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1.
Anal Methods ; 16(19): 3142-3153, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38713147

RESUMO

We develop and validate a method for the rapid determination and identification of 20 ß-lactamase antibiotics traces in goat's milk by combining the solid phase extraction technology with ultra-high performance liquid chromatography-tandem mass spectrometry. Goat milk samples were extracted with acetonitrile twice. The supernatant was then extracted and cleaned by solid-phase extraction using divinylbenzene and N-vinylpyrrolidone copolymer. The method was validated, with limits of quantification (LOQs) of 0.3 µg kg-1, specificities of 1/3 LOQ, linearities (R2) > 0.99, recoveries of 80-110%, repeatabilities <10.0%, and intermediate precisions <10.0%. The developed method was suitable for the routine analysis of ß-lactamase antibiotics residues in goat's milk and was used to test 76 goat milk samples produced in China.


Assuntos
Antibacterianos , Cabras , Leite , Extração em Fase Sólida , Espectrometria de Massas em Tandem , beta-Lactamases , Animais , Extração em Fase Sólida/métodos , Leite/química , Espectrometria de Massas em Tandem/métodos , Antibacterianos/análise , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Reprodutibilidade dos Testes , Resíduos de Drogas/análise , Contaminação de Alimentos/análise , Espectrometria de Massa com Cromatografia Líquida
2.
Int Immunopharmacol ; 132: 111924, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38531201

RESUMO

BACKGROUND: T helper (Th) cell imbalances have been associated with the pathophysiology of sepsis, including the Th1/Th2 and Th17/T regulatory cells (Treg) paradigms. Cold-inducible RNA-binding protein (CIRP), a novel damage-associated molecular pattern (DAMP) was reported that could induce T cell activation, and skew CD4+ T cells towards a Th1 profile. However, the effect and underlying mechanisms of CIRP on Th17/Treg differentiation in sepsis still remains unknown. METHODS: A prospective exploratory study including patients with sepsis was conducted. Blood samples were collected from patients on days 0, 3 and 7 on admission. The serum CIRP and peripheral blood Treg/Th17 percentage was determined by ELISA and flow cytometry. CD4+ T cells from the spleen and lymph nodes of mice with experimental sepsis were collected after treatment with normal saline (NS), recombinant murine CIRP (rmCIRP) and C23 (an antagonist for CIRP-TLR4) at late stage of sepsis. RNA-seq was conducted to reveal the pivotal molecular mechanism of CIRP on Treg/Th17 differentiation. Naïve CD4+ T cell was isolated from the Tlr4 null and wildtype mice in the presence or absence rmCIRP and C23 to confirmed above findings. RESULTS: A total of 19 patients with sepsis finally completed the study. Serum CIRP levels remained high in the majority of patients up to 1 week after admittance was closely associated with high Treg/Th17 ratio of peripheral blood and poor outcome. A univariate logistic analysis demonstrated that higher CIRP concentration at Day 7 is an independent risk factor for Treg/Th17 ratio increasing. CIRP promotes Treg development and suppresses Th17 differentiation was found both in vivo and in vitro. Pretreated with C23 not only alleviated the majority of negative effect of CIRP on Th17 differentiation, but also inhibited Treg differentiation, to some extent. Tlr4 deficiency could abolish almost all downstream effects of rmCIRP. Furthermore, IL-2 is proved a key downstream molecules of the effect CIRP, which also could amplify the activated CD4+ T lymphocytes. CONCLUSIONS: Persistent high circulating CIRP level may lead to Treg/Th17 ratio elevated through TLR4 and subsequent active IL-2 signaling which contribute to immunosuppression during late phases of sepsis.


Assuntos
Fatores de Transcrição Forkhead , Interleucina-2 , Camundongos Endogâmicos C57BL , Proteínas de Ligação a RNA , Sepse , Transdução de Sinais , Linfócitos T Reguladores , Células Th17 , Receptor 4 Toll-Like , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Diferenciação Celular , Células Cultivadas , Fatores de Transcrição Forkhead/metabolismo , Interleucina-2/metabolismo , Camundongos Knockout , Estudos Prospectivos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Sepse/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética
3.
J Extracell Vesicles ; 13(3): e12423, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38491216

