RESUMO
The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air-blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein's regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.
Assuntos
Apolipoproteína A-I/deficiência , Doenças Cardiovasculares/etiologia , Nanopartículas/efeitos adversos , Adsorção/efeitos dos fármacos , Animais , Apolipoproteína A-I/sangue , Sistema Cardiovascular , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanopartículas/química , Nanotecnologia , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Transdução de Sinais/efeitos dos fármacos , Dióxido de Silício/efeitos adversos , Dióxido de Silício/químicaRESUMO
Nanoparticles (NPs) can make their way to the brain and cause in situ damage, which is a concern for nanomaterial application and airborne particulate matter exposure. Our recent study indicated that respiratory exposure to silica nanoparticles (SiO2 NPs) caused unexpected cardiovascular toxic effects. However, the toxicities of SiO2 NPs in other organs have warranted further investigation. To confirm the accumulation of SiO2 NPs in the brain, we introduced SiO2 NPs with different diameters into mice via intranasal instillation (INI) and intravenous injection (IVI) in parallel. We found that SiO2 NPs may target the brain through both olfactory and systemic routes, but the size of SiO2 NPs and delivery routes both significantly affected their brain accumulation. Surprisingly, while equivalent SiO2 NPs were found in the brain regions, brain lesions were distinctly much higher in INI than in the IVI group. Mechanistically, we showed that SiO2 NPs introduced via INI induced brain apoptosis and autophagy, while the SiO2 NPs introduced via IVI only induced autophagy in the brain.
Assuntos
Nanopartículas , Dióxido de Silício , Animais , Apoptose , Encéfalo , Camundongos , Nanopartículas/toxicidade , Material Particulado , Dióxido de Silício/toxicidadeRESUMO
BACKGROUND: With the development of zinc oxide nanoparticles (ZnO NPs) in the field of nanotechnology, their toxicological effects are attracting increasing attention, and the mechanisms for ZnO NPs neurotoxicity remain obscure. In an attempt to address concerns regarding neurotoxicity of ZnO NPs, we explored the relationship between free zinc ions, reactive oxygen species (ROS) and neurotoxic mechanisms in ZnO NPs-exposed PC12 cells. RESULT: This study demonstrated the requirement of free zinc ions shed by ZnO NPs to over generation of intracellular ROS. Next, we identified autophagic cell death was the major mode of cell death induced by ZnO NPs, and autophagosome accumulation resulted from not only induction of autophagy, but also blockade of autophagy flux. We concluded that autophagic cell death, resulting from zinc ions-ROS-c-Jun N-terminal kinase (JNK)-autophagy positive feedback loop and blockade of autophagosomal-lysosomal fusion, played a major role in the neurotoxicity of ZnO NPs. CONCLUSION: Our study contributes to a better understanding of the neurotoxicity of ZnO NPs and might be useful for designing and developing new biosafety nanoparticles in the future.
Assuntos
Nanopartículas Metálicas/toxicidade , Óxido de Zinco/toxicidade , Morte Celular Autofágica , Autofagossomos , Autofagia , Morte Celular , Nanopartículas , Espécies Reativas de Oxigênio , Testes de ToxicidadeRESUMO
Plastic products have played an indispensable role in our daily lives for several decades, primarily due to their cost-effectiveness and unmatched convenience. Nevertheless, recent developments in nanotechnology have propelled our attention toward a distinct category of plastic fine particulates known as micro(nano)-plastics (MPs/NPs). The investigation of the cytotoxic effects of MPs/NPs has emerged as a central and burgeoning area of research in environmental toxicology and cell biology. In the scope of this comprehensive review, we have meticulously synthesized recent scientific inquiries to delve into the intricate interplay between MPs/NPs and programmed cell death mechanisms, which encompass a range of highly regulated processes. First, the signaling pathways and molecular mechanisms of different programmed death modalities induced by MPs/NPs were elaborated, including apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. The causes of different programmed deaths induced by MPs/NPs, such as size, surface potential, functional group modification, aging, biological crown, and co-exposure of MPs/NPs are further analyzed. In contrast, the various cellular programmed death modes induced by MPs/NPs are not alone most of the time, and lastly, the connections between different cellular programmed death modes induced by MPs/NPs, such as interconversion, mutual promotion, and mutual inhibition, are explained. Our primary objective is to unveil the multifaceted toxicological implications of MPs/NPs on the intricate web of cellular fate and biological homeostasis. This endeavor not only broadens our understanding of the potential risks associated with MPs/NPs exposure but also underscores the urgent need for comprehensive risk assessments and regulatory measures in the context of environmental health.
