RESUMO
Trametes lactinea polysaccharides have a high medicinal value; however, we still know little about the structure and bioactivity of intracellular and extracellular polysaccharides in the mycelial liquid fermentation of T. lactinea. This study analyzed the structures of intracellular (IP-1, IP-2, and IP-3) and extracellular (EP-1 and EP-2) polysaccharide components isolated from T. lactinea liquid fermentation, as well as investigated their antioxidant, antibacterial, and immunomodulatory properties. The results showed that IP-3 was the only component with a triple-helix structure, while the other four components did not possess this structure. IP3 has a higher molecular weight, flavonoid, and total phenolic content compared to other components. Both intracellular and extracellular polysaccharide components exhibited strong scavenging abilities against ABTS and DPPH radicals. The components showed limited antibacterial effects against four types of bacteria (Staphylococcus aureus, Bacillus subtilis, Erwinia carotovora, and Escherichia coli), and were found to be non-toxic to RAW264.7 cells, even promoting cell proliferation. Furthermore, within a specific concentration range, all components enhanced the phagocytic activity of RAW264.7 cells, increased the secretion of NO, TNF-α, and IL-6, and demonstrated concentration-dependent effects, with IP-3 displaying the most potent immunomodulatory activity. This study shows a high potential for the development and utilization of polysaccharides derived from the liquid fermentation of T. lactinea mycelium.
RESUMO
Immune escape is the main reason that immunotherapy is ineffective in hepatocellular carcinoma (HCC). Here, this study illustrates a pathway mediated by neutrophil extracellular traps (NETs) that can promote immune escape of HCC. Mechanistically, we demonstrated that NETs up-regulated CD73 expression through activating Notch2 mediated nuclear factor kappa B (NF-κB) pathway, promoting regulatory T cells (Tregs) infiltration to mediate immune escape of HCC. In addition, we found the similar results in mouse HCC models by hydrodynamic plasmid transfection. The treatment of deoxyribonuclease I (DNase I) could inhibit the action of NETs and improve the therapeutic effect of anti-programmed cell death protein 1 (PD-1). In summary, our results revealed that targeting of NETs was a promising treatment to improve the therapeutic effect of anti-PD-1.
RESUMO
Lithium-rich antiperovskites promise to be a compelling class of high-capacity cathode materials due to the existence of both cationic and anionic redox activity. Little is however known about the effect of separating the electrochemical cationic process from the anionic process and the associated implications on the electrochemical performance. In this context, we report the electrochemical properties of the illustrative example of three different (Li2Fe)SO materials with a focus on separating cationic from anionic effects. With the high-voltage anionic process, an astonishing electrochemical capacity of around 400 mAh g-1 can initially be reached. Our results however identify the anionic process as the cause of poor cycling stability and demonstrate that the fading reported in previous literature is avoided by restricting to only the cationic processes. Following this path, our (Li2Fe)SO-BM500 shows strongly improved performance as indicated by constant electrochemical cycling over 100 cycles at a capacity of around 175 mAh g-1 at 1 C. Our approach also allows us to investigate the electrochemical performance of the bare antiperovskite phase excluding extrinsic activity from initial or cycling-induced impurity phases. Our results underscore that synthesis conditions are a critical determinant of electrochemical performance in lithium-rich antiperovskites, especially with regard to the amount of electrochemical secondary phases, while the particle size has not been found to be a crucial parameter. Overall, separating and understanding the effects of the cationic from the anionic redox activity in lithium-rich antiperovskites provides the route to further improve their performance in electrochemical energy storage.
RESUMO
CTL recognition of non-mutated tumor-associated antigens (TAA), present on cancer cells but also in healthy tissues, is an important element of cancer immunity, but the mechanism of its selectivity for cancer cells and opportunities for its enhancement remain elusive. In this study, we found that CTL expression of the NK receptors (NKR) DNAM-1 and NKG2D was associated with the effector status of CD8+ tumor-infiltrating lymphocytes (TIL) and long-term survival of melanoma patients. Using MART-1 and NY-ESO-1 as model TAAs, we demonstrated that DNAM-1 and NKG2D regulate T-cell receptor (TCR) functional avidity and set the threshold for TCR activation of human TAA-specific CTLs. Superior costimulatory effects of DNAM-1 over CD28 involved enhanced TCR signaling, CTL killer function and polyfunctionality. Double transduction of human CTLs with TAA-specific TCR and NKRs resulted in strongly enhanced antigen sensitivity, without a reduction in the antigen specificity and selectivity of killer function. In addition, the elevation of NKR-Ligand expression on cancer cells by chemotherapy also increased CTL recognition of cancer cells expressing low levels of TAA. Our data help to explain the ability of self-antigens to mediate tumor rejection in the absence of autoimmunity and support the development of dual-targeting adoptive T cell therapies that use NKRs to enhance the potency and selectivity of recognition of TAA-expressing cancer cells.
