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1.
J Nanosci Nanotechnol ; 20(2): 701-708, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383065

RESUMO

In the present study we developed novel luminescent magnetic nanocomposites termed Fe3O4@polyaniline/carbon dots. First, Fe3O4 magnetic nanoparticles were prepared by the coprecipitation method. The nanoparticles were then coated with polyaniline using the in situ growth method to form Fe3O4@polyaniline nanohybrids, which were endowed with amino functional groups on the surface and avoided the aggregation of Fe3O4 nanoparticles. The X-ray diffraction pattern demonstrated that the crystalline phase of the Fe3O4 nanoparticles was an inverse spinel structure and was not changed in the Fe3O4@polyaniline nanohybrids. The saturation magnetization and the coercive force of the as-prepared Fe3O4@polyaniline nanohybrids measured by a vibrating sample magnetizer were 63.7 emu·g-1 and zero respectively, which indicated that the Fe3O4@polyaniline nanohybrids exhibited excellent superparamagnetism. The Fe3O4@polyaniline nanohybrids were conjugated with carbon dots, prepared from orange juice, via the amide bond between the amino groups on the surface of the Fe3O4@polyaniline nanohybrids and the carboxyl groups on the surface of carbon dots. The obtained luminescent magnetic nanocomposites Fe3O4@polyaniline/carbon dots showed good photoluminescent properties, which hinted that the nanocomposites have potential in drug tracing and magnetic targeted drug delivery. Finally, the anticancer drug methotrexate was loaded into the Fe3O4@polyaniline/carbon dots nanocomposites, forming a novel magnetic targeted drug delivery system. The results confirmed that the novel drug delivery system exhibited excellent drug-loading capability for methotrexate of ca. 70%, and emits strong fluorescence at the wavelength of 360 nm. An in vitro release experiment of the drug delivery system indicated that the cumulative release percentage of methotrexate was 17.2% in the phosphate-buffered saline (pH = 7.4) within 36 h.

2.
Bioresour Technol ; 291: 121849, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31387051

RESUMO

Anaerobic digestion (AD) has been widely applied as an economic option for food waste (FW) treatment. In this study, the group treated with ethanol pre-fermentation (EP) for 12 h (EP12) exhibited the highest cumulative biogas yield (206 mL/g-volatile solid) during AD process and therefore it was used to illuminate the underlying metabolic processes of AD with EP. Carbon isotope labeled glucose was supplemented to FW substrate, and the EP process was found to alleviate the acidification inhibition with conducting extremely high carbon flux towards ethanol formation (43.7%). Then an efficient acetogenesis phase was also observed in EP12 group, because of high carbon conversion rate from ethanol to acetate. Overall, higher carbon conversion rate to methane (90.1%) during methanogenesis was found in the AD system with EP than in the control experiment (80.3%). Thus, we quantitatively confirmed that EP affects the AD metabolism of FW in terms of carbon flow distribution.


Assuntos
Alimentos , Metano/biossíntese , Anaerobiose , Biocombustíveis , Isótopos de Carbono , Etanol/metabolismo , Fermentação , Marcação por Isótopo
3.
Exp Cell Res ; : 111555, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31415763