Assuntos
Apoptose , Poluentes Químicos da Água , Piroptose , Autofagia , Diferenciação Celular , PlásticosRESUMO
Rapid advancements in nanotechnology have been integrated into various disciplines, leading to an increased prevalence of nanoparticle exposure. The widespread utilization of nanomaterials and heightened levels of particulate pollution have prompted government departments to intensify their focus on assessing the safety of nanoparticles (NPs). The cardiovascular system, crucial for maintaining human health, has emerged as vulnerable to damage from nanoparticle exposure. A mounting body of evidence indicates that interactions can occur when NPs come into contact with components of the cardiovascular system, contributing to adverse cardiovascular disease (CVD). However, the underlying molecular mechanisms driving these events remain elusive. This work provides a comprehensive review of recent advance on nanoparticle-induced adverse cardiovascular events and offers insight into the associated molecular mechanisms. Finally, the influencing factors of NPs-induced cardiovascular toxicity are discussed.
RESUMO
The Yellow River Delta (YRD) wetland is one of the largest and youngest wetland ecosystems in the world. It plays an important role in regulating climate and maintaining ecological balance in the region. This study analyzes the spatiotemporal changes in land use, wetland migration, and landscape pattern from 2013 to 2022 using Landsat-8 and Sentinel-1 data in YRD. Then wetland landscape changes and the impact of human activities are determined by analyzing correlation between landscape and socio-economic indicators including nighttime light centroid, total light intensity, cultivated land area and centroid, building area and centroid, economic and population. The results show that the total wetland area increased 1426 km2 during this decade. However, the wetland landscape pattern tended to be fragmented from 2013 to 2022, with wetlands of different types interlacing and connectivity decreasing, and distribution becoming more concentrated. Different types of human activities had influences on different aspects of wetland landscape, with the expansion of cultivated land mainly compressing the core area of wetlands from the edge, the expansion of buildings mainly disrupting wetland connectivity, and socio-economic indicators such as total light intensity and the centroid mainly causing wetland fragmentation. The results show the changes of the YRD wetland and provide an explanation of how human activities effect the change of its landscape, which provides available data to achieve sustainable development goals 6.6 and may give an access to measure the change of wetland using human-activity data, which could help to adject behaviors to protect wetlands.
Assuntos
Ecossistema , Áreas Alagadas , Humanos , Rios , Conservação dos Recursos Naturais , Atividades Humanas , ChinaRESUMO
MicroRNA (miRNA) is a potential biomarker for the early screening and diagnosis of cancers and is widely present in human blood, urine and saliva. Here, we report a microfluidics-assembled tool for miRNA detection based on the regulation of DNA locked and unlocked states and explore its application in complex samples. Microfluidic techniques are used to continuously assemble the locked-to-unlocked transforming system using a rapid one-step method. It only takes 2 min to produce enough locked-to-unlocked systems for a miRNA detection experiment. DNA molecules with a recognition sequence and a G-rich reporter sequence (G4m) are locked by attaching both ends to the surface of magnetic beads (MBs) in microchannels. The presence of the target miRNA can initiate the specific cleavage of one end of G4m by duplex-specific nuclease, resulting in the transition of G4m from a locked state to an unlocked state. This transition enables G4m to freely fold into a G-quadruplex, which can participate in the catalysis of ABTS oxidation and result in a turquoise color. During the whole process, the target miRNA remains intact and continuously initiate specific cleavage, facilitating signal amplification. Magnetic separation steps are employed to assist in miRNA enrichment and interference reduction. As a proof of concept, we quantified miRNA-21 using the locked-to-unlocked system. The assay allows specific detection of miRNA-21 in the range of 3.2-570 pM with a detection limit of 2.01 pM (S/N = 3). Furthermore, the locked-to-unlocked system is used to analyze miRNA-spiked urine, saliva and serum samples and shows robust performance in different matrices.
Assuntos
Biomarcadores Tumorais , MicroRNAs , Microfluídica , Humanos , DNA/química , MicroRNAs/análise , MicroRNAs/sangue , MicroRNAs/urina , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Saliva/químicaRESUMO
MicroRNAs (miRNAs) are types of endogenous non-coding small RNAs found in eukaryotes that are 18-25 nucleotides long. miRNAs are considered to be key regulatory factors of the expression of target mRNA. The roles of miRNAs involved in the regulation of anthocyanin accumulation in pigmented potatoes have not been systematically reported. In this study, the differentially expressed miRNAs and their target genes involved in the accumulation of anthocyanin during different developmental stages in purple potato (Solanum tuberosum L.) were identified using small RNA (sRNA) and degradome sequencing. A total of 275 differentially expressed miRNAs were identified in the sRNA libraries. A total of 69,387,200 raw reads were obtained from three degradome libraries. The anthocyanin responsive miRNA-mRNA modules were analyzed, and 37 miRNAs and 23 target genes were obtained. Different miRNAs regulate the key enzymes of anthocyanin synthesis in purple potato. The structural genes included phenylalanine ammonia lyase, chalcone isomerase, flavanone 3-hydroxylase, and anthocyanidin 3-O-glucosyltransferase. The regulatory genes included WD40, MYB, and SPL9. stu-miR172e-5p_L-1R-1, stu-miR828a, stu-miR29b-4-5p, stu-miR8019-5p_L-4R-3, stu-miR396b-5p, stu-miR5303f_L-7R + 2, stu-miR7997a_L-3, stu-miR7997b_L-3, stu-miR7997c_L + 3R-5_2ss2TA3AG, stu-miR156f-5p_L + 1, stu-miR156a, stu-miR156a_R-1, stu-miR156e, stu-miR858, stu-miR5021, stu-miR828 and their target genes were validated by qRT-PCR. They play important roles in the coloration and accumulation of purple potatoes. These results provide new insights into the biosynthesis of anthocyanins in pigmented potatoes.
