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1.
J Agric Food Chem ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817168

RESUMO

Metabolic-associated fatty liver disease (MAFLD) is currently one of the main causes of chronic liver disease, but its potential mechanism remains unclear. This study proved that estrogen receptor α (ERα) could negatively control hepatocyte pyroptosis by inhibiting NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, gasdermin D (GSDMD)-N generation, propidium iodide (PI) uptake, lactate dehydrogenase (LDH) release, and pro-inflammatory cytokine (IL-1ß and IL-18) release. Furthermore, inhibition of pyroptosis ameliorated ERα deletion-induced metabolic dysfunction, insulin resistance, and liver injury. Mechanistically, ERα was confirmed to inhibit pyroptosis by directly interacting with GSDMD, and GSDMD blockade reversed the ERα inhibition-induced pyroptosis and improved lipid accumulation in hepatocytes. Notably, the treatment of wild-type (WT) mice with genistein, a phytoestrogen, could attenuate high-fat diet (HFD)-induced liver lipid steatosis and inhibit NLRP3-GSDMD-mediated pyroptosis. Results provide new insights into the underlying mechanism of pyroptosis regulation and uncover the potential treatment target of MAFLD.

2.
Food Funct ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34812468

RESUMO

Long-term use of antibiotic growth promoter (AGP) in animal production is the main cause of antimicrobial resistance of pathogenic bacteria. Therefore, seeking alternatives to AGP is crucial for animal husbandry. Among all AGP alternatives, probiotics are promising candidates. In this study, two strains of lactic acid bacteria, L. johnsonii 3-1 and L. crispatus 7-4, were isolated from the feces of wild Gallus gallus, which exhibited obvious anti-pathogenic activity and improved the growth performance of broilers. Furthermore, we found that these two strains participated in the lipid metabolism of broilers by reducing the content of TC and TG in ileal epithelial cells and up-regulating the liver AMPKα/PPARα/CPT-1 pathway, which affects abdominal fat deposition. In summary, L. johnsonii 3-1 and L. crispatus 7-4 have the potential to be used as AGP substitutes and participate in the lipid metabolism of broilers to reduce abdominal fat deposition. Importantly, our study reveals for the first time that L. crispatus participates in liver lipid metabolism to reduce abdominal fat deposition in broilers.

3.
Virus Res ; 305: 198573, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34555436

RESUMO

The PB2 protein of avian influenza virus (AIV) is essential for transcription and replication of virus genome. In this study, we reported that chicken heterogenous nuclear riboncleoprotein AB (hnRNPAB) cooperated with avian influenza viral protein PB2 and inhibited the polymerase activity and virus replication. We found that hnRNPAB was associated with PB2 mRNA and overexpression of hnRNPAB reduced PB2 mRNA nuclear export and PB2 protein level, but had no influence on PB2 mRNA level. At the same time, overexpression of hnRNPAB also reduced protein levels rather than mRNA levels of PA, PB1 and NP. In addition, overexpression of hnRNPAB restricted the polymerase activity and virus replication, while knockdown of hnRNPAB resulted in enhanced polymerase activity and virus replication. Lastly, virus infection induced the nuclear accumulation of hnRNPAB, but did not cause the change of expression level of endogenous hnRNPAB in DF-1 cells. Collectively, these findings suggested that hnRNPAB played a restrictive role in polymerase activity and virus replication potentially through inhibiting PB2 mRNA nuclear export and PB2 protein level.

