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1.
Neurosurg Rev ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643829

RESUMO

Hematoma growth (HG) affects the prognosis of patients with spontaneous intracranial hematoma (ICH), but there is still a lack of evidence about the effects of aspirin (acetylsalicylic acid, ASA) on HG in patients with severe ICH. This study retrospectively analyzed patients with severe ICH who met the inclusion and exclusion criteria in Beijing Tiantan Hospital, Capital Medical University, between January 1, 2015, and July 31, 2019. Severe ICH patients were divided into ASA group and nASA groups according to ASA usage, and the incidence of HG between the groups was compared. Univariate analysis was performed by the Mann-Whitney U test, chi-square test, or Fisher exact test. Multivariate logistic regression analysis was used to analyze the impact of ASA on HG and to screen for risk factors of HG. In total, 221 patients with severe ICH were consecutively enrolled in this study. There were 72 (32.6%) patients in the ASA group and 149 patients in the nASA group. Although the incidence of HG in the nASA group was higher than that in the ASA group (34.9% VS 22.2%, p = 0.056), ASA did not significantly affect the occurrence of HG (p = 0.285) after adjusting for initial hematoma volume, high blood pressure at admission, coronary heart disease, and GCS at admission. In addition, we found that high blood pressure at admission was a risk factor for HG. Prior ASA does not increase the incidence of HG in severe ICH patients, and high blood pressure at admission is a risk factor for HG.

2.
Toxicol Lett ; 352: 26-33, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34571075

RESUMO

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants. They are constantly detected in terrestrial, ocean, and atmospheric systems, and it is of particular concern that these fat-soluble xenobiotics may have a negative impact on human health. This study aimed to evaluate the toxic effect and underlying mechanism of decabromodiphenyl ether (BDE-209) on human liver in a HepG2 cell model. The results showed that BDE-209 significantly induced HepG2 cells apoptosis, increased intracellular reactive oxygen species (ROS), disturbed [Ca 2+] homeostasis and mitochondrial membrane potential (MMP), and caused nuclear shrinkage and DNA double-strand breaks. BDE-209 also significantly decreased the activities of antioxidant parameters, superoxide dismutase (SOD), total antioxygenic capacity (T-AOC), glutathione (GSH), and total glutathione (T-GSH). The up-regulation of the Aryl hydrocarbon receptor (AhR)/cytochrome P4501A1 (CYP1A1) signaling pathway indicates that after long-term and high-dose exposure, BDE-209 may be a liver carcinogen. Interestingly, HepG2 cells attempt to metabolize BDE-209 through the Nrf2-mediated antioxidant pathway. These findings help elucidate the mechanisms of BDE-209-induced hepatotoxicity in humans.

3.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(3): 279-289, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34402257

RESUMO

To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. C57BL/6 pregnant mice were given drinking water containing carbaryl dimethoate glyphosate methomyl methyl parathion triadimefon aspartame sodium benzoate calcium disodium ethylene diamine tetra-acetate ethylparaben butylparaben bisphenol A and acacia gum The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level (<0.05). CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, and TNF-α and hippocampus IFN-γ levels in the offspring(all <0.01). In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring. Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.


Assuntos
Transtorno Autístico , Efeitos Tardios da Exposição Pré-Natal , Adulto , Animais , Transtorno Autístico/induzido quimicamente , Feminino , Humanos , Masculino , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
4.
Toxins (Basel) ; 13(7)2021 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-34357953

