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1.
Mol Immunol ; 120: 130-135, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32120180

RESUMO

BACKGROUND AND OBJECTIVES: The complement system plays an important role in the development of acute coronary syndrome (ACS). Complement C1q is an important initial component of the classical complement pathway and closely related to many chronic inflammatory diseases, including atherosclerosis (AS). We aimed to determine whether there was association between serum complement C1q and the severity of coronary stenosis. SUBJECTS AND METHODS: 320 patients who underwent coronary arteriography (CAG) were stratified into non-ACS group (control group, n = 74), unstable angina group (UA group, n = 197) and acute myocardial infarction group (AMI group, n = 49) according to the severity of coronary stenosis and clinical manifestations. The severity of coronary stenosis was represented in Gensini score, and serum complement C1q level was compared using immunity transmission turbidity among three groups. RESULTS: The level of complement C1q in AMI group was lower significantly than control group and UA group (P < 0.05), but there was no correlation between serum complement C1q and Gensini score (ß=-0.086, P = 0.125). In nitrate-taking patients, serum complement C1q had a negative association with Gensini score (r=-0.275, P = 0.001), and in non-smokers, there was also a negative correlation (ß=-0.159, P = 0.036). After calibrating smoking, drinking or statins, the serum complement C1q levels of control group, UA group and AMI group decreased in sequence (P <  0.05). Logistic regression analysis showed that the decreasing of serum complement C1q was an unfavorable factor for acute myocardial infarction (OR=0.984, 95 %CI=0.972∼0.997, P = 0.015) and for ACS (OR=0.984, 95 %CI=0.971∼0.984, P = 0.025) in drinking patients. Regrettably, ROC curve suggested that the accuracy in diagnosing coronary atherosclerotic heart disease by serum complement C1q was low (AUC=0.568, 95 %CI= 0.492-0.644, P = 0.076, sensitivity 73.6 %, specificity 58.1 %). CONCLUSION: Serum complement C1q in ACS patients, in particular AMI patients, showed lower level. This finding suggests further decrease of complement C1q level in ACS patients may be a contributory factor to instability or rupture of atherosclerotic plaques. Combined with other clinical indicators, it can be helpful to predict the risk and severity of coronary stenosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32096609

RESUMO

BACKGROUND: Sarcopenia causes several adverse events in elderly people. Muscle fibre atrophy and interstitial fibrosis are the main histopathological changes in sarcopenia and account for decreased muscle function. Tribbles homologue 3 (TRB3) was previously reported to exhibit age-related expression and play a vital role in cell proliferation, differentiation, and fibrosis. We aimed to investigate how TRB3 affects sarcopenia. METHODS: Wild-type and TRB3 knockout C57/BL6J mice were randomly divided into young and old groups. Exercise capacity was evaluated, and single-muscle function was detected by electrophysiological techniques, after which the mice were sacrificed to collect their gastrocnemius muscles for assessment of atrophy and fibrosis by histopathological and molecular biological methods. TRB3 expression, autophagy level, and MAPK signalling pathway activity were evaluated through western blotting. The interaction of TRB3 with P62 and the association between TRB3 and the MAPK signalling pathway were detected by co-immunoprecipitation. RESULTS: In aged mice, exercise capacity and cross-sectional area of skeletal muscle fibres were decreased significantly, whereas TRB3, atrophy-related markers atrogin 1 and MuRF 1, and interstitial fibrosis, including collagen volume fraction, contents of collagens I and III, and ratio of collagens I to III, were increased significantly (P < 0.05 for all). Following TRB3 knockout, the cross-sectional area of muscle fibres, mainly fast fibres, was elevated (P < 0.05 for both), the atrogin 1 expression was decreased (P = 0.0163), and the corresponding tetanic force of fast muscles was increased (P = 0.0398). Conversely, interstitial fibrosis was substantially decreased and exercise capacity was significantly increased in the knockout mice. In terms of the underlying mechanisms, the autophagy receptor p62 was markedly increased and the MAPK signalling pathway was activated in aged skeletal muscles, which might be attributed to the interaction of TRB3 with p62 and MAPKKs, including MEK1/MEK2, MEK3/MEK6, and MEK4/MKK4. Notably, TRB3 knockout reduced the accumulation of p62 and LC3 (P < 0.05 for both), decreased the phosphorylation of JNK (P = 0.0015), and increased p38 phosphorylation (P = 0.0021). CONCLUSIONS: TRB3 knockout in mice attenuated muscle fibre atrophy and reduced skeletal muscle fibrosis by increasing autophagy and inhibiting the MAPK signalling pathway. Correspondingly, in aged knockout mice, exercise capacity was improved. Interfering with TRB3 expression in aged skeletal muscles may serve as a target for the prevention and treatment of age-related sarcopenia.