4.
Chem Biol Interact ; 347: 109616, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34363818

RESUMO

The reproductive toxicity of endocrine-disrupting chemicals has become a matter of great concern. However, the potential toxicological mechanism of typical environmental estrogens, bisphenol A (BPA) and genistein (GEN), on adult ovary remains ambiguous. In this study, we used laying hens as the experimental model and aimed to clarify the effect of long-term exposure to safe reference doses of BPA and GEN on adult ovary. Results demonstrated that 1/10 no-observable-adverse effect-level dose (1/10 NOAEL, 500 µg/kg body weight [bw]/day) of BPA significantly reduced the production performance and caused the degeneration of follicles and stromal cells and the increase of atretic follicles. Moreover, 1/10 NOAEL dose of BPA undermined the redox homeostasis of the ovary through activating Keap1 and suppressing the Nrf2-signaling pathway (Nrf2, NQO1, and HO-1). On the contrary, GEN (20, 40 mg/kg bw/day) dramatically improved the antioxidant capacity of the ovary by regulating the Nrf2-Keap1 pathway, enhancing the activities of antioxidant-related enzymes (CAT, GSH-Px, and T-SOD), and inhibiting the excessive accumulation of lipid peroxidation products (MDA). Parallel in vitro studies confirmed that the differential role of BPA and GEN on ovarian redox balance was directly mediated by Nrf2-Keap1 antioxidant system. And GEN could ameliorate BPA-induced oxidative stress. Importantly, our research found that exposure to BPA and GEN altered estrogen receptor alpha (ERα) expression in the ovary. And the use of specific ERα agonist/antagonist confirmed that BPA and GEN have opposite regulatory effects on the Nrf2-Keap1 pathway by targeting ERα.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Genisteína/toxicidade , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Galinhas , Receptor alfa de Estrogênio/metabolismo , Feminino , Homeostase/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ovário/metabolismo , Ovário/patologia
5.
ACS Appl Mater Interfaces ; 13(34): 40249-40266, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34424682

RESUMO

Disruption of intestinal homeostasis is an important event in the development of inflammatory bowel disease (IBD), and genistein (GEN) is a candidate medicine to prevent IBD. However, the clinical application of GEN is restricted owing to its low oral bioavailability. Herein, a reactive oxygen species (ROS)-responsive nanomaterial (defined as GEN-NP2) containing superoxidase dismutase-mimetic temporally conjugated ß-cyclodextrin and 4-(hydroxymethyl)phenylboronic acid pinacol ester-modified GEN was prepared. GEN-NP2 effectively delivered GEN to the inflammation site and protected GEN from rapid metabolism and elimination in the gastrointestinal tract. In response to high ROS levels, GEN was site-specifically released and accumulated at inflammatory sites. Mechanistically, GEN-NP2 effectively increased the expression of estrogen receptor ß (ERß), simultaneously reduced the expression of proinflammatory mediators (apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase1-p20), attenuated the infiltration of inflammatory cells, promoted autophagy of intestinal epithelial cells, inhibited the secretion of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), modulated the gut microbiota, and ultimately alleviated colitis. In addition, the oral administration of these nanoparticles showed excellent safety, thereby providing confidence in the further development of precise treatments for IBD.

6.
Environ Pollut ; 288: 117795, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34274649

RESUMO

Bisphenol A (BPA) and genistein (GEN) are selective estrogen receptor modulators, which are involved in the occurrence and development of metabolic syndrome. However, their roles in non-alcoholic fatty liver disease (NAFLD) of laying hens have not been reported. Here, we investigated the effects of different concentrations of GEN and BPA on the NAFLD of laying hens. Results showed that GEN ameliorated the high-energy and low-protein diet (HELP)-induced NAFLD by improving pathological damage, hepatic steatosis, and insulin resistance and blocking the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related factors. By contrast, high dose of BPA could aggravate these changes with serious symptom of NAFLD and suppress the level of ERα in the liver considerably, while GEN could reverse this phenomenon in a dose-dependent manner. In general, our research shows that the protective effect of GEN on NAFLD aims to improve the metabolic disorders and inflammation closely connected to ERα, while BPA can inhibit the expression of ERα and exacerbate the symptom of NAFLD. In conclusion, we elucidate the opposing effects of GEN and BPA in NAFLD of laying hens, thus providing a potential mechanism related to ERα and inflammation.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Compostos Benzidrílicos/toxicidade , Galinhas , Feminino , Genisteína/toxicidade , Fígado , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Fenóis
7.
BMC Vet Res ; 17(1): 64, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531001