RESUMO

Osteoclast adhesion is important for bone resorption. Osteoprotegerin inhibits osteoclast differentiation and bone resorption via Ca2+ signaling. Purinergic receptor P2X7 (P2X7R) affects osteoclastogenesis by activating transcription factor nuclear factor of activated T cells 1 (NFATc1). However, the detailed mechanism of osteoprotegerin-mediated P2X7R modulation of osteoclast adhesion is unclear. This study aimed to determine the effect of P2X7R on osteoprotegerin-induced damage to osteoclast adhesion. Osteoprotegerin reduced the expression of P2X7R, and protein tyrosine kinase 2 (PYK2) and SRC phosphorylation, and reduced calcium concentration, significantly decreasing Ca2+-NFATc1 signaling. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM)/N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) partly or absolutely recovered osteoprotegerin-induced osteoclasts adhesion structure damage, including increased the PYK2 and SRC phosphorylation, changed the distribution of PYK2/SRC and integrinαvß3, and inhibited retraction of lamellipodia and filopodia and recovered osteoclast bone resorption activity. In addition, BAPTA-AM/W-7 also increased osteoprotegerin-induced activation of Ca2+-NFATc1 signaling, and restored normal P2X7R levels. P2X7R knockdown significantly inhibited osteoclast differentiation, and the formation of lamellipodia and filopodia, reduced the PYK2 and SRC phosphorylation, and inhibited Ca2+-related protein activation. However, P2X7R knockdown aggravated osteoprotegerin-induced osteoclast adhesion damage via Ca2+ signaling. In conclusion, the P2X7R-Ca2+ NFATc1 signaling pathway has a key functional role in osteoprotegerin-induced osteoclast adhesion structure damage.

4.
Molecules ; 24(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284444

RESUMO

Zearalenone (ZEA) interferes with the function of the male reproductive system, but its molecular mechanism has yet to be completely elucidated. Sertoli cells (SCs) are important in the male reproductive system. Silencing information regulator 1 (SIRT1) is a cell metabolism sensor and resveratrol (RSV) is an activator of SIRT1. In this study we investigated whether SIRT1 is involved in the regulation of ZEA-induced lactate metabolism disorder in SCs. The results showed that the cytotoxicity of ZEA toward SCs increased with increasing ZEA concentration. Moreover, ZEA induced a decrease in the production of lactic acid and pyruvate of SCs and inhibited the expression of glycolytic genes and lactic acid production-related proteins. ZEA also led to a decreased expression of SIRT1 in energy receptors and decreased ATP levels in SCs. However, the ZEA-induced cytotoxicity and decline in lactic acid production in SCs were alleviated by the use of RSV, which is an activator of SIRT1. In summary, ZEA decreased lactic acid production in SCs, while the treatment with an SIRT1 activator, RSV, restored the inhibition of lactic acid production in SCs and reduced cytotoxicity of ZEA toward SCs.

6.
J Cell Biochem ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31264285

RESUMO

Recent studies have shown that monounsaturated oleic acid induces steatosis in cultured hepatocyte steatosis in the form of nonalcoholic fatty liver disease models in vitro. However, the underlying mechanism of steatosis development is not completely understood. Therefore, we investigated the molecular mechanism of steatosis and the role of mitogen-activated protein kinase (MAPK)/toll-like receptor 4-related protein (TLR4) expression in this study. Rat hepatocyte cells were subjected to oleic acid in different concentrations (1.2-2.4 mM) for 24 hours. The cell morphological injury index and the changes in the MAPK/TLR4 signaling pathway-related proteins were evaluated. We found that the microstructure of the cells in the oleic acid treatment group was damaged, and higher phosphorylation levels of the MAPK pathway-related proteins were detected than those in the control group. In addition, the protein expression of TLR4, sterol regulatory element-binding protein-1, and fatty acid synthase were increased in the oleic acid treatment group. Our findings demonstrate that oleic acid causes toxic damage to rat hepatocyte cells, and the MAPK/TLR4 signaling pathway plays a significant role in lipid storage.