RESUMO
The implementation of a dual-source water supply system offers an increased level of reliability in water provision; however, intricate hydraulic dynamics introduce apprehensions regarding water safety at the hydraulic junction. In this study, we gathered data of the water quality at the hydraulic junction of a dual-source water supply system (plant A and plant B, sampling site A10 was near plant A, and sampling site A12 was near plant B) for one year in Suzhou Industrial Park. Our findings indicated that seasonal variations and water temperature exerted significant influence on the composition and formation of disinfection byproducts (DBPs). Notably, during the warmer months spanning from June to September, the concentration of trihalomethanes was the highest at the hydraulic junction, whereas the concentration of residual chloride was the lowest. The analysis on DBPs revealed that more Br-containing precursors in water in plant A resulted in the accumulation of more Br-containing DBPs at A10, whereas the highest concentration of Cl-containing DBPs accumulated at A12. The analysis of the dissolved organic matter (DOM) composition indicated an increase in concentration at A10 and A12 compared with that in plant A and plant B. The highest concentration of humic acids was observed at A10, whereas A12 accumulated the highest concentration of aromatic proteins and microbial metabolites. Owing to the fluctuations in water consumption patterns at the hydraulic junction, the water quality was susceptible to variability, thereby posing an elevated risk. Consequently, extensive efforts are warranted to ensure the maintenance of water safety and quality at this critical interface.
RESUMO
Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic "partner" in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-ß/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-ß/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.
Assuntos
Vesículas Extracelulares , Cirrose Hepática , Schistosoma japonicum , Esquistossomose Japônica , Animais , Vesículas Extracelulares/metabolismo , Cirrose Hepática/parasitologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/patologia , Camundongos , Interações Hospedeiro-Parasita/fisiologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/parasitologia , Células Estreladas do Fígado/patologia , MicroRNAs/metabolismo , MicroRNAs/genética , Transdução de Sinais , Humanos , Proteínas de Helminto/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The Jahn-Teller (JT) distortion is one of the fundamental processes in molecules and condensed phase matters. For photoionized organic molecules with high symmetry, the JT effect leads to geometric instability in certain electron configurations and thus has a significant effect on the subsequent isomerization and proton migration processes. Utilizing the femtosecond pump-probe Coulomb explosion method, we probe the isomerization dynamics process of a monovalent cyclopropane cation (C3H6+) caused by proton migration and reveal the relationship between proton migration and JT distortion. We found that the C3H6+ cation evolves from the D3h symmetric equilateral triangle geometry either to the acute triangle via two elongated C-C bonds (JT1) or to the obtuse triangle via a single elongated C-C bond (JT2). The JT1 pathway does not involve proton migration, while the JT2 pathway drives proton migration and can be mapped into the indirect dissociation channel of Coulomb explosion. The time-resolved experiment indicates that the delay time between those two JT pathways can be as large as â¼600 fs. After the JT distortion, the cyclopropane cation undergoes a subsequent structural evolution, which brings a greater variety of dissociation channels.
RESUMO
Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.