RESUMO

BACKGROUND: H7 subtype avian influenza has caused great concern in the global poultry industry and public health. The conventional serological subtype-specific diagnostics is implemented by hemagglutination inhibition (HI) assay despite lengthy operation time. In this study, an efficient, rapid and high-throughput competitive enzyme-linked immunosorbent assay (cELISA) was developed for detection of antibodies against H7 avian influenza virus (AIV) based on a novel monoclonal antibody specific to the hemagglutinin (HA) protein of H7 AIV. RESULTS: The reaction parameters including antigen coating concentration, monoclonal antibody concentration and serum dilution ratio were optimized for H7 antibody detection. The specificity of the cELISA was tested using antisera against H1 ~ H9, H11 ~ H14 AIVs and other avian viruses. The selected cut-off values of inhibition rates for chicken, duck and peacock sera were 30.11, 26.85 and 45.66% by receiver-operating characteristic (ROC) curve analysis, respectively. With HI test as the reference method, the minimum detection limits for chicken, duck and peacock positive serum reached 20, 21 and 2- 1 HI titer, respectively. Compared to HI test, the diagnostic accuracy reached 100, 98.6, and 99.3% for chicken, duck and peacock by testing a total of 400 clinical serum samples, respectively. CONCLUSIONS: In summary, the cELISA assay developed in this study provided a reliable, specific, sensitive and species-independent serological technique for rapid detection of H7 antibody, which was applicable for large-scale serological surveillance and vaccination efficacy evaluation programs.


Assuntos
Anticorpos Antivirais/análise , Glicoproteínas de Hemaglutininação de Vírus da Influenza/análise , Vírus da Influenza A/imunologia , Influenza Aviária/diagnóstico , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Aves , Galinhas , Patos , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Influenza Aviária/virologia , Camundongos Endogâmicos BALB C
8.
Arch Virol ; 166(4): 1113-1124, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33576898

RESUMO

Avian influenza virus (AIV), Newcastle disease virus (NDV), and avian infectious bronchitis virus (IBV) inflict immense damage on the global poultry industry annually. Serological diagnostic methods are fundamental for the effective control and prevention of outbreaks caused by these viruses. In this study, a novel triplex protein microarray assay was developed and validated for the rapid and simultaneous visualized detection of antibodies against AIV, NDV, and IBV in chicken sera. The AIV nuclear protein (NP), NDV phosphoprotein (P), and IBV nonstructural protein 5 (nsp5) were produced in a prokaryotic expression system, purified, and immobilized onto an initiator integrated poly(dimethylsiloxane) (iPDMS) film as probes to detect antibodies against these viruses in chicken sera. After optimization of the reaction conditions, no cross-reactivity was detected with infectious bursal disease virus, avian leukosis virus subgroup J and chicken anemia virus antisera. The lowest detectable antibody titers in this assay corresponded to hemagglutination inhibition (HI) titers of 24 and 21 for AIV and NDV, respectively, and to an IDEXX antibody titer of 103 for IBV, using the HI assay and IDEXX commercial ELISA kit as the reference methods. When156 serum samples were tested using the new assay, the HI test and the IBV IDEXX ELISA kit, the assay showed 96.8% (151/156), 97.4% (152/156) and 99.4% (155/156) diagnostic accuracy for detection of AIV, NDV and IBV antibody, respectively. The current study suggests that the newly developed triplex microarray is rapid, sensitive, and specific, providing a viable alternative assay for AIV, NDV, and IBV antibody screening in epidemiological investigations and vaccination evaluations.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Bronquite Infecciosa/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Doença de Newcastle/isolamento & purificação , Doenças das Aves Domésticas/diagnóstico , Análise Serial de Proteínas/veterinária , Animais , Antígenos Virais/genética , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Galinhas , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/veterinária , Imunoensaio/normas , Imunoensaio/veterinária , Vírus da Bronquite Infecciosa/imunologia , Vírus da Influenza A/imunologia , Influenza Aviária/diagnóstico , Doença de Newcastle/diagnóstico , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/virologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Sensibilidade e Especificidade , Testes Sorológicos/normas , Testes Sorológicos/veterinária
9.
Environ Pollut ; 271: 116362, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33387782