RESUMO

Deoxynivalenol (DON) is a major mycotoxin with high toxicity that often contaminates grains, foods and feeds. The traditional approaches for DON removal are difficult to meet industry and agriculture demands due to the high stability of the DON molecule. Therefore, there is an urgent need to develop green and effective strategies for DON degradation. In this study, a batch of photocatalytic nanomaterials of cerium (Ce) doped titanium dioxide (TiO2) were successfully prepared by sol-gel method. The catalysts were systematically characterized by XRD, HRTEM, FT-IR, UV-Vis and XPS. The catalyst 0.5Ce-TiO2 showed superior photocatalytic activity for DON degradation in aqueous solution under ultraviolet light irradiation, better than that of traditional photocatalyst pure TiO2, and 96% DON with initial concentration of 5.0 mg/L could be degraded in 4 h. In addition, the two possible degradation intermediate products C5H8O3 and C17H18O6 were identified, the photocatalytic degradation mechanism and degradation pathway were studied. The results indicate that Ce doped TiO2 photocatalyst can be used to reduce DON effectively.

5.
Clin Cardiol ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34378199

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. Circumferential pulmonary vein ablation (CPVA) is an effective rhythm control strategy, however, recurrence is an important factor influencing treatment decisions. HYPOTHESIS: To develop a predictive model based on left atrial (LA) structure and function, and evaluate its efficiency in predicting the recurrence of AF after CPVA. METHODS: Patients with paroxysmal AF who underwent CPVA were enrolled in this study and randomly divided into a development set and a validation set. The clinical and echocardiographic data of each patient were collected. In the development set, a least absolute shrinkage and selection operator (LASSO) regression was used to establish a LA ultrasound feature. By combining that LA ultrasound feature with independent clinical risk factors, we established an echocardiographic model using multivariate logistic regression and plotted the corresponding nomogram. RESULTS: The LA ultrasound feature established by LASSO regression included nine echocardiographic indicators related to LA structure and function. It also exhibited good predictive ability in both the development set and the validation set (AUC:0.944, 95%CI: 0.910-0.978; AUC:0.878, 95%CI: 0.816-0.942). Logistic regression analysis indicated that LA ultrasound feature and AF duration were independent predictors for AF recurrence. The combined model including LA ultrasound feature and AF duration also showed good discriminability in both the development set (AUC: 0.950, 95% CI:0.914-0.985) and the validation set (AUC: 0.890, 95% CI: 0.831-0.949). The calibration curve showed good agreement between the predicted value and observed value. CONCLUSIONS: Our model that is based on LA structure and function measured by echocardiography is a useful non-invasive preoperative tool, which exhibits good accuracy in predicting the recurrence of AF after CPVA.

6.
Life Sci Alliance ; 4(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34301806

RESUMO

Fecal microbiota transplantation is widely used. Large intestinal microbiota (LIM) is more similar to fecal microbiota than small intestinal microbiota (SIM). The SIM communities are very different from those of LIM. Therefore, SIM transplantation (SIMT) and LIM transplantation (LIMT) might exert different influences. Here, healthy adult male C57Bl/6 mice received intragastric SIMT, LIMT, or sterile PBS administration. Microbiota graft samples were collected from small/large intestine of healthy mice of the same age, sex, and strain background. Compared with PBS treatment, SIMT increased pellet number, stool wet weight, and stool water percentage; induced a fecal microbiota profile shift toward the microbial composition of the SIM graft; induced a systemic anti-inflammatory cytokines profile; and ameliorated depressive-like behaviors in recipients. LIMT, however, induced merely a slight alteration in fecal microbial composition and no significant influence on the other aspects. In sum, SIMT, rather than LIMT, affected defecation features, fecal microbial composition, cytokines profile, and depressive-like behaviors in healthy mice. This study reveals the different effects of SIMT and LIMT, providing an interesting clue for further researches involving gut microbial composition change.