7.
Acta Trop ; 197: 105048, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31173738

RESUMO

Schistosomiasis remains one of the world's most significant neglected tropical diseases, second only to malaria in terms of socioeconomic impact. In 2014, China proposed the goal of schistosomiasis japonicum elimination by 2025. However, one major challenge is the widely distributed, and in certain cases potentially increasing, habitats of Oncomelania hupensis, the snail intermediate hosts of S. japonicum. Therefore, an understanding of population genetics of O. hupensis in new or re-emerged habitats, together with that of the established habitats with snail persistence, would be valuable in controlling and predicting the future transmission dynamics of schistosomiasis in China. Using nine microsatellite loci, we conducted population genetic analyses of snails sampled from one habitat where snails were detected for the first time, one (previously eliminated) habitat with re-emerged snails, and one habitat with established snail persistence. Results showed lower diversities, in terms of number of observed alleles per locus (Na), number of effective alleles per locus (NeA), observed (Ho) and expected heterozygosity (He), in snails from new or re-emerged snail habitats than from the habitat with snail persistence. The smallest effective population size was inferred in the re-emerged snail habitat, but the largest was in the new habitat rather than in the habitat with snail persistence. No bottleneck effects were detected in new or re-merged habitats. No or low sub-structure was inferred in new and persistent snail habitats. Snails from the three sites were clearly separated and low gene flow was estimated between sites. We propose that snails at the new habitat may have been introduced through immigration, whereas snails at the re-emerged habitat may be the consequence of those few snails remaining subsequently expanding through reproduction. We discuss our results in terms of their theoretical and applied implications.

8.
PLoS Negl Trop Dis ; 13(6): e0007475, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31173590

RESUMO

BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease. After nearly 70 years of control efforts in China, Schistosomiasis transmission has been reduced to a much lower level. The absence or near absence of infections in humans or livestock, based on traditional fecal and serological tests, has made the targets and priorities of future control efforts difficult to determine. However, detection of schistosome cercariae in waters using sentinel mice could be an alternative way of identifying remaining foci of infection, or even serve as a tool for evaluation of control efficacy. This method has been employed in China over last forty years. We therefore performed a meta-analysis of the relevant research to investigate if infections in sentinel mice mirror the ongoing trend of schistosomiasis transmission in China. METHODS: We conducted a meta-analysis of studies reporting infection rates of S. japonicum in sentinel mice in China before Sep 1, 2018 in accordance with the PRISMA guidelines. We retrieved all relative studies based on five databases (CNKI, WanFang, VIP, PubMed and Web of Science) and the reference lists of resulting articles. For each individual study, the infection rate in sentinel mice is presented together with its 95% confidence interval (CI). Point estimates of the overall infection rates and their 95% CIs were calculated. Subgroup analyses were performed according to study periods, seasons or regions. RESULTS: We identified 90 articles, including 290 studies covering eight endemic provinces. The overall rate in sentinel mice was 12.31% (95% CI: 10.14-14.65%) from 1980 to 2018. The value of 3.66% (95% CI: 2.62-4.85%) estimated in 2004 to 2018 was significantly lower than in 1980 to 2003 (22.96%, 95% CI: 19.25-26.89%). The estimate was significantly higher in the middle and lower reaches than in the upper reaches of the Yangtze River. The highest estimates were obtained in Hunan (30.11%, 95% CI: 25.64-34.77%) followed by Anhui (26.34%, 95% CI: 12.88-42.44%) and then Jiangxi (13.73%, 95% CI: 6.71-22.56%). Unlike the other provinces in the middle and lower reaches, no significant reduction was seen in Hubei after 2003. Even in Hubei two studies carried out after 2014 reported infections in sentinel mice, although no infected snails were reported across the province. Infections were most found in April (17.40%, 95% CI: 1.13-45.49%), July (24.98%, 95% CI: 15.64-35.62%) and October (17.08%, 95% CI 5.94-32.05%). High degrees of heterogeneity were observed. CONCLUSION: This meta-analysis provides a comprehensive analysis of schistosome infection in sentinel mice across China. The estimates largely mirror the ongoing trends of transmission in terms of periods and regions. Infections were most likely to occur in April, July and October. In areas where no infected snails were reported infections in sentinel mice were still observed. Due to the presence of snails and infected wildlife, detection of schistosomes in waters using such a highly sensitive method as the deployment of sentinel mice, remains of importance in schistosomiasis monitoring. We would suggest the current criteria for transmission interruption or elimination of schistosomiasis in China be adjusted by integrating the results of sentinel mice based surveys.