3.
Chemosphere ; 246: 125661, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31891846

RESUMO

Neonicotinoids are increasingly being used for pest control, and their potential health risks are now receiving attention. In this study, the toxic effects of three neonicotinoids (dinotefuran, nitenpyram and acetamiprid) were evaluated in ICR mice. After 30 days of exposure to neonicotinoids (1/200 LD50), oxidative stress levels, biochemical parameters, free fatty acids contents, and 1H NMR-based hepatic metabolomics were tested. All treatment groups showed signs of amino acid metabolism disorders especially elevated branched chain amino acids and phenylalanine. Furthermore, animals exposed to neonicotinoids had elevated lipid levels, which induced oxidative stress. Overall, we found that oxidative stress is a common toxic effect of exposure to neonicotinoids. In addition, lipid accumulation induced by amino acid metabolism disorder may be the cause of oxidative stress. Our results further our understanding of the toxicological effects of neonicotinoids on mammals.

4.
J Hazard Mater ; 388: 122034, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31951990

RESUMO

The environmental health risks of a new type of organophosphate flame retardant, 2-ethylhexyl diphenyl phosphate (EHDPHP), which is present in large quantities in various Nordic foods, have attracted the attention of scientists recently. In this study, the metabolic homeostasis of low-fat diet (LFD) and high-fat diet (HFD) fed male mice offspring was assessed after perinatal exposure to two doses (30 µg/kg bw/day and 300 µg/kg bw/day) of EHDPHP. Perinatal exposure to EHDPHP resulted in weight changes in male mice offspring, altered glucose tolerance and induced liver damage, and surprisingly these changes were dose- and diet- specific. Then the 1H NMR-based metabolomics, 16S rRNA sequencing, and qRT-PCR techniques were used to explore the mechanisms of these specific changes. The results indicate that the increase in short-chain fatty acids and the increase in Clostridium in the high-dose group may be responsible for the dose-specificity, while the attenuation of the purine metabolic pathway and the decrease in glutamine levels in the HFD group are accountable for the diet-specificity. In addition, down-regulation of PPARG (peroxisome proliferator-activated receptor gamma) gene expression levels might have caused the decrease in body weight in the H + HFD (high dose exposure with HFD feeding) group. Over all, these results elucidated the effects of dosage and diet on the toxicology of EHDPHP.

5.
Environ Pollut ; 257: 113555, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31733957

RESUMO

(±) - PEN is a chiral fungicide widely used to control powdery mildew in agriculture. Currently, only a few studies have investigated the toxic effects of (±) - penconazole ((±) - PEN) on non-target organisms, and whether (±) - PEN from the enantiomeric level have toxic effects remains unclear. In this study, we systematically evaluated the effects of exposure to (±) - PEN, (+) - PEN and (-) - PEN on liver function in mice. Biochemical and histopathological analyses showed that exposure to (±) - PEN and (-) - PEN led to significant liver damage and inflammation. However, exposure to (+) - PEN treatment did not cause no adverse effects on liver function and inflammation. 1H-NMR-based metabolomics revealed that exposure to (±) - PEN, (+) - PEN and (-) - PEN led to the animals developing liver metabolic disorder that was caused by changes in glycolipid metabolism. Quantitative analysis of genes regulating glycolipid metabolism revealed that expression of gluconeogenesis and glycolytic pathway genes were altered in individuals exposed to (±) - PEN, (+) - PEN and (-) - PEN. We also found that (±) - PEN, (+) - PEN and (-) - PEN have different effects on lipid metabolism of the liver. Exposure to (±) - PEN and (-) - PEN resulted in significant accumulation of lipids by regulating fatty acid synthesis, triglyceride synthesis, and fatty acid ß oxidation pathways. In summary, we found different toxicological effects in individuals exposed to (±) - PEN, (+) - PEN and (-) - PEN. The results of this study are important for assessing the potential health risks of (±) - PEN.