RESUMO

Atrazine (ATR) is one of the most commonly used herbicides that could directly impair the growth and health of organisms in mariculture areas and adversely affect human health through the food chain. This study investigated the contaminant occurrence, migration, and transformation of ATR and three of its chlorinated metabolites, namely deethylatrazine (DEA), deisopropylatrazine (DIA), and didealkylatrazine (DDA), in surface seawater, sediment, and aquatic organisms from the Xiangshan Harbor. ATR was detected in all samples, while DIA and DDA were only respectively detected in aquatic and seawater samples. The distribution of ATR and its metabolites presented different patterns depending on the geographic location and showed a higher level in the aquaculture area than that in the non-aquaculture area. The bioaccumulation of ATR in aquaculture organisms showed that benthic organisms, such as Ditrema, and Sinonovacula constricta (Sin), had increased levels. The ecological risks indicated that ATR posed medium or high risks to algae in the water phase of the study area. The microcosm experiment showed that the main fate of ATR in the simulated microenvironment was sedimentation, which followed the first-order kinetic equation. The ATR in the sediment could be enriched 3-5 times in Sin, and its major metabolites were DEA and DIA.


Assuntos
Atrazina , Herbicidas , Aquicultura , Baías , Herbicidas/análise , Humanos , Água do Mar
10.
Ecotoxicol Environ Saf ; 206: 111398, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33010594

RESUMO

Bisphenol A (BPA) is an endocrine-disrupting chemical. Its influence on lipid homeostasis remains to be proven. In this study, the obese model of laying hens were induced using high-fat diet (HFD) to determine the lipid metabolism interference of BPA, especially its influence on estrogen receptors (ERs) and oxidative damage, at the dose of tolerable daily intake (TDI, 50 µg/kg body weight [BW]/day) and no observable adverse effect level (NOAEL, 5000 µg/kg BW/day). The results demonstrated that the TDI dose of BPA interacted with ERα more effectively than the NOAEL dose of BPA. The TDI dose of BPA increased the expression of ERα (esr1), which further changed the expression of lipid metabolism-related genes, such as cpt-1, lpl, creb1, and apov1. Furthermore, the abdominal fat rate, hematoxylin-eosin staining of adipocytes, and the average area of the hens were reduced. Therefore, the TDI dose of BPA played an estrogen-compensating role and weakened the effect of HFD on obesity in aged hens. By contrast, BPA at NOAEL dose exhibited great oxidative stress, which remarkably inhibited the activities of antioxidant-related enzymes (total superoxide dismutase and glutathione peroxidase) and promoted the excessive accumulation of lipid peroxidation products (malondialdehyde). Moreover, the increase in oxidative stress corresponded well with the increase in the expression of fat-forming genes (srebp-1, fas, acc, and ppar γ). That is, BPA at NOAEL may accelerate the process of fat formation.


Assuntos
Gordura Abdominal/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/induzido quimicamente , Fenóis/toxicidade , Gordura Abdominal/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Galinhas/metabolismo , Dieta Hiperlipídica , Receptor alfa de Estrogênio/genética , Feminino , Metabolismo dos Lipídeos/genética , Masculino , Obesidade/genética , Obesidade/metabolismo
11.
Food Chem Toxicol ; 143: 111516, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32615238