7.
Ecotoxicol Environ Saf ; 222: 112549, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34325200

RESUMO

2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced nephrotoxicity is closely associated with oxidative stresses and mitochondrial abnormalities. Mitochondrial fusion and fission dynamics are crucial for maintaining mitochondrial and cellular physiological homeostasis. However, the detailed mechanisms through which BDE-47 disrupts this dynamic and contributes to renal injuries are still not fully understood. The porcine kidney-15 (PK15) cell line, a well-defined in vitro animal renal toxicological model, was exposed to BDE-47 with concentrations of 12.5, 25, 50, and 100 µM, respectively. Cell viability, the levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP), the mitochondrial membrane potential (MMP), and the expression levels of key mitochondrial fusion and fission proteins were assessed. BDE-47 reduced cell viability and disrupted mitochondrial dynamics by inhibiting mitochondrial fusion and fission simultaneously, leading to MMP decreases, ROS overgeneration, ATP depletion, and cellular disintegration in a dose-dependent manner. Additionally, the mitochondrial division inhibitor (Mdivi-1) with the concentration of 20 µM observed to restore the downregulation of mitochondrial fusion and fission proteins, alleviate damages in mitochondrial morphology and functionality, correct ROS overproduction, and enable cell survival. The antioxidant N-acety-L-cysteine (NAC) with the concentration of 1 mM also simultaneously reversed the imbalance of mitochondrial dynamics, decreased ROS production, and restored mitochondrial morphology in PK15 cells exposed to BDE-47. Our data provide new insights indicating that BDE-47 disrupts mitochondrial fusion/fission dynamics to induce mitochondrial abnormalities, triggering oxidative stresses and thus contributing to PK15 cell dysfunction. ROS-dependent pathways in mitochondrial dynamics may provide a new avenue for developing effective strategies to protect cells against BDE-47-induced nephrotoxicity.


Assuntos
Éteres Difenil Halogenados , Dinâmica Mitocondrial , Animais , Éteres Difenil Halogenados/toxicidade , Rim , Estresse Oxidativo , Espécies Reativas de Oxigênio , Suínos
8.
Bioengineered ; 12(1): 4385-4396, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34304702

RESUMO

Myocardial ischemia/hypoxia-reperfusion injury mediates the progression of multiple cardiovascular diseases. It has been reported that knockdown of adaptor protein containing a PH domain, PTB domain and leucine zipper motif 1 (APPL1) is a significant factor for the progression of myocardial injury. However, the role of APPL1 in myocardial ischemia remains unclear. Hence, the aim of the present study was to investigate the specific mechanism underlying the role of APPL1 in myocardial ischemia.In our study, the mRNA level of APPL1 was detected by quantitative real-time PCR (RT-qPCR). The expressions of APPL1, Apoptotic protease activating factor-1 (APAF-1), cleaved caspase9 and other inflammation- and apoptosis-related proteins were determined by western blotting. The secretion of inflammatory cytokines and lactate dehydrogenase (LDH) levels were measured by commercial assay kits. The H9C2 cell viability was analyzed by cell counting kit-8 (CCK-8) assay. The apoptosis rate of H9C2 cells was analyzed by TUNEL assay. The interaction between APPL1 and APAF-1/caspase9 was determined by Immunoprecipitation (IP).Our findings demonstrated that APPL1 was low expressed in myocardial ischemia tissues and cells. APPL1 knockdown suppressed the viability of myocardial ischemia cells and aggravated hypoxia/reperfusion-induced LDH hypersecretion, inflammation and apoptosis. In addition, the overexpression of APPL1 induced inactivation of APAF-1/Caspase9 signaling pathway. Significantly, APAF1 inhibitor reversed the effect of APPL1 knockdown on viability, LDH secretion, inflammation and apoptosis.We conclude that APPL1 inhibits myocardial ischemia/hypoxia-reperfusion injury via inactivation of APAF-1/Caspase9 signaling pathway. Hence, APPL1 may be a novel and effective target for the treatment of myocardial ischemia.