6.
Environ Pollut ; 257: 113564, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753638

RESUMO

In the context of global warming, an important issue is that many pesticides become more toxic, putting non-target organisms at higher risk of pesticide exposure. Eremias argus (a native Chinese lizard) was selected as animal model in this study. As a kind of poikilothermic vertebrate, E.argus is sensitive to temperature change. The experimental design [(with or without L-Glufosinate-ammonium (L-GLA) pollution × two temperatures (25 and 30 °C)] was used in this study for 90 days to identify the chronic effects of the pesticide-temperature interaction on the lizards' neuroendocrine-regulated reproduction. Survival rate, body weight, clutch characteristics, testicular histopathology, the content of neurotransmitters and related enzyme activity, the level of sex steroid, the expression of Heat shock protein 70 (HSP70), antioxidant system, the accumulation and degradation of L-GLA were examined. Results showed that L-GLA disrupt reproduction of lizards through hypothalamus-pituitary-gonad (HPG) axis. In addition, temperature can not only change the environmental behavior of pesticides, but also alter the physiological characteristics of lizards. Thus, our results emphasized that temperature is an essential abiotic factor that should not be overlooked in ecotoxicological studies.

7.
IEEE Trans Biomed Circuits Syst ; 13(6): 1583-1592, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31751285

RESUMO

A dual-band dual-polarized wearable array is proposed, based on a miniaturized innovating button radiator topology. The diameter of the rigid button is only 19.5 mm (0.29 λ at 4.5 GHz), which optimizes the users' comfort, and makes it the smallest up to date in literature. The operational bands are 4.50-4.61 GHz and 5.04-5.50 GHz. The antenna thus covers the 4.5-4.6 unlicensed future 5th generation (5G) communication band for the internet of things (IoT), and the 5.1-5.5 GHz wireless local area network (WLAN) band, respectively. Two orthogonal linear polarizations are obtained in each band. A low mutual coupling between the button antenna elements (below -18 dB) and between the two ports within each element (below -20 dB) is achieved, guaranteeing a good diversity performance. The envelope correlation coefficient (ECC) and the specific absorption rate (SAR) performance are also analyzed. In order to demonstrate the robustness of the button antenna and to mimic realistic situations, a more complicated asymmetrical ground plane model of the button antenna is studied for the first time. A prototype of a two-element button array has been fabricated. The measurement results match well with the simulations. A 10-element button array is studied within the context of a 3-D channel model, taking into account the button element's radiation pattern. A high achievable spectral efficiency (SE) is obtained.

8.
Cancer Biol Med ; 16(3): 486-497, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31565479

RESUMO

Cancer immunotherapy is an artificial stimulation of the immune system to recognize cancer cells and activate specific immune cells to target and attack cancer cells. In clinical trials, immunotherapy has recently shown impressive results in the treatment of multiple cancers. Thus, cancer immunotherapy has gained a lot of attention for its unique advantages and promising future. With extensive research on cancer immunotherapy, its safety and effectiveness has gradually been revealed. However, it is still a huge challenge to expand and drive this therapy while maintaining low toxicity, high specificity, and long-lasting efficacy. As a unique technology, nanotechnology has been applied in many fields, the advantages of which will promote the development of cancer immunotherapies. Researchers have tried to apply nanomaterials to cancer immunotherapy due to their advantageous properties, such as large specific surface areas, effective drug delivery, and controlled surface chemistry, to improve treatment efficacy. Here, we briefly introduce the current applications of nanomaterials in cancer immunotherapy, including adoptive cell therapy (ACT), therapeutic cancer vaccines, and monoclonal antibodies, and throw light on future directions of nanotechnology-based cancer immunotherapy.