9.
Analyst ; 144(13): 3967-3971, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31140474

RESUMO

An OFF-ON detection method for Cu2+ was developed at the AgAu bimetallic nanoparticle decorated nitrogen-doped graphene (AgAu-NG) nanocomposite modified electrode. The measurement was based on the copper-catalyzed oxidation of cysteamine (Cys) to regulate the oxidation peak current of Ag. In the absence of Cu2+, Cys can bind to the surface of AgAu-NG via the Ag-S or Au-S bond, thus leading to an obvious decrease of the oxidation peak current of Ag. However, in the presence of Cu2+, Cu2+ can greatly catalyze the oxidation of Cys by dissolved O2 to form cystamine, which would fall off the surface of AgAu-NG nanocomposites, leading to the partial recovery of the oxidation peak current of Ag. With the increase in the concentration of Cu2+, the oxidation peak current of Ag in the presence of Cys increases accordingly. So, the concentration of Cu2+ can be measured. By using the optimum conditions, this method can detect Cu2+ concentrations down to 0.3 nM (S/N = 3) with a linear response range of 1 nM-1 mM. Furthermore, this method was applied to determine Cu2+ concentrations in river water samples and showed excellent analytical performance.

10.
Enzyme Microb Technol ; 127: 50-57, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31088616

RESUMO

Macrophages eliminate and destroy invading bacteria and contaminants by engulfing them or secreting cytokines that trigger downstream immune responses. Consequently, impairment of the phagocytic functions of macrophages and/or suppressing their cytokine secretion are dangerous to organisms that rely on immune protection. Accordingly, exposure to environmental nanoparticles (NPs) that display immunomodulatory properties are serious. In this work, two types of NPs, i.e., mild-toxicity CuInS2 NPs and high-toxicity CdTe NPs, were used to evaluate the effects of NP exposure for macrophages. Following incubation for 24 h, THP-1-derived macrophage viability was assessed using an MTT method after exposing the THP-1 cells to different concentrations of CuInS2 or CdTe NPs. Phagocytosis assays demonstrated that both CuInS2 and CdTe NPs impair phagocytic activity toward Staphylococcus aureus (S. aureus). After pretreatment with CuInS2 and CdTe NPs at 4 µmol/L, THP-1 macrophages exhibited decreases in phagocytic ratio from ca. 32.9% to ca. 18.5% and 18.7%, respectively. Since the zeta potentials of intact and weathered CuInS2 NPs were distributed over a wide range from positive to negative, large quantities of intact and weathered CuInS2 NPs bore sufficient positive charge on their surfaces to induce membrane depolarization, thus theoretically providing electrostatic forces between S. aureus and THP-1, which could induce downstream intracellular events that increase phagocytosis. However, real time polymerase chain reaction arrays revealed that transcription of the pro-inflammatory factors IL-1ß, IL-6, and TNF-α decreased while that of the anti-inflammatory factor IL-10 increased after treatment with CuInS2 NPs. Furthermore, transcription of TNF-α decreased while IL-10 increased after treatment with CdTe NPs. Thus, both kinds of NPs inhibited phagocytosis of S. aureus by THP-1 to some extent, confirming that immunosuppression can occur when macrophages are exposed to environmental NPs.


Assuntos
Citocinas/metabolismo , Fatores Imunológicos/metabolismo , Macrófagos/efeitos dos fármacos , Nanopartículas/metabolismo , Fagocitose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Fatores Imunológicos/química , Macrófagos/metabolismo , Nanopartículas/química , Staphylococcus aureus/imunologia , Células THP-1
11.
Artigo em Inglês | MEDLINE | ID: mdl-31035709