9.
Chemosphere ; 284: 131346, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34217936

RESUMO

Food is often exposed to multiple types of contaminants, and the coexistence of contaminants may have antagonistic, additive or synergistic effects. This study investigated the combinatorial toxicity of the three most widespread exogenous contaminants, decabrominated diphenyl ether (BDE-209), bisphenol A (BPA), and acrylamide (ACR) to HepG2 cells. A mathematical model (Chou-Talalay) and high-content analysis (HCA) were used to probe the nature of the contaminants' interactions and their cytotoxicity mechanisms, respectively. The results highlighted that for the individual pollutants, the cytotoxicity order was BDE-209> BPA > ACR, and varying combinations of contaminants exhibited additive/synergistic effects. In general, combining multiple contaminants significantly increased intracellular reactive oxygen species (ROS), Ca2+ flux, DNA damage and Caspase-3, and decreased mitochondrial membrane potential (MMP) and nucleus roundness, indicating that the additive or synergistic mechanism of the combined contaminations was disturbance to multiple organelles. This study emphasizes the complexity of human exposure to food contaminants and provides a scientific basis for formulating strict regulatory standards.


Assuntos
Acrilamida , Éteres Difenil Halogenados , Acrilamida/toxicidade , Compostos Benzidrílicos/toxicidade , Éteres Difenil Halogenados/toxicidade , Humanos , Fenóis , Espécies Reativas de Oxigênio
10.
Transl Stroke Res ; 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34105079

RESUMO

Aneurysm wall remodeling (AWR) is an important pathological characteristic in aneurysm wall, which was characterized by abnormal histological structure and inflammation infiltration. In the present study, the aim is to determine the relationships of morphological-hemodynamic characteristics, inflammation, and AWR in intracranial aneurysms (IAs), as well as the pathological basis of morphological-hemodynamic predictors to achieve IA development. For this end, 113 unruptured IAs were prospectively collected from 110 cases. In addition, patient-specific computational fluid dynamics and geometry were adopted to determine hemodynamic and morphological parameters. Moreover, Hematoxylin-Eosin staining was performed to identify the AWR. By performing immunofluorescence, the inflammatory markers were detected. Masson staining was conducted to characterize the characteristics of atherosclerosis in aneurysm wall. To demonstrate the parameters regarding the AWR, a multivariate logistic analysis was conducted. Besides, correlation analyses were conducted to verify the relationship between morphological-hemodynamic and pathological characteristics. For 113 unruptured IAs, no difference was identified in baseline information. AWR was demonstrated in 92 (81.4%) IAs. To be specific, the aneurysm size (odds ratio (OR), 2.63; confidence interval (CI), 1.04-6.67; P = 0.041), size ratio (SR; OR, 1.95; CI, 1.38-2.76; P < 0.001), normalized wall shear stress average (NWSSA; OR, 0.05; CI, 0.01-0.15; P = 0.007), and relative resident time (RRT; OR, 1.28; CI, 1.07-1.53; P = 0.007) were proved as the factors of AWR. As revealed from the results of immunofluorescence, aneurysm size, SR, NWSSA, and RRT were significantly correlated with the level of inflammation in IA tissues. Furthermore, Masson staining revealed that atherosclerosis area in IA tissues and NWSSA was correlated with RRT. In this study, SR, NWSSA, and RRT were demonstrated as the risk factors of AWR. The mentioned parameters could also reflect the characteristics of inflammation and atherosclerosis in aneurysm wall as well. This study revealed that biomechanical stress and inflammation in aneurysm wall are correlated, which might suggest the pathological evidence of morphological-hemodynamic predictors for IA development.