RESUMO

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common life-threatening syndrome with no effective pharmacotherapy. Sepsis-related ARDS is the main type of ARDS and is more fatal than other types. Extracellular vesicles (EVs) are considered novel mediators in the development of inflammatory diseases. Our previous research suggested that endothelial cell-derived EVs (EC-EVs) play a crucial role in ALI/ARDS development, but the mechanism remains largely unknown. Here, we demonstrated that the number of circulating EC-EVs was increased in sepsis, exacerbating lung injury by targeting monocytes and reprogramming them towards proinflammatory macrophages. Bioinformatics analysis and further mechanistic studies revealed that vascular cell adhesion molecule 1 (VCAM1), overexpressed on EC-EVs during sepsis, activated the NF-κB pathway by interacting with integrin subunit alpha 4 (ITGA4) on the monocyte surface, rather than the tissue resident macrophage surface, thereby regulating monocyte differentiation. This effect could be attenuated by decreasing VCAM1 levels in EC-EVs or blocking ITGA4 on monocytes. Furthermore, the number of VCAM1+ EC-EVs was significantly increased in patients with sepsis-related ARDS. These findings not only shed light on a previously unidentified mechanism underling sepsis-related ALI/ARDS, but also provide potential novel targets and strategies for its precise treatment.


Assuntos
Lesão Pulmonar Aguda , Vesículas Extracelulares , Monócitos , Sepse , Molécula 1 de Adesão de Célula Vascular , Humanos , Lesão Pulmonar Aguda/metabolismo , Células Endoteliais/metabolismo , Vesículas Extracelulares/metabolismo , Monócitos/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Sepse/complicações , Sepse/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
4.
Viruses ; 14(10)2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36298816

RESUMO

Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, and has caused significant economic losses in the pig industry. There are currently no specific drugs available to treat PEDV. Viruses depend exclusively on the cellular machinery to ensure an efficient replication cycle. In the present study, we found that small-molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of RAF, reduced viral loads of PEDV by 4 orders of magnitude in Vero cells, and protected piglets from virus challenge. RAF265 reduced PEDV production by mediating cytoskeleton arrangement and targeting the host cell's translation machinery. Treatment with RAF265 inhibited viral entry of PEDV S-glycoprotein pseudotyped viral vector particle (PEDV-pp), at half maximal effective concentrations (EC50) of 79.1 nM. RAF265 also presented potent inhibitory activity against viral infection by SARS-CoV-2-pp and SARS-CoV-pp. The present work may provide a starting point for further progress toward the development of antiviral strategies effective against coronavirus PEDV.


Assuntos
COVID-19 , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Chlorocebus aethiops , Animais , Suínos , Células Vero , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/uso terapêutico
5.
Int J Mol Sci ; 23(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35008712

RESUMO

Aflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protective effects of LF on the compromised intestinal barrier induced by AFM1 has not been investigated. In the present study, results using Balb/C mice and differentiated Caco-2 cells showed that LF intervention decreased AFM1-induced increased intestinal permeability, improved the protein expression of claudin-3, occludin and ZO-1, and repaired the injured intestinal barrier. The transcriptome and proteome were used to clarify the underlying mechanisms. It was found that LF reduced the intestinal barrier dysfunction caused by AFM1 and was associated with intestinal cell survival related pathways, such as cell cycle, apoptosis and MAPK signaling pathway and intestinal integrity related pathways including endocytosis, tight junction, adherens junction and gap junction. The cross-omics analysis suggested that insulin receptor (INSR), cytoplasmic FMR1 interacting protein 2 (CYFIP2), dedicator of cytokinesis 1 (DOCK1) and ribonucleotide reductase regulatory subunit M2 (RRM2) were the potential key regulators as LF repaired the compromised intestinal barrier. These findings indicated that LF may be an alternative treatment for the compromised intestinal barrier induced by AFM1.