Assuntos
Neoplasias dos Ductos Biliares , Armadilhas Extracelulares , Humanos , Animais , Camundongos , Armadilhas Extracelulares/metabolismo , Angiogênese , DNA/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neutrófilos/metabolismoRESUMO
Decabromodiphenyl ether (BDE-209) is a widely used brominated flame retardant that can easily detach from materials and enter into feed and foodstuffs, posing a serious risk to human and animal health and food safety of animal origin. However, the immunotoxic effects of BDE-209 on the avian spleen and the exact mechanism of the toxicity remain unknown. Therefore, we established an experimental model of BDE-209-exposed chickens and a positive control model of cyclophosphamide-induced immunosuppression in vivo and treated MDCC-MSB-1 cells and chicken splenic primary lymphocytes with BDE-209 in vitro. The results showed that BDE-209 treatment caused morphological and structural abnormalities in the chicken spleens. Mechanistically, indicators related to oxidative stress, endoplasmic reticulum stress (ERS), autophagy, and apoptosis were significantly altered by BDE-209 exposure in both the spleen and lymphocytes, but the use of the N-acetylcysteine or the 4-phenylbutyric acid significantly reversed these changes. In addition, BDE-209 exposure decreased the spleen antimicrobial peptide and immunoglobulin gene expression. In conclusion, the present research revealed that BDE-209 exposure enhanced lymphocyte autophagy and apoptosis in chicken spleen via the ROS-mediated ERS pathway. This signaling cascade regulatory relationship not only opens up a new avenue for studying BDE-209 immunotoxicity but also provides important insights into preventing BDE-209 hazards to animal health.
Assuntos
Galinhas , Retardadores de Chama , Humanos , Animais , Galinhas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Baço/metabolismo , Éteres Difenil Halogenados/toxicidade , Éteres Difenil Halogenados/metabolismo , Apoptose , Autofagia , Estresse do Retículo Endoplasmático , Retardadores de Chama/toxicidadeRESUMO
Decabromodiphenyl ether (BDE-209) is one of the most widely used flame retardants that can infect domestic and wildlife through contaminated feed. Nanoselenium (Nano-Se) has the advantage of enhancing the anti-oxidation of cells. Nonetheless, it remains uncertain whether Nano-Se can alleviate vascular Endothelial cells damage caused by BDE-209 exposure in chickens. Therefore, we established a model with 60 1-day-old chickens, and administered BDE-209 intragastric at a ratio of 400 mg/kg bw/d, and mixed Nano-Se intervention at a ratio of 1 mg/kg in the feed. The results showed that BDE-209 could induce histopathological and ultrastructural changes. Additionally, exposure to BDE-209 led to cardiovascular endoplasmic reticulum stress (ERS), oxidative stress and thioredoxin-interacting protein (TXNIP)-pyrin domain-containing protein 3 (NLRP3) pathway activation, ultimately resulting in pyroptosis. Using the ERS inhibitor 4-PBA in Chicken arterial endothelial cells (PAECs) can significantly reverse these changes. The addition of Nano-Se can enhance the body's antioxidant capacity, inhibit the activation of NLRP3 inflammasome, and reduce cellular pyroptosis. These results suggest that Nano-Se can alleviate the pyroptosis of cardiovascular endothelial cells induced by BDE-209 through ERS-TXNIP-NLRP3 pathway. This study provides new insights into the toxicity of BDE-209 in the cardiovascular system and the therapeutic effects of Nano-Se.
Assuntos
Sistema Cardiovascular , Éteres Difenil Halogenados , Selênio , Animais , Células Endoteliais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Galinhas/metabolismo , Piroptose , Selênio/metabolismo , Estresse do Retículo EndoplasmáticoRESUMO
The energy and power industry is an important field for CO2 emission reduction. The CO2 emitted by thermal power enterprises is a major cause of global climate change, and also a key challenge for China to achieve the goals of "carbon peaking and carbon neutrality." Therefore, it is essential to scientifically and accurately predict the CO2 emissions of key thermal power enterprises in the region. This will guide carbon reduction strategies and policy recommendations for leaders, and also provide a valuable reference for similar regions globally. This study utilizes the factor analysis method to extract the common factors influencing CO2 emissions based on the carbon verification data of 17 thermal power enterprises in Gansu Province. Additionally, the DISO (distance between indices of simulation and observation) index is employed to comprehensively evaluate three prediction models, namely multiple linear regression, support vector regression, and GA-BP neural network. Ultimately, this study provides a reasonable prediction of CO2 emissions for the aforementioned enterprises in Gansu Province. The results show that the three common factors obtained by factor analysis, namely energy consumption and output factor, energy quality factor, and energy efficiency factor, can effectively predict the CO2 emissions from thermal power enterprises. In the three prediction models, GA-BP neural network has the best overall performance with DISO value of 0.95, RMSE value of 11848.236, and MAE value of 7880.543. Over the period 2022-2030, CO2 emissions from 17 thermal power enterprises in Gansu Province are predicted to increase. Under the low-carbon, scenario baseline, and high-carbon scenarios, the CO2 emissions will reach 71.58 Mt, 79.25 Mt, and 87.97 Mt, respectively, by 2030.
