RESUMO
The introduction of single or multiple heterometal atoms into metal nanoparticles is a well-known strategy for altering their structures (compositions) and properties. However, surface single nonmetal atom doping is challenging and rarely reported. For the first time, we have developed synthetic methods, realizing "surgery"-like, successive surface single nonmetal atom doping, replacement, and addition for ultrasmall metal nanoparticles (metal nanoclusters, NCs), and successfully synthesized and characterized three novel bcc metal NCs Au38I(S-Adm)19, Au38S(S-Adm)20, and Au38IS(S-Adm)19 (S-Adm: 1-adamantanethiolate). The influences of single nonmetal atom replacement and addition on the NC structure and optical properties (including absorption and photoluminescence) were carefully investigated, providing insights into the structure (composition)-property correlation. Furthermore, a bottom-up method was employed to construct a metal-organic framework (MOF) on the NC surface, which did not essentially alter the metal NC structure but led to the partial release of surface ligands and stimulated metal NC activity for catalyzing p-nitrophenol reduction. Furthermore, surface MOF construction enhanced NC stability and water solubility, providing another dimension for tunning NC catalytic activity by modifying MOF functional groups.
RESUMO
Metal nanoclusters with precisely modulated structures at the nanoscale give us the opportunity to synthesize and investigate 1D nanomaterials at the atomic level. Herein, it realizes selective 1D growth of building block nanocluster "Au13 Cd2 " into three structurally different nanoclusters: "hand-in-hand" (Au13 Cd2 )2 O, "head-to-head" Au25 , and "shoulder-to-shoulder" Au33 . Detailed studies further reveals the growth mechanism and the growth-related tunable properties. This work provides new hints for the predictable structural transformation of nanoclusters and atomically precise construction of 1D nanomaterials.
RESUMO
Objective: This study aims to investigate the utility of shear wave elastography (SWE) in quantitatively assessing the surrounding tissue hardness of breast masses and its diagnostic significance in distinguishing between benign and malignant masses of varying sizes. Methods: A retrospective analysis was conducted on 60 patients with breast masses diagnosed at our hospital between January 1, 2022, and December 31, 2022. All patients underwent standard breast ultrasound examination and SWE assessment. Masses were categorized based on diameter (≤20mm and >20mm) for comparative analysis. SWE parameters, including maximum shear wave velocity (Max SWV), mean shear wave velocity (Mean SWV), and elasticity ratio (Eratio) of surrounding tissue, were recorded. Histopathological results determined mass nature. SWE parameters were correlated with pathological diagnoses for discrimination analysis. Results: Of all patients, 37 had benign masses, and 23 had malignant masses. Malignant masses exhibited significantly higher Max SWV, Mean SWV, and Eratio in surrounding tissue compared to benign masses (P < .05). Statistically significant differences in SWE parameters were observed between different-sized masses; smaller masses (≤20mm) showed higher SWE parameters in malignant masses compared to benign masses (P < .05). In masses larger than 20mm, though SWE parameters still differed between benign and malignant masses, the significance was less pronounced (P < .05). Receiver operating characteristic (ROC) analysis demonstrated higher diagnostic accuracy of SWE parameters in discriminating malignancy in smaller breast masses. Conclusions: SWE parameters effectively quantify surrounding tissue hardness in breast masses and have diagnostic value in distinguishing between benign and malignant masses of varying sizes, particularly in masses ≤20mm. SWE offers crucial quantitative parameters for the clinical discrimination of breast masses, enhancing diagnostic accuracy and sensitivity. Future studies should expand sample sizes and optimize diagnostic models to enhance SWE's utility further in discriminating breast mass malignancy.