RESUMO

Ochratoxin A (OTA) was reported to induce proximal tubules nephrotoxicity in humans and animals. However, the toxicity of OTA on glomeruli has rarely been studied. We investigated OTA-induced glomerular injury and the underlying mechanisms. Mice were intraperitoneally treated with OTA (0, 0.5, 1.5 and 2.5 mg/kg b.w.) on alternate day for 3 weeks. OTA exposure decreased the weight gain ratio, the kidney index and increased the levels of serum creatinine and blood urea nitrogen. It induced also fragmentation and atrophy in glomeruli, and increased the expression of TNF-α, IL-6, COX-2, TGF-ß, α-SMA and vimentin in a dose-dependent manner. Human mesangial cells (HMC) were treated with OTA (0-8 µM) for 48 h. Treatment of HMC cells with OTA increased cell inhibition rate, up-regulated the expression of IL-6, TGF-ß, α-SMA and vimentin in a dose-dependent manner. Additionally, it enhanced the phosphorylation of ERK1/2 and p65, degradation of IκB-α and translocation of p65 into the nucleus. OTA-induced toxicity was attenuated by NF-κB and ERK1/2 inhibitors. In conclusion, these results suggest that OTA exposure induces glomerular injury via activation of the ERK/NF-κB signaling pathway, and provide novel insights into the research of OTA induced nephrotoxicity.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glomérulos Renais/efeitos dos fármacos , NF-kappa B/metabolismo , Ocratoxinas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular , Citocinas/genética , Citocinas/metabolismo , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Células Mesangiais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Ocratoxinas/administração & dosagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória
12.
J Nutr Biochem ; 83: 108438, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32563803

RESUMO

Soy isoflavones (SIFs) are selective estrogen receptor modulators (SERMs) that have anti-inflammatory activities. Our previous study found that estrogen receptor α (ERα) directly regulates the NLRP3 transcription and NLRP3 inflammasome assembly. Therefore, we hypothesized that SIFs alleviate colitis via an ERα-dependent mechanism by targeting the NLRP3 inflammasome. The influence of SIFs on colitis and the potential mechanisms were thoroughly determined in this study. The results suggested that SIFs ameliorated dextran sodium sulfate (DSS)-induced body weight loss, reduced disease activity index and promoted the recovery of colon pathological damage in mice. Moreover, expression of the NLRP3 inflammasome was significantly inhibited, and the release of IL-1ß and IL-18 was suppressed by SIFs. Furthermore, ERα blockade ameliorated DSS-induced inflammatory responses in the intestine, and SIFs markedly suppressed the expression of ERα in a dose-dependent manner. Our study demonstrated that the protective therapeutic action of SIFs on DSS-induced colitis depended on inhibition of ERα and subsequent NLRP3 inflammasome activation, and SIFs are promising therapeutic agents for the treatment of colitis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Colite/tratamento farmacológico , Receptor alfa de Estrogênio/imunologia , Inflamassomos/efeitos dos fármacos , Isoflavonas/administração & dosagem , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Extratos Vegetais/administração & dosagem , Animais , Colite/genética , Colite/imunologia , Receptor alfa de Estrogênio/genética , Humanos , Inflamassomos/genética , Inflamassomos/imunologia , Interleucina-18/genética , Interleucina-18/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Soja/química
13.
J Nutr Biochem ; 71: 110-121, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31325892

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver-related morbidity and mortality disease in the world. However, no effective pharmacological treatment for NAFLD has been found. In this study, we used a high fat diet (HFD)-induced NAFLD model to investigate hepatoprotective effect of apigenin (API) against NAFLD and further explored its potential mechanism. Our results demonstrated that gavage administration of API could mitigate HFD-induced liver injury, enhance insulin sensitivity and markedly reduce lipid accumulation in HFD-fed mice livers. In addition, histological analysis showed that hepatic steatosis and macrophages recruitment in the API treatment group were recovered compared with mice fed with HFD alone. Importantly, API could reverse the HFD-induced activation of the NLRP3 inflammasome, further reduced inflammatory cytokines IL-1ß and IL-18 release, accompanied with the inhibition of xanthine oxidase (XO) activity and the reduction of uric acid and reactive oxygen species (ROS) production. The pharmacological role of API was further confirmed using free fatty acid (FFA) induced cell NAFLD model. Taking together, our results demonstrated that API could protect against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation. These protective effects may be partially attributed to the regulation of XO by API, which further modulated NLRP3 inflammasome activation and inflammatory cytokines IL-1ß and IL-18 release. Therefore API is a potential therapeutic agent for the prevention of NAFLD.


