).Conclusion: Although parasitemia is more frequent in primigravid than multigravid women, the converse is true in their offspring, especially in offspring of PM-positive women. While placental malaria is known to increase mortality risk for first-born infants, it surprisingly reduced their risk of parasitemia in this study. Placental malaria of multigravidae, on the other hand, is a strong risk factor for parasitemia during infancy, and therefore preventive antimalarial chemotherapy administered to multigravid women close to term may reduce the frequency of parasitemia in their offspring. [ABSTRACT FROM AUTHOR]