9.
Environ Pollut ; 255(Pt 2): 113269, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31574395

RESUMO

Triazole fungicides are widely used in agriculture production and have adverse impacts on aquatic organisms. As one of the triazole fungicides, prothioconazole has been reported to cause many toxicological effects, but its risks to aquatic organisms are unknown. In this study, we systematically explored the toxicity effects of prothioconazole exposure on zebrafish embryos (Danio rerio) involving in developmental toxicity, oxidative damage and metabolism disorders. The results showed that prothioconazole exposure to zebrafish embryos produced a series of toxic symptoms, including hatching inhibition, shortening of body length, pericardial cyst and yolk cyst. In addition, prothioconazole exposure caused significant lipid peroxidation and oxidative damage. Particularly, we also found that metabolites and genes involved in lipid metabolism also showed significant changes. This study may provide theoretical basis for systematically assessing the potential risks of zebrafish embryos with prothioconazole exposure.


Assuntos
Embrião não Mamífero/fisiologia , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Organismos Aquáticos , Embrião não Mamífero/efeitos dos fármacos , Metabolismo dos Lipídeos , Peroxidação de Lipídeos , Poluentes Químicos da Água/análise , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-31523760

RESUMO

BACKGROUND: Levosimendan, a calcium sensitizer and potassium channel opener, has been demonstrated to improve myocardial function without increasing oxygen consumption and to show protective effects in other organs. Recently, a prospective, randomized controlled trial (RCT) revealed an association between levosimendan use and a possible increased risk of bleeding postoperatively. Levosimendan's anti-platelet effects have been shown in in vitro studies. Current studies do not provide sufficient data to support a relation between perioperative levosimendan administration and increased bleeding risk. PURPOSE: Our goal was to investigate the relation between perioperative levosimendan administration and increased bleeding risk using a meta-analysis study design. METHODS: The PubMed, Ovid, EMBASE and Cochrane Library databases were searched for relevant RCTs before July 1, 2019. The outcome parameters included reoperation secondary to increased bleeding in the postoperative period, the amount of postoperative recorded blood loss, and the need for transfusion of packed red blood cells (RBCs) and other blood products. RESULTS: A total of 1160 patients in nine RCTs (576 in the levosimendan group and 584 in the control group) were included according to our inclusion criteria. Analysis showed that perioperative levosimendan administration neither increased the rate of reoperation secondary to bleeding nor increased the amount of postoperative chest tube drainage when compared with the control group. In terms of blood product transfusion, levosimendan did not influence the requirement for RBC transfusion, platelet transfusion nor fresh frozen plasma (FFP) transfusion. Levosimendan also did not shorten or prolong the aortic cross-clamp time or the cardiopulmonary bypass time. CONCLUSION: The analyzed parameters, including reoperations due to bleeding, postoperative chest drainage and the requirement for blood products, revealed that levosimendan did not increase postoperative bleeding risk. More studies with a larger sample size are needed to address a more reliable conclusion due to study limitations.

11.
J Agric Food Chem ; 67(30): 8303-8311, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31298535

RESUMO

Exposure to chiral pesticides poses many potential health risks. In this study, we examined the impacts of exposure to penconazole and its enantiomers on gut microbiota and metabolic profiles in mice. The relative abundance of microbiota in cecal content significantly changed following exposure to penconazole and its enantiomers. At the genus level, the relative abundances of seven gut microflora were altered following exposure to (-)-penconazole. Both (±)-penconazole and (+)-penconazole caused significant changes in the relative abundances of five gut microflora. In addition, targeted serum metabolomics analysis showed disturbed metabolic profiles following exposure. Respectively, (±)-penconazole, (+)-penconazole, and (-)-penconazole exposure significantly altered the relative levels of 29, 23, and 36 metabolites. In general, exposure to penconazole and its enantiomers caused disorders in gut microbiota and metabolic profiles of mice. The potential health risks of penconazole and its enantiomers now require further evaluation.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos/metabolismo , Praguicidas/química , Praguicidas/farmacologia , Triazóis/química , Triazóis/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Trato Gastrointestinal/microbiologia , Masculino , Camundongos Endogâmicos ICR , Filogenia , Estereoisomerismo
12.
Cell Regen (Lond) ; 8(1): 9-11, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31205683