Assuntos
Dióxido de Carbono , Carbono , Dióxido de Carbono/análise , Carbono/análise , China , Indústrias , Desenvolvimento EconômicoRESUMO
Decabromodiphenyl ether (BDE209) is a toxic environmental pollutant that can cause neurotoxicity, behavioral abnormalities, and cognitive impairment in animals. However, the specific mechanisms of BDE209-induced neurological injury and effective preventative and therapeutic interventions are lacking. Even though selenomethionine (Se-Met) has a significant detoxification effect and protects the nervous system, it remains unclear whether Se-Met can counteract the toxic effects of BDE209. For the in vivo test, we randomly divided 60 1-week-old hy-line white variety chicks into the Con, BDE209, Se-Met, and BDE209 +Se-Met groups. In vitro experiments were performed, exposing chick embryo brain neurons to BDE209, Se-Met, N-Acetylcysteine (NAC, a ROS inhibitor), and RSL3 (a GPX4 inhibitor). We demonstrated that BDE209 induced oxidative stress and ferroptosis in the chicken brain, which mainly manifested as mitochondrial atrophy, cristae breakage, increased Fe2+ and MDA content, decreased antioxidant enzyme activity, and the inhibition of the NRF2/GPX4 signaling pathway in the brain neurons. However, Se-Met supplementation reversed these changes by activating the NRF2/GPX4 pathway, reducing mitochondrial damage, enhancing antioxidant enzyme activity, and alleviating ferroptosis. This study provides insight into the mechanism of BDE209-related neurotoxicity and suggests Se-Met as an effective preventative and control measure against BDE209 poisoning.
Assuntos
Ferroptose , Éteres Difenil Halogenados , Selenometionina , Embrião de Galinha , Animais , Galinhas , Fator 2 Relacionado a NF-E2 , Antioxidantes , Estresse Oxidativo , EncéfaloRESUMO
Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.
Assuntos
Schistosoma japonicum , Esquistossomose , Humanos , Feminino , Animais , Schistosoma japonicum/genética , Esquistossomose/veterinária , Imunoglobulina G , Reprodução , Anexinas/metabolismoRESUMO
[This corrects the article DOI: 10.3389/fnhum.2023.1276994.].
RESUMO
Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL4)-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the α2 chain of collagen type 1 (Col1α2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1α2 and the TGF-ß/Smad signaling pathway.
RESUMO
Disruptions in the inter-regional connective correlation within the brain are believed to contribute to memory impairment. To detect these corresponding correlation networks in Alzheimer's disease (AD), we conducted three types of inter-regional correlation analysis, including structural covariance, functional connectivity and group-level independent component analysis (group-ICA). The analyzed data were obtained from the Alzheimer's Disease Neuroimaging Initiative, comprising 52 cognitively normal (CN) participants without subjective memory concerns, 52 individuals with late mild cognitive impairment (LMCI) and 52 patients with AD. We firstly performed vertex-wise cortical thickness analysis to identify brain regions with cortical thinning in AD and LMCI patients using structural MRI data. These regions served as seeds to construct both structural covariance networks and functional connectivity networks for each subject. Additionally, group-ICA was performed on the functional data to identify intrinsic brain networks at the cohort level. Through a comparison of the structural covariance and functional connectivity networks with ICA networks, we identified several inter-regional correlation networks that consistently exhibited abnormal connectivity patterns among AD and LMCI patients. Our findings suggest that reduced inter-regional connectivity is predominantly observed within a subnetwork of the default mode network, which includes the posterior cingulate and precuneus regions, in both AD and LMCI patients. This disruption of connectivity between key nodes within the default mode network provides evidence supporting the hypothesis that impairments in brain networks may contribute to memory deficits in AD and LMCI.