RESUMO

Zearalenone (ZEA) is a non-steroidal estrogen mycotoxin produced by several Gibberella and Fusarium species. Accumulating evidence has indicated that ZEA strongly stimulates cell proliferation. However the detailed molecular and cellular mechanisms of ZEA-mediated induction of cell proliferation have not yet been completely explained. The aim of this study was to detect the role of miRNAs in ZEA-mediated induction of cell proliferation. The effects of ZEA on cell proliferation were assessed using a cell counting kit assay and xCELLigence system. Micro-RNA sequencing was performed after treatment of TM3 cells with ZEA (0.01 µmol/L) for different time periods (0, 2, 6 and 18 h). Cell function and pathway analysis of the miRNA target genes were performed by Ingenuity Pathway Analysis (IPA). We found that ZEA promotes TM3 cell proliferation at low concentrations. miRNA sequenceing revealed 66 differentially expressed miRNAs in ZEA-treated cells in comparison to the untreated control ( p < 0.05). The miRNA sequencing indicated that compared to control group, there were 66 miRNAs significant change (p < 0.05) in ZEA-treated groups. IPA analysis showed that the predicated miRNAs target gene involved in cell Bio-functions including cell cycle, growth and proliferation, and in signaling pathways including MAPK and RAS-RAF-MEK-ERK pathways. Results from flow cytometry and Western Blot analysis validated the predictions that ZEA can affect cell cycle, and the MAPK signaling pathway. Taking these together, the cell proliferation induced ZEA is regulated by miRNAs. The results shed light on the molecular and cellular mechanisms for the mediation of ZEA to induce proliferation.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(4): 370-374, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31014431

RESUMO

This study analyzed the clinical features of 5 children with hereditary spherocytosis (HS) and the characteristics of ANK1 and SPTB gene mutations. All 5 children were confirmed with HS by peripheral blood genetic detection. Anemia, jaundice and splenomegaly were observed in all 5 children. Three children had an increase in erythrocyte osmotic fragility. All 5 children had negative results of the Coombs test, glucose 6 phosphate dehydrogenase test, sucrose hemolysis test, acidified-serum hemolysis test and thalassemia gene test. Peripheral blood smear showed an increase in spherocyte count in one child. High-throughput sequencing revealed ANK1 gene mutations in patients 1 to 3, namely c.3398(exon29)delA, c.4306C>T and c.957(exon9)_c.961(exon9)delAATCT, among which c.3398(exon29)delA had not been reported before. Patient 4 had c.318delGExon3 mutation in the SPTB gene. Patient 5 had mutations in the SPTB and SLC4A1 genes, among which c.3484delC in the SPTB gene was a spontaneous mutation; the mutation site of the SLCA4A1 gene was inherited from the father and was a non-pathogenic gene. This study suggests that anemia, jaundice and splenomegaly are major clinical manifestations of HS children. Most children with HS do not have the typical spherocytic changes. Genetic detection may help with the accurate diagnosis of HS.


Assuntos
Anquirinas/genética , Espectrina/genética , Esferocitose Hereditária , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Esferocitose Hereditária/genética
13.
J Asian Nat Prod Res ; : 1-6, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30982343

RESUMO

A new isoflavone glycoside named as 8-O-methylrelusin-7-O-ß-D-apifuranosyl-(1→2)-ß-D-glucopyranoside (1), together with two known compounds, 8-O-methylrelusin-7-O-ß-D-glucopyranoside (2) and isobiflorin (3), were isolated from Abrus cantoniensis. The structure of the new compound was elucidated on the basis of spectroscopic methods including extensive 1D NMR, 2D NMR, and HRESIMS. This is the first report of isoflavone from Abrus cantoniensis. Moreover, all isolated compounds were evaluated for their cytotoxicity against SMMC-7721 and MHCC97-H cell lines.