RESUMO

Animal models that can mimic human diseases are the important tools for investigating the pathogenesis of the diseases and finding a way for treatment. There is no doubt that small animal models have provided a wealth of information regarding disease pathogenesis and also offered widely used tools to develop therapeutic strategies. Rodent models have been very valuable for investigators to understand the mechanisms underlying misfolded protein-mediated neuronal dysfunction and behavioral phenotypes in a variety of neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's diseases (HD). However, most of genetically modified rodent models of these diseases lack the overt and selective neurodegeneration seen in the patient brains. Since large animals are more similar to humans than small animals and rodents, the large animal models are likely to mimic important neuropathological features in humans. Here we discuss the application of large animal models in neurodegenerative disease research with focus on the HD large animal models, aiming to provide insight into the application of animal models to study neurodegenerative diseases.

13.
J Agric Food Chem ; 67(16): 4623-4631, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30950260

RESUMO

Propiconazole is a triazole fungicide that has been widely used in agriculture and has been detected in the aquatic environment. This study aimed to investigate the effects of propiconazole exposure on lipid metabolism in the early life stages of zebrafish for 120 h postfertilization (hpf). Using the early life stages of zebrafish to address scientific questions is lower in cost, more efficient, and suitable to meeting current legislation than those in other traditional fish species. Exposure to propiconazole significantly inhibited the development of zebrafish embryos and larvae. This exposure also caused reduced locomotor activities in zebrafish. Furthermore, total cholesterol levels, lipoprotein lipase, and fatty acid synthase activities were significantly decreased. The expression levels of genes involved in lipid metabolism were significantly up-regulated in response to propiconazole exposure. GC-MS/MS analysis revealed that fatty acids were significantly decreased. Together, the findings indicate the potential environmental risks of propiconazole exposure in the aquatic ecosystem.


Assuntos
Fungicidas Industriais/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Triazóis/toxicidade , Peixe-Zebra/embriologia , Animais , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Feminino , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
14.
Chemosphere ; 226: 520-533, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953897

RESUMO

Hexaconazole and epoxiconazole are the worldwidely used fungicides. However, limited information is known about the toxicological effects of their enantiomers on aquatic organisms. In this study, zebrafish were separately exposed to 100 and 1000 µgL-1 hexaconazole and epoxiconazole enantiomers for 21 d 1H NMR-based metabolomics analysis showed that the exposure of low and high dose of hexaconazole enantiomers altered energy metabolism, lipid metabolism and amino acid metabolism of zebrafish, with the different metabolic profiles resulted from the same dose of (+)-hexaconazole and (-)-hexaconazole. Similar to hexaconazole enantiomers, the metabolic profiles, including the changes related to energy metabolism, lipid metabolism and amino acid metabolism, were demonstrated in low and high dose epoxiconazole enantiomers treatment groups. There are differences in the metabolic profiles of zebrafish between exposed to (+)-epoxiconazole and (-)-epoxiconazole of the same dose. The results of histological examination revealed that the exposure of both enantiomers for hexaconazole and epoxiconazole resulted in the similar histopathological changes. The exposure of hexaconazole and epoxiconazole enantiomers at low and high dose resulted the vacuolization and swell in the liver of the female and male zebrafish. Compared to female zebrafish, more liver damage was found in male zebrafish in the hexaconazole enantiomers exposure groups. The reduction of spermatids was observed in hexaconazole and epoxiconazole enantiomers treatment groups of both doses. Hexaconazole enantiomers exposure of low and high dose resulted the increase in the number of mature eggs, while such effect was not observed in epoxiconazole enantiomers exposure groups. Hexaconazole and epoxiconazole enantiomers exposure resulted in no changes in brains of female and male zebrafish. As a result, both triazole-based chiral bactericides, hexaconazole and epoxiconazole, have similar toxicological effects but their mechanisms of action are not exactly the same. The above results will play an important part in making the differences in toxic effects of hexaconazole and epoxiconazole enantiomers clear. What's more, it is an indispensable part for an integrated environmental risk assessment.