Assuntos
Aflatoxina M1/toxicidade , Intestinos/patologia , Lactoferrina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Células CACO-2 , Permeabilidade da Membrana Celular/efeitos dos fármacos , Claudina-3/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ocludina/metabolismo , Proteoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma/genética , Proteína da Zônula de Oclusão-1/metabolismo
6.
Foods ; 11(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35010149

RESUMO

Aflatoxin M1 (AFM1) is the only mycotoxin with maximum residue limit in milk, which may result in serious human diseases. On the contrary, lactoferrin (Lf) is an active protein with multiple functions. Studies have confirmed that Lf has a powerful potential to protect the intestines, but the influence of Lf on mycotoxins is not clear. This study aims to explore whether Lf can protect the cytotoxicity induced by AFM1, and determine the underlying mechanisms in human normal colonic epithelial NCM460 cells. The results indicated that AFM1 decreased the cell viability, and increased the levels of apoptosis and autophagy of NCM460 cells. Lf can alleviate the cytotoxicity induced by AFM1 through enhancing cell viability, significantly down-regulated the expression of apoptotic genes and proteins (BAX, caspase3, caspase9, caspase3, and caspase9), and regulated the gene and protein expression of autophagy factors (Atg5, Atg7, Atg12, Beclin1, ULK1, ULK2, LC3, and p62). Furthermore, interference of the key gene Atg5 of autophagy can reduce AFM1-induced apoptosis, which is consistent with the role of Lf, implying that Lf may protect AFM1-induced intestinal injury by inhibiting excessive autophagy-mediated apoptosis. Taken together, our data indicated that Lf has a mitigating effect on apoptosis induced by AFM1 through the autophagy pathway.

7.
PeerJ ; 8: e8742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32257637

RESUMO

BACKGROUND: Previous studies on the effects of mycotoxins have solely focused on their biochemical profiles or products in dairy ruminants. Changes in metabolism that occur after exposure to mycotoxins, as well as biochemical changes, have not been explored. METHODS: We measured the biochemical and metabolic changes in dairy cows after exposure to mycotoxins using biochemical analyses and nuclear magnetic resonance. Twenty-four dairy cows were randomly assigned to three different treatment groups. Control cows received diets with 2 kg uncontaminated cottonseed. Cows in the 50% replacement group received the same diet as the control group, but with 1 kg of uncontaminated cottonseed and 1 kg of cottonseed contaminated with mycotoxins. Cows in the 100% replacement group received the same diet as the control, but with 2 kg contaminated cottonseed. RESULTS: The results showed that serum γ-glutamyl transpeptidase and total antioxidant capacities were significantly affected by cottonseed contaminated with mycotoxins. There were also significant differences in isovalerate and NH3-N levels, and significant differences in the eight plasma metabolites among the three groups. These metabolites are mainly involved in amino acid metabolism pathways. Therefore, the results suggest that amino acid metabolism pathways may be affected by mycotoxins exposure.

8.
Food Res Int ; 128: 108760, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31955735

RESUMO

Milk yield and several components of milk that are affected by physiological factors have been widely investigated. However, the effects of lactation stage and parity on bovine milk whey proteins have not been well elucidated. To aid in unraveling the proteome profile and exploring the protein biosynthesis of mammary glands, a label-free proteomic approach was used to characterize whey proteomes depending on the lactation stage and parity of dairy cows. The results of this study show that the abundances of several proteins, such as early lactation protein, syntenin, and heparanase, were associated with specific stages of the lactation cycle; this was evidenced by a principal component analysis. In addition, several proteins, such as hemoglobin subunits beta and alpha, ß-lactoglobulin, CD320, and apolipoprotein E, corresponded to the parity of the dairy cows and were herein considered as useful biomarkers to distinguish different parities. Most of the differentially expressed proteins from specific lactation stages and parity milk groups were annotated in the response to stimulus and protein metabolic processes. The findings reveal that developmental changes in whey proteomes correspond to lactation stages and parities, which in turn provides new insight into the underlying implications of the production of specific proteins to meet the health benefits of offspring and host, and allow us to explore the mechanisms of protein biosynthesis in mammary glands associated with physiological changes in dairy cows.


Assuntos
Lactação/metabolismo , Paridade , Proteoma/metabolismo , Proteômica/métodos , Proteínas do Soro do Leite/metabolismo , Animais , Bovinos , Feminino
9.
Toxins (Basel) ; 11(4)2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995739