14.
Food Chem Toxicol ; 126: 262-276, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825585

RESUMO

Zearalenone (ZEA), a non-steroidal estrogen mycotoxin produced by several species of Fusarium fungi, can be metabolized into many other derivatives by microorganisms, plants, animals and humans. It can affect mammalian reproductive capability by impacting the synthesis and secretion of sex hormones, including testosterone, estradiol and progesterone. This review summarizes the mechanisms in which ZEA and its derivatives disturb the synthesis and secretion of sex steroid hormones. Because of its structural analogy to estrogen, ZEA and its derivatives can exert a variety of estrogen-like effects and engage in estrogen negative feedback regulation, which can result in mediating the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the pituitary gland. ZEA and its derivatives can ultimately reduce the number of Leydig cells and granulosa cells by inducing oxidative stress, endoplasmic reticulum (ER) stress, cell cycle arrest, cell apoptosis, and cell regeneration delay. Additionally, they can disrupt the mitochondrial structure and influence mitochondrial functions through overproduction of reactive oxygen species (ROS) and aberrant autophagy signaling ways. Finally, ZEA and its derivatives can disturb the expressions and activities of the related steroidogenic enzymes through cross talking between membrane and nuclear estrogen receptors.


Assuntos
Hormônios Esteroides Gonadais/biossíntese , Mamíferos/fisiologia , Zearalenona/química , Zearalenona/toxicidade , Animais , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Reprodução/efeitos dos fármacos
15.
J Gen Intern Med ; 34(6): 960-968, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30887438

RESUMO

BACKGROUND: Meta-analysis combines multiple independent studies, which can increase power and provide better estimates. However, it is unclear how best to deal with studies with zero events; such studies are also known as double-zero-event studies (DZS). Several statistical methods have been proposed, but the agreement among different approaches has not been systematically assessed using real-world published systematic reviews. METHODS: The agreement of five commonly used methods (i.e., the inverse-variance, Mantel-Haenszel, Peto, Bayesian, and exact methods) was assessed using the Cohen's κ coefficients using 368 meta-analyses with rare events selected from the Cochrane Database of Systematic Reviews. Three continuity corrections, including the correction of a constant 0.5, the treatment arm continuity correction (TACC), and the empirical (EMP) correction, were used to handle DZS when applying inverse-variance and Mantel-Haenszel methods. RESULTS: When the proportion of DZS studies was lower than 50% in a meta-analysis, different methods had moderately high agreement. However, when this proportion was increased to be over 50%, the agreement among the methods decreased to different extents. For the Bayesian, exact, and Peto methods and the inverse-variance and Mantel-Haenszel methods using the EMP correction, their agreement coefficients with the inverse-variance and Mantel-Haenszel methods using a constant 0.5 and TACC decreased from larger than 0.70 to smaller than 0.30. In contrast, the agreement coefficients only decreased slightly among the Bayesian, exact, and Peto methods and the inverse-variance and Mantel-Haenszel methods using the EMP correction. CONCLUSIONS: To utilize all available information and reduce research waste and avoid overestimating the effect, meta-analysts should incorporate DZS, rather than simply removing them. The Peto and other conventional methods with continuity correction should be avoided when the proportion of DZS is extremely high. The exact and Bayesian methods are highly recommended, except when none of the included studies have an event in one or both treatment arms.