Assuntos
Aminoácidos/metabolismo , Metabolismo Energético/efeitos dos fármacos , Compostos de Epóxi/toxicidade , Fungicidas Industriais/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Espermátides/efeitos dos fármacos , Triazóis/toxicidade , Peixe-Zebra/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Feminino , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Modelos Animais , Óvulo/citologia , Contagem de Espermatozoides , Espermátides/citologia , Estereoisomerismo
15.
Polymers (Basel) ; 11(3)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30960386

RESUMO

We present a novel approach for the preparation of polymer-TiO2 composite microgels. These microgels were prepared by the in situ hydrolysis and condensation of titanium tetrabutoxide (TBOT) in a mixed ethanol/acetonitrile solvent system, using poly(styrene-co-N-isopropylacrylamide)/poly(N-isopropylacrylamide-co-methacrylic acid) (P(St-NIPAM/P(NIPAM-co-MAA)) as the core component. Silver nanoparticles (AgNPs) were controllably loaded onto the polymer-TiO2 composite microgels through the reduction of an ammoniacal silver solution in ethanol catalyzed by NaOH. The results showed that the P(St-NIPAM)/P(NIPAM-co-MAA)-TiO2 (polymer-TiO2) organic-inorganic composite microgels were less thermally sensitive than the polymer gels themselves, owing to rigid O⁻Ti⁻O chains introduced into the three-dimensional framework of the polymer microgels. The sizes of the AgNPs and their loading amount were controlled by adjusting the initial concentration of [Ag(NH3)2]⁺. The surface plasmon resonance (SPR) band of the P(St-NIPAM)/P(NIPAM-co-MAA)-TiO2/Ag (polymer-TiO2/Ag) composite microgels can be tuned by changing the temperature of the environment. The catalytic activities of the polymer-TiO2/Ag composite microgels were investigated in the NaBH4 reduction of 4-nitrophenol. It was demonstrated that the organic-inorganic network chains of the polymer microgels not only favor the mass transfer of the reactant but can also modulate the catalytic activities of the AgNPs by tuning the temperature.

16.
Environ Res ; 173: 189-198, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30921577

RESUMO

Bisphenol S (BPS), a substitute of bisphenol A (BPA), is widely used for manufacturing different polymers. Due to its wide range of applications, BPS has been frequently detected in the foodstuffs, environment and human blood and excreta. In this study, we examined the effects of the perinatal exposure to BPS on obesity development using 1H NMR based on metabolomics strategy combined with gene expression analysis in male mouse offspring at a dosage of 100 ng/g bw/day. We found that perinatal exposure to BPS significantly increased the body weight, the weights of liver and epididymal white adipose tissue (epiWAT), serum alanine aminotransferase (ALT) activity, and the contents of triglyceride (TG) and cholesterol (T-Cho) in the liver. Histopathological analysis showed that lipids were accumulated significantly in liver tissues and epiWAT with BPS exposure. Furthermore, expressions of genes involved in the inflammatory pathways were significantly increased in liver tissues and epiWAT. Meanwhile, serum metabolomics study showed significant changes in the contents of metabolites associated with lipid and glucose metabolism. Correspondingly, the relative expression levels of genes involved in lipid and glucose metabolism were significantly changed in the liver tissue and epiWAT of male mouse offspring. In conclusion, these results showed that perinatal exposure to BPS may increase the risk of obesity by interfering with lipid and glucose metabolism in male mouse offspring. The potential health risks of BPS in the human required further detailed studies evaluating.