RESUMO
Silica nanoparticles (SiO2 NPs) are extensively applied in various field, which increased their health risks to humans. SiO2 NPs were reported to enter into blood through inhalation and meanwhile, the potential use of SiO2 NPs as drug carriers in vivo allows them to present in blood circulation to induce inflammation of vascular endothelial cells which can be closely related with cardiovascular diseases, whilst the intrinsic mechanism has not been well understood. In this study, we found a regulation of signal axis induced by amorphous SiO2 NPs that triggers pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs). HUVECs exposed with SiO2 NPs generate excess amount of reactive oxygen species (ROS) and lactate dehydrogenase (LDH), together with the up-regulation of cell inflammatory factors [interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrotic factor-α (TNF-α)] and cell adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1)]. In addition, SiO2 NPs were found to promote the translocation and release of high-mobility group box 1 (HMGB1) from nucleus to cytoplasm, which was demonstrated to be regulated by ROS and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Subsequently, toll-like receptor 4 (TLR4) could bind with HMGB1, up-regulate the expression of myeloid differentiation factor 88 (MyD88) and then activate nuclear factor kappa-B (NF-κB) signaling pathway, ultimately induced the inflammatory response of HUVECs. Overall, out results revealed the related signaling pathways of cell inflammation induced by amorphous SiO2 NPs, which provided new insights in understanding SiO2 NPs-induced cytotoxicity and offered safety guidance for further nanomaterial application.
Assuntos
Proteína HMGB1 , Nanopartículas , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nanopartículas/toxicidade , Transdução de Sinais , Dióxido de Silício/toxicidade , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Due to the blooming development of nanotechnology, the further understanding of nanomaterials-induced toxicity has been demanded. Following their introduction into a biological matrix, the surface of nanoparticles (NPs) is covered by protein layer, namely corona, which imparts a new biological identity to NPs. Here, we showed that fibrinogen (Fg), but not albumin (BSA) or hemoglobin (Hb), decoration on the surface of silica nanoparticles (SiO2 NPs) ameliorate their pro-autophagic activity in non-phagocytic cells. Surprisingly, this effect of Fg was compromised in phagocytic cells. Further mechanistic investigation suggested coronal Fg has dual effects on the tuning of SiO2 NPs-induced autophagic response. First, Fg decoration blocks SiO2 NPs sedimentation through stabilize SiO2 NPs suspension; secondly, Fg coverage inhibits SiO2 NPs' cellular internalization. These findings provided important insights into the understanding of NPs-corona complexes behaviors and indicate future directions for the investigation of corona-mediated biological activities.
Assuntos
Autofagia , Fibrinogênio , Nanopartículas , Nanopartículas/toxicidade , Fagócitos , Fenômenos Físicos , Dióxido de Silício/toxicidadeRESUMO
The molecular structure and vibrational frequencies of cis-[Pt(CH(3)CN)(2)Cl(2)] were calculated by five density functional theory (DFT) and HF methods using several basis sets. The theoretical results are discussed and compared with the experimental data. It is remarkable that mPW1PW91 and PBE1PBE methods at SDD basis sets are clearly superior to the remaining density functional methods in predicting the structures of cis-[Pt(CH(3)CN)(2)Cl(2)]. Mean deviation between the calculated harmonic and observed fundamental vibrational frequencies for each method is also calculated. The results indicate that mPW1PW91 and PBE1PBE methods at SDD basis sets are also the best to predict vibrational spectra of cis-[Pt(CH(3)CN)(2)Cl(2)].
Assuntos
Antineoplásicos/química , Modelos Teóricos , Compostos de Platina/química , Espectrofotometria Infravermelho/métodos , Desenho de Fármacos , Estrutura Molecular , VibraçãoRESUMO
Comparisons of various density functional theory (DFT) methods at different basis sets in predicting the molecular structures and (13)C NMR spectra for [Pt(en)(CBDCA-O, O')], an analogue of the antitumor drug carboplatin, are reported. DFT methods including B3LYP, B3PW91, mPW1PW91, PBE1PBE, BPV86, PBEPBE, and LSDA are examined. Different basis sets including LANL2DZ, SDD, LANL2MB, CEP-4G, CEP-31G, and CEP-121G are also considered. It is remarkable that the LSDA/SDD level is clearly superior to all of the remaining density functional methods in predicting the structure of [Pt(en)(CBDCA-O, O')]. The results also indicate that the B3LYP/SDD level is the best to predict (13)C NMR spectra for [Pt(en)(CBDCA-O, O')] among all DFT methods.