16.
Ecotoxicol Environ Saf ; 175: 263-271, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30903882

RESUMO

Zearalenone (ZEA) is a phenolic resorcylic acid lactone mycotoxin produced by several Fusarium species that grow on temperate and tropical crops. The number of reports documenting the immunotoxic effects of ZEA is increasing, but the underlying mechanism is not clear. The purpose of this study was to investigate the effects of ZEA on T cell chemotaxis and evaluate changes in adhesion and migration proteins associated with this process. Specifically, T cells were isolated from BALB/C mouse splenic lymphocytes, activated by concanavalin A (Con A), and then exposed to different concentrations of ZEA. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used observe the ultrastructural changes inside the cell and on the cell surface, respectively. The transwell migration assay was used to evaluate the effect of ZEA on T cell chemotaxis in the presence of CCL19 or CCL21. A confocal 3D laser was used to capture the morphology of perforated cells and western blot was used to detect the expression of proteins associated with cell migration and adhesion. Additionally, we used flow cytometry to examine the expression of chemokine receptors on T cells. Finally, the chemokine (RANTES and MIP-1α) levels secreted by T cells were assessed using cytometric bead array. Overall, our data showed that treatment with ZEA caused ultrastructural damage on the surface as well as inside of T cells. Moreover, ZEA inhibited T cell chemotaxis which was mediated by CCL19 or CCL21 and disrupted the balance of T cell subtypes. The expression of T cell adhesion and migration proteins was also inhibited by ZEA. The expression of T cell chemokine receptor as well as secretion of RANTES and MIP-1α by T cells was suppressed after ZEA treatment. In summary, our results indicate that ZEA reduced the chemotactic effect of T cells mediated by chemokines, which was likely linked to the inhibition of T cell motility and accompanied by decreased expression of adhesion and migration proteins.


Assuntos
Adesão Celular/efeitos dos fármacos , Quimiocinas/biossíntese , Quimiotaxia/efeitos dos fármacos , Receptores de Quimiocinas/biossíntese , Linfócitos T/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Movimento Celular/efeitos dos fármacos , Quimiocina CCL19/biossíntese , Quimiocina CCL21/biossíntese , Quimiocina CCL5/biossíntese , Citometria de Fluxo , Humanos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia
17.
Food Chem ; 285: 22-30, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30797338

RESUMO

The effects of high pressure processing on the binding interactions of α-lactalbumin and pelargonidin-3-glucoside were studied using the fluorescence quenching, molecular dynamic simulation and molecular docking analysis. The results of fluorescence quenching indicated that the high pressure processing significantly increased the quenching constants of α-lactalbumin at pH 7.4 and pH 8.0. The accessible fraction at pH 8.0 was significantly increased, while the fractions at pH 6.0 and pH 7.4 were increased without significant difference. Molecular dynamic simulation and docking results demonstrated that the coil structures and locations, and the residues structures in the binding site of α-lactalbumin were affected, the binding site was the typical binding site of calcium ion and not changed during the processing. The dissociation constant of histidine residues was in the range of 6.13 to 6.83, the charge on the residues increased when pH value increased, affected the binding interactions and caused the quenching constant difference.


Assuntos
Antocianinas/metabolismo , Lactalbumina/metabolismo , Animais , Antocianinas/química , Sítios de Ligação , Concentração de Íons de Hidrogênio , Lactalbumina/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pressão , Ligação Proteica , Estrutura Terciária de Proteína , Espectrometria de Fluorescência
18.
Methods Mol Biol ; 1880: 481-489, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30610716

RESUMO

The autophagy pathway in hepatocytes is well characterized. Autophagy plays a critical role in the normal function of the liver. A growing number of studies suggest that there is a mechanistic relationship between autophagy and the pathogenesis of human diseases including liver diseases. Here we focus on the methods assessing the level of lipids, lipid peroxidation, and lipophagy in the liver, which would be particularly relevant to the study of fatty liver diseases.


Assuntos
Autofagia/fisiologia , Bioensaio/métodos , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Animais , Bioensaio/instrumentação , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Linhagem Celular , Fígado Gorduroso/patologia , Hepatócitos/metabolismo , Gotículas Lipídicas/metabolismo , Lipídeos/análise , Fígado/patologia , Camundongos , Microscopia Confocal/instrumentação , Microscopia Confocal/métodos , Microscopia de Fluorescência/instrumentação , Microscopia de Fluorescência/métodos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
19.
Environ Toxicol ; 34(4): 424-433, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30600648

