RESUMO
Severe systemic inflammation following myocardial infarction (MI) is a major cause of patient mortality. MI-induced inflammation can trigger the production of free radicals, which in turn ultimately leads to increased inflammation in cardiac lesions (i.e., inflammation-free radicals cycle), resulting in heart failure and patient death. However, currently available anti-inflammatory drugs have limited efficacy due to their weak anti-inflammatory effect and poor accumulation at the cardiac site. Herein, a novel Fe-Cur@TA nanozyme is developed for targeted therapy of MI, which is generated by coordinating Fe3+ and anti-inflammatory drug curcumin (Cur) with further modification of tannic acid (TA). Such Fe-Cur@TA nanozyme exhibits excellent free radicals scavenging and anti-inflammatory properties by reducing immune cell infiltration, promoting macrophage polarization toward the M2-like phenotype, suppressing inflammatory cytokine secretion, and blocking the inflammatory free radicals cycle. Furthermore, due to the high affinity of TA for cardiac tissue, Fe-Cur@TA shows an almost tenfold greater in cardiac retention and uptake than Fe-Cur. In mouse and preclinical beagle dog MI models, Fe-Cur@TA nanozyme preserves cardiac function and reduces scar size, suggesting promising potential for clinical translation in cardiovascular disease.
Assuntos
Macrófagos , Infarto do Miocárdio , Polifenóis , Humanos , Animais , Camundongos , Cães , Macrófagos/metabolismo , Infarto do Miocárdio/patologia , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Radicais LivresRESUMO
Nickel and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are two environmental pollutants commonly and simultaneously present in aquatic systems. Nickel and BDE-47 are individually toxic to various aquatic organisms. However, their toxicity mechanisms are species-dependent, and the toxic effects of combined mixtures of BDE-47 and nickel have not yet been investigated. The present study investigated the toxic effects of combined mixtures of BDE-47 and nickel in the diatom Phaeodactylum tricornutum. BDE-47 and nickel mixtures significantly decreased cell abundance and photosynthetic efficiency, while these cells' reactive oxygen species (ROS) production significantly increased. The EC50-72 h for BDE-47 and mixtures of BDE-47 and nickel were 16.46 ± 0.93 and 1.35 ± 0.06 mg/L, respectively. Thus, combined mixtures of the two pollutants enhance their toxic effects. Interactions between BDE-47 and nickel were evaluated, revealing synergistic interactions that contributed to toxicity in P. tricornutum. Moreover, transcriptomic analyses revealed photosynthesis, nitrogen metabolism, the biosynthesis of amino acids, the biosynthesis of secondary metabolites, oxoacid metabolism, organic acid metabolism, carboxylic acid metabolism, and oxidation-reduction processes were considerably affected by the mixtures. This study provides evidence for the mechanisms of toxicity from combined BDE-47 and nickel exposure while also improving our understanding of the ecological risks of toxic chemicals on microalgae.
RESUMO
Nickel acts as an essential trace nutrient or toxicant for organisms, depending on its concentration. The increased concentrations of nickel, due to anthropogenic activity, in the aquatic environment are potential threats to aquatic organisms. However, the knowledge on toxic mechanisms of nickel to microalgae remains incompletely understood. In the present study, we investigated the toxic effects of nickel in the cosmopolitan diatom Phaeodactylum tricornutum via evaluation of physiological and transcriptome responses. The results showed that the median effective concentration-72 h (EC50-72 h) and EC50-96 h of nickel was 2.48 ± 0.33 and 1.85 ± 0.17 mg/L, respectively. The P. tricornutum cell abundance and photosynthesis significantly decreased by 1 mg/L of nickel. Results from photosynthetic parameters including efficiency of the oxygen evolving complex (OEC) of photosystem II (PSII) (Fv/F0), maximum photosynthetic efficiency of PS II (Fv/Fm), electron transport rate (ETR), actual photosynthetic efficiency of PS II (Y(II)), non-photochemical quenching (NPQ), and photochemical quenching (qP) indicated that OEC of PS II might be impaired by nickel. The transcriptome data also reveal that OEC apparatus coding gene PS II oxygen-evolving enhancer protein 2 (PsbP) was regulated by nickel. Moreover, induced reactive oxygen species (ROS) production and chlorophyll a content were also detected under nickel stress. Transcriptome analysis revealed that nickel affected a variety of differentially expressed genes (DEGs) that involved in redox homeostasis, nitrogen metabolisms, fatty acids, and DNA metabolism. However, thiol-disulfide redox system might play important roles in nickel-induced oxidative stress resistance. This study improved the understanding of the toxic effect of nickel on the diatom P. tricornutum.
Assuntos
Diatomáceas , Microalgas , Clorofila/metabolismo , Clorofila A/metabolismo , Clorofila A/farmacologia , Diatomáceas/fisiologia , Níquel/metabolismo , Oxigênio/metabolismo , Fotossíntese , Complexo de Proteína do Fotossistema IIRESUMO
Recent molecular phylogenetic studies of Gambierdiscus species flagged several new species and genotypes, thus leading to revitalizing its systematics. The inter-relationships of clades revealed by the primary sequence information of nuclear ribosomal genes (rDNA), however, can sometimes be equivocal, and therefore, in this study, the taxonomic status of a ribotype, Gambierdiscus sp. type 6, was evaluated using specimens collected from the original locality, Marakei Island, Republic of Kiribati; and specimens found in Rawa Island, Peninsular Malaysia, were further used for comparison. Morphologically, the ribotype cells resembled G. scabrosus, G. belizeanus, G. balechii, G. cheloniae and G. lapillus in thecal ornamentation, where the thecal surfaces are reticulate-foveated, but differed from G. scabrosus by its hatchet-shaped Plate 2', and G. belizeanus by the asymmetrical Plate 3'. To identify the phylogenetic relationship of this ribotype, a large dataset of the large subunit (LSU) and small subunit (SSU) rDNAs were compiled, and performed comprehensive analyses, using Bayesian-inference, maximum-parsimony, and maximum-likelihood, for the latter two incorporating the sequence-structure information of the SSU rDNA. Both the LSU and SSU rDNA phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between Gambierdiscus sp. type 6 and G. balechii was monophyletic. As a result, the taxonomic status of Gambierdiscus sp. type 6 was revised, and assigned as Gambierdiscus balechii. Toxicity analysis using neuroblastoma N2A assay confirmed that the Central Pacific strains were toxic, ranging from 1.1 to 19.9 fg P-CTX-1 eq cell-1, but no toxicity was detected in a Western Pacific strain. This suggested that the species might be one of the species contributing to the high incidence rate of ciguatera fish poisoning in Marakei Island.