RESUMO
Constructing ambient-stable, single-atom-layered metal-based materials with atomic precision and understanding their underlying stability mechanisms are challenging. Here, stable single-atom-layered nanoclusters of Pd were synthesized and precisely characterized through electrospray ionization mass spectrometry and single-crystal X-ray crystallography. A pseudo-pentalene-like Pd8 unit was found in the nanocluster, interacting with two syn PPh units through nonmetal-to-metal -ring coordination. The unexpected coordination, which is distinctly different from the typical organoring-to-metal coordination in half-sandwich-type organometallic compounds, contributes to the ambient stability of the as-obtained single-atom-layered nanocluster as revealed through theoretical and experimental analyses. Furthermore, quantum chemical calculations revealed dominant electron transition along the horizontal x-direction of the Pd8 plane, indicating high photothermal conversion efficiency (PCE) of the nanocluster, which was verified by the experimental PCE of 73.3 %. Therefore, this study unveils the birth of a novel type of compound and the finding of the unusual nonmetal-to-metal -ring coordination and has important implications for future syntheses, structures, properties, and structure-property correlations of single-atom-layered metal-based materials.
RESUMO
Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiolate), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785â nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.
RESUMO
Atomically precise ~1-nm Pt nanoparticles (nanoclusters, NCs) with ambient stability are important in fundamental research and exhibit diverse practical applications (catalysis, biomedicine, etc.). However, synthesizing such materials is challenging. Herein, by employing the mixture ligand protecting strategy, we successfully synthesized the largest organic-ligand-protected (~1-nm) Pt23 NCs precisely characterized with mass spectrometry and single-crystal X-ray diffraction analyses. Interestingly, natural population analysis and Bader charge calculation indicate an alternate, varying charge -layer distribution in the sandwich-like Pt23 NC kernel. Pt23 NCs can catalyze the oxygen reduction reaction under acidic conditions without requiring calcination and other treatments, and the resulting specific and mass activities without further treatment are sevenfold and eightfold higher than those observed for commercial Pt/C catalysts, respectively. Density functional theory and d-band center calculations interpret the high activity. Furthermore, Pt23 NCs exhibit a photothermal conversion efficiency of 68.4 % under 532-nm laser irradiation and can be used at least for six cycles, thus demonstrating great potential for practical applications.
RESUMO
Fowl adenovirus serotype 4 (FAdV-4) infection results in serious hepatitis-hydropericardium syndrome (HHS) in broilers, which has caused great economic losses to the poultry industry; however, the specific host responses to FAdV-4 remain unknown. In this study, we identified 141 high-confidence protein-protein interactions (PPIs) between the main viral proteins (Hexon, Fiber 1, Fiber 2, and Penton bases) and host proteins via a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. We found that heat shock protein 70 (Hsp70), the protein with the highest score, and its cofactor DnaJ heat shock protein 40 family member C7 (DnaJC7) could negatively regulate the replication of FAdV-4. Furthermore, the nucleotide binding domain (NBD) of Hsp70 and the J domain of DnaJC7 were necessary for inhibiting FAdV-4 replication. We verified that DnaJC7 as a bridge could bind to Hsp70 and Hexon, assisting the indirect interaction between Hsp70 and Hexon. In addition, we found that FAdV-4 infection strongly induced the expression of autophagy proteins and cellular Hsp70 in a dose-dependent manner. Blockage of Hexon by Hsp70 overexpression was significantly reduced when the autophagy pathway was blocked by the specific inhibitor chloroquine (CQ). Our results showed that Hsp70 was co-opted by DnaJC7 to interact with viral Hexon and inhibited Hexon through the autophagy pathway, leading to a considerable restriction of FAdV-4 replication. IMPORTANCE FAdV-4, as the main cause of HHS, has quickly spread all over the world in recent years, seriously threatening the poultry industry. The aim of this study was to identify the important host proteins that have the potential to regulate the life cycle of FAdV-4. We found that Hsp70 and DnaJC7 played crucial roles in regulating the amount of viral Hexon and extracellular viral titers. Moreover, we demonstrated that Hsp70 interacted with viral Hexon with the assistance of DnaJC7, followed by suppressing Hexon protein through the autophagy pathway. These results provide new insight into the role of the molecular chaperone complex Hsp70-DnaJC7 in FAdV-4 infection and suggest a novel strategy for anti-FAdV-4 drug development by targeting the specific interactions among Hsp70, DnaJC7 and Hexon.