Assuntos
Compostos Benzidrílicos , Obesidade , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Sulfonas/toxicidade , Animais , Feminino , Glucose , Humanos , Lipídeos , Masculino , Camundongos , Gravidez
17.
Environ Pollut ; 247: 935-943, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30823348

RESUMO

Bisphenols (BPs) are common environmental pollutants that are ubiquitous in the natural environment and can affect human health. In this study, we explored the effects of perinatal exposure to BPA, BPF and BPAF on liver function involving in oxidative damage and metabolic disorders in male mouse offspring. We found that BPA exposure impairs the antioxidant defense system, increases lipid peroxidation, and causes oxidative damage in the liver. Furthermore, the levels of 13 metabolites were significantly altered following BPA exposure. We found that BPF exposure significantly increased the expression and activity of CAT, suggesting disturbances in the antioxidant defense system. Moreover, BPF exposure led to metabolic disorders in the liver due to changes in the levels of 8 key metabolites. Exposure to BPAF caused no negative effects on oxidative damage, but altered the levels of ß-glucose and glycogen. In summary, perinatal exposure to BPA, BPF and BPAF differentially influence oxidative damage and metabolic disorders in the livers of male mouse offspring. The impact of early life exposure to BPs now warrants future investigations.


Assuntos
Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Fígado/efeitos dos fármacos , Troca Materno-Fetal , Fenóis/toxicidade , Animais , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/metabolismo , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Gravidez
19.
Acta Neuropathol ; 137(6): 919-937, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30810811

RESUMO

The cytoplasmic accumulation of the nuclear TAR DNA-binding protein 43 (TDP-43) is a pathologic hallmark in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and other neurological disorders. However, most transgenic TDP-43 rodent models show predominant nuclear distribution of TDP-43 in the brain. By expressing mutant TDP-43 (M337V) in the brains of rhesus monkeys and mice, we verified that mutant TDP-43 is distributed in the cytoplasm of the monkey brain and that the majority of mutant TDP-43 remains in the nuclei of the mouse brain. The primate-specific caspase-4, but not mouse homologue caspase-11, could remove the NLS-containing N-terminal domain and generate fragmented TDP-43 that accumulates in the cytoplasm. Moreover, increased expression of caspase-4 in the monkey brain promotes the cytoplasmic accumulation of endogenous TDP-43, and suppressing caspase-4 reduces the cytoplasmic distribution of endogenous TDP-43 in cultured human neural cells. Our findings suggest that primate-specific caspase-4-mediated cleavage of TDP-43 accounts for its cytoplasmic mislocalization in the primate brains and may serve as a potential therapeutic target.

20.
Braz J Med Biol Res ; 52(2): e7739, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30698226

RESUMO

Alteplase (tPA) intravenous thrombolysis is an effective treatment for acute ischemic stroke (AIS) when administered within 4.5 h of initial stroke symptoms. Here, its safety and efficacy were evaluated among AIS patients with a previous history of cerebral hemorrhage. Patients who arrived at the hospital within 4.5 h of initial stroke symptoms and who were treated with tPA intravenous thrombolysis or conventional therapies were analyzed. The 90-day modified Rankin scale (90-d mRS) was used alongside mortality and incidence of symptomatic intracerebral hemorrhage (SICH) rates to evaluate the curative effect of these therapies. Among 1,694 AIS patients, 805 patients were treated with intravenous thrombolysis, including patients with (n=793) or without (n=12) a history of cerebral hemorrhage, and the rate of incidence of SICH significantly differed between them (8.3 vs 4.3%, P=0.039). No significant difference was found in 90-d mRS measurements (41.7 vs 43.6%, P=0.530) and 90-d mortality rates (8.3 vs 6.5%, P=0.946). A total of 76 AIS patients with a history of cerebral hemorrhage received tPA thrombolytic therapy (n=12) or conventional therapy (n=64), and a significant difference was noted in the 90-d mRS scores between the two groups (41.7 vs 23.4%, P=0.029), while no significant difference was found in SICH measurements (8.3 vs 4.6%, P=0.610) and 90-d mortality rates (8.3 vs 9.4%, P=0.227). A history of cerebral hemorrhage is not an absolute contraindication for thrombolytic therapy; tPA intravenous thrombolysis does not increase SICH measurements and mortality rates in patients with a history of cerebral hemorrhage, and they may benefit from thrombolytic therapy.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Hemorragias Intracranianas/etiologia , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Trombolítica/métodos , Resultado do Tratamento
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