11.
Ecotoxicol Environ Saf ; 219: 112305, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34029840

RESUMO

The wide usage of decabromodiphenyl ether (BDE-209) results in its increasing occurrence in the environment and increasing attention in regard to human and animal health. BDE-209 is an endocrine disruptor for hypothyroidism, but the toxicity mechanism is unclear. Here, the histopathology and transcriptome sequencing of thyroid tissue from broiler chicks were investigated by supplemental feeding with different concentrations of BDE-209 for 42 days (0-4 g/kg in basal diet), followed by determining the levels of thyroid hormones in serum. The results showed ruptured and even hyperplastic follicular epithelial cells in the thyroid, and a total of 501 differentially expressed genes were screened out: 222 upregulated and 279 downregulated. Based on the Kyoto Encyclopedia of Genes and Genomes database, neuroactive ligand-receptor interaction pathway was significantly enriched, and α1D-adrenergic receptor, follicle-stimulating hormone receptor, thyroid stimulating hormone receptor, and somatostatin receptor type 2 were shown to be candidate biomarkers. Thyroxine was a possible biomarker due to clear reduction in serum and significant correlation with exposure concentrations. These results suggested that oral intake of BDE-209 can cause structural injuries and even hyperplasia, and affect gene transcription involved in the neuroactive ligand-receptor interaction pathway of thyroid, as well as thyroid hormones in serum.


Assuntos
Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Animais , Galinhas/metabolismo , Disruptores Endócrinos/toxicidade , Perfilação da Expressão Gênica , Humanos , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Tiroxina/metabolismo , Transcriptoma
12.
Neurosurg Rev ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33877464

RESUMO

Spontaneous intracranial hematoma (ICH) is the second leading cause of stroke and has a high risk of postoperative ischemic events (PIEs). But, the evidence on PIEs in ICH patients still lacks. Therefore, a retrospective study was carried out to screen the risk factors for PIEs and construct a visual predictive model. This was a retrospective study whose population were divided into two groups based on the occurrence of PIEs. Univariate logistic regression analysis was used to determine factors associated with PIEs. Multifactorial logistic regression analysis was used to screen risk factors and construct the early PIEs risk nomogram. In addition, impact of PIEs on patient prognosis and surgery related costs was assessed. Out of 122 ICH patients, 24 (19.7%) were diagnosed with PIEs. Coronary heart disease history, ischemic stroke history, regular shaped hematoma and platelet number were identified as risk factors for early PIEs. Early PIEs risk nomogram showed good calibration and discrimination of the data with concordance index of 0.846 (95% confidence interval, 0.747-0.945) which was confirmed to be 0.827 through bootstrapping validation. In addition, there was statistical difference in discharged Glasgow Coma Scale score (P = 0.046) and surgery related costs (p = 0.031) between PIEs group and nPIEs group. These results showed the early PIEs risk nomogram was accurate for prediction risks of PIEs and the occurrence of PIEs affects prognosis of patients, and increases surgery related costs.

13.
Brain Res Bull ; 171: 103-112, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33766557

RESUMO

Neonatal lipopolysaccharide (LPS) exposure can cause depressive-like behaviors in rodents involving elevated interferon (IFN)-γ. Studies have linked down-regulation of prefrontal cortex (PFC) ATPase phospholipid transporting 8A2(ATP8A2) expression to depressive-like behaviors. In non-neuronal cells, IFN-γ could reduce ATP8A2 expression. Therefore, we hypothesized that neonatal LPS exposure might induce PFC ATP8A2 down-regulation by increasing the IFN-γ level. Here, C57BL6/J mice of both sexes received 3-dose-injections of LPS (50 µg/kg body weight, i.p.) on postnatal day (PND)5, PND7, and PND9. LPS-treated mice showed a transiently decreased PFC ATP8A2 expression indicated by western blot results. Moreover, a significant negative correlation of PFC ATP8A2 expression was found with the IFN-γ level. Using neutralizing mAb, IFN-γ was identified as the key mediator of LPS-induced PFC ATP8A2 decrease indicated by western blot and immunofluorescence results. In sum, neonatal LPS exposure reduced ATP8A2 level in PFC in mice via increasing IFN-γ level. This finding may help further understand the mechanism underlying LPS-induced impairments in brain development and function.