RESUMO
CD28-driven "signal 2" is critical for naïve CD8+ T cell responses to dendritic cell (DC)-presented weak antigens, including non-mutated tumor-associated antigens (TAAs). However, it is unclear how DC-primed cytotoxic T lymphocytes (CTLs) respond to the same TAAs presented by cancer cells which lack CD28 ligands. Here, we show that NK receptors (NKRs) DNAM-1 and NKG2D replace CD28 during CTL re-activation by cancer cells presenting low levels of MHC I/TAA complexes, leading to enhanced proximal TCR signaling, immune synapse formation, CTL polyfunctionality, release of cytolytic granules and antigen-specific cancer cell killing. Double-transduction of T cells with recombinant TCR and NKR constructs or upregulation of NKR-ligand expression on cancer cells by chemotherapy enabled effective recognition and killing of poorly immunogenic tumor cells by CTLs. Operational synergy between TCR and NKRs in CTL recognition explains the ability of cancer-expressed self-antigens to serve as tumor rejection antigens, helping to develop more effective therapies.
RESUMO
This study addresses the problem of maize disease detection in agricultural production, proposing a high-accuracy detection method based on Attention Generative Adversarial Network (Attention-GAN) and few-shot learning. The method introduces an attention mechanism, enabling the model to focus more on the significant parts of the image, thereby enhancing model performance. Concurrently, data augmentation is performed through Generative Adversarial Network (GAN) to generate more training samples, overcoming the difficulties of few-shot learning. Experimental results demonstrate that this method surpasses other baseline models in accuracy, recall, and mean average precision (mAP), achieving 0.97, 0.92, and 0.95, respectively. These results validate the high accuracy and stability of the method in handling maize disease detection tasks. This research provides a new approach to solving the problem of few samples in practical applications and offers valuable references for subsequent research, contributing to the advancement of agricultural informatization and intelligence.
RESUMO
Background: The aim of this study is to explore the role of acetyl-CoA acyltransferase 2 (ACAA2) in the progression of hepatocellular carcinoma (HCC). Methods: Bulk RNA data and single-cell RNA data were acquired from The Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism. Results: We found downregulation of ACAA2 was involved in the malignant progression of HCC. The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and predicted to have a poor prognosis. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway might be responsible for low level of ACAA2 related immunosuppressive microenvironment. Furthermore, the expression of ACAA2 was also detected in immune cells. The expression of ACAA2 in CD4+TCF7+T, CD4+FOXP3+T, CD8+GZMK+T, and CD8+KLRD1+T cells was inversely correlated with the composition of CD8+PDCD1+T cells in HCC. This effect might be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks. Conclusion: In a conclusion, downregulated ACAA2 promoted the progression of hepatocellular carcinoma and might be participated in the formation of immunosuppressive microenvironment. ACAA2 could be served as a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.
RESUMO
As environmental pollutants, polybrominated diphenyl ethers (PBDEs) can have toxic effects on living organisms and has a bioaccumulative effect. Low doses of selenium nanoparticles (SeNPs) can exert antioxidant, anti-inflammatory and anti-toxin functions on the organism. This experiment evaluated SeNPs' ability to prevent chicken's intestinal damage from decabromodiphenyl ether (BDE-209) exposure. Sixty layer chickens were separated into four groups at randomly and equally: Control group, SeNPs group (1 mg/kg SeNPs), BDE-209 group (400 mg/kg BDE-209), and BDE-209 +SeNPs group (400 mg/kg BDE-209 and 1 mg/kg SeNPs), for 42 days. The results showed that BDE-209 increased MDA content, decreased the activities of T-SOD, T-AOC, GSH and iNOS, up-regulated the expression of TNF-α, RIPK1, RIPK3 and MLKL, promoted the production of inflammatory factors, reduced the levels of tight junction proteins (Claudin-1, Occludin, ZO-1). SeNPs attenuated intestinal oxidative stress, necroptosis, inflammation and intestinal barrier damage caused by BDE-209. This protective effect is associated with the MAPK/NF-κB signaling pathway. Moreover, SeNPs restores flora alpha and beta diversity, improves intestinal flora composition and its abundance. It shifts the dysbiosis of intestinal flora caused by BDE-209 to normal. Overall, SeNPs can alleviate BDE-209-induced intestinal barrier damage and intestinal flora disorders, which are associated with intestinal oxidative stress, necroptosis and inflammation.