RESUMO

The toxicity and related mechanisms of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the mouse kidney were studied, and the role of l-proline in alleviating kidney damage was investigated. In a 28-day toxicity mouse model, thirty mice were divided into six groups: control (without treatment), l-proline group (10 g/kg body weight (b.w.)), AFB1 group (0.5 mg/kg b.w.), AFM1 (3.5 mg/kg b.w.), AFB1 + l-proline group and AFM1 + l-proline group. Kidney index and biochemical indicators were detected, and pathological staining was observed. Using a human embryonic kidney 293 (HEK 293) cell model, cell apoptosis rate and apoptotic proteins expressions were detected. The results showed that AFB1 and AFM1 activated pathways related with oxidative stress and caused kidney injury; l-proline significantly alleviated abnormal expressions of biochemical parameters and pathological kidney damage, as well as excessive cell apoptosis in the AF-treated models. Moreover, proline dehydrogenase (PRODH) was verified to regulate the levels of l-proline and downstream apoptotic factors (Bax, Bcl-2, and cleaved Caspase-3) compared with the control (p < 0.05). In conclusion, l-proline could protect mouse kidneys from AFB1 and AFM1 through alleviating oxidative damage and decreasing downstream apoptosis, which deserves further research and development.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Aflatoxina B1/toxicidade , Aflatoxina M1/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Prolina/uso terapêutico , Substâncias Protetoras/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Células HEK293 , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Prolina/farmacologia , Prolina Oxidase/metabolismo , Substâncias Protetoras/farmacologia , Testes de Toxicidade Subaguda
10.
Toxins (Basel) ; 11(2)2019 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-30813459

RESUMO

Aflatoxin M1 (AFM1) and ochratoxin A (OTA), which widely coexist in milk, may pose a serious threat to human health. Mucin is a major component of the intestinal mucus layer, which plays an important role in maintaining intestinal mucosal homeostasis. However, the effect of mycotoxins AFM1 and OTA on intestinal mucin production is still not clear. This study aimed to investigate individual and interactive effects of mycotoxins AFM1 and OTA on the intestinal barrier and the mRNA expression of intestinal mucin (MUC2, MUC5AC and MUC5B) and on protein production in Caco-2/HT29-MTX cultures after 48 h of exposure. Our results show that individual mycotoxins and their mixtures significantly reduced intestinal cell viability and transepithelial electrical resistance (TEER) values, as well as significantly altered intestinal mucin mRNA expression and protein abundance. Moreover, OTA showed toxicity similar to AFM1 in cell viability and TEER value at the same concentration. When the two mycotoxins acted in combination, the synergistic effects observed in the assessment of cell viability and protein abundance in all mono- and co-cultures. In general, this study provides evidence that AFM1 and OTA can damage the intestine, and it contributes to optimized maximum permissible limits of mycotoxins in milk.


Assuntos
Aflatoxina M1/toxicidade , Mucina-5AC/genética , Mucina-2/genética , Mucina-5B/genética , Ocratoxinas/toxicidade , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Células HT29 , Humanos , Mucina-5AC/metabolismo , Mucina-2/metabolismo , Mucina-5B/metabolismo , RNA Mensageiro/metabolismo
11.
Toxicol Lett ; 309: 1-9, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30904571

RESUMO

Aflatoxin M1 (AFM1), ochratoxin A (OTA), and zearalenone (ZEA) are mycotoxins commonly found in milk. Mycotoxin contamination has caused food safety concerns worldwide since most of the toxic effects in humans are serious. The combined toxic effects of these mycotoxins on intestinal epithelial cells have not been reported. Herein, we investigated the combined effects of AFM1, OTA, and ZEA on intestinal integrity and define the underlying mechanisms(s) of their effects in Caco-2/HT29-MTX co-cultures. Our results showed that the mixtures of AFM1 + OTA, AFM1 + ZEA, and AFM1 + ZEA + OTA significantly increased epithelial permeability. Immunofluorescence analysis and transmission electron microscopy revealed that mycotoxins altered TJ proteins morphology and disrupted their structures. Also, the present study showed that mixtures of mycotoxins significantly modulated MUC5AC and MUC5B mRNA levels and protein secretion. This study demonstrated that the effects of mixtures of mycotoxins on intestinal barrier function were more significant than AFM1 alone. More importantly, the damage of intestinal integrity caused by mycotoxins was correlated to the change of the TJ proteins location and the decrease of mucin secretion. Mixtures of AFM1, OTA, and ZEA in food might pose a health risk to consumers, particularly in children, and toxin risks should be considered.