Assuntos
Apigenina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Xantina Oxidase/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Hepatite/tratamento farmacológico , Hepatite/patologia , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ganho de Peso/efeitos dos fármacos , Xantina Oxidase/antagonistas & inibidores
14.
J Agric Food Chem ; 67(26): 7485-7495, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31180669

RESUMO

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium, contaminating in a wide variety of foods and feeds. Mycotoxins, including OTA, could cause immunosuppression in almost all previous studies in vivo. However, the vast majority of results in vitro showed that mycotoxins caused immunostimulation. Why the results of studies in vitro are contrary to studies in vivo is unknown. Our study aims to explore the underlying reason and mechanism of the paradoxical effect. In this study, porcine alveolar macrophage cell line 3D4/21 was chosen as an in vitro model and treated with 1.0 µg/mL OTA for different times. Some indexes, such as expression of inflammatory cytokines, migration, phagocytosis, macrophage polarization, autophagy-related proteins, and Akt1 phosphorylation, were detected. The results showed that pro-inflammatory cytokine expression, migration, and phagocytosis were increased, with macrophage polarization to the M1 phenotype at 24 h of OTA exposure. Surprisedly, anti-inflammatory cytokine expression was increased, cell phagocytosis and migration were decreased, and macrophage polarization was switched from M1 to M2 at 72 h of OTA exposure. Furthermore, we found that long-time exposure of OTA also suppressed autophagy, and the autophagy activator blocked the OTA-induced immunosuppression. Phosphorylation of Akt1 plays a positive role in autophagy inhibition. In conclusion, long-time instead of short-time exposure of OTA in vitro induced immunosuppression. The immunosuppression mechanism of OTA in vitro involved inhibition of autophagy through upregulating p-Akt1. Our results provide new insight into research on the mechanism of mycotoxin-induced immunosuppression in vitro.


Assuntos
Imunossupressores/toxicidade , Macrófagos Alveolares/efeitos dos fármacos , Ocratoxinas/toxicidade , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/imunologia , Imunossupressores/administração & dosagem , Macrófagos Alveolares/imunologia , Ocratoxinas/administração & dosagem , Fagocitose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Suínos , Fatores de Tempo
15.
Food Chem Toxicol ; 131: 110527, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31173817

RESUMO

Zearalenone (ZEA) can widely contaminate crops and agricultural products. The ingestion of ZEA-contaminated food or feed affects the integrity and functions of the intestines. In this study, we aimed to find the potential protective mechanism against ZEA ingestion. We found that ZEA induced cell death in IPEC-J2 cells. Meanwhile, the cytoprotective autophagy was activated in ZEA-treated cells. Further studies demonstrated that a p38/MAPK inhibitor down-regulated autophagy and increased cell death compared to those of the controls. Furthermore, ZEA could induce the accumulation of ROS, and eliminating ROS with NAC resulted in a decline in cell death, p38/MAPK phosphorylation, and the expression of LC3-II compared to those of ZEA-group. In addition, cytochrome P450 reductase (CYPOR) was significantly increased in ZEA-treated cells compared to that in the controls, and an inhibitor of CYPOR decreased ROS levels and mitigated cell death compared to those of the ZEA-group. More importantly, we found that blocking both p38/MAPK signalling and autophagy could enhance CYPOR expression and elevate ROS levels. Overall, our study indicated that the p38/MAPK pathway could activate protective autophagy in response to the CYPOR-dependent oxidative stress that was induced by ZEA in IPEC-J2 cells.


Assuntos
Autofagia/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Zearalenona/toxicidade , Acetilcisteína/farmacologia , Animais , Células Epiteliais/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Intestinos/efeitos dos fármacos , MAP Quinase Quinase 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Suínos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Cell Signal ; 61: 86-92, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31121307