RESUMO

Zearalenone (ZEA) is an estrogen-like toxin produced by Fusarium that is widely found in cereals worldwide. In recent years, ZEA has been found to cause reproductive dysfunction in male animals, but the underlying mechanism remains unclear. This study examined the apoptosis of rat Sertoli cells induced by different concentrations (0, 5, 10, and 20 µmol/L) of ZEA via Fas-Fas ligand and mitochondrial signaling pathway in vitro. Apoptosis rate was detected by flow cytometry. The mitochondrial membrane potential was detected by immunofluorescence assay and flow cytometry. Western Blot and qRT-PCR were used to identify the signaling pathway. The results revealed that ZEA induced apoptosis of rat Sertoli cells, significantly reduced the transcription and expression of the anti-apoptotic protein Bcl-2, increased the transcription and expression of pro-apoptotic proteins Bax and tBID, and Fas, FasL, FADD, and caspase-8. ZEA also increased the activation of caspase-8 and caspase-9, and promoted the release of cytochrome C from mitochondria to cytoplasm. Moreover, addition of caspase-8 inhibitor Z-IETD-FMK led to significant decrease in the mitochondrial membrane potential and apoptosis rate of the ZEA + Z-IETD-FMK group as compared to the ZEA treatment group. The release of cytochrome C from mitochondria to cytoplasm and the activation of caspase-9 and caspase-3 were significantly decreased in the ZEA + Z-IETD-FMK group. These results suggested that ZEA can induce apoptosis of rat Sertoli cells, activate the Fas-Fas ligand signaling pathway and participate in the regulation of mitochondrial apoptosis pathway.


Assuntos
Apoptose/efeitos dos fármacos , Proteína Ligante Fas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Zearalenona/toxicidade , Receptor fas/metabolismo , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Masculino , Ratos Wistar , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Transdução de Sinais
20.
Toxicology ; 414: 1-13, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30605698

RESUMO

The heavy metal cadmium (Cd) is well known to be neurotoxic. Studies have shown that apoptosis plays an essential role in Cd-induced brain injury; however, the mechanisms underlying this injury accompanied by apoptosis have yet to be elucidated. The endoplasmic reticulum (ER) stress plays a key part in the regulation of apoptosis. ER stress is defined as accumulation of unfolded or misfolded proteins in the ER. Here, we demonstrated the role of ER stress on Cd-evoked apoptosis in neuronal cells, as well as the neuroprotective effects of the antioxidant alpha-lipoic acid (α-LA) on Cd-induced ER stress and neuronal injury. In vitro, we observed that Cd activated ER associated proteins via the eIF2α-ATF4 pathway in primary rat cerebral cortical neurons. Furthermore, the ER-stress inhibitor salubrinal blocked the dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and significantly reduced the induction of ER stress marker CHOP, the increase of the B-cell lymphoma-2 associate X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, and apoptosis induced by Cd. In addition, Z-ATAD-FMK (a caspase-12 inhibitor) counteracted the Cd-induced activation of caspase-12 and -3, and apoptosis. These in vitro results collectively suggested that ER stress was required for Cd-induced neuronal apoptosis. Importantly, α-LA inhibited the activation of the ER stress eIF2α-ATF4 pathway, the increase of the Bax/Bcl-2 ratio, the activation of caspase-12 and -3, and the apoptosis induced by Cd. In vivo, we also found that the administration of α-LA alleviated Cd-induced neuronal injury, inhibited the activation of the ER stress eIF2α-ATF4 pathway, restored the Bax/Bcl-2 ratio, and prevented the activation of caspase-12 and -3. Taken together, our results demonstrated that Cd triggered protein changes in the ER accompanied by apoptosis via the eIF2α-ATF4 signaling pathway in the neuronal cells of rats, both in vitro and in vivo. Furthermore, we demonstrated for the first time that α-LA protected neurons from Cd-induced injury partly by inhibiting ER stress in rat cerebral cortical neurons.


Assuntos
Acetatos/toxicidade , Fator 4 Ativador da Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Córtex Cerebral/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Ácido Tióctico/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Citoproteção , Feminino , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
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