Assuntos
Aflatoxina M1/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Mucinas/metabolismo , Ocratoxinas/toxicidade , Zearalenona/toxicidade , Células CACO-2 , Técnicas de Cocultura , Contaminação de Alimentos , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Mucina-5AC/análise , Mucina-5AC/genética , Mucina-2/análise , Mucina-2/genética , Mucina-5B/análise , Mucina-5B/genética , Mucinas/genética , Permeabilidade , RNA Mensageiro/análise , Proteínas de Junções Íntimas/análise
12.
Food Res Int ; 113: 1-8, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195502

RESUMO

The milk fat globule membrane (MFGM) plays an important role in stabilizing fat in the aqueous phase, and the components of this membrane are involved in multiple biological functions. Here, we investigated changes in the protein composition of the MFGM fraction between raw and heated whole milk using a label free proteomic approach. In total, 612 MFGM-related proteins were identified in all groups. Compared with raw milk, the number of proteins that were not identified in the MFGM fraction was increased from pasteurized milk to ultra-high-temperature milk, whereas the number of milk proteins incorporated into the MFGM fraction was similar among heated groups. The abundances of several milk proteins (ß-lactoglobulin and ß-casein) were increased in the heated milk groups in a temperature-dependent manner. From our functional analysis, proteins that were not identified in the MFGM fraction of heated milk were mainly associated with multiple biological functions. These findings provided novel insights into the effects of heat procedures on MFGM protein components and their potential physiological functions, thereby yielding data on the appropriate heating procedures to use for raw milk.


Assuntos
Glicolipídeos/química , Glicoproteínas/química , Temperatura Alta , Proteínas do Leite/química , Leite/química , Proteômica/métodos , Animais , Caseínas/análise , Bovinos , Manipulação de Alimentos/métodos , Glicolipídeos/fisiologia , Glicoproteínas/fisiologia , Lactoglobulinas/análise , Gotículas Lipídicas , Proteínas do Leite/análise , Pasteurização
13.
J Proteome Res ; 17(9): 3128-3142, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30079738

RESUMO

Aflatoxin M1 (AFM1) is a common mycotoxin in dairy milk, and it is typically concurrently present with other mycotoxins that may represent a threat to food safety. However, knowledge of how AFM1, alone or in combination with other mycotoxins, may affect human intestinal epithelial integrity remain to be established. We employed transcriptome and proteome analysis integrated with biological validation to reveal the molecular basis underlining the effect of exposure to AFM1, ochratoxin A (OTA), or both on the intestinal epithelial integrity of differentiated Caco-2 cells. Exposure to 4 µg/mL of OTA was found to disrupt human gut epithelial integrity, whereas 4 µg/mL of AFM1 did not. The integrated transcriptome and proteome analysis of AFM1 and OTA, alone or in combination, indicate the synergistic effect of the two mycotoxins in disrupting intestinal integrity. This effect was mechanistically linked to a broad range of pathways related to intestinal integrity enriched by down-regulated genes and proteins, associated with focal adhesion, adheren junction, and gap junction pathways. Furthermore, the cross-omics analysis of mixed AFM1 and OTA compared to OTA alone suggest that kinase family members, including myosin light-chain kinase, mitogen-activated protein kinases, and protein kinase C, are the potential key regulators in modulating intestinal epithelial integrity. These findings provide novel insight into the synergistic detrimental role of multiple mycotoxins in disrupting intestinal integrity and, therefore, identify potential targets to improve milk safety related to human health.


Assuntos
Aflatoxina M1/toxicidade , Adesões Focais/efeitos dos fármacos , Ocratoxinas/toxicidade , Proteoma/genética , Transcriptoma , Junções Aderentes/efeitos dos fármacos , Células CACO-2 , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Junções Comunicantes/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo , Mapas de Interação de Proteínas , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Proteoma/classificação , Proteoma/metabolismo
14.
Toxicon ; 150: 77-85, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29753785