Assuntos
Infecções por Adenoviridae , Adenoviridae , Proteínas do Capsídeo , Galinhas , Proteínas de Choque Térmico HSP70 , Chaperonas Moleculares , Replicação Viral , Adenoviridae/classificação , Adenoviridae/efeitos dos fármacos , Adenoviridae/crescimento & desenvolvimento , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Animais , Autofagia/efeitos dos fármacos , Proteínas do Capsídeo/antagonistas & inibidores , Proteínas do Capsídeo/metabolismo , Galinhas/virologia , Cloroquina/farmacologia , Cromatografia Líquida , Proteínas de Choque Térmico HSP70/metabolismo , Chaperonas Moleculares/metabolismo , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/virologia , Sorogrupo , Espectrometria de Massas em Tandem , Replicação Viral/efeitos dos fármacosRESUMO
To propose the concept of single-atom-kernelled nanocluster, we synthesized a Pd-based trimetal nanocluster with a single-Ag atom-kernel for the first time by introducing some steric hindrance factors and employing a joint alloying strategy that combines the coreduction with an antigalvanic reduction (AGR). Although the AGR-derived Pd-based trimetal nanoclusters with single-silver atom kernels have low contents of gold, they show higher activity and selectivity than those of the bimetal precursor nanocluster in the electrocatalytical reduction of CO2 to CO. Furthermore, it is revealed that the kernel single atoms from both Au4Pd6(TBBT)12 and Au3AgPd6(TBBT)12 are not the active sites for catalysis, but greatly influence the catalytical performance by effecting the electronic configuration. Thus, it is demonstrated that the single-atom-kernelled nanocluster can not only improve the precious metal utilization (even to 100%) but also better the properties and provide insight into the structure-property correlation for metal nanoclusters.
Assuntos
Ouro , Prata , Catálise , Ouro/química , Prata/químicaRESUMO
Cross-collection topic models extend previous single-collection topic models, such as Latent Dirichlet Allocation (LDA), to multiple collections. The purpose of cross-collection topic modeling is to model document-topic representations and reveal similarities between each topic and differences among groups. However, the restriction of Dirichlet prior and the significant privacy risk have hampered those models' performance and utility. Training those cross-collection topic models may, in particular, leak sensitive information from the training dataset. To address the two issues mentioned above, we propose a novel model, cross-collection latent Beta-Liouville allocation (ccLBLA), which operates a more powerful prior, Beta-Liouville distribution with a more general covariance structure that enhances topic correlation analysis. To provide privacy protection for the ccLBLA model, we leverage the inherent differential privacy guarantee of the Collapsed Gibbs Sampling (CGS) inference scheme and then propose a hybrid privacy protection algorithm for the ccLBLA model (HPP-ccLBLA) that prevents inferring data from intermediate statistics during the CGS training process without sacrificing its utility. More crucially, our technique is the first attempt to use the cross-collection topic model in image classification applications and investigate the cross-collection topic model's capabilities beyond text analysis. The experimental results for comparative text mining and image classification will show the merits of our proposed approach.
RESUMO
Metal nanoclusters have recently attracted extensive interest from the scientific community. However, unlike carbon-based materials and metal nanocrystals, they rarely exhibit a sheet kernel structure, probably owing to the instability caused by the high exposure of metal atoms (particularly in the relatively less noble Ag or Cu nanoclusters) in such a structure. Herein, we synthesized a novel AgCu nanocluster with a sandwich-like kernel (diameter≈0.9â nm and length≈0.25â nm) by introducing the furfuryl mercaptan ligand (FUR) and the alloying strategy. Interestingly, the kernel consists of a centered silver atom and two planar Ag10 pentacle units with completely mirrored symmetry after a rotation of 36 degrees. The two Ag10 pentacles and some extended structures show an unreported golden ratio geometry, and the two inner five-membered rings and the centered Ag atom form an unanticipated full-metal ferrocene-like structure. The featured kernel structure causes the dominant radial direction transition of excitation electrons, as determined via time-dependent density functional theory calculations, which affords the protruding absorption at 612â nm and contributes to the promising photothermal conversion efficiency of 67.6 % of the as-obtained nanocluster, having important implications for structure-property correlation and the development of nanocluser-based photothermal materials.