RESUMO

It has been reported that estrogen receptors (ERs) participate in carcinogenesis by directly regulating NOD-like receptors (NLRs). However, the expression profiles of ERs and NLRs in tumor and the ER-NLR regulated signaling pathway are not clear. In this study, we summarized gene expression profiles of ERs and NLRs across normal and tumor tissue by comprehensive data mining. Then we explored the ER-NLR regulated signaling pathway by RNA sequencing (RNA-seq). The results showed that the NLRs and ERs were differentially expressed in different neoplasm tissues. Such expression discrepancies might influence inflammatory regulation and tumorigenesis. Importantly, we identified that ER-NLR regulate Wnt/ß-catenin pathway in colon cancer. Taking colon adenocarcinoma (COAD) as example, we found that Wnt2b/LRP8/Dvl1/Axin2/GSK3a/APC/ß-catenin genes were differentially expressed in ER-/- mouse colon tissue and colon cancer cells. The selective ERα antagonist could significantly decrease Wnt2b/LRP8/Dvl1 expression, increase destruction complex (Axin2/GSK3a/APC) expression, and promote degradation of ß-catenin in colon carcinoma cell by inhibited NLRP3 expression. In short, the research demonstrates that NLRs are potential biomarkers for cancer, and ERs can regulate the Wnt/ß-catenin signaling pathway in cancer by targeting the NLRs. Our results provide a possible signaling pathway in which ER-NLR is correlated with Wnt/ß-catenin.


Assuntos
Neoplasias do Colo/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Cinamatos/farmacologia , Neoplasias do Colo/patologia , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/genética , Regulação Neoplásica da Expressão Gênica/genética , Glicoproteínas/metabolismo , Células HCT116 , Humanos , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fenóis/farmacologia , Pirazóis/farmacologia , RNA Interferente Pequeno/genética , Transcriptoma , Proteínas Wnt/metabolismo
17.
Vet Microbiol ; 231: 238-245, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955816

RESUMO

Circular RNAs (circRNAs) play critical roles in various diseases. However, whether and how circular RNA regulates influenza A virus (IAV) infection is unknown. Here, we studied the role of circular RNA GATA Zinc Finger Domain Containing 2A (circ-GATAD2A) in the replication of IAV H1N1 in A549 cells. Circ-GATAD2A was formed upon H1N1 infection. Knockdown of circ-GATAD2A in A549 cells enhanced autophagy and inhibited H1N1 replication. By contrast, overexpression of circ-GATAD2A impaired autophagy and promoted H1N1 replication. Similarly, knockout of vacuolar protein sorting 34 (VPS34) blocked autophagy and increased H1N1 replication. However, the expression of circ-GATAD2A could not further enhance H1N1 replication in VPS34 knockout cells. Collectively, these data indicated that circ-GATAD2A promotes the replication of H1N1 by inhibiting autophagy.


Assuntos
Autofagia/genética , Fatores de Transcrição GATA/genética , Interações entre Hospedeiro e Microrganismos/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , RNA/genética , Replicação Viral , Células A549 , Classe III de Fosfatidilinositol 3-Quinases/genética , Técnicas de Silenciamento de Genes , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , RNA Circular , Regulação para Cima
18.
BMC Vet Res ; 15(1): 103, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935399

RESUMO

BACKGROUND: Major viruses, including duck-origin avian influenza virus, duck-origin Newcastle disease virus, novel duck parvovirus, duck hepatitis A virus, duck Tembusu virus, fowl adenovirus, and duck enteritis virus, pose great harm to ducks and cause enormous economic losses to duck industry. This study aims to establish a multiplex polymerase chain reaction (m-PCR) method for simultaneous detection of these seven viruses. RESULTS: Specific primers were designed and synthesized according to the conserved region of seven viral gene sequences. Then, seven recombinant plasmids, as the positive controls, were reconstructed in this study. Within the study, D-optimal design was adopted to optimize PCR parameters. The optimum parameters for m-PCR were annealing temperature at 57 °C, Mg2+ concentration at 4 mM, Taq DNA polymerase concentration at 0.05 U/µL, and dNTP concentration at 0.32 mM. With these optimal parameters, the m-PCR method produced neither cross-reactions among these seven viruses nor nonspecific reactions with other common waterfowl pathogens. The detection limit of m-PCR for each virus was 1 × 104 viral DNA copies/µL. In addition, the m-PCR method could detect a combination of several random viruses in co-infection analysis. Finally, the m-PCR method was successfully applied to clinical samples, and the detection results were consistent with uniplex PCR. CONCLUSION: Given its rapidity, specificity, sensitivity, and convenience, the established m-PCR method is feasible for simultaneous detection of seven duck-infecting viruses and can be applied to clinical diagnosis of viral infection in ducks.