RESUMO

Aflatoxins, including aflatoxin B1 (AFB1) and M1 (AFM1), are natural potent carcinogens produced by Aspergillus spp. These compounds, which can often be detected in dairy foods, can cause diseases in human beings. However, the molecular mechanisms involved in cytotoxicity, as well as methods for intervention, remain largely unexplored. For example, it is unclear whether lactoferrin (LF), a major antioxidant in milk, can inhibit the cytotoxicity of AFB1 and AFM1. In this study, we assessed AFB1- and AFM1-induced cell toxicity by measuring cell viability, membrane permeability, and genotoxicity, and then investigated the ability of LF to protect cells against AFB1 and AFM1. In Caco-2, HEK, Hep-G2, and SK-N-SH cells, 4 µg/mL AFB1 or AFM1 significantly inhibited cell growth, increased the level of lactate dehydrogenase, induced genetic damage, and increased the levels of signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) (p < 0.05). AFB1 was more genotoxic than AFM1 in all four cell lines, especially in Hep-G2. In Caco-2, Hep-G2, and SK-N-SH, incubation of AF-treated cells with 1000 µg/mL LF significantly decreased cytotoxicity, oxidation level, DNA damage, and levels of ERK1/2 and JNK (p < 0.05). Our data demonstrate that AFB1 or AFM1 induced cytotoxicity and DNA damage in these four cell lines, and that LF alleviated toxicity by decreasing oxidative stress mediated by mitogen-activated protein kinase pathways.


Assuntos
Aflatoxina B1/toxicidade , Aflatoxina M1/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Lactoferrina/farmacologia , Linhagem Celular Tumoral , Humanos
15.
Artigo em Inglês | MEDLINE | ID: mdl-29710778

RESUMO

This survey was performed to investigate the occurrence of aflatoxin M1 (AFM1) contamination of raw milk from manufacturers of infant milk powder in China. A total of 1207 raw milk samples were collected overall from four seasons of 2016 in Northeast China, Northwest China, Northern China, and Central China (11 provinces and one municipality). Results showed that 56 of the 1207 raw milk samples (4.64%) were positive for AFM1, which were obtained from Heilongjiang (two samples), Gansu (one sample), Shaanxi (46 samples), Beijing (one sample), and Hunan (six samples) provinces. None of the raw milk samples from manufacturers of infant milk powder exceeded the Chinese limit (62.5 ng/L) in 2016. Only a few raw milk samples were not suitable for use in infant milk according to EU (European Union) or U.S. infant milk limits. Furthermore, based on this survey and previous studies, it is particularly important to avoid AFM1 contamination in raw milk during the winter.


Assuntos
Aflatoxina M1/análise , Contaminação de Alimentos/estatística & dados numéricos , Fórmulas Infantis/química , Leite/química , Venenos/análise , Animais , China , Contaminação de Alimentos/análise , Humanos , Lactente , Fórmulas Infantis/análise , Pós
16.
Biol Trace Elem Res ; 183(1): 92-101, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28825229

RESUMO

The object of this study is to analyze the levels of seven toxic elements residues in raw bovine milk in China and assess the potential health risk of those residues. The 178 raw bovine milk samples were collected from eight main milk-producing provinces and from three types of milk stations in China, and were analyzed for arsenic (As), lead (Pb), cadmium (Cd), chromium (Cr), mercury (Hg), aluminum (Al), and nickel (Ni) using inductively coupled plasma-mass spectrometry (ICP-MS). Al, Pb, Hg, Ni, Cr, and As were detected in 47.8, 29.2, 28.1, 23.6, 12.4, and 9.0% of total milk samples, respectively, and Cd were not detected in all samples. The raw bovine milk samples with high levels of toxic elements were found in industrial areas, such as Heilongjiang and Shanxi. Nemerow pollution index analysis showed that the levels were lower in the samples from the processing plants than that from the large-scale farms and small farm cooperatives. The margin of exposure (MOE) values suggest that the levels of As, Pb, Hg, Cr, Al, and Ni in the raw milk samples are not causing a health risk for Chinese consumers, including adults and children. Nevertheless, the risk of Pb for infant and young children was more serious than adult.


Assuntos
Análise de Alimentos , Metais Pesados/análise , Leite/química , Adulto , Animais , Bovinos , Criança , Pré-Escolar , Humanos , Espectrometria de Massas , Medição de Risco
17.
Toxins (Basel) ; 10(1)2017 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-29280945

RESUMO

Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 µM) and OTA (0.2 and 20 µM) individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC)-dextrans (4 and 40 kDa) and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indicating increased epithelial permeability. Immunoblotting and immunofluorescent analysis revealed that AFM1, OTA, and their combination decreased the expression levels of tight junction (TJ) proteins and disrupted their structures, namely, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1), and p44/42 mitogen-activated protein kinase (MAPK) partially involved in the mycotoxins-induced disruption of intestinal barrier. The effects of a combination of AFM1 and OTA on intestinal barrier function were more significant (p < 0.05) than those of AFM1 and OTA alone, yielding additive or synergistic effects. The additive or synergistic effects of AFM1 and OTA on intestinal barrier function might affect human health, especially in children, and toxin risks should be considered.