RESUMO
Since the outbreak of COVID-19, widespread utilization of disinfectants has led to a tremendous increase in the generation of disinfection byproducts worldwide. Bromoacetic acid (BAA), one of the common disinfection byproducts in the environment, has triggered public concern because of its adverse effects on urinary system in mammals. Nevertheless, the BAA-induced nephrotoxicity and potential mechanism in birds still remains obscure. According to the detected content in the Taihu Lake Basin, the model of BAA exposure in chicken was established at doses of 0, 3, 300, 3000 µg/L for 4 weeks. Our results indicated that BAA exposure caused kidney swelling and structural disarrangement. BAA led to disorder in renal function (CRE, BUN, UA) and increased apoptosis (Bax, Bcl-2, caspase3). BAA suppressed the expression of mitochondrial biogenesis genes (PGC-1α, Nrf1, TFAM) and OXPHOS complex I genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6). Subsequently, BAA destroyed the expression of Nrf2 antioxidant reaction genes (Nrf2, Keap1, HO-1, NQO1, GCLM, GCLC). Furthermore, renal oxidative damage led to disorder in uric acid metabolism genes (Mrp2, Mrp4, Bcrp, OAT1, OAT2, OAT3) and exacerbated destruction in renal function. Overall, our study provided insights into the potential mechanism of BAA-induced nephrotoxicity, which were important for the clinical monitoring and prevention of BAA.
Assuntos
COVID-19 , Fator 2 Relacionado a NF-E2 , Animais , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Galinhas/metabolismo , Ácido Úrico/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transdução de Sinais , Proteínas de Neoplasias , Estresse Oxidativo , Mitocôndrias/metabolismo , Rim , Mamíferos/metabolismoRESUMO
A 69-year-old male was referred to our center for further evaluation and treatment of a gastric mass. Esophagogastroduodenoscopy found a 30-mm submucosal tumor (SMT) in the gastric body. Endoscopic ultrasound revealed a hypoechoic lesion originating from the muscularis propria layer. Computed tomography showed that the tumor presented a predominately intraluminal growth pattern.
Assuntos
Ressecção Endoscópica de Mucosa , Neurilemoma , Neoplasias Gástricas , Idoso , Mucosa Gástrica/patologia , Gastroscopia/métodos , Humanos , Masculino , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Neurilemoma/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
Pancreaticoduodenal artery aneurysm (PDAA) is a rare visceral aneurysm with a high risk of rupture and mortality. Herein, we presented a case of duodenal obstruction associated with a ruptured PDAA during the postoperative course after successful embolization.
Assuntos
Aneurisma Roto , Obstrução Duodenal , Embolização Terapêutica , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Artérias , Obstrução Duodenal/diagnóstico por imagem , Obstrução Duodenal/etiologia , Duodeno , Humanos , Pâncreas/cirurgiaRESUMO
A case series recently published in REED again highlighted the importance of early diagnosis and treatment in preventing complications of esophageal fishbone impaction. As the most common foreign body (FB) in China, fishbone ingestion is frequently encountered in our daily clinical practice. Although the majority could be managed effectively with endoscopy, rare particular cases still present challenges. We described the case of esophageal fishbone in which the first two endoscopic examinations were negative, emphasizing the role of computed tomography in its management.