14.
Neurol Sci ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725231

RESUMO

OBJECTIVES: The stability of intracranial aneurysms (IAs) may involve in multidimensional factors. Backpropagation (BP) neural network could be adopted to support clinical work. This preliminary study aimed to delve into the feasibility of BP neural network in assessing the risk of IA rupture/growth and to prove the advantage of multidimensional model over single/double-dimensional model. METHODS: Thirty-six IA patients were recruited from a prospective registration study (ChiCTR1900024547). All patients were followed up until aneurysm ruptured/grew or 36 months after being diagnosed with the IAs. The multidimensional data regarding clinical, morphological, and hemodynamic characteristics were acquired. Hemodynamic analyses were conducted with patient-specific models. Based on these characteristics, seven models were built with BP neural network (the ratio of training set to validation set as 8:1). The area under curves (AUC) was calculated for subsequent comparison. RESULTS: Forty-five characteristics were determined from 36 patients with 37 IAs. In the models based on the single dimension of IA characteristics, only morphological characteristics exhibited high performance in assessing 3-year IA stability (AUC = 0.703, P = 0.035). Among the models integrating two dimensions of IA characteristics, clinical-morphological (AUC = 0.731, P = 0.016), clinical-hemodynamic (AUC = 0.702, P = 0.036), and morphological-hemodynamic (AUC = 0.785, P = 0.003) models were capable of assessing the risk of 3-year IA rupture/growth. Moreover, the models including all three dimensions exhibited the maximum predicting significance (AUC = 0.811, P = 0.001). CONCLUSION: The present preliminary study reported that BP neural network might support assessing the 3-year stability of IAs. Models based on multidimensional characteristics could improve the assessment accuracy for IA rupture/growth.

15.
Sci Total Environ ; 776: 145911, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33647655

RESUMO

Dissolved organic carbon (DOC) and nitrogen (N) play essential roles in global C and N cycles. To address the possible role of DOC and N in precipitation and enrich the related global database, the characteristics of DOC and N in precipitation were investigated in a typical remote permafrost region (upper Heihe River Basin) of the northern Tibetan Plateau (TP) from February 2019 to March 2020. The results demonstrated that the average DOC and total dissolved N (TDN) concentrations in the precipitation were 1.41 ± 1.09 µg mL-1 and 0.84 ± 0.48 µg mL-1, respectively, with relatively lower concentrations in the summer. The annual DOC and TDN fluxes were estimated to be 6.42 kg ha-1 yr-1 and 3.39 kg ha-1 yr-1, respectively, indicating that precipitation was a significant factor in C and N deposition. The light-absorbing properties of precipitation DOC from the SUVA254 and spectral slope revealed that precipitation DOC containing more aromatic components and lower molecular weights mostly was present during the summer; the mass cross-section (at the wavelength of 365 nm) ranged 0.26-1.84 m2 g-1, suggesting the potential impact of DOC on climatic forcing in the area. The principal component analysis combined with air mass backward trajectories indicated that the air masses from west Siberia, Central Asia, and northwestern China most significantly influenced the precipitation C and N in the study area. The WRF-Chem simulations and aerosol vertical distributions further illustrated the air mass transport pathways, demonstrating that dust and anthropogenic emissions could be transported over the studied area by westerlies and monsoonal winds. In the study basin, the precipitation deposition of DOC and N contributed largely to the riverine DOC and N exportation during the summer and had potential ecological effects. These results highlight the importance of DOC and N deposition from precipitation in the northern TP.