Assuntos
Aflatoxina M1/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Ocratoxinas/farmacologia , Células CACO-2 , Diferenciação Celular , Dextranos/farmacologia , Sinergismo Farmacológico , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacologia , Corantes Fluorescentes/farmacologia , Humanos , Mucosa Intestinal/metabolismo , Isoquinolinas/farmacologia , Permeabilidade/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-29278385

RESUMO

In recent years, high levels of hormone residue in food, capable of damaging the health of consumers, have been recorded frequently. In this study, 195 raw milk samples were obtained from Tangshan City, China, and the concentrations of 22 steroid hormones were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Cortisol was detected in 12.5% of raw milk samples (mean 0.61 µg/kg; range:

Assuntos
Contaminação de Alimentos/análise , Leite/química , Esteroides/isolamento & purificação , Animais , Criança , Pré-Escolar , China , Cromatografia Líquida de Alta Pressão , Humanos , Lactente , Medição de Risco , Inquéritos e Questionários , Espectrometria de Massas em Tandem/métodos
19.
PLoS One ; 12(11): e0187261, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29095869

RESUMO

Ceftiofur hydrochloride (CEF) is occasionally used for the intramammary (IMM) treatment of mastitis. This extralabel manner could result in a drug-residue violation of the milk. The objective of this study was to determine the elimination kinetics of IMM CEF in lactating dairy cattle. The pharmacokinetic profile of CEF after repeated IMM administration in nine healthy cows and nine Staphylococcus aureus infected cows was investigated, alongside determining the MICs of Staph. aureus field strains. The MIC 90 value for CEF in Staph. aureus field strains (n = 31) was 0.25 µg/mL. The t >MIC CEF values for low- production quarters were longer than those for high- and mid- production quarters. The results showed that ceftiofur was detected in milk up to 108 h after the last infusion in both healthy and infected cows. Cows with low milk production eliminate IMM drugs more slowly than cows with higher production. Our findings suggest that this extralabel use is not encouraged and a prudent use is recommended for mastitis therapy. The use of CEF should be reserved for infections where susceptibility tests indicate its efficacy and when alternatives are not available.


Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Glândulas Mamárias Animais , Mastite Bovina/tratamento farmacológico , Leite/metabolismo , Infecções Estafilocócicas/veterinária , Animais , Antibacterianos/administração & dosagem , Área Sob a Curva , Bovinos , Cefalosporinas/administração & dosagem , Feminino , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos
20.
J Dairy Res ; 84(4): 401-406, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29154733

RESUMO

The purposes of this study were to investigate the systemic and characteristic metabolites in the serum of dairy goats induced by aflatoxin B1 (AFB1) exposure and to further understand the endogenous metabolic alterations induced by it. A nuclear magnetic resonance (NMR)-based metabonomic approach was used to analyse the metabolic alterations in dairy goats that were induced by low doses of AFB1 (50 µg/kg DM). We found that AFB1 exposure caused significant elevations of glucose, citrate, acetate, acetoacetate, betaine, and glycine yet caused reductions of lactate, ketone bodies (acetate, ß-hydroxybutyrate), amino acids (citrulline, leucine/isoleucine, valine, creatine) and cell membrane structures (choline, lipoprotein, N-acetyl glycoproteins) in the serum. These data indicated that AFB1 caused endogenous metabolic changes in various metabolic pathways, including cell membrane-associated metabolism, the tricarboxylic acid cycle, glycolysis, lipids, and amino acid metabolism. These findings provide both a comprehensive insight into the metabolic aspects of AFB1-induced adverse effects on dairy goats and a method for monitoring dairy animals exposed to low doses of AFB1.


Assuntos
Aflatoxina B1/toxicidade , Aminoácidos/sangue , Carboidratos/sangue , Cabras/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Metabolômica , Acetatos/sangue , Animais , Glicemia/análise , Ácido Cítrico/sangue , Indústria de Laticínios , Exposição Ambiental , Corpos Cetônicos/sangue , Ácido Láctico/sangue , Espectroscopia de Ressonância Magnética , Redes e Vias Metabólicas/efeitos dos fármacos
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