Assuntos
Corpos Estranhos , China , Endoscopia Gastrointestinal/métodos , Esôfago/diagnóstico por imagem , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) has been used for gastric outlet obstruction (GOO) with promising clinical outcomes. Therefore, we aimed to determine the clinical outcomes of EUS-GE for GOO. MATERIAL AND METHODS: We used the keyword 'EUS-guided gastroenterostomy' to search in Pubmed, Web of science, Cochrane databases. Clinical outcomes of EUS-GE were evaluated in terms of technical success, clinical success and complications. RESULTS: Ten studies reported 297 patients managed with EUS-GE. Weighted pooled rates (WPR) for technical success, clinical success and complications of EUS-GE were 91% (95%CI 87%-94%), 88% (95%CI 83%-91%) and 6.8% (95%CI 4.1%-11.0%). The most common complications were abdominal pain, 6.7% (95%CI 2.5%-16.5%) and bleeding, 4.8% (95%CI 1.5%-13.9%). Two studies compared EUS-GE with surgical gastrojejunostomy (SGJ). Pooled risk ratio (RR) for technical success, clinical success and complications were 0.87 (0.78, 0.97), I2 = 0%; 0.92 (0.82, 1.04), I2 = 0%; 0.28 (0.11, 0.68), I2 = 0%. Three studies compared benign GOO with malignant GOO. RR for technical success and clinical success were 1.05 (0.82, 1.34), I2 = 0%; 0.98 (0.72, 1.33), I2 = 0%. CONCLUSIONS: Although EUS-GE and SGJ had similar clinical success rates, EUS-GE had a lower complication rate. EUS-GE is a safe, effective, and minimally invasive choice for patients with GOO.
Assuntos
Obstrução da Saída Gástrica , Ultrassonografia de Intervenção , Endossonografia , Obstrução da Saída Gástrica/cirurgia , Gastroenterostomia/efeitos adversos , Humanos , StentsRESUMO
Although thiolated, reduced Group 11 metal nanoclusters with atomic monodispersity have been repeatedly reported in the past decade, their Pd analogues have not been reported thus far. In this work, we provide a resolution for the challenging synthesis and obtain for the first time an atomically monodisperse thiolated, reduced Pd (q=+0.75) nanocluster with a di-tetrahedron Pd8 kernel and a +3 charged interstitial B atom, as revealed by ESI-MS, SCXRD, etc. µ-6 B is found for the first time in Group 10 and 11 metal nanoclusters. More importantly, the as-obtained Pd nanoclusters show better catalytic activity compared to 1.4â nm Pd nanoparticles, Pd2 complexes and even a commercial Pt/C catalyst for the oxygen reduction reaction (ORR), having significant implications for the influence of the metal charge state and space structure on the catalytic activity.
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/veterináriaRESUMO
OBJECTIVE: miR-155-5p as an important microRNA has been extensively studied for its biological functions and mechanisms in various cancers. However, the role and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain to be further elucidated. METHODS: Bioinformatics methods were implemented to analyze differentially expressed genes in the cancer genome atlas database. qRT-PCR and Western blot were employed to detect the expression of miR-155-5p and paternally expressed gene 3 (PEG3) mRNA as well as protein expression. Cell lines with miR-155-5p knockdown or miR-155-5p/PEG3 co-overexpression were constructed. A series of experiments including the MTT method, wound healing assay, and transwell assay were carried out to detect the proliferation, migration, and invasion of cancer cells in different treatment groups. Bioinformatics analysis and dual-luciferase assay were conducted to confirm the targeting relationship between PEG3 and miR-155-5p in ccRCC. RESULTS: miR-155-5p was found to be significantly upregulated in ccRCC cells, while PEG3 exhibited significantly low expression. The downregulation of miR-155-5p could inhibit cell proliferation, migration, and invasion of ccRCC. miR-155-5p could inhibit the expression of PEG3. The overexpression of miR-155-5p could promote cell proliferation, migration, and invasion, whereas overexpression of PEG3 could significantly attenuate such effect. Therefore, miR-155-5p may promote cell growth of ccRCC via inhibiting PEG3 expression. CONCLUSION: These findings validated the effect of miR-155-5p/PEG3 on ccRCC cells and provided novel potential targets for the prognosis and treatment of patients with ccRCC.
Assuntos
Carcinoma de Células Renais/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Renais/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Invasividade Neoplásica , Transdução de SinaisRESUMO
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/metabolismoRESUMO
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.