16.
Animals (Basel) ; 11(2)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671620

RESUMO

Decabrominated diphenyl ether (BDE-209) is widely used as a flame retardant and is detected at high levels in the environment. Its toxicities have been reported and have attracted attention. In the present study, broilers were used to determine the response in growth performance, carcass traits, meat quality, blood profiles and antioxidant system to BDE-209 exposure at doses of 0, 0.02, 0.4 and 4 mg/kg. The results showed that BDE-209 exposure at levels of 0.02 or 0.4 mg/kg increased feed intake and decreased feed efficiency. BDE-209 altered the blood profiles, such as reducing the numbers of white blood cells, lymphocytes and neutrophilic granulocytes. As compared with the control, BDE-209 exposure significantly increased abdominal fat percentages of broilers at 64.9-159.5% and adversely affected the selected biochemical indicators, including alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine (CRE), which indicated its toxicity to liver and kidney functions. Moreover, BDE-209 exposure significantly increased plasma malondialdehyde (MDA) concentrations and decreased the activities of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD), which implied aggravating oxidant stress and decline of antioxidant capacity in broilers. In conclusion, our data demonstrated that the environmental pollutant BDE-209 adversely influenced growth performance, increased the deposition of abdominal fat, impaired antioxidant capacity and the immune system and had potential toxicity to the liver and kidney of broilers.

17.
Clin Cardiol ; 44(3): 407-414, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33559195

RESUMO

AIM: A predictive model using left atrial function indexes obtained by real-time three-dimensional echocardiography (RT-3DE) and the blood B-type natriuretic peptide (BNP) level was constructed, and its value in predicting recurrence in patients with early persistent atrial fibrillation (AF) after radiofrequency ablation was explored. METHODS: A total of 228 patients with early persistent AF who were scheduled to receive the first circular pulmonary vein ablation (CPVA) were enrolled. Clinical data of patients were collected: (1) The blood BNP level was measured before radiofrequency ablation; (2) RT-3DE was used to obtain the left atrial (LA) time-volume curve; (3) The clinical characteristics, BNP level and LA function parameters were compared, and logistic regression was used to construct a prediction model with combined parameters; (4) The receiver operating characteristic (ROC) curve was used to examine the diagnostic efficacy of the model. RESULTS: (1) 215 patients with early persistent AF completed CPVA and the follow-up. After 3-6 months of follow-up, the patients were divided into sinus rhythm group (160 cases) and recurrence group (55 cases); (2) The recurrence group showed higher minimum LA volume index, diastolic ejection index, and preoperative BNP (all p ≤ .001), while the sinus rhythm group exhibited higher expansion index (PI) and left atrial appendage peak emptying velocity (p ≤ .001); (3) In univariate analysis, BNP level had the best diagnostic performance in predicting the recurrence of AF(AUC = 0.703). We constructed a model based on LA function and BNP level to predict the recurrence of persistent AF after CPVA. This combined model was better than BNP alone in predicting the recurrence of persistent AF after CPVA (AUC: 0.814 vs. 0.703, z = 2.224, p = .026). CONCLUSION: The combined model of LA function and blood BNP level has good predictive value for the recurrence of early persistent AF after CPVA.

18.
Ecotoxicol Environ Saf ; 208: 111638, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396158

RESUMO

The flame retardant decabrominated diphenyl ether (BDE-209) is a widely used chemical in a variety of products and exists extensively in the environment. BDE-209 has been reported to induce kidney injury and dysfunction. However, the causes and mechanisms of its nephrotoxicity are still under investigation. In this study, 150 male broilers were exposed to BDE-209 concentrations of 0, 0.004, 0.04, 0.4, 4.0 g/kg for 42 days. The relative kidney weight, histopathology, markers of renal injury, oxidative stress, inflammation, apoptosis and the expression of MAPK signaling pathways-related proteins were assessed. The results showed that the concentrations of blood urea nitrogen (BUN), creatinine (CRE) and the neutrophil gelatinase-associated lipocalin (NGAL), significantly increased after exposure to BDE-209 with the doses more than 0.04 g/kg. Similarly, severe damage of renal morphology was observed, including atrophy and necrosis of glomeruli, and swelling and granular degeneration of the renal tubular epithelium. In the renal homogenates, the oxidative stress was evidenced by the elevated concentrations of MDA and NO, and decreased levels of GSH-Px, GSH and SOD. Due to the inflammatory response, the level of NF-κB and the pro-inflammatory cytokines TNF-α, IL-1ß, IL-18 were remarkably upregulated, while the content of the anti-inflammatory cytokine IL-10 decreased. Additionally, the apoptotic analysis showed notable upregulations of Bax/Bcl-2 ratio, the relative expression of p-ERK1/2 and p-JNK1/2, and the expression of Bax, cytochrome c and caspase 3. The present study indicates that BDE-209 exposure can cause nephrotoxicity in broilers through oxidative stress and inflammation, which activate the phosphorylation of key proteins of the MAPK signaling pathways, and subsequently induce mitochondria-mediated kidney apoptosis.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Poluentes Ambientais/toxicidade , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Galinhas , Inflamação/induzido quimicamente , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos
19.
Cell Rep ; 34(4): 108683, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33503418