Assuntos
Patos/virologia , Reação em Cadeia da Polimerase Multiplex/veterinária , Doenças das Aves Domésticas/virologia , Animais , Coinfecção/diagnóstico , Coinfecção/veterinária , Coinfecção/virologia , Flavivirus , Adenovirus A das Aves , Vírus da Hepatite do Pato , Reação em Cadeia da Polimerase Multiplex/métodos , Vírus da Doença de Newcastle , Orthomyxoviridae , Parvovirinae , Doenças das Aves Domésticas/diagnóstico , Sensibilidade e Especificidade
19.
Biochem Biophys Res Commun ; 511(2): 468-475, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30797557

RESUMO

Increasing evidence indicates that the NOD-like receptors (NLRs) family may act as critical back-up defenses and provide synergistic responses when confronted with persistent danger. However, the precise regulatory mechanism of NLRs and the contribution of NLRs to cancer are still unknown. In our previous study, we found that estrogen receptors (ERs) have a close connection with NLRs in the inflammatory response. Here, ERs are first identified as NLRs transcription regulation factors, both regulate NLRs expression and promote inflammasome co-localization. Furthermore, we identified that NLRP3 was differentially expressed in colon normal and cancer cells, selective ERα antagonist could significantly decrease pro-inflammatory cytokines expression, suppress proliferation and promote apoptosis by inhibited NLRP3 expression and inflammasome activity. In short, the research demonstrates that ERs participate in the NLR-associated signaling pathway in cancer by directly regulating NLRs. Our results provide novel insight into ERs as therapeutic targets in NLR-related inflammation and cancer.


Assuntos
Carcinogênese/imunologia , Inflamassomos/imunologia , Proteínas NLR/imunologia , Receptores de Estrogênio/imunologia , Carcinogênese/patologia , Linhagem Celular Tumoral , Humanos , Inflamassomos/análise , Inflamação/imunologia , Inflamação/patologia , Modelos Moleculares , Proteína 3 que Contém Domínio de Pirina da Família NLR/análise , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteínas NLR/análise , Receptores de Estrogênio/análise , Transdução de Sinais
20.
Food Chem Toxicol ; 122: 120-131, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30287338

RESUMO

Ochratoxin A (OTA) could cause a variety of toxicological effects especially nephrotoxicity in animals and humans. Autophagy is a highly conserved metabolic process that plays an important role in the maintenance of cellular homeostasis under stress. However, the role of autophagy in OTA-induced nephrotoxicity is unknown. In the present study, we demonstrated that OTA treatment at 2.0-8.0 µM could increase cytotoxicity of PK-15 cells by inducing apoptosis as shown by the increased Annexin V/PI staining, increased caspase-3 and PARP cleavage and increased apoptotic nuclei. Meantime, autophagy was triggered when OTA was administrated, as indicated by markedly increased expressions of LC3-II, ATG5 and Beclin-1, accumulation of GFP-LC3 dots and increased double- or single-membrane vesicles. OTA treatment decreased p-AKT and p-mTOR activities, and OTA-induced autophagy was inhibited when insulin was applied. Furthermore, OTA treatments with autophagy inhibitors (3-methyladenine or chloroquine) or knockdown of autophagy-related genes (ATG5 or Beclin-1) resulted in significantly reduced autophagy level and enhanced cytotoxicity. In conclusion, OTA induces cytoprotective autophagy against its cytotoxicity and inactivation of AKT/mTOR axis plays a critical role in autophagy induction.


Assuntos
Autofagia/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Rim/efeitos dos fármacos , Ocratoxinas/toxicidade , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Proteína Beclina-1/genética , Linhagem Celular , Relação Dose-Resposta a Droga , Técnicas de Silenciamento de Genes , Humanos , Ocratoxinas/administração & dosagem , Serina-Treonina Quinases TOR/metabolismo
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