RESUMO

During vesicular acidification, chloride (Cl-), as the counterion, provides the electrical shunt for proton pumping by the vacuolar H+ ATPase. Intracellular CLC transporters mediate Cl- influx to the endolysosomes through their 2Cl-/H+ exchange activity. However, whole-endolysosomal patch-clamp recording also revealed a mysterious conductance releasing Cl- from the lumen. It remains unknown whether CLCs or other Cl- channels are responsible for this activity. Here, we show that the newly identified proton-activated Cl- (PAC) channel traffics from the plasma membrane to endosomes via the classical YxxL motif. PAC deletion abolishes the endosomal Cl- conductance, raises luminal Cl- level, lowers luminal pH, and increases transferrin receptor-mediated endocytosis. PAC overexpression generates a large endosomal Cl- current with properties similar to those of endogenous conductance, hypo-acidifies endosomal pH, and reduces transferrin uptake. We propose that the endosomal Cl- PAC channel functions as a low pH sensor and prevents hyper-acidification by releasing Cl- from the lumen.

20.
Neurosurg Rev ; 44(2): 1205-1216, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32468316

RESUMO

The necessity of emergency surgery for severe spontaneous intracerebral hemorrhage (SSICH) patients on long-term oral antiplatelet therapy (LOAPT) remains unclear. The aim of this study was to investigate the effect and safety of emergency surgery for SSICH patients on LOAPT (SSICH-LOAPT patients). In this study, a retrospective review of patients admitted to our institution for SSICH from January 2012 to December 2018 was conducted. The collected data included demographic, clinical, and surgical information. The outcome was recorded at 3 months after primary hemorrhage. The outcome of SSICH-LOAPT patients receiving emergency surgery and conservative treatment were compared. The risk of postoperative intracranial bleeding (PIB) in operated SSICH-LOAPT patients was further investigated. A total of 522 SSICH patients were retrospectively reviewed, including 181 SSICH-LOAPT patients and 269 operated patients. The total mortality and in-hospital mortality were 40.6% and 19.3%, respectively. As compared with SSICH-LOAPT patients receiving conservative treatment, the operated SSICH-LOAPT patients showed a lower total (p = 0.043) and in-hospital mortality (p = 0.024). When compared with operated patients not on LOAPT, the operated patients on LOAPT exhibited a higher rate of PIB (OR, 2.34; 95% CI 1.14-4.79; p = 0.018). As demonstrated by the multivariate logistic analysis, dual antiplatelet therapy were independent risk factors associated with PIB in operated SSICH-LOAPT patients (OR, 3.42; CI, 1.01-11.51; p = 0.047). Despite of increasing risk of PIB, emergency surgery could improve the outcome of SSICH-LOAPT patients as it could be effective in reducing mortality. Dual antiplatelet therapy was the independent risk factor related to the PIB in operated SSICH-LOAPT patients.


Assuntos
Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/cirurgia , Tratamento de Emergência/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/cirurgia , Índice de Gravidade de Doença , Adulto , Idoso , Hemorragia Cerebral/diagnóstico , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Hemorragia Pós